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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Published in:PLoS biology 2004-12, Vol.2 (12), p.e393-e393
Main Authors: 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
Format: Article
Language:English
Subjects:
Adenylyl Cyclases - genetics
Alleles
Animals
Bioinformatics/Computational Biology
Chromosome Mapping
Colleges & universities
Computational Biology - methods
Confidence intervals
Crosses, Genetic
Gallstones - metabolism
Genetics
Genetics/Genomics/Gene Therapy
Genome
Genomes
Genomics
Genotype & phenotype
Haplotypes
Linkage Disequilibrium
Lipoproteins, HDL - metabolism
Logistic Models
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Inbred Strains
Models, Genetic
Models, Statistical
Mus (Mouse)
Phenotype
Phylogeny
Polymorphism
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Rodents
Species Specificity
Statistical methods
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creator Pletcher, Mathew T
McClurg, Philip
Batalov, Serge
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Bogue, Molly A
Mural, Richard J
Paigen, Beverly
Wiltshire, Tim
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.
doi_str_mv 10.1371/journal.pbio.0020393
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subjects Adenylyl Cyclases - genetics
Alleles
Animals
Bioinformatics/Computational Biology
Chromosome Mapping
Colleges & universities
Computational Biology - methods
Confidence intervals
Crosses, Genetic
Gallstones - metabolism
Genetics
Genetics/Genomics/Gene Therapy
Genome
Genomes
Genomics
Genotype & phenotype
Haplotypes
Linkage Disequilibrium
Lipoproteins, HDL - metabolism
Logistic Models
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Inbred Strains
Models, Genetic
Models, Statistical
Mus (Mouse)
Phenotype
Phylogeny
Polymorphism
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Rodents
Species Specificity
Statistical methods
title Use of a dense single nucleotide polymorphism map for in silico mapping in the mouse
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