<i>NPEPPS</i> segmental duplication drives position effect expression of <i>TBC1D3</i> in the human brain.

ABSTRACT: In humans, the TBC1D3 gene family is thought to play a critical role in the expansion of the frontal cortex by promoting neuronal proliferation during brain development. This gene family shows some of the greatest structural heterozygosity (~97%) with haplotype copy numbers ranging from 3-39 among different human haplotypes. This raises the question as to how a gene so crucial in the evolutionary expansion of the human frontal cortex can be so variable in the human population. Here, we characterize the regulatory architecture that explains this paradox. We show that 45-96% of TBC1D3 expression is attributable to a single paralog located at the most telomeric position at the edge of a cluster of TBC1D3 genes. We find that its >3-fold higher expression relative to other

SUBMITTER: Guitart X 

PROVIDER: S-EPMC12871316 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature