baseball is a team sport in which a fistsized ball is thrown by a player called a pitcher and hit with a bat
scoring involves running and touching markers on the ground called bases
the ball itself is called a baseball
baseball is sometimes called hardball to differentiate it from the closely related sport of softball and other similar games
baseball is popular in the americas and east asia
in japan the dominican republic cuba panama south korea taiwan and some other countries it is the most popular sport by any measurement
in the united states baseball has often been called the national pastime
the total attendance for major league games is more than that of all other american professional team sports combined
although the three most popular team sports in north america are ball games 
baseball basketball and american football
baseballs popularity grew so great that the word ballgame in the united states almost always refers to a game of baseball and ballpark to a baseball field
among american television viewers however it has been surpassed in popularity 
in terms of television ratings
by american football and auto racing
baseball is played between two teams of nine players each on a baseball field usually under the authority of one or more officials called umpires
there are usually four umpires in major league games and as few as one
may officiate depending on the league and the importance of the game
there are four bases
numbered counterclockwise first second and third bases are cushions shaped as inch squares which are raised above the ground
together with home plate the fourth base they form a square with sides of feet called the diamond
home base is a pentagonal rubber slab known as home plate
the field is divided into two main sections
the infield contains the four bases and beyond two adjacent sides of the diamond there is an outfield
the other two sides of the diamond form the start of the foul lines which extend straight and form the boundary in the outfield as well
the game is played in nine innings in which each team gets one turn to bat and try to score runs while the other pitches and defends in the field
in baseball the defense always has the ball a fact that differentiates it from most other team sports
the teams switch every time the defending team gets three players of the batting team out
the winner is the team with the most runs after nine innings
in the case of a tie additional innings are played until one team comes out ahead
at the start of the game all nine players of the home team play the field while players on the visiting team come to bat one at a time
the basic contest is always between the pitcher for the fielding team and a batter
the pitcher throwspitchesthe ball towards home plate where the catcher for the fielding team waits to receive it
the batter stands in one of the batters boxes and tries to hit the ball with a bat
the catchers job is to catch any ball that the batter misses or does not swing at and most importantly to call the game by a series of hand signals to the pitcher what pitch to throw and where
if the pitcher disagrees with the call he will shake off the catcher by shaking his head no
he accepts the sign by nodding
the catchers role becomes more crucial depending on how the game is going and how the pitcher responds to a given situation
each pitch begins a new play which might consist of nothing more than the pitch itself
each halfinning the goal of the defending team is to get three members of the other team out
a player who is out must leave the field and wait for his next turn at bat
there are many ways to get batters and baserunners out
some of the most common are catching a batted ball in the air tag outs force outs and strikeouts
after the fielding team has put out three of the batting teams players the halfinning is over and the team in the field and the team at bat switch places
thus a complete inning consists of each opposing side having a turn on offense
the goal of the team at bat is to score runs
a player may do so only by batting then becoming a base runner touching all the bases in order and finally touching home plate
via one or more plays
to that end the goal of each batter is to enable baserunners to score or become a baserunner himself
the batter attempts to hit the ball into fair territorybetween the foul linesin such a way that the defending players cannot get him or the baserunners out
in general the pitcher attempts to prevent this by pitching the ball in such a way that the batter cannot hit it cleanly
a baserunner who successfully touches home plate after touching all previous bases in order scores a run
in an enclosed field a fair ball hit over the fence on the fly is normally an automatic home run which entitles the batter and all runners to touch all the bases and score
the team in the field is the defensive team
they attempt to prevent the team at bat from scoring
the fielding team has a pitcher who stands on the mound and a catcher who squats behind home plate
this pair is often called the battery
the remaining seven fielders may be positioned anywhere in fair territory but the standard defensive alignment places four infielders at the edge of the infield and three outfielders in the outfield
the pitchers main role is to pitch the ball toward home plate with the goal of getting the batter out
pitchers also play defense by fielding batted balls covering bases 
for a potential tag out or force out on an approaching runner or backing up throws
the catchers main role is to receive the pitch if the batter does not hit it
together with the pitcher and coaches the catcher plots game strategy by suggesting different pitches and by shifting the starting positions of the other fielders
catchers are also responsible for defense in the area near home plate
the four infielders are the first baseman second baseman shortstop and third baseman
the first and third basemen play near their respective bases
the second baseman and the shortstop position themselves in the gaps on either side of second base toward first and third base respectively
originally the second baseman played very close to second base
this positioning shifted when teams found it necessary to have four infielders rather than four outfielders
the first basemans job consists largely of making force plays at first base on ground balls hit to the other infielders
the first baseman also fields balls hit near first base but because the position is less demanding than the others the teams strongest hitter is often also their first baseman
the second baseman covers the area to the right of second base and provides backup for the first baseman
the shortstop fills the critical gap between second and third baseswhere righthanded batters generally hit ground ballsand also covers second or third base and the near part of left field
this position is the most demanding defensively so a good shortstop need not necessarily be a good batter
the third basemans primary requirement is a strong throwing arm in order to make the long throw across the infield to the first baseman
quick reaction time is also important for third basemen as they tend to see more sharply hit balls than the other infielders
the three outfielders are called the left fielder the center fielder and the right fielder the positions being named from the catchers perspective
the right fielder generally has the strongest arm of all the outfielders due to the need to make throws on runners attempting to take third base
the center fielder has more territory to cover than the corner outfielders so this player must be quick and agile with a strong arm to throw balls in to the infield
as with the shortstop teams tend to emphasize defense at this position
also the center fieldecmr is considered the outfield leader and left and rightfielders should cede to his direction when fielding fly balls
the locations of the fielders are not specified by the rules
players often shift their positioning in response to specific batters or game situations and they may exchange positions with one another at any time
effective pitching is vitally important to a baseball team as pitching is the key for the defensive team to retiring batters and runners to hold the other team at bay
a full game usually involves over one hundred pitches thrown by each team and most pitchers begin to tire before they reach this point
multiple pitchers are often needed in a single game including the starting pitcher and members of the bullpen 
an area where pitchers warm up before they play
pitchers are substituted for one another like any other player and the rules do not limit the number of pitchers that can be used in a game
the pitchers main weapon is the variation of his pitches the three variables being accuracy velocity and movement
most pitchers attempt to master two or more pitches
the pitcher must keep one foot in contact with the top or side of the pitchers rubbera x plate located atop the pitchers moundduring the entire pitch so he cannot take more than one step forward in delivering the ball
nevertheless the average majorleague pitcher can throw the ball up to ninety miles per hour and a few pitchers have even exceeded miles per hour 
the act of throwing a baseball overhand at high speed is unnatural to the body and somewhat damaging to human musclespitchers are very susceptible to injuries and soreness so baseball teams always have several pitchers
the ultimate goal of the team at bat is to score runs
the team at bat sends its nine players up to home plate as batters in an order called a lineup
each team sets its batting lineup at the beginning of the game and may not change the order except by sending in substitute players
a substitute player fills the same spot in the order as the player he replaced
however he is not required to play the same position in the field
after the ninth player has batted the order returns to the beginning with the first player in the lineup
batting out of turn is not allowed
once a runner reaches home plate they score a run and are no longer a base runner
they must leave the playing area until their spot in the order comes up again
a runner may only circle the bases once per plate appearance and thus can score no more than a single run
each players turn at the plate is a plate appearance
when the batter hits a fair ball he must run to first base and may continue or stop at any base unless he is put out
a successful hit where the batter reaches only first base is a single
if he reaches second base a double
or third base a triple
a hit that allows the batter to touch all bases in order on the same play is a home run whether or not the ball is hit over the fence
if a player has hit all four types of base hits in a single game he is said to have hit for the cycleonce a runner is held to a base he may attempt to advance at any time but is not required to do so unless the batter or another runner displaces him
depending on the way the ball comes off the bat the play has different names
a batted ball is called a fly ball if it was hit in the air in a way causing the fielder to catch it on its descent or a line drive if it is hit in the air but almost level to the ground
a batted ball which is not hit into the air and which touches the ground within the infield before it can be caught is called a ground ball
once the batter and any existing runners have all stopped at a base or been put out the ball is returned to the pitcher and the next batter comes to the plate
this continues until three outs have been recorded at which point all runners are removed from the bases and the teams exchange sides for the next halfinning
after the opposing team bats in its own order and three more outs are recorded the first teams batting order will continue again from where it left off
each plate appearance consists of a series of pitches in which the pitcher throws the ball towards home plate while a batter is standing in the batters box
with each pitch the batter must decide whether or not to swing the bat at the ball in an attempt to hit it
the pitches arrive fast so the decision must be made in less then a second
this decision is largely based on whether or not the ball is in the strike zone a region defined by the area directly above home plate and between the batters knees and underarms
in addition to swinging at the ball a batter who wishes to put the ball in play may hold his bat over home plate and attempt to tap a pitch very lightly
this is called a bunt
on any pitch if the batter swings at the ball and misses he is charged with a strike
if the batter does not swing the home plate umpire judges whether or not the ball passed through the strike zone
if the ball passes through the zone it is ruled a strike
otherwise it is declared to be a ball
the number of balls and strikes thrown to the current batter is known as the count
if the batter swings and makes contact with the ball but does not put it in play in fair territorya foul ballhe is charged with a strike except when there are already two strikes
thus a foul ball with two strikes leaves the count unchanged though a ball that is bunted foul with two strikes always counts as a third strike
if a pitch is batted foul and a member of the defensive team is able to catch it before the ball strikes the ground the batter is declared out
in the event that a batter makes contact with the ball but the ball continues directly into the catchers mitt without striking the ground a foul tip is called and the batter is charged with a strike even if he currently has strikes in the count
on the third strike the batter is declared out a strikeout
