Genome-wide survey indicates involvement of loci on canine chromosomes 7 and 31 in patellar luxation in Flat-Coated Retrievers

Ineke C M Lavrijsen; Peter A J Leegwater; Chalika Wangdee; Frank G van Steenbeek; Monique Schwencke; Gert J Breur; Freek J Meutstege; Isaac J Nijman; Edwin Cuppen; Henri C M Heuven; Herman A W Hazewinkel

doi:10.1186/1471-2156-15-64

Genome-wide survey indicates involvement of loci on canine chromosomes 7 and 31 in patellar luxation in Flat-Coated Retrievers

Ineke C M Lavrijsen, Peter A J Leegwater, Chalika Wangdee, Frank G van Steenbeek, Monique Schwencke, Gert J Breur, Freek J Meutstege, Isaac J Nijman, Edwin Cuppen, Henri C M Heuven, Herman A W Hazewinkel

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

16 Citations (Scopus)

Abstract

BACKGROUND: Patellar luxation is an orthopedic disorder in which the patella moves out of its normal location within the femoral trochlea of the knee and it can lead to osteoarthritis, lameness, and pain. In dogs it is a heritable trait, with both environmental and genetic factors contributing to the phenotype. The prevalence of patellar luxation in the Dutch Flat-Coated Retriever population is 24%. In this study, we investigated the molecular genetics of the disorder in this population.

RESULTS: Genome-wide association analysis of 15,823 single nucleotide polymorphisms (SNPs) in 45 cases and 40 controls revealed that patellar luxation was significantly associated with a region on chromosome CFA07, and possibly with regions on CFA03, CFA31, and CFA36. The exons of the genes in these regions, 0.5 Mb combined, were analyzed further. These exons from 15 cases and a pooled sample from 15 controls were enriched using custom genomic hybridization arrays and analyzed by massive parallel DNA sequencing. In total 7257 variations were detected. Subsequently, a selection of 144 of these SNPs were genotyped in 95 Flat-Coated Retrievers. Nine SNPs, in eight genes on CFA07 and CFA31, were associated with patellar luxation (P <10-4). Genotyping of these SNPs in samples from a variety of breeds revealed that the disease-associated allele of one synonymous SNP in a pseudogene of FMO6 was unique to Flat-Coated Retrievers.

CONCLUSION: Genome-wide association analysis followed by targeted DNA sequencing identified loci on chromosomes 7 and 31 as being involved in patellar luxation in the Flat-Coated Retriever breed.

Original language	English
Pages (from-to)	64
Journal	BMC Genetics
Volume	15
DOIs	https://doi.org/10.1186/1471-2156-15-64
Publication status	Published - 2014

Keywords

Animals
Breeding
Case-Control Studies
Dog Diseases
Dogs
Exons
Female
Genetic Loci
Genome-Wide Association Study
Genotype
Male
Netherlands
Patella
Patellar Dislocation
Polymorphism, Single Nucleotide
Sequence Analysis, DNA

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10.1186/1471-2156-15-64

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Lavrijsen, I. C. M., Leegwater, P. A. J., Wangdee, C., van Steenbeek, F. G., Schwencke, M., Breur, G. J., Meutstege, F. J., Nijman, I. J., Cuppen, E., Heuven, H. C. M., & Hazewinkel, H. A. W. (2014). Genome-wide survey indicates involvement of loci on canine chromosomes 7 and 31 in patellar luxation in Flat-Coated Retrievers. BMC Genetics, 15, 64. https://doi.org/10.1186/1471-2156-15-64

@article{b2f1a617dcba4e52b7c4784742ae5e56,

title = "Genome-wide survey indicates involvement of loci on canine chromosomes 7 and 31 in patellar luxation in Flat-Coated Retrievers",

abstract = "BACKGROUND: Patellar luxation is an orthopedic disorder in which the patella moves out of its normal location within the femoral trochlea of the knee and it can lead to osteoarthritis, lameness, and pain. In dogs it is a heritable trait, with both environmental and genetic factors contributing to the phenotype. The prevalence of patellar luxation in the Dutch Flat-Coated Retriever population is 24%. In this study, we investigated the molecular genetics of the disorder in this population.RESULTS: Genome-wide association analysis of 15,823 single nucleotide polymorphisms (SNPs) in 45 cases and 40 controls revealed that patellar luxation was significantly associated with a region on chromosome CFA07, and possibly with regions on CFA03, CFA31, and CFA36. The exons of the genes in these regions, 0.5 Mb combined, were analyzed further. These exons from 15 cases and a pooled sample from 15 controls were enriched using custom genomic hybridization arrays and analyzed by massive parallel DNA sequencing. In total 7257 variations were detected. Subsequently, a selection of 144 of these SNPs were genotyped in 95 Flat-Coated Retrievers. Nine SNPs, in eight genes on CFA07 and CFA31, were associated with patellar luxation (P <10-4). Genotyping of these SNPs in samples from a variety of breeds revealed that the disease-associated allele of one synonymous SNP in a pseudogene of FMO6 was unique to Flat-Coated Retrievers.CONCLUSION: Genome-wide association analysis followed by targeted DNA sequencing identified loci on chromosomes 7 and 31 as being involved in patellar luxation in the Flat-Coated Retriever breed.",

