Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Exome Sequencing of Health Condition Extremes Can Reveal Susceptibility Genes

Published: Tuesday, July 17, 2012
Last Updated: Tuesday, July 17, 2012
Bookmark and Share
Comparing the DNA from patients at the best and worst extremes of a health condition can reveal genes for resistance and susceptibility.

This approach discovered rare variations in the DCTN4 gene among cystic fibrosis patients most prone to early, chronic airway infections.

The DCTN4 gene codes for dynactin 4. This protein is a component of a molecular motor that moves trouble-making microbes along a cellular conveyer belt into minuscule chemical vats, called lysosomes, for annihilation.

This study, led by the University of Washington, is part of the National Heart Lung and Blood Institute GO Exome Sequencing Project and its Lung GO, both major National Institutes of Health chronic disease research efforts.

Similar “testing the extremes” strategies may have important applications in uncovering genetic factors behind other more common, traits, such as healthy and unhealthy hearts.

The results of the cystic fibrosis infection susceptibility study appear July 8 in Nature Genetics.  The infection in question was "Pseudomonas aeruginosa," an opportunistic soil bacterium that commonly infects the lungs of people with cystic fibrosis and other airway-clogging disorders.  The bacteria can unite into a slithery, hard-to-treat biofilm that hampers breathing and harms lung tissue.  Chronic infections are linked to poor lung function and shorter lives among cystic fibrosis patients.  These bacteria rarely attack people with normal lungs and well-functioning immune systems.

In the study, these rare variations in DCTN4 did not appear in any of the cystic fibrosis patients who were the most resistant to Pseudomonas infection. The study subjects most susceptible to early, chronic infection had at least one DCTN4 missense variant. A missense variant produces a protein that likely can’t function properly.

The lead author of the Nature Genetics report is Dr. Mary J. Emond, research associate professor of biostatistics at the UW School of Public Health in Seattle. The senior author is medical geneticist Dr. Michael Bamshad, a UW professor of pediatrics in the Division of Genetic Medicine.

To the extent of their knowledge, the researchers think that this might be the first time that genetic variants underlying complex trait were discovered by sequencing all the protein-coding portions of the genomes of people at each extreme of a disease spectrum.

“We did not have a candidate gene in mind when we did this study,” said Emond.  Statistical analysis of the DNA of 91 patients led the research team to this particular gene.  Of the initial study group, 43 children had their first onset of chronic lung infection with Pseudomonas as when they were very young, and the 48 oldest individuals had not yet reached a state of chronic infection.  The patients selected for sequencing were from the Early Pseudomonas Infection Control (EPIC) Observational Study, a project at the Seattle Children’s Research Institute, and the North American Cystic Fibrosis Genetic Modifiers Study.   Exome sequencing was done by UW researchers in the laboratory of Deborah Nickerson, UW professor of genome sciences.

Comparisons of the protein coding portions of the study subjects’ DNA called the researchers attention to missense variations of the DCTN4 gene.  The researchers went on to screen a selected group of 1,322 other EPIC participants to check  their findings.

Exome Sequencing Project scientists are using an approach similar to the one in this study to examine the genetics behind resistance and susceptibility to other chronic conditions like obesity, heart attacks and hypertension. They plumb for gene variations linked to heart disease, for example by putting DNA maps from people with ideal cholesterol levels up against those from people with exceptionally poor levels.

Adapting a similar strategy to determine the genetics underlying other complex human traits may require exome sequencing of a much larger sample sizes, the researchers noted.
“As the costs of exome sequencing are dropping rapidly and more efficient statistical analysis is becoming available, we think medical researchers’ enthusiasm for this approach will continue,” Bamshad predicted.

In addition to National Heart Lung and Blood Institute funding, the study released today was supported by grants from the National Human Genome Research Institute, the Cystic Fibrosis Foundation, and the Life Sciences Discovery Fund.

Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,500+ scientific posters on ePosters
  • More than 5,200+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Microsatellites Linked to Cancer
DNA repeat stretches, called microsatellites, play a greater role in cancer progression and survival that previously thought.
Wednesday, October 05, 2016
Modified Yeast Shows Plant Response to Key Hormone
Researchers have developed a toolkit based on modified yeast to determine plant responses to auxin.
Thursday, September 29, 2016
Mutations in DNA-Repair Gene Higher in Prostate Cancer
Men with aggressive prostate cancer have higher incidence of inherited DNA-repair gene mutations.
Friday, July 08, 2016
Neanderthal DNA Influences Human Disease Risk
Large-scale, evolutionary analysis compares genetic data alongside electronic health records.
Friday, February 12, 2016
Draining Speeds up Bioassays
New methodology means biological assays that once took hours could instead take minutes.
Thursday, January 14, 2016
$12-Million Awarded to Study the Human Genome in 4-D
Project seeks to understand how a 6.5 feet of DNA folds to fit inside a cell.
Tuesday, October 20, 2015
Editing Genes to Create HIV Killers
Seattle scientists have managed to genetically transform human cells in the lab from HIV targets to HIV killers, and the technique could have implications for cancer and other diseases.
Monday, October 05, 2015
A New Single-Molecule Tool to Observe Enzymes at Work
A team of scientists at the University of Washington and the biotechnology company Illumina have created an innovative tool to directly detect the delicate, single-molecule interactions between DNA and enzymatic proteins.
Wednesday, September 30, 2015
Genetic Errors Linked To Aging Underlie Leukemia That Develops After Cancer Treatment
New research by Daniel Link, MD, and colleagues at The Genome Institute at Washington University has revealed that mutations that accumulate randomly as a person ages can play a role in a fatal form of leukemia that develops after treatment for another cancer.
Wednesday, December 10, 2014
Genetically Identical Bacteria Can Behave in Radically Different Ways
Although a population of bacteria may be genetically identical, individual bacteria within that population can act in radically different ways.
Friday, January 03, 2014
Depletion of ‘Traitor’ Immune Cells Slows Cancer Growth in Mice
When a person has cancer, some of the cells in his or her body have changed and are growing uncontrollably.
Wednesday, September 25, 2013
Breakthrough in Detecting DNA Mutations Could Help Treat Tuberculosis and Cancer
The slightest variation in a sequence of DNA can have profound effects.
Tuesday, July 30, 2013
Extra Chromosome 21 Removed from Down Syndrome Cell Line
Scientists have succeeded in removing the extra copy of chromosome 21 in cell cultures derived from a person with Down syndrome, a condition in which the body’s cells contain three copies of chromosome 21.
Monday, November 12, 2012
Chemical Makes Blind Mice See
Researchers who discovered the chemical are working on an improved compound that may someday allow people with degenerative blindness to see again.
Wednesday, August 01, 2012
Gene Therapy Delivered Once to Blood Vessel Wall Protects Against Atherosclerosis in Rabbit Studies By Leila Gray
The results came from research in rabbits, published July 19 in the journal Molecular Therapy.
Tuesday, July 26, 2011
Scientific News
Integrated Omics Analysis
Studying multi-omics promises to give a more holistic picture of the organism and its place in its ecosystem, however despite the complexities involved those within the field are optimistic.
Unravelling the Role of Key Genes and DNA Methylation in Blood Cell Malignancies
Researchers from the University of Nebraska Medical Center have demonstrated the role of Dnmt3a in safeguarding normal haematopoiesis.
Drug Target for Triple-Negative Breast Cancer Found
A team of researchers led by UC San Francisco scientists has identified a new drug target for triple-negative breast cancer.
Wrapping up the Genome
Researchers successfully package complete yeast genome using purified components, yielding new insights into genome mechanisms.
Gene Therapy Going Global with Portable Device
Portable 'gene therapy in a box' could make future cancer and HIV cures affordable in developing countries.
Smartphone Laboratory Detects Cancer
Researchers develop low-cost, portable laboratory on a smartphonecapable of analysing multiple samples simultaneously.
Fighting Cancer with Immune Response
New treatment elicits two-pronged immune response that destroys tumors in mice.
Nanomedicine for Breast Cancer Treatment
Using nanoparticles measuring only billionths of a meter in size, doctors are able to deliver drug molecules directly to the affected tissue.
Zika Virus Infection Alters Human and Viral RNA
Researchers have discovered that Zika infections results in human and viral genetic modification.
Cell Metabolism Linked to Spread of Cancer
Scientists discover macrophage metabolism can be attuned to prevent the spread of cancer.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,200+ scientific videos