The ridges and valleys of the human cortex look sculpted—and in a sense, they are. In fact, these undulating shapes reflect the work of many tiny sculptors, genetic factors that work together to realize a developmental program that is remarkably consistent from individual to individual. These genetic factors remain mostly anonymous, but a new study suggests that a new approach to attribution may be at hand.
Like art historians examining distinct lines of evidence, scientists based at the University of California, San Diego and the J. Craig Venter Institute scrutinized three independent data sets. Specifically, they looked at brain imaging, twin study, and transcriptomic data to reveal genetic relationships between the lobes of the human cortex. The genetic patterns found by the scientists suggest that the cortical surface is shaped, to a large degree, by genetic factors. Furthermore, these patterns likely reflect underlying anatomical and possibly functional relationships among cortical regions.
These patterns were described July 26 in PLOS Genetics, in an article entitled “Conservation of Distinct Genetically-Mediated Human Cortical Pattern.” The article describes how genetic relationships among 12 cortical surface areas were assessed using brain images and genotype information on 2364 unrelated individuals, brain images on 466 twin pairs, and transcriptome data on six postmortem brains. These very different data sets were analyzed to determine whether consistent and biologically meaningful patterns would emerge.
“We find that the patterns revealed by each data set are highly consistent (p<10−3), and are biologically meaningful on several fronts,” wrote the article’s authors. “For example, close genetic relationships are seen in cortical regions within the same lobes and, the frontal lobe, a region showing great evolutionary expansion and functional complexity, has the most distant genetic relationship with other lobes. The frontal lobe also exhibits the most distinct expression pattern relative to the other regions, implicating a number of genes with known functions mediating immune and related processes.”
The current study, which was led by Chi-Hua Chen of the University of California, San Diego, and Nicholas Schork of the J. Craig Venter Institute, reflects one of the first attempts to assess the relationship between the brain’s surface patterns and the underlying genetic patterns, using very different types of data. Moreover, the study suggests that both patterns reflect a common evolutionary and developmental pattern of cortical regionalization.
The authors of the current study note that little is known about the degree to which genetic factors may contribute to cortical patterns. They add that genome-wide association studies have found only a small number of genetic variants with effect on human brain structures.
“Although we know that several transcription factors are key players in intrinsic genetic mechanisms of cortical regionalization, especially based on animal data, there is a large knowledge gap regarding our understanding of polygenic contribution by common genetic polymorphisms to human cortical regions,” the authors indicated. “Identifying the specific variants underlying the likely polygenic pleiotropic effects we observed, however, will require further, likely very large-scale, studies.”
“Despite considerable individual variability in the size and folding patterns of the cortex, the overall organizational patterns seem highly consistent,” said Chen. “Our study shows that genetic factors are likely to be important for laying down this basic cortical patterning. The challenge for the future work will be to identify these specific genetic variants.”