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Spectrum: Autism Research News

Software tool homes in on disease-linked mutations

by  /  5 December 2012

This article is more than five years old. Autism research — and science in general — is constantly evolving, so older articles may contain information or theories that have been reevaluated since their original publication date.

Select sequence: Information about family pedigrees can help researchers identify genetic regions shared by individuals with a disorder.

By combining pedigree information with sequencing data, a new software tool helps focus on genetic variants likely to be responsible for disease, researchers reported 10 October in Bioinformatics1.

Over the past few years, the cost of sequencing the genome or the sum of its protein-coding regions, called the exome, has fallen dramatically. As a result, researchers are struggling to make sense of large amounts of sequencing data.

For example, just because someone with a disorder has a DNA variant that disrupts a disease-linked protein does not mean that this mutation caused the disease. The genetics of autism is particularly complex, as multiple variants may need to be present to lead to the disorder.

One method for filtering sequence information is to focus on areas of the genome most likely to contain the disease-causing mutation. Because researchers can identify regions with identical variants on both copies of the chromosome, it is relatively easy to focus on recessive mutations. These are most common in populations in which marriage between cousins is prevalent.

The new software, called Olorin, applies a similar approach to all types of families. It uses pedigree information to identify the genetic regions that are shared by affected individuals in a family. The tool then identifies genetic variants in these shared regions.

Not all mutations are fully penetrant, meaning that they do not always lead to disease. To account for this, the tool allows researchers to set a minimum number of individuals who share a genetic region.

For example, if there are three people with the disorder, the researchers can require that the three people share a variant for it to be included in the analysis, even if four people in the family carry the variant.

Researchers can also filter out variants that are common in the general population.


1: Morris J.A. and J.C. Barrett Bioinformatics Epub ahead of print (2012) PubMed