Schork N J, Guo S W
Department of Medicine, University of Michigan, Ann Arbor 48109-0500.
Am J Hum Genet. 1993 Dec;53(6):1320-37.
Recent biochemical and molecular-genetic discoveries concerning variations in human mtDNA have suggested a role for mtDNA mutations in a number of human traits and disorders. Although the importance of these discoveries cannot be emphasized enough, the complex natures of mitochondrial biogenesis, mutant mtDNA phenotype expression, and the maternal inheritance pattern exhibited by mtDNA transmission make it difficult to develop models that can be used routinely in pedigree analyses to quantify and test hypotheses about the role of mtDNA in the expression of a trait. In the present paper, we describe complexities inherent in mitochondrial biogenesis and genetic transmission and show how these complexities can be incorporated into appropriate mathematical models. We offer a variety of likelihood-based models which account for the complexities discussed. The derivation of our models is meant to stimulate the construction of statistical tests for putative mtDNA contribution to a trait. Results of simulation studies which make use of the proposed models are described. The results of the simulation studies suggest that, although pedigree models of mtDNA effects can be reliable, success in mapping chromosomal determinants of a trait does not preclude the possibility that mtDNA determinants exists for the trait as well. Shortcomings inherent in the proposed models are described in an effort to expose areas in need of additional research.
最近有关人类线粒体DNA（mtDNA）变异的生物化学和分子遗传学发现表明，mtDNA突变在许多人类性状和疾病中发挥作用。尽管这些发现的重要性无论如何强调都不为过，但线粒体生物发生、突变型mtDNA表型表达以及mtDNA传递所呈现的母系遗传模式的复杂性，使得难以建立可常规用于系谱分析的模型，以量化和检验关于mtDNA在性状表达中作用的假设。在本文中，我们描述了线粒体生物发生和遗传传递中固有的复杂性，并展示了如何将这些复杂性纳入适当的数学模型。我们提供了多种基于似然性的模型，这些模型考虑了所讨论的复杂性。我们模型的推导旨在促进构建关于假定的mtDNA对性状贡献的统计检验。描述了利用所提出模型的模拟研究结果。模拟研究结果表明，尽管mtDNA效应的系谱模型可能是可靠的，但成功定位性状的染色体决定因素并不排除该性状也存在mtDNA决定因素的可能性。为了揭示需要进一步研究的领域，我们描述了所提出模型中固有的缺点。
