A Population-based Study of Autosomal-recessive Disease-causing Mutations in a Founder Population

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2012 Sep 18

PMID 22981120

Citations 32

Authors

Jessica X Chong

Rebecca Ouwenga

Rebecca L Anderson

Darrel J Waggoner

Carole Ober

Affiliations

Soon will be listed here.

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.

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