Journal compilation # 2009 Blackwell Publishing Ltd/International Behavioural and Neural Genetics Society Geneticmodulation of striatal volume by loci on Chrs 6

Natural variation in the absolute and relative size of different parts of the human brain is substantial, with a range that often exceeds a factor of 2. Much of this variation is generated by the cumulative effects of sets of unknown gene variants that modulate the proliferation, growth and death of neurons and glial cells. Discovering and testing the functions of these genes should contribute significantly to our understanding of differences in brain development,behavioranddiseasesusceptibility.Wehave exploited a large population of genetically well-character-ized strains of mice (BXD recombinant inbred strains) to map gene variants that influence the volume of the dorsal striatum (caudate–putamenwithout nucleus accumbens). Weusedunbiasedmethodstoestimatevolumesbilaterally in a sex-balanced sample taken from the Mouse Brain Library (www.mbl.org). We generated a matched micro-array data set to efficiently evaluate candidate genes (www.genenetwork.org). As in humans, volume of the striatum is highly heritable, with greater than twofold differences among strains. We mapped a locus that modulates striatal volume on chromosome (Chr) 6 at 88 6 5 Mb. We also uncovered an epistatic interaction between loci on Chr 6 and Chr 17 that modulates striatal volume. Using bioinformatic tools and the correspond-ing expression database, we have identified positional candidates in these quantitative trait locus intervals