The Characterization of Twenty Sequenced Human Genomes

被引：115

作者：

Pelak, Kimberly ^{[1
]}

Shianna, Kevin V. ^{[1
]}

Ge, Dongliang ^{[1
]}

Maia, Jessica M. ^{[1
]}

Zhu, Mingfu ^{[1
]}

Smith, Jason P. ^{[1
]}

Cirulli, Elizabeth T. ^{[1
]}

Fellay, Jacques ^{[1
]}

Dickson, Samuel P. ^{[1
]}

Gumbs, Curtis E. ^{[1
]}

Heinzen, Erin L. ^{[1
]}

Need, Anna C. ^{[1
]}

Ruzzo, Elizabeth K. ^{[1
]}

Singh, Abanish ^{[1
]}

Campbell, C. Ryan ^{[1
]}

Hong, Linda K. ^{[1
]}

Lornsen, Katharina A. ^{[1
]}

McKenzie, Alexander M. ^{[1
]}

Sobreira, Nara L. M. ^{[2
]}

Hoover-Fong, Julie E. ^{[2
]}

Milner, Joshua D. ^{[3
]}

Ottman, Ruth ^{[4
,5
,6
,7
]}

Haynes, Barton F. ^{[8
]}

Goedert, James J. ^{[9
]}

Goldstein, David B. ^{[1
]}

机构：

[1] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27710 USA

[2] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA

[3] NIAID, Allerg Inflammat Unit, Lab Allerg Dis, Bethesda, MD 20892 USA

[4] Columbia Univ, GH Sergievsky Ctr, New York, NY USA

[5] Columbia Univ, Dept Epidemiol, New York, NY USA

[6] Columbia Univ, Dept Neurol, New York, NY USA

[7] New York State Psychiat Inst & Hosp, Div Epidemiol, New York, NY 10032 USA

[8] Duke Univ, Duke Human Vaccine Inst, Durham, NC USA

[9] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA

来源：

PLOS GENETICS | 2010年 / 6卷 / 09期

基金：

美国国家卫生研究院;

关键词：

COPY NUMBER; WHOLE; CAPTURE;

D O I：

10.1371/journal.pgen.1001111

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten "case" genomes from individuals with severe hemophilia A and ten "control" genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs) discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways.

引用

页数：10

共 35 条

[1] The first Korean genome sequence and analysis: Full genome sequencing for a socio-ethnic group [J].

Ahn, Sung-Min ;

Kim, Tae-Hyung ;

Lee, Sunghoon ;

Kim, Deokhoon ;

Ghang, Ho ;

Kim, Dae-Soo ;

Kim, Byoung-Chul ;

Kim, Sang-Yoon ;

Kim, Woo-Yeon ;

Kim, Chulhong ;

Park, Daeui ;

Lee, Yong Seok ;

Kim, Sangsoo ;

Reja, Rohit ;

Jho, Sungwoong ;

Kim, Chang Geun ;

Cha, Ji-Young ;

Kim, Kyung-Hee ;

Lee, Bonghee ;

Bhak, Jong ;

Kim, Seong-Jin .

GENOME RESEARCH, 2009, 19 (09) :1622-1629

[2] Personalized copy number and segmental duplication maps using next-generation sequencing [J].

Alkan, Can ;

Kidd, Jeffrey M. ;

Marques-Bonet, Tomas ;

Aksay, Gozde ;

Antonacci, Francesca ;

Hormozdiari, Fereydoun ;

Kitzman, Jacob O. ;

Baker, Carl ;

Malig, Maika ;

Mutlu, Onur ;

Sahinalp, S. Cenk ;

Gibbs, Richard A. ;

Eichler, Evan E. .

NATURE GENETICS, 2009, 41 (10) :1061-U29

[3] MOLECULAR ETIOLOGY OF FACTOR-VIII DEFICIENCY IN HEMOPHILIA-A [J].

ANTONARAKIS, SE ;

KAZAZIAN, HH ;

TUDDENHAM, EGD .

HUMAN MUTATION, 1995, 5 (01) :1-22

[4] Accurate whole human genome sequencing using reversible terminator chemistry [J].

