View source for Biology:1000 Genomes Project

{{short description|International research effort on genetic variation}}
The '''1000 Genomes Project''' ('''1KGP'''), taken place from January 2008 to 2015, was an international research effort to establish the most detailed catalogue of [[Biology:Human genetic variation|human genetic variation]] at the time. Scientists planned to [[Biology:DNA sequencing|sequence]] the [[Biology:Genome|genome]]s of at least one thousand anonymous healthy participants from a number of different ethnic groups within the following three years, using advancements in [[Biology:DNA sequencing#Next-generation methods|newly developed technologies]]. In 2010, the project finished its pilot phase, which was described in detail in a publication in the journal ''Nature''.<ref name="Pilot phase">{{cite journal | vauthors = Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA | display-authors = 6 | title = A map of human genome variation from population-scale sequencing | journal = Nature | volume = 467 | issue = 7319 | pages = 1061–73 | date = October 2010 | pmid = 20981092 | pmc = 3042601 | doi = 10.1038/nature09534 |  bibcode = 2010Natur.467.1061T | author-link1 = Richard M. Durbin }}</ref> In 2012, the sequencing of 1092 genomes was announced in a ''Nature'' publication.<ref name="nature.com">{{cite journal | vauthors = Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA | display-authors = 6 | title = An integrated map of genetic variation from 1,092 human genomes | journal = Nature | volume = 491 | issue = 7422 | pages = 56–65 | date = November 2012 | pmid = 23128226 | pmc = 3498066 | doi = 10.1038/nature11632 | bibcode = 2012Natur.491...56T }}</ref>  In 2015, two papers in ''Nature'' reported results and the completion of the project and opportunities for future research.<ref>{{cite journal | vauthors = Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR | display-authors = 6 | title = A global reference for human genetic variation | journal = Nature | volume = 526 | issue = 7571 | pages = 68–74 | date = October 2015 | pmid = 26432245 | pmc = 4750478 | doi = 10.1038/nature15393 | bibcode = 2015Natur.526...68T }}</ref><ref>{{cite journal | vauthors = Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, Zhang Y, Ye K, Jun G, Fritz MH, Konkel MK, Malhotra A, Stütz AM, Shi X, Casale FP, Chen J, Hormozdiari F, Dayama G, Chen K, Malig M, Chaisson MJ, Walter K, Meiers S, Kashin S, Garrison E, Auton A, Lam HY, Mu XJ, Alkan C, Antaki D, Bae T, Cerveira E, Chines P, Chong Z, Clarke L, Dal E, Ding L, Emery S, Fan X, Gujral M, Kahveci F, Kidd JM, Kong Y, Lameijer EW, McCarthy S, Flicek P, Gibbs RA, Marth G, Mason CE, Menelaou A, Muzny DM, Nelson BJ, Noor A, Parrish NF, Pendleton M, Quitadamo A, Raeder B, Schadt EE, Romanovitch M, Schlattl A, Sebra R, Shabalin AA, Untergasser A, Walker JA, Wang M, Yu F, Zhang C, Zhang J, Zheng-Bradley X, Zhou W, Zichner T, Sebat J, Batzer MA, McCarroll SA, Mills RE, Gerstein MB, Bashir A, Stegle O, Devine SE, Lee C, Eichler EE, Korbel JO | display-authors = 6 | title = An integrated map of structural variation in 2,504 human genomes | journal = Nature | volume = 526 | issue = 7571 | pages = 75–81 | date = October 2015 | pmid = 26432246 | pmc = 4617611 | doi = 10.1038/nature15394 | bibcode = 2015Natur.526...75. }}</ref>

Many rare variations, restricted to closely related groups, were identified, and eight structural-variation classes were analyzed.<ref>{{cite news | url=http://www.nature.com/news/variety-of-life-1.18454 | title=Variety of life | work=Nature News & Comment | date=2015-09-30 | access-date=2015-10-15 }}</ref>

The project united multidisciplinary research teams from institutes around the world, including {{wipe|China}}, Italy, {{wipe|Japan}}, Kenya, Nigeria, Peru, the {{wipe|United Kingdom}}, and the {{wipe|United States}} contributing to the sequence dataset and to a refined [[Biology:Human Genome Project|human genome map]] freely accessible through public databases to the scientific community and the general public alike.<ref name="nature.com"/>

The International Genome Sample Resource was created to host and expand on the data set after the project's end.<ref>{{Cite web |date=2020-07-07 |title=1000 Genomes Project {{!}} Scientific Computing and Data |url=https://labs.icahn.mssm.edu/minervalab/resources/data-ark/1000-genomes/ |access-date=2023-10-01 |website=Mount Sinai School of Medicine}}</ref>

[[Image:Genetic Variation.jpg|thumb|400px|Changes in the number and order of genes (A-D) create genetic diversity within and between populations.]]

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== Background ==
Since the completion of the [[Biology:Human Genome Project|Human Genome Project]] advances in human [[Biology:Population genetics|population genetics]] and [[Biology:Comparative genomics|comparative genomics]] enabled further insight into genetic diversity.<ref name=neilsen2012>{{cite journal | vauthors = Nielsen R | title = Genomics: In search of rare human variants | journal = Nature | volume = 467 | issue = 7319 | pages = 1050–1 | date = October 2010 | pmid = 20981085 | doi = 10.1038/4671050a | doi-access = free | bibcode = 2010Natur.467.1050N }}</ref> The understanding about [[Biology:Mutation|structural variations]] (insertions/deletions ([[Biology:Indel|indel]]s), copy number variations (CNV), retroelements), [[Biology:Single-nucleotide polymorphism|single-nucleotide polymorphism]]s (SNPs), and [[Biology:Natural selection|natural selection]] were being solidified.<ref name="ref2">JC Long, Human Genetic Variation: The mechanisms and results of microevolution, American Anthropological Association (2004)</ref><ref name="ref3">{{cite journal | vauthors = Anzai T, Shiina T, Kimura N, Yanagiya K, Kohara S, Shigenari A, Yamagata T, Kulski JK, Naruse TK, Fujimori Y, Fukuzumi Y, Yamazaki M, Tashiro H, Iwamoto C, Umehara Y, Imanishi T, Meyer A, Ikeo K, Gojobori T, Bahram S, Inoko H | display-authors = 6 | title = Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 13 | pages = 7708–13 | date = June 2003 | pmid = 12799463 | pmc = 164652 | doi = 10.1073/pnas.1230533100 | bibcode = 2003PNAS..100.7708A | doi-access = free }}</ref><ref name="ref4">{{cite journal | vauthors = Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, Andrews TD, Fiegler H, Shapero MH, Carson AR, Chen W, Cho EK, Dallaire S, Freeman JL, González JR, Gratacòs M, Huang J, Kalaitzopoulos D, Komura D, MacDonald JR, Marshall CR, Mei R, Montgomery L, Nishimura K, Okamura K, Shen F, Somerville MJ, Tchinda J, Valsesia A, Woodwark C, Yang F, Zhang J, Zerjal T, Zhang J, Armengol L, Conrad DF, Estivill X, Tyler-Smith C, Carter NP, Aburatani H, Lee C, Jones KW, Scherer SW, Hurles ME | display-authors = 6 | title = Global variation in copy number in the human genome | journal = Nature | volume = 444 | issue = 7118 | pages = 444–54 | date = November 2006 | pmid = 17122850 | pmc = 2669898 | doi = 10.1038/nature05329 | bibcode = 2006Natur.444..444R }}</ref><ref name="ref5">{{cite journal | vauthors = Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L | title = Natural selection has driven population differentiation in modern humans | journal = Nature Genetics | volume = 40 | issue = 3 | pages = 340–5 | date = March 2008 | pmid = 18246066 | doi = 10.1038/ng.78 | s2cid = 205357396 }}</ref>

The diversity of [[Biology:Human genetic variation|Human genetic variation]] such as that Indels were being uncovered and investigating human genomic variations{{cn|date=December 2023}}

=== Natural selection ===
It also aimed to provide evidence that can be used to explore the impact of [[Biology:Natural selection|Natural selection]] on population differences. Patterns of [[Biology:Polymorphism|DNA polymorphisms]] can be used to reliably detect signatures of selection and may help to identify genes that might underlie variation in disease resistance or drug metabolism.<ref name="ref7">EE Harris et al., The molecular signature of selection underlying human adaptations, Yearbook of Physical Anthropology 49: 89-130 (2006)</ref><ref name="ref8">{{cite journal | vauthors = Bamshad M, Wooding SP | title = Signatures of natural selection in the human genome | journal = Nature Reviews. Genetics | volume = 4 | issue = 2 | pages = 99–111 | date = February 2003 | pmid = 12560807 | doi = 10.1038/nrg999 | s2cid = 13722452 }}</ref> Such insights could improve understanding of [[Biology:Phenotype#Phenotypic variation|phenotypic variations]], [[Medicine:Genetic disorder|genetic disorder]]s and [[Biology:Mendelian inheritance|Mendelian inheritance]] and their effects on survival and/or reproduction of different human populations.

