• Disease Gene Discovery for Microcephaly in Consanguineous Pakistani Families

      Sivised, Vattika; College of Science and Mathematics; Kim, Hyung-Goo; Department of Obstetrics & Gynecology; Augusta University (2018-02-12)
      Microcephaly is a genetic condition where the brain does not develop normally resulting in a reduced head circumference, and the disorder can be non-syndromicor syndromic.There are two types of microcephaly: primaryand secondary. Microcephaly is passed down through family lines as an X-linked recessive autosomal dominant or recessive disorder.Microcephaly can be segregated in families through consanguineous marriages. These interfamilial marriages can lead to the child inheriting identical defective copies of genes from both parents, which results in an autosomal recessive disease.This paper will explore four Pakistani families, each practicing consanguineous marriages that have resulted in individuals displaying syndromic and non-syndromic microcephaly.A list of chromosomal regions obtained from genotyping methods allowed for the narrowing down of potential causative genes in each family. Using online search engines, including Endeavour and the Human Genome Browser, four lists of candidate genes were obtained, one for each family.For two families, a defect in the ASPMgene, a gene that is reported to cause primary microcephaly,has beendiscovered. Potential candidate genes, including SCN7AandPKIB, present in chromosomal regions found through homozygosity mapping of the remaining two families could be the cause of the phenotype and will be discussed.

      Brown, Jason; Department of Biological Sciences; Kim, Hyung-Goo; Department of Obstetrics & Gynecology; Augusta University (2018-02-12)
      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.