IDENTIFYING CANDIDATE GENES INVOLVED IN SYNDROMIC AND NON-SYNDROMIC INTELLECTUAL DISABILITY IN CONSANGUINEOUS PAKISTANI FAMILIES

Abstract

Intellectual disability (ID) is characterized by substantial limitations in intellectual functioningbefore the age of 18. One of its causes is genetic etiology. Around 300 genesarebelieved to beinvolved in autosomal recessive ID (ARID). It is thought that there are still many more genes as yet undiscovered. Consanguineous families have higher rates of autosomal recessive disorders and so make a good population in which to study ARID. Phenol-chloroform extraction was performed on the bloodof five consanguineous Pakistani families with syndromic and non-syndromic ID to obtain DNA. The DNA wasgenotyped using an SNP microarray and homozygosity mapping was used to analyze the genotyping data to provide candidate regions within the chromosomes likely to contain genes involved in ID. A review of current literaturewasperformed to identify the most likely candidate genes among the identified regions in each family. In the most likely region from each family, 36 genes in total were identified as candidates for involvement with ID, with 17 identified as stronger candidates. This paves the way for future studies to provide more evidence for causation. DNA sequencing could be used to identify potentially causative mutations, which could then be tested in animal models.