A second generation human haplotype map of over 3.1 million SNPs.
We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.
The Scripps Research Institute, 10550 North Torrey Pines Road MEM275, La Jolla, California 92037, USA.
Frazer
Kelly A
KA
Ballinger
Dennis G
DG
Cox
David R
DR
Hinds
David A
DA
Stuve
Laura L
LL
Gibbs
Richard A
RA
Belmont
John W
JW
Boudreau
Andrew
A
Hardenbol
Paul
P
Leal
Suzanne M
SM
Pasternak
Shiran
S
Wheeler
David A
DA
Willis
Thomas D
TD
Yu
Fuli
F
Yang
Huanming
H
Zeng
Changqing
C
Gao
Yang
Y
Hu
Haoran
H
Hu
Weitao
W
Li
Chaohua
C
Lin
Wei
W
Liu
Siqi
S
Pan
Hao
H
Tang
Xiaoli
X
Wang
Jian
J
Wang
Wei
W
Yu
Jun
J
Zhang
Bo
B
Zhang
Qingrun
Q
Zhao
Hongbin
H
Zhao
Hui
H
Zhou
Jun
J
Gabriel
Stacey B
SB
Barry
Rachel
R
Blumenstiel
Brendan
B
Camargo
Amy
A
Defelice
Matthew
M
Faggart
Maura
M
Goyette
Mary
M
Gupta
Supriya
S
Moore
Jamie
J
Nguyen
Huy
H
Onofrio
Robert C
RC
Parkin
Melissa
M
Roy
Jessica
J
Stahl
Erich
E
Winchester
Ellen
E
Ziaugra
Liuda
L
Altshuler
David
D
Shen
Yan
Y
Yao
Zhijian
Z
Huang
Wei
W
Chu
Xun
X
He
Yungang
Y
Jin
Li
L
Liu
Yangfan
Y
Shen
Yayun
Y
Sun
Weiwei
W
Wang
Haifeng
H
Wang
Yi
Y
Wang
Ying
Y
Xiong
Xiaoyan
X
Xu
Liang
L
Waye
Mary M Y
MM
Tsui
Stephen K W
SK
Xue
Hong
H
Wong
J Tze-Fei
JT
Galver
Luana M
LM
Fan
Jian-Bing
JB
Gunderson
Kevin
K
Murray
Sarah S
SS
Oliphant
Arnold R
AR
Chee
Mark S
MS
Montpetit
Alexandre
A
Chagnon
Fanny
F
Ferretti
Vincent
V
Leboeuf
Martin
M
Olivier
Jean-François
JF
Phillips
Michael S
MS
Roumy
Stéphanie
S
Sallée
Clémentine
C
Verner
Andrei
A
Hudson
Thomas J
TJ
Kwok
Pui-Yan
PY
Cai
Dongmei
D
Koboldt
Daniel C
DC
Miller
Raymond D
RD
Pawlikowska
Ludmila
L
Taillon-Miller
Patricia
P
Xiao
Ming
M
Tsui
Lap-Chee
LC
Mak
William
W
Song
You Qiang
YQ
Tam
Paul K H
PK
Nakamura
Yusuke
Y
Kawaguchi
Takahisa
T
Kitamoto
Takuya
T
Morizono
Takashi
T
Nagashima
Atsushi
A
Ohnishi
Yozo
Y
Sekine
Akihiro
A
Tanaka
Toshihiro
T
Tsunoda
Tatsuhiko
T
Deloukas
Panos
P
Bird
Christine P
CP
Delgado
Marcos
M
Dermitzakis
Emmanouil T
ET
Gwilliam
Rhian
R
Hunt
Sarah
S
Morrison
Jonathan
J
Powell
Don
D
Stranger
Barbara E
BE
Whittaker
Pamela
P
Bentley
David R
DR
Daly
Mark J
MJ
de Bakker
Paul I W
PI
Barrett
Jeff
J
Chretien
Yves R
YR
Maller
Julian
J
McCarroll
Steve
S
Patterson
Nick
N
Pe'er
Itsik
I
Price
Alkes
A
Purcell
Shaun
S
Richter