on the fourth ball the batter is entitled to advance to first base without risk of being put out
this is called a base on balls or walk
if the batter puts the ball in play in fair territory he becomes a baserunner and must get to first base safely
a batter always drops his bat when running to first basethe bat otherwise would slow him down and also be a danger to fielders
if the pitcher either intentionally or unintentionally hits the batter the umpire will declare a hit by pitch and the batter is awarded first base
the goal of each batter is to become a baserunner himself 
usually by a safe hit or a base on balls
or to help move other baserunners along
once a batter gets a hit a base on balls or otherwise reaches base he is said to be on that base until he attempts to advance to the next base until he is put out or until the halfinning ends
runners on second or third base are considered to be in scoring position since ordinary hits even singles will often score them
a runner who is touching a base which he is entitled to occupy is safehe may not be tagged out
runners may attempt to advance from base to base on any fair ball that touches the ground
when a ball is hit in the air a fly ball and caught by the defending team runners must return and touch the base they occupied at the time of the pitchcalled tagging upafter the ball is caught
once they do this they may attempt to advance at their own risk
baserunners may attempt to advance or steal a base while the pitcher is throwing a pitch
the pitcher in lieu of delivering the pitch may try to prevent this by throwing the ball to one of the infielders in order to tag the runner
if successful it is called a pickoff
if the runner attempts to steal the next base but is tagged out before reaching it safely he is caught stealing
the standard dimensions of a baseball field with feet between bases generate many close baserunning plays
in tag plays a good slide can affect the outcome of the play
even routine ground ball outs are recorded by a margin of less than a second
in general baserunning is a tactical part of the game requiring good judgment by runners and their coaches to assess the risk in attempting to advance
an inning consists of each team having one turn in the field and one turn to hit with the visiting team batting before the home team
a standard game lasts nine innings although some leagues such as minor leagues and high school baseball use seven inning games
the team with the most runs at the end of the game wins
if the home team is ahead after eightandahalf innings have been played it is declared the winner and the last halfinning is not played
if the home team is trailing or tied in the last inning and they score to take the lead the game ends as soon as the winning run crosses touches home plate
however if the last batter hits a home run to win the game he and any runners on base are all permitted to score
if both teams have scored the same number of runs at the end of a regularlength game a tie is avoided by the addition of extra innings
as many innings as necessary are played until one team has the lead at the end of an inning
thus the home team always has a chance to respond if the visiting team scores in the top half of the inning
this gives the home team a small tactical advantage
in theory a baseball game could go on forever
in practice however they eventually end
in major league baseball the longest game played was a inning affair between the brooklyn robins and boston braves on may 
the game ended in a tie called on account of darkness
in major league baseball games end with tie scores only because conditions have made it impossible to continue play
a tie game does not count as an official game in the standings unless it is finished later or replayed
however individual player statistics from tie games are counted
inclement weather may also shorten games but at least five innings must be played for the game to be considered official
fourandahalf innings are enough if the home team is ahead
previously curfews and the absence of adequate lighting caused more ties and shortened games
in japanese baseball if the score remains tied after nine innings up to three extra innings may be played before the game is called a tie
some youth or amateur leagues will end a game early if one team is ahead by ten or more runs a practice known as the mercy rule or slaughter rule
rarely a game can also be won or lost by forfeit
there is a short break between each halfinning during which the new defensive team takes the field and the pitcher warms up
traditionally the break between the top half and the bottom half of the seventh inning is known as the seventhinning stretch
during the stretch fans often sing the chorus of take me out to the ball game each team is allowed to substitute for any player at any time but no player once removed from the game may return
a batter who replaces another batter is referred to as a pinch hitter
similarly a pinch runner may be used as a replacement for a baserunner
any replacement is a permanent substitution
the replaced player may not return to the game
it is common for a pitcher to pitch for several innings and then be removed in favor of a relief pitcher
because pitching is a specialized skill most pitchers are relatively poor hitters
it is common to substitute for a pitcher when he is due to bat
this pinch hitter is typically then replaced by a relief pitcher when the team returns to the field on defense but more complicated substitutions are possible most notably the double switch
many amateur leagues allow a starting player who was removed to return to the game in the same position in the batting order under a reentry rule
youth leagues often allow free and open substitution to encourage player participation
most leagues notably major league baseballs american league allow a designated hitter a player whose sole purpose is to hit when it would normally be the pitchers turn
this is not considered a substitution but rather a position albeit a purely offensive one
a designated hitter does not play in the field on defense and may remain in the game regardless of changes in pitchers
each team is run by a manager whose primary responsibility during the game is to assign players to fielding positions determine the lineup and decide how to substitute players
managers are also assisted by coaches in helping players to develop their skills
when a team is atbat they will position a coach or manager in each coachs box
these coaches must help the players decide whether they should try to run to the next base
also the coaches will signal plays to the batter and runners
any baseball game involves one or more umpires who make rulings on the outcome of each play
at a minimum one umpire will stand behind the catcher to have a good view of the strike zone and call each pitch a ball or a strike
additional umpires may be stationed near the bases thus making it easier to see plays in the field
in major league baseball four umpires are used for each game one near each base
in the allstar game and playoffs six umpires are used
one at each base and two in the outfield along either foul line
another notable role in baseball is that of the official scorer
the results of baseball games are summarized in tables called box scores
the scorer is responsible for a number of judgments that go into the boxscore
for example if a batted ball is misplayed by a fielder the scorer may choose to charge the fielder with an error instead of crediting the batter with a hit
within certain guidelines the scorer also determines which pitchers are credited with winning and losing the game and whether a relief pitcher will be awarded a hold or save specific situations in which a relief pitcher keeps a lead intact for his team
american football basketball ice hockey and soccer all use a clock and fans must often watch games end as one team kills the clock rather than compete directly against the opposing team
in contrast baseball has no clock
a team cannot win without getting the last batter out and a rally can start at any time
in recent decades observers have criticized professional baseball for the length of its games with some justification as the time required to play a baseball game has increased steadily through the years
one hundred years ago games typically took an hour and a half to play
today the average major league baseball game is finished in just under three hours
this is due to longer commercial breaks increased offense more pitching changes and a slower pace of play
in response major league baseball has instructed umpires to be more strict in enforcing speedup rules and the size of the strike zone
although the official rules specify that when the bases are empty the pitcher should deliver the ball within seconds of receiving it 
with the penalty of a ball called if he fails to do so
this rule is rarely if ever enforced
baseball is fundamentally a team sporteven two or three hall of famecaliber players are no guarantee of a pennantyet it places individual players under great pressure and scrutiny
the pitcher must make good pitches or risk losing the game
the hitter has a mere fraction of a second to decide what pitch has been thrown and whether or not to swing at it
while their respective managers andor coaches can sometimes signal players regarding the strategies the manager wants to employ no one can help the pitcher while he pitches or the hitter while he bats
if the batter hits a line drive the outfielder as the last line of defense makes the lone decision to try to catch it or play it on the bounce
baseball history is full of heroes and goatsmen who in the heat of the moment distinguished themselves with a timely hit or catch or an untimely strikeout or error
baseball requires skill and athleticism but also has a depth of strategy and anticipation which often goes unrecognized by those less familiar with the sport
pitchers develop strategies on how to pitch to the batter by studying the batters previous plate appearances throughout the year
pitchers will vary their approach with each time they see the same batter
defensive players are positioned based on statistics about where the batter is likely to hit the ball and what specific type of pitches will be thrown
hitters are given signals about what to hit coordinated plays the manager is calling even when not to swing
pitchers are given signals to throw a specific pitch or even not to pitch at all 
eg an intentional base on balls or a pitchout the goals of a team vary across scope from individual pitch to the season
teams develop strategy to match this varying scope
they have a broad set of goals for the season but more specific strategies for the early part of the season varying that by the team and even by home games vs away games
meanwhile they have very specific strategies for a single game and even down to the inning the players who are due to bat including the next pitch
as with many sports and perhaps even more so statistics are very important to baseball
statistics have been kept for the major leagues since their creation and presumably statistics were around even before that
general managers baseball scouts managers and players alike study player statistics to help them decide from various strategies to best help their team
traditionally statistics like batting average for battersthe number of hits divided by the number of at batsand earned run averageapproximately the number of runs given up by a pitcher per nine inningshave governed the statistical world of baseball
however the advent of sabermetrics has brought an onslaught of new statistics that better gauge a players performance and contributions to his team from year to year
some sabermetrics have entered the mainstream baseball statistic world
onbase plus slugging 
is a somewhat complicated formula that gauges a hitters performance better than batting average
it combines the hitters on base percentagehits plus walks plus times hit by pitches divided by plate appearanceswith their slugging percentagetotal bases divided by at bats
walks plus hits per inning pitched gives a good representation of a pitchers abilities
it is calculated exactly as its name suggests
also important are more specific statistics for a certain situation
for example a certain hitters ability to hit lefthanded pitchers might cause his manager to give him more chances to face lefties
some hitters hit better with runners in scoring position so an opposing manager knowing this statistic might elect to intentionally walk him in order to face a poorer hitter
baseball is thought to be a direct descendant of cricket rounders and town ball though the games origins are uncertain
alexander cartwright published the first known list of rules in to meet the demands of the already popular sport and todays rules of baseball have evolved from them
professional baseball began in the united states around and the national league was founded in 
several other leagues formed and failed but the american league formed in as the western league did succeed
while rivals who fought for the best players the two major leagues began playing a world series in 
compared to modern times games in the early part of the th century were lower scoring and pitchers more successful
this period which has since become known as the deadball era ended in the s with several rules changes that gave advantages to hitters and the rise of the legendary baseball player babe ruth who showed the world what power hitting could produce
during the first half of the th century a gentlemens agreement effectively barred nonwhite players from the major leagues resulting in the formation of several negro leagues
