A Comprehensive Analysis of Common Copy-Number Variations in the Human Genome

Abstract

Segmental copy-number variations (CNVs) in the human genome are associated with developmental disorders and susceptibility to diseases. More importantly, CNVs may represent a major genetic component of our phenotypic diversity. In this study, using a whole-genome array comparative genomic hybridization assay, we identified 3,654 autosomal segmental CNVs, 800 of which appeared at a frequency of at least 3%. Of these frequent CNVs, 77% are novel. In the 95 individuals analyzed, the two most diverse genomes differed by at least 9 Mb in size or varied by at least 266 loci in content. Approximately 68% of the 800 polymorphic regions overlap with genes, which may reflect human diversity in senses (smell, hearing, taste, and sight), rhesus phenotype, metabolism, and disease susceptibility. Intriguingly, 14 polymorphic regions harbor 21 of the known human microRNAs, raising the possibility of the contribution of microRNAs to phenotypic diversity in humans. This in-depth survey of CNVs across the human genome provides a valuable baseline for studies involving human genetics.

Recurrent copy number changes in mentally retarded children harbour genes involved in cellular localization and the glutamate receptor complex

“…In an analogy to Wong et al, 32 we assumed that CNCs are identical to the BAC probe representing them. This has been confirmed by SNP array mapping of break points in a small sample from our patient cohort (Table 1).…”

“…After analysis, the averages of all triplicate spots were calculated. Subsequently, data were analyzed essentially according to Wong et al 32 Briefly, all spots with an aberrant shape, signal to noise ratios o5.0 or with an SD above 0.3 were excluded. Using the signals of all autosomal probes, the 95% confidence interval (95% CI) was calculated.…”

“…26,[28][29][30][31] Efforts to systematically compile CNCs have led to the identification of well over 6000 of such CNCs in DNA samples derived from lymphoblastoid cell lines of individuals of the HapMap population 18 or from peripheral blood-derived DNA samples. [32][33][34] The very existence of this type of structural genomic variability among apparently healthy individuals complicates a straightforward identification of pathogenetic segmental aneuploidy in patients.…”

Population structure in copy number variation and SNPs in the CCL4L chemokine gene

“…3,4 CNV involves DNA fragments about 1 kb or larger and, despite their heterogeneous distribution throughout the genome, there are no large stretches of the genome exempt from CNV. 5 Nonetheless, fine sequence analyses among the members of a CNV have only been reported for very specific cases known before the CNV concept, such as color vision or immunologic functions. 6,7 Several examples of CNV affecting genes of the immune system have been previously described (for example, a/b-defensins and FcgrIII).…”

Extraordinary Diversity of Chemosensory Receptor Gene Repertoires Among Vertebrates

“…On the basis of the analysis of 50 orthologous OR genes, suggested that humans also have fewer functional genes and more pseudogenes than chimpanzees, which was later substantiated by a genome-wide comparison of human and chimpanzee OR repertoires ) . More recently, the variation of OR gene number was also identified among different human individuals, which is known as the copy number variation (Trask et al 1998 ;Wong et al 2007) . Interestingly, the level of interspecific divergence relative to that of intraspecific variation in OR gene copy number is not significantly different between functional genes and pseudogenes, suggesting that human intraspecific and human-chimpanzee interspecific OR gene number variations may not have any fitness consequence (Nozawa et al 2007 ;Zhang 2007) .…”