Kärrman C, Bäckman B, Dixon M, Holmgren G, Forsman K
Department of Clinical Genetics, University Hospital, Umeå, Sweden.
Genomics. 1997 Jan 15;39(2):164-70. doi: 10.1006/geno.1996.4485.
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.
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陷。我们最近将常染色体显性局部发育不全性釉质发育不全（AIH2）的一个基因座定位到了4号染色体的长臂上。疾病基因定位于标记D4S392和D4S395之间17.6厘摩的区域。位于同一区间的白蛋白基因（ALB）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作用。在此，我们描述了AIH2基因座的精细定位以及通过辐射杂种图谱和基于酵母人工染色体（YAC）的序列标签位点含量图谱构建标记图谱。构建了一个由位于D4S409和D4S1558之间5厘摩区间内的11个微卫星标记组成的辐射杂种图谱。六个瑞典ADAI家族中的重组单倍型表明疾病基因位于D4S2421和ALB之间的区间。因此，ALB不太可能是致病基因。所有六个家族中的患病成员共享相同的等位基因单倍型，表明所有家族存在一个共同的祖先突变。根据辐射杂种图谱判断，AIH2关键区域小于4厘摩，跨越约4兆碱基的物理距离。构建了一个覆盖AIH2关键区域的YAC重叠群，其中包括几个潜在的候选基因。
