title: Variation in MLH1 distribution in recombination maps for individual chromosomes from human males.
abstract: Meiotic recombination is essential for the segregation of homologous chromosomes and the formation of normal haploid gametes. Little is known about patterns of meiotic recombination in human germ cells or the mechanisms that control these patterns. Documentation of the normal range of variability of recombination distribution over the genome among individuals is an essential prerequisite for understanding abnormal recombination patterns, which may be associated with non-disjunction and chromosome rearrangements. In this article, variation in recombination maps for individual chromosomes among 10 normal human males is examined for the first time. An immunocytogenetic approach allowed analysis of pachytene cells, using antibodies to detect the mature synaptonemal complex (SCP1/SCP3), the centromere (CREST) and sites of crossing over (MLH1). Individual bivalents were identified with centromere-specific multicolor fluorescence in situ hybridization. Significant heterogeneity in MLH1 focus frequency across donors was observed for larger chromosome arms (P<0.05, one-way ANOVA). Significant inter-donor variation in the overall crossover frequency per cell was also found (P<0.0001, one-way ANOVA). Furthermore, several chromosome arms showed significant differences in crossover distribution along the SCs among donors. Inter-individual variation in interference distances was observed for all chromosomes. The significance of altered recombination patterns among individuals and the role of interference are discussed.
authors.affiliation: Department of Medical Genetics, University of Calgary, Calgary, Canada T2N 4N1.
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.forename: Maria
authors.initials: M
authors.lastname: Oliver-Bonet
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.forename: Heike
authors.initials: H
authors.lastname: Starke
authors.forename: Paul
authors.initials: P
authors.lastname: Turek
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ko
authors.forename: Alfred
authors.initials: A
authors.lastname: Rademaker
authors.forename: Renée H
authors.initials: RH
authors.lastname: Martin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D003434:Crossing Over, Genetic; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D011995:Recombination, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1