Quantitative trait loci for hip dysplasia in a crossbreed canine pedigree

Abstract

Canine hip dysplasia is a common developmental inherited trait characterized by hip laxity, subluxation or incongruity of the femoral head and acetabulum in affected hips. The inheritance pattern is complex and the mutations contributing to trait expression are unknown. In the study reported here, 240 microsatellite markers distributed in 38 autosomes and the X chromosome were genotyped on 152 dogs from three generations of a crossbred pedigree based on trait-free Greyhound and dysplastic Labrador Retriever founders. Interval mapping was undertaken to map the QTL underlying the quantitative dysplastic traits of maximum passive hip laxity (the distraction index), the dorsolateral subluxation score, and the Norberg angle. Permutation testing was used to derive the chromosome-wide level of significance at p<0.05 for each QTL. Chromosomes 4, 9, 10, 11 (p<0.01), 16, 20, 22, 25, 29 (p<0.01), 30, 35, and 37 harbor putative QTL for one or more traits. Successful detection of QTL was due to the cross-breed pedigree, multiple-trait measurements, control of environmental background, and marked advancement in canine mapping tools.

Single-Nucleotide-Polymorphism-Based Association Mapping of Dog Stereotypes

“…Segregation in planned crosses or within a breed population can be used to identify loci for simple and complex phenotypes. This approach takes advantage of the large LD distances that can be attributed to founder effects and bottlenecks (for example, Mignot et al 1991;Acland et al 1998Acland et al , 1999Lingaas et al 1998;Van de Sluis et al 1999;Jonasdottir et al 2000;Chase et al 2005aChase et al , 2006Todhunter et al 2005). 2.…”

Exclusion of COL2A1 and VDR as Developmental Dysplasia of the Hip Genes

“…Nonsyndromic DDH is widely considered a multifactorial polygenic disorder, but the nature of its genetic component is still unknown [14][15][16]. Carter and Wilkinson [3] hypothesized two different genetic systems could be responsible for the etiology of DDH, one related to the dysplasia of the acetabulum and another controlling the capsule around the hip.…”

Genetic markers of canine hip dysplasia

“…Wykorzystano wówczas rzadko stosowane podejście, jakim było krzyżowanie psów rasy labrador retriever obciążonych CHD oraz zdrowych (bez objawów CHD) zwierząt z rasy greyhound. W trzech uzyskanych pokoleniach (152 psów) ustalono genotyp w 240 loci sekwencji mikrosatelitarnych, rozproszonych równomiernie we wszystkich autosomach i chromosomie X. Potencjalne regiony QTL dla CHD wskazano aż w 12 chromosomach: CFA4, CFA9, CFA10, CFA11, CFA16, CFA20, CFA22, CFA25, CFA29, CFA30, CFA35, CFA37 (25). W kolejnych badaniach, również opartych na markerach mikrosatelitarnych, analizowano genotyp w 276 takich loci, a ich efektem było wskazanie QTL w 7 chromosomach: CFA1, CFA2, CFA10, CFA20, CFA22 i CFA32 (22).…”

“…Kolejny region, zlokalizowany w chromosomie CFA1, wykazał słabszy związek z CHD, jednakże jego pozycja pokrywa się z wcześniejszymi wynikami, które także dotyczyły labradorów (22). W chromosomie CFA20 również potwierdzono obecność wcześniej wskazanego regionu zasocjowanego z CHD (25). Spośród wielu genów, których loci znajdują się we wskazanych regionach, wytypowano kilka genów kandydujących (LAMA2, LRR1, COL6A3, GDF15, COMP i CILP2).…”