Implications of gene copy-number variation in health and diseases

Inter-individual genomic variations have recently become evident with advances in sequencing techniques and genome-wide array comparative genomic hybridization. Among such variations single nucleotide polymorphisms (SNPs) are widely studied and better defined because of availability of large-scale detection platforms. However, insertion-deletions, inversions, copy-number variations (CNVs) also populate our genomes. The large structural variations (> 3 Mb) have been known for past 20 years, however, their link to health and disease remain ill-defined. CNVs are defined as the segment of DNA > 1 kb in size, and compared with reference genome vary in its copy number. All these types of genomic variations are bound to have vital role in disease susceptibility and drug response. In this review, the discussion is confined to CNVs and their link to health, diseases and drug response. There are several CNVs reported till date, which have important roles in an individual's susceptibility to several complex and common disorders. This review compiles some of these CNVs and analyzes their involvement in diseases in different populations, analyses available evidence and rationalizes their involvement in the development of disease phenotype. Combined with SNP, additional genomic variations including CNV, will provide better correlations between individual genomic variations and health. Journal of Human Genetics (2012) 57, 6-13; doi: 10.1038/jhg.2011.108; published online 29 September 2011