Localization of a recessive gene for North American Indian childhood cirrhosis to chromosome region 16q22 -: and identification of a shared haplotype
Localization of a recessive gene for North American Indian childhood cirrhosis to chromosome region 16q22 -: and identification of a shared haplotype
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DOI：
10.1086/302993
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发表时间：
2000-07-01
影响因子：
9.8
通讯作者：
Mitchell, GA
中科院分区：
文献类型：
--
作者：
Bétard, C;Rasquin-Weber, A;Mitchell, GA
北美印第安儿童肝硬化（NAIC，或 CIRH1A）是一种孤立的非综合征型家族性胆汁淤积，在魁北克西北部的奥及布韦-克里族儿童和年轻人中报告。传播模式与常染色体隐性遗传模式一致。为了绘制 NAIC 基因座图，我们对三个 DNA 池样本进行了全基因组扫描，这些样本来自 13 名患者、16 名未受影响的兄弟姐妹以及来自 5 个家庭的 22 名父母。对 333 个高度多态性标记的分析显示，受影响个体之间有 3 个标记具有明显过多的等位基因共享。额外的绘图确定了所有受影响个体共有的染色体 16q 片段。当使用程序 FASTLINK/LINKAGE 并假设完全渗透常染色体隐性遗传模式时，对于标记为 D16S3067 的重组分数为 0，观察到最大 LOD 得分为 4.44。所有患者共有跨度为 4.9 cM 的五标记单倍型（D16S3067、D16S752、D16S2624、D16S3025 和 D16S3106）。这些结果提供了染色体 16q22 上候选基因连锁的重要证据。
North American Indian childhood cirrhosis (NAIC, or CIRH1A) is an isolated nonsyndromic form of familial cholestasis reported in Ojibway-Cree children and young adults in northwestern Quebec. The pattern of transmission is consistent with an autosomal recessive mode of inheritance. To map the NAIC locus, we performed a genomewide scan on three DNA pools of samples from 13 patients, 16 unaffected siblings, and 22 parents from five families. Analysis of 333 highly polymorphic markers revealed 3 markers with apparent excess allele sharing among affected individuals. Additional mapping identified a chromosome 16q segment shared by all affected individuals. When the program FASTLINK/LINKAGE was used and a completely penetrant autosomal recessive mode of inheritance was assumed, a maximum LOD score of 4.44 was observed for a recombination fraction of 0, with marker D16S3067. A five-marker haplotype (D16S3067, D16S752, D16S2624, D16S3025, and D16S3106) spanning 4.9 cM was shared by all patients. These results provide significant evidence of linkage for a candidate gene on chromosome 16q22.