== Project description ==
=== Goals ===
The 1000 Genomes Project was designed to bridge the gap of knowledge between rare genetic variants that have a severe effect predominantly on simple traits (e.g. [[Medicine:Cystic fibrosis|cystic fibrosis]], Huntington disease) and common genetic variants have a mild effect and are implicated in complex traits (e.g. [[Cognition|cognition]], [[Medicine:Diabetes|diabetes]], heart disease).<ref name="ref1">G Spencer, International Consortium Announces the 1000 Genomes Project, EMBARGOED (2008) http://www.nih.gov/news/health/jan2008/nhgri-22.htm</ref>

The primary goal of this project was to create a complete and detailed catalogue of [[Biology:Human genetic variation|human genetic variation]]s, which can be used for association studies relating genetic variation to disease. The consortium aimed to discover >95 % of the variants (e.g. SNPs, CNVs, indels) with [[Biology:Minor allele frequency|minor allele frequencies]] as low as 1% across the genome and 0.1-0.5% in gene regions, as well as to estimate the population frequencies, [[Biology:Haplotype|haplotype]] backgrounds and [[Biology:Linkage disequilibrium|linkage disequilibrium]] patterns of variant alleles.<ref name="ref9">Meeting Report: A Workshop to Plan a Deep Catalog of Human Genetic Variation, (2007) http://www.1000genomes.org/sites/1000genomes.org/files/docs/1000Genomes-MeetingReport.pdf</ref>

Secondary goals included the support of better SNP and probe selection for [[Biology:Genotyping|genotyping]] platforms in future studies and the improvement of the [[Biology:Human Genome Project|human reference sequence]]. The completed database was expected be a useful tool for studying regions under selection, variation in multiple populations and understanding the underlying processes of mutation and [[Biology:Genetic recombination|recombination]].<ref name="ref9"/>

=== Outline ===
The [[Biology:Human genome|human genome]] consists of approximately 3 billion DNA base pairs and is estimated to carry around 20,000 [[Biology:Protein|protein]] coding genes. In designing the study the consortium needed to address several critical issues regarding the project metrics such as technology challenges, data quality standards and sequence coverage.<ref name="ref9"/>

Over the course of the next three years,{{clarify|date=April 2015}} scientists at the Sanger Institute, [[Organization:Beijing Genomics Institute|BGI Shenzhen]] and the [[Organization:National Human Genome Research Institute|National Human Genome Research Institute]]’s Large-Scale Sequencing Network planned to sequence a minimum of 1,000 human genomes. Due to the large amount of sequence data that was required, recruiting additional participants was maintained.<ref name="ref1"/>

Almost 10 billion bases were to be sequenced per day over a period of the two year production phase, equating to more than two human genomes every 24 hours. The intended sequence dataset was to comprise 6 trillion DNA bases, 60-fold more sequence data than what has been published in [[Biology:DNA|DNA]] databases at the time.<ref name="ref1"/>

To determine the final design of the full project three pilot studies were to be carried out within the first year of the project. The first pilot intends to genotype 180 people of 3 major geographic groups at low coverage (2×). For the second pilot study, the genomes of two nuclear families (both parents and an adult child) are going to be sequenced with deep coverage (20× per genome). The third pilot study involves sequencing the coding regions ([[Biology:Exon|exon]]s) of 1,000 genes in 1,000 people with deep coverage (20×).<ref name="ref1"/><ref name="ref9"/>

It was estimated that the project would likely cost more than $500 million if standard DNA sequencing technologies were used. Several newer technologies (e.g. Solexa, [[Company:454 Life Sciences|454]], [[Biology:ABI Solid Sequencing|SOLiD]]) were to be applied, lowering the expected costs to between $30 million and $50 million. The major support will be provided by the Wellcome Trust Sanger Institute in Hinxton, England; the [[Organization:Beijing Genomics Institute|Beijing Genomics Institute]], Shenzhen (BGI Shenzhen), China; and the NHGRI, part of the National Institutes of Health (NIH).<ref name="ref1"/>

In keeping with [http://www.genome.gov/pages/research/wellcomereport0303.pdf Fort Lauderdale principles] {{Webarchive|url=https://web.archive.org/web/20131228183230/http://www.genome.gov/pages/research/wellcomereport0303.pdf |date=2013-12-28 }}, all genome sequence data (including variant calls) is freely available as the project progresses and can be downloaded via ftp from the [http://www.1000genomes.org/data 1000 genomes project webpage].

