Scientists develop new method to detect copy number variants using DNA sequencing technologies

Aug 24, 2009

A research team led by Associate Professor Jonathan Sebat, Ph.D., of Cold Spring Harbor Laboratory (CSHL) has developed a sensitive and accurate way of identifying gene copy number variations (CNVs). The method, which is described in a paper published online ahead of print in Genome Research, uses new DNA sequencing technologies to look for regions of the genome that vary in copy number between individuals in the population. Capable of detecting a wide range of different classes of CNVs, large and small, this method allows researchers to extract more genetic information from the complete genome sequence of an individual.

CNVs are regions of the genome that vary in the number of copies between individuals. These variants were once considered to be anomalies that occurred rarely among healthy individuals. As the result of a discovery by CSHL Professor Michael Wigler and Dr. Sebat in 2004, CNVs are now recognized as a major source of human genetic variation and methods for detecting CNVs have proven to be an effective approach for identifying genetic risk factors for disease.

Genome sequencing technologies are improving at a rapid pace. The current challenge is to find ways to extract all of the genetic information from the data. One of the biggest challenges has been the detection of CNVs. Sebat, in collaboration with Seungtai Yoon of CSHL and Kenny Ye, Ph.D., at the Albert Einstein College of Medicine, developed a to estimate DNA copy number of a genomic region based on the number of sequences that map to that location (or "read depth"). When the genomes of multiple individuals are compared, regions that differ in copy number between individuals can be identified.

The new method allows the detection of small structural variants that could not be detected using earlier microarray-based methods. This is significant because most of the CNVs the genome are less than 5000 nucleotides in length. The new method is also able to detect certain classes of CNVs that other sequencing-based approaches struggle with, particularly those located in complex genomic regions where rearrangements occur frequently.

The development of this novel method is timely. The 1000 Genomes Project was launched in 2008, as an international effort to sequence the genomes of 2000 individuals across geographic and ethnic regions to catalog human genetic variation. Sebat's team along with many other groups has contributed to the production and analysis of these data.

This innovation improves the detection of structural variants from whole genome sequence data, which will lead to improved sensitivity to detect disease-causing CNVs.

More information: "Sensitive and accurate detection of copy number variants using read depth of coverage" can be found online at http://.cshlp.org/content/early/2009/08/05/gr.092981.109.long

Source: Cold Spring Harbor Laboratory (news : web)

Explore further: New guide to the genetic jungle of muscles can help health research

add to favorites email to friend print save as pdf

Related Stories

Mutant sperm guide clinicians to new diseases

Dec 02, 2007

Research published today in Nature Genetics shows that some rearrangements of the human genome occur more frequently than previously thought. The work is likely to lead to new identification of genes involved in disease and to ...

15 human genomes each week

Jul 02, 2008

The Wellcome Trust Sanger Institute has sequenced the equivalent of 300 human genomes in just over six months. The Institute has just reached the staggering total of 1,000,000,000,000 letters of genetic code that will be ...

DNA chunks, chimps and humans

Nov 06, 2008

Researchers have carried out the largest study of differences between human and chimpanzee genomes, identifying regions that have been duplicated or lost during evolution of the two lineages. The study, published in Genome Re ...

We're more different than we thought, says gene study

Nov 22, 2006

New research shows that at least 10 percent of genes in the human population can vary in the number of copies of DNA sequences they contain--a finding that alters current thinking that the DNA of any two humans ...

Recommended for you

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.