A Researcher's guide to rodent models of Down syndrome: Recent insights and translational perspectives.

Meiotic recombination plays a fundamental role in shaping population genetic diversity. Utilizing whole genome data from three multi-sibling families, we here provide the first estimates of the rates and patterns of crossover and noncrossover recombination in coppery titi monkeys ()—a socially monogamous, pair-bonded primate that serves as an important model in behavioral research. Along with germline mutations, meiotic recombination plays a fundamental role in generating and shaping observed genetic diversity (see the review of ). A requisite for the faithful segregation of homologous chromosomes during gametogenesis (), recombination in primates is thought to primarily take place at PRDM9-mediated hotspots (; ; ). Localizing these hotspots by binding DNA at specific sequence motifs with its C-terminal zinc-finger domain (), the histone methyltransferase PRDM9 trimethylates H3K4 and H3K36 (), thereby creating an open chromatin environment permissive to the formation of DNA double-strand breaks (). Programed meiotic double-strand breaks are subsequently repaired using the homologous chromosome as a template (), leading to either a reciprocal exchange of large segments of genetic material between the homologs (crossover; CO) or, more commonly, a nonreciprocal transfer of a short segment from a donor homolog (noncrossover; NCO) (; and see the reviews of ; ). Although a common determinant of recombination landscapes in primates, the location of PRDM9-mediated hotspots appears generally nonconserved between species (e.g. ; ; and see ), as the rapid evolution of the PRDM9 zinc-finger domain alters the recognition of, and binding specificity to, the sequence motif (; ; ; ; ). In many organisms, there also exist sex-specific differences with regards to both the positioning and usage of recombination hotspots as well as the overall rate of recombination; for example, in humans, females generally exhibit higher rates of COs and lower rates of NCOs than males (though NCO tracts tend to be longer), whereas males display a more prominent elevation of recombination rates toward the telomeric ends of the chromosomes compared to the more uniformly distributed rates observed in females (, ; ; , ; ; and see ).