finally in major league baseballs color barrier was broken when jackie robinson was signed by the national leagues brooklyn dodgers
although it was not instantaneous baseball has since become fully integrated
the middle of the century led baseball to the west of the united states and also became a time when pitchers dominated
scoring became so low in the american league due to pitching dominance that the designated hitter was introduced
this rule now constitutes the primary difference between the two leagues
despite the popularity of baseball the players became unsatisfied as they believed the owners had too much controla stance that many baseball fans found objectionable
a series of strikes and lockouts began in baseball affecting portions of the and seasons and culminating in the infamous strike of that led to the cancellation of the world series
the popularity of baseball diminished greatly as a result and fans were slow to return until the home run race of between mark mcgwire and sammy sosa
since then baseball has enjoyed another surge in popularity in america
the thrilling playoffs of followed by the al west having the closest race in the history of the game and the red soxs epic comeback against the yankees has resulted in what some have called the new golden age for baseball
genetics from the greek genno give birth
genetics is the science of genes heredity and the variation of organisms
the word genetics was first applied to describe the study of inheritance and the science of variation by english scientist william bateson in a letter to adam sedgewick dated april 
humans began applying knowledge of genetics in prehistory with the domestication and breeding of plants and animals
in modern research genetics provides important tools in the investigation of the function of a particular gene eg analysis of genetic interactions
within organisms genetic information generally is carried in chromosomes where it is represented in the chemical structure of particular dna molecules
genes encode the information necessary for synthesizing proteins which in turn play a large role in influencing although in many instances do not completely determine the final phenotype of the organism
the phrase to code for is often used to mean a gene contains the instructions on how to build a particular protein as in the gene codes for the protein
note that the one gene one protein concept is now known to be simplistic
for example a single gene may produce multiple products depending on how its transcription is regulated
it was not until that gregor mendel first traced inheritance patterns of certain traits in pea plants and showed that they obeyed simple statistical rules
although not all features show these patterns of mendelian inheritance his work acted as a proof that application of statistics to inheritance could be highly useful
since that time many more complex forms of inheritance have been demonstrated
from his statistical analysis mendel defined a concept that he described as an allele which was the fundamental unit of heredity
the term allele as mendel used it is nearly synonymous with the term gene whilst the term allele now means a specific variant of a particular gene
the significance of mendels work was not understood until early in the twentieth century after his death when his research was rediscovered by other scientists working on similar problems
mendel was unaware of the physical nature of the gene
we now know that genetic information is normally carried on dna certain viruses store their genetic information in rna
manipulation of dna can in turn alter the inheritance and features of various organisms
classical genetics consists of the techniques and methodologies of genetics that predate the advent of molecular biology
after the discovery of the genetic code and such tools of cloning as restriction enzymes the avenues of investigation open to geneticists were greatly broadened
some classical genetic ideas have been supplanted with the mechanistic understanding brought by molecular discoveries but many remain intact and in use such as mendels laws
patterns of inheritence still remain a useful tool for the study of genetic diseases
molecular genetics builds upon the foundation of classical genetics but focuses on the structure and function of genes at a molecular level
molecular genetics employs the methods of both classical genetics such as hybridization and molecular biology
it is socalled to differentiate it from other sub fields of genetics such as ecological genetics and population genetics
an important area within molecular genetics is the use of molecular information to determine the patterns of descent and therefore the correct scientific classification of organisms
this is called molecular systematics
the study of inherited features not strictly associated with changes in the dna sequence is called epigenetics
some take the view that life can be defined in molecular terms as the set of strategies which rna polynucleotides have used and continue to use to perpetuate themselves
this definition grows out of work on the origin of life specifically the rna world hypothesis
population quantitative and ecological genetics are all very closely related subfields and also build upon classical genetics 
supplemented with modern molecular genetics
they are chiefly distinguished by a common theme of studying populations of organisms drawn from nature but differ somewhat in the choice of which aspect of the organism on which they focus
the foundational discipline is population genetics which studies the distribution of and change in allele frequencies of genes under the influence of the four evolutionary forces
natural selection genetic drift mutation and migration
it is the theory that attempts to explain such phenomena as adaptation and speciation
the related subfield of quantitative genetics which builds on population genetics aims to predict the response to selection given data on the phenotype and relationships of individuals
a more recent development of quantitative genetics is the analysis of quantitative trait loci
traits that are under the influence of a large number of genes are known as quantitative traits and their mapping to a location on the chromosome requires accurate phenotypic pedigree and marker data from a large number of related individuals
ecological genetics again builds upon the basic principles of population genetics but is more explicitly focused on ecological issues
while molecular genetics studies the structure and function of genes at a molecular level ecological genetics focuses on wild populations of organisms and attempts to collect data on the ecological aspects of individuals as well as molecular markers from those individuals
a more recent development is the rise of genomics which attempts the study of largescale genetic patterns across the genome for 
and in principle all the dna in
a given species
genomics depends on the availabilty of whole genome sequences and compuational tools developed in the field of bioinformatics for analysis of large set of data
the science which grew out of the union of biochemistry and genetics is widely known as molecular biology
the term genetics is often widely conflated with the notion of genetic engineering where the dna of an organism is modified for some kind of practical end but most research in genetics is aimed at understanding and explaining the effect of genes on phenotypes and in the role of genes in populations 
see population genetics and ecological genetics
rather than genetic engineering
achondroplasia is a type of genetic disorder that is a common cause of dwarfism
people with this condition have short stature usually reaching a full adult height of around meters
the disorder is a result of an autosomal dominant mutation in the fibroblast growth factor receptor gene fbfr which causes an abnormality of cartilage formation
it occurs at a frequency of about in to in births
people with achondroplasia have one normal copy of the fibroblast growth factor receptor gene and one mutant copy
only one copy of the gene needs to be present for the disorder to be seen
thus a person with achondroplasia has a chance of passing on the gene to their offspring meaning that in of their children will have achondroplasia
however in out of cases people with achondroplasia are born to parents who dont have the condition
this is the result of a new mutation
new gene mutations are associated with increasing paternal age over years
studies have demonstrated that new gene mutations are exclusively inherited from the father and occur during spermatogenesis 
as opposed to resulting from a germline mosaicism
achondroplasia can be detected before birth by the use of prenatal ultrasound
a dna test can be performed before birth to detect homozygosity where two copies of the mutant gene are inherited a condition which is lethal and leads to stillbirths
growth hormone therapy has been proposed as a possible treatment for the short stature of achondroplasia
however the people who participated in the studies on the subject have not yet reached adult size so this type of therapy has unknown results
early experience with surgical limb lengthening procedures resulted in a high incidence of complications but recent experiences have improved results considerably
for the genetic details
more than of achondroplasia is caused by two different mutations in the fibroblast growth factor receptor fgfr
in about of cases the mutation is a glyarg substitution resulting from a g to a point mutation at nucleotide of the fgfr gene bellus et al shiang et al rousseau et al 
about of cases are caused by a g to c point mutation at nucleotide 
adenine is one of the two purine nucleobases used in forming nucleotides of the nucleic acids dna and rna
in dna adenine binds to thymine to assist in stabilizing the nucleic acid structures
in rna adenine binds to uracil 
adenine forms adenosine a nucleoside when attached to ribose and deoxyadenosine when attached to deoxyribose and it forms adenosine triphosphate 
a nucleotide when three phosphate groups are added to adenosine
adenosine triphosphate is used in cellular metabolism as one of the basic methods of transferring chemical energy between reactions
in chemistry an amino acid is any molecule that contains both amino and carboxylic acid functional groups
in biochemistry this shorter and more general term is frequently used to refer to alpha amino acids
those amino acids in which the amino and carboxylate functionalities are attached to the same carbon
amino acids are biochemical building blocks
they form short polymer chains called peptides or polypeptides which in turn form structures called proteins
twenty amino acids are encoded by the standard genetic code and are called proteinogenic or standard amino acids
rarer more complicated ones are produced by the body and are called nonstandard
proline is the only proteinogenic amino acid whose side group is cyclic and links to the aamino group forming a secondary amino group
formerly proline was misleadingly called an imino acid
other amino acids contained in proteins are usually formed by posttranslational modification that is modification after translation 
protein synthesis
these modifications are often essential for the function of the protein
at least two amino acids other than the standard are sometimes incorporated into proteins during translation although only amino acids are genetically coded over have been found in nature
some of those were found in meteoritic material
microorganisms and plants often produce very uncommon amino acids which can be found in peptidic antibiotics eg nisin or alamethicin
lanthionine is a sulfidebridged alanine dimer which is found together with unsaturated amino acids in lantibiotics antibiotic peptides of microbial origin
aminocyclopropanecarboxylic acid acc is a small disubstituted cyclic amino acid and a key intermediate in the production of the plant hormone ethylene
in addition to amino acids for protein synthesis there are other biologically important amino acids such as the neurotransmitters glycine gaba and glutamate as well as carnitine 
used in lipid transport within a cell
ornithine citrulline homocysteine hydroxyproline hydroxylysine and sarcosine
some of the standard amino acids are called essential amino acids because they cannot be synthesized by the body from other compounds through chemical reactions but instead must be taken in with food
in humans the essential amino acids are lysine leucine isoleucine methionine phenylalanine threonine tryptophan valine and in children histidine and arginine
peptide sequence or amino acid sequence is the order in which amino acid residues connected by peptide bonds lie in the chain
the sequence is generally reported from the nterminal end containing free amino group to the cterminal end containing free carboxyl group
peptide sequence is often called protein sequence if it represent the primary structure of a protein
several deductions can be made from the sequence
long stretches of hydrophobic residues may indicate transmembrane helices
certain residues indicate a beta sheet area
if fulllenght protein sequence is available it is possible to estimate the isoelectric point of the protein
methods for determining the peptide sequence include deduction from dna sequence edman degradation and mass spectrometry
an antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses
each antibody recognizes a specific antigen unique to its target
immunoglobulins are glycoproteins that function as antibodies
