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Use of a Dense Single Nucleotide Polymorphism Map for In Silico Mapping in the Mouse

Rapid expansion of available data, both phenotypic and genotypic, for multiple strains of mice has enabled the development of new methods to interrogate the mouse genome for functional genetic perturbations. In silico mapping provides an expedient way to associate the natural diversity of phenotypic...

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Autores principales: Pletcher, Mathew T, McClurg, Philip, Batalov, Serge, Su, Andrew I, Barnes, S. Whitney, Lagler, Erica, Korstanje, Ron, Wang, Xiaosong, Nusskern, Deborah, Bogue, Molly A, Mural, Richard J, Paigen, Beverly, Wiltshire, Tim
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526179/
https://www.ncbi.nlm.nih.gov/pubmed/15534693
http://dx.doi.org/10.1371/journal.pbio.0020393
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author Pletcher, Mathew T
McClurg, Philip
Batalov, Serge
Su, Andrew I
Barnes, S. Whitney
Lagler, Erica
Korstanje, Ron
Wang, Xiaosong
Nusskern, Deborah
Bogue, Molly A
Mural, Richard J
Paigen, Beverly
Wiltshire, Tim
author_facet Pletcher, Mathew T
McClurg, Philip
Batalov, Serge
Su, Andrew I
Barnes, S. Whitney
Lagler, Erica
Korstanje, Ron
Wang, Xiaosong
Nusskern, Deborah
Bogue, Molly A
Mural, Richard J
Paigen, Beverly
Wiltshire, Tim
author_sort Pletcher, Mathew T
collection PubMed
description Rapid expansion of available data, both phenotypic and genotypic, for multiple strains of mice has enabled the development of new methods to interrogate the mouse genome for functional genetic perturbations. In silico mapping provides an expedient way to associate the natural diversity of phenotypic traits with ancestrally inherited polymorphisms for the purpose of dissecting genetic traits. In mouse, the current single nucleotide polymorphism (SNP) data have lacked the density across the genome and coverage of enough strains to properly achieve this goal. To remedy this, 470,407 allele calls were produced for 10,990 evenly spaced SNP loci across 48 inbred mouse strains. Use of the SNP set with statistical models that considered unique patterns within blocks of three SNPs as an inferred haplotype could successfully map known single gene traits and a cloned quantitative trait gene. Application of this method to high-density lipoprotein and gallstone phenotypes reproduced previously characterized quantitative trait loci (QTL). The inferred haplotype data also facilitates the refinement of QTL regions such that candidate genes can be more easily identified and characterized as shown for adenylate cyclase 7.
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spelling pubmed-5261792004-11-08 Use of a Dense Single Nucleotide Polymorphism Map for In Silico Mapping in the Mouse Pletcher, Mathew T McClurg, Philip Batalov, Serge Su, Andrew I Barnes, S. Whitney Lagler, Erica Korstanje, Ron Wang, Xiaosong Nusskern, Deborah Bogue, Molly A Mural, Richard J Paigen, Beverly Wiltshire, Tim PLoS Biol Research Article Rapid expansion of available data, both phenotypic and genotypic, for multiple strains of mice has enabled the development of new methods to interrogate the mouse genome for functional genetic perturbations. In silico mapping provides an expedient way to associate the natural diversity of phenotypic traits with ancestrally inherited polymorphisms for the purpose of dissecting genetic traits. In mouse, the current single nucleotide polymorphism (SNP) data have lacked the density across the genome and coverage of enough strains to properly achieve this goal. To remedy this, 470,407 allele calls were produced for 10,990 evenly spaced SNP loci across 48 inbred mouse strains. Use of the SNP set with statistical models that considered unique patterns within blocks of three SNPs as an inferred haplotype could successfully map known single gene traits and a cloned quantitative trait gene. Application of this method to high-density lipoprotein and gallstone phenotypes reproduced previously characterized quantitative trait loci (QTL). The inferred haplotype data also facilitates the refinement of QTL regions such that candidate genes can be more easily identified and characterized as shown for adenylate cyclase 7. Public Library of Science 2004-12 2004-11-09 /pmc/articles/PMC526179/ /pubmed/15534693 http://dx.doi.org/10.1371/journal.pbio.0020393 Text en Copyright: © 2004 Pletcher 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
Pletcher, Mathew T
McClurg, Philip
Batalov, Serge
Su, Andrew I
Barnes, S. Whitney
Lagler, Erica
Korstanje, Ron
Wang, Xiaosong
Nusskern, Deborah
Bogue, Molly A
Mural, Richard J
Paigen, Beverly
Wiltshire, Tim
Use of a Dense Single Nucleotide Polymorphism Map for In Silico Mapping in the Mouse
title Use of a Dense Single Nucleotide Polymorphism Map for In Silico Mapping in the Mouse
title_full Use of a Dense Single Nucleotide Polymorphism Map for In Silico Mapping in the Mouse
title_fullStr Use of a Dense Single Nucleotide Polymorphism Map for In Silico Mapping in the Mouse
title_full_unstemmed Use of a Dense Single Nucleotide Polymorphism Map for In Silico Mapping in the Mouse
title_short Use of a Dense Single Nucleotide Polymorphism Map for In Silico Mapping in the Mouse
title_sort use of a dense single nucleotide polymorphism map for in silico mapping in the mouse
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC526179/
https://www.ncbi.nlm.nih.gov/pubmed/15534693
http://dx.doi.org/10.1371/journal.pbio.0020393
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