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Association of Common Genetic Variants in the CPSF7 and SDHAF2 Genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier
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)...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349241/ https://www.ncbi.nlm.nih.gov/pubmed/32486318 http://dx.doi.org/10.3390/genes11060609 |
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author | Piras, Ignazio S. Bleul, Christiane Siniard, Ashley Wolfe, Amanda J. De Both, Matthew D. Hernandez, Alvaro G. Huentelman, Matthew J. |
author_facet | Piras, Ignazio S. Bleul, Christiane Siniard, Ashley Wolfe, Amanda J. De Both, Matthew D. Hernandez, Alvaro G. Huentelman, Matthew J. |
author_sort | Piras, Ignazio S. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7349241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73492412020-07-22 Association of Common Genetic Variants in the CPSF7 and SDHAF2 Genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier Piras, Ignazio S. Bleul, Christiane Siniard, Ashley Wolfe, Amanda J. De Both, Matthew D. Hernandez, Alvaro G. Huentelman, Matthew J. Genes (Basel) Article 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. MDPI 2020-05-30 /pmc/articles/PMC7349241/ /pubmed/32486318 http://dx.doi.org/10.3390/genes11060609 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Piras, Ignazio S. Bleul, Christiane Siniard, Ashley Wolfe, Amanda J. De Both, Matthew D. Hernandez, Alvaro G. Huentelman, Matthew J. Association of Common Genetic Variants in the CPSF7 and SDHAF2 Genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier |
title | Association of Common Genetic Variants in the CPSF7 and SDHAF2 Genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier |
title_full | Association of Common Genetic Variants in the CPSF7 and SDHAF2 Genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier |
title_fullStr | Association of Common Genetic Variants in the CPSF7 and SDHAF2 Genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier |
title_full_unstemmed | Association of Common Genetic Variants in the CPSF7 and SDHAF2 Genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier |
title_short | Association of Common Genetic Variants in the CPSF7 and SDHAF2 Genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier |
title_sort | association of common genetic variants in the cpsf7 and sdhaf2 genes with canine idiopathic pulmonary fibrosis in the west highland white terrier |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349241/ https://www.ncbi.nlm.nih.gov/pubmed/32486318 http://dx.doi.org/10.3390/genes11060609 |
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