Kirk R, Furlong R A, Amos W, Cooper G, Rubinsztein J S, Walsh C, Paykel E S, Rubinsztein D C
Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
Am J Hum Genet. 1999 Aug;65(2):508-18. doi: 10.1086/302507.
Previous reports of preferential transmission of bipolar affective disorder (BP) from the maternal versus the paternal lines in families suggested that this disorder may be caused by mitochondrial DNA mutations. We have sequenced the mitochondrial genome in 25 BP patients with family histories of psychiatric disorder that suggest matrilineal inheritance. No polymorphism identified more than once in this sequencing showed any significant association with BP in association studies using 94 cases and 94 controls. To determine whether our BP sample showed evidence of selection against the maternal lineage, we determined genetic distances between all possible pairwise comparisons within the BP and control groups, based on multilocus mitochondrial polymorphism haplotypes. These analyses revealed fewer closely related haplotypes in the BP group than in the matched control group, suggesting selection against maternal lineages in this disease. Such selection is compatible with recurrent mitochondrial mutations, which are associated with slightly decreased fitness. Although such mismatch distribution comparisons have been used previously for analyses of population histories, this is, as far as we are aware, the first report of this method being used to study disease.
先前关于双相情感障碍（BP）在家族中母系与父系优先遗传的报道表明，这种疾病可能由线粒体DNA突变引起。我们对25名有精神疾病家族史且提示母系遗传的BP患者的线粒体基因组进行了测序。在使用94例病例和94例对照的关联研究中，此次测序中不止一次鉴定出的多态性与BP均无显著关联。为了确定我们的BP样本是否显示出针对母系血统的选择证据，我们基于多位点线粒体多态性单倍型，确定了BP组和对照组内所有可能的两两比较之间的遗传距离。这些分析显示，BP组中密切相关的单倍型比匹配的对照组少，表明该疾病中存在针对母系血统的选择。这种选择与反复出现的线粒体突变相符，这些突变与适应性略有下降有关。尽管这种错配分布比较以前曾用于分析种群历史，但据我们所知，这是首次报道使用该方法研究疾病。