they are found in the blood and tissue fluids as well as many secretions
structurally they are globulins 
in the region of protein electrophoresis
they are synthesized and secreted by b cells of the immune system
b cells are activated upon binding to their specific antigen
in some cases the interaction of the b cell with a t helper cell is also necessary
according to differences in their heavy chain constant domains immunoglobulins are grouped into five classes or isotypes
igg iga igm igd and ige the isotypes are also defined with light chains but they do not define classes so they are often neglectedother immune cells partner with antibodies to eliminate pathogens depending on which igg iga igm igd and ige constant binding domain receptors it can express on its surface
the antibodies a single b lymphocyte produces can differ in their heavy chain and the b cell often expresses different classes of antibodies at the same time
however they are identical in their specificity for antigen conferred by their variable region
to achieve the large number of specificities the body needs to protect itself against many different foreign antigens it must produce millions of b lymphoyctes
it is important to note that to produce such a diversity of antigen binding sites with a separate gene for each possible antigen the immune system would require many more genes than exist in the genome
instead as susumu tonegawa showed in portions of the genome in b lymphocytes can recombine to form all the variation seen in the antibodies and more
tonegawa won the nobel prize in physiology or medicine in for his discovery
when a macrophage ingests a pathogen it attaches parts of its proteins to a class ii mhc protein
this complex is moved to the outside of the cell membrane where it can be recognized by a t lymphocyte which compares it to similar structures on the cell membrane of a b lymphocyte
if it finds a matching pair the t lymphocyte activates the b lymphocyte which starts producing antibodies
a b lymphocyte can only produce antibodies against the structure it presents on its surface
antibodies exist freely in the bloodstream or bound to cell membranes
they are part of the humoral immune system
antibodies exist in clonal lines that are specific to only one antigen eg a virus hull protein
in binding to such antigens they can cause agglutination and precipitation of antibodyantigen products prime for phagocytosis by macrophages and other cells block viral receptors and stimulate other immune responses such as the complement pathway
antibodies that recognize viruses can block these directly by their sheer size
the virus will be unable to dock to a cell and infect it hindered by the antibody
they can also agglutinate them so the phagocytes can capture them
antibodies that recognize bacteria mark them for ingestion by macrophages
together with the plasma component complement antibodies can kill bacteria directly
they neutralize toxins by binding with them
it is important to note that antibodies cannot attack pathogens within cells and certain viruses hide inside cells for long periods of time to avoid them
this is the reason for the chronic nature of many minor skin diseases such as cold sores
any given outbreak is quickly suppressed by the immune system but the infection is never truly eradicated because some cells retain viruses that will resume it later
in biochemistry antibodies are used for immunological identification of proteins using the western blot method
a similar technique is used in elispot and elisa assays in which detection antibodies are used to detect cell secretions such as cytokines or antibodies
antibodies are also used to separate proteins 
and anything bound to them
from the other molecules in a cell lysate
these purified antibodies are often produced by injecting the antigen into a small mammal such as a mouse or rabbit
blood isolated from these animals contains polyclonal antibodies multiple antibodies that stick to the same antigen the serum 
blood from which bloodclotting proteins and redblood cells were removed
also known as the antiserum because it now contains the desired antibodies is commonly purified with protein ag purification or antigen affinity chromatography
if the lymphocytes that produce the antibodies can be isolated and immortalized then a monoclonal antibody can be obtained
monoclonal antibodies have much greater specificity than polyclonal antibodies
romeo and juliet is a famous play by william shakespeare concerning the fate of two young starcrossed lovers
january 
the story originates from a story of mariotto and gianozza by masuccio salernitano in il novelino
luigi da portos istoria novellamente ritrovata di due nobili amanti gave the story much of its modern form renaming the lovers to romeus and giulietta and shifting the action from siena to verona
da portos story was taken up and included by matteo bandello in his novelle of and versified by arthur brooke whose narrative poem tragicall historye of romeus and juliet written in was the source for shakespeares romeo and juliet
shakespeare enriched its texture through his vivid characterizations of both major and minor characters in particular the nurse and mercutio
the play begins with a prologue in the form of a sonnet
the speaker explains to the audience that the story concerns two warring families in verona italy and how the feud between them is ended in a manner which neither side could have wanted or expected
the action proper starts with a typical streetbrawl between the two families montague and capulet started by their servants and put down by the prince of verona
he fines the heads of both families and declares severe penalties including death for those who disturb the peace again
paris a nobleman talks to old capulet about marrying his daughter juliet
capulet demurs citing the girls youth
my child is yet a stranger in the world
she hath not seen the change of fourteen yearsparis persists arguing younger than she are happy mothers madecapulet asks him to attract the attention of juliet during a masquerade ball that he is hosting the next day
meanwhile juliets mother tries to persuade her daughter to accept pariss wooing during their coming ball
the question of juliets age is again raised as her mother echoing paris declares younger than you here in verona ladies of esteem are made already mothersjuliet does not desire marriage but being a dutiful daughter accedes to her mothers wishes
this scene also introduces juliets nurse a comedic character who recounts a bawdy anecdote about juliet punctuated with religious ejaculations
in the meantime old montague and his wife fret to their nephew benvolio about their son romeo who has long been moping for reasons unknown to them
benvolio promises montague that he will try to determine the cause
benvolio queries romeo and finds that his melancholy has its roots in his unrequited love for old capulets niece a girl named rosaline
benvolio tries to snap romeo out of his funk to no avail
despite the goodnatured taunts of his fellows including the witty nobleman mercutio romeo resolves to attend the masque at the capulet house relying on not being spotted in his costume in the hopes of meeting up with rosaline
romeo attends the ball as planned but he does not see rosaline and falls instead for juliet
tybalt juliets hotblooded cousin recognizes romeo under his disguise and calls for his sword
old capulet however speaks kindly of romeo and having resolved that his family will not be first to violate the princes decree sternly forbids tybalt from confronting romeo
tybalt stalks off in a huff
emboldened romeo risks his life by remaining on the capulet estate after the party breaks up to catch another glimpse of juliet at her room and in the famous balcony scene the two eloquently declare their love for each other
the young lovers decide to marry without informing their parents because they would undoubtedly disallow it due to the planned union between paris and juliet
with the help of juliets nurse and the franciscan priest friar lawrence the two are wedded days later
friar lawrence performs the ceremony hoping to bring the two families to peace with each other through their mutual union
things take a darker turn in the next act
tybalt still smarting from the incident at the capulets ball meets up with romeo and attempts to provoke a fight
romeo refuses to fight tybalt because they are now kinsmen although tybalt doesnt know it
mercutio who is also unaware of the marriage is incensed by tybalts actions and takes up the challenge himself
in the ensuing swordplay mercutio is fatally wounded by tybalt and romeo in his anger kills tybalt
although under the prince of veronas prior proclamation romeo would be subject to the death penalty the prince reduces romeos punishment to exile in light of the fact that tybalt had killed mercutio who was not only romeos friend but a relative of the prince
romeo flees to mantua
juliet is extremely grieved when she hears this and when she realizes that her father will force her to go through with the marriage to paris she seeks the help of friar lawrence once more
friar lawrence an expert in herbal medicines and potions gives juliet a potion and a plan
the potion will put her in a deathlike coma for two days
she is to take it before her marriage day and when discovered dead she will be laid in the family crypt
meanwhile the friar will send a messenger to inform romeo so that he can rejoin her when she awakes
the two can then leave for mantua and live happily ever after
juliet takes the potion and things proceed as planned
unfortunately the friars messenger is unable to reach romeo due to mantua being under quarantine and romeo learns only of juliets supposed death through a family servant
griefstricken he buys some strong poison returns to verona in secret and proceeds to the capulets crypt determined to join juliet in death
upon arrival he encounters paris who has also come to mourn privately for his lost love
after killing paris in a duel romeo drinks the poison after seeing juliet one last time
seconds later juliet awakens and sees romeo dead
juliet cannot imagine a rewarding life without romeo and so she stabs herself fatally with his dagger
the two lovers lie dead by each others sides madly in love and devoted until the last breath of life
all three are found dead shortly thereafter by a squire who runs off to alert others
as word spreads throughout verona about the deaths the two feuding families meet at the tomb with the prince
they are horrified to find romeo juliet and paris all lying dead and friar lawrence who has hurried to the crypt but is too late to prevent the tragedy reveals to them the love and secret marriage of romeo and juliet
the feuding families are reconciled by their childrens deaths and agree to end their violent feud as explained by the prologue 
in common with many of shakespeares plays the majority of romeo and juliet is written in iambic pentameter
however the play is also notable for its heavy use of rhymed verse especially in the sonnet contained in romeo and juliets dialogue in the scene where they first meet
this sonnet figures romeo as a pilgrim praying before an image of the the virgin mary as many persons in earlysixteenthcentury england did at shrines such as the shrine of our lady of walsingham because of its use of rhyme its extravagant expressions of love and its implausible plot romeo and juliet is considered to belong to shakespeares lyrical period along with the similarly poetic plays a midsummer nights dream and richard ii
romeo and juliet is one of the earlier works in the shakespearean canon and while it is often classified as a tragedy it does not bear the hallmarks of the great tragedies like hamlet and macbeth
some argue that romeo and juliets demise does not stem from their own individual flaws but from the actions of others or from accidents
unlike the great tragedies romeo and juliet is more a tragedy of mistiming and ill fate
however others consider rashness and youth to be the tragic flaws of romeo and juliet
it has been noted that the plot of romeo and juliet is more that of a farce or comedy of errors than a tragedy except that it lacks the vital lastminute save and everyone dies at the end instead of living happily ever after
however it can also be argued that not all is woe at the end
a longrunning feud is ended although at the price of the two lovers lives thus no doubt future deaths have been prevented
the play satirizes italy in shakespeares time attacking the catholic church 
largely to please queen elizabeth
and by making romeo marry a girl who was seen as scandalously young making a form of the modern redneck joke
macbeth is a tragedy by william shakespeare based loosely on the historical king macbeth of scotland
scholars think it an archetypal jacobean play with plenty of references to the reign of james i and place its composition around 
there is considerable evidence that the text of the play as we have it incorporates later revisions by thomas middleton which insert popular passages 
notably extra scenes involving the witches for such scenes proved highly popular with audiences from his own play the witch 
actors often consider this play to be unlucky and usually refer to it as the scottish play rather than by name
to say the name of the play inside a theatre is considered to doom the production to failure
on the stage lady macbeth is seen by many as one of the most challenging roles in western theater for women
she is driven mad for her part in the kings crimes and dies off stage in the final act
