Article

Identification of copy number variants in horses.

Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
Genome Research (impact factor: 13.61). 03/2012; 22(5):899-907. DOI:10.1101/gr.128991.111
Source: PubMed

ABSTRACT Copy number variants (CNVs) represent a substantial source of genetic variation in mammals. However, the occurrence of CNVs in horses and their subsequent impact on phenotypic variation is unknown. We performed a study to identify CNVs in 16 horses representing 15 distinct breeds (Equus caballus) and an individual gray donkey (Equus asinus) using a whole-exome tiling array and the array comparative genomic hybridization methodology. We identified 2368 CNVs ranging in size from 197 bp to 3.5 Mb. Merging identical CNVs from each animal yielded 775 CNV regions (CNVRs), involving 1707 protein- and RNA-coding genes. The number of CNVs per animal ranged from 55 to 347, with median and mean sizes of CNVs of 5.3 kb and 99.4 kb, respectively. Approximately 6% of the genes investigated were affected by a CNV. Biological process enrichment analysis indicated CNVs primarily affected genes involved in sensory perception, signal transduction, and metabolism. CNVs also were identified in genes regulating blood group antigens, coat color, fecundity, lactation, keratin formation, neuronal homeostasis, and height in other species. Collectively, these data are the first report of copy number variation in horses and suggest that CNVs are common in the horse genome and may modulate biological processes underlying different traits observed among horses and horse breeds.

0 0
 · 
0 Bookmarks
 · 
51 Views
  • Source
    Article: Genome Sequence, Comparative Analysis, and Population Genetics of the Domestic Horse
    C. M. Wade, E. Giulotto, S. Sigurdsson, M. Zoli, S. Gnerre, F. Imsland, T. L. Lear, D. L. Adelson, E. Bailey, R. R. Bellone, [......], L. Skow, J. E. Swinburne, A. C. Syvänen, T. Tozaki, S. J. Valberg, M. Vaudin, J. R. White, M. C. Zody, E. S. Lander, K. Lindblad-Toh
    [show abstract] [hide abstract]
    ABSTRACT: We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.
    Science 11/2009; 326(5954):865-867. · 31.20 Impact Factor
  • Article: Detection of clinically relevant exonic copy-number changes by array CGH.
    Philip M Boone, Carlos A Bacino, Chad A Shaw, Patricia A Eng, Patricia M Hixson, Amber N Pursley, Sung-Hae L Kang, Yaping Yang, Joanna Wiszniewska, Beata A Nowakowska, [......], Katarzyna Derwinska, Barbara Wisniowiecka-Kowalnik, Seema R Lalani, Frank J Probst, Weimin Bi, Arthur L Beaudet, Ankita Patel, James R Lupski, Sau Wai Cheung, Pawel Stankiewicz
    [show abstract] [hide abstract]
    ABSTRACT: Array comparative genomic hybridization (aCGH) is a powerful tool for the molecular elucidation and diagnosis of disorders resulting from genomic copy-number variation (CNV). However, intragenic deletions or duplications--those including genomic intervals of a size smaller than a gene--have remained beyond the detection limit of most clinical aCGH analyses. Increasing array probe number improves genomic resolution, although higher cost may limit implementation, and enhanced detection of benign CNV can confound clinical interpretation. We designed an array with exonic coverage of selected disease and candidate genes and used it clinically to identify losses or gains throughout the genome involving at least one exon and as small as several hundred base pairs in size. In some patients, the detected copy-number change occurs within a gene known to be causative of the observed clinical phenotype, demonstrating the ability of this array to detect clinically relevant CNVs with subkilobase resolution. In summary, we demonstrate the utility of a custom-designed, exon-targeted oligonucleotide array to detect intragenic copy-number changes in patients with various clinical phenotypes.
    Human Mutation 12/2010; 31(12):1326-42. · 5.69 Impact Factor
  • Article: Mapping DNA structural variation in dogs.
    Wei-Kang Chen, Joshua D Swartz, Laura J Rush, Carlos E Alvarez
    [show abstract] [hide abstract]
    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.
    Genome Research 12/2008; 19(3):500-9. · 13.61 Impact Factor

Show more

Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

15 distinct breeds
 
16 horses
 
array comparative genomic hybridization methodology
 
Biological process enrichment analysis
 
CNVs
 
Copy number variants
 
Equus asinus
 
genes regulating blood group antigens
 
genetic variation
 
horse breeds
 
individual gray donkey
 
keratin formation
 
mammals
 
Merging identical CNVs
 
neuronal homeostasis
 
phenotypic variation
 
sensory perception
 
sizes
 
subsequent impact
 
whole-exome tiling array