Pathogenic Mitochondrial tRNA Mutations - Which Mutations Are Inherited and Why?

被引：44

作者：

Elson, Joanna L. ^{[1
]}

Swalwell, Helen ^{[1
]}

Blakely, Emma L. ^{[1
]}

McFarland, Robert ^{[1
]}

Taylor, Robert W. ^{[1
]}

Turnbull, Doug M. ^{[1
]}

机构：

[1] Newcastle Univ, Sch Med, Mitochondrial Res Grp, Inst Ageing & Hlth, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

来源：

HUMAN MUTATION | 2009年 / 30卷 / 11期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会; 英国工程与自然科学研究理事会; 英国惠康基金;

关键词：

mitochondrial DNA; tRNA mutation; threshold; inheritance; genetic counseling; RAGGED-RED FIBERS; POINT MUTATION; DNA MUTATIONS; SPORADIC PATIENT; EXERCISE INTOLERANCE; TRNA(LYS) GENE; MYOPATHY; MERRF; MELAS; PREVALENCE;

D O I：

10.1002/humu.21113

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Mitochondrial transfer RNA (mt-tRNA) mutations are the commonest mitochondrial (mtDNA) mutations to cause human disease. The majority of mt-tRNA mutations are heteroplasmic and while some exhibit maternal transmission within families, many others are only seen as sporadic mutations. Using the available clinical, biochemical and genetic data from published pathogenic mt-tRNA mutations, we have explored several different factors thought to influence the transmission of mt-tRNA mutations. Our data show that the most important factor in predicting whether a mutation is transmitted to offspring is whether the mt-tRNA mutation is selected against in a rapidly replicating tissue such as blood. This suggests that those mt-tRNA mutations which exert a major phenotype in dividing cells are unlikely to be inherited. This is entirely compatible with recent observations on the mitochondrial genetic bottleneck in early development and has important implications for families with mt-tRNA disease. (C) 2009 Wiley-Liss, Inc.

引用

页码：E984 / E992

页数：9

共 53 条

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