Navigation Links
Genetic interactions are the key to understanding complex traits
Date:1/22/2009

Jan. 23, 2009 -- In recent years, genetic studies have uncovered hundreds of DNA variations linked to common diseases, such as cancer or diabetes, raising the prospect that scientists can gauge disease risk based on information in an individual's genome. But the variations identified to date only account for a small percentage typically one to three percent of the overall genetic risk of any common disease.

This disappointment has led geneticist Barak Cohen, Ph.D., of Washington University School of Medicine in St. Louis, to suggest that scientists need to get a better handle on the ways genes interact to influence disease risk.

"For diseases that are major health problems, many different genetic variants combine to affect an individual's risk," says Cohen. "The problem is that we as scientists are really lousy at predicting how these variations interact to determine whether an individual is likely to develop a common disease or respond to a particular drug."

This reality begs the question: Is it possible to tease apart a complex genetic trait to reveal the precise genetic variations that have combined to produce it? Yes, Cohen and his group report in the Jan. 23 issue of Science. If the research can be replicated, it suggests that scientists need better statistical models and other tools to understand genetic interactions.

The researchers turned to a simple organism, the yeast Saccharomyces cerevisiae, culled from North American oak trees and vineyards, where it grows naturally, to find their answer.

"This was a test case," Cohen explains. "If we can't dissect a complex genetic trait that occurs naturally in yeast and show how multiple genes interact to produce a particular trait, then there's no hope for doing it in humans."

The researchers probed the genome of yeast to find the DNA variations that determine the efficiency with which the yeast undergo sexual reproduction, a process called sporulation. Cohen acknowledges it's not a particularly fascinating trait, but it is one that can be measured easily and precisely.

"We don't have any particular fondness for sporulation," he says. "We are simply using it as a model to understand how multiple genes interact to influence variation in a biological process. Our hope is that a complex trait is put together in yeast in a similar way as it is in humans."

When it comes to sporulation, the yeast from the oak tree samples produce spores with 99 percent efficiency; the vineyard strains are far less efficient, at seven percent.

The scientists discovered that just four variants, or single nucleotide polymorphisms (SNPs), in three yeast genes account for nearly 90 percent of the genetic contribution to sporulation efficiency. By moving each of the four variants from one yeast strain to the other, they produced oak strains that sporulated like vineyard strains and vice versa.

"To put this into context, there are about 85,000 SNP differences between the two strains of yeast, and by moving just four of them, we effectively reversed the phenotype of the two strains," Cohen says.

The researchers also exchanged every combination of the four SNPs between the yeast strains to determine how the genetic variations interacted. Interestingly, any two or more of variants from the oak tree strain increased sporulation efficiency far more than would have been expected based on the individual contributions of each SNP.

"The variations interacted like crazy," Cohen says. "The combined effects of variants were always larger than the sum of their individual effects."

Understanding these interactions was critical for the scientists to accurately predict how a strain would behave based on the variations it carries in its genome. Only by accounting for the interactions between variants could they predict how particular variants combine to increase or decrease sporulation.

The researchers also were surprised to discover that the four SNPs occurred in genes known as transcription factors, which have the ability to turn on other genes. This finding lends weight to the emerging theory that transcription factors may be a rich source of meaningful genetic variations, he says.

"It's a big genome with many different types of genes," Cohen says. "The probability that all four SNPs would be in transcription factor genes is very, very low. This suggests transcription factors may be more likely to harbor significant variations than other classes of genes."

Cohen acknowledges that dissecting a complex genetic trait in humans is far more difficult due to the sheer number of SNPs in the human genome. But his research points to the need for a better understanding of genetic interactions so that information in the human genome can one day accurately predict the diseases an individual is susceptible to and a list of drugs that are most effective for that individual. In other words, a new era of personalized medicine.


'/>"/>

Contact: Caroline Arbanas
arbanasc@wustl.edu
314-286-0109
Washington University School of Medicine
Source:Eurekalert  

Related medicine news :

1. The 2009 Damon Runyon-Rachleff Innovation Award Granted for Pioneering Ideas for Early Detection of Ovarian and Lung Cancers, Bone Marrow Transplant Safety, and Discovery of New Genetic Markers for Cancer
2. Interleukin Genetics to Present Data Highlighting Link Between Inflammatory Gene Variations and Less Effective Weightloss
3. Genetic Data May Not Boost Heart Disease Predictions
4. Genetic Data May Predict Colon Cancer Odds
5. FDA Issues Final Regulations for Genetically Engineered Animals
6. UT leads $2.5 million training program in pioneering area of genetic research
7. Identification of genetic markers for ulcerative colitis could lead to treatment
8. CellCyte Genetics Corporation: Seattle Times Erroneously Reports That CellCyte Closes
9. Beta Release of a New Genetics Website- ItRunsInMyFamily.com
10. New Genetic Analysis Might Boost Breast Cancer Care
11. Genetic Variants Tied to Obesity
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Genetic interactions are the key to understanding complex traits
(Date:2/14/2016)... ... February 14, 2016 , ... ... of Heart Failure Nurses (AAHFN) is promoting healthier living with heart failure by ... of Life! Healthy Living with Heart Failure will kick-off February 14 and includes ...
(Date:2/13/2016)... ... February 13, 2016 , ... ... Voices of Recovery, the leading national organization representing the growing community of recovering ... public office to include Family Recovery in policies addressing addiction. , Although ...
(Date:2/13/2016)... ... February 13, 2016 , ... In ... states that vein visualization technology should be used to ensure patient safety when ... world, the INS Standards mandate the use of vein visualization technology in patients ...
(Date:2/13/2016)... ... , ... DDi , a Makro company, makes it ... expertise in eClinical Solutions. DDi has built its solution competency with a unique ... clients. DDi provides smarter technology for Clinical Development, Regulatory and Enterprise domains by ...
(Date:2/12/2016)... WA, and Washington, DC (PRWEB) , ... ... ... PATH and the Siemens Foundation today announced a new initiative—the Siemens Foundation-PATH ... for low-resource settings. The partnership will recruit top students from U.S. universities ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... Feb. 12, 2016  Aralez Pharmaceuticals Inc. (Nasdaq: ... the Company will ring the Nasdaq Closing Bell at ... York at 4:00 p.m. ET on Tuesday, ... Adrian Adams , will perform the ... to 4:00 p.m. ET.  A live webcast will be ...
(Date:2/12/2016)... BUDAPEST , Ungarn, February 12, 2016 ... ein Medizintechnikunternehmen, das sich auf den ungedeckten ... gab heute positive Ergebnisse seines klinischen Forschungsprogramms ... und Asthma-Patienten beschäftigt, ergab Verbesserungen ihrer respiratorischen ... Indiso ltd , ein Medizintechnikunternehmen, das ...
(Date:2/11/2016)... LONDON , Feb. 11, 2016 Stem ... that are characterized by self-renewal and the capacity to ... a relatively new discovery, as the first mouse embryonic ... it was not until 1995 that the first culturing ... pluripotent stem cells were not produced until 2006 As ...
Breaking Medicine Technology: