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: Copy number variations (CNVs), which represent a significant source of genetic diversity in mammals, have been shown to be associated with phenotypes of clinical relevance and to be causative of disease. Notwithstanding, little is known about the extent to which CNV contributes to genetic variation in cattle. We designed and used a set of NimbleGen CGH arrays that tile across the assayable portion of the cattle genome with approximately 6.3 million probes, at a median probe spacing of 301 bp. This study reports the highest resolution map of copy number variation in the cattle genome, with 304 CNV regions (CNVRs) being identified among the genomes of 20 bovine samples from 4 dairy and beef breeds. The CNVRs identified covered 0.68% (22 Mb) of the genome, and ranged in size from 1.7 to 2,031 kb (median size 16.7 kb). About 20% of the CNVs co-localized with segmental duplications, while 30% encompass genes, of which the majority is involved in environmental response. About 10% of the human orthologous of these genes are associated with human disease susceptibility and, hence, may have important phenotypic consequences. Together, this analysis provides a useful resource for assessment of the impact of CNVs regarding variation in bovine health and production traits.BMC Genomics 05/2010; 11(1):284. DOI:10.1186/1471-2164-11-284 · 4.04 Impact Factor
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ABSTRACT: We have performed an analysis of a family with kidney-yang deficiency syndrome (KDS) in order to determine the structural genomic variations through a novel approach designated as "copy number variants" (CNVs). Twelve KDS subjects and three healthy spouses from this family were included in this study. Genomic DNA samples were genotyped utilizing an Affymetrix 100 K single nucleotide polymorphism array, and CNVs were identified by Copy Number Algorithm (CNAT4.0, Affymetrix). Our results demonstrate that 447 deleted and 476 duplicated CNVs are shared among KDS subjects within the family. The homologus ratio of deleted CNVs was as high as 99.78%. One-copy-duplicated CNVs display mid-range homology. For two copies of duplicated CNVs (CNV(4)), a markedly heterologous ratio was observed. Therefore, with the important exception of CNV(4), our data shows that CNVs shared among KDS subjects display typical Mendelian inheritance. A total of 113 genes with established functions were identified from the CNV flanks; significantly enriched genes surrounding CNVs may contribute to certain adaptive benefit. These genes could be classified into categories including: binding and transporter, cell cycle, signal transduction, biogenesis, nerve development, metabolism regulation and immune response. They can also be included into three pathways, that is, signal transduction, metabolic processes and immunological networks. Particularly, the results reported here are consistent with the extensive impairments observed in KDS patients, involving the mass-energy-information-carrying network. In conclusion, this article provides the first set of CNVs from KDS patients that will facilitate our further understanding of the genetic basis of KDS and will allow novel strategies for a rational therapy of this disease.Evidence-based Complementary and Alternative Medicine 06/2011; 2011(1741-427X):548358. DOI:10.1093/ecam/neq069 · 1.88 Impact Factor
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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