Analysis of copy number variation in dogs implicates genomic structural variation in the development of anterior cruciate ligament rupture
Anterior cruciate ligament (ACL) rupture is an important condition of the human knee. Second ruptures are common and societal costs are substantial. Canine cranial cruciate ligament (CCL) rupture closely models the human disease. CCL rupture is common in the Labrador Retriever (5.79% prevalence), ~1...
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ftzenodo:oai:zenodo.org:4341965 2024-09-15T18:01:29+00:00 Analysis of copy number variation in dogs implicates genomic structural variation in the development of anterior cruciate ligament rupture Binversie, Emily Baker, Lauren Engelman, Corinne Hao, Zhengling Moran, John Piazza, Alexander Sample, Susannah Muir, Peter 2020-12-17 https://doi.org/10.5061/dryad.jdfn2z39b unknown Zenodo https://support.illumina.com/array/array_software/genomestudio/downloads.html https://support.illumina.com/content/dam/illumina-support/documents/documentation/software_documentation/genomestudio/genomestudio-2011-1/genomestudio-gt-module-v1-0-user-guide-11319113-a.pdf https://support.illumina.com/array/array_kits/caninehd_whole-genome_genotyping_kit/downloads.html https://www.illumina.com/content/dam/illumina-marketing/documents/products/technotes/custom-cluster-file-cnv-tech-note-770-2017-017.pdf https://www.youtube.com/embed/4JTrbMUbVN0?autoplay=1&rel=0 https://zenodo.org/communities/dryad https://doi.org/10.5061/dryad.jdfn2z39b oai:zenodo.org:4341965 info:eu-repo/semantics/openAccess Creative Commons Zero v1.0 Universal https://creativecommons.org/publicdomain/zero/1.0/legalcode ACL copy number variation (CNV) CNV CanineHD BeadChip Canis lupus familiaris Labrador Retriever complex disease Knee Structural variation homeobox transcription factors info:eu-repo/semantics/other 2020 ftzenodo https://doi.org/10.5061/dryad.jdfn2z39b 2024-07-26T14:48:45Z Anterior cruciate ligament (ACL) rupture is an important condition of the human knee. Second ruptures are common and societal costs are substantial. Canine cranial cruciate ligament (CCL) rupture closely models the human disease. CCL rupture is common in the Labrador Retriever (5.79% prevalence), ~100-fold more prevalent than in humans. Labrador Retriever CCL rupture is a polygenic complex disease, based on genome-wide association study (GWAS) of single nucleotide polymorphism (SNP) markers. Dissection of genetic variation in complex traits can be enhanced by studying structural variation, including copy number variants (CNVs). Dogs are an ideal model for CNV research because of reduced genetic variability within breeds and extensive phenotypic diversity across breeds. We studied the genetic etiology of CCL rupture by association analysis of CNV regions (CNVRs) using 110 case and 164 control Labrador Retrievers. CNVs were called from SNPs using three different programs (PennCNV, CNVPartition, and QuantiSNP). After quality control, CNV calls were combined to create CNVRs using ParseCNV and an association analysis was performed. We found no strong effect CNVRs but found 46 small effect (max(T) permutation P<0.05) CCL rupture associated CNVRs in 22 autosomes; 25 were deletions and 21 were duplications. Of the 46 CCL rupture associated CNVRs, we identified 39 unique regions. Thirty four were identified by a single calling algorithm, 3 were identified by two calling algorithms, and 2 were identified by all three algorithms. For 42 of the associated CNVRs, frequency in the population was <10% while 4 occurred at a frequency in the population ranging from 10-25%. Average CNVR length was 198,872bp and CNVRs covered 0.11 to 0.15% of the genome. All CNVRs were associated with case status. CNVRs did not overlap previous canine CCL rupture risk loci identified by GWAS. Associated CNVRs contained 152 annotated genes; 12 CNVRs did not have genes mapped to CanFam3.1. Using pathway analysis, a cluster of 19 homeobox ... Other/Unknown Material Canis lupus Zenodo |
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ACL copy number variation (CNV) CNV CanineHD BeadChip Canis lupus familiaris Labrador Retriever complex disease Knee Structural variation homeobox transcription factors |
spellingShingle |
ACL copy number variation (CNV) CNV CanineHD BeadChip Canis lupus familiaris Labrador Retriever complex disease Knee Structural variation homeobox transcription factors Binversie, Emily Baker, Lauren Engelman, Corinne Hao, Zhengling Moran, John Piazza, Alexander Sample, Susannah Muir, Peter Analysis of copy number variation in dogs implicates genomic structural variation in the development of anterior cruciate ligament rupture |
