定位于12q24的腓骨肌萎缩症2L型10个候选基因的排除克隆  

Cloning to rule out 10 candidate genes located in chromosome 12q24 for Charcot-Marie-Tooth disease type 2L

作　　者：张如旭[1] 唐北沙[1] 资晓宏[2] 罗巍[3] 夏昆[4] 潘乾[4] 胡政茂[4] 赵国华[1] 郭科[2] 

机构地区：[1]中南大学湘雅医院神经内科,长沙湘雅三医院神经内科410008 [2]湘雅三医院神经内科 [3]浙江医科大学附属二医院神经内科 [4]中国医学遗传学国家重点实验室

出　　处：《中华医学遗传学杂志》2006年第2期189-191,共3页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(30300200);国家863计划项目(2004AA227040)~~

摘　　要：目的克隆定位于12号染色体微卫星标记D12S1720和D12S1611之间约6.8cM的区间内的腓骨肌萎缩症2L型的致病基因。方法应用生物信息学方法筛选10个候选基因,设计合成扩增10个基因外显子及外显子与内含子交界的引物,DNA直接测序法进行序列变异分析。结果在基因外显子及侧翼区共发现11个序列变异,其中杂合序列变异共5个,纯合序列变异共6个。上述序列变异与疾病表型无共分离现象。结论排除了10个候选基因(TAOK3、RAB35、RPLP0、PXN、RNF10、RHOF、VPS33A、RSN、DENR、RNP24)为腓骨肌萎缩症2L型致病基因的可能。发现了以上10个候选基因共11个单核苷酸多态,除镜影细胞(reed-steinbergcell,RS)细胞特异性中间丝相关蛋白基因的3207G→C在多态数据库已报道,其余均为新发现的单核苷酸多态。Objective To clone the disease-causing genes possibly existing in 6.8 cM distance between microsatellite markers D12S1720 and D12S1611 in chromosome 12q24 for Charcot-Marie-Tooth disease type 2L（CMT2L）. Methods Ten positional and functional candidate genes were chosen among all known genes in this locus region by bioinformatics inqury. Mutation detection was performed by sequencing the exons and intron-exon junctions of the candidate genes. Results Eleven sequence variations, that included 5 heterozygous and 6 homozygons variations, were detected in the exons and flanking areas of the 10 candidate genes. All the variations showed no co-segregation with disease phenotype. Conclusion Ten candidate genes （TAOK3,RAB35,RPLPO,PXN, RNFlO,RHOF, VPS33A,RSN, DENR, RNP24） were ruled out as the disease-causing gene for CMT＇2L. Ten single nucleotide polymorphisms （SNP） were reported for the first time.

关 键 词：腓骨肌萎缩症2L型 候选基因 基因克隆 单核苷酸多态性 

分 类 号：R746.4[医药卫生—神经病学与精神病学] R544.1[医药卫生—临床医学]