Introduction The Human Genome Project (HGP) is an international endeavor to understand the hereditary instructions that make each

of us unique. The initial goals of the project are to catalogue the 3 illion or so !"# ase pairs that makeup all of the $$ somatic chromosomes% the & and ' chromosomes and to find and identify the products of the ())%))) or so human genes. *t is% in essence% a study of +hat makes humans human. There are t+o very good online documents descri ing the techniques used in the HGP% ,Primer on -olecular Genetics, and ,To .no+ /urselves,. These documents can e vie+ed or do+nloaded from the /ak 0idge "ational 1a +e site /0"1 Tech 0esources . The genome is all the genetic material of a particular organism. 2hen +e speak of the human genome% +e mean the full complement of genetic material in a human cell. 3ven +ith five and a half illion unique individuals on the planet% the

differences from one genome to the ne4t are minute5 therefore +e speak a out the human genome as if there +ere only one. The genome is distri uted among $3 sets of chromosomes% +hich% in each of us% have een replicated since our conception. The source of our personal uniqueness% our full genome% is preserved in each of our ody6s several trillion cells.

"ormal Human -ale .aryotype

The t+o main forces ehind this project in the 7nited 8tates are the !epartment of 3nergy and the "ational *nstitute of Health. The main formative meeting for the HGP +as held in 8anta 9e% "e+ -e4ico in (:;<. *n (:;=% funding egan. *n (:;: the joint +orking group for the ethical% legal and social issues (318*) +as formed. The international (>?year Human Genome Project formally egan in /cto er (::). The human genome

+ill e completely sequenced y the year $))>. 8ince scientists from many different countries had already started +orking independently +ith genes that they +ere personally interested in%the chromosomes used in the study don6t come from just one individual% ut from individuals from every corner of the +orld. The original (>?year project is only the eginning. The ultimate goal is a molecular?level understanding of human development from em ryo to adult% +hy +e get diseases and +hy +e age. return to top Model Organisms in HGP 8cientists are also mapping and sequencing the genomes of a num er of ,model, organisms as +ell as humans. -odel organisms offer a great +ay to follo+ the inheritance of genes that are very similar to human genes through many generations in a relatively short time. There are several +e sites +hich update the progress of the sequencing efforts on model organisms as +ell as a collection of micro ial genomes. The Genome -onitoring Ta le updates monthly the sequencing activity on the human genome as +ell as a fe+ model organisms% this site also dynamically predicts the end date for these sequencing efforts ased on the current rates of

sequencing. The -agpie Genome 8equencing Project 1ist is a complete list of all organisms +ith genome sequencing activity. This site also indicates the progress on each genome% and provides links to sites +ith primary sequence and mapping information. The information presented in the follo+ing ta le +as a stracted from genetics te4t ooks and the Genome -onitoring Ta le . Genome 8equencing 3fforts in -odel /rganisms % se u DNA # of ence # of ( ge d Organism M mug shot chromosomes ne b (!anuar" s ) #$$%) Escherichia coli ( @= ()) 3%))) ( acterium) Saccharomyces cerevisae (< ($ ()) <%))) (yeast) Caenorhabditis < := ()) A elegans

(nematode) Arabidopsis thaliana (#ra idopsis) Drosophila melanogaster (fruit fly) Fugu rubripes (puffer fish) Mus musculus (mouse) Homo sapiens sapiens (human) return to top Genome Ma&&ing # primary goal of the Human Genome Project is to make a series of descriptive maps of each human chromosome at increasingly finer resolutions. (: C &D' 3%)>: (.= B;)%))) @ (3> ()) A () ((; ()) B>)%)))

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-apping involves (() dividing the chromosomes into smaller fragments that can e propagated and characteriFed and ($) ordering the fragments to correspond to their respective locations on the chromosomes. #dditionally% the project researchers +ill e improving the instruments and techniques used in mapping and sequencing the genome% along +ith automating methods and optimiFing techniques used to e4tract information from maps and sequences. There are t+o types of maps. The first is a genetic map% also called a linkage map% +hich sho+s the relative locations of specific !"# markers along the chromosome. #ny inherited physical or molecular characteristic that differs among individuals and is easily detecta le is a potential genetic marker.-arkers can e e4pressed !"# regions (genes) or !"# segments that have no kno+n coding function ut +hose inheritance pattern can e follo+ed. !"# sequence differences are especially useful markers ecause they are plentiful and easy to characteriFe precisely. The second type of map is a physical map. !ifferent types of physical maps vary in their degree of resolution. The lo+est resolution physical map is the

