Stacey B. Gabriel,1
Stephen F. Schaffner,1
Huy Nguyen,1
Jamie M. Moore,1
Jessica Roy,1
Brendan Blumenstiel,1
John Higgins,1
Matthew DeFelice,1
Amy Lochner,1
Maura Faggart,1
Shau Neen Liu-Cordero,12
Charles Rotimi,3
Adebowale Adeyemo,4
Richard Cooper,5
Ryk Ward,6
Eric S. Lander,12
Mark J. Daly,1
David Altshuler17*
Haplotype-based methods offer a powerful approach to disease gene
mapping, based on the association between causal mutations and the
ancestral haplotypes on which they arose. As part of The SNP Consortium
Allele Frequency Projects, we characterized haplotype patterns across
51 autosomal regions (spanning 13 megabases of the human genome) in
samples from Africa, Europe, and Asia. We show that the human genome
can be parsed objectively into haplotype blocks: sizable regions over
which there is little evidence for historical recombination and within
which only a few common haplotypes are observed. The boundaries of
blocks and specific haplotypes they contain are highly correlated
across populations. We demonstrate that such haplotype frameworks
provide substantial statistical power in association studies of common
genetic variation across each region. Our results provide a foundation
for the construction of a haplotype map of the human genome,
facilitating comprehensive genetic association studies of human
disease.
1 Whitehead/MIT Center for Genome Research,
Cambridge, MA 02139, USA.
2 Department of Biology,
Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
3 National Human Genome Center, Howard University,
Washington, DC 20059, USA.
4 Department of
Pediatrics, College of Medicine, University of Ibadan, Ibadan, Nigeria.
5 Department of Preventive Medicine and
Epidemiology, Loyola University Medical School, Maywood, IL 60143, USA.
6 Institute of Biological Anthropology, University
of Oxford, Oxford, England OX2 6QS.
7 Departments of
Genetics and Medicine, Harvard Medical School; Department of Molecular
Biology and Diabetes Unit, Massachusetts General Hospital, Boston, MA
02114, USA.
*
To whom correspondence should be addressed. E-mail:
altshuler{at}molbio.mgh.harvard.edu
