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A population-based study of autosomal-recessive disease-causing mutations in a founder population.

Abstract：

:The decreasing cost of whole-genome and whole-exome sequencing has resulted in a renaissance for identifying Mendelian disease mutations, and for the first time it is possible to survey the distribution and characteristics of these mutations in large population samples. We conducted carrier screening for all autosomal-recessive (AR) mutations known to be present in members of a founder population and revealed surprisingly high carrier frequencies for many of these mutations. By utilizing the rich demographic, genetic, and phenotypic data available on these subjects and simulations in the exact pedigree that these individuals belong to, we show that the majority of mutations were most likely introduced into the population by a single founder and then drifted to the high carrier frequencies observed. We further show that although there is an increased incidence of AR diseases overall, the mean carrier burden is likely to be lower in the Hutterites than in the general population. Finally, on the basis of simulations, we predict the presence of 30 or more undiscovered recessive mutations among these subjects, and this would at least double the number of AR diseases that have been reported in this isolated population.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Chong JX,Ouwenga R,Anderson RL,Waggoner DJ,Ober C

doi

10.1016/j.ajhg.2012.08.007

subject

Has Abstract

pub_date

2012-10-05 00:00:00

pages

608-20

issue

4

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(12)00419-3

journal_volume

91

pub_type

杂志文章

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