Single-nucleotide variations in the genes encoding the mitochondrial Hsp60/Hsp10 chaperone system and their disease-causing potential

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• 作者：Peter Bross ; Zhijie Li ; Jakob Hansen ; Jens Jacob Hansen ; Marit Nyholm Nielsen ; Thomas Juhl Corydon ; Costa Georgopoulos ; Debbie Ang ; Jytte Banner Lundemose and Klary Niezen-Koning ; et al.
• 关键词：Hsp60 ; Hsp10 ; Mitochondria ; Modifier gene ; Molecular chaperone ; Protein quality control ; Short ; chain acyl ; CoA dehydrogenase ; Sudden infant death syndrome
• 刊名：Journal of Human Genetics
• 出版年：2007
• 出版时间：January, 2007
• 年：2007
• 卷：52
• 期：1
• 页码：56-65
• 全文大小：256 KB

文摘

Molecular chaperones assist protein folding, and variations in their encoding genes may be disease-causing in themselves or influence the phenotypic expression of disease-associated or susceptibility-conferring variations in many different genes. We have screened three candidate patient groups for variations in the HSPD1 and HSPE1 genes encoding the mitochondrial Hsp60/Hsp10 chaperone complex: two patients with multiple mitochondrial enzyme deficiency, 61 sudden infant death syndrome cases (MIM: #272120), and 60 patients presenting with ethylmalonic aciduria carrying non-synonymous susceptibility variations in the ACADS gene (MIM: *606885 and #201470). Besides previously reported variations we detected six novel variations: two in the bidirectional promoter region, and one synonymous and three non-synonymous variations in the HSPD1 coding region. One of the non-synonymous variations was polymorphic in patient and control samples, and the rare variations were each only found in single patients and absent in 100 control chromosomes. Functional investigation of the effects of the variations in the promoter region and the non-synonymous variations in the coding region indicated that none of them had a significant impact. Taken together, our data argue against the notion that the chaperonin genes play a major role in the investigated diseases. However, the described variations may represent genetic modifiers with subtle effects.