1000 Genomes Project

International research effort on genetic variation October 2023 The 1000 Genomes Project (1KGP), taken place from January 2008 to 2015, was an international research effort to establish the most detailed catalogue of human genetic variation at the time. Scientists planned to sequence the genomes of at least one thousand anonymous healthy participants from a number of different ethnic groups within the following three years, using advancements in newly developed technologies. In 2010, the project finished its pilot phase, which was described in detail in a publication in the journal Nature.Gonçalo Abecasis David Altshuler (physician) 6 Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA October 2010 A map of human genome variation from population-scale sequencing Nature 467 7319 1061–73 2010Natur.467.1061T 10.1038/nature09534 3042601 20981092 In 2012, the sequencing of 1092 genomes was announced in a Nature publication. Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA 6 An integrated map of genetic variation from 1,092 human genomes Nature 491 7422 56–65 November 2012 23128226 3498066 10.1038/nature11632 2012Natur.491...56T In 2015, two papers in Nature reported results and the completion of the project and opportunities for future research. Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR 6 A global reference for human genetic variation Nature 526 7571 68–74 October 2015 26432245 4750478 10.1038/nature15393 2015Natur.526...68T 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 6 An integrated map of structural variation in 2,504 human genomes Nature 526 7571 75–81 October 2015 26432246 4617611 10.1038/nature15394 2015Natur.526...75. Many rare variations, restricted to closely related groups, were identified, and eight structural-variation classes were analyzed.http://www.nature.com/news/variety-of-life-1.18454 Variety of life Nature News & Comment 2015-09-30 2015-10-15 The project united multidisciplinary research teams from institutes around the world, including China, Italy, Japan, Kenya, Nigeria, Peru, the United Kingdom, and the United States contributing to the sequence dataset and to a refined human genome map freely accessible through public databases to the scientific community and the general public alike. The International Genome Sample Resource was created to host and expand on the data set after the project's end.2020-07-07 1000 Genomes Project Scientific Computing and Data https://labs.icahn.mssm.edu/minervalab/resources/data-ark/1000-genomes/ 2023-10-01 Mount Sinai School of Medicine thumb|400px|Changes in the number and order of genes (A-D) create genetic diversity within and between populations. __TOC__ Background Since the completion of the Human Genome Project advances in human population genetics and comparative genomics enabled further insight into genetic diversity. Nielsen R Genomics: In search of rare human variants Nature 467 7319 1050–1 October 2010 20981085 10.1038/4671050a free 2010Natur.467.1050N The understanding about structural variations (insertions/deletions (indels), copy number variations (CNV), retroelements), single-nucleotide polymorphisms (SNPs), and natural selection were being solidified.JC Long, Human Genetic Variation: The mechanisms and results of microevolution, American Anthropological Association (2004) 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 6 Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence Proceedings of the National Academy of Sciences of the United States of America 100 13 7708–13 June 2003 12799463 164652 10.1073/pnas.1230533100 2003PNAS..100.7708A free 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 6 Global variation in copy number in the human genome Nature 444 7118 444–54 November 2006 17122850 2669898 10.1038/nature05329 2006Natur.444..444R Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L Natural selection has driven population differentiation in modern humans Nature Genetics 40 3 340–5 March 2008 18246066 10.1038/ng.78 205357396 The diversity of Human genetic variation such as that Indels were being uncovered and investigating human genomic variationsDecember 2023 Natural selection It also aimed to provide evidence that can be used to explore the impact of natural selection on population differences. Patterns of 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.EE Harris et al., The molecular signature of selection underlying human adaptations, Yearbook of Physical Anthropology 49: 89-130 (2006) Bamshad M, Wooding SP Signatures of natural selection in the human genome Nature Reviews. Genetics 4 2 99–111 February 2003 12560807 10.1038/nrg999 13722452 Such insights could improve understanding of phenotypic variations, genetic disorders and Mendelian inheritance and their effects on survival and/or reproduction of different human populations. Project description section April 2021 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. cystic fibrosis, Huntington disease) and common genetic variants have a mild effect and are implicated in complex traits (e.g. cognition, diabetes, heart disease).G Spencer, International Consortium Announces the 1000 Genomes Project, EMBARGOED (2008) https://archive.today/20131212175826/http://www.nih.gov/news/health/jan2008/nhgri-22.htm The primary goal of this project was to create a complete and detailed catalogue of human genetic variations, 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 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, haplotype backgrounds and linkage disequilibrium patterns of variant alleles.