chromosomal or cytogenetic map% +hich is ased on the anding patterns of stained chromosomes o served through a light microscope. # c!"# map sho+s the locations of e4pressed !"# regions (e4ons) on the chromosomal map. The more detailed cosmid contig map depicts the order of overlapping !"# fragments spanning the genome. # macro restriction map descri es the order and distance et+een enFyme cleavage sites. The highest? resolution physical map is the complete !"# ase pair sequence of each chromosome. Greating a cytogenetics map is like creating a map sho+ing the @; states5 c!"# and cosmid maps +ould e like +riting the names of the to+ns and cities5 and sequencing the asepairs is equivalent to filling in the names of the streets. return to top Mutations #nother +ay that scientists are studying the genes is y studying the proteins for +hich these genes code. The ,central dogma, of genetics% !"# directs 0"# to protein% is rapidly changing to ,sequence implies structure% structure implies

function., Gomputers no+ analyFe the structure of proteins% determining ho+ they fold% and their functions. This data is then used to find the gene in the chromosome. There are a out @%))) hereditary diseases that seem to e caused y a defect in a single gene some+here in the genome. #lthough it is not al+ays the same defect ? it could e an addition% a deletion% ora repeat of one or more ase pairs ? it is a defect in just one gene. The sequence of ase pairs is different from ,normal., 9or instance% the cystic fi rosis gene is a $>)%))) ase pair gene and the only thing different from disease?causing and normal genes is that one ase pair triplet is missing out of the middle.

"ormal 8trand of !"# 8trand of !"#

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#lthough researchers still look for a single gene that could e the cause of a pro lem% emphasis is no+ eing placed on more comple4 diseases% like heart disease% cancer% psychiatric disorders% and dia etes% +here there are almost surely multiple genes involved. 2hile the initial thrust of the genome project is to sequence and identify genes% researchers are already gearing up to use this information in the study of diseases. #s the HGP continues% genes involved in various diseases +ill e found% and it +ill e determined ho+ greatly those genes contri ute to the diseases.-edical practices +ill e radically altered +hen po+erful ne+ clinical technologies ased on !"# diagnostics are com ined +ith information emerging from genome maps. 3mphasis +ill shift from treatment to prevention. 0esearchers +ill e a le to identify individuals predisposed to particular diseases and +ill devise therapeutic regimens ased on ne+ classes of drugs% immunotherapy techniques% avoidance of environmental conditions that may trigger disease% and% possi ly% replacement of defective genes through gene therapy.

# percentage of the HGP research monies has een set aside to fund studies on the ethical% legal% and social issues (318*) that arise during the project. !iscussion% education% and legislation are the results from 318*.
Human Genome Project
Human Genome Project, international scientific effort to map all of the genes on the 23 pairs of human chromosomes and, to sequence the 3.1 billion DNA base pairs that make up the chromosomes (see nucleic acid). egun in 1!!" #ith the goal of enabling scientists to understand the basis of genetic diseases and to gain insight into human e$olution, the pro%ect #as largel& completed in 2""" #hen '() of the human genome #as decoded, and ended in 2""3 #ith !!) decoded* detailed anal&ses of all the pairs #ere published b& 2""+. ,n the process, scientists identified genes for c&stic fibrosis, neurofibromatosis, -untington.s disease, and an inherited form of breast cancer. ,n addition, the pro%ect decoded the genome of the bacterium E. coli, a fruit fl&, and a nematode #orm (see ph&lum Nematoda), in order to stud& genetic similarities among species, and a mouse genome #as also decoded. /he -uman 0enome 1ro%ect in$ol$ed laboratories in the 2nited 3tates, 4rance, 0reat ritain, 0erman&, and 5apan. ,t #as financed in the 2nited 3tates b& the National ,nstitutes of -ealth and b& the Department of 6nerg& and in 0reat ritain b& the 7ellcome /rust of 8ondon. A comparable pro%ect using ne# DNA (genetic material) sequencing machines #as begun as a pri$ate industr& $enture in the 2nited 3tates in 1!!', #ith a stated goal of completing the mapping of the genome in three &ears. 6arl& in 2""1 scientists from both teams %ointl& announced the 9completion: of the mapping of the human genome, indicating that the& had identified an estimated 3",""" genes (instead of the e;pected 1"","""), constituting %ust 1) of the total human DNA. 3ubsequent comparison of the t#o teams. data has indicated that, because of differences in the genes identified b& the teams, there ma& in fact be as man& as <",""" human genes. A subsequent, more refined estimate (2""<) based on additional #ork on the genome #as that there are bet#een 2",""" and 2(,""" genes. 7ork continues on further refining the sequencing of the genes on the chromosomes, eliminating the remaining gaps in the genome map, and identif&ing the e;tent of $ariation in the human genome. ,n 2""= the first sequences of human

indi$iduals (5ames D. 7atson and 5. >raig ?enter, #ho led the public and pri$ate human genome sequencing efforts, respecti$el&) #ere released. /he N,-.s National >enter for iotechnolog& ,nformation maintains 0en ank, a database of publicl& a$ailable genetic sequences from the genomes of plants and animals, including some e;tinct species.
7hether bacterium or human, the genome of an& organism to too large to be deciphered in one go. /he genome is therefore broken into smaller pieces of DNA, each piece is sequenced and computers fit all the sequences back together.

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1 of 8 /he human chromosome to be sequenced.

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2 of 8 /he chromosome is first chopped randoml& into con$enientl& si@ed chunks.

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3 of 8 /hese large fragments are inserted into bacterial artificial chromosomes ( A>s) and cloned in bacteria.

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4 of 8 /hese fragments are then mapped so it is kno#n #hich region of the chromosome the& came from.

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5 of 8 6ach A> is shotgunned A broken randoml& into man& small pieces. /his process is repeated se$eral times to gi$e different sets of fragments. (/he #holeAgenome shotgun method goes directl& to this stage.)

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6 of 8 /he fragments are cloned in small $ectors and then sequenced. About ("" bases of sequence information is produced from each fragment.

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7 of 8 /he sequences are fed into a computer, #hich looks for o$erlaps at the end of the sequence to find neighbouring fragments.

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8 of 8 7hen man& fragments ha$e been sequenced the sequence of the original A> insert can be assembled. /he process is carried out for all the A>s to gi$e a complete chromosomal sequence. 4or e;ample, the human genome is about 3 billion base pairs, arra&ed in 2< chromosomes. /he chromosomes themsel$es are ("B2(" million bases (megabases) long. /hese tracts of DNA are much too large for e$en the latest automated machines, #hich sequence fragments of DNA bet#een <"" and ="" bases long. /he genome is first broken into con$enientl& si@ed chunks, fragments of about 1(" kilobases. 6ach fragment is inserted into a bacterial artificial chromosome ( A>), a cloning $ector used to propagate DNA in bacteria gro#n in culture. /he A>s are then mapped, so that it is kno#n e;actl& #here the inserts ha$e come from. /his process makes reAassembling the sequenced fragments to reflect their original position in the genome easier and more accurate, and an& one piece of human DNA sequence can automaticall& be placed to an accurac& of 1 part in 3" """. 6ach of the large clones is then .shotgunned. A broken into pieces of perhaps 1("" base pairs, either b& en@&mes or b& ph&sical shearing A and the fragments are sequenced separatel&. 3hotgunning the original large clone randoml& se$eral times ensures that some of the fragments #ill o$erlap* computers then anal&se the sequences of these small fragments, looking for end sequences that o$erlap A indicating neighbouring fragments A and assembling the original sequence of the clone. An alternati$e approach, .#hole genome shotgun sequencing., #as first used in 1!'2 b& the in$entor of shotgun sequencing, 4red 3anger, #hile #orking on phages ($iruses of bacteria). As its name suggests, in this technique the #hole genome is broken into small fragments that can be sequenced and reassembled. /his method is $er& useful for organisms #ith smaller genomes, or #hen a related genome is alread& kno#n.

What i the Human Genome Project an! ho" !oe it re#ate to the i!entification an! treatment of $irth !efect % /he -uman 0enome 1ro%ect, #hich began in 1!!", is a go$ernment funded pro%ect to map all of the human genes (3",""" total) on the <+ chromosomes. After the atomic bomb #as de$eloped and used, the 23 >ongress charged the Department of 6nerg& to stud& and anal&@e the effects of b&A products of radiation such as those caused b& the atomic bomb. ,t #as determined that the best #a& to do this #as to anal&@e the entire human genome. ,n con%unction #ith the National

,nstitutes of -ealth (N,-), the follo#ing goals #ere setC /o identif& all genes in human DNA. /o determi ne the sequenc es of the three billion chemica l base pairs that make up human DNA and store this informat ion in databas es. /o de$elop tools for data anal&sis .

/o address the

ethical, legal, and social issues (683,) that ma& arise from the pro%ect. Although kno#ing the location of all of the human genes on the chromosomes is a monumental achie$ement, there is much more #ork to do before this information can be used to diagnose, treat, or predict the occurrence of disease. /herefore, the completion of this pro%ect #ill not automaticall& mean that there #ill be testing for all diseaseA causing genes, and that #e #ill suddenl&

kno# all causes of birth defects. -o#e$er, the hope is that the -uman 0enome 1ro%ect #ill e$entuall& lead to the abilit& to test for more causes of birth defects, and #ill allo# scientists and ph&sicians to better understand the causes of birth defects. ,n time, the role that multiple genes pla& in causing birth defects should be better understood, #ith the possibilit& of de$eloping treatments or pre$ention strategies.