1Department of Anatomy and Neurobiology, Washington University School of Medicine, 2Department of Ecology and Evolution, Stony Brook University, 3Human Genome Sequencing Center and Department of Molecular and Human Genetics, Baylor College of Medicine, 4Department of Genetics and Southwest National Primate Research Center, Texas Biomedical Research Institute, 5Department of Biology, Loyola University Chicago
March 28, 2015 , Gateway Ballroom 2/3/4/5
Folding of the cerebral cortex is a relatively poorly understood but evolutionarily significant phenotype with far-reaching implications for brain development and function. Using a pedigreed population of ~1000 Papio baboons, we investigated critical questions about the genetic architecture of primate cortical gyrification, the interplay between genetics, anatomy, development, and connectivity, and gyrification’s potential for future evolution.
Our analyses of cortical features in CT-scan-based virtual endocasts find 14 out of 20 metric traits are significantly heritable (mean h²=0.26), while non-metric shape features are more environmentally labile. Using Mantel testing and cluster analysis, we detect significant similarity in the pattern of variation between the genotype and phenotype, which would allow for ready future adaptive alteration of the cortex. Similar partitioning of variation was also detected between development, anatomy, and connectivity (the neural network). This provides indirect support for the predictions of tension-based models for cortical development and evolution over competing models. Finally, we identified 18 novel QTL affecting variation in gyrification (highest LOD=3.23, trait Llu) and parsed the genetic architecture for this complex phenotype, finding both polygeny and pleiotropy in this population.
This inter-disciplinary project characterized the genetic basis of variation in cortical gyrification and investigated the biological underpinnings contributing to structural and, ultimately, functional differences in the cerebral cortex between primate species. Our findings provide a foundation for further examination of the molecular causes of variation in primate brain folding. Though this work was done in the baboon, the results are more widely applicable and inform human genetics and neuroscience.
This work was supported by NSF [BCS-1260844, BCS-0725068]. Nonhuman primate resources were supported by the Southwest National Primate Research Center grant from NIH [P51 OD011133, formerly P51 RR013986].