Daniel J
DJ
Sabeti
Pardis
P
Saxena
Richa
R
Schaffner
Stephen F
SF
Sham
Pak C
PC
Varilly
Patrick
P
Altshuler
David
D
Stein
Lincoln D
LD
Krishnan
Lalitha
L
Smith
Albert Vernon
AV
Tello-Ruiz
Marcela K
MK
Thorisson
Gudmundur A
GA
Chakravarti
Aravinda
A
Chen
Peter E
PE
Cutler
David J
DJ
Kashuk
Carl S
CS
Lin
Shin
S
Abecasis
Gonçalo R
GR
Guan
Weihua
W
Li
Yun
Y
Munro
Heather M
HM
Qin
Zhaohui Steve
ZS
Thomas
Daryl J
DJ
McVean
Gilean
G
Auton
Adam
A
Bottolo
Leonardo
L
Cardin
Niall
N
Eyheramendy
Susana
S
Freeman
Colin
C
Marchini
Jonathan
J
Myers
Simon
S
Spencer
Chris
C
Stephens
Matthew
M
Donnelly
Peter
P
Cardon
Lon R
LR
Clarke
Geraldine
G
Evans
David M
DM
Morris
Andrew P
AP
Weir
Bruce S
BS
Tsunoda
Tatsuhiko
T
Mullikin
James C
JC
Sherry
Stephen T
ST
Feolo
Michael
M
Skol
Andrew
A
Zhang
Houcan
H
Zeng
Changqing
C
Zhao
Hui
H
Matsuda
Ichiro
I
Fukushima
Yoshimitsu
Y
Macer
Darryl R
DR
Suda
Eiko
E
Rotimi
Charles N
CN
Adebamowo
Clement A
CA
Ajayi
Ike
I
Aniagwu
Toyin
T
Marshall
Patricia A
PA
Nkwodimmah
Chibuzor
C
Royal
Charmaine D M
CD
Leppert
Mark F
MF
Dixon
Missy
M
Peiffer
Andy
A
Qiu
Renzong
R
Kent
Alastair
A
Kato
Kazuto
K
Niikawa
Norio
N
Adewole
Isaac F
IF
Knoppers
Bartha M
BM
Foster
Morris W
MW
Clayton
Ellen Wright
EW
Watkin
Jessica
J
Gibbs
Richard A
RA
Belmont
John W
JW
Muzny
Donna
D
Nazareth
Lynne
L
Sodergren
Erica
E
Weinstock
George M
GM
Wheeler
David A
DA
Yakub
Imtaz
I
Gabriel
Stacey B
SB
Onofrio
Robert C
RC
Richter
Daniel J
DJ
Ziaugra
Liuda
L
Birren
Bruce W
BW
Daly
Mark J
MJ
Altshuler
David
D
Wilson
Richard K
RK
Fulton
Lucinda L
LL
Rogers
Jane
J
Burton
John
J
Carter
Nigel P
NP
Clee
Christopher M
CM
Griffiths
Mark
M
Jones
Matthew C
MC
McLay
Kirsten
K
Plumb
Robert W
RW
Ross
Mark T
MT
Sims
Sarah K
SK
Willey
David L
DL
Chen
Zhu
Z
Han
Hua
H
Kang
Le
L
Godbout
Martin
M
Wallenburg
John C
JC
L'Archevêque
Paul
P
Bellemare
Guy
G
Saeki
Koji
K
Wang
Hongguang
H
An
Daochang
D
Fu
Hongbo
H
Li
Qing
Q
Wang
Zhen
Z
Wang
Renwu
R
Holden
Arthur L
AL
Brooks
Lisa D
LD
McEwen
Jean E
JE
Guyer
Mark S
MS
Wang
Vivian Ota
VO
Peterson
Jane L
JL
Shi
Michael
M
Spiegel
Jack
J
Sung
Lawrence M
LM
Zacharia
Lynn F
LF
Collins
Francis S
FS
Kennedy
Karen
K
Jamieson
Ruth
R
Stewart
John
J
D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics; D012641:Selection, Genetic