Cutting through the genomic thicket in search of disease variants

September 25, 2012 by Richard Harth

(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

Distinct human mutations can alter the effect of medicine

December 18, 2017
Every person has a unique DNA sequence. Now, researchers from the University of Copenhagen and the MRC Laboratory of Molecular Biology in Cambridge have tried to quantify what these differences in the genome mean in the context ...

Association found between abnormal cerebral connectivity and variability in the PPARG gene in developing preterm infants

December 12, 2017
(Medical Xpress)—A team of researchers with King's College London and the National Institute for Health Research Biomedical Research Centre, both in the U.K., has found what they describe as a strong association between ...

Large genetic study links tendency to undervalue future rewards with ADHD, obesity

December 11, 2017
Researchers at University of California San Diego School of Medicine have found a genetic signature for delay discounting—the tendency to undervalue future rewards—that overlaps with attention-deficit/hyperactivity disorder ...

Gene variants identified that may influence sexual orientation in men and boys

December 8, 2017
(Medical Xpress)—A large team of researchers from several institutions in the U.S. and one each from Australia and the U.K. has found two gene variants that appear to be more prevalent in gay men than straight men, adding ...

Disease caused by reduction of most abundant cellular protein identified

December 8, 2017
An international team of scientists and doctors has identified a new disease that results in low levels of a common protein found inside our cells.

Study finds genetic mutation causes 'vicious cycle' in most common form of amyotrophic lateral sclerosis

December 8, 2017
University of Michigan-led research brings scientists one step closer to understanding the development of neurodegenerative disorders such as ALS.

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.