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Genome-Wide Analysis Reveals a Complex Pattern of Genomic Imprinting in Mice

Parent-of-origin–dependent gene expression resulting from genomic imprinting plays an important role in modulating complex traits ranging from developmental processes to cognitive abilities and associated disorders. However, while gene-targeting techniques have allowed for the identification of impr...

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Autores principales: Wolf, Jason B., Cheverud, James M., Roseman, Charles, Hager, Reinmar
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2390766/
https://www.ncbi.nlm.nih.gov/pubmed/18535661
http://dx.doi.org/10.1371/journal.pgen.1000091
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author Wolf, Jason B.
Cheverud, James M.
Roseman, Charles
Hager, Reinmar
author_facet Wolf, Jason B.
Cheverud, James M.
Roseman, Charles
Hager, Reinmar
author_sort Wolf, Jason B.
collection PubMed
description Parent-of-origin–dependent gene expression resulting from genomic imprinting plays an important role in modulating complex traits ranging from developmental processes to cognitive abilities and associated disorders. However, while gene-targeting techniques have allowed for the identification of imprinted loci, very little is known about the contribution of imprinting to quantitative variation in complex traits. Most studies, furthermore, assume a simple pattern of imprinting, resulting in either paternal or maternal gene expression; yet, more complex patterns of effects also exist. As a result, the distribution and number of different imprinting patterns across the genome remain largely unexplored. We address these unresolved issues using a genome-wide scan for imprinted quantitative trait loci (iQTL) affecting body weight and growth in mice using a novel three-generation design. We identified ten iQTL that display much more complex and diverse effect patterns than previously assumed, including four loci with effects similar to the callipyge mutation found in sheep. Three loci display a new phenotypic pattern that we refer to as bipolar dominance, where the two heterozygotes are different from each other while the two homozygotes are identical to each other. Our study furthermore detected a paternally expressed iQTL on Chromosome 7 in a region containing a known imprinting cluster with many paternally expressed genes. Surprisingly, the effects of the iQTL were mostly restricted to traits expressed after weaning. Our results imply that the quantitative effects of an imprinted allele at a locus depend both on its parent of origin and the allele it is paired with. Our findings also show that the imprinting pattern of a locus can be variable over ontogenetic time and, in contrast to current views, may often be stronger at later stages in life.
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spelling pubmed-23907662008-06-06 Genome-Wide Analysis Reveals a Complex Pattern of Genomic Imprinting in Mice Wolf, Jason B. Cheverud, James M. Roseman, Charles Hager, Reinmar PLoS Genet Research Article Parent-of-origin–dependent gene expression resulting from genomic imprinting plays an important role in modulating complex traits ranging from developmental processes to cognitive abilities and associated disorders. However, while gene-targeting techniques have allowed for the identification of imprinted loci, very little is known about the contribution of imprinting to quantitative variation in complex traits. Most studies, furthermore, assume a simple pattern of imprinting, resulting in either paternal or maternal gene expression; yet, more complex patterns of effects also exist. As a result, the distribution and number of different imprinting patterns across the genome remain largely unexplored. We address these unresolved issues using a genome-wide scan for imprinted quantitative trait loci (iQTL) affecting body weight and growth in mice using a novel three-generation design. We identified ten iQTL that display much more complex and diverse effect patterns than previously assumed, including four loci with effects similar to the callipyge mutation found in sheep. Three loci display a new phenotypic pattern that we refer to as bipolar dominance, where the two heterozygotes are different from each other while the two homozygotes are identical to each other. Our study furthermore detected a paternally expressed iQTL on Chromosome 7 in a region containing a known imprinting cluster with many paternally expressed genes. Surprisingly, the effects of the iQTL were mostly restricted to traits expressed after weaning. Our results imply that the quantitative effects of an imprinted allele at a locus depend both on its parent of origin and the allele it is paired with. Our findings also show that the imprinting pattern of a locus can be variable over ontogenetic time and, in contrast to current views, may often be stronger at later stages in life. Public Library of Science 2008-06-06 /pmc/articles/PMC2390766/ /pubmed/18535661 http://dx.doi.org/10.1371/journal.pgen.1000091 Text en Wolf et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wolf, Jason B.
Cheverud, James M.
Roseman, Charles
Hager, Reinmar
Genome-Wide Analysis Reveals a Complex Pattern of Genomic Imprinting in Mice
title Genome-Wide Analysis Reveals a Complex Pattern of Genomic Imprinting in Mice
title_full Genome-Wide Analysis Reveals a Complex Pattern of Genomic Imprinting in Mice
title_fullStr Genome-Wide Analysis Reveals a Complex Pattern of Genomic Imprinting in Mice
title_full_unstemmed Genome-Wide Analysis Reveals a Complex Pattern of Genomic Imprinting in Mice
title_short Genome-Wide Analysis Reveals a Complex Pattern of Genomic Imprinting in Mice
title_sort genome-wide analysis reveals a complex pattern of genomic imprinting in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2390766/
https://www.ncbi.nlm.nih.gov/pubmed/18535661
http://dx.doi.org/10.1371/journal.pgen.1000091
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