Pairwise shared genomic segment analysis in three Utah high-risk breast cancer pedigrees.
Pairwise shared genomic segment analysis in three Utah high-risk breast cancer pedigrees.
复制标题
DOI：
10.1186/1471-2164-13-676
复制
发表时间：
2012-11-28
期刊：
影响因子：
4.4
通讯作者：
Camp NJ
中科院分区：
文献类型：
--
作者：
Cai Z;Thomas A;Teerlink C;Farnham JM;Cannon-Albright LA;Camp NJ
我们应用了一种新的加权两两共享基因组片段（pSGS）分析，对三个扩展的高风险乳腺癌家系的高密度全基因组SNP数据进行易感基因定位。利用该方法，在染色体2、4、7和8上鉴定出4个全基因组暗示区，在染色体14上鉴定出一个边缘暗示区。另外还观察到七个至少有名义证据的地区。特别值得注意的是，在这12个区域中，有3个区域分别在两个谱系中被确定；染色体4,7和14。后续的双家系pSGS分析进一步表明，这三个地区的家系之间存在过多的基因组共享，这表明这些地区的潜在易感等位基因可能是共同的。总体而言，所确定的pSGS区域相当大（平均32.2 Mb），但范围很宽（0.3 - 88.2 Mb）。发现的几个区域与先前涉及乳腺癌风险的位点和基因重叠，包括NBS1、BRCA1和RAD51L1。我们的分析提供了在这些高风险家系中寻找的几个感兴趣的位点，并说明了加权pSGS方法和扩展家系在复杂疾病基因定位中的效用。在共享个体中对这些基因座进行集中测序是进一步绘制这些区域关键潜在易感性变异的自然下一步。
We 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. Using 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. Our 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.
登录
查看更多内容
影响因子：
3.8
作者：
Sliwinski, Tomasz;Ziemba, Pawel;Blasiak, Janusz
通讯作者：
Blasiak, Janusz
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Smith, Paula;McGuffog, Lesley;Easton, Douglas F;Mann, Graham J;Pupo, Gulietta M;Newman, Beth;Chenevix-Trench, Georgia;Szabo, Csilla;Southey, Melissa;Renard, Helene;Odefrey, Fabrice;Lynch, Henry;Stoppa-Lyonnet, Dominique;Couch, Fergus;Hopper, John L;Giles, Graham G;McCredie, Margaret R E;Buys, Saundra;Andrulis, Irene;Senie, Ruby;Goldgar, David E;Oldenburg, Rogier;Kroeze-Jansema, Karin;Kraan, Jaennelle;Meijers-Heijboer, Hanne;Klijn, Jan G M;van Asperen, Christi;van Leeuwen, Inge;Vasen, Hans F A;Cornelisse, Cees J;Devilee, Peter;Baskcomb, Linda;Seal, Sheila;Barfoot, Rita;Mangion, Jon;Hall, Anita;Edkins, Sarah;Rapley, Elizabeth;Wooster, Richard;Chang-Claude, Jenny;Eccles, Diana;Evans, D Gareth;Futreal, P Andrew;Nathanson, Katherine L;Weber, Barbara L;Rahman, Nazneen;Stratton, Michael R
通讯作者：
Stratton, Michael R
影响因子：
2.6
作者：
Long, Ji-Rong;Egan, Kathleen M.;Zheng, Wei
通讯作者：
Zheng, Wei
影响因子：
1.8
作者：
Albright, Lisa A. Cannon
通讯作者：
Albright, Lisa A. Cannon