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 Secondary goals included the support of better SNP and probe selection for genotyping platforms in future studies and the improvement of the 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 recombination. Outline The human genome consists of approximately 3 billion DNA base pairs and is estimated to carry around 20,000 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. Over the course of the next three years,April 2015 scientists at the Sanger Institute, BGI Shenzhen and the 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. 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 DNA databases at the time. 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 (exons) of 1,000 genes in 1,000 people with deep coverage (20×). 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, 454, SOLiD) were to be applied, lowering the expected costs to between $30 million and $50 million. The major support was provided by the Wellcome Trust Sanger Institute in Hinxton, England; the Beijing Genomics Institute, Shenzhen (BGI Shenzhen), China; and the NHGRI, part of the National Institutes of Health (NIH). In keeping with Fort Lauderdale principles[http://www.genome.gov/pages/research/wellcomereport0303.pdf https://web.archive.org/web/20131228183230/http://www.genome.gov/pages/research/wellcomereport0303.pdf 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 1000 genomes project webpage.1000 genomes project data webpage Human genome samples thumb|400px|Locations of population samples of 1000 Genomes Project. Oleksyk TK, Brukhin V, O'Brien SJ The Genome Russia project: closing the largest remaining omission on the world Genome map GigaScience 4 53 2015 26568821 4644275 10.1186/s13742-015-0095-0 free 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. 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 ENCODE sequence, genome-wide genotypes, fosmid-end sequence, structural variation assays, and gene expression) to be able to compare the results with those from other projects. Complying with extensive ethical procedures, the 1000 Genomes Project will then use samples from volunteer donors. The following populations will be included in the study: Yoruba in Ibadan (YRI), Nigeria; Japanese in Tokyo (JPT); Chinese in Beijing (CHB); Utah residents with ancestry from northern and western Europe (CEU); Luhya in Webuye, Kenya (LWK); Maasai in Kinyawa, Kenya (MKK); Toscani in Italy (TSI); Peruvians in Lima, Peru (PEL); Gujarati Indians in Houston (GIH); Chinese in metropolitan Denver (CHD); people of Mexican ancestry in Los Angeles (MXL); and people of African ancestry in the southwestern United States (ASW). ID Place Population DetailASWUSA*African Ancestry in Southwestern USACBBRB*African Caribbean in BarbadosBEBBGDBengali in BangladeshGBRGBRBritish from England and ScotlandCDXCHNChinese Dai in Xishuangbanna, ChinaCLMCOLColombian in Medellín, ColombiaESNNGREsan in NigeriaFINFINFinnish in FinlandGWDGMBGambian in Western Division – MandinkaGIHUSA*Gujarati Indians in Houston, Texas, United StatesCHBCHNHan Chinese in Beijing, ChinaCHSCHNHan Chinese South ChinaIBSSPAIberian populations in SpainITUGBR*Indian Telugu in the United KingdomJPTJPNJapanese in Tokyo, JapanKHVVNMKinh in Ho Chi Minh City, VietnamLWKKENLuhya in Webuye, KenyaMSLSLEMende in Sierra LeoneMXLUSA*Mexican Ancestry in Los Angeles, California, United StatesPELPERPeruvian in Lima, PeruPURPURPuerto Rican in Puerto RicoPJLPAKPunjabi in Lahore, PakistanSTUUK*Sri Lankan Tamil in the United KingdomTSIITAToscani in ItalyYRINGRYoruba in Ibadan, NigeriaCEUUSA*Utah residents with Northern and Western European ancestry from the CEPH collection * 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.C. King (2012) The Hottest Research of 2011. Science Watch http://archive.sciencewatch.com/newsletter/2012/201203/hottest_research_2012/ 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.1000 Genomes Project Community Analysis Meeting http://1000gconference.sph.umich.edu/ https://web.archive.org/web/20120409022538/http://1000gconference.sph.umich.edu/ 2012-04-09 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 10−8 per base per generation. See also Biology Human Genome Project HapMap Project Personal genomics Population groups in biomedicine 1000 Plant Genomes Project List of biological databases References External links 1000 Genomes - A Deep Catalog of Human Genetic Variation - official web page International HapMap Project https://web.archive.org/web/20140416084248/http://www.hapmap.org/ 2014-04-16 - official web page Human Genome Project Information https://web.archive.org/web/20080315062131/http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml 2008-03-15 Category:Human genome projects Category:Population genetics organizations Category:Single-nucleotide polymorphisms Category:Genome projects Category:Genomics Category:Bioinformatics