The landscape of recombination in African Americans

Anjali G. Hinch; Arti Tandon; Nick Patterson; Yunli Song; Nadin Rohland; Cameron D. Palmer; Gary K. Chen; Kai Wang; Sarah G. Buxbaum; Ermeg L. Akylbekova; Melinda C. Aldrich; Christine B. Ambrosone; Christopher Amos; Elisa V. Bandera; Sonja I. Berndt; Leslie Bernstein; William J. Blot; Cathryn H. Bock; Eric Boerwinkle; Qiuyin Cai; Neil Caporaso; Graham Casey; L. Adrienne Cupples; Sandra L. Deming; W. Ryan Diver; Jasmin Divers; Myriam Fornage; Elizabeth M. Gillanders; Joseph Glessner; Curtis C. Harris; Jennifer J. Hu; Sue A. Ingles; William Isaacs; Esther M. John; W. H.Linda Kao; Brendan Keating; Rick A. Kittles; Laurence N. Kolonel; Emma Larkin; Loic Le Marchand; Lorna H. McNeill; Robert C. Millikan; Adam Murphy; Solomon Musani; Christine Neslund-Dudas; Sarah Nyante; George J. Papanicolaou; Michael F. Press; Bruce M. Psaty; Alex P. Reiner; Stephen S. Rich; Jorge L. Rodriguez-Gil; Jerome I. Rotter; Benjamin A. Rybicki; Ann G. Schwartz; Lisa B. Signorello; Margaret Spitz; Sara S. Strom; Michael J. Thun; Margaret A. Tucker; Zhaoming Wang; John K. Wiencke; John S. Witte; Margaret Wrensch; Xifeng Wu; Yuko Yamamura; Krista A. Zanetti; Wei Zheng; Regina G. Ziegler; Xiaofeng Zhu; Susan Redline; Joel N. Hirschhorn; Brian E. Henderson; Herman A. Taylor; Alkes L. Price; Hakon Hakonarson; Stephen J. Chanock; Christopher A. Haiman; James G. Wilson; David Reich; Simon R. Myers

doi:10.1038/nature10336

The landscape of recombination in African Americans

Anjali G. Hinch, Arti Tandon, Nick Patterson, Yunli Song, Nadin Rohland, Cameron D. Palmer, Gary K. Chen, Kai Wang, Sarah G. Buxbaum, Ermeg L. Akylbekova, Melinda C. Aldrich, Christine B. Ambrosone, Christopher Amos, Elisa V. Bandera, Sonja I. Berndt, Leslie Bernstein, William J. Blot, Cathryn H. Bock, Eric Boerwinkle, Qiuyin CaiNeil Caporaso, Graham Casey, L. Adrienne Cupples, Sandra L. Deming, W. Ryan Diver, Jasmin Divers, Myriam Fornage, Elizabeth M. Gillanders, Joseph Glessner, Curtis C. Harris, Jennifer J. Hu, Sue A. Ingles, William Isaacs, Esther M. John, W. H.Linda Kao, Brendan Keating, Rick A. Kittles, Laurence N. Kolonel, Emma Larkin, Loic Le Marchand, Lorna H. McNeill, Robert C. Millikan, Adam Murphy, Solomon Musani, Christine Neslund-Dudas, Sarah Nyante, George J. Papanicolaou, Michael F. Press, Bruce M. Psaty, Alex P. Reiner, Stephen S. Rich, Jorge L. Rodriguez-Gil, Jerome I. Rotter, Benjamin A. Rybicki, Ann G. Schwartz, Lisa B. Signorello, Margaret Spitz, Sara S. Strom, Michael J. Thun, Margaret A. Tucker, Zhaoming Wang, John K. Wiencke, John S. Witte, Margaret Wrensch, Xifeng Wu, Yuko Yamamura, Krista A. Zanetti, Wei Zheng, Regina G. Ziegler, Xiaofeng Zhu, Susan Redline, Joel N. Hirschhorn, Brian E. Henderson, Herman A. Taylor, Alkes L. Price, Hakon Hakonarson, Stephen J. Chanock, Christopher A. Haiman, James G. Wilson, David Reich, Simon R. Myers

Research output: Contribution to journal › Article › peer-review

186 Scopus citations

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	https://doi.org/10.1038/nature10336
State	Published - Aug 11 2011
Externally published	Yes

ASJC Scopus subject areas

General

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Hinch, A. G., Tandon, A., Patterson, N., Song, Y., Rohland, N., Palmer, C. D., Chen, G. K., Wang, K., Buxbaum, S. G., Akylbekova, E. L., Aldrich, M. C., Ambrosone, C. B., Amos, C., Bandera, E. V., Berndt, S. I., Bernstein, L., Blot, W. J., Bock, C. H., Boerwinkle, E., ... Myers, S. R. (2011). The landscape of recombination in African Americans. Nature, 476(7359), 170-175. https://doi.org/10.1038/nature10336

