Relevance of Copy Number Variation to Human Genetic Disease


Copy number changes involving dosage‐sensitive genes are well‐known causes of human genetic diseases and syndromes. Genome‐wide analytical techniques such as array comparative genomic hybridization (aCGH) and single nucleotide polymorphism (SNP) genotyping have revealed that polymorphic copy number variations (CNVs), manifesting as duplications or deletions, represent normal variants that contribute to human genomic diversity. Not all CNVs in the human genome have so far been discovered, however it is already clear that CNVs contribute much more to human genomic variation than SNPs. Since many human CNVs contain genes, the expression differences associated with these genes are very likely to influence normal phenotypic variation. Further, since not all CNVs are going to be neutral variants, at least some CNVs are expected to alter drug metabolism or to influence disease predisposition as is already evident in the context of HIV/AIDS susceptibility, Crohn disease and immunologically mediated glomerulonephritis.

Keywords: genomic duplication/deletion polymorphisms; genomic diversity; pathological genomic copy number changes

Figure 1.

Contribution of differentially sized copy number variations to human genomic structural diversity according to Eichler . Fine‐scale deletions vary in size from ∼0.5 to 10 kb whereas large‐scale variations encompass >50 kb with intermediate‐sized variations spanning ∼6–50 kb.



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Kehrer‐Sawatzki, Hildegard(Apr 2007) Relevance of Copy Number Variation to Human Genetic Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020226]