Branchio-oto-renal syndrome （BOR） is autosomal dominant disorder which generates hearing impairment and kidney failures in affected individuals. The disease genomic maps were drawn back in recent years, demonstratin...Branchio-oto-renal syndrome （BOR） is autosomal dominant disorder which generates hearing impairment and kidney failures in affected individuals. The disease genomic maps were drawn back in recent years, demonstrating, missense mutations responsible in disease were located in SIX1, EYA1 and EYA2 genes. We try to uncover molecular biology of the syndrome with bioinformatics perspective, taking S1X1 and EYA2 protein interaction at center point. The study initiated with 23 natural mutations of SIX1 gene. They were first analyzed with prediction servers like SIFT, PolyPhen2, I Mutant, SNPs＆GO, PHD-SNP and Panther, to identify their impact on their structural stability and function. Subsequently it narrowed down to seven consistent with our quest. They were analyzed on IUPred disorder prediction server. Later SIX1 and its all mutant proteins were docked with EYA2 protein using GRAMM-X server. The binding affinity of docked structures was analyzed using DFIRE2 algorithm. The results justify the earlier wet laboratory studies and indicate the reason behind them. Finally we summarize that the proven inactivity of all other mutants is due to the structural disorder created by mutations, hence usual molecular interaction is hindered; strangely protein interaction takes place at DNA binding site of SIX1 mutants.展开更多
文摘Branchio-oto-renal syndrome （BOR） is autosomal dominant disorder which generates hearing impairment and kidney failures in affected individuals. The disease genomic maps were drawn back in recent years, demonstrating, missense mutations responsible in disease were located in SIX1, EYA1 and EYA2 genes. We try to uncover molecular biology of the syndrome with bioinformatics perspective, taking S1X1 and EYA2 protein interaction at center point. The study initiated with 23 natural mutations of SIX1 gene. They were first analyzed with prediction servers like SIFT, PolyPhen2, I Mutant, SNPs＆GO, PHD-SNP and Panther, to identify their impact on their structural stability and function. Subsequently it narrowed down to seven consistent with our quest. They were analyzed on IUPred disorder prediction server. Later SIX1 and its all mutant proteins were docked with EYA2 protein using GRAMM-X server. The binding affinity of docked structures was analyzed using DFIRE2 algorithm. The results justify the earlier wet laboratory studies and indicate the reason behind them. Finally we summarize that the proven inactivity of all other mutants is due to the structural disorder created by mutations, hence usual molecular interaction is hindered; strangely protein interaction takes place at DNA binding site of SIX1 mutants.
文摘目的明确1例腮-耳-肾综合征孕妇及其家族成员的遗传学病因,并对其胎儿进行产前诊断.方法采用外周血染色体核型分析及染色体微阵列分析(chromosomal microarray analysis,CMA)技术对表型异常的孕妇进行遗传学检查,了解其拷贝数变异(copy number variants,CNVs)的情况.同时行其家族成员的相关检测,明确其遗传学特征,在此基础上实施产前诊断.结果该孕妇及其女儿均携带染色体8q13.3微缺失,带有EYA1致病基因,同为腮-耳-肾综合征患者,胎儿亦携带有该CNVs,其他家系成员未发现表型及基因型的异常.结论位于染色体8q13.3区的EYA1基因突变是该家系鳃-耳-肾综合征的分子基础,符合常染色体显性遗传的规律.
