GENOME SCREENING BY SEARCHING FOR SHARED SEGMENTS - MAPPING A GENE FOR BENIGN RECURRENT INTRAHEPATIC CHOLESTASIS
GENOME SCREENING BY SEARCHING FOR SHARED SEGMENTS - MAPPING A GENE FOR BENIGN RECURRENT INTRAHEPATIC CHOLESTASIS
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DOI：
10.1038/ng1294-380
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发表时间：
1994-12-01
期刊：
影响因子：
30.8
通讯作者：
FREIMER, NB
中科院分区：
文献类型：
--
作者：
HOUWEN, RHJ;BAHARLOO, S;FREIMER, NB
现在，通过筛选基因组中疾病和标记等位基因之间的连锁不平衡来定位疾病基因是可行的。本报告提出了这种方法的第一个应用程序为以前未映射的位点。良性复发性肝内胆汁淤积症（BRIC）的基因定位到18号染色体上，通过寻找只有三个远亲患者共有的染色体片段。通过鉴定患者之间保守的扩展单倍型来证实筛选结果。概率计算表明，这种分部共享不太可能偶然出现。在基因组中搜索患者共有的片段是绘制疾病基因图谱的一种强有力的经验方法。计算机模拟表明，在适当的人群中，该方法可用于定位常见疾病的基因。
It is now feasible to map disease genes by screening the genome for linkage disequilibrium between the disease and marker alleles. This report presents the first application of this approach for a previously unmapped locus. A gene for benign recurrent intrahepatic cholestasis (BRIC) was mapped to chromosome 18 by searching for chromosome segments shared by only three distantly related patients. The screening results were confirmed by identyifying an extended haplotype conserved between the patients. Probability calculations indicate that such segment sharing is unlikely to arise by chance. Searching the genome for segments shared by patients is a powerful empirical method for mapping disease genes. Computer simulations suggest that, in appropriate populations, the approach may be used to localize genes for common diseases.