Mapping and sequencing of structural variation from eight human genomes (Reprinted from Nature, vol 453, pg 56-64, 2008)

被引：791

作者：

Kidd, Jeffrey M. ^{[1
,2
]}

Cooper, Gregory M. ^{[1
,2
]}

Donahue, William F. ^{[3
]}

Hayden, Hillary S. ^{[4
,5
]}

Sampas, Nick ^{[6
]}

Graves, Tina ^{[7
]}

Hansen, Nancy ^{[8
]}

Teague, Brian ^{[9
]}

Alkan, Can ^{[1
,2
]}

Antonacci, Francesca ^{[1
,2
]}

Haugen, Eric ^{[4
,5
]}

Zerr, Troy ^{[1
,2
]}

Yamada, N. Alice ^{[6
]}

Tsang, Peter ^{[6
]}

Newman, Tera L. ^{[1
,2
]}

Tuzun, Eray ^{[1
,2
]}

Cheng, Ze ^{[1
,2
]}

Ebling, Heather M. ^{[3
]}

Tusneem, Nadeem ^{[3
]}

David, Robert ^{[3
]}

Gillett, Will ^{[4
,5
]}

Phelps, Karen A. ^{[4
,5
]}

Weaver, Molly ^{[1
,2
]}

Saranga, David ^{[3
]}

Brand, Adrianne ^{[3
]}

Tao, Wei ^{[3
]}

Gustafson, Erik ^{[3
]}

McKernan, Kevin ^{[3
]}

Chen, Lin ^{[1
,2
]}

Malig, Maika ^{[1
,2
]}

Smith, Joshua D. ^{[1
,2
]}

Korn, Joshua M. ^{[10
]}

McCarroll, Steven A. ^{[10
]}

Altshuler, David A. ^{[10
]}

Peiffer, Daniel A. ^{[11
]}

Dorschner, Michael ^{[1
,2
]}

Stamatoyannopoulos, John ^{[1
,2
]}

Schwartz, David ^{[9
]}

Nickerson, Deborah A. ^{[1
,2
]}

Mullikin, James C. ^{[8
]}

Wilson, Richard K. ^{[7
]}

Bruhn, Laurakay ^{[6
]}

Olson, Maynard V. ^{[4
,5
]}

Kaul, Rajinder ^{[4
,5
]}

Smith, Douglas R. ^{[3
]}

Eichler, Evan E. ^{[1
,2
]}

机构：

[1] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[2] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA

[3] Agencourt Biosci Corp, Beverly, MA 01915 USA

[4] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA

[5] Univ Washington, Genome Ctr, Seattle, WA 98195 USA

[6] Agilent Technol, Santa Clara, CA 95051 USA

[7] Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA

[8] NIH, Human Genome Res Inst, Bethesda, MD 20892 USA

[9] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA

[10] Broad Inst MIT & Harvard, Program Med & Populat Genet, Boston, MA 02114 USA

[11] Illumina Inc, San Diego, CA 92121 USA

来源：

NATURE GENETICS | 2009年

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

COPY NUMBER POLYMORPHISM; SEGMENTAL DUPLICATIONS; PREDISPOSES; INVERSION; VARIANTS; REVEALS; MAPS;

D O I：

10.1038/nature06862

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale-particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence map of human structural variation-a standard for genotyping platforms and a prelude to future individual genome sequencing projects.

引用

页码：S22 / S30

页数：9

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