Editing Human genome (section)

== Sequencing ==
{{main|Human Genome Project}}

The first human [[Genome#Sequencing and mapping|genome sequences]] were published in nearly complete draft form in February 2001 by the [[Human Genome Project]]<ref>{{cite web | url = https://www.genome.gov/10002192 | title = International Human Genome Sequencing Consortium Publishes Sequence and Analysis of the Human Genome | work = National Human Genome Research Institute | publisher = National Institutes of Health, U.S. Department of Health and Human Resources | date = 12 February 2001 }}</ref> and [[Celera Corporation]].<ref name="Celera2001">{{cite journal | vauthors = Pennisi E | author-link = Elizabeth Pennisi | title = The human genome | journal = Science | volume = 291 | issue = 5507 | pages = 1177–1180 | date = February 2001 | pmid = 11233420 | doi = 10.1126/science.291.5507.1177 | s2cid = 38355565 }}</ref> Completion of the Human Genome Project's sequencing effort was announced in 2004 with the publication of a draft genome sequence, leaving just 341 gaps in the sequence, representing highly repetitive and other DNA that could not be sequenced with the technology available at the time.<ref name="IHSGC2004" /> The human genome was the first of all vertebrates to be sequenced to such near-completion, and as of 2018, the diploid genomes of over a million individual humans had been determined using [[next-generation sequencing]].<ref>{{cite magazine | vauthors = Molteni M | date=19 November 2018 | title=Now You Can Sequence Your Whole Genome For Just $200 | magazine=Wired |url=https://www.wired.com/story/whole-genome-sequencing-cost-200-dollars/}}</ref>

These data are used worldwide in [[biomedical science]], [[biological anthropology|anthropology]], [[Forensic DNA|forensics]] and other branches of science. Such genomic studies have led to advances in the diagnosis and treatment of diseases, and to new insights in many fields of biology, including [[human evolution]].{{citation needed|date=March 2023}}

By 2018, the total number of genes had been raised to at least 46,831,<ref>{{cite journal | journal= Science News | title=A recount of human genes ups the number to at least 46,831 | vauthors = Saey TH | date=17 September 2018| url=https://www.sciencenews.org/article/recount-human-genes-ups-number-least-46831}}</ref> plus another 2300 [[micro-RNA]] genes.<ref>{{cite journal | vauthors = Alles J, Fehlmann T, Fischer U, Backes C, Galata V, Minet M, Hart M, Abu-Halima M, Grässer FA, Lenhof HP, Keller A, Meese E | title = An estimate of the total number of true human miRNAs | journal = Nucleic Acids Research | volume = 47 | issue = 7 | pages = 3353–3364 | date = April 2019 | pmid = 30820533 | doi = 10.1093/nar/gkz097 | pmc = 6468295 }}</ref> A 2018 population survey found another 300 million bases of human genome that was not in the reference sequence.<ref name="divers">{{cite journal |journal=The Atlantic|title= 300 Million Letters of DNA Are Missing From the Human Genome | vauthors = Zhang S | date=28 November 2018}}</ref> Prior to the acquisition of the full genome sequence, estimates of the number of human genes ranged from 50,000 to 140,000 (with occasional vagueness about whether these estimates included non-protein coding genes).<ref>{{cite news | title=Number of Human Genes Is Put at 140,000, a Significant Gain | date= 23 September 1999 | vauthors = Wade N | journal=The New York Times | url=https://archive.nytimes.com/www.nytimes.com/library/national/science/092399sci-human-genome.html}}</ref> As genome sequence quality and the methods for identifying protein-coding genes improved,<ref name="IHSGC2004">{{cite journal | author = International Human Genome Sequencing Consortium | title = Finishing the euchromatic sequence of the human genome | journal = Nature | volume = 431 | issue = 7011 | pages = 931–945 | date = Oct 2004 | pmid = 15496913 | doi = 10.1038/nature03001 | bibcode = 2004Natur.431..931H | doi-access = free }}</ref> the count of recognized protein-coding genes dropped to 19,000–20,000.<ref>{{cite journal | vauthors = Ezkurdia I, Juan D, Rodriguez JM, Frankish A, Diekhans M, Harrow J, Vazquez J, Valencia A, Tress ML | title = Multiple evidence strands suggest that there may be as few as 19,000 human protein-coding genes | journal = Human Molecular Genetics | volume = 23 | issue = 22 | pages = 5866–5878 | date = November 2014 | pmid = 24939910 | pmc = 4204768 | doi = 10.1093/hmg/ddu309 }}</ref>

In 2022, the Telomere-to-Telomere (T2T) consortium reported the complete sequence of a human female genome,<ref name="Complete"/> filling all the gaps in the [[X chromosome]] (2020) and the 22 autosomes (May 2021).<ref name="Complete"/><ref name="NatureMile">{{cite journal | vauthors = Wrighton K | title = Filling in the gaps telomere to telomere |journal=Nature Milestones: Genomic Sequencing |date=February 2021 |page=S21 |url=https://www.nature.com/articles/d42859-020-00117-1}}</ref> The previously unsequenced parts contain [[immune response]] genes that help to adapt to and survive infections, as well as genes that are important for predicting [[drug response]].<ref name="cnn">{{cite web | url =https://edition.cnn.com/2022/03/31/health/first-complete-human-genome-sequence/index.html |title=Scientists sequence the complete human genome for the first time|work=CNN| date=31 March 2022| accessdate =1 April 2022}}</ref> The completed human genome sequence will also provide better understanding of human formation as an individual organism and how humans vary both between each other and other species.<ref name="cnn"/>

