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Homozygosity mapping of autosomal recessive intellectual disability loci in 11 consanguineous Pakistani families

Published online by Cambridge University Press:  01 December 2014

Iltaf Ahmed ,
Muhammad Arshad Rafiq ,
John B. Vincent ,
Attya Bhatti ,
Muhammad Ayub  and
Peter John
Iltaf Ahmed
Affiliation:
Molecular Neuropsychiatry & Development (MiND) Lab, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, Ontario, Canada Atta-ur-Rehman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan
Muhammad Arshad Rafiq
Affiliation:
Molecular Neuropsychiatry & Development (MiND) Lab, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, Ontario, Canada
John B. Vincent
Affiliation:
Molecular Neuropsychiatry & Development (MiND) Lab, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
Attya Bhatti
Affiliation:
Atta-ur-Rehman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan
Muhammad Ayub*
Affiliation:
Department of Psychiatry, Division of Developmental Disabilities, Queen’s University, Kingston, Ontario, Canada
Peter John
Affiliation:
Atta-ur-Rehman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan
*
Muhammad Ayub, Department of Psychiatry, Division of Developmental Disabilities, Queen’s University, Kingston, Ontario, Canada. E-mail: [email protected] Tel: +1 613 549 7944; Fax: +1 613 549 7387;
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Abstract

Background

Autosomal recessive intellectual disability (ID) is genetically heterogeneous and most of the genes causing it remain undiscovered.

Objective

We have ascertained 11 consanguineous families multiplex for IDs in order to identify new loci for autosomal recessive genes for non-syndromic ID, or to aid pinpointing mutations in known causative gene/loci.

Methodology

Microarray genotyping (Affymatrix 250K) was performed to identify homozygosity-by-descent (HBD) in all affected families.

Results

Analysis of genotypes revealed 45 potential HBD regions across the families, although these may be rationalised down to 39. Two families share an overlapping HBD region on 7q11.21. In one family, X-linkage also looks plausible, and a new ID gene near the centromere may be a likely cause. In one family, no HBD region was found, and thus we exclude autosomal recessive mutation as the likely cause in this family. Copy-number variation (CNV) was also performed and revealed no CNVs, homozygous or heterozygous, segregating with the phenotype.

Conclusion

The homozygous loci identified in this study might harbour candidate genes for ID in these studied families. Therefore, we are proceeding with next-generation sequencing analysis of the families, using whole-exome approaches, and anticipate that this will identify the causative gene/mutation within the identified HBD regions for many of the families studied here.

Keywords

autosomal recessive intellectual disabilityconsanguineous Pakistani familieshomozygosity mappingloci
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 27 , Issue 1 , February 2015 , pp. 38 - 47
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Copyright
© Scandinavian College of Neuropsychopharmacology 2014 

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