broad-scale recombination patterns underlying proper disjunction in humans人类大规模重组模式的潜在合适的分离.pdfVIP

Broad-Scale Recombination Patterns Underlying Proper Disjunction in Humans 1 1 2 3 1 4 Adi Fledel-Alon , Daniel J. Wilson , Karl Broman , Xiaoquan Wen , Carole Ober , Graham Coop , Molly Przeworski1,5* 1 Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America, 2 Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin, United States of America, 3 Department of Statistics, University of Chicago, Chicago, Illinois, United States of America, 4 Evolution and Ecology Section, University of California Davis, Davis, California, United States of America, 5 Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, United States of America Abstract Although recombination is essential to the successful completion of human meiosis, it remains unclear how tightly the process is regulated and over what scale. To assess the nature and stringency of constraints on human recombination, we examined crossover patterns in transmissions to viable, non-trisomic offspring, using dense genotyping data collected in a large set of pedigrees. Our analysis supports a requirement for one chiasma per chromosome rather than per arm to ensure proper disjunction, with additional chiasmata occurring in proportion to physical length. The requirement is not absolute, however, as chromosome 21 seems to be frequently transmitted properly in the absence of a chiasma in females, a finding that raises the possibility of a back-up mechanism aiding in its correct segregation. We also found a set of double crossovers in surprisingly close proximity, as expected from a second pathway that is not subject to crossover