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Comprehensive resequence analysis of a 123‐kb region of chromosome 11q13 associated with prostate cancer
Author(s) -
Chung Charles C.,
Boland Joseph,
Yeager Meredith,
Jacobs Kevin B.,
Zhang Xijun,
Deng Zuoming,
Matthews Casey,
Berndt Sonja I.,
Chanock Stephen J.
Publication year - 2012
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21450
Subject(s) - international hapmap project , single nucleotide polymorphism , linkage disequilibrium , genetics , biology , 1000 genomes project , indel , genetic association , snp , snp array , dbsnp , genome wide association study , prostate cancer , tag snp , computational biology , cancer , gene , genotype
BACKGROUND Genome‐wide association studies of prostate cancer have identified single nucleotide polymorphism (SNP) markers in a region of chromosome 11q13.3 in men of European decent. A fine‐mapping analysis with tag SNPs in the cancer genetic markers of susceptibility study identified three independent loci, marked by rs10896438, rs12793759, and rs10896449. This study further annotates common and uncommon variation across this region. METHODS A next generation resequence analysis of a 122.9‐kb region of 11q13.3 (68,642,755‐68,765,690) was conducted in 78 unrelated individuals of European background, 1 CEPH trio, and 1 YRI trio. RESULTS In total, 644 polymorphic loci were identified by our sequence analysis. Of these, 166 variants—118 SNPs and 48 insertion‐deletion polymorphisms (indels)—were novel, namely not present in the 1000 Genomes or International HapMap Projects. We identified 22, 25, 6, and 4 variants strongly correlated (r 2 ≥ 0.8) with rs10896438, rs10896449, rs12793759, and rs11228565, respectively. HapMap SNPs were in linkage disequilibrium (r 2 ≥ 0.8) with 48%, 69%, 14%, and 60% of SNPs marking bins by rs10896438, rs10896449, rs12793759, and rs11228565, respectively. CONCLUSIONS Our next generation resequence analysis compliments publicly available datasets of European descent (HapMap, build 28 and 1000 Genome, Pilot 1, October 2010), underscoring the value of targeted resequence analysis prior to initiating functional studies based on public databases alone. Increasing the number of common variants enables investigators to better prioritize variants for functional studies designed to uncover the biological basis of the direct association(s) in the region. Prostate 72:476–486, 2012. © 2011 Wiley Periodicals, Inc.