Navigation Links
Exome sequencing of health condition extremes can reveal susceptibility genes
Date:7/8/2012

Comparing the DNA from patients at the best and worst extremes of a health condition can reveal genes for resistance and susceptibly. 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 miniscule 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 this Sunday, 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 report published July 8 in Nature Genetics is Mary J. Emond, research associate professor of biostatistics at the University of Washington School of Public Health in Seattle. The senior author is medical geneticist Michael Bamshad, 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 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.


'/>"/>

Contact: Leila Gray
leilag@uw.edu
206-685-0381
University of Washington
Source:Eurekalert  

Related biology news :

1. Exome sequencing gives cheaper, faster diagnosis in heterogeneous disease
2. An error-eliminating fix overcomes big problem in 3rd-gen genome sequencing
3. University of North Texas Health Science Center Advances Forensic Research by Investing in Semiconductor DNA Sequencing Technology
4. Next-generation sequencing technology opens doors to discoveries
5. DNA Sequencing: Emerging Technologies and Applications
6. The sequencing of the tomato genome
7. Sequencing works in clinical setting to help -- finally -- get a diagnosis
8. Powerful sequencing technology decodes DNA folding pattern
9. Pollutants could pose health risks for 5 sea turtle species
10. Kids who cook hungrier for healthy food choices
11. VTT and GE Healthcare developing novel biomarkers to predict Alzheimers disease
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Exome sequencing of health condition extremes can reveal susceptibility genes
(Date:4/11/2017)... No two people are believed to ... York University Tandon School of Engineering and Michigan ... partial similarities between prints are common enough that ... and other electronic devices can be more vulnerable ... in the fact that fingerprint-based authentication systems feature ...
(Date:4/5/2017)... Today HYPR Corp. , leading innovator ... of the HYPR platform is officially FIDO® Certified ... architecture that empowers biometric authentication across Fortune 500 enterprises ... over 15 million users across the financial services industry, ... product suites and physical access represent a growing portion ...
(Date:3/30/2017)... March 30, 2017  On April 6-7, 2017, Sequencing.com ... Genome hackathon at Microsoft,s headquarters in ... will focus on developing health and wellness apps that ... Hack the Genome is the first hackathon for ... world,s largest companies in the genomics, tech and health ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... 2017  VMS BioMarketing, a leading provider of patient support ... Nurse Educator (CNE) network, which will launch this week. The ... health care professionals to enhance the patient care experience by ... other health care professionals to help women who have been ... ...
(Date:10/11/2017)... , ... October 11, 2017 , ... ... the implantation and pregnancy rates in frozen and fresh in vitro fertilization ... progesterone and maternal age to IVF success. , After comparing the results from ...
(Date:10/10/2017)... ... October 10, 2017 , ... ... advancing targeted antibody-drug conjugate (ADC) therapeutics, today confirmed licensing rights that give ... Liposomal Nanoparticle), a technology developed in collaboration with Children’s Hospital Los Angeles ...
(Date:10/10/2017)... 10, 2017 International research firm Parks Associates announced ... at the TMA 2017 Annual Meeting , October 11 in ... residential home security market and how smart safety and security products impact ... Parks Associates: Smart Home ... "The residential security market has ...
Breaking Biology Technology: