RESUMO
The basal cell nevus syndrome (Gorlin syndrome) is characterized by multiple basal cell carcinomas and diverse developmental defects. The gene responsible for this syndrome has been mapped previously to a 2 cM interval between D9S196 and D9S 180 at 9q22.3, and very recently mutations of a candidate gene in this region--the human homolog of the Drosophila patched gene have been identified. We report here on physical mapping studies integrating a contig of yeast artificial chromosomes and bacterial artificial chromosomes with a long-range map spanning approximately 5 Mb between the recombination-determined flanking markers. Six genes have been mapped to this interval.
Assuntos
Síndrome do Nevo Basocelular/genética , Mapeamento Cromossômico , 17-Hidroxiesteroide Desidrogenases/genética , Animais , Cromossomos Artificiais de Levedura , Cromossomos Humanos Par 9/genética , Drosophila/genética , Frutose-Bifosfatase/genética , Genes de Insetos , Marcadores Genéticos , Humanos , Polimorfismo Genético , Proteínas de Ligação ao Cap de RNA , Proteínas de Ligação a RNA/genética , Sequências Repetitivas de Ácido Nucleico , Homologia de Sequência do Ácido Nucleico , Sitios de Sequências RotuladasRESUMO
Nail-patella syndrome (NPS), or onychoosteodysplasia, is an autosomal dominant, pleiotropic disorder characterized by nail dysplasia, absent or hypoplastic patellae, iliac horns, and nephropathy. Previous studies have demonstrated linkage of the nail-patella locus to the ABO and adenylate kinase loci on human chromosome 9q34. As a first step toward isolating the NPS gene, we present linkage analysis with 13 polymorphic markers in five families with a total of 69 affected persons. Two-point linkage analysis with the program MLINK showed tight linkage of NPS and the anonymous markers D9S112 (LOD = 27.0; theta = .00) and D9S315 (LOD = 22.0; theta = .00). Informative recombination events place the NPS locus within a 1-2-cM interval between D9S60 and the adenylate kinase gene (AK1).
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 9 , Síndrome da Unha-Patela/genética , Feminino , Ligação Genética , Genótipo , Humanos , Masculino , Repetições de Microssatélites , LinhagemRESUMO
A complete overlapping clone map of a 1.7-Mb region from DBH to D9S67 that includes the TSC1 candidate region has been constructed. The map includes YAC and cosmid clones, contains STS approximately every 50 kb on average, and establishes the order of five previously unordered loci. The overall physical length of this segment of chromosome 9q34 (1.7 Mb) is significantly less than expected compared to its estimated genetic length (approximately 10 cM). Consequently, the physical length of the TSC1 candidate region is substantially less than predicted by a genetic distance of approximately 2 cM.