Abstract
Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P value < 10 -245). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution.
Original language | English (US) |
---|---|
Pages (from-to) | 170-175 |
Number of pages | 6 |
Journal | Nature |
Volume | 476 |
Issue number | 7359 |
DOIs | |
State | Published - Aug 11 2011 |
Externally published | Yes |
ASJC Scopus subject areas
- General
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The landscape of recombination in African Americans. / Hinch, Anjali G.; Tandon, Arti; Patterson, Nick; Song, Yunli; Rohland, Nadin; Palmer, Cameron D.; Chen, Gary K.; Wang, Kai; Buxbaum, Sarah G.; Akylbekova, Ermeg L.; Aldrich, Melinda C.; Ambrosone, Christine B.; Amos, Christopher; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Bock, Cathryn H.; Boerwinkle, Eric; Cai, Qiuyin; Caporaso, Neil; Casey, Graham; Cupples, L. Adrienne; Deming, Sandra L.; Diver, W. Ryan; Divers, Jasmin; Fornage, Myriam; Gillanders, Elizabeth M.; Glessner, Joseph; Harris, Curtis C.; Hu, Jennifer J.; Ingles, Sue A.; Isaacs, William; John, Esther M.; Kao, W. H.Linda; Keating, Brendan; Kittles, Rick A.; Kolonel, Laurence N.; Larkin, Emma; Marchand, Loic Le; McNeill, Lorna H.; Millikan, Robert C.; Murphy, Adam; Musani, Solomon; Neslund-Dudas, Christine; Nyante, Sarah; Papanicolaou, George J.; Press, Michael F.; Psaty, Bruce M.; Reiner, Alex P.; Rich, Stephen S.; Rodriguez-Gil, Jorge L.; Rotter, Jerome I.; Rybicki, Benjamin A.; Schwartz, Ann G.; Signorello, Lisa B.; Spitz, Margaret; Strom, Sara S.; Thun, Michael J.; Tucker, Margaret A.; Wang, Zhaoming; Wiencke, John K.; Witte, John S.; Wrensch, Margaret; Wu, Xifeng; Yamamura, Yuko; Zanetti, Krista A.; Zheng, Wei; Ziegler, Regina G.; Zhu, Xiaofeng; Redline, Susan; Hirschhorn, Joel N.; Henderson, Brian E.; Taylor, Herman A.; Price, Alkes L.; Hakonarson, Hakon; Chanock, Stephen J.; Haiman, Christopher A.; Wilson, James G.; Reich, David; Myers, Simon R.
In: Nature, Vol. 476, No. 7359, 11.08.2011, p. 170-175.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - The landscape of recombination in African Americans
AU - Hinch, Anjali G.
AU - Tandon, Arti
AU - Patterson, Nick
AU - Song, Yunli
AU - Rohland, Nadin
AU - Palmer, Cameron D.
AU - Chen, Gary K.
AU - Wang, Kai
AU - Buxbaum, Sarah G.
AU - Akylbekova, Ermeg L.
AU - Aldrich, Melinda C.
AU - Ambrosone, Christine B.
AU - Amos, Christopher
AU - Bandera, Elisa V.
AU - Berndt, Sonja I.
AU - Bernstein, Leslie
AU - Blot, William J.
AU - Bock, Cathryn H.
AU - Boerwinkle, Eric
AU - Cai, Qiuyin
AU - Caporaso, Neil
AU - Casey, Graham
AU - Cupples, L. Adrienne
AU - Deming, Sandra L.
AU - Diver, W. Ryan
AU - Divers, Jasmin
AU - Fornage, Myriam
AU - Gillanders, Elizabeth M.
AU - Glessner, Joseph
AU - Harris, Curtis C.
AU - Hu, Jennifer J.
AU - Ingles, Sue A.
AU - Isaacs, William
AU - John, Esther M.
AU - Kao, W. H.Linda
AU - Keating, Brendan
AU - Kittles, Rick A.
AU - Kolonel, Laurence N.
AU - Larkin, Emma
AU - Marchand, Loic Le
AU - McNeill, Lorna H.
AU - Millikan, Robert C.
AU - Murphy, Adam
AU - Musani, Solomon
AU - Neslund-Dudas, Christine
AU - Nyante, Sarah
AU - Papanicolaou, George J.
AU - Press, Michael F.
AU - Psaty, Bruce M.
AU - Reiner, Alex P.
AU - Rich, Stephen S.
AU - Rodriguez-Gil, Jorge L.
AU - Rotter, Jerome I.
AU - Rybicki, Benjamin A.
AU - Schwartz, Ann G.
AU - Signorello, Lisa B.
AU - Spitz, Margaret
AU - Strom, Sara S.