=== Human genome samples ===
[[File:1000 Genomes Project.svg|thumb|400px|Locations of population samples of 1000 Genomes Project.<ref name="pmid26568821">{{cite journal | vauthors = Oleksyk TK, Brukhin V, O'Brien SJ | title = The Genome Russia project: closing the largest remaining omission on the world Genome map | journal = GigaScience | volume = 4 | pages = 53 | year = 2015 | pmid = 26568821 | pmc = 4644275 | doi = 10.1186/s13742-015-0095-0 | doi-access = free }}</ref> Each circle represents the number of sequences in the final release.]]
Based on the overall goals for the project, the samples will be chosen to provide power in populations where association studies for common diseases are being carried out. Furthermore, the samples do not need to have medical or phenotype information since the proposed catalogue will be a basic resource on human variation.<ref name="ref9"/>

For the pilot studies human genome samples from the HapMap collection will be sequenced. It will be useful to focus on samples that have additional data available (such as [[Biology:ENCODE|ENCODE]] sequence, genome-wide genotypes, [[Biology:Fosmid|fosmid]]-end sequence, structural variation assays, and [[Biology:Gene expression|gene expression]]) to be able to compare the results with those from other projects.<ref name="ref9"/>


{| class="wikitable"
! ID
! Place
! Population
! Detail
|-
|ASW
|{{flagicon|USA}}*
|African Ancestry in Southwestern USA
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/African-Ancestry-in-SW-USA-ASW Detail]
|-
|ACB
|{{flagicon|BRB}}*
|African Caribbean in Barbados
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/African-Caribbean-in-Barbados-ACB Detail]
|-
|BEB
|{{flagicon|BGD}}
|[[Social:Bengalis|Bengali]] in Bangladesh
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Bengali-in-Bangladesh-BEB Detail]
|-
|GBR
|{{flagicon|GBR}}
|British from {{wipe|England}} and Scotland
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/British-from-England-and-Scotland-UK-GBR Detail]
|-
|CDX
|{{flagicon|CHN}}
|Chinese Dai in Xishuangbanna, {{wipe|China}}
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Chinese-Dai---Xishuangbanna-CDX Detail]
|-
|CLM
|{{flagicon|COL}}
|Colombian in Medellín, Colombia
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Colombian-in-Medellin-Colombia-CLM Detail]
|-
|ESN
|{{flagicon|NGR}}
|Esan in Nigeria
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Esan-in-Nigeria-ESN Detail]
|-
|FIN
|{{flagicon|FIN}}
|Finnish in {{wipe|Finland}}
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Finnish-in-Finland-FIN Detail]
|-
|GWD
|{{flagicon|GMB}}
|Gambian in Western Division – Mandinka
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Gambian-in-Western-Division--Mandinka-GWD Detail]
|-
|GIH
|{{flagicon|USA}}*
|[[Social:Gujarati people|Gujarati]] Indians in Houston, {{wipe|Texas}}, {{wipe|United States}}
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Gujarati-Indians-in-Houston-TX-USA-GIH Detail]
|-
|CHB
|{{flagicon|CHN}}
|Han Chinese in [[Place:Beijing|Beijing]], {{wipe|China}}
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Han-Chinese-in-Beijing-China-CHB Detail]
|-
|CHS
|{{flagicon|CHN}}
|Han Chinese South, {{wipe|China}}
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Han-Chinese-South-China-CHS Detail]
|-
|IBS
|{{flagicon|SPA}}
|[[Place:Iberian Peninsula|Iberian]] populations in {{wipe|Spain}}
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Iberian-populations-in-Spain-IBS Detail]
|-
|ITU
|{{flagicon|GBR}}*
|Indian Telugu in the U.K.
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Indian-Telugu-in-the-UK-ITU Detail]
|-
|JPT
|{{flagicon|JPN}}
|Japanese in [[Place:Tokyo|Tokyo]], {{wipe|Japan}}
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Japanese-in-Tokyo-Japan-JPT Detail]
|-
|KHV
|{{flagicon|VNM}}
|Kinh in Ho Chi Minh City, Vietnam
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Kinh-in-Ho-Chi-Minh-City-Vietnam-KHV Detail]
|-
|LWK
|{{flagicon|KEN}}
|Luhya in Webuye, Kenya
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Luhya-in-Webuye-Kenya-LWK Detail]
|-
|MSL
|{{flagicon|SLE}}
|Mende in Sierra Leone
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Mende-in-Sierra-Leone-MSL Detail]
|-
|MXL
|{{flagicon|USA}}*
|Mexican Ancestry in {{wipe|Los Angeles}}, {{wipe|California}}, {{wipe|United States}}
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Mexican-Ancestry-in-Los-Angeles-CA-USA-MXL Detail]
|-
|PEL
|{{flagicon|PER}}
|Peruvian in [[Place:Lima|Lima]], Peru
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Peruvian-in-Lima-Peru-PEL Detail]
|-
|PUR
|{{flagicon|PUR}}
|Puerto Rican in Puerto Rico
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Puerto-Rican-in-Puerto-Rico-PUR Detail]
|-
|PJL
|{{flagicon|PAK}}
|[[Social:Punjabis|Punjabi]] in Lahore, {{wipe|Pakistan}}
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Punjabi-in-Lahore-Pakistan-PJL Detail]
|-
|STU
|{{flagicon|UK}}*
|Sri Lankan Tamil in the U.K.
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Sri-Lankan-Tamil-in-the-UK-STU Detail]
|-
|TSI
|{{flagicon|ITA}}
|Toscani in Italia
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Toscani-in-Italia-TSI Detail]
|-
|YRI
|{{flagicon|NGR}}
|Yoruba in Ibadan, Nigeria
|[https://catalog.coriell.org/1/NHGRI/Collections/1000-Genomes-Collections/Yoruba-in-Ibadan-Nigeria-YRI Detail]
|-
|CEU
|{{flagicon|USA}}*
|Utah residents with Northern and Western European ancestry from the CEPH collection
|[https://catalog.coriell.org/1/NIGMS/Collections/CEPH-Resources Detail]
|}
<nowiki>*</nowiki> Population that was collected in diaspora

