Cargando…

High-Resolution Sex-Specific Linkage Maps of the Mouse Reveal Polarized Distribution of Crossovers in Male Germline

Since the publication of the first comprehensive linkage map for the laboratory mouse, the architecture of recombination as a basic biological process has become amenable to investigation in mammalian model organisms. Here we take advantage of high-density genotyping and the unique pedigree structur...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Eric Yi, Morgan, Andrew P., Chesler, Elissa J., Wang, Wei, Churchill, Gary A., Pardo-Manuel de Villena, Fernando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012503/
https://www.ncbi.nlm.nih.gov/pubmed/24578350
http://dx.doi.org/10.1534/genetics.114.161653
_version_ 1782314939471364096
author Liu, Eric Yi
Morgan, Andrew P.
Chesler, Elissa J.
Wang, Wei
Churchill, Gary A.
Pardo-Manuel de Villena, Fernando
author_facet Liu, Eric Yi
Morgan, Andrew P.
Chesler, Elissa J.
Wang, Wei
Churchill, Gary A.
Pardo-Manuel de Villena, Fernando
author_sort Liu, Eric Yi
collection PubMed
description Since the publication of the first comprehensive linkage map for the laboratory mouse, the architecture of recombination as a basic biological process has become amenable to investigation in mammalian model organisms. Here we take advantage of high-density genotyping and the unique pedigree structure of the incipient Collaborative Cross to investigate the roles of sex and genetic background in mammalian recombination. Our results confirm the observation that map length is longer when measured through female meiosis than through male meiosis, but we find that this difference is modified by genotype at loci on both the X chromosome and the autosomes. In addition, we report a striking concentration of crossovers in the distal ends of autosomes in male meiosis that is absent in female meiosis. The presence of this pattern in both single- and double-recombinant chromosomes, combined with the absence of a corresponding asymmetry in the distribution of double-strand breaks, indicates a regulated sequence of events specific to male meiosis that is anchored by chromosome ends. This pattern is consistent with the timing of chromosome pairing and evolutionary constraints on male recombination. Finally, we identify large regions of reduced crossover frequency that together encompass 5% of the genome. Many of these “cold regions” are enriched for segmental duplications, suggesting an inverse local correlation between recombination rate and mutation rate for large copy number variants.
format Online
Article
Text
id pubmed-4012503
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Genetics Society of America
record_format MEDLINE/PubMed
spelling pubmed-40125032014-05-14 High-Resolution Sex-Specific Linkage Maps of the Mouse Reveal Polarized Distribution of Crossovers in Male Germline Liu, Eric Yi Morgan, Andrew P. Chesler, Elissa J. Wang, Wei Churchill, Gary A. Pardo-Manuel de Villena, Fernando Genetics Investigations Since the publication of the first comprehensive linkage map for the laboratory mouse, the architecture of recombination as a basic biological process has become amenable to investigation in mammalian model organisms. Here we take advantage of high-density genotyping and the unique pedigree structure of the incipient Collaborative Cross to investigate the roles of sex and genetic background in mammalian recombination. Our results confirm the observation that map length is longer when measured through female meiosis than through male meiosis, but we find that this difference is modified by genotype at loci on both the X chromosome and the autosomes. In addition, we report a striking concentration of crossovers in the distal ends of autosomes in male meiosis that is absent in female meiosis. The presence of this pattern in both single- and double-recombinant chromosomes, combined with the absence of a corresponding asymmetry in the distribution of double-strand breaks, indicates a regulated sequence of events specific to male meiosis that is anchored by chromosome ends. This pattern is consistent with the timing of chromosome pairing and evolutionary constraints on male recombination. Finally, we identify large regions of reduced crossover frequency that together encompass 5% of the genome. Many of these “cold regions” are enriched for segmental duplications, suggesting an inverse local correlation between recombination rate and mutation rate for large copy number variants. Genetics Society of America 2014-05 2014-02-27 /pmc/articles/PMC4012503/ /pubmed/24578350 http://dx.doi.org/10.1534/genetics.114.161653 Text en Copyright © 2014 by the Genetics Society of America Available freely online through the author-supported open access option.
spellingShingle Investigations
Liu, Eric Yi
Morgan, Andrew P.
Chesler, Elissa J.
Wang, Wei
Churchill, Gary A.
Pardo-Manuel de Villena, Fernando
High-Resolution Sex-Specific Linkage Maps of the Mouse Reveal Polarized Distribution of Crossovers in Male Germline
title High-Resolution Sex-Specific Linkage Maps of the Mouse Reveal Polarized Distribution of Crossovers in Male Germline
title_full High-Resolution Sex-Specific Linkage Maps of the Mouse Reveal Polarized Distribution of Crossovers in Male Germline
title_fullStr High-Resolution Sex-Specific Linkage Maps of the Mouse Reveal Polarized Distribution of Crossovers in Male Germline
title_full_unstemmed High-Resolution Sex-Specific Linkage Maps of the Mouse Reveal Polarized Distribution of Crossovers in Male Germline
title_short High-Resolution Sex-Specific Linkage Maps of the Mouse Reveal Polarized Distribution of Crossovers in Male Germline
title_sort high-resolution sex-specific linkage maps of the mouse reveal polarized distribution of crossovers in male germline
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012503/
https://www.ncbi.nlm.nih.gov/pubmed/24578350
http://dx.doi.org/10.1534/genetics.114.161653
work_keys_str_mv AT liuericyi highresolutionsexspecificlinkagemapsofthemouserevealpolarizeddistributionofcrossoversinmalegermline
AT morganandrewp highresolutionsexspecificlinkagemapsofthemouserevealpolarizeddistributionofcrossoversinmalegermline
AT cheslerelissaj highresolutionsexspecificlinkagemapsofthemouserevealpolarizeddistributionofcrossoversinmalegermline
AT wangwei highresolutionsexspecificlinkagemapsofthemouserevealpolarizeddistributionofcrossoversinmalegermline
AT churchillgarya highresolutionsexspecificlinkagemapsofthemouserevealpolarizeddistributionofcrossoversinmalegermline
AT pardomanueldevillenafernando highresolutionsexspecificlinkagemapsofthemouserevealpolarizeddistributionofcrossoversinmalegermline