Newbury Alex J, Rosen Glenn D
Department of Neurology, Beth Israel Deaconess Medical Center Boston, MA, USA.
Front Genet. 2012 May 31;3:91. doi: 10.3389/fgene.2012.00091. eCollection 2012.
The corpus callosum is the main commissure connecting left and right cerebral hemispheres, and varies widely in size. Differences in the midsagittal area of the corpus callosum (MSACC) have been associated with a number of cognitive and behavioral phenotypes, including obsessive-compulsive disorders, psychopathy, suicidal tendencies, bipolar disorder, schizophrenia, autism, and attention deficit hyperactivity disorder. Although there is evidence to suggest that MSACC is heritable in normal human populations, there is surprisingly little evidence concerning the genetic modulation of this variation. Mice provide a potentially ideal tool to dissect the genetic modulation of MSACC. Here, we use a large genetic reference panel - the BXD recombinant inbred line - to dissect the natural variation of the MSACC. We estimated the MSACC in over 300 individuals from nearly 80 strains. We found a 4-fold difference in MSACC between individual mice, and a 2.5-fold difference among strains. MSACC is a highly heritable trait (h(2) = 0.60), and we mapped a suggestive QTL to the distal portion of Chr 14. Using sequence data and neocortical expression databases, we were able to identify eight positional and plausible biological candidate genes within this interval. Finally, we found that MSACC correlated with behavioral traits associated with anxiety and attention.
胼胝体是连接左右大脑半球的主要连合纤维，其大小差异很大。胼胝体矢状面中部面积（MSACC）的差异与多种认知和行为表型相关，包括强迫症、精神病态、自杀倾向、双相情感障碍、精神分裂症、自闭症和注意力缺陷多动障碍。尽管有证据表明MSACC在正常人群中具有遗传性，但令人惊讶的是，关于这种变异的基因调控的证据却很少。小鼠提供了一个潜在的理想工具来剖析MSACC的基因调控。在这里，我们使用一个大型遗传参考面板——BXD重组近交系——来剖析MSACC的自然变异。我们估计了来自近80个品系的300多个个体的MSACC。我们发现个体小鼠之间的MSACC有4倍的差异，品系之间有2.5倍的差异。MSACC是一个高度可遗传的性状（h(2) = 0.60），我们将一个提示性的数量性状基因座定位到第14号染色体的远端部分。利用序列数据和新皮质表达数据库，我们能够在这个区间内识别出8个位置上和生物学上合理的候选基因。最后，我们发现MSACC与焦虑和注意力相关的行为特征相关。