keywords = "Animals, Breeding, Case-Control Studies, Dog Diseases, Dogs, Exons, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Male, Netherlands, Patella, Patellar Dislocation, Polymorphism, Single Nucleotide, Sequence Analysis, DNA",

author = "Lavrijsen, {Ineke C M} and Leegwater, {Peter A J} and Chalika Wangdee and {van Steenbeek}, {Frank G} and Monique Schwencke and Breur, {Gert J} and Meutstege, {Freek J} and Nijman, {Isaac J} and Edwin Cuppen and Heuven, {Henri C M} and Hazewinkel, {Herman A W}",

year = "2014",

doi = "10.1186/1471-2156-15-64",

language = "English",

volume = "15",

pages = "64",

journal = "BMC Genetics",

issn = "1471-2156",

publisher = "BioMed Central Ltd.",

}

TY - JOUR

T1 - Genome-wide survey indicates involvement of loci on canine chromosomes 7 and 31 in patellar luxation in Flat-Coated Retrievers

AU - Lavrijsen, Ineke C M

AU - Leegwater, Peter A J

AU - Wangdee, Chalika

AU - van Steenbeek, Frank G

AU - Schwencke, Monique

AU - Breur, Gert J

AU - Meutstege, Freek J

AU - Nijman, Isaac J

AU - Cuppen, Edwin

AU - Heuven, Henri C M

AU - Hazewinkel, Herman A W

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Patellar luxation is an orthopedic disorder in which the patella moves out of its normal location within the femoral trochlea of the knee and it can lead to osteoarthritis, lameness, and pain. In dogs it is a heritable trait, with both environmental and genetic factors contributing to the phenotype. The prevalence of patellar luxation in the Dutch Flat-Coated Retriever population is 24%. In this study, we investigated the molecular genetics of the disorder in this population.RESULTS: Genome-wide association analysis of 15,823 single nucleotide polymorphisms (SNPs) in 45 cases and 40 controls revealed that patellar luxation was significantly associated with a region on chromosome CFA07, and possibly with regions on CFA03, CFA31, and CFA36. The exons of the genes in these regions, 0.5 Mb combined, were analyzed further. These exons from 15 cases and a pooled sample from 15 controls were enriched using custom genomic hybridization arrays and analyzed by massive parallel DNA sequencing. In total 7257 variations were detected. Subsequently, a selection of 144 of these SNPs were genotyped in 95 Flat-Coated Retrievers. Nine SNPs, in eight genes on CFA07 and CFA31, were associated with patellar luxation (P <10-4). Genotyping of these SNPs in samples from a variety of breeds revealed that the disease-associated allele of one synonymous SNP in a pseudogene of FMO6 was unique to Flat-Coated Retrievers.CONCLUSION: Genome-wide association analysis followed by targeted DNA sequencing identified loci on chromosomes 7 and 31 as being involved in patellar luxation in the Flat-Coated Retriever breed.

AB - BACKGROUND: Patellar luxation is an orthopedic disorder in which the patella moves out of its normal location within the femoral trochlea of the knee and it can lead to osteoarthritis, lameness, and pain. In dogs it is a heritable trait, with both environmental and genetic factors contributing to the phenotype. The prevalence of patellar luxation in the Dutch Flat-Coated Retriever population is 24%. In this study, we investigated the molecular genetics of the disorder in this population.RESULTS: Genome-wide association analysis of 15,823 single nucleotide polymorphisms (SNPs) in 45 cases and 40 controls revealed that patellar luxation was significantly associated with a region on chromosome CFA07, and possibly with regions on CFA03, CFA31, and CFA36. The exons of the genes in these regions, 0.5 Mb combined, were analyzed further. These exons from 15 cases and a pooled sample from 15 controls were enriched using custom genomic hybridization arrays and analyzed by massive parallel DNA sequencing. In total 7257 variations were detected. Subsequently, a selection of 144 of these SNPs were genotyped in 95 Flat-Coated Retrievers. Nine SNPs, in eight genes on CFA07 and CFA31, were associated with patellar luxation (P <10-4). Genotyping of these SNPs in samples from a variety of breeds revealed that the disease-associated allele of one synonymous SNP in a pseudogene of FMO6 was unique to Flat-Coated Retrievers.CONCLUSION: Genome-wide association analysis followed by targeted DNA sequencing identified loci on chromosomes 7 and 31 as being involved in patellar luxation in the Flat-Coated Retriever breed.

KW - Animals

KW - Breeding

KW - Case-Control Studies

KW - Dog Diseases

KW - Dogs

KW - Exons

KW - Female

KW - Genetic Loci

KW - Genome-Wide Association Study

KW - Genotype

KW - Male

KW - Netherlands

KW - Patella

KW - Patellar Dislocation

KW - Polymorphism, Single Nucleotide

KW - Sequence Analysis, DNA

U2 - 10.1186/1471-2156-15-64

DO - 10.1186/1471-2156-15-64

M3 - Article

C2 - 24886090

SN - 1471-2156

VL - 15

SP - 64

JO - BMC Genetics

JF - BMC Genetics

ER -

Genome-wide survey indicates involvement of loci on canine chromosomes 7 and 31 in patellar luxation in Flat-Coated Retrievers

Abstract

Keywords

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