Mapping and sequencing of structural variation from eight human genomes.
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.
Kidd
Jeffrey M
JM
Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
Cooper
Gregory M
GM
Donahue
William F
WF
Hayden
Hillary S
HS
Sampas
Nick
N
Graves
Tina
T
Hansen
Nancy
N
Teague
Brian
B
Alkan
Can
C
Antonacci
Francesca
F
Haugen
Eric
E
Zerr
Troy
T
Yamada
N Alice
NA
Tsang
Peter
P
Newman
Tera L
TL
Tüzün
Eray
E
Cheng
Ze
Z
Ebling
Heather M
HM
Tusneem
Nadeem
N
David
Robert
R
Gillett
Will
W
Phelps
Karen A
KA
Weaver
Molly
M
Saranga
David
D
Brand
Adrianne
A
Tao
Wei
W
Gustafson
Erik
E
McKernan
Kevin
K
Chen
Lin
L
Malig
Maika
M
Smith
Joshua D
JD
Korn
Joshua M
JM
McCarroll
Steven A
SA
Altshuler
David A
DA
Peiffer
Daniel A
DA
Dorschner
Michael
M
Stamatoyannopoulos
John
J
Schwartz
David
D
Nickerson
Deborah A
DA
Mullikin
James C
JC
Wilson
Richard K
RK
Bruhn
Laurakay
L
Olson
Maynard V
MV
Kaul
Rajinder
R
Smith
Douglas R
DR
Eichler
Evan E
EE
D007446:Chromosome Inversion / Q000235:genetics; D022041:Euchromatin / Q000235:genetics; D017353:Gene Deletion; D014644:Genetic Variation / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D005843:Geography; D006239:Haplotypes; D006801:Humans; D016254:Mutagenesis, Insertional / Q000235:genetics; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044469:Racial Groups / Q000235:genetics; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA
D022041:Euchromatin