Project

CHRFAM7A is a human-specific chimeric gene derived from the CHRNA7 locus and is proposed to modulate the α7 nicotinic acetylcholine receptor, a key regulator of synaptic signalling, neuroinflammation and cognition. CHRFAM7A displays marked genetic diversity, including copy-number variation and structural rearrangements, which may contribute to inter-individual differences in neuronal physiology and therapeutic responses in neurodegenerative disorders such as Alzheimer’s disease. However, robust genotyping of CHRFAM7A remains technically challenging because CHRFAM7A and CHRNA7 share extensive sequence identity, causing short-read sequencing to misassign reads and variants across paralogous segments. This project will generate a locus-resolved, high-confidence genetic map of the CHRFAM7A/CHRNA7 region in human induced pluripotent stem cell (hiPSC) lines carrying two copies of CHRFAM7A. By providing definitive locus resolution, this work will de-risk downstream functional studies in hiPSC-derived neurons and support future translational efforts linking CHRFAM7A genotype to cholinergic mechanisms relevant to Alzheimer’s disease.