The long (and winding) road to gene discovery for canine hip dysplasia

Lan Zhu; Zhiwu Zhang; Steven Friedenberg; Seung Woo Jung; Janjira Phavaphutanon; Margaret Vernier-Singer; Elizabeth Corey; Raluca Mateescu; Nathan Dykes; Jody Sandler; Gregory Acland; George Lust; Rory Todhunter

doi:10.1016/j.tvjl.2009.02.008

The long (and winding) road to gene discovery for canine hip dysplasia

Lan Zhu, Zhiwu Zhang, Steven Friedenberg, Seung Woo Jung, Janjira Phavaphutanon, Margaret Vernier-Singer, Elizabeth Corey, Raluca Mateescu, Nathan Dykes, Jody Sandler, Gregory Acland, George Lust, Rory Todhunter

Veterinary Clinical Sciences

Research output: Contribution to journal › Review article › peer-review

39 Scopus citations

Abstract

Hip dysplasia is a common inherited trait of dogs that results in secondary osteoarthritis. In this article the methods used to uncover the mutations contributing to this condition are reviewed, beginning with hip phenotyping. Coarse, genome-wide, microsatellite-based screens of pedigrees of greyhounds and dysplastic Labrador retrievers were used to identify linked quantitative trait loci (QTL). Fine-mapping across two chromosomes (CFA11 and 29) was employed using single nucleotide polymorphism (SNP) genotyping. Power analyses and preferential selection of dogs for ongoing SNP-based genotyping is described with the aim of refining the QTL intervals to 1-2 megabases on these and several additional chromosomes prior to candidate gene screening. The review considers how a mutation or a genetic marker such as a SNP or haplotype of SNPs might be combined with pedigree and phenotype information to create a 'breeding value' that could improve the accuracy of predicting a dog's hip conformation.

Original language	English (US)
Pages (from-to)	97-110
Number of pages	14
Journal	Veterinary Journal
Volume	181
Issue number	2
DOIs	https://doi.org/10.1016/j.tvjl.2009.02.008
State	Published - Aug 2009

Bibliographical note

Funding Information:
We gratefully acknowledge the support of The Morris Animal Foundation, The Orthopedic Foundation for Animals, Cornell Biotechnology, The Collaborative Grants Programme, NIH for R21, Pfizer Incorporated, Masterfoods Incorporated, and that of private donations. We greatly miss our colleague, Dr. Nancy Burton-Wurster, who passed away last year leaving us to carry on her important work.

Keywords

Breeding values
Canine hip dysplasia
Genome wide screen
Microsatellites
Single nucleotide polymorphisms (SNP)

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10.1016/j.tvjl.2009.02.008

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abstract = "Hip dysplasia is a common inherited trait of dogs that results in secondary osteoarthritis. In this article the methods used to uncover the mutations contributing to this condition are reviewed, beginning with hip phenotyping. Coarse, genome-wide, microsatellite-based screens of pedigrees of greyhounds and dysplastic Labrador retrievers were used to identify linked quantitative trait loci (QTL). Fine-mapping across two chromosomes (CFA11 and 29) was employed using single nucleotide polymorphism (SNP) genotyping. Power analyses and preferential selection of dogs for ongoing SNP-based genotyping is described with the aim of refining the QTL intervals to 1-2 megabases on these and several additional chromosomes prior to candidate gene screening. The review considers how a mutation or a genetic marker such as a SNP or haplotype of SNPs might be combined with pedigree and phenotype information to create a 'breeding value' that could improve the accuracy of predicting a dog's hip conformation.",

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AU - Vernier-Singer, Margaret

AU - Corey, Elizabeth

AU - Mateescu, Raluca

AU - Dykes, Nathan

AU - Sandler, Jody

AU - Acland, Gregory

AU - Lust, George

AU - Todhunter, Rory

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N2 - Hip dysplasia is a common inherited trait of dogs that results in secondary osteoarthritis. In this article the methods used to uncover the mutations contributing to this condition are reviewed, beginning with hip phenotyping. Coarse, genome-wide, microsatellite-based screens of pedigrees of greyhounds and dysplastic Labrador retrievers were used to identify linked quantitative trait loci (QTL). Fine-mapping across two chromosomes (CFA11 and 29) was employed using single nucleotide polymorphism (SNP) genotyping. Power analyses and preferential selection of dogs for ongoing SNP-based genotyping is described with the aim of refining the QTL intervals to 1-2 megabases on these and several additional chromosomes prior to candidate gene screening. The review considers how a mutation or a genetic marker such as a SNP or haplotype of SNPs might be combined with pedigree and phenotype information to create a 'breeding value' that could improve the accuracy of predicting a dog's hip conformation.

AB - Hip dysplasia is a common inherited trait of dogs that results in secondary osteoarthritis. In this article the methods used to uncover the mutations contributing to this condition are reviewed, beginning with hip phenotyping. Coarse, genome-wide, microsatellite-based screens of pedigrees of greyhounds and dysplastic Labrador retrievers were used to identify linked quantitative trait loci (QTL). Fine-mapping across two chromosomes (CFA11 and 29) was employed using single nucleotide polymorphism (SNP) genotyping. Power analyses and preferential selection of dogs for ongoing SNP-based genotyping is described with the aim of refining the QTL intervals to 1-2 megabases on these and several additional chromosomes prior to candidate gene screening. The review considers how a mutation or a genetic marker such as a SNP or haplotype of SNPs might be combined with pedigree and phenotype information to create a 'breeding value' that could improve the accuracy of predicting a dog's hip conformation.

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The long (and winding) road to gene discovery for canine hip dysplasia

Abstract

Bibliographical note

Keywords

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