Emerging insights on canine hip dysplasia diagnosis: clues from radiology and genetics
Ficheiros
Data
2016
Autores
Título da revista
ISSN da revista
Título do Volume
Editora
Resumo
A displasia da anca no cão (DA) é caracterizada por um anormal desenvolvimento da
anca e da articulação coxofemoral sendo usualmente ambos os lados afetados, e é uma
condição frequente que afeta essencialmente cães de grande porte. A lassitude articular é o
maior fator de risco levando a subluxação e a incongruência entre o acetábulo e a cabeça do
fémur. Com o decorrer do tempo, a degeneração da articulação ocorre. Os sinais clínicos
incluem dor, decréscimo de atividade e claudicação. A radiografia tem sido o método mais
recorrente para avaliar a articulação e quantificar as modificações associadas mas, com o
desenvolvimento de técnicas genómicas, existe agora a possibilidade de tentar descortinar a
base genética para a DA.
Uma das raças nativas de cães pastores Portuguesas mais populares é o “Cão da Serra
da Estrela” (CSE) onde se verifica uma elevada prevalência de DA. Uma vasta base de dados
de informação radiográfica para DA nos CSE já estava disponível, justificando, assim, o
desenvolvimento de estudos genéticos na tentativa de compreender que regiões do genoma
podem estar associadas à DA.
Um artigo de revisão foi publicado com a descrição e discussão de diferentes
abordagens de diagnóstico de DA, com especial atenção prestada aos métodos radiográficos e
moleculares.
Um artigo original foi publicado que consistiu num estudo radiográfico retrospetivo
em 437 cães de diversas raças (dos quais 33 CSE) com o objetivo de determinar a capacidade
do ângulo de Norberg ≥105° de prever uma anca não displásica baseado no índice de
distração ≤0.3 ou no índice de subluxação dorsolateral ≥55%. Foi possível estabelecer que
com o cut-point recomendado de 105º, o ângulo de Norberg não foi uma medida precisa da
conformação normal da anca. A especificidade do diagnóstico de uma anca não displásica foi
maximizado com um cut-point de 112º (quando comparado com o índice de distração) ou de
109º (índice de subluxação dorsolateral).
Um estudo em 60 CSE e, para efeitos de comparação, em 10 cães de rua Portugueses e
em 10 Lobos Ibéricos, foi conduzido com o objetivo de investigar a diversidade genética e a
estrutura populacional na raça CSE usando polimorfismos de uma única base nucleotídica
(SNPs). Utilizaram-se, ainda, marcadores específicos do cromossoma Y para aferir relações
filogenéticas e a composição haplotípica. A raça CSE demonstrou elevados índices de
variabilidade genética com consanguinidade negligenciável. Foi detetada sub-estrutura subtil nos CSE possivelmente explicada por diferentes linhagens familiares associadas a diferentes
criadores em cada uma das zonas geográficas de amostragem, isto é, Norte, Centro e Sul de
Portugal. Todos os CSE partilharam um único haplotipo do cromossoma Y pertencente ao
haplogrupo H1 que é o mais prevalente em cães Europeus.
Os sistemas de diagnóstico têm como principal objectivo identificar os indivíduos
portadores de informação genotípica e/ou fenotípica associada a DA para os remover dos
programas de reprodução. Desta forma, conseguimos eliminar portadores, evitar a
transmissão desta informação genética e reduzir a prevalência da DA nas gerações seguintes.
Estas análises são a chave para uma investigação subsequente, nesta raça, da base genética de
traços específicos associados a DA, como a lassitude articular.