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

Hinch, AG, Tandon, A, Patterson, N, Song, Y, Rohland, N, Palmer, CD, Chen, GK, Wang, K, Buxbaum, SG, Akylbekova, EL, Aldrich, MC, Ambrosone, CB, Amos, C, Bandera, EV, Berndt, SI, Bernstein, L, Blot, WJ, Bock, CH, Boerwinkle, E, Cai, Q, Caporaso, N, Casey, G, Cupples, LA, Deming, SL, Diver, WR, Divers, J, Fornage, M, Gillanders, EM, Glessner, J, Harris, CC, Hu, JJ, Ingles, SA, Isaacs, W, John, EM, Kao, WHL, Keating, B, Kittles, RA, Kolonel, LN, Larkin, E, Marchand, LL, McNeill, LH, Millikan, RC, Murphy, A, Musani, S, Neslund-Dudas, C, Nyante, S, Papanicolaou, GJ, Press, MF, Psaty, BM, Reiner, AP, Rich, SS, Rodriguez-Gil, JL, Rotter, JI, Rybicki, BA, Schwartz, AG, Signorello, LB, Spitz, M, Strom, SS, Thun, MJ, Tucker, MA, Wang, Z, Wiencke, JK, Witte, JS, Wrensch, M, Wu, X, Yamamura, Y, Zanetti, KA, Zheng, W, Ziegler, RG, Zhu, X, Redline, S, Hirschhorn, JN, Henderson, BE, Taylor, HA, Price, AL, Hakonarson, H, Chanock, SJ, Haiman, CA, Wilson, JG, Reich, D & Myers, SR 2011, 'The landscape of recombination in African Americans', Nature, vol. 476, no. 7359, pp. 170-175. https://doi.org/10.1038/nature10336

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. / The landscape of recombination in African Americans. In: Nature. 2011 ; Vol. 476, No. 7359. pp. 170-175.

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title = "The landscape of recombination in African Americans",

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.",

author = "Hinch, {Anjali G.} and Arti Tandon and Nick Patterson and Yunli Song and Nadin Rohland and Palmer, {Cameron D.} and Chen, {Gary K.} and Kai Wang and Buxbaum, {Sarah G.} and Akylbekova, {Ermeg L.} and Aldrich, {Melinda C.} and Ambrosone, {Christine B.} and Christopher Amos and Bandera, {Elisa V.} and Berndt, {Sonja I.} and Leslie Bernstein and Blot, {William J.} and Bock, {Cathryn H.} and Eric Boerwinkle and Qiuyin Cai and Neil Caporaso and Graham Casey and Cupples, {L. Adrienne} and Deming, {Sandra L.} and Diver, {W. Ryan} and Jasmin Divers and Myriam Fornage and Gillanders, {Elizabeth M.} and Joseph Glessner and Harris, {Curtis C.} and Hu, {Jennifer J.} and Ingles, {Sue A.} and William Isaacs and John, {Esther M.} and Kao, {W. H.Linda} and Brendan Keating and Kittles, {Rick A.} and Kolonel, {Laurence N.} and Emma Larkin and Marchand, {Loic Le} and McNeill, {Lorna H.} and Millikan, {Robert C.} and Adam Murphy and Solomon Musani and Christine Neslund-Dudas and Sarah Nyante and Papanicolaou, {George J.} and Press, {Michael F.} and Psaty, {Bruce M.} and Reiner, {Alex P.} and Rich, {Stephen S.} and Rodriguez-Gil, {Jorge L.} and Rotter, {Jerome I.} and Rybicki, {Benjamin A.} and Schwartz, {Ann G.} and Signorello, {Lisa B.} and Margaret Spitz and Strom, {Sara S.} and Thun, {Michael J.} and Tucker, {Margaret A.} and Zhaoming Wang and Wiencke, {John K.} and Witte, {John S.} and Margaret Wrensch and Xifeng Wu and Yuko Yamamura and Zanetti, {Krista A.} and Wei Zheng and Ziegler, {Regina G.} and Xiaofeng Zhu and Susan Redline and Hirschhorn, {Joel N.} and Henderson, {Brian E.} and Taylor, {Herman A.} and Price, {Alkes L.} and Hakon Hakonarson and Chanock, {Stephen J.} and Haiman, {Christopher A.} and Wilson, {James G.} and David Reich and Myers, {Simon R.}",

note = "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{\textquoteright}s Hospital of Pennsylvania (CHOP) was supported by an Institutional Development Award to the Center for Applied Genomics from the Children{\textquoteright}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).",

year = "2011",

month = aug,

day = "11",

doi = "10.1038/nature10336",

language = "English (US)",

volume = "476",

pages = "170--175",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7359",

}

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.

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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 -