Whole-genome molecular haplotyping of single cells

被引：279

作者：

Fan, H. Christina ^{[1
]}

Wang, Jianbin ^{[1
]}

Potanina, Anastasia ^{[2
]}

Quake, Stephen R. ^{[1
,2
,3
]}

机构：

[1] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

[2] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA

来源：

NATURE BIOTECHNOLOGY | 2011年 / 29卷 / 01期

基金：

美国国家卫生研究院;

关键词：

HIGH-RESOLUTION HLA; GENETIC-ANALYSIS; DNA; SEQUENCE; MAP; RECONSTRUCTION; AMPLIFICATION; ASSOCIATION; EXPRESSION; INFERENCE;

D O I：

10.1038/nbt.1739

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Conventional experimental methods of studying the human genome are limited by the inability to independently study the combination of alleles, or haplotype, on each of the homologous copies of the chromosomes. We developed a microfluidic device capable of separating and amplifying homologous copies of each chromosome from a single human metaphase cell. Single-nucleotide polymorphism (SNP) array analysis of amplified DNA enabled us to achieve completely deterministic, whole-genome, personal haplotypes of four individuals, including a HapMap trio with European ancestry (CEU) and an unrelated European individual. The phases of alleles were determined at similar to 99.8% accuracy for up to similar to 96% of all assayed SNPs. We demonstrate several practical applications, including direct observation of recombination events in a family trio, deterministic phasing of deletions in individuals and direct measurement of the human leukocyte antigen haplotypes of an individual. Our approach has potential applications in personal genomics, single-cell genomics and statistical genetics.

引用

页码：51 / +

页数：9

共 48 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] A haplotype map of the human genome [J].

Altshuler, D ;

Brooks, LD ;

Chakravarti, A ;

Collins, FS ;

Daly, MJ ;

Donnelly, P ;

Gibbs, RA ;

Belmont, JW ;

Boudreau, A ;

Leal, SM ;

Hardenbol, P ;

Pasternak, S ;

Wheeler, DA ;

Willis, TD ;

Yu, FL ;

Yang, HM ;

Zeng, CQ ;

Gao, Y ;

Hu, HR ;

Hu, WT ;

Li, CH ;

Lin, W ;

Liu, SQ ;

Pan, H ;

Tang, XL ;

Wang, J ;

Wang, W ;

Yu, J ;

Zhang, B ;

Zhang, QR ;

Zhao, HB ;

Zhao, H ;

Zhou, J ;

Gabriel, SB ;

Barry, R ;

Blumenstiel, B ;

Camargo, A ;

Defelice, M ;

Faggart, M ;

Goyette, M ;

Gupta, S ;

Moore, J ;

Nguyen, H ;

Onofrio, RC ;

Parkin, M ;

Roy, J ;

Stahl, E ;

Winchester, E ;

Ziaugra, L ;

Shen, Y .

NATURE, 2005, 437 (7063) :1299-1320

[3] Understanding the accuracy of statistical haplotype inference with sequence data of known phase [J].

Andres, Aida M. ;

Clark, Andrew G. ;

Shimmin, Lawrence ;

Boerwinkle, Eric ;

Sing, Charles F. ;

Hixson, James E. .

GENETIC EPIDEMIOLOGY, 2007, 31 (07) :659-671

[4] Clinical assessment incorporating a personal genome [J].

Ashley, Euan A. ;

Butte, Atul J. ;

Wheeler, Matthew T. ;

Chen, Rong ;

Klein, Teri E. ;

Dewey, Frederick E. ;

Dudley, Joel T. ;

Ormond, Kelly E. ;

Pavlovic, Aleksandra ;

Morgan, Alexander A. ;

Pushkarev, Dmitry ;

Neff, Norma F. ;

Hudgins, Louanne ;

Gong, Li ;

Hodges, Laura M. ;

Berlin, Dorit S. ;

Thorn, Caroline F. ;

Sangkuhl, Katrin ;

Hebert, Joan M. ;

Woon, Mark ;

Sagreiya, Hersh ;

Whaley, Ryan ;

Knowles, Joshua W. ;

Chou, Michael F. ;

Thakuria, Joseph V. ;

Rosenbaum, Abraham M. ;

Zaranek, Alexander Wait ;

Church, George M. ;

Greely, Henry T. ;

Quake, Stephen R. ;

Altman, Russ B. .

LANCET, 2010, 375 (9725) :1525-1535

[5] 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

[6] Amplification of whole tumor genomes and geneby-gene mapping of genomic aberrations from limited sources of fresh-frozen and paraffin-embedded DNA [J].

Bredel, M ;

Bredel, C ;

Juric, D ;

Kim, Y ;

Vogel, H ;

Harsh, GR ;

Recht, LD ;

Pollack, JR ;

Sikic, BI .

JOURNAL OF MOLECULAR DIAGNOSTICS, 2005, 7 (02) :171-182

[7] Comprehensive human genetic maps: Individual and sex-specific variation in recombination [J].

Broman, KW ;

Murray, JC ;

Sheffield, VC ;

White, RL ;

Weber, JL .

AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 63 (03) :861-869

[8] Clone-based systematic haplotyping (CSH): A procedure for physical haplotyping of whole genomes [J].

Burgtorf, C ;

Kepper, P ;

Hoehe, M ;

Schmitt, C ;

Reinhardt, R ;

Lehrach, H ;

Sauer, S .

GENOME RESEARCH, 2003, 13 (12) :2717-2724

[9] Origins and functional impact of copy number variation in the human genome [J].

Conrad, Donald F. ;

Pinto, Dalila ;

Redon, Richard ;

Feuk, Lars ;

Gokcumen, Omer ;

Zhang, Yujun ;

Aerts, Jan ;

Andrews, T. Daniel ;

Barnes, Chris ;

Campbell, Peter ;

Fitzgerald, Tomas ;

Hu, Min ;

Ihm, Chun Hwa ;

Kristiansson, Kati ;

MacArthur, Daniel G. ;

MacDonald, Jeffrey R. ;

Onyiah, Ifejinelo ;

Pang, Andy Wing Chun ;

Robson, Sam ;

Stirrups, Kathy ;

Valsesia, Armand ;

Walter, Klaudia ;

Wei, John ;

Tyler-Smith, Chris ;

Carter, Nigel P. ;

Lee, Charles ;

Scherer, Stephen W. ;

Hurles, Matthew E. .

NATURE, 2010, 464 (7289) :704-712

[10] A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC [J].

de Bakker, Paul I. W. ;

McVean, Gil ;

Sabeti, Pardis C. ;

Miretti, Marcos M. ;

Green, Todd ;

Marchini, Jonathan ;

Ke, Xiayi ;

Monsuur, Alienke J. ;

Whittaker, Pamela ;

Delgado, Marcos ;

Morrison, Jonathan ;

Richardson, Angela ;

Walsh, Emily C. ;

Gao, Xiaojiang ;

Galver, Luana ;

Hart, John ;

Hafler, David A. ;

Pericak-Vance, Margaret ;

Todd, John A. ;

Daly, Mark J. ;

Trowsdale, John ;

Wijmenga, Cisca ;

Vyse, Tim J. ;

Beck, Stephan ;

Murray, Sarah Shaw ;

Carrington, Mary ;

Gregory, Simon ;

Deloukas, Panos ;

Rioux, John D. .

NATURE GENETICS, 2006, 38 (10) :1166-1172

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