Canine hip dysplasia (CHD) is characterized by an abnormal hip and coxofemoral joint development with both hips usually affected, and is a common disorder that affects mainly large dog breeds. Hip joint laxity is the major risk factor leading to subluxation and poor congruence between the femoral head and acetabulum. Over time, degeneration of the joint occurs. Clinical sings include pain, decreased activity and lameness. Radiograph has been the gold standard to assess and quantify the joint changes associated but, with the development of genomic techniques, there is now the possibility to try to understand the genetic basis for CHD. One of the most popular and ancient Portuguese native breeds of shepherd dogs is the “Cão da Serra da Estrela” (CSE) (Estrela Mountain Dog). This is a large, mastiff-type molossoid dog, with high prevalence of CHD. A large database of radiographic information for CHD in CSE animals already existed, thus further justifying the development of this genetic study to try to understand which regions of the genome are associated with this condition. A review was published to describe and discuss the different diagnostic approaches concerning this condition, with special attention given to radiographic and molecular methods. A retrospective radiographic study on 437 dogs of several breeds (33 of CSE breed) was completed to determine the ability of the Norberg angle at ≥105° to predict a nondysplastic hip based on a distraction index cut-off of ≤0.3 or a dorsolateral subluxation score cut-off of ≥55%. It was possible to establish that at the commonly used cutpoint of 105°, the Norberg angle is not an accurate measurement of normal hip conformation. The specificity of a non-dysplastic diagnosis was maximized with a cut-off of 112º (when compared to the distract index) or 109º (dorsolateral subluxation score). A study on 60 CSE animals, and for comparison purposes of an additional 10 Portuguese stray dogs and 10 Iberian wolves, was conducted to investigate within-breed genetic diversity and population structure using a whole-genome SNP approach. Ychromosomal markers were also used to investigate phylogenetic relationships and withinbreed haplotype composition. These analyses are key for the subsequent investigation of the genetic basis for specific CHD traits, e.g. hip joint laxity. CSE has high genetic diversity with negligible inbreeding. Weak genetic sub-structure was observed within CSE possibly explained by lineage sorting associated with different breeders in each geographic location where the samples were collected, i.e. the northern, central and southern regions of Portugal. All CSE animals shared the same Y-haplotype which belongs to the most prevalent H1- haplogroup found in European dogs. The main purpose of the diagnosis and breeding schemes is to identify the individuals carrying hip dysplasia information in order to remove them from the breeding pool. This allows to eliminate carriers, to avoid the genetic inheritance associated with this condition and reduce its prevalence in the next generations. This study sets the basis for the future development of more comprehensive genomic studies to try to understand the genetic basis for CHD traits in this breed.
Canine hip dysplasia (CHD) is characterized by an abnormal hip and coxofemoral joint development with both hips usually affected, and is a common disorder that affects mainly large dog breeds. Hip joint laxity is the major risk factor leading to subluxation and poor congruence between the femoral head and acetabulum. Over time, degeneration of the joint occurs. Clinical sings include pain, decreased activity and lameness. Radiograph has been the gold standard to assess and quantify the joint changes associated but, with the development of genomic techniques, there is now the possibility to try to understand the genetic basis for CHD. One of the most popular and ancient Portuguese native breeds of shepherd dogs is the “Cão da Serra da Estrela” (CSE) (Estrela Mountain Dog). This is a large, mastiff-type molossoid dog, with high prevalence of CHD. A large database of radiographic information for CHD in CSE animals already existed, thus further justifying the development of this genetic study to try to understand which regions of the genome are associated with this condition. A review was published to describe and discuss the different diagnostic approaches concerning this condition, with special attention given to radiographic and molecular methods. A retrospective radiographic study on 437 dogs of several breeds (33 of CSE breed) was completed to determine the ability of the Norberg angle at ≥105° to predict a nondysplastic hip based on a distraction index cut-off of ≤0.3 or a dorsolateral subluxation score cut-off of ≥55%. It was possible to establish that at the commonly used cutpoint of 105°, the Norberg angle is not an accurate measurement of normal hip conformation. The specificity of a non-dysplastic diagnosis was maximized with a cut-off of 112º (when compared to the distract index) or 109º (dorsolateral subluxation score). A study on 60 CSE animals, and for comparison purposes of an additional 10 Portuguese stray dogs and 10 Iberian wolves, was conducted to investigate within-breed genetic diversity and population structure using a whole-genome SNP approach. Ychromosomal markers were also used to investigate phylogenetic relationships and withinbreed haplotype composition. These analyses are key for the subsequent investigation of the genetic basis for specific CHD traits, e.g. hip joint laxity. CSE has high genetic diversity with negligible inbreeding. Weak genetic sub-structure was observed within CSE possibly explained by lineage sorting associated with different breeders in each geographic location where the samples were collected, i.e. the northern, central and southern regions of Portugal. All CSE animals shared the same Y-haplotype which belongs to the most prevalent H1- haplogroup found in European dogs. The main purpose of the diagnosis and breeding schemes is to identify the individuals carrying hip dysplasia information in order to remove them from the breeding pool. This allows to eliminate carriers, to avoid the genetic inheritance associated with this condition and reduce its prevalence in the next generations. This study sets the basis for the future development of more comprehensive genomic studies to try to understand the genetic basis for CHD traits in this breed.
Descrição
Dissertação de Mestrado Integrado em Medicina Veterinária
Palavras-chave
Cão Serra da Estrela , Displasia da anca , Polimorfismo de nucleotídeo único , Radiologia veterinária