Genetic heritage of the Old Order Mennonites of Southeastern Pennsylvania
Genetic heritage of the Old Order Mennonites of Southeastern Pennsylvania
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DOI：
10.1002/ajmg.c.20003
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发表时间：
2003-08-15
影响因子：
3.1
通讯作者：
Puffenberger, EG
中科院分区：
文献类型：
--
作者：
Puffenberger, EG
宾夕法尼亚州东南部的旧秩序门诺派是一个宗教孤立与起源于16世纪的瑞士。瑞士门诺派移民到宾夕法尼亚州超过50年的时间在世纪初。美国这一人群的历史提供了对几种遗传性疾病发病率增加的见解，最值得注意的是枫糖浆尿病（MSUD），先天性巨结肠病（HSCR）和先天性肾病综合征。旧秩序门诺派和旧秩序阿米什人之间的比较表明，尽管有共同的宗教和地理历史，但每个群体都有独特的遗传遗产。出乎意料的是，两组中的几种疾病表现出等位基因和/或基因座异质性。1312 T-->A BCKDHA基因突变的群体遗传学，导致经典的MSUD，详细介绍。MSUD的发病率估计为1/358出生的旧秩序门诺派教徒，产生的校正载波频率为7.96%和突变等位基因频率为4.15%。对群体的分析表明，重复周期的采样效应、群体瓶颈和随后的遗传漂变在塑造当前等位基因频率方面很重要。1312 T->A突变单倍型的连锁不平衡分析提供和讨论的背景下，已知的系谱历史的人口。最后，从微卫星标记基因分型的数据提供的旧秩序门诺人口的遗传多样性和背景连锁不平衡的水平升高显着，但适度的减少。(C)2003 Wiley-Liss，Inc.
The Old Order Mennonites of southeastern Pennsylvania are a religious isolate with origins in 16th-century Switzerland. The Swiss Mennonites immigrated to Pennsylvania over a 50-year period in the early 18th century. The history of this population in the United States provides insight into the increased incidence of several genetic diseases, most notably maple syrup urine disease (MSUD), Hirschsprung disease (HSCR), and congenital nephrotic syndrome. A comparison between the Old Order Mennonites and the Old Order Amish demonstrates the unique genetic heritage of each group despite a common religious and geographic history. Unexpectedly, several diseases in both groups demonstrate allelic and/or locus heterogeneity. The population genetics of the 1312T-->A BCKDHA gene mutation, which causes classical MSUD, are presented in detail. The incidence of MSUD in the Old Order Mennonites is estimated to be 1/358 births, yielding a corrected carrier frequency of 7.96% and a mutation allele frequency of 4.15%. Analysis of the population demonstrates that repeated cycles of sampling effects, population bottlenecks, and subsequent genetic drift were important in shaping the current allele frequencies. A linkage disequilibrium analysis of 1312T-->A mutation haplotypes is provided and discussed in the context of the known genealogical history of the population. Finally, data from microsatellite marker genotyping within the Old Order Mennonite population are provided that show a significant but modest decrease in genetic diversity and elevated levels of background linkage disequilibrium. (C) 2003 Wiley-Liss, Inc.