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A large deletion on CFA28 omitting ACSL5 gene is associated with intestinal lipid malabsorption in the Australian Kelpie dog breed.
- Source :
-
Scientific reports [Sci Rep] 2020 Oct 26; Vol. 10 (1), pp. 18223. Date of Electronic Publication: 2020 Oct 26. - Publication Year :
- 2020
-
Abstract
- Inborn errors of metabolism are genetic conditions that can disrupt intermediary metabolic pathways and cause defective absorption and metabolism of dietary nutrients. In an Australian Kelpie breeding population, 17 puppies presented with intestinal lipid malabsorption. Juvenile dogs exhibited stunted postnatal growth, steatorrhea, abdominal distension and a wiry coat. Using genome-wide association analysis, an associated locus on CFA28 (P <subscript>raw</subscript> = 2.87E <superscript>-06</superscript> ) was discovered and validated in a closely related population (P <subscript>raw</subscript> = 1.75E <superscript>-45</superscript> ). A 103.3 kb deletion NC&#95;006610.3CFA28:g.23380074&#95;23483377del, containing genes Acyl-CoA Synthetase Long Chain Family Member 5 (ACSL5) and Zinc Finger DHHC-Type Containing 6 (ZDHHC6), was characterised using whole transcriptomic data. Whole transcriptomic sequencing revealed no expression of ACSL5 and disrupted splicing of ZDHHC6 in jejunal tissue of affected Kelpies. The ACSL5 gene plays a key role in long chain fatty acid absorption, a phenotype similar to that of our affected Kelpies has been observed in a knockout mouse model. A PCR-based diagnostic test was developed and confirmed fully penetrant autosomal recessive mode of inheritance. We conclude the structural variant causing a deletion of the ACSL5 gene is the most likely cause for intestinal lipid malabsorption in the Australian Kelpie.
- Subjects :
- Animals
Coenzyme A Ligases metabolism
Dog Diseases metabolism
Dog Diseases pathology
Dogs
Female
Gene Deletion
Intestine, Small metabolism
Malabsorption Syndromes genetics
Malabsorption Syndromes metabolism
Malabsorption Syndromes pathology
Male
Metabolism, Inborn Errors genetics
Metabolism, Inborn Errors metabolism
Metabolism, Inborn Errors pathology
Pedigree
Phenotype
Coenzyme A Ligases genetics
Dog Diseases genetics
Genome-Wide Association Study methods
Intestine, Small pathology
Lipid Metabolism genetics
Malabsorption Syndromes veterinary
Metabolism, Inborn Errors veterinary
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33106515
- Full Text :
- https://doi.org/10.1038/s41598-020-75243-x