Published online before print
January 14, 2003
Genome Research, DOI: 10.1101/gr.302003
Linkage Disequilibrium and Haplotype Diversity in the Genes of the Renin-Angiotensin System: Findings From the Family Blood Pressure Program
Xiaofeng
Zhu,1,4,5
Denise
Yan,2,4
Richard S.
Cooper,1
Amy
Luke,1
Morna A.
Ikeda,2
Yen-Pei C.
Chang,2
Alan
Weder,3 and
Aravinda
Chakravarti2
1 Department of Preventive Medicine and Epidemiology,
Loyola Stritch School of Medicine, Maywood, Illinois 60153, USA;
2 McKusick-Nathans Institute of Genetic Medicine, Johns
Hopkins University, Baltimore, Maryland 21287, USA; 3 Division
of Hypertension, University of Michigan School of Medicine,
Ann Arbor, Michigan 48109, USA
Association studies of candidate genes with complex traits have
generally used one or a few single nucleotide polymorphisms (SNPs),
although variation in the extent of linkage disequilibrium (LD) within
genes markedly influences the sensitivity and precision of association
studies. The extent of LD and the underlying haplotype structure for
most candidate genes are still unavailable. We sampled 193 blacks
(African-Americans) and 160 whites (European-Americans) and
estimated the intragenic LD and the haplotype structure in four genes
of the renin-angiotensin system. We genotyped 25 SNPs, with all but
one of the pairs spaced between 1 and 20 kb, thus providing resolution
at small scale. The pattern of LD within a gene was very heterogeneous.
Using a robust method to define haplotype blocks, blocks of limited
haplotype diversity were identified at each locus; between these
blocks, LD was lost owing to the history of recombination events. As
anticipated, there was less LD among blacks, the number of haplotypes
was substantially larger, and shorter haplotype segments were found,
compared with whites. These findings have implications for
candidate-gene association studies and indicate that variation between
populations of European and African origin in haplotype diversity is
characteristic of most genes.
[The sequence data described
in this paper are available in GenBank under the following accession
nos: AGT, MIM 106150; Renin, MIM 179820;
ACE, MIM 106180; Angiotensin receptor I, MIM 106165. Supplementary material is available online at
http://www.genome.org.]
4
These authors contributed equally to this work.
5
Corresponding author.
13:000-000 © by Cold Spring Harbor Laboratory Press ISSN 1088-9051/03 $5.00
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