A genome-wide association study identifies novel candidate genes for susceptibility to diabetes mellitus in non-obese cats.
Animals
Case-Control Studies
Cat Diseases
/ genetics
Cats
Chromosome Mapping
Diabetes Mellitus
/ genetics
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
/ genetics
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
/ veterinary
Male
Membrane Proteins
/ genetics
Polymorphism, Single Nucleotide
Protein Tyrosine Phosphatases
/ genetics
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
28
04
2021
accepted:
01
11
2021
entrez:
7
12
2021
pubmed:
8
12
2021
medline:
7
1
2022
Statut:
epublish
Résumé
Diabetes mellitus (DM) is a common feline endocrinopathy, which is similar to human type 2 diabetes (T2DM) in terms of its pathophysiology. T2DM occurs due to peripheral insulin resistance and/or β-cell dysfunction. Several studies have identified genetic and environmental factors that contribute to susceptibility to human T2DM. In cats, environmental factors such as obesity and physical inactivity have been linked with DM, although to date, the only genetic association that has been demonstrated is with a polymorphism in the feline MC4R gene. The aim of this study was to perform a genome-wide association study (GWAS) to identify polymorphisms associated with feline DM. Illumina Infinium 63k iSelect DNA arrays were used to analyse genomic DNA samples from 200 diabetic domestic shorthair cats and 399 non-diabetic control cats. Data was analysed using PLINK whole genome data analysis toolset. A linear model analysis, EMMAX, was done to test for population structure and HAPLOVIEW was used to identify haplotype blocks surrounding the significant SNPs to assist with candidate gene nomination. A total of 47,497 SNPs were available for analysis. Four SNPs were identified with genome-wide significance: chrA2.4150731 (praw = 9.94 x10-8); chrUn17.115508 (praw = 6.51 x10-8); chrUn17.394136 (praw = 2.53 x10-8); chrUn17.314128 (praw = 2.53 x10-8) as being associated with DM. The first SNP is located within chromosome A2, less than 4kb upstream of the dipeptidyl-peptidase-9 (DPP9) gene, a peptidase involved in incretin inactivation. The remaining three SNPs are located within a haplotype block towards the end of chromosome A3; within this region, genes of interest include TMEM18 and ACP1, both previously associated with T2DM. This study indicates a polygenic component to susceptibility to DM in cats and has highlighted several loci and candidate genes worthy of further investigation.
Identifiants
pubmed: 34874954
doi: 10.1371/journal.pone.0259939
pii: PONE-D-21-14116
pmc: PMC8651108
doi:
Substances chimiques
Membrane Proteins
0
Protein Tyrosine Phosphatases
EC 3.1.3.48
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
EC 3.4.14.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0259939Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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