Homozygosity mapping in outbred families with mental retardation

Janneke H.M. Schuurs-Hoeijmakers (1) , Bert Ba de Vries (1) , Jane y Hehir-Kwa (1) , Rolph Pfundt (1) , Bregje Wm van Bon (1) , Nicole de Leeuw (1) , Tjitske Kleefstra (1) , Michel Aap Willemsen (1) , Ad Geurts van Kessel (1) , Han G Brunner (1) , Joris A Veltman (1) , Hans J. van Bokhoven (1) , Arjan Pm de Brouwer (1)

1 Human Genetics

Autosomal Recessive Mental Retardation (AR-MR) may account for up to 25% of genetic MR. So far, mapping of AR-MR genes in consanguineous families has resulted in six non-syndromic genes whereas more than 2,000 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 250K SNP array revealed on average 57 homozygous regions over 1Mb 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 non-syndromic genes. Thirteen 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.

Mots clés: homozygosity mapping; mental retardation/intellectual disability; outbred families

Janneke H.M. Schuurs-Hoeijmakers, Bert Ba de Vries, Jane y Hehir-Kwa, Rolph Pfundt, Bregje Wm van Bon, et al.. Homozygosity mapping in outbred families with mental retardation. European Journal of Human Genetics, 2011, ⟨10.1038/ejhg.2010.167⟩. ⟨hal-00609414⟩