the play is one of shakespeares most popular worksas well as his shortest tragedyand is frequently performed at professional and community theatres around the world
it is seen as an archetypal tale of dangers of the lust for power macbeth thane of glamis has recently distinguished himself by killing the traitorous thane of cawdor who tried to rebel against duncan king of scotland
duncan decides to reward macbeth by awarding him cawdors lands and sends a messenger to tell macbeth the good news
at this time macbeth and his friend banquo are wandering along a heath where they meet three witches
the first witch greets macbeth as thane of glamis the second as thane of cawdor and the third tells him that he shall be king hereafterthe witches also inform banquo
thou shalt get kings though thou be nonemacbeth is confused at being called thane of cawdor until the messenger arrives and tells macbeth of his new title
immediately macbeth wonders whether the witches were also correct in predicting that he would become king
macbeth writes about the witches prophecies in a letter to his wife referred to only as lady macbeth
she immediately resolves that her husband will be king and moreover will do it by killing duncan
as luck would have it duncan is coming to stay in the macbeths castle that very night
in the dead of night macbeth and his lady kill duncan and arrange the bloody daggers to make it look like two servants committed the murder
duncans body is discovered by macduff another lord who is immediately suspicious of macbeth
however macbeth kills the two servants who ostensibly committed the crime and also insinuates that duncans sons malcolm and donalbain committed the murder
the princes flee scotland leaving the popular macbeth free to be crowned king
macbeth is still uneasy though
he is apparently childless 
although lady macbeth claims to have nursed a baby i have given suck and worries about the witches prophecy that banquo would be the father of kings
he hires three murderers to kill banquo and his son fleance
the murderers successfully kill banquo but fleance escapes
that night at the royal banquet banquos ghost enters and sits in macbeths place
macbeth is the only person who can see the ghost and frightens his guests with his display of terror and guilt
macbeth goes to the witches again and receives three more prophecies
the first to beware macduff the second that no man of woman borncan harm macbeth and the third that his reign is safe until birnam wood to high dunsinane hill shall come macduff has gone to england at this time leaving his wife and young son behind
since macbeth hates and fears macduff he sends the murderers to kill macduffs family
in england malcolm and macduff lament macbeths seizing of power and lay plans for an invasion of scotland
lady macbeth eventually goes mad with guilt for the crimes she has committed
in a famous scene she sleepwalks and tries to wash imaginary bloodstains off her hands
she eventually dies which causes macbeth to ruminate on the futility of life
meanwhile malcolm macduff and their army enter scotland
in order to camouflage themselves as they storm macbeths castle they cut branches from trees in birnam wood and hold them in front of their bodies
this fulfills the witches third prophecy
that macbeth will be in danger when birnam wood comes to dunsinane
macbeths army is defeated and macduff finds macbeth and engages him in single combat
macbeth boasts that he will surely win for none of woman born can harm him
macduff triumphantly announces that he was from his mothers wombuntimely ripped 
ie born by a caesarian section
and proceeds to kill macbeth
at plays end all rejoice in malcolms victory and hail him as king of scotland
macbeths visions
macbeth sees an imaginary bloody knife in the air pointing to king duncans resting chamber is this not a dagger which i see before me the hand toward my hand 
act ii scene i
macbeth knows what he is doing will change his life
committing regicide is a sin that cant be forgiven
macbeth may see this through the supernatural powers of the three witches or it may be another hallucination
lady macbeth believes there is blood on her hands that wont come off out damned spot
out i say
act scene 
lady macbeth here is sleepwalking and spot is being referred to as blood stained hands
lady macbeth cant cleanse herself of the guilt of plotting king duncans murder
blood and bloodshed
at the beginning of the play macbeths army has just defeated norwegian invaders in a gruesome battle
a captain in mortally wounded and the king remarks on it what bloody man is that
he can report as seemeth by his plight 
act i scene ii
the shedding of blood continues throughout the play until the very end when macbeth is slain by macduff hail king
for so thou art
behold where stands th usurpers cursed head
macduff then shows malcolm the new king macbeths head dripping with blood
blood can also be shown as representing guilt
when macbeth kills king duncan blood on his hand symbolizes guilt
later in the play lady macbeth believes that she sees blood on her hands
macbeth is seen as warning of the dangers of ambition showing that ambition can be a morally corrupting agent
however this theme is never stated outright but only implied
king lear is generally regarded as one of william shakespeares greatest tragedies
it is believed to have been written in and is based on the legend of llyr a king of preroman britain
his story had already been told in chronicles poems and sermons as well as on the stage when shakespeare undertook the task of retelling it
after the restoration the play was often modified by theatre practitioners who disliked its nihilistic flavour but since world war ii it has come to be regarded as one of shakespeares greatest achievements
the part of king lear has been played by many great actors but is generally considered a role to be taken on only by those who have reached an advanced age
king lear is ruler of britain
hes a patriarchal figure whose misjudgement of his daughters brings about his downfall
goneril is lears treacherous eldest daughter and wife to the duke of albany
regan is lears treacherous second daughter and wife to the duke of cornwall
cordelia poss heart of a lion 
is lears youngest daughter
the duke of albany is gonerils husband
goneril scorns him for his milky gentlenesshe turns against his wife later in the play
the duke of cornwall is regans husband
he has the earl of kent put in the stocks leaves lear out on the heath during a storm and gouges out gloucesters eyes
after his attack on gloucester one of his servants attacks and mortally wounds him
the earl of gloucester is edgars father and the father of the illegitimate son edmund
edmund deceives him against edgar and edgar flees taking on the disguise of tom of bedlam
the earl of kent is always faithful to lear but he is banished by the king after he protests against lears treatment of cordelia
he takes on a disguise and serves the king without letting him know his true identity
edmund is gloucesters illegitimate son
he works with goneril and regan to further his ambitions and the three of them form a romantic triangle
edgar is the legitimate son of the earl of gloucester
disguised as tom of bedlam he helps his blind father
at the end of the play he assumes reign of the kingdom
oswald is gonerils servant and is described as a serviceable villainhe tries to murder gloucester but is instead murdered by edgar
the fool is a jester who is devoted to lear and cordelia
he appears in act i scene four and disappears in act iii scene six
his final line is and ill go to bed at noon a line that many think might mean that he is to die at the highest point of his life when he lies in prison separated from his friends
the fool and cordelia never appear on stage together
it is likely that in original productions they were played by the same actor robin armin but some have also speculated that the characters themselves could be identical 
near the end of the play lear says and my poor fool is hanged a line which could refer to the fool but in context is more likely to refer to the hanged cordelia
assuming that cordelias frame was not too voluptious for her to conceal it beneath a tightfitting renaissance doublet
the play begins with the earl of gloucester commending his bastard son edmund to the earl of kent
thereafter we find king lear taking the decision to abdicate the throne and divide his kingdom equally between his three daughters
goneril regan and cordelia
the eldest two are married but cordelia is much sought after as a bride partly because she is her fathers favourite
however when lear attempts to auction off his kingdom to the most admiring and flattering of his daughters the plan backfires
cordelia refuses to outdo the flattery of her elder sisters she feels it would only cheapen her true feelings to flatter him purely for reward and lear in a fit of pique divides her share of the kingdom between goneril and regan and cordelia is banished
the king of france however sees value in her honesty and insists on wedding her even after she has been disinherited
almost as soon as lear abdicates the throne he finds that goneril and regan have betrayed him and arguments ensue
the earl of kent who has spoken up for cordelia and been banished for his pains returns disguised as the servant caius who will eat no fish in order to protect the king to whom he remains loyal
meanwhile goneril and regan fall out with one another over their attraction to edmund and are forced to deal with an army from france led by cordelia sent to restore lear to his throne
eventually goneril poisons regan over their differences and stabs herself when edmund is wounded
another subplot involves the earl of gloucester whose two sons the good edgar and the evil edmund are at loggerheads the bastard edmund having concocted false stories about his legitimate halfbrother
edgar is forced into exile affecting lunacy
edmund engages in liaisons with goneril and regan and gloucester is blinded by regans husband but is saved from death by edgar whose voice he fails to recognise
lear appears in dover where he wanders about raving and talking to mice
gloucester attempts to throw himself from a cliff but is deceived by edgar and comes off safely encountering the king shortly after
besides the subplot involving the earl of gloucester and his two sons the principal innovation shakespeare made to this story was the death of cordelia and lear at the end
during the eighteenth and nineteenth centuries this tragic ending was much criticised and alternative versions were written and performed in which the leading characters survived and edgar and cordelia were married
king llyr was a semilegendary king who reigned in cornwall and devonshire in presentday england
according to the historia britonum llyr may have been taken as a prisoner to rome and this traditional lore may be the origin of shakespeares play
lear may also be lir a god of the sea in celtic mythology
there lirs children include bran and mannanan eponymous creator of the isle of man
one of shakespeares sources was an earlier play king leir
in this play cordella and the king of france serve leir disguised as rustics
however the ancient folk tale of lear had existed in many versions prior to that and its likely that shakespeare was familiar with them
one of them is the historia regum britanniae by geoffrey of monmouth in the th century
shakespeares most important source is thought to be the second edition of the chronicles of england scotlande and irelande by raphael holinshed published in he name of cordelia was probably taken from edmund spensers the faerie queene published in 
spensers cordelia also dies from hanging as in king learther likely sources are a mirror for magistrates 
by john higgins
the malcontent 
by john marston
the london prodigal 
arcadia 
by sir philip sidney
montaignes essays which were translated into english by john florio in 
an historical description of iland of britaine by william harrison
remaines concerning britaine by william camden 
albions england by william warner 
and a declaration of egregious popish impostures by samuel harsnett 
the modern reader of king lear could benefit from the demystification of some subtleties in the text as shakespeare often brushes over details that are made clearer in his sources and were perhaps more familiar to elizabethan theatregoers than to modern ones
scene one features king lear testing the extent of his daughters loyalty and love for him
he is preparing to abdicate
lacking a male heir he decides to divide his land between the sisters and for two of them their husbands
he devises a test for them asking which of you shall we say doth love us most
this may strike us as somewhat senile because if lear has already made up his mind as to how the land is shared the trial appears pointless
on the other hand shakespeare may have intended lears statement 
which of you shall we say doth love us most
that we our largest bounty may extend where nature doth with merit challenge
to have been a mere formality or piece of rhetoric
shakespeare has overlooked 
purposely or absentmindedly
the crux of the situation which is that in another version 
the anonymous play the true chronicle history of king leir
cordelia has already vowed to marry for love not whoever her father should choose and lear assumes that his youngest daughter will play along with his game
on receiving her proclamations of devout love and loyalty he plans to force her into a marriage which she could not possibly object to after claiming such stolid obedience
of course the trap fails disastrously for all parties
