播散性浅表汗孔角化病的基因定位

Gene Mapping of Disseminated Superficial Porokeratosis

目的对收集的汉族山东籍一家系6代共254人的播散性浅表汗孔角化病家系进行基因定位,以期识别该病的致病基因.方法收集家系成员的临床资料及血液样本,抽提外周血基因组DNA,选用382对来自常染色体的荧光标记引物,进行全基因组扫描,用Genescan和Genotyper软件进行基因分型,用Linkage软件包进行连锁分析,初步明确致病基因的区域.然后,在该区域内选择覆盖密度更高的10对引物进行精细定位,缩小致病基因的范围.结果定位结果发现DSP致病基因与微卫星标记D12S78两点之间LOD值最大,为3.06(重组率θ=0.00).精细定位后将DSP的致病基因定位于标记物D12S326和D12S79之间约38.5 cM区域内.结论DSP的致病基因位于染色体12q21.2～24.2.

Objective To target the disease gene of disseminated superficial form of porokeratosis (DSP) in a six-generation of a Chinese family including a total of 254 family members in Shandong province. Methods The clinical data and the peripheral blood samples were collected in the pedigree members. The genomic DNA was extracted from the blood samples. A genome-wide scan was performed using 382 pairs of primers labelled with fluorescent stain. The primers were designed for human autosomes. The sequencing results were analyzed by the software of Genescan and Genotype. Linkage analysis was processed by Linkage software package to define the region of disease gene. For fine targeting the disease gene, other 10 micro-satellite markers for the above region were set up for further fine sequencing. Results We obtained the maximum two-point LOD scores of 3.06 at micro-satellite marker D12S78 (recombination fraction θ = 0.00). After fine mapping, the DSP gene is located within a 38.5 cM region between markers D12S326 and D12S79. Conclusion The DSP gene is mapped to chromosome 12q21.2~24.2.