Cutting through the genomic thicket in search of disease variants

September 25, 2012 by Richard Harth, Arizona State University

(Medical Xpress)—In the early stages of that vast undertaking known as the Human Genome Project, enthusiasm ran high. The enterprise would be costly and laborious but the clinical rewards, unprecedented. Once the complete blueprint of life was unlocked, the genetic underpinnings for a broad range of human maladies would be laid bare, allowing custom-tailored diagnosis and treatment and revolutionizing the field of medicine.

Or so it was thought.

Instead, "scientists were confronted with thousands of mutations in the collection of proteins in personal genomes, with no ready guide about what they meant in terms of health or disease," according to Sudhir Kumar, a researcher who directs the Center for Evolutionary Medicine and Informatics at Arizona State Unive rsity's Biodesign Institute.

Kumar explains that scientists and clinicians have turned to computer tools that sift meaningful variants from the glut of mutations they face. But the accuracy of these tools may be low, says Kumar.

Now Kumar, Li Liu and their colleagues describe a new technique that can reduce the rate of false positives in such tests, thereby increasing their reliability. The group's results recently appeared in the advanced online issue of the journal Nature Methods.

The new technique, labeled EvoD (for Evolutionary Diagnosis) capitalizes in part on —an examination of DNA positions across and between diverse species—to analyze the likely significance of particular human gene variants. EvoD was shown to work much better for positions that are the most evolutionarily conserved in the protein-coding portion of the human genome—known as the exome.

As co-author Liu explains, researchers have taken a keen interest in mutations occurring at ultra-conserved sites in the exome, as these are usually the most critical in terms of . Variants that are functionally damaging at such locations—where evolution is highly resistant to change—are likely to have profound effects on health, often producing so-called Mendelian diseases, which negatively impact health. EvoD performs better than existing methods in diagnosing these mutations.

The Center for Evolutionary Medicine and Informatics now provides EvoD as an online tool and genomic researchers have begun to use it already. The new technique and the tool pave the way for a deeper understanding of genomic variance and advances the quest for personalized disease diagnoses.

Explore further: Evolutionary information improves discovery of mutations associated with diseases

Related Stories

Evolutionary information improves discovery of mutations associated with diseases

July 18, 2012
A book containing misprints may cause annoyance for the reader, but typos in an individual’s genetic blueprint (DNA) can mean serious disease or even death. The search for genetic correlates for the wide range of diseases ...

Inactive genes surprisingly common in humans

February 16, 2012
(Medical Xpress) -- Every person carries on average 100 variants that disable genes - yet very few suffer ill effects, an international team of researchers led by Yale University and Wellcome Trust Sanger Institute report ...

Informatics approach helps doctors, patients make sense of genome data

September 20, 2012
The cost of sequencing the entire human genome, or exome – the regions of the genome that are translated into proteins that affect cell behavior – has decreased significantly, to the point where the cost of looking at ...

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

0 comments

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.