TY - JOUR
T1 - Comprehensive resequence analysis of a 123-kb region of chromosome 11q13 associated with prostate cancer
AU - Chung, Charles C.
AU - Boland, Joseph
AU - Yeager, Meredith
AU - Jacobs, Kevin B.
AU - Zhang, Xijun
AU - Deng, Zuoming
AU - Matthews, Casey
AU - Berndt, Sonja I.
AU - Chanock, Stephen J.
PY - 2012/4
Y1 - 2012/4
N2 - 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 variantsa118 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 20.8) with rs10896438, rs10896449, rs12793759, and rs11228565, respectively. HapMap SNPs were in linkage disequilibrium (r 20.8) 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.
AB - 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 variantsa118 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 20.8) with rs10896438, rs10896449, rs12793759, and rs11228565, respectively. HapMap SNPs were in linkage disequilibrium (r 20.8) 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.
KW - 11q13
KW - SNP
KW - prostate cancer
KW - resequence
UR - http://www.scopus.com/inward/record.url?scp=84857508188&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857508188&partnerID=8YFLogxK
U2 - 10.1002/pros.21450
DO - 10.1002/pros.21450
M3 - Article
C2 - 22468268
AN - SCOPUS:84857508188
SN - 0270-4137
VL - 72
SP - 476
EP - 486
JO - Prostate
JF - Prostate
IS - 5
ER -