Genomic regulation of natural variation in cortical and noncortical brain volume

Abstract

Background: The relative growth of the neocortex parallels the emergence of complex cognitive functions across species. To determine the regions of the mammalian genome responsible for natural variations in cortical volume, we conducted a complex trait analysis using 34 strains of recombinant inbred (Rl) strains of mice (BXD), as well as their two parental strains (C57BL/6J and DBA/2J). We measured both neocortical volume and total brain volume in 155 coronally sectioned mouse brains that were Nissl stained and embedded in celloidin. After correction for shrinkage, the measured cortical and noncortical brain volumes were entered into a multiple regression analysis, which removed the effects of body size and age from the measurements. Marker regression and interval mapping were computed using WebQTL.

The genetic basis of natural variation in mushroom body size in Drosophila melanogaster

“…These natural variations have been associated with multiple behaviours 20 49 50 . Furthermore, natural variation in volumes of brain regions, as well as in neuron numbers has been observed in humans and mice 51 52 . However, this is the first (to our knowledge) systematic analysis of natural variation in brain structures.…”

Teaching Bioinformatics and Neuroinformatics by Using Free Web-based Tools

“…GeneNetwork uses a specific interface in which the data from a given trait can be entered, and a likelihood ratio statistic (LRS) is calculated as a function of markers across the genome (for a good discussion of the LRS, see Beatty and Laughlin, 2006 ). The LRS will be high if there is a large discrepancy in the phenotype between mice with the B versus D marker at a given chromosomal locus and low when the phenotypes are not discrepant.…”

“…QTL analyses are currently being applied to humans, animals, and even plants to determine the locus of genetically determined or influenced morphological and behavioral traits. Among the growing list of traits are olfactory bulb size ( Williams et al , 2001 ), cerebellum size ( Airey et al , 2002 ), cortex size ( Beatty and Laughlin, 2006 ), alcoholism ( Grisel, 2000 ; Bergen et al , 2003 ), Alzheimer's disease proteins ( Ryman et al , 2008 ), attention-deficit hyperactivity disorder ( Doyle et al , 2008 ), pain susceptibility ( Nissenbaum et al , 2008 ), IQ ( Butcher et al , 2008 ), obesity ( Casellas et al , 2009 ), and dyslexia ( Deffenbacher et al , 2004 ). In short, almost any morphological, physiological, or behavioral trait that could have at least some genetic basis can be examined by QTL analysis.…”

OTX1 regulates cell cycle progression of neural progenitors in the developing cerebral cortex

“…To reveal the genomic regions responsible for natural variation in cortical volume, a complex trait analysis of 34 recombinant inbred strains plus two parental strains of mice was conducted. A quantitative trait locus linking to neocortical volume was mapped at 25.5 mbp on chromosome 11 where the Otx1 gene is located (9). It was speculated that this locus may contain part of the Otx1 enhancer that contributes to the regulation of neocortical volume (9).…”

“…A quantitative trait locus linking to neocortical volume was mapped at 25.5 mbp on chromosome 11 where the Otx1 gene is located (9). It was speculated that this locus may contain part of the Otx1 enhancer that contributes to the regulation of neocortical volume (9). OTX1 is a transcription factor expressed in cortical progenitor cells and emerging cortical plate during the embryonic development (10,11).…”