Bentley, David R. ;

Balasubramanian, Shankar ;

Swerdlow, Harold P. ;

Smith, Geoffrey P. ;

Milton, John ;

Brown, Clive G. ;

Hall, Kevin P. ;

Evers, Dirk J. ;

Barnes, Colin L. ;

Bignell, Helen R. ;

Boutell, Jonathan M. ;

Bryant, Jason ;

Carter, Richard J. ;

Cheetham, R. Keira ;

Cox, Anthony J. ;

Ellis, Darren J. ;

Flatbush, Michael R. ;

Gormley, Niall A. ;

Humphray, Sean J. ;

Irving, Leslie J. ;

Karbelashvili, Mirian S. ;

Kirk, Scott M. ;

Li, Heng ;

Liu, Xiaohai ;

Maisinger, Klaus S. ;

Murray, Lisa J. ;

Obradovic, Bojan ;

Ost, Tobias ;

Parkinson, Michael L. ;

Pratt, Mark R. ;

Rasolonjatovo, Isabelle M. J. ;

Reed, Mark T. ;

Rigatti, Roberto ;

Rodighiero, Chiara ;

Ross, Mark T. ;

Sabot, Andrea ;

Sankar, Subramanian V. ;

Scally, Aylwyn ;

Schroth, Gary P. ;

Smith, Mark E. ;

Smith, Vincent P. ;

Spiridou, Anastassia ;

Torrance, Peta E. ;

Tzonev, Svilen S. ;

Vermaas, Eric H. ;

Walter, Klaudia ;

Wu, Xiaolin ;

Zhang, Lu ;

Alam, Mohammed D. ;

Anastasi, Carole .

NATURE, 2008, 456 (7218) :53-59

[5]

Chen K, 2009, NAT METHODS, V6, P677, DOI [10.1038/NMETH.1363, 10.1038/nmeth.1363]

[6] Genetic diagnosis by whole exome capture and massively parallel DNA sequencing [J].

Choi, Murim ;

Scholl, Ute I. ;

Ji, Weizhen ;

Liu, Tiewen ;

Tikhonova, Irina R. ;

Zumbo, Paul ;

Nayir, Ahmet ;

Bakkaloglu, Aysin ;

Ozen, Seza ;

Sanjad, Sami ;

Nelson-Williams, Carol ;

Farhi, Anita ;

Mane, Shrikant ;

Lifton, Richard P. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (45) :19096-19101

[7] Uncovering the roles of rare variants in common disease through whole-genome sequencing [J].

Cirulli, Elizabeth T. ;

Goldstein, David B. .

NATURE REVIEWS GENETICS, 2010, 11 (06) :415-425

[8] The HUGO gene nomenclature database, 2006 updates [J].

Eyre, Tina A. ;

Ducluzeau, Fabrice ;

Sneddon, Tam P. ;

Povey, Sue ;

Bruford, Elspeth A. ;

Lush, Michael J. .

NUCLEIC ACIDS RESEARCH, 2006, 34 :D319-D321

[9] A second generation human haplotype map of over 3.1 million SNPs [J].

Frazer, Kelly A. ;

Ballinger, Dennis G. ;

Cox, David R. ;

Hinds, David A. ;

Stuve, Laura L. ;

Gibbs, Richard A. ;

Belmont, John W. ;

Boudreau, Andrew ;

Hardenbol, Paul ;

Leal, Suzanne M. ;

Pasternak, Shiran ;

Wheeler, David A. ;

Willis, Thomas D. ;

Yu, Fuli ;

Yang, Huanming ;

Zeng, Changqing ;

Gao, Yang ;

Hu, Haoran ;

Hu, Weitao ;

Li, Chaohua ;

Lin, Wei ;

Liu, Siqi ;

Pan, Hao ;

Tang, Xiaoli ;

Wang, Jian ;

Wang, Wei ;

Yu, Jun ;

Zhang, Bo ;

Zhang, Qingrun ;

Zhao, Hongbin ;

Zhao, Hui ;

Zhou, Jun ;

Gabriel, Stacey B. ;

Barry, Rachel ;

Blumenstiel, Brendan ;

Camargo, Amy ;

Defelice, Matthew ;

Faggart, Maura ;

Goyette, Mary ;

Gupta, Supriya ;

Moore, Jamie ;

Nguyen, Huy ;

Onofrio, Robert C. ;

Parkin, Melissa ;

Roy, Jessica ;

Stahl, Erich ;

Winchester, Ellen ;

Ziaugra, Liuda ;

Altshuler, David ;

Shen, Yan .

NATURE, 2007, 449 (7164) :851-U3

[10]

GE D, 2010, ANNOTATION VIS UNPUB

← 1 2 3 4 →