Variation in MLH1 distribution in recombination maps for individual chromosomes from human males
| Autor: | Heike Starke, Paul J. Turek, Maria Oliver-Bonet, Renée H. Martin, Alfred Rademaker, Evelyn Ko, Thomas Liehr, F. Sun |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Pseudoautosomal region Biology Genetic recombination Chromosomal crossover Gene Frequency Meiosis Genetics Homologous chromosome Humans Crossing Over Genetic Molecular Biology In Situ Hybridization Fluorescence Genetics (clinical) Adaptor Proteins Signal Transducing Aged Aged 80 and over Recombination Genetic Synapsis Chromosome Mapping Genetic Variation Nuclear Proteins General Medicine Middle Aged Immunohistochemistry Synaptonemal complex Ploidy Carrier Proteins MutL Protein Homolog 1 |
| Zdroj: | Human Molecular Genetics. 15:2376-2391 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddl162 |
| Popis: | Meiotic recombination is essential for the segregation of homologous chromosomes and the formation ofnormal haploid gametes. Little is known about patterns of meiotic recombination in human germ cells orthe mechanisms that control these patterns. Documentation of the normal range of variability of recombina-tion distribution over the genome among individuals is an essential prerequisite for understanding abnormalrecombination patterns, which may be associated with non-disjunction and chromosome rearrangements. Inthis article, variation in recombination maps for individual chromosomes among 10 normal human males isexamined for the first time. An immunocytogenetic approach allowed analysis of pachytene cells, using anti-bodies to detect the mature synaptonemal complex (SCP1/SCP3), the centromere (CREST) and sites of cross-ing over (MLH1). Individual bivalents were identified with centromere-specific multicolor fluorescence in situhybridization. Significant heterogeneity in MLH1 focus frequency across donors was observed for largerchromosome arms (P < 0.05, one-way ANOVA). Significant inter-donor variation in the overall crossover fre-quency per cell was also found (P < 0.0001, one-way ANOVA). Furthermore, several chromosome armsshowed significant differences in crossover distribution along the SCs among donors. Inter-individual vari-ation in interference distances was observed for all chromosomes. The significance of altered recombinationpatterns among individuals and the role of interference are discussed.INTRODUCTIONMeiotic crossing over, the exchange of genetic materialsbetween homologous chromosomes, generates not onlygenetic variation but is also vital for the correct segregation(disjunction) of homologous chromosomes during meiosis I(1). Historically, meiotic recombination in humans has beeninvestigated by cytological and genetical methods and, morerecently, by immunocytogenetic approaches. The cytologicalmethod is based on recording the numbers and locations ofchiasmata in bivalents at late prophase I or metaphase I ofmeiosis (2–5). Genetic measures of recombination in thehuman are derived from the identification of genotype datain families (6). Immunocytogenetic assays of the mismatchrepair protein MLH1 allow the precise identification of recom-bination foci along the synaptonemal complexes (SCs; theproteinaceous structure linking homologous chromosomes inprophase of meiosis I) (7–12). This assay, combined withcentromere-specific multicolor fluorescence in situ hybridiz-ation (cenM-FISH) (12–14), permits the analysis of crossoverfrequencies and distributions in individual chromosomes inhuman germ cells in a precise manner (12,13,15). Thus,immunocytogenetic methods provide a means to directlydetermine the pattern of recombination across the whole |
| Databáze: | OpenAIRE |
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