Genetic background check may explain why mutations produce different results

August 1, 2013, Michigan State University
These images show how wild type genetic background affects how genetic mutations manifest. The fruit fly wings in the top two images are from two healthy individuals with different genetic background. The two middle images show how the same genetic mutation caused different outcomes in the two individuals' wings. Genetic background also affects how genetic mutations interact with each other, as shown in the bottom two images. In the image at bottom left, the two mutations together have a milder effect, while the same mutations are enhanced in the bottom right photo. Credit: Ian Dworkin and Sudarshan Chari, Department of Zoology, Michigan State University

Two women have the same genetic mutation – an abnormal BRCA1 gene that puts them both at much higher-than-average risk for breast cancer – but only one woman develops the disease. Why? Michigan State University genetic scientists have begun to understand the mechanisms behind the phenomena.

"It's been known for a while that genetic mutations can modify each other," explained Ian Dworkin, MSU associate professor of zoology. "And we also know that the subtle differences in an individual's genome – what scientists call wild type —also affects how mutations are manifested. We wanted to know how common it was for wild type genetic background to alter the way genetic mutations interact with each other. No one has really looked at this in a systematic manner before."

Using the fruit fly genome, Dworkin and Sudarshan Chari, zoology doctoral student, found that wild type genetic background affected the outcomes of interactions between about 75 percent of the time, which could have huge implications in how scientists construct genetic networks—maps of how genes interact with each other.

"It may be that some crucial portions of are missing," Dworkin said. "It also seems that network descriptions are more fluid than we thought."

The research, "The conditional nature or genetic interactions: the consequences of wild-type backgrounds on mutational interactions in a genome-wide modifier screen," is published in the Aug. 1, 2013 issue of PLoS Genetics.

For their study, Dworkin and Chari looked at a fruit fly genetic mutation in the gene scalloped, which affects the size and shape of the flies' wings. They painstakingly went through the entire fly genome and crossed the scalloped mutation with another mutation that was in almost all the other DNA in the genome, one segment at a time, to see how often the genetic background affected the physical outcome of the scalloped mutation.

"We were surprised that the influence of wildtype genetic background on was so common," Dworkin said. "We knew it could happen, but no one had demonstrated that it was this prevalent. The broader implication is that even for diseases with a simple genetic basis, variation in the genome may matter for both understanding and treatment."

While the fruit fly and human genomes are different, the two species share a number of genes, with the fruit fly often having one copy of a gene while humans have multiple copies. The human version of the fruit fly scalloped gene is called TEF-1, which regulates tissue growth among other things. The flies have one copy of the scalloped gene while humans have multiple copies of the TEF genes.

So going back to the example of the two women with the same BRCA1 mutation, each woman's genetic background is likely influencing how the mutation is expressed, causing two very different disease outcomes.

The research also may help explain why some people benefit from a specific treatment for a disease, while others get no benefits or become resistant to a drug after a short time.

It's likely that most diseases with a suspected genetic component, such as cancer, asthma, or Parkinson's, involve reactions between more than one set of genes. For Dworkin and Chari, the next step is to start to tease apart the intricacies of what's happening.

"Is it just the two pairs of genes that are interacting?" Dworkin said. "Or is it that the two genes are interacting and then many other genes are modifying that reaction? This will help us understand how much complexity is involved."

Explore further: Researchers identify genetic mutation linked to congenital heart disease

Related Stories

Researchers identify genetic mutation linked to congenital heart disease

July 29, 2013
A mutation in a gene crucial to normal heart development could play a role in some types of congenital heart disease—the most common birth defect in the U.S. The finding, from a team in The Research Institute at Nationwide ...

Scientists analyze genetic makeup of human and mouse embryos in unprecedented detail

July 31, 2013
(Medical Xpress)—UCLA scientists, in collaboration with teams in China, have used the powerful technology of single-cell RNA sequencing to track the genetic development of a human and a mouse embryo at an unprecedented ...

Getting to the heart of genetic cardiac defects

July 29, 2013
(Medical Xpress)—With modern surgical techniques increasingly able to save babies born with heart defects, biomedical researchers are hunting for ways to manage the subsequent rising prevalence of congenital heart disease.

Three mutations at BRCA1 gene responsible for breast and ovarian hereditary cancer

April 18, 2013
Researchers of the hereditary cancer research group at the Bellvitge Biomedical Research Institute (IDIBELL) and the Catalan Institute of Oncology (ICO) conducted a functional and structural study of seven missense variants ...

Understanding the effects of genes on human traits

July 31, 2013
Recent technological developments in genomics have revealed a large number of genetic influences on common complex diseases, such as diabetes, asthma, cancer or schizophrenia. However, discovering a genetic variant predisposing ...

Recommended for you

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. ...

Study advances gene therapy for glaucoma

January 16, 2018
While testing genes to treat glaucoma by reducing pressure inside the eye, University of Wisconsin-Madison scientists stumbled onto a problem: They had trouble getting efficient gene delivery to the cells that act like drains ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

How incurable mitochondrial diseases strike previously unaffected families

January 15, 2018
Researchers have shown for the first time how children can inherit a severe - potentially fatal - mitochondrial disease from a healthy mother. The study, led by researchers from the MRC Mitochondrial Biology Unit at the University ...

Genes that aid spinal cord healing in lamprey also present in humans

January 15, 2018
Many of the genes involved in natural repair of the injured spinal cord of the lamprey are also active in the repair of the peripheral nervous system in mammals, according to a study by a collaborative group of scientists ...

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.