表皮松解性掌跖角化病一维吾尔家系致病基因研究

发布时间：2018-05-17 21:35

本文选题：表皮松解性掌跖角化病 + 连锁分析　；参考：《新疆医科大学》2010年硕士论文

【摘要】： 目的:对一表皮松解性掌跖角化病(Epidermolytic Palmoplantar Keratoderma,EPPK)家系致病基因进行定位研究,对角蛋白9、角蛋白14、角蛋白16、角蛋白17进行测序以检测其是否为该病的致病基因。方法:提取新疆地区一维吾尔族EPPK家系外周血基因组DNA,针对已知候选基因KRT9和KRT1,分别对其所在染色体位置17q12-q21和12q13选取遗传标记进行连锁分析研究,确定连锁区域后,对区域内角蛋白9(KRT9)、角蛋白14(KRT14)、角蛋白16(KRT16)、角蛋白17(KRT17)基因所有外显子进行测序分析。结果:分别得到48个家庭成员遗传标记的基因型和单倍型,经Linkage软件计算分析,发现标记D17S1787在θ=0时LOD值达到8.65,并最终将该病候选区域定位于遗传标记17/TG/36620115-D17S846之间约1Mb范围内。排除该病与位于染色体12q13上的遗传标记D12S96(θ=0时LOD=-∞)连锁。未发现KRT9、KRT14、KRT16、KRT17基因存在致病性突变。结论:提示该表皮松解性掌跖角化病家系的致病基因位于染色体17q 21.2上(chr17:36620083-37146934)约1Mb区域内,且突变位点不位于KRT9、KRT14、KRT16、KRT17基因编码区。
[Abstract]:Objective: to study the pathogenicity genes of Epidermolytic Palmoplantar Keratoderma-EPPKK in a family of epidermolytic palmoplantar keratosis, and to sequence keratin 9, keratin 14, keratin 16 and keratin 17. Methods: genomic DNA of peripheral blood was extracted from a Uygur EPPK pedigree from Xinjiang area. For known candidate genes KRT9 and KRT1, the genetic markers of 17q12-q21 and 12q13 were selected for linkage analysis, and the linkage regions were determined. All exons of keratin 9 (KRT9), keratin 14 (KRT14), keratin 16 (KRT16) and keratin 17 (KRT17) were sequenced. Results: the genotypes and haplotypes of 48 family members were obtained respectively. The LOD value of the marker D17S1787 was 8.65 at 胃 = 0, and the candidate region of the disease was located within the range of 1Mb between the genetic markers 17/TG/36620115-D17S846. The exclusion of the disease was linked to the genetic marker D12S96 (胃 = 0) located on the chromosome 12q13. No pathogenicity mutation was found in KRT9, KRT14, KRT16, KRT17 gene. Conclusion: the pathogenetic gene of this epidermolytic palmoplantar keratosis family is located in the 1Mb region of chromosome 17q21.2), and the mutation site is not located in the coding region of KRT9 / KRT14 / KRT16 / KRT17 gene.
【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R758.5

【参考文献】