paperKB
coga / coga-kb
Help
Sign in

Chunk #23 — Results — Complex Genetic Regulation of the Chromosome 4p12 GABAA Cluster

Source
GABRA2 Alcohol Dependence Risk Allele is Associated with Reduced Expression of Chromosome 4p12 GABAA Subunit Genes in Human Neural Cultures.
Embedded
yes

Text

A potential alternative genetic model more consistent with these results would include a cis-acting genetic locus influencing expression of the chr4p12 GABAA gene cluster paired with a random, mitotically-stable, allelic expression bias. In this model, a stochastic clonal allelic expression bias for the chromosome carrying a cis-acting repressive functional variant linked with the rs279858*C-allele would determine Cluster 1 vs. 2 membership for a given iPSC line. Support for a model that includes allelic expression bias in this region was obtained using RT-qPCR and TaqMan allele-specific probes to examine neural cell RNA from 16 Cluster 2 cell lines heterozygous for exonic SNPs in at least one of the chr4p12 GABAA genes (GABRG1, GABRA2, GABRA4 and GABRB1). We observed allelic imbalance [a 50% or greater increase in RNA from one of the two alleles, i.e. >±0.5ΔCT (Serre et al., 2008, Jeffries et al., 2012)] in chr4p12 GABAA RNA expression compared to fibroblast genomic DNA in 7 of 16 lines (44%). In contrast, 0 of 11 lines (0%) heterozygous for an exonic SNP in the AKR1C3 gene (chr10p15) showed an imbalance in expression