Abstract
BackgroundThe size of the cerebral cortex varies widely within human populations, and a large portion of this variance is modulated by genetic factors. The discovery and characterization of these genes and their variants can contribute to an understanding of individual differences in brain development, behavior, and disease susceptibility. Here we use unbiased stereological techniques to map quantitative trait loci (QTLs) that modulate the volume of neocortex.ResultsWe estimated volumes bilaterally in an expanded set of BXD recombinant inbred strains (n = 56 strains and 223 animals) taken from the Mouse Brain Library . We generated matched microarray data for the cerebral cortex in the same large panel of strains and in parental neonates to efficiently nominate and evaluate candidate genes. Volume of the neocortex varies widely, and is a heritable trait. Genome-wide mapping of this trait revealed two QTLs – one on chromosome (Chr) 6 at 88 ± 5 Mb and another at Chr 11 (41 ± 8 Mb). We generated both neonatal and adult neocortical gene expression databases using microarray technology. Using these databases in combination with other bioinformatic tools we have identified positional candidates on these QTL intervals.ConclusionThis study is the first to use the expanded set of BXD strains to map neocortical volume, and we found that normal variation of this trait is, at least in part, genetically modulated. These results provide a baseline from which to assess the genetic contribution to regional variation in neocortical volume, as well as other neuroanatomic phenotypes that may contribute to variation in regional volume, such as proliferation, death, and number and packing density of neurons
Highlights
The size of the cerebral cortex varies widely within human populations, and a large portion of this variance is modulated by genetic factors
These results provide a baseline from which to assess the genetic contribution to regional variation in neocortical volume, as well as other neuroanatomic phenotypes that may contribute to variation in regional volume, such as proliferation, death, and number and packing density of neurons
[3,4], as well as with differences in susceptibility to disorders including developmental dyslexia [5], anxiety-related personality traits [6], and schizophrenia [7,8]. Dissecting those genetic variants that modulate normal variation of the cerebral cortex could have an impact on our understanding of cortical development, normal function, and the etiology of several pervasive diseases
Summary
All experiments were approved by the Institutional Animal Care and Use Committees at Beth Israel Deaconess. Medical Center and University of Tennessee Health Science Center. Days of age (mean ± SEM = 103 ± 5), with most of the cases ranging from 50 – 120 days. Mice were obtained from either the Jackson Laboratory (Bar Harbor, ME) or the University of Tennessee Health Science Center (UTHSC) as detailed previously [24]. All procedures were approved by institutional animal care and use committees and conform to NIH guidelines for humane treatment of animals. Mice were deeply anesthetized with Avertin (0.8 ml i.p.) and transcardially perfused with 0.9%saline, followed by fixative (1.25% glutaraldehyde/1.0% paraformaldehyde in phosphate buffer), and their brains removed and weighed. Actual section thickness was determined by direct examination of 10 sections for each brain using an ×100 oil immersion objective and a z-axis micrometer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
