Highly significant associations were found between cortical surface area and polymorphisms in possible regulatory regions near the gene CDK5RAP2. This gene codes for a protein involved in cell-cycle regulation in neuronal progenitor cells — cells that migrate to the cerebral cortex during the second trimester of gestation and eventually become fully functioning neurons. The cerebral cortex is the outer layer of the brain, often referred to as “gray matter.” The most highly developed part of the human brain, the cerebral cortex is responsible for higher cognitive functions, such as thinking, perceiving, producing and understanding language, some of which is considered uniquely human.
Similar but less significant findings were made for polymorphisms in two other microcephaly genes, known as MCPH1 and ASPM. All findings were exclusive to either males or females but the functional significance of this sex-segregated effect is unclear.
“One particularly interesting feature of this new discovery is that the strongest links with cortical area were found in regulatory regions, rather than coding regions of the genes,” said Andreassen. “One upshot of this may be that in order to further understand the molecular and evolutionary processes that have determined human brain size, we need to focus on regulatory processes rather than further functional characterization of the proteins of these genes. This has huge implications for future research on the link between genetics and brain morphology.”
Wouldn’t be the first time that genes which have a connection to pathologies turn out to be useful in illuminating normal human variation. It’ll be on the site of PNAS someday.