AU - Thun, Michael J.
AU - Tucker, Margaret A.
AU - Wang, Zhaoming
AU - Wiencke, John K.
AU - Witte, John S.
AU - Wrensch, Margaret
AU - Wu, Xifeng
AU - Yamamura, Yuko
AU - Zanetti, Krista A.
AU - Zheng, Wei
AU - Ziegler, Regina G.
AU - Zhu, Xiaofeng
AU - Redline, Susan
AU - Hirschhorn, Joel N.
AU - Henderson, Brian E.
AU - Taylor, Herman A.
AU - Price, Alkes L.
AU - Hakonarson, Hakon
AU - Chanock, Stephen J.
AU - Haiman, Christopher A.
AU - Wilson, James G.
AU - Reich, David
AU - Myers, Simon R.
N1 - Funding Information: Acknowledgements We are grateful to the participants who donated DNA samples, to D. Altshuler, J. Buard, K. Bryc, J. Kovacs, B. de Massy, G. McVean, B. Pasaniuc and S. Sankararaman for conversations and critiques, and to A. Auton for facilitating analysis of the 1000 Genomes Project data. Analysis was supported by the Wellcome Trust and NIH grants HL084107 and GM091332. CARe was supported by a contract from the National Heart, Lung and Blood Institute (HHSN268200960009C) to create a phenotype and genotype database for dissemination to the biomedical research community. Eight parent studies contributed phenotypic data and DNA samples through theBroad Institute (N01-HC-65226): the AtherosclerosisRiskinCommunities study (ARIC), the Cleveland Family Study (CFS), the Coronary Artery Risk Development in Young Adults study (CARDIA), the Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis (MESA) study, the Cardiovascular Health Study (CHS), the Framingham Heart Study (FHS) and the Sleep Heart Health Study (SHHS). Support for CARe also came from the individual research institutions, investigators, field staff and study participants. Individual funding information is available at http:// public.nhlbi.nih.gov/GeneticsGenomics/home/care.aspx. All genome-wide genotyping of samples from the Children’s Hospital of Pennsylvania (CHOP) was supported by an Institutional Development Award to the Center for Applied Genomics from the Children’s Hospital of Philadelphia, a research award from the Landenberger Foundation and the Cotswold Foundation. We thank all study participants and the staff at the Center for Applied Genomics for performing the genotyping. The African American Breast Cancer Consortium (AABCC) was supported by a DoD Breast Cancer Research Program Era of Hope Scholar Award to C.A.H. and the Norris Foundation, and by grants to the component studies: MEC (CA63464, CA54281); CARE (HD33175); WCHS (CA100598, DAMD 170100334, Breast Cancer Research Foundation); SFBC (CA77305, DAMD 17966071); CBCS (CA58223, ES10126), PLCO (NCI Intramural Research Program); NHBS (CA100374); WFBC (R01-CA73629); and CPS-II (the AmericanCancer Society). The AfricanAmerican Prostate Cancer Consortium (AAPCC) was supported by grants CA63464, CA54281, CA1326792, CA148085 and HG004726, and by grants to the component studies: PLCO (NCI Intramural Research Program), LAAPC (Cancer Research Fund 99-00524V-10258), both MEC and LAAPC (PC35139, DP000807); MDA (CA68578, CA140388, ES007784, DAMD W81XWH0710645); GECAP (ES011126); CaP Genes (CA88164); IPCG (W81XWH0710122); DCPC (GM08016, DAMD W81XWH0710203, DAMD W81XWH0610066); and SCCS (CA092447, CA68485). The African American Lung Cancer Consortium(AALCC) was supported bygrants CA060691,CA87895,PC35145 and CA22453, CA68578, CA140388, ES007784, ES06717, CA55769, CA127219, CA1116460S1, CA1116460, CA121197, CA141716, CA121197S2, CPRIT RP100443, CA148127, DAMD W81XWH0710645, University Cancer Foundation, Duncan Family institute, Center for Community, Implementation and Dissemination Research Core, and by grants to the component studies: PLCO and the Maryland Studies (NCI Intramural Research Program), LAAPC (Cancer Research Fund 99-00524V-10258), and both MEC and LAAPC (PC35139, DP000807).
PY - 2011/8/11
Y1 - 2011/8/11
N2 - Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P value < 10 -245). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution.
AB - Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P value < 10 -245). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution.
UR - http://www.scopus.com/inward/record.url?scp=80051679387&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80051679387&partnerID=8YFLogxK
U2 - 10.1038/nature10336
DO - 10.1038/nature10336
M3 - Article
C2 - 21775986
AN - SCOPUS:80051679387
VL - 476
SP - 170
EP - 175
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7359
ER -