Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients.
Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients.
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DOI：
10.1371/journal.pone.0025059
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kawakami H
中科院分区：
文献类型：
--
作者：
Hagiwara K;Morino H;Shiihara J;Tanaka T;Miyazawa H;Suzuki T;Kohda M;Okazaki Y;Seyama K;Kawakami H
与疾病相关的不常见的基因通常很难识别；从少数无关患者中找出它们的方法将会有很大帮助。为了建立这样一种检测隐性基因的方法，我们对纯合作图(HM)进行了改进，使其建立在纯合单倍型(HM On HH)分析的基础上。对6例由创始人基因引起的Siiyama型α-1抗胰蛋白酶缺乏症患者的分析表明，任何2例患者(长度：1.2-21.8厘米器官，中位数：1.6厘米器官)都能准确地找到正确的基因位点。对于这6名患者和54名健康受试者的测试人群，该方法准确地识别了这6名患者，并将基因座精确地定位到1.4厘米长的片段。使用合成数据的分析表明，该分析对来自最近的共同祖先(MRCA)的IBD片段非常有效，该祖先生活在不到60代人之前。该分析不适用于一般人群中频率大于0.1的基因。因此，HM on HH分析是一项强大的技术，适用于少数未知亲缘关系的患者，并将加快隐性疾病致病基因的鉴定。
Genes involved in disease that are not common are often difficult to identify; a method that pinpoints them from a small number of unrelated patients will be of great help. In order to establish such a method that detects recessive genes identical-by-descent, we modified homozygosity mapping (HM) so that it is constructed on the basis of homozygosity haplotype (HM on HH) analysis. An analysis using 6 unrelated patients with Siiyama-type α1-antitrypsin deficiency, a disease caused by a founder gene, the correct gene locus was pinpointed from data of any 2 patients (length: 1.2–21.8 centimorgans, median: 1.6 centimorgans). For a test population in which these 6 patients and 54 healthy subjects were scrambled, the approach accurately identified these 6 patients and pinpointed the locus to a 1.4-centimorgan fragment. Analyses using synthetic data revealed that the analysis works well for IBD fragment derived from a most recent common ancestor (MRCA) who existed less than 60 generations ago. The analysis is unsuitable for the genes with a frequency in general population more than 0.1. Thus, HM on HH analysis is a powerful technique, applicable to a small number of patients not known to be related, and will accelerate the identification of disease-causing genes for recessive conditions.
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DOI：
10.1056/nejmra0808700
发表时间：
2009-04-23
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hardy J;Singleton A
通讯作者：
Singleton A
DOI：
10.1097/gim.0b013e318203cff2
发表时间：
2011-03
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Berg JS;Evans JP;Leigh MW;Omran H;Bizon C;Mane K;Knowles MR;Weck KE;Zariwala MA
通讯作者：
Zariwala MA
影响因子：
3
作者：
Huqun;Fukuyama, Shun-ichiro;Hagiwara, Koichi
通讯作者：
Hagiwara, Koichi
影响因子：
9.8
作者：
Browning, Sharon R.;Browning, Brian L.
通讯作者：
Browning, Brian L.
影响因子：
64.8
作者：
Maruyama, Hirofumi;Morino, Hiroyuki;Kawakami, Hideshi
通讯作者：
Kawakami, Hideshi