播散性浅表性光线性汗孔角化症DSAP1位点的精细定位和候选基因的突变检测(英文)  

Refinement of DSAP1 Locus and Mutation Detection for Candidate Genes

作　　者：张正华[1] 牛振民[1] 袁文涛[1] 赵敬军[2] 蒋法兴[2] 张静[1] 柴宝[2] 熊晓燕[1] 项蕾红[3] 王艺[1] 徐世杰[1] 刘维达[2] 郑志忠[3] 黄薇[1] 

机构地区：[1]国家人类基因组南方研究中心 [2]中国协和医科大学中国医学科学院皮肤病研究所,南京210042 [3]复旦大学附属华山医院皮肤科,上海200040

出　　处：《Acta Genetica Sinica》2005年第7期667-674,共8页

基　　金：国家自然科学基金项目(编号:39993420);科技部基础研究重点项目(编号:G1998051019);国家"863"攻关计划(编号: 2002BA711A10);上海科学技术发展基金项目(批准号:00DJ14003)资助~~

摘　　要：播散性浅表性光线性汗孔角化症(DSAP)是一种以多个浅表的角化性皮损,边缘轻微嵴状角化性隆起为特征的少见的慢性角化性皮肤病,呈常染色体显性遗传。以往的研究将该病基因定位于12q23.2 24.1区域(DSAP1)和15q25.1 26.1区域(DSAP2)。本研究对2个无关的六代DSAP家系进行了全基因组扫描和连锁分析,结果显示,这2个DSAP家系在D12S84位点的最高累积LOD值为8.28(θ=0.00)。单倍型分析结果显示,这2个DSAP家系致病基因位于12q24.1～q24.2(D12S330和D12S354)之间8.0cM的区域内。该区域与DSAP1 的致病区域部分重叠。对重叠区域内6个候选基因(CRY1,PWP1,ASCL4,PRDM4,KIAA0789和CMKLR1)的编码区进行序列分析,在DSAP病人中未发现突变位点。提示该6个候选基因可能与这2个DSAP家系的发病机理无关。Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant chronic keratinization disorder,characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border.In previous studies,the disease gene was mapped to 12q23.2-24.1 (DSAP1),and 15q25.1-26.1 (DSAP2).In this study,genome-wide scan was performed in two unrelated six-generation DSAP pedigrees to localize and identify the candidate gene(s) of disease.Linkage analysis showed that the cumulative maximum two-point lod score of 8.28 was obtained with the marker D12S84 at a recombination fraction θ of 0.00.Haplotype analysis defined an 8.0 cM critical region for DSAP gene(s) between markers D12S330 and D12S354 on 12q24.1-q24.2,which partially overlapped with the region identified for DSAP1.DNA sequencing of the coding exons of six candidate genes (CRY1,PWP1,ASCL4,PRDM4,KIAA0789 and CMKLR1) on the basis of their location in the critical overlap interval,failed to detect any mutation in DSAP patients.Thus,it is likely that these genes are not involved in DSAP.

关 键 词：播散性浅表性光线性汗孔角化症(DSAP) 全基因组扫描 连锁分析 突变检测 

分 类 号：R758.5[医药卫生—皮肤病学与性病学]