MAPPING OF THE LOCUS FOR AUTOSOMAL-DOMINANT - AMELOGENESIS IMPERFECTA(AIH2) TO A 4-MB YAC CONTIG ON CHROMOSOME 4Q11-Q21

Amelogenesis imperfecta (AI) is a clinically and genetically heterogen eous group of inherited enamel defects. We recently mapped a locus for autosomal dominant local hypoplastic amelogenesis imperfecta (AIH2) t o 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 matur ation. Here we describe refined mapping of the AIH2 locus and the cons truction of marker maps by radiation hybrid mapping and yeast artifici al chromosome (YAC)-based sequence tagged site-content mapping. A radi ation hybrid map consisting of 11 microsatellite markers in the 5-cM i nterval between D4S409 and D4S1558 was constructed. Recombinant haplot ypes in six Swedish ADAI families suggest that the disease gene is loc ated in the interval between D4S2421 and ALB. ALB is therefore not lik ely to be the disease-causing gene. Affected members in all six famili es share the same allele haplotypes, indicating a common ancestral mut ation in all families. The AIH2 critical region is less than 4 cM and spans a physical distance of approximately 4 Mb as judged from radiati on hybrid maps. A YAC contig over the AIH2 critical region including s everal potential candidate genes was constructed. (C) 1997 Academic Pr ess