Thanks to engrained lessons from cytogenetics, researchers largely regarded variations in gene copy a rarity, synonymous with defects. Increasingly, however, researchers have found that large-scale deletions and duplications are the norm and represent a significant source of human variation.

Jonathan Sebat and colleagues based at Cold Spring Harbor Laboratory published a highly cited paper on this topic in 2004,1 as did Charles Lee at Brigham and Women's Hospital in Boston.2

Sebat and his team were running two normal DNA controls for a cancer genome study, and "copy number differences jumped out at us," he says. When they analyzed the high-resolution genomic arrays of 20 people, they found 76 unique copy-number polymorphisms (CNPs) of roughly 465 K, many affecting key functional genes. On average, individuals differed by eleven CNPs. Lee is now databasing such variants, which he says account for a staggering 100 million nucleotides of reference DNA.



1. J. Sebat et al., "Large-scale copy number polymorphism in the human genome," Science, 305:525-8, 2004. (Cited in 167 papers)2. A.J. Iafrate et al., "Detection of large-scale variation in the human genome," Nat Genet, 36:949-51, 2004. (Cited in 123 papers)

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