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目的一个命名为HB-S037的常染色体显性非综合征遗传性耳聋中国家系致病基因定位及MYO7A基因突变分析。方法通过对该家系参与连锁分析的23名成员应用Affymetrix5.0SNP(Single Nucleotide Polymorphisms,单核苷酸多态性)芯片进行全基因组扫描及连锁分析,致病基因的染色体定位;之后,选取微卫星标记进行精细扫描,确定候选基因,MYO7A基因外显子扩增及测序。结果应用Affymetrix 5.0 SNP芯片进行全基因组扫描及连锁分析,将HB-S037家系的致病基因初步定位于第11号染色体11q13.4-14.1之间(最大LOD值=4.346),选取初步定位区域内及附近的12个微卫星标记进行精细定位及单倍型分析,将致病基因定位于微卫星标记D11S1314和D11S4166之间的区域(最大LOD值=4.18)。对定位区域内候选基因MY07A的49个外显子直接测序,在MYO7A第17外显子有一个新的突变位点c.2011G>A,该位点突变与此家系疾病表型共分离,并引起编码第671位的甘氨酸替换为丝氨酸(G671S)。该位点在多物种之间保守。100个听力正常人未发现此突变。结论 HB-S037家系定位于第11号染色体的长臂11q13.4-14.1之间,致病基因为MYO7A,MYO7A第17外显子c.2011G>A突变引起第671位氨基酸甘氨酸替换为丝氨酸,该突变为HB-S037家系的致病突变,为MYO7A基因的一个新发现的突变位点。
OBJECTIVE: To determine the pathogenicity of MYO7A gene in Chinese families with autosomal dominant non-syndromic hereditary deafness named HB-S037. METHODS: 23 members of this pedigree participated in the linkage analysis using genome-wide scan and linkage analysis of Affymetrix 5.0 SNP (Single Nucleotide Polymorphisms) chip to identify the chromosomal location of disease-causing genes. After that, microsatellite The marker was finely scanned to determine the candidate gene, exon extension of the MYO7A gene and sequencing. Results Affymetrix 5.0 SNP chip was used to perform genome-wide scan and linkage analysis. The virulence gene of HB-S037 was initially located on chromosome 11q13.4-14.1 (maximum LOD = 4.346) And the nearby 12 microsatellite markers for fine mapping and haplotype analysis. The pathogenic genes were located in the region between microsatellite markers D11S1314 and D11S4166 (maximum LOD = 4.18). The 49 exons of MY07A, a candidate gene in the locus, were sequenced directly. There was a new mutation c.2011G> A in exon 17 of MYO7A, which was co-segregated with the disease phenotype of this pedigree Glycine at position 671 was substituted for serine (G671S). The site is conserved among multiple species. 100 normal hearing people did not find this mutation. Conclusion The HB-S037 pedigree locates on the long arm 11q13.4-14.1 of chromosome 11, the pathogenic gene is MYO7A, the mutation of c.2011G> A in exon 17 of MYO7A causes the amino acid 671 to be replaced by serine, This mutation is a causative mutation in the HB-S037 pedigree and is a newly discovered mutation site of the MYO7A gene.