Open AccessHomozygosity mapping in outbred families with mental retardation
Author(s) -
Janneke Schuurs-Hoeijmakers,
Jayne Y. Hehir-Kwa,
Rolph Pfundt,
Bregje W.M. van Bon,
Nicole de Leeuw,
Tjitske Kleefstra,
M.A.A.P. Willemsen,
Ad Geurts van Kessel,
Han G. Brunner,
Joris A. Veltman,
Hans van Bokhoven,
Arjan P.M. de Brouwer,
Bert B.A. de Vries
Publication year - 2011
Publication title -
european journal of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.587
H-Index - 125
eISSN - 1476-5438
pISSN - 1018-4813
DOI - 10.1038/ejhg.2010.167
Subject(s) - disease gene identification , genetics , locus (genetics) , biology , gene , gene mapping , genetic linkage , consanguinity , single nucleotide polymorphism , runs of homozygosity , candidate gene , chromosome , phenotype , genotype , exome sequencing
Autosomal recessive mental retardation (AR-MR) may account for up to 25% of genetic mental retardation (MR). So far, mapping of AR-MR genes in consanguineous families has resulted in six nonsyndromic genes, whereas more than 2000 genes might contribute to AR-MR. We propose to use outbred families with multiple affected siblings for AR-MR gene identification. Homozygosity mapping in ten outbred families with affected brother-sister pairs using a 250 K single nucleotide polymorphism array revealed on average 57 homozygous regions over 1 Mb in size per affected individual (range 20-74). Of these, 21 homozygous regions were shared between siblings on average (range 8-36). None of the shared regions of homozygosity (SROHs) overlapped with the nonsyndromic genes. A total of 13 SROHs had an overlap with previously reported loci for AR-MR, namely with MRT8, MRT9, MRT10 and MRT11. Among these was the longest observed SROH of 11.0 Mb in family ARMR1 on chromosome 19q13, which had 2.9 Mb (98 genes) in common with the 5.4 Mb MRT11 locus (195 genes). These data support that homozygosity mapping in outbred families may contribute to identification of novel AR-MR genes.