it is not clear whether or not shakespeare intended his audience to be aware of this subtext or whether he assumed the details of the situation were not relevant
the adaptations that shakespeare made to the legend of king lear to produce his tragic version are quite telling of the effect they would have had on his contemporary audience
the story of king lear was familiar to the average elizabethan theatre goer 
as were many of shakespeares sources
and any discrepancies between versions would have been immediately apparent
shakespeares tragic conclusion gains its sting from such a discrepancy
the traditional legend and all adaptations preceding shakespeares have it that after lear is restored to the throne he remains there until made ripe for death 
edmund spencer
cordelia her sisters also deceased takes the throne as rightful heir but after a few years is overthrown and imprisoned by nephews leading to her suicide
shakespeare shocks his audience by bringing the worn and haggard lear onto the stage carrying his dead youngest daughter
he taunts them with the possibility that she may live yet with lear saying this feather stirs
she lives but cordelia is dead
this was indeed too bleak for some to take even many years later
king lear was at first unsuccessful on the restoration stage and it was only with nahum tates happyending version of that it became part of the repertory
tates lear where lear survives and triumphs and edgar and cordelia get married held the stage until 
samuel johnson endorsed the use of tates version in his edition of shakespeares plays 
cordelia from the time of tate has always retired with victory and felicity
and if my sensations could add anything to the general suffrage i might relate that i was many years ago so shocked by cordelias death that i know not whether i ever endured to read again the last scenes of the play till i undertook to revise them as an editor the character of lears fool important in the first act disappears without explanation in the third
a popular explanation for this is that the actor playing the fool also played cordelia
the two characters are never on stage simultaneously and dualroling was popular in shakespeares time
without going that far the play does ask us to at least compare the two
lear chides cordelia for foolishness in act i and chides himself as equal in folly in act v
a more elaborate suggestion is that cordelia never went to france but stayed behind disguised as lears fool serving her father in much the same manner as edgar served his father gloucester in the subplot
it has been suggested that cordelia was aided in this service by the king of france who was disguised as a servantknightgentleman
it has been objected that the fool was in lears service long before cordelia was dismissed and one of lears knights observes since my young lady cordelias going into france sir the fool hath much pined away the play hobsons choice by harold brighouse is a comic version which takes place in manchester in the s
this in turn has been adapted to film numerous times most notably by david lean in 
directed by andrew mccullough with orson welles as lear
this one does not feature the subplot of gloucester and his sons and has poor tom as a character in his own right
directed by grigori kozintsev with jri jrvet as lear music by dmitri shostakovich
what makes this movie unique is the original interpretation of the king lears character and plots clarity
it is considered one of the best adaptations of the tragedy by some critics
see at the internet movie database directed by peter brook with paul scofield as lear
the text has been severely cut and the remainder has been reassembled
all is bleak in this black and white existential experience
a live recorded performance directed by edwin sherin
directed by jonathan miller with michael hordern as lear
part of the shakespeare plays series this version follows the text closely
directed by michael elliott with laurence olivier as lear
the film begins and ends at stonehenge and features diana rigg as regan john hurt as the fool and robert lindsay as edmund
akira kurosawa adapted king lear for the basis of his film ran
jeanluc godards version is set in a postapocalyptic world with burgess meredith as gangster don learo and molly ringwald as cordelia
a modern retelling set on a farm in iowa was jane smileys a thousand acres
this novel attempted to explain the elder sisters hatred of their father was later adapted as a film directed by jocelyn moorhouse and starring jason robards jennifer jason leigh jessica lange michelle pfeiffer and colin firth
directed by richard eyre with ian holm as lear
and directed by brian blessed
patrick stewart played john lear in a television adaptation called king of texas set in frontier texas and directed by uli edel
while it has been claimed that cordelia derives from the latin cor 
followed by delia an anagram of ideal this is highly questionable
a more likely etymology is that her name is a feminine form of coeur de lion meaning lionhearted
another possible source is a welsh word of uncertain meaning
it may mean jewel of the sea or lady of the sea these titles are anachronistic
the first use of the title of duke of albany occurred in 
the first use of the title of duke of cornwall took place about 
the first use of the title of earl of gloucester took place in 
the first use of the title duke of kent was in 
the tragedy of hamlet prince of denmark is a tragedy by william shakespeare and one of his most wellknown and oftquoted plays
written between and the summer of this masterpiece of elizabethan theatre first appeared in print in in a version known as the bad quarto a pirated version with no authority
the authorised second quarto followed shortly after the first while a slightly altered and reduced version was published in the first folio of shakespeares complete works
see folios and quartos 
shakespeare
the text in modern editions is a compromise between the second quarto text and the folio text
in theatre hamlet is possibly the most often produced work in almost every western country and it is considered a crucial test for mature actors 
somewhat unfortunately since hamlet is supposed to be a young man
hamlets to be or not to be soliloquy 
act three scene one
the most popular passage of the play is so well known that it has become a stumblingblock for many modern actors
prince hamlet the title character is the son of the late king of denmark who was also named hamlet
he is charged by the ghost of his father to avenge his murder which he finally succeeds in doing but only after the rest of the royal house has been wiped out and he himself has been mortally wounded with a poisoned rapier by laertes
claudius is the current king of denmark hamlets uncle who succeeded to the throne upon the death of his brother
the ghost of king hamlet tells prince hamlet that he was murdered by brother claudius who poured hebenon in his ear while he was asleep
claudius is killed with a poisoned rapier by hamlet who for good measure also forces him to drink the wine with which he had intended to poison hamlet
king hamlet 
ghost
was hamlets father
at the start of the play he is not long dead
he appears to hamlet as a ghost and urges him to avenge his murder
he is referred to in the stage direction as ghost
king hamlet was killed by poison emptied into one of his ears
gertrude is hamlets mother the widow of king hamlet who became the wife of claudius a relationship considered incestuous in shakespeares time
she dies by drinking poisoned wine intended for hamlet
polonius is claudiuss chief councillor who is distrustful of hamlets relationship with ophelia
he is a fatuous bore and hamlet frequently teases him while pretending to be mentally unbalanced
he is fatally stabbed by hamlet while hidden behind an arras while trying to eavesdrop upon a conversation between hamlet and his mother
laertes is polonius son who kills hamlet with a poisoned rapier to avenge the deaths of polonius and ophelia
he is killed by hamlet with the same rapier although at the time hamlet did not realise it was poisoned
ophelia is polonius daughter
she and hamlet have had romantic feelings for each other although she and hamlet 
at least implicitly
have been warned that it would be politically inexpedient for them to marry
jilted by hamlet as part of his insanity ruse her fathers death causes her to actually go insane and she drowns herself possibly accidentally
horatio is a friend of hamlets from university
he is not directly involved in the intrigue among the royals which enables the author to use him as a foil or sounding board for hamlet
he is the most important character alive at the end of the play though he threatens to commit suicide
rosencrantz and guildenstern are old schoolfellows of hamlet who were summoned to the castle by claudius to keep a watch on hamlet
hamlet soon suspects that they are spies
though their roles in the play are relatively minor tom stoppard created a popular play and movie rosencrantz and guildenstern are dead in which the two title characters contemplate their roles as minor players in a bigger drama
they die offstage in england executed by the kings warrant for hamlets death altered by hamlet to name them
fortinbras is the norwegian crown prince who has only a couple of brief scenes in the play but who delivers its final lines and appears to represent the hope for a better future for the danish monarchy and its subjects
the play concerns the dilemma of prince hamlet whose father the erstwhile king of denmark died suddenly while hamlet was away at university
the kings brother claudius had himself proclaimed king and cemented his claim to the throne by marrying hamlets mother gertrude the widowed queen
hamlet expresses his anger at the accession of his uncle claudius and particularly with his mothers hasty remarriage
hamlet soon encounters the ghost of his dead father who informs him that he was murdered by claudius and commands hamlet to avenge him
hamlet then decides to put on an antic disposition 
act insane
in order to kill claudius but hamlet is unsure whether the ghost he has seen is truly his father and suspects that it might be the devil taking his fathers appearance in order to cause havoc
he therefore sets out to test the kings conscience through feigning insanity and by enlisting a traveling company to stage a play he has written reenacting the circumstances of the murder
the kings outrageous reaction to the performance convinces hamlet of his guilt
shortly afterwards claudius privately expresses his disgust at what he has done and offers up a prayer of repentance
hamlet discovers him at prayer and prepares to kill him but then stops reasoning that he does not want his revenge to have the result of sending the repentant claudius to heaven
in a double irony after hamlet slips away claudius concludes that he is unable to repent in his current state of mind
thus if hamlet had not attempted to arrogate to himself the destiny of claudiuss soul rather than just his life he would have gotten the ultimate justice he sought
hamlet confronts his mother about the murder of his father and her sexual relations with her new husband and during their conversation he stabs polonius the kings councillor who has been hiding behind a tapestry thinking it may have been the king
king hamlets ghost makes a reappearance to chastise hamlet for abusing his mother
the king who has realised that hamlet knows about the murder he committed sends hamlet to england with a message to the english ordering his death
on the way to england hamlets ship is attacked by pirates who take hamlet prisoner but then return him to denmark
meanwhile hamlets romantic partner ophelia goes mad having been already disturbed by hamlets feigned rejection of her and by the death of polonius her father
in what may have been a suicide attempt she falls into a river and drowns
hamlet returning from his voyage meets horatio in a graveyard outside elsinore just as ophelias funeral cortege arrives there
hamlet finds the skull of yorick and proclaims of it here hung those lips that i have kissed i know not how oft laertes son of polonius and brother of ophelia who is standing in an open grave when hamlet lands on top of him is determined to kill hamlet in revenge for the havoc that has been wreaked on his family
he and claudius engineer a scheme to kill hamlet while making the death look like an accident
to this end claudius instructs laertes to challenge hamlet to a fencing match
unknown to hamlet laertes will be fighting with a sharpened and poisoned foil instead of the customary blunted blade
in addition claudius prepares some poisoned wine for hamlet to drink as a toast in the event that laertes is unable to hit him
after hamlet wins the first two rounds of the match gertrude inadvertently drinks the poisoned wine
hamlet is pricked with the sword and fatally poisoned but in the ensuing brawl he swaps blades with laertes and deals a deep wound to laertes with the poisoned sword
gertrude dies from the poison and in his dying breaths laertes confesses the whole plot to hamlet
enraged hamlet kills claudius with the poisoned weapon finally avenging his fathers death
horatio horrified at the turn of events seizes the poisoned wine and proposes to join his friend in death but hamlet wrestles the cup away from him and orders him to tell the true story of the royal familys troubles to the world at large thus restoring hamlets good name
hamlet also recommends that the norwegian prince fortinbras be chosen as the rightful successor to the danish throne
hamlet dies and horatio mourns his passing
