Identity-by-descent mapping in a Scandinavian multiple sclerosis cohort.
Identity-by-descent mapping in a Scandinavian multiple sclerosis cohort.
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DOI：
10.1038/ejhg.2014.155
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发表时间：
2015-05
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影响因子：
--
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在试图绘制携带导致多发性硬化症（MS）风险的罕见基因变异的染色体区域时，我们使用BEAGLE 4.0软件的精细IBD分析确定了共有的IBD片段。IBD定位的目的是识别从共同祖先继承的片段，并且在病例-病例对中更频繁地共享。在Illumina Human Quad 660芯片上对总共2106名北欧来源的MS患者和624名匹配的对照进行基因分型，并添加了在Illumina HumanHap 550和Illumina 1 M上分型的另外1352名种族匹配的对照。质量控制总共留下441731个标记用于分析。在通过下降和显著性检验鉴定共享的片段后，应用具有低IBD共享的标记物的过滤函数。发现染色体5、9、14和19上的四个区域与MS的风险显著相关。然而，除了一个标记之外，所有标记都位于端粒，包括非常远端的标记。由于方法的原因，这样的片段具有低的IBD信号共享，并且容易成为假阳性。19号染色体上的一个标记达到全基因组显著性，并且不是远端标记之一。该标记位于GNA 11基因内，该基因先前与MS没有关联。我们得出结论，IBD映射不足以识别MS风险基因座，即使在种族相对同质的人群中，或者罕见的变异不充分存在。
In an attempt to map chromosomal regions carrying rare gene variants contributing to the risk of multiple sclerosis (MS), we identified segments shared identical-by-descent (IBD) using the software BEAGLE 4.0's refined IBD analysis. IBD mapping aims at identifying segments inherited from a common ancestor and shared more frequently in case–case pairs. A total of 2106 MS patients of Nordic origin and 624 matched controls were genotyped on Illumina Human Quad 660 chip and an additional 1352 ethnically matched controls typed on Illumina HumanHap 550 and Illumina 1M were added. The quality control left a total of 441 731 markers for the analysis. After identification of segments shared by descent and significance testing, a filter function for markers with low IBD sharing was applied. Four regions on chromosomes 5, 9, 14 and 19 were found to be significantly associated with the risk for MS. However, all markers but for one were located telomerically, including the very distal markers. For methodological reasons, such segments have a low sharing of IBD signals and are prone to be false positives. One marker on chromosome 19 reached genome-wide significance and was not one of the distal markers. This marker was located within the GNA11 gene, which contains no previous association with MS. We conclude that IBD mapping is not sufficiently powered to identify MS risk loci even in ethnically relatively homogenous populations, or that alternatively rare variants are not adequately present.
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DOI：
10.1186/bcr811
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Wedrén S;Lovmar L;Humphreys K;Magnusson C;Melhus H;Syvänen AC;Kindmark A;Landegren U;Fermér ML;Stiger F;Persson I;Baron J;Weiderpass E
通讯作者：
Weiderpass E
影响因子：
7
作者：
Gusev, Alexander;Lowe, Jennifer K.;Pe'er, Itsik
通讯作者：
Pe'er, Itsik
影响因子：
2.1
作者：
Palin, Kimmo;Campbell, Harry;Durbin, Richard
通讯作者：
Durbin, Richard
影响因子：
120.7
作者：
Barcellos, LF;Thomson, G;Klitz, W
通讯作者：
Klitz, W
影响因子：
5.8
作者：
Gray, O. M.;Abdeen, H.;Hawkins, S. A.
通讯作者：
Hawkins, S. A.