Copy number polymorphisms

Genomics

See Also

• DNA?
• Polymorphism
• [Single nucleotide polymorphisms (SNPs)]?

Description

Abbreviated CNP, Copy number polymorphisms are a normal variation in DNA due to variation in the number of copies of a sequence within the DNA. Large-scale copy number polymorphisms are common and widely distributed in the human genome.

Copy-number polymorphisms (CNPs) represent a greatly underestimated aspect of human genetic variation. Recently, two landmark studies reported genome-wide analyses of CNPs in normal individuals andrepresent the beginning of an understanding of thistype of large-scale variation. It is only when parallel analyses of CNPs and SNPs are performed in an integrated format that we will obtain a global picture of our genetic diversity.

Discussion

Baylor College of Medicine pediatrician and genetics professor James Lupski argued in 1991 that a common inherited neuropathy, Charcot-Marie-Tooth disease, was due to the duplication of a large segment of chromosome 17. The 1.5-megabase segment comprises 21 different genes, and only the one for peripheral myelin protein 22 is gene-dosage sensitive. "At the time, there was a lot of resistance to the idea that you could get clinical phenotype related to just gene dosage, not having an aberrant protein or abnormal gene," Lupski says. Yet it was already well known that Down syndrome, caused by duplication of an entire chromosome 21, is the most common genetic disease, affecting one in 600 live births. "We were so fixated on mutations," Lupski says. "Dosage can obviously have phenotypic consequences." [1]

The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Here, we show that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number differences representing 76 unique CNPs. On average, individuals differed by 11 CNPs, and the average length of a CNP interval was 465 kilobases. We observed copy number variation of 70 different genes within CNP intervals, including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease. [2]

Links

• Copy-number polymorphisms: mining the tip of an iceberg
• Looking at variation in numbers