hamlet or amleth was a legendary danish prince 
whose exploits were recorded by saxo grammaticus in his gesta danorum around ad
francois de belleforest adapted saxos story in his histoires tragiques 
shakespeares main source however is believed to be an earlier play about hamlet 
the urhamlet
which is attributed to thomas kyd and is known to have introduced a ghost to the story
some scholars however believe that the urhamlet may have been written by shakespeare himself
shakespeare may also have taken some elements from kyds other play the spanish tragedy especially the heros procrastination
hamlet is possibly the most discussed and contentious character in the whole of world drama and indeed in the whole of western literature
while conceding he is one of shakespeares greatest creations critics are at loggerheads over the inner motivations and psyche of this character
his relationships with the various characters of the story including his father his uncle claudius his mother gertrude and his beloved ophelia have all been subjected to multiple speculations including modern psychological theories
critics as varied as goethe coleridge hegel nietzsche turgenev freud t
s eliot and asimov have written essays on him all with their own special insights
besides being shakespeares most demanding role 
with over lines
hamlet is also the most introspective
actors have traditionally struggled with this role and it can be safely said that any one performance can only capture some facets of the creation
the plot summary above presents the simplest view of hamlet as a person seeking truth in order to be certain that he is justified in carrying out the revenge called for by a ghost that claims to be the spirit of his father
the most standard view is that hamlet is highly indecisive
the movie with laurence olivier in the title role considered by many a standard is introduced by a voiceover
this is a story of a man who could not make up his mind others see hamlet as a person charged to carry out a duty that he both knows and feels he must do yet doesnt want to
in this view all of his efforts to satisfy himself of king claudius guilt or his failure to act when he can are evidence of this unwillingness and hamlet berates himself for his inability to carry out his task
after observing a playactor performing a scene he notes that the actor was moved to tears in the passion of the story and compares this passion for a fictional character hecuba in light of his own situation
othello
the moor of venice is a play by shakespeare written about 
othello is a tragedy like hamlet macbeth and king lear
shakespeare probably wrote othello after hamlet but before the latter two
the first recorded performance was on november at whitehall palace in london
the title character othello is a noble moor 
north african muslim
who commands an army in cyprus
he is presented sympathetically despite his race
this is unusual for english literature of shakespeares time which commonly depicted moors and other darkskinned peoples as villains
there is some controversy among scholars whether othello was meant to be black 
by todays standards of ethnicity
or arab or both though popular consensus among average readers and audiences today lean towards the former
shakespeare avoids any discussion of islam in the play
othello who has just eloped with desdemona when the play opens leaves venice to command the venetian armies in cyprus
when desdemona and cassio join othello in cyprus the treacherous standardbearer iago persuades othello that desdemona has been unfaithful to him with cassio
othello kills desdemona in anger
iagos wife emilia then reveals that desdemonas affair was an invention of iagos
iago kills emilia and othello commits suicide
cassio rules cyprus and iagos punishment is left for cassio to decide 
see also othello list of characters
the plot for othello was developed from giraldi cinthios hecatommithi which it follows closely
the only named character in cinthios story is disdemona 
greek for unfortunate
the other characters were identified only as the standardbearer the captain and the moorin the original the standardbearer lusts after disdemona and is spurred to revenge when she rejects him
shakespeare invented a new character roderigo who pursues the moors wife and is killed while trying to kill cassio
the moor in cinthios story never repents of murdering his wife and both he and the standardbearer escape venice and are killed only much later
cinthio also drew a moral 
which he placed in the mouth of the lady
that european women are unwise to marry the hotblooded uncontrollable males of other nations
shakespeare suppressed this observation
genetic engineering genetic modification and gene splicing 
once in widespread use but now deprecated
are terms for the process of manipulating genes in an organism usually outside of the organisms normal reproductive process
it often involves the isolation manipulation and reintroduction of dna into model organisms usually to express a protein
the aim is to introduce new characteristics to an organism to increase its usefulness such as increasing the yield of a crop species introducing a novel characteristic or producing a new protein or enzyme
examples are the production of human insulin through the use of modified bacteria and the production of new types of experimental mice like the oncomouse 
cancer for research through genetic redesign
since a protein is specified by a segment of dna called a gene future versions of that protein can be modified by changing the genes underlying dna
one way to do this is to isolate the piece of dna containing the gene precisely cut the gene out and then reintroduce the gene 
splice into a different dna segment
daniel nathans and hamilton smith received the nobel prize in physiology or medicine for their isolation of restriction endonucleases which are able to cut dna at specific sites
together with ligase which can join together fragments of dna restriction enzymes formed the initial basis of recombinant dna technology
genetic modification or genetic manipulation are claimed to be neutral and possibly more technically correct terms for what is claimed controversially to be genetic engineering
opponents question whether the concept of modification with its implications of progress are applicable here
many opponents of the use of the term genetic engineering argue the operations of genes in combination with cell biochemistry are rather poorly understood and sometimes lead to unexpected side effects
reluctance to recognize this field as engineering has become popular in the antiglobalization movement and safe trade movement and is also widely held by most green parties and the major parties of france and germany which have resisted any agricultural policy favoring genetically modified food
these groups tend to resist the label engineer as applied to such genetic modification most strongly
defenders of the term genetic engineering argue that animal husbandry and crop breeding are also forms of genetic engineering that use artificial selection instead of modern genetic modification techniques
it is politics they argue not economics or science that causes their work to be closely investigated and for different standards to apply to it than to other fields of engineering
these scientists however do not object to the term genetic modification as applied to what they do although it is sometimes used to deny them the status of professionals serving society in an ethical manner which is one implication of the term engineer
the term genetic engineering is sometimes informally abbreviated as genegineeringtransgenic organism is now the preferred term for genetically modified organisms with extragenome information as opposed to genetically engineered organisms
one of the best known applications of genetic engineering is genetically modified organisms 
there are potentially momentous biotechnology applications of gm for example oral vaccines produced naturally in fruit at very low cost
this represents however a spread of genetic modification to medical purposes and opens an ethical door to other uses of the technology to directly modify human genomes
these effects are often not traceable back to direct causes in the genome but rather in the environment or interaction of proteins
the means by which genes 
in fact dna strands that are assumed to have discrete effects
are detected and inserted are inexact including such means as coating gold particles with dna to be inserted and literally firing it at strands of target dna 
see gene gun
which is guaranteed to cause insertions in at least some random locations which can on rare occasion cause unplanned characteristics
similar objections apply to protein engineering and molecular engineering for use as drugs
however a single protein or a molecule is easier to examine for quality control than a complete genome and there are more limited claims made for the reliability of proteins and molecules than for the genomes of whole organisms
while protein and molecule engineers often times acknowledge the requirement to test their products in a wide variety of environments to determine if they pose dangers to life the position of many genetic engineers is that they do not need to do so since the outputs of their work are substantially the same as the original organism which was produced by the original genome
an extreme ambition of some groups is human enhancement via genetics eventually by artificial intelligence or molecular engineering
although a there has been a tremendous revolution in the biological sciences in the past twenty years there is still a great deal that remains to be discovered
the completion of the sequencing of the human genome as well as the genomes of most agriculturally and scientifically important plants and animals have increased the possibilities of genetic research immeasurably
expedient and inexpensive access to comprehensive genetic data has become a reality with billions of sequenced nucleotides already online and annotated
now that the rapid sequencing of arbitrarily large genomes has become a simple if not trivial affair a much greater challenge will be elucidating function of the extraordinarily complex web of interacting proteins dubbed the proteome that constitutes and powers all living things
genetic engineering has become the gold standard in protein research and major research process has been made using a wide variety of techniques including loss of function such as in a knockout experiment in which an organism is engineered to lack one or more genes
this allows the experimenter to analyze the defects caused by this mutation and can be considerably useful in unearthing the function of a gene
it is used especially frequently in developmental biology
a knockout experiment involves the creation and manipulation of a dna construct in vitro which in a simple knockout consists of a copy of the desired gene which has been slightly altered such as to cripple its function
the construct is then taken up by embryonic stem cells where the engineered copy of the gene replaces the organisms own gene
these stem cells are injected into blastocysts which are implanted into surrogate mothers
another method useful in organisms such as drosophila is to induce mutations in a large population and then screen the progeny for the desired mutation
a similar process can be used in both plants and prokaryotes
gain of function experiments the logical counterpart of knockouts
these are sometimes performed in conjunction with knockout experiments to more finely establish the function of the desired gene
the process is much the same as that in knockout engineering except that the construct is designed to increase the function of the gene usually by providing extra copies of the gene or attracting more frequent transcription
tracking experiments which seek to gain information about the localization and interaction of the desired protein
one way to do this is to replace the wildtype gene with a fusion gene which is a juxtaposition of the wildtype gene with a reporting element such as green fluorescent protein that will allow easy visualization of the products of the genetic modification
while this is a useful technique the manipulation can destroy the function of the gene creating secondary effects and possibly calling into question the results of the experiment
more sophisticated techniques are now in development that can track protein products without mitigating their function such as the addition of small sequences which will serve as binding motifs to monoclonal antibodies
proponents of genetic engineering argue that the technology is safe and that it is necessary in order to maintain food production that will continue to match population growth
however others argue that food distribution not production is the biggest problem citing that the population growth is actually a result of uneven distribution of food and wealth
others oppose genetic engineering on the grounds that genetic modifications may have unforeseen consequences both in the initially modified organisms and their environments
for example certain strains of maize have been developed that are toxic to plant eating insects 
however when those strains crosspolinated with other varieties of wild and domestic maize the relevant genes were passed on
this introduced a new gene into the gene pool of the maize population outside of the crop field
the ecological and environmental effects of transgenic plants are constantly being investigated
