Pairwise shared genomic segment analysis in three Utah high-risk breast cancer pedigrees

BMC Genomics

Research Article

Zheng Cai¹  Craig Teerlink²  Nicola J Camp²  Alun Thomas²  James M Farnham²  Lisa A Cannon-Albright³ 

[1] Department of Biomedical Informatics, University of Utah Medical School, Health Sciences Education Building, 84112, Salt Lake City, UT, USA;Division of Genetic Epidemiology, University of Utah Medical School, 391 Chipeta Way Suite D, 84108, Salt Lake City, UT, USA;Division of Genetic Epidemiology, University of Utah Medical School, 391 Chipeta Way Suite D, 84108, Salt Lake City, UT, USA;George E. Wahlen Department of Veterans Affairs Medical Center, 500 Foothill Drive, 84148, Salt Lake City, UT, USA;

关键词: Breast cancer;    High-risk pedigrees;    Susceptibility;    Germline;    Genomic sharing;   

DOI  :  10.1186/1471-2164-13-676

 received in 2012-05-04, accepted in 2012-11-23,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundWe applied a new weighted pairwise shared genomic segment (pSGS) analysis for susceptibility gene localization to high-density genomewide SNP data in three extended high-risk breast cancer pedigrees.ResultsUsing this method, four genomewide suggestive regions were identified on chromosomes 2, 4, 7 and 8, and a borderline suggestive region on chromosome 14. Seven additional regions with at least nominal evidence were observed. Of particular note among these total twelve regions were three regions that were identified in two pedigrees each; chromosomes 4, 7 and 14. Follow-up two-pedigree pSGS analyses further indicated excessive genomic sharing across the pedigrees in all three regions, suggesting that the underlying susceptibility alleles in those regions may be shared in common. In general, the pSGS regions identified were quite large (average 32.2 Mb), however, the range was wide (0.3 – 88.2 Mb). Several of the regions identified overlapped with loci and genes that have been previously implicated in breast cancer risk, including NBS1, BRCA1 and RAD51L1.ConclusionsOur analyses have provided several loci of interest to pursue in these high-risk pedigrees and illustrate the utility of the weighted pSGS method and extended pedigrees for gene mapping in complex diseases. A focused sequencing effort across these loci in the sharing individuals is the natural next step to further map the critical underlying susceptibility variants in these regions.

【 授权许可】

Unknown   
© Cai et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.