Mapping of the locus for autosomal dominant amelogenesis imperfecta (AIH2) to a 4-Mb YAC contig on chromosome 4q11-q21.
Mapping of the locus for autosomal dominant amelogenesis imperfecta (AIH2) to a 4-Mb YAC contig on chromosome 4q11-q21.
复制标题
将常染色体显性釉质生成不全 (AIH2) 基因座映射到染色体 4q11-q21 上的 4-Mb YAC 重叠群。
DOI：
10.1006/geno.1996.4485
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发表时间：
1997
期刊：
影响因子：
4.4
通讯作者：
K. Forsman
中科院分区：
文献类型：
--
作者：
C. Kärrman;B. Bäckman;M. Dixon;G. Holmgren;K. Forsman
牙釉质发育不全（AI）是一组临床和遗传异质性的遗传性釉质缺损。我们最近绘制了一个常染色体显性局部发育不全性釉质发育不全性牙釉质形成（AIH2）的基因位点的长臂4号染色体。该疾病基因定位于标记D4S392和D4S395之间的17.6 cM区域。白蛋白基因（ALB）位于同一区间，是常染色体显性AI（ADAI）的候选基因，因为白蛋白在釉质成熟中具有潜在的作用。在这里，我们描述了精细的AIH2基因座的映射和标记地图的建设辐射杂交映射和酵母人工染色体（YAC）为基础的序列标记的位点内容映射。利用D4S409和D4S1558之间的11个微卫星标记构建了一张辐射杂交图谱。在6个瑞典ADAI家族中的重组单倍型表明，该疾病基因位于D4S2421和ALB之间的区间。因此，ALB不太可能是致病基因。所有六个家族中的受影响成员共享相同的等位基因单倍型，表明所有家族中存在共同的祖先突变。AIH2的临界区域小于4厘米，从辐射混合图判断，跨越的物理距离约为4 Mb。构建了AIH2关键区的YAC重叠群，包括几个潜在的候选基因。
Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of inherited enamel defects. We recently mapped a locus for autosomal dominant local hypoplastic amelogenesis imperfecta (AIH2) to the long arm of chromosome 4. The disease gene was localized to a 17.6-cM region between the markers D4S392 and D4S395. The albumin gene (ALB), located in the same interval, was a candidate gene for autosomal dominant AI (ADAI) since albumin has a potential role in enamel maturation. Here we describe refined mapping of the AIH2 locus and the construction of marker maps by radiation hybrid mapping and yeast artificial chromosome (YAC)-based sequence tagged site-content mapping. A radiation hybrid map consisting of 11 microsatellite markers in the 5-cM interval between D4S409 and D4S1558 was constructed. Recombinant haplotypes in six Swedish ADAI families suggest that the disease gene is located in the interval between D4S2421 and ALB. ALB is therefore not likely to be the disease-causing gene. Affected members in all six families share the same allele haplotypes, indicating a common ancestral mutation in all families. The AIH2 critical region is less than 4 cM and spans a physical distance of approximately 4 Mb as judged from radiation hybrid maps. A YAC contig over the AIH2 critical region including several potential candidate genes was constructed.