antigeneticengineering activists say that with current recombinant technology there is no way to ensure that genetically modified organisms will remain under control and the use of this technology outside of secure laboratory environments carries unacceptable risks for the future
some fear that certain types of genetically engineered crops will further reduce biodiversity in the cropland
herbicidetolerant crops will for example be treated with the relevant herbicide to the extent that there are no wild plants able to survive and plants toxic to insects will mean insectfree crops
this could result in declines in other wildlife eg birds which depend on weed seeds andor insects for food resources
farm scale studies in the uk found this to be the case with gm sugar beet and gm rapeseed but not with gm maize 
though in the last instance the nongm comparison maize crop had also been treated with environmentally damaging pesticides subsequently 
withdrawn from use in the eu
proponents of current genetic techniques as applied to food plants cite the benefits that the technology can have for example in the harsh agricultural conditions of third world countries
they say that with modifications existing crops would be able to thrive under the relatively hostile conditions providing much needed food to their people
proponents also like to cite golden rice a genetically engineered rice variety 
still under development
that contains elevated vitamin a levels
there is hope that this rice may alleviate vitamin a deficiency that contributes to the death of millions annually
proponents say that genetically engineered crops are not significantly different from those modified by nature or humans in the past and by extension are as safe or even safer than such methods
there is gene transfer between unicellular eukaryotes and prokaryotes
there have been no known genetic catastrophes as a result of this
in biology the genome of an organism is the whole hereditary information of an organism that is encoded in the dna 
or for some viruses rna
this includes both the genes and the noncoding sequences
the term was first coined in by hans winkler professor of botany at the university of hamburg
more precisely the genome of an organism is a complete dna sequence of one set of chromosomes
for example one of the two sets that a diploid individual carries in every somatic cell
when people say that the genome of a sexually reproducing species has been sequenced typically they are referring to a determination of the sequences of one set of autosomes and one of each type of sex chromosome which together represent both of the possible sexes
even in species that exist in only one sex what is described as a genome sequence may be a composite from the chromosomes of various individuals
in general use the phrase genetic makeup is sometimes used conversationally to mean the genome of a particular individual or organism
the study of the global properties of genomes of related organisms is usually referred to as genomics which distinguishes it from genetics which generally studies the properties of single genes or groups of genes
most biological entities more complex than a virus sometimes or always carry additional genetic material besides that which resides in their chromosomes
in some contexts such as sequencing the genome of a pathogenic microbe genome is meant to include this auxiliary material which is carried in plasmids
in such circumstances then genome describes all of the genes and noncoding dna that have the potential to be presentn vertebrates such as humans however genome carries the typical connotation of only chromosomal dna
so although human mitochondria contain genes these genes are not considered part of the genome
in fact mitochondria are sometimes said to have their own genome often referred to as the mitochondrial genome
note that a genome does not capture the genetic diversity or the genetic polymorphism of a species
for example the human genome sequence in principle could be determined from just half the dna of one cell from one individual
to learn what variations in dna underlie particular traits or diseases requires comparisons across individuals
this point explains the common usage of genome 
which parallels a common usage of gene
to refer not to any particular dna sequence but to a whole family of sequences that share a biological context
although this concept may seem counter intuitive it is the same concept that says there is no particular shape that is the shape of a cheetah
cheetahs vary and so do the sequences of their genomes
yet both the individual animals and their sequences share commonalities so one can learn something about cheetahs and cheetahness from a single example of either
genomes are more than the sum of an organisms genes and have traits that may be measured and studied without reference to the details of any particular genes and their products
researchers compare traits such as chromosome number chromosome size gene order codon usage bias and gccontent to determine what mechanisms could have produced the great variety of genomes that exist today
duplications play a major role in shaping the genome
duplications may range from extension of short tandem repeats to duplication of a cluster of genes and all the way to duplications of entire chromosomes or even entire genomes
such duplications are probably fundamental to the creation of genetic novelty
horizontal gene transfer is invoked to explain how there is often extreme similarity between small portions of the genomes of two organisms that are otherwise very distantly related
horizontal gene transfer seems to be common among many microbes
also eukaryotic cells seem to have experienced a transfer of some genetic material from their chloroplast and mitochondrial genomes to their nuclear chromosomes
the human genome project endeavoured to map the human genome down to the nucleotide or base pair level and to identify all the genes present in it
the billion project was founded in by the united states department of energy and the u national institutes of health and was expected to take years
due to widespread international cooperation and advances in the field of genomics 
especially in sequence analysis
as well as huge advances in computing technology a rough draft of the genome was finished in 
announced jointly by us president bill clinton and british prime minister tony blair on june 
two years earlier than planned  initiation of the project was the culmination of several years of work supported by the us department of energy in particular a feasibility workshop in and a subsequent detailed description of the human genome initiative in a report that led to the formal sanctioning of the initiative by the department of energy
this report stated boldly the ultimate goal of this initiative is to understand the human genome and knowledge of the human genome is as necessary to the continuing progress of medicine and other health sciences as knowledge of human anatomy has been for the present state of medicine
though leaders had already been considering technologies required for such an undertaking at least as early as 
eight years after the hgp was being initiated an identical quest was initiated separately with private venture capital by a company called celera genomics 
founded by craig venter
while the hgp was still being pursued
celera genomics used a newer albeit riskier technique called shotgun sequencing and proceeded at a faster pace and at a fraction of the cost of the taxpayerfunded project 
approximately billion of taxpayer dollars versus about million of private research funding
celera initially planned to patent all genes found unlike the gene sequences found by the original publiclyfunded hgp which are in line with the so called bermuda statement 
made freely available to the public hours a day
however celera later decided to release its findings to the public after president clinton announced that that the information could not be patented sending celeras stock plummeting and the nasdaq paticularly the biotech sector into a precipitous decline
the competition between the rivals proved to be very good for the project and they agreed to pool their data
on april a joint press release announced that the project had been successfully completed with of the genome sequenced with accuracy
although the working draft was announced in june it was not until february that celera and the hgp scientists published actual details of their drafts
special issues of nature 
which published the publiclyfunded projects scientific paper
and science 
which published celeras paper
contained descriptions of the methods used to produce the draft sequence as well as analysis of said sequence
these drafts are hoped to provide a scaffold of about of the genome upon which gaps can be closed
each draft sequence has been checked at least four to five times to increase depth of coverage or accuracy
approximately of the draft were highquality sequences the final version will have been checked eight to nine times giving an error rate of just in bases
the human genome project is one of a number of international genome projects in biology each aimed at sequencing the dna of a specific organism
while the human dna sequence offers the most tangible benefits important developments in biology and medicine are predicted as a result of the sequencing of model organisms including mice fruitflies zebrafish yeast nematodes and many microbial organisms and parasites
in october researchers of the hgp announced a new estimate of to genes in the human genome
previously to had been predicted while estimates at the start of the project reached up to as high as 
the goals of the original hgp were not only to determine all billion base pairs in the human genome with a minimal error rate but also to identify all the genes in this vast amount of data
this part of the project is still ongoing although a preliminary count indicates about genes in the human genome which is far fewer than predicted by most scientists
another goal of the hgp was to develop faster more efficient methods for dna sequencing and sequence analysis and the transfer of these technologies to industry
today the sequence of the human dna is stored in databases and is available for everyone on the internet
the u national center for bioinformatics 
and sister organizations in europe and japan
houses the genomic sequence along with sequences of known and hypothetical genes and proteins
other organizations such as the university of california santa cruz and ensembl present additional data and annotation and powerful tools for visualizing and searching through it
computer programs have been developed to analyse that data as the data itself is next to useless without interpretation
the process of identifying the boundaries of genes and other features in raw dna sequence is called annotation and is the domain of bioinformatics
while expert biologists make the best annotators such annotation proceeds slowly and computer programs are increasingly used to meet the highthroughput demands of genome sequencing projects
the best current technologies for annotation make use of statistical models that take advantage of parallels between dna sequences and human language using concepts from computer science such as formal grammars
all humans have unique genomic sequence as such the data published by the hgp does not represent the exact sequence of each and every individuals genome
it is the combined genome of a small number of anonymous donors
the hgp genome is a scaffold for future work in identifying differences between individuals
most of the current effort in identifying differences between individuals involves single nucleotide polymorphisms
clear practical results of the project emerged even before the work was finished
for example a number of companies such as myriad genetics started offering inexpensive and easy to administer genetic tests that can show predesposition to a variety of illnesses including breast cancer blood clotting cystic fibrosis liver diseases and many others
there are also many tangible benefits for biological scientists
for example a researcher investigating a certain form of cancer may have narrowed down his search to a particular gene
by visiting the human genome database on the worldwide web this researcher can examine what other scientists have written about this gene including its threedimensional structure its function
its evolutionary relationships to other human genes or to genes in mice or yeast or fruitflies possible detrimental mutations interactions with other genes body tissues in which this gene is activated diseases associated with this gene the list of datatypes is long one reason why bioinformatics is so challenging
the work on interpretation of genome data is still in its initial stages
in the future the knowledge gained by the understanding of the genome will boost the fields of medicine and biotechnology eventually leading to cures for cancer alzheimers disease and other diseases
on a more philosophical level the analysis of similarities between dna sequences from different organisms is opening new avenues in the study of evolution
in many cases evolutionary questions can now be framed in terms of molecular biology
indeed many major evolutionary milestones 
the emergence of the ribosome and organelles the development of embryos with body plans the vertebrate immune system
can be related to the molecular level
many questions about the similarities and differences between humans and our closest relatives 
the primates and indeed the other mammals
are expected to be illuminated by the data from this project