Genome Wide Discovery of DNA Structural Variation in Dogs for Human Comparative Disease Genetics

2.50
Hdl Handle:
http://hdl.handle.net/10755/160993
Type:
Presentation
Title:
Genome Wide Discovery of DNA Structural Variation in Dogs for Human Comparative Disease Genetics
Abstract:
Genome Wide Discovery of DNA Structural Variation in Dogs for Human Comparative Disease Genetics
Conference Sponsor:Midwest Nursing Research Society
Conference Year:2010
Author:Rowell, Jennie, MS, RN
P.I. Institution Name:The Ohio State University
Contact Address:249 W. 10th Ave, Neil 467, Columbus, OH, 43201, USA
Contact Telephone:937-532-6822
Co-Authors:J.L. Rowell, College of Nursing, The Ohio State University, Columbus, OH; J.L. Rowell, W. Chen, J. Swartz, W. Ray, C. Alvarez, Center for Human and Molecular Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, OH; L. Rush, Depart
Purpose: DNA segments that are 1kb or larger and present at a variable copy number (gain or loss) in comparison with a reference group are known as DNA copy-number variation (CNV). Many CNV's span genes and likely affect genetic networks, suggesting significant effects on phenotypes. In the last 150 years, hundreds of pure dog breeds were created by selection of mostly morphological and behavioral traits. Those extreme population bottlenecks generated a powerful resource for studying CNV genetics. Furthermore, dogs are an excellent model to study many human diseases, as they share 650 Mb of additional genetic material with humans beyond that of the mouse. Many genes identified in dogs have a homolog in humans, making them an ideal model study CNV and disease for comparative genomics. We are conducting studies to identify biologically relevant genetic variation that predisposes specific breeds to certain diseases. Methods: Our lab conducted CNV discovery in a small panel of normal pure bred dogs that represent the four classes of breeds. We quantified CNV by Comparative Genome Hybridization on a high resolution whole genome microarray (isothermal long-oligonucleotides at <5 kb mean spacing; Nimblegen). Selected regions were validated by other hybridization and PCR-based methods. Results: In total, we identified 204 variants at high confidence. The CNV regions generally affect multiple genes, as in humans and mice. We identified several CNV's in biologically significant genes. A putative tumor suppressor gene, CSMD1, was found to have a microduplication within CSMD1 in 14 of 22 Rottweilers (64%), but not in any of 29 non-Rottweilers. Rottweiler-specific breeds are known to have predisposition to cancer and in humans, deletion and reduced expression of this CSMD1 have been associated with poor clinical outcomes in patients with certain cancers. Further screening is necessary to confirm whether it contributes to the development of cancer in this breed. Conclusion: Dogs represent a unique model for studying human relevant diseases. We suspect that CNV contributes the increased prevalence of cancer among some dog breeds and are currently mapping CNV in normal dogs with future directions to specifically isolate CNV's that contribute to cancer in dogs.
Repository Posting Date:
26-Oct-2011
Date of Publication:
17-Oct-2011
Sponsors:
Midwest Nursing Research Society

Full metadata record

DC FieldValue Language
dc.typePresentationen_GB
dc.titleGenome Wide Discovery of DNA Structural Variation in Dogs for Human Comparative Disease Geneticsen_GB
dc.identifier.urihttp://hdl.handle.net/10755/160993-
dc.description.abstract<table><tr><td colspan="2" class="item-title">Genome Wide Discovery of DNA Structural Variation in Dogs for Human Comparative Disease Genetics</td></tr><tr class="item-sponsor"><td class="label">Conference Sponsor:</td><td class="value">Midwest Nursing Research Society</td></tr><tr class="item-year"><td class="label">Conference Year:</td><td class="value">2010</td></tr><tr class="item-author"><td class="label">Author:</td><td class="value">Rowell, Jennie, MS, RN</td></tr><tr class="item-institute"><td class="label">P.I. Institution Name:</td><td class="value">The Ohio State University</td></tr><tr class="item-address"><td class="label">Contact Address:</td><td class="value">249 W. 10th Ave, Neil 467, Columbus, OH, 43201, USA</td></tr><tr class="item-phone"><td class="label">Contact Telephone:</td><td class="value">937-532-6822</td></tr><tr class="item-email"><td class="label">Email:</td><td class="value">rowell.14@buckeyemail.osu.edu</td></tr><tr class="item-co-authors"><td class="label">Co-Authors:</td><td class="value">J.L. Rowell, College of Nursing, The Ohio State University, Columbus, OH; J.L. Rowell, W. Chen, J. Swartz, W. Ray, C. Alvarez, Center for Human and Molecular Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, OH; L. Rush, Depart</td></tr><tr><td colspan="2" class="item-abstract">Purpose: DNA segments that are 1kb or larger and present at a variable copy number (gain or loss) in comparison with a reference group are known as DNA copy-number variation (CNV). Many CNV's span genes and likely affect genetic networks, suggesting significant effects on phenotypes. In the last 150 years, hundreds of pure dog breeds were created by selection of mostly morphological and behavioral traits. Those extreme population bottlenecks generated a powerful resource for studying CNV genetics. Furthermore, dogs are an excellent model to study many human diseases, as they share 650 Mb of additional genetic material with humans beyond that of the mouse. Many genes identified in dogs have a homolog in humans, making them an ideal model study CNV and disease for comparative genomics. We are conducting studies to identify biologically relevant genetic variation that predisposes specific breeds to certain diseases. Methods: Our lab conducted CNV discovery in a small panel of normal pure bred dogs that represent the four classes of breeds. We quantified CNV by Comparative Genome Hybridization on a high resolution whole genome microarray (isothermal long-oligonucleotides at &lt;5 kb mean spacing; Nimblegen). Selected regions were validated by other hybridization and PCR-based methods. Results: In total, we identified 204 variants at high confidence. The CNV regions generally affect multiple genes, as in humans and mice. We identified several CNV's in biologically significant genes. A putative tumor suppressor gene, CSMD1, was found to have a microduplication within CSMD1 in 14 of 22 Rottweilers (64%), but not in any of 29 non-Rottweilers. Rottweiler-specific breeds are known to have predisposition to cancer and in humans, deletion and reduced expression of this CSMD1 have been associated with poor clinical outcomes in patients with certain cancers. Further screening is necessary to confirm whether it contributes to the development of cancer in this breed. Conclusion: Dogs represent a unique model for studying human relevant diseases. We suspect that CNV contributes the increased prevalence of cancer among some dog breeds and are currently mapping CNV in normal dogs with future directions to specifically isolate CNV's that contribute to cancer in dogs.</td></tr></table>en_GB
dc.date.available2011-10-26T23:14:09Z-
dc.date.issued2011-10-17en_GB
dc.date.accessioned2011-10-26T23:14:09Z-
dc.description.sponsorshipMidwest Nursing Research Societyen_GB
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