=== Community meeting ===

Data generated by the 1000 Genomes Project is widely used by the genetics community, making the first 1000 Genomes Project one of the most cited papers in biology.<ref name="hotpapers">C. King (2012) The Hottest Research of 2011. ''Science Watch'' http://archive.sciencewatch.com/newsletter/2012/201203/hottest_research_2012/</ref> To support this user community, the project held a community analysis meeting in July 2012 that included talks highlighting key project discoveries, their impact on population genetics and human disease studies, and summaries of other large-scale sequencing studies.<ref name="community">1000 Genomes Project Community Analysis Meeting http://1000gconference.sph.umich.edu/</ref>

== Project findings ==

=== Pilot phase ===
The pilot phase consisted of three projects:
* low-coverage whole-genome sequencing of 179 individuals from 4 populations
* high-coverage sequencing of 2 trios (mother-father-child)
* exon-targeted sequencing of 697 individuals from 7 populations
It was found that on average, each person carries around 250–300 loss-of-function variants in annotated genes and 50-100 variants previously implicated in inherited disorders. Based on the two trios, it is estimated that the rate of de novo germline mutation is approximately 10<sup>−8</sup> per base per generation.<ref name="Pilot phase" />

== See also ==
* [[Biology:Human Genome Project|Human Genome Project]]
* HapMap Project
* [[Biology:Personal genomics|Personal genomics]]
* Population groups in biomedicine
* [[Biology:1000 Plant Genomes Project|1000 Plant Genomes Project]]
* [[Biology:List of biological databases|List of biological databases]]

== References ==
{{reflist}}

== External links ==
* [http://www.1000genomes.org/ 1000 Genomes] - A Deep Catalog of Human Genetic Variation - official web page
* [http://www.hapmap.org/ International HapMap Project] {{Webarchive|url=https://web.archive.org/web/20140416084248/http://www.hapmap.org/ |date=2014-04-16 }} - official web page
* [http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml Human Genome Project Information]

{{Personal genomics}}

{{DEFAULTSORT:1000 Genomes Project, The}}
[[Category:Human genome projects]]
[[Category:Population genetics organizations]]
[[Category:Single-nucleotide polymorphisms]]
[[Category:Genome projects]]
[[Category:Genomics]]
[[Category:Bioinformatics]]

{{Sourceattribution|1000 Genomes Project}}