Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder

J Neurogenet. 2001;15(3-4):245-59. doi: 10.3109/01677060109167380.

Abstract

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, acting via the GABAA receptors. The GABAA receptors are comprised of several different homologous subunits, forming a group of receptors that are both structurally and functionally diverse. Three of the GABAA receptor subunit genes (GABRB3, GABRA5 and GABRG3) form a cluster on chromosome 15q11-q13, in a region that has been genetically associated with autistic disorder (AutD). Based on these data, we examined 16 single nucleotide polymorphisms (SNPs) located within GABRB3, GABRA5 and GABRG3 for linkage disequilibrium (LD) in 226 AutD families (AutD patients and parents). Genotyping was performed using either OLA (oligonucleotide ligation assay), or SSCP (single strand conformation polymorphism) followed by DNA sequencing. We tested for LD using the Pedigree Disequilibrium Test (PDT). PDT results gave significant evidence that AutD is associated with two SNPs located within the GABRG3 gene (exon5_539T/C, p=0.02 and intron5_687T/C, p=0.03), suggesting that the GABRG3 gene or a gene nearby contributes to genetic risk in AutD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autistic Disorder / genetics*
  • Chromosomes, Human, Pair 15 / genetics*
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Polymorphism, Single Nucleotide
  • Polymorphism, Single-Stranded Conformational
  • Receptors, GABA-A / genetics*

Substances

  • Receptors, GABA-A