FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs.
Proc Natl Acad Sci U S A
; 114(43): 11476-11481, 2017 10 24.
Article
em En
| MEDLINE
| ID: mdl-29073074
ABSTRACT
Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed (PBonferroni = 0.01) and intervertebral disc disease (IVDD) across breeds (PBonferroni = 4.0 × 10-10) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed FGF4 retrogene within this shared region. The FGF4 retrogene segregated with limb length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species. FGF signaling abnormalities have been associated with skeletal dysplasia in humans, and our findings present opportunities for both selective elimination of a medically and financially devastating disease in dogs and further understanding of the ever-growing complexity of retrogene biology.
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MEDLINE
Assunto principal:
Osteocondrodisplasias
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Doenças do Cão
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Fator 4 de Crescimento de Fibroblastos
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Degeneração do Disco Intervertebral
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Deslocamento do Disco Intervertebral
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article