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:10/13/2017)... ... October 13, 2017 , ... ... Arkansas that offers insurance and financial preparation services, is providing an update on ... Rescue organization. , Rock City Rescue is a locally recognized nonprofit that provides ...
(Date:10/13/2017)... ... October 13, 2017 , ... The American Board of Family Medicine's (ABFM) ... and Chief Executive Officer, succeeding Dr. James C. Puffer upon his retirement. Dr. Newton ... until Dr. Puffer’s retirement at the end of 2018. Upon assuming the role of ...
(Date:10/13/2017)... , ... October 13, 2017 ... ... of Pharmacy (SOP) alumni Hannah Randall, PharmD ‘17, and Jennifer Huggins, PharmD ... on guideline updates for the primary prevention of cardiovascular diseases during the ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... Many families ... However, many long-term care insurance companies have a waiver for care if the client ... elimination period, when the family pays for care, is often waived, so the benefits ...
(Date:10/13/2017)... ... 2017 , ... Global Healthcare Management’s 4th Annual Kids Fun Run brought out ... free event, sponsored by Global Healthcare Management’s CEO, Jon Letko, is aimed at getting ... children of all ages; it is a non-competitive, non-timed event, which is all about ...
Breaking Medicine News(10 mins):
(Date:9/28/2017)... , Sept. 28, 2017 Hill-Rom Holdings, Inc. ... earnings conference call and webcast on Friday, November 3, ... (EDT) and ending at approximately 8:30 a.m. (CDT) / ... the company,s 2017 financial performance and guidance for 2018, ... initiatives to enhance operational performance, and long-range financial outlook ...
(Date:9/25/2017)... , Sept. 25, 2017   Montrium , ... File solutions, today—from the IQPC Trial Master Files ... , NL)—announced that EastHORN Clinical Services has selected ... programs and TMF management. EastHORN, a leading European ... platform to increase transparency to enable greater collaboration ...
(Date:9/22/2017)... SAN DIEGO , Sept. 22, 2017 ... ll medical device is now successfully helping those with ... Union. Fibromyalgia diagnosed Amanda in ... getting dressed and washing my hair, experiencing no sleep ... body in painful spasm… I cannot recommend [the AVACEN ...
Breaking Medicine Technology: