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Genes
Volume 11
Issue 6
10.3390/genes11060609
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Article

Association of Common Genetic Variants in the CPSF7 and SDHAF2 Genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier

by
Ignazio S. Piras
1,
Christiane Bleul
1,
Ashley Siniard
1,
Amanda J. Wolfe
1,
Matthew D. De Both
1,
Alvaro G. Hernandez
2 and
Matthew J. Huentelman
1,*
1
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
2
Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
*
Author to whom correspondence should be addressed.
Genes 2020, 11(6), 609; https://doi.org/10.3390/genes11060609
Received: 7 April 2020 / Revised: 24 April 2020 / Accepted: 29 May 2020 / Published: 30 May 2020
(This article belongs to the Section Animal Genetics and Genomics)
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Abstract

Canine idiopathic pulmonary fibrosis (CIPF) is a chronic fibrotic lung disease that is observed at a higher frequency in the West Highland White Terrier dog breed (WHWT) and may have molecular pathological overlap with human lung fibrotic disease. We conducted a genome-wide association study (GWAS) in the WHWT using whole genome sequencing (WGS) to discover genetic variants associated with CIPF. Saliva-derived DNA samples were sequenced using the Riptide DNA library prep kit. After quality controls, 28 affected, 44 unaffected, and 1,843,695 informative single nucleotide polymorphisms (SNPs) were included in the GWAS. Data were analyzed both at the single SNP and gene levels using the GEMMA and GATES methods, respectively. We detected significant signals at the gene level in both the cleavage and polyadenylation specific factor 7 (CPSF7) and succinate dehydrogenase complex assembly factor 2 (SDHAF2) genes (adjusted p = 0.016 and 0.024, respectively), two overlapping genes located on chromosome 18. The top SNP for both genes was rs22669389; however, it did not reach genome-wide significance in the GWAS (adjusted p = 0.078). Our studies provide, for the first time, candidate loci for CIPF in the WHWT. CPSF7 was recently associated with lung adenocarcinoma, further highlighting the potential relevance of our results because IPF and lung cancer share several pathological mechanisms. View Full-Text
Keywords: animal genetics; pulmonary fibrosis; genomics animal genetics; pulmonary fibrosis; genomics
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MDPI and ACS Style

Piras, I.S.; Bleul, C.; Siniard, A.; Wolfe, A.J.; De Both, M.D.; Hernandez, A.G.; Huentelman, M.J. Association of Common Genetic Variants in the CPSF7 and SDHAF2 Genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier. Genes 2020, 11, 609. https://doi.org/10.3390/genes11060609

AMA Style

Piras IS, Bleul C, Siniard A, Wolfe AJ, De Both MD, Hernandez AG, Huentelman MJ. Association of Common Genetic Variants in the CPSF7 and SDHAF2 Genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier. Genes. 2020; 11(6):609. https://doi.org/10.3390/genes11060609

Chicago/Turabian Style

Piras, Ignazio S., Christiane Bleul, Ashley Siniard, Amanda J. Wolfe, Matthew D. De Both, Alvaro G. Hernandez, and Matthew J. Huentelman. 2020. "Association of Common Genetic Variants in the CPSF7 and SDHAF2 Genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier" Genes 11, no. 6: 609. https://doi.org/10.3390/genes11060609

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