Genome wide analysis indicates genes for basement membrane and cartilage matrix proteins as candidates for hip dysplasia in Labrador Retrievers - PubMed (original) (raw)

Genome wide analysis indicates genes for basement membrane and cartilage matrix proteins as candidates for hip dysplasia in Labrador Retrievers

Ineke C M Lavrijsen et al. PLoS One. 2014.

Abstract

Hip dysplasia, an abnormal laxity of the hip joint, is seen in humans as well as dogs and is one of the most common skeletal disorders in dogs. Canine hip dysplasia is considered multifactorial and polygenic, and a variety of chromosomal regions have been associated with the disorder. We performed a genome-wide association study in Dutch Labrador Retrievers, comparing data of nearly 18,000 single nucleotide polymorphisms (SNPs) in 48 cases and 30 controls using two different statistical methods. An individual SNP analysis based on comparison of allele frequencies with a χ(2) statistic was used, as well as a simultaneous SNP analysis based on Bayesian variable selection. Significant association with canine hip dysplasia was observed on chromosome 8, as well as suggestive association on chromosomes 1, 5, 15, 20, 25 and 32. Next-generation DNA sequencing of the exons of genes of seven regions identified multiple associated alleles on chromosome 1, 5, 8, 20, 25 and 32 (p<0.001). Candidate genes located in the associated regions on chromosomes 1, 8 and 25 included LAMA2, LRR1 and COL6A3, respectively. The associated region on CFA20 contained candidate genes GDF15, COMP and CILP2. In conclusion, our study identified candidate genes that might affect susceptibility to canine hip dysplasia. These genes are involved in hypertrophic differentiation of chondrocytes and extracellular matrix integrity of basement membrane and cartilage. The functions of the genes are in agreement with the notion that disruptions in endochondral bone formation in combination with soft tissue defects are involved in the etiology of hip dysplasia.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: It should be noted that the co-authors AJ Martin and SJ Harris are employed by Waltham Centre for Pet Nutrition, a division of Mars Petcare, which also funded this study. This company has applied for patents based on the results of this work: Application 1310552.3; Name: Composition for Canine Animals and Application 1310558.0; Name: Genetic Test. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1

Figure 1. Genome wide association analysis of hip dysplasia in Labrador retrievers.

Genotypes of 17,859 SNPs were compared between 48 cases and 30 controls. A. Allele frequency based χ2 statistics. The dotted line indicates the significance threshold after Bonferroni correction. B. Multiple testing correction of the χ2 statistics by 1,000 permutations of the phenotypes to determine empirical p-values. The dotted line indicates the significance threshold (α = 0.05). C. Genome wide association analysis using Bayesian variable selection to detect SNPs with a high probability to have an effect on the CHD phenotype. The dotted line indicates the significance level.

Similar articles

Cited by

References

    1. Todhunter RJ, Lust G (2003) Canine hip dysplasia pathogenesis. In: Slatter D, editor. Textbook of small animal surgery. Philadelphia: WB Saunders Co. 2009–2019.
    1. Boere-Boonekamp MM, Verkerk PH (1998) Screening for developmental dysplasia of the hip. Seminars in Neonatology 3: 49–59.
    1. Peled E, Eidelman M, Katzman A, Bialik V (2008) Neonatal incidence of hip dysplasia: Ten years of experience. Clin Orthop Relat Res 466: 771–775. - PMC - PubMed
    1. Priester WA, Mulvihill JJ (1972) Canine hip dysplasia: Relative risk by sex, size, and breed, and comparative aspects. J Am Vet Med Assoc 160: 735–739. - PubMed
    1. Malm S, Strandberg E, Danell B, Audell L, Swenson L, et al. (2007) Impact of sedation method on the diagnosis of hip and elbow dysplasia in swedish dogs. Prev Vet Med 78: 196–209. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources