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,
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.
Several groups have been looking to see how these heritable or spontaneous structural variations contribute to variations in disease susceptibility. Sebat says his team will soon publish on CNPs they have connected to autism. They provide a new tool, he says, to understanding complex diseases and have altered how scientists view evolution.