Copy number variation and susceptibility to human disorders (Review)
ABSTRACT A large number of analyses of a new form of genetic variation, known as copy number variation (CNV), have been published recently as a new tool for understanding the genetic basis of complex traits such as diabetes, asthma, Crohn's disease, autism and bipolar disorder. Through the use of different types of genome-wide scanning procedures, CNVs have been shown to be associated with several complex and common disorders, including nervous system disorders. One of the common features of the regions associated with the complex and common disorders identified thus far is the presence of CNVs and segmental duplications. Segmental duplications lead to genome instability. Because of their location and nature (several contain genes), many CNVs have functional consequences, such as gene dosage alteration, the disruption of genes and the modulation of the activities of other genes. Therefore, these genetic variations have an influence on phenotypes, the susceptibility of an individual to disease, drug response and human genome evolution. These types of variants (gain and loss of DNA) are not restricted to humans, having also been identified in other organisms. Our current knowledge regarding CNVs and their heritability is still rudimentary, due to their location in regions of complex genomic structure and to the technical limitations of association studies. Future advances in the technology will aid in the construction of a new CNV map, used to find the genes underlying common diseases and to understand familial genetic conditions, severe developmental defects in humans and other organisms, and genome evolution.
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ABSTRACT: Recent studies of mammalian genomes have uncovered the vast extent of copy number variations (CNVs) that contribute to phenotypic diversity. Compared to SNP, a CNV can cover a wider chromosome region, which may potentially incur substantial sequence changes and induce more significant effects on phenotypes. CNV has been becoming an alternative promising genetic marker in the field of genetic analyses. Here we firstly report an account of CNV regions in the cattle genome in Chinese Holstein population. The Illumina Bovine SNP50K Beadchips were used for screening 2047 Holstein individuals. Three different programes (PennCNV, cnvPartition and GADA) were implemented to detect potential CNVs. After a strict CNV calling pipeline, a total of 99 CNV regions were identified in cattle genome. These CNV regions cover 23.24 Mb in total with an average size of 151.69 Kb. 52 out of these CNV regions have frequencies of above 1%. 51 out of these CNV regions completely or partially overlap with 138 cattle genes, which are significantly enriched for specific biological functions, such as signaling pathway, sensory perception response and cellular processes. The results provide valuable information for constructing a more comprehensive CNV map in the cattle genome and offer an important resource for investigation of genome structure and genomic variation underlying traits of interest in cattle.PLoS ONE 11/2012; 7(11):e48732. DOI:10.1371/journal.pone.0048732 · 3.53 Impact Factor
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ABSTRACT: In recent years, copy number variations (CNVs), which associate with complex traits such as disease and quantitative phenotypes, are increasingly recognized as an important and abundant source of genetic variation and phenotypic diversity. CNVs have been studied in several breeds of cattle with the goal of improving selection methods for commercial use; however, little is known about the extent to which CNVs contribute to genetic variation in Qinchuan cattle. The BovineHD Genotyping BeadChip array was used for analyzing the whole genomic CNVs of Qinchuan cattle breed; we discovered 367 unique CNV events from 6 Qinchuan cattle. Accounting for overlapping regions, a total of 365 autosomal copy number variation regions (CNVRs) (131 losses and 234 gains) were identified with an average number of 60.8 CNV events per individual, which covered 13.13 Mb of the cattle genomic sequence corresponding to 0.4 % of the whole cattle genome. The average and median sizes of CNVRs were 35.07 and 18.56 kb, respectively. The CNVRs map of Qinchuan cattle was first constructed based on the BovineHD Genotyping Beadchip array. Functional analysis indicated that most genes in CNVRs that were significantly enriched are involved in environmental stress. Comparison of CNVRs in ten published studies and the 365 CNVRs identified in our study overlapped 0.7–42.7 %. These findings are the first report of CNVs mapping in Qinchuan cattle and contribute to the greater understanding of CNV genetics in commercial cattle phenotypes.MGG Molecular & General Genetics 09/2014; 290(1). DOI:10.1007/s00438-014-0923-4 · 2.83 Impact Factor
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ABSTRACT: Background Triplication is a rare chromosomal anomaly. We identified a de novo triplication of 11q12.3 in a patient with developmental delay, distinctive facial features, and others. In the present study, we discuss the mechanism of triplications that are not embedded within duplications and potential genes which may contribute to the phenotype. Results The identified triplication of 11q12.3 was 557 kb long and not embedded within the duplicated regions. The aberrant region was overlapped with the segment reported to be duplicated in 2 other patients. The common phenotypic features in the present patient and the previously reported patient were brain developmental delay, finger abnormalities (including arachnodactuly, camptodactyly, brachydactyly, clinodactyly, and broad thumbs), and preauricular pits. Conclusions Triplications that are not embedded within duplicated regions are rare and sometimes observed as the consequence of non-allelic homologous recombination. The de novo triplication identified in the present study is novel and not embedded within the duplicated region. In the 11q12.3 region, many copy number variations were observed in the database. This may be the trigger of this rare triplication. Because the shortest region of overlap contained 2 candidate genes, STX5 and CHRM1, which show some relevance to neuronal functions, we believe that the genomic copy number gains of these genes may be responsible for the neurological features seen in these patients.Molecular Cytogenetics 04/2013; 6(1):15. DOI:10.1186/1755-8166-6-15 · 2.66 Impact Factor