Mapping The Disease Gene In A Disseminated Superficial Actinic Porokeratosis Family And Study Susceptibility Genes Of Late-onset Type 2 Diabetes Mellitus

CHAPTER I Mapping the locus of the disease gene in adisseminated superficial actinic porokeratosis family[Abstract] Background Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant skin disorder characterized by numerous annular papules with subtle raised hyperkeratotic borders and slightly atrophic centers, which develops in teenages in sun-exposed areas of skin. Our previous studies showed DSAP was a genetically heterogeneous disorder and identified two loci for the DSAP. DSAP1 was mapped to a 9.6 cM region on chromosome 12q23.2-24.1 with the most likely position between the markers D12S1727 and D12S1605, while DSAP2 was located to a 6.4 cM region between markers D15S1023 and D15S1030 on chromosome 15q25.1-26.1, Objective To confirm these finding and refine the location of DSAP loci. Methods Genome-wide scan and linkage analysis were carried out in a Chinese DSAP family. We have ascertained the interval of the disease locus by haplotype analysis and reduced the interval by comparing previous data. Results Genome-wide scan and linkage analysis suggested that the disease locus of this family is also linked to chromosome 12q. Fine mapping and evaluation of recombinants suggested that the disease gene of this family lies in the 10.6-cM interval between D12S338 and D12S1341 at chromosome 12q23.2-24.1. Our data, together with our previously published ones that define D12S1605 as a distally flanking marker, possible refine the location of DSAP1 to a 4.4-cM interval between D12S338 and D12S1605 at chromosome 12q23.2-24.1. Conclusions This study confirmed and possibly refined genetic localization of DSAP1 to a 4.4cM region between markers D12S338 and D12S1605 at chromosome 12q23.2-24.1.