Frank Albert | bioRxiv Science

bioRxiv2014

Genetic Influences on Brain Gene Expression in Rats Selected for Tameness and Aggression

Inter-individual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior towards humans for more than 64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection. We used RNA sequencing in 150 F2 animals to identify hundreds of loci that influence brain gene expression. Several of these loci colocalize with tameness loci and may reflect the same genetic variants. Through analyses of correlations between allele effects on behavior and gene expression, differential expression between the tame and aggressive rat selection lines, and correlations between gene expression and tameness in F2 animals, we identify the genes Gltscr2, Lgi4, Zfp40 and Slc17a7 as candidate contributors to the strikingly different behavior of the tame and aggressive animals.

Genomics↗

bioRxiv2013

Genetics of single-cell protein abundance variation in large yeast populations

Many DNA sequence variants influence phenotypes by altering gene expression. Our understanding of these variants is limited by sample sizes of current studies and by measurements of mRNA rather than protein abundance. We developed a powerful method for identifying genetic loci that influence protein expression in very large populations of the yeast Saccharomyes cerevisiae. The method measures single-cell protein abundance through the use of green-fluorescent-protein tags. We applied this method to 160 genes and detected many more loci per gene than previous studies. We also observed closer correspondence between loci that influence protein abundance and loci that influence mRNA abundance of a given gene. Most loci cluster at hotspot locations that influence multiple proteins--in some cases, more than half of those examined. The variants that underlie these hotspots have profound effects on the gene regulatory network and provide insights into genetic variation in cell physiology between yeast strains.

Genomics↗