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Mapping DNA structural variation in dogs

ABSTRACT: DNA structural variation (SV) comprises a major portion of genetic diversity, but its biological impact is unclear. We propose that the genetic history and extraordinary phenotypic variation of dogs make them an ideal mammal in which to study the effects of SV on biology and disease. The hundreds of existing dog breeds were created by selection of extreme morphological and behavioral traits. And along with those traits, each breed carries increased risk for different diseases. We used array CGH to create the first map of DNA copy number variation (CNV) or SV in dogs. The extent of this variation, and some of the gene classes affected, are similar to those of mice and humans. Most canine CNVs affect genes, including disease and candidate disease genes, and are thus likely to be functional. We identified many CNVs that may be breed or breed class specific. Cluster analysis of CNV regions showed that dog breeds tend to group according to breed classes. Our combined findings suggest many CNVs are (1) in linkage disequilibrium with flanking sequence, and (2) associated with breed specific traits. We discuss how a catalog of structural variation in dogs will accelerate the identification of the genetic basis of canine traits and diseases, beginning with the use of whole genome association and candidate CNV/gene approaches. Chen WK, Swartz JD, Rush LJ, Alvarez, CE. Mapping DNA structural variation in dogs. Genome Res. 2009. 19: 500 509 PMID: 19015322 Array comparitive genomic hybridization analysis of structural variation in 9 dogs, and 1 lymphoma cell line.

ORGANISM(S): Canis lupus familiaris

SUBMITTER: Joshua Swartz

PROVIDER: E-GEOD-18317 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Mapping DNA structural variation in dogs.

Chen Wei-Kang WK Swartz Joshua D JD Rush Laura J LJ Alvarez Carlos E CE

Genome research 20081117 3

DNA structural variation (SV) comprises a major portion of genetic diversity, but its biological impact is unclear. We propose that the genetic history and extraordinary phenotypic variation of dogs make them an ideal mammal in which to study the effects of SV on biology and disease. The hundreds of existing dog breeds were created by selection of extreme morphological and behavioral traits. And along with those traits, each breed carries increased risk for different diseases. We used array CGH ...[more]

PMID: 19015322

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Project description:Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in modern domesticated cattle using array comparative genomic hybridization (array CGH), quantitative PCR (qPCR) and fluorescent in situ hybridization (FISH). The array CGH panel included 90 animals from 11 Bos taurus, 3 Bos indicus and 3 composite breeds for beef, dairy or dual purpose. We identified over 200 candidate CNV regions (CNVRs) in total and 177 within known chromosomes, which harbor or are adjacent to gains or losses. These 177 high-confidence CNVRs cover 28.1 mega bases or ~1.07% of the genome. Over 50% of the CNVRs (89/177) were found in multiple animals or breeds and analysis revealed breed-specific frequency differences and reflected aspects of the known ancestry of these cattle breeds. Selected CNVs were further validated by independent methods using qPCR and FISH. Approximately 67% of the CNVRs (119/177) completely or partially span cattle genes and 61% of the CNVRs (108/177) directly overlap with segmental duplications. The CNVRs span about 400 annotated cattle genes that are significantly enriched for specific biological functions such as immunity, lactation, reproduction and rumination. Multiple gene families, including ULBP, have gone through ruminant lineage-specific gene amplification. We detected and confirmed marked differences in their CNV frequencies across diverse breeds, indicating that some cattle CNVs are likely to arise independently in breeds and contribute to breed differences. Our results provide a valuable resource beyond microsatellites and single nucleotide polymorphisms to explore the full dimension of genetic variability for future cattle genomic research. The custom aCGH chips that interrogated the whole genome CNVs were build for 90 cattles from diverse breeds, with Hereford L1 Dominette 01449 as refference sample.

Dataset Information

Mapping DNA structural variation in dogs

Publications

Mapping DNA structural variation in dogs.

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