An evolutionary perspective on pathogenic mtDNA mutations: haplogroup associations of clinical disorders
An evolutionary perspective on pathogenic mtDNA mutations: haplogroup associations of clinical disorders
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DOI：
10.1016/j.mito.2004.07.041
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发表时间：
2004-09-01
期刊：
影响因子：
4.4
通讯作者：
Howell, N
中科院分区：
文献类型：
--
作者：
Herrnstadt, C;Howell, N
超过75种人类疾病与线粒体功能障碍有关，其中许多是由线粒体基因组（mtDNA）中的明显致病突变直接引起的。此外，还有一些报道指出mtDNA取代在疾病过程中的不同的、微妙的作用。正如我们在这里回顾，线粒体DNA进化导致的序列分布到大陆特异性单倍型群，这是由相对较少的多态性。因此，线粒体DNA序列可以分配给欧洲、非洲或亚洲/美洲原住民单倍群。有许多报道称，各种疾病都与单倍型群相关，并且已经表明这些单倍型群相关多态性中的一些在这些疾病中充当风险因素。也有人提出，有单倍型群协会的老化。然而，正如我们在这里所指出的，这种关联通常只在单个研究中观察到，很难根据现有证据得出广泛的结论。至少，我们建议，单倍型组组协会必须在多个亚群或在一个大的，仔细控制的人口调查中检测到。(C)2004年Elsevier B. V.和线粒体研究学会。All rights reserved.
More than 75 human diseases have been associated with mitochondrial dysfunction, and many of these are directly caused by overtly pathogenic mutations in the mitochondrial genome (mtDNA). In addition, there have been a number of reports that posit a different, subtler role for mtDNA substitutions in the disease process. As we review here, mtDNA evolution has resulted in the distribution of sequences into continent-specific haplogroups, which are defined by a relatively small number of polymorphisms. Thus, mtDNA sequences can be assigned to European, African, or Asian/Native American haplogroups. There are numerous reports that various diseases are haplogroup-associated, and it has been suggested that some of these haplogroup-associated polymorphisms act as risk factors in these disorders. It has also been suggested that there are haplogroup-associations for aging. As we note here, however, such associations have usually been observed only in single studies and it is difficult to draw broad conclusions on the basis of the available evidence. At a minimum, we suggest that, a haplogroup-group association must be detected in multiple subpopulations or in a large, carefully controlled population survey. (C) 2004 Elsevier B.V. and Mitochondria Research Society. All rights reserved.