Abstract
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.
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Acknowledgements
We are grateful to the patients and their families for their support and cooperation. This work has been supported by grants from the Dutch Organisation for Health Research and Development (ZON-MW) (917-86-319 to BBAdV), Hersenstichting Nederland (BBAdV).
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Schuurs-Hoeijmakers, J., Hehir-Kwa, J., Pfundt, R. et al. Homozygosity mapping in outbred families with mental retardation. Eur J Hum Genet 19, 597–601 (2011). https://doi.org/10.1038/ejhg.2010.167
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DOI: https://doi.org/10.1038/ejhg.2010.167
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