topic_facet |
ACL copy number variation (CNV) CNV CanineHD BeadChip Canis lupus familiaris Labrador Retriever complex disease Knee Structural variation homeobox transcription factors |
description |
Anterior cruciate ligament (ACL) rupture is an important condition of the human knee. Second ruptures are common and societal costs are substantial. Canine cranial cruciate ligament (CCL) rupture closely models the human disease. CCL rupture is common in the Labrador Retriever (5.79% prevalence), ~100-fold more prevalent than in humans. Labrador Retriever CCL rupture is a polygenic complex disease, based on genome-wide association study (GWAS) of single nucleotide polymorphism (SNP) markers. Dissection of genetic variation in complex traits can be enhanced by studying structural variation, including copy number variants (CNVs). Dogs are an ideal model for CNV research because of reduced genetic variability within breeds and extensive phenotypic diversity across breeds. We studied the genetic etiology of CCL rupture by association analysis of CNV regions (CNVRs) using 110 case and 164 control Labrador Retrievers. CNVs were called from SNPs using three different programs (PennCNV, CNVPartition, and QuantiSNP). After quality control, CNV calls were combined to create CNVRs using ParseCNV and an association analysis was performed. We found no strong effect CNVRs but found 46 small effect (max(T) permutation P<0.05) CCL rupture associated CNVRs in 22 autosomes; 25 were deletions and 21 were duplications. Of the 46 CCL rupture associated CNVRs, we identified 39 unique regions. Thirty four were identified by a single calling algorithm, 3 were identified by two calling algorithms, and 2 were identified by all three algorithms. For 42 of the associated CNVRs, frequency in the population was <10% while 4 occurred at a frequency in the population ranging from 10-25%. Average CNVR length was 198,872bp and CNVRs covered 0.11 to 0.15% of the genome. All CNVRs were associated with case status. CNVRs did not overlap previous canine CCL rupture risk loci identified by GWAS. Associated CNVRs contained 152 annotated genes; 12 CNVRs did not have genes mapped to CanFam3.1. Using pathway analysis, a cluster of 19 homeobox ... |
format |
Other/Unknown Material |
author |
Binversie, Emily Baker, Lauren Engelman, Corinne Hao, Zhengling Moran, John Piazza, Alexander Sample, Susannah Muir, Peter |
author_facet |
Binversie, Emily Baker, Lauren Engelman, Corinne Hao, Zhengling Moran, John Piazza, Alexander Sample, Susannah Muir, Peter |
author_sort |
Binversie, Emily |
title |
Analysis of copy number variation in dogs implicates genomic structural variation in the development of anterior cruciate ligament rupture |
title_short |
Analysis of copy number variation in dogs implicates genomic structural variation in the development of anterior cruciate ligament rupture |
title_full |
Analysis of copy number variation in dogs implicates genomic structural variation in the development of anterior cruciate ligament rupture |
title_fullStr |
Analysis of copy number variation in dogs implicates genomic structural variation in the development of anterior cruciate ligament rupture |
title_full_unstemmed |
Analysis of copy number variation in dogs implicates genomic structural variation in the development of anterior cruciate ligament rupture |
title_sort |
analysis of copy number variation in dogs implicates genomic structural variation in the development of anterior cruciate ligament rupture |
publisher |
Zenodo |
publishDate |
2020 |
url |
https://doi.org/10.5061/dryad.jdfn2z39b |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_relation |
https://support.illumina.com/array/array_software/genomestudio/downloads.html https://support.illumina.com/content/dam/illumina-support/documents/documentation/software_documentation/genomestudio/genomestudio-2011-1/genomestudio-gt-module-v1-0-user-guide-11319113-a.pdf https://support.illumina.com/array/array_kits/caninehd_whole-genome_genotyping_kit/downloads.html https://www.illumina.com/content/dam/illumina-marketing/documents/products/technotes/custom-cluster-file-cnv-tech-note-770-2017-017.pdf https://www.youtube.com/embed/4JTrbMUbVN0?autoplay=1&rel=0 https://zenodo.org/communities/dryad https://doi.org/10.5061/dryad.jdfn2z39b oai:zenodo.org:4341965 |
op_rights |
info:eu-repo/semantics/openAccess Creative Commons Zero v1.0 Universal https://creativecommons.org/publicdomain/zero/1.0/legalcode |
op_doi |
https://doi.org/10.5061/dryad.jdfn2z39b |
_version_ |
1810438626710913024 |