The structural maintenance of chromosomes complex, SMC5/6, is crucial for brain development and function as it ensures proficient DNA replication in neural progenitor cells prior to chromosome segregation.
Prdm9-generated meiotic asynapsis of homologous chromosomes in mouse subspecific hybrids causes hybrid sterility and can be reversed by introducing random stretches of consubspecific sequence (≥ 27Mb) on four chromosomes most sensitive to asynapsis.
Female-inherited supernumerary chromosomes that lack a male-inherited homolog are transmitted to all meiotic products instead of the expected half, which indicates an additional amplification of unpaired chromosomes during meiosis.
Evolutionary adaptation to a constitutive perturbation of DNA replication reveals that adaptive mutations in three conserved pathways interact to restore faithful chromosome replication and segregation.
TcMAC21 is an appropriate “next gen” mouse model for DS research, and provides a proof of concept of using artificial chromosomes to generate non-mosaic humanized animal models of chromosome disorders.