Although the 'completion' of the human genome project was announced in 2001,<ref name="IHSGC2001">{{cite journal | vauthors = Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann Y, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blöcker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowki J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ, Szustakowki J | title = Initial sequencing and analysis of the human genome | journal = Nature | volume = 409 | issue = 6822 | pages = 860–921 | date = February 2001 | pmid = 11237011 | doi = 10.1038/35057062 | doi-access = free | bibcode = 2001Natur.409..860L | hdl = 2027.42/62798 | hdl-access = free }}</ref> there remained hundreds of gaps, with about 5–10% of the total sequence remaining undetermined. The missing genetic information was mostly in repetitive [[Heterochromatin|heterochromatic]] regions and near the [[centromere]]s and [[telomere]]s, but also some gene-encoding [[Euchromatin|euchromatic]] regions.<ref>{{Cite web|url=https://www.theatlantic.com/science/archive/2018/11/human-genome-300-million-missing-letters-dna/576481/|title=300 Million Letters of DNA Are Missing From the Human Genome| vauthors = Zhang S |date=28 November 2018|website=The Atlantic|language=en-US|access-date=2019-08-16}}</ref> There remained 160 euchromatic gaps in 2015 when the sequences spanning another 50 formerly unsequenced regions were determined.<ref name="Chaisson">{{cite journal | vauthors = Chaisson MJ, Huddleston J, Dennis MY, Sudmant PH, Malig M, Hormozdiari F, Antonacci F, Surti U, Sandstrom R, Boitano M, Landolin JM, Stamatoyannopoulos JA, Hunkapiller MW, Korlach J, Eichler EE | title = Resolving the complexity of the human genome using single-molecule sequencing | journal = Nature | volume = 517 | issue = 7536 | pages = 608–611 | date = January 2015 | pmid = 25383537 | pmc = 4317254 | doi = 10.1038/nature13907 | author-link12 = John Stamatoyannopoulos | bibcode = 2015Natur.517..608C }}</ref> Only in 2020 was the first truly complete telomere-to-telomere sequence of a human chromosome determined, namely of the [[X chromosome]].<ref name=":1">{{cite journal | vauthors = Miga KH, Koren S, Rhie A, Vollger MR, Gershman A, Bzikadze A, Brooks S, Howe E, Porubsky D, Logsdon GA, Schneider VA, Potapova T, Wood J, Chow W, Armstrong J, Fredrickson J, Pak E, Tigyi K, Kremitzki M, Markovic C, Maduro V, Dutra A, Bouffard GG, Chang AM, Hansen NF, Wilfert AB, Thibaud-Nissen F, Schmitt AD, Belton JM, Selvaraj S, Dennis MY, Soto DC, Sahasrabudhe R, Kaya G, Quick J, Loman NJ, Holmes N, Loose M, Surti U, Risques RA, Graves Lindsay TA, Fulton R, Hall I, Paten B, Howe K, Timp W, Young A, Mullikin JC, Pevzner PA, Gerton JL, Sullivan BA, Eichler EE, Phillippy AM | title = Telomere-to-telomere assembly of a complete human X chromosome | journal = Nature | volume = 585 | issue = 7823 | pages = 79–84 | date = September 2020 | pmid = 32663838 | pmc = 7484160 | doi = 10.1038/s41586-020-2547-7 | bibcode = 2020Natur.585...79M | author-link = Karen Miga }}</ref> The first complete telomere-to-telomere sequence of a human autosomal chromosome, [[chromosome 8]], followed a year later.<ref>{{cite journal | vauthors = Logsdon GA, Vollger MR, Hsieh P, Mao Y, Liskovykh MA, Koren S, Nurk S, Mercuri L, Dishuck PC, Rhie A, de Lima LG, Dvorkina T, Porubsky D, Harvey WT, Mikheenko A, Bzikadze AV, Kremitzki M, Graves-Lindsay TA, Jain C, Hoekzema K, Murali SC, Munson KM, Baker C, Sorensen M, Lewis AM, Surti U, Gerton JL, Larionov V, Ventura M, Miga KH, Phillippy AM, Eichler EE | title = The structure, function and evolution of a complete human chromosome 8 | journal = Nature | volume = 593 | issue = 7857 | pages = 101–107 | date = May 2021 | pmid = 33828295 | pmc = 8099727 | doi = 10.1038/s41586-021-03420-7 | bibcode = 2021Natur.593..101L }}</ref> The complete human genome (without Y chromosome) was published in 2021, while with Y chromosome in January 2022.<ref name="Complete"/><ref name=":3">{{Cite web|title=CHM13 T2T v1.1 – Genome – Assembly – NCBI|url=https://www.ncbi.nlm.nih.gov/assembly/GCA_009914755.3|access-date=2021-07-26|website=www.ncbi.nlm.nih.gov}}</ref><ref>{{Cite web|title=Genome List – Genome – NCBI|url=https://www.ncbi.nlm.nih.gov/genome/browse/#!/eukaryotes/51/|access-date=2021-07-26|website=www.ncbi.nlm.nih.gov}}</ref>

In 2023, a draft human [[pan-genome|pangenome]] reference was published.<ref name="2023-human-pangenome-47"/> It is based on 47 genomes from persons of varied ethnicity.<ref name="2023-human-pangenome-47"/> Plans are underway for an improved reference capturing still more biodiversity from a still wider sample.<ref name="2023-human-pangenome-47"/>