Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Powerful New Tool Combs Family Genomes to Identify Disease-Causing Variations

30.05.2014

Scientists at the University of Utah (U of U), the University of Texas MD Anderson Cancer Center in Houston and colleagues have developed a powerful tool called pVAAST that combines linkage analysis with case control association to help researchers and clinicians identify disease-causing mutations in families faster and more precisely than ever before.

In a study in Nature Biotechnology, the researchersdescribe cases in which pVAAST (the pedigree Variant Annotation, Analysis and Search Tool) identified mutations in two families with separate diseases and a de novo or new variation in a 12-year-old who was the only one in his family to suffer from a mysterious and life threatening intestinal problem.


Mark Yandell, Ph.D.

“Linkage analysis and case control association traditionally have been used to find gene mutations,” says Chad Huff, Ph.D., corresponding author on the study, assistant professor of epidemiology at the MD Anderson Cancer Center and former postdoctoral fellow in human genetics at the U of U. “Bringing those methods together provides a strong increase in the power to find gene variations that cause disease.”

The advent of genome sequencing has allowed researchers to search for disease-causing mutations in the genomes of individual patients, larger groups of unrelated people or small and large families. The researchers in this study believe the most powerful way to identify these variants is by sequencing the genomes of families that experience unusually high occurrences of a particular illness. By identifying gene variations that family members share, it’s possible to identify mutations in a gene that causes the disease, according to Mark Yandell, Ph.D., U of U professor of human genetics and a senior author on the paper.

“The issue with whole genome sequences has been that sequencing one person’s genome to find a single disease-causing gene is difficult,” Yandell says. “If you can sequence the whole family it gives a fuller picture of the sequence and variations potentially involved in disease.”

Humans carry two healthy copies of each gene in the body. But mutations in a gene can cause disease or other health problems.  These mutations occur randomly and rarely, but once they happen in a family member, they are often passed down to subsequent generations.

pVAAST was designed to search the sequenced genomes of families to find shared mutations and thus identify the gene with the highest probability of causing disease. Unlike other gene-finding tools, pVAAST accounts for people being related as it searches for gene variations that have the highest probabilities of causing disease. A big advantage of pVAAST, according to Huff and Yandell, is its ability to simultaneously search multiple families with the same disease to find mutations; this reduces the amount of time and effort to find a disease-causing variant. For example, if three families have the same disease, two might have different mutations damaging the same gene, while the third family might have a different damaged gene. “pVAAST has the power to determine the true disease-causing mutations across all those families in one analysis,” Yandell says.

In related work, Yandell, Huff, and their colleagues vastly improved the results of individual and small family sequencing by developing another gene-finding tool, Phevor (Phenotype Driven Variant Ontological Re-ranking tool), which combines the probabilities of mutations being involved with a disease with databases of phenotypes and information on gene functions. In doing this Phevor and pVAAST in combination can identify disease genes with much greater precision than other tools.

Sequencing genomes of unrelated patients with the same disease also increases the ability to find gene variations, and a third software tool Yandell and colleagues developed, VAAST (Variant Annotation, Analysis and Search Tool), has greatly advanced the speed and precision of doing that.

If VAAST or pVAAST can’t identify the mutation most likely to cause a disease, Phevor can take the results from those tools and combine them with a description of the patients’ disease called a ‘phenotype’ to find the most likely causative gene.

“We hope that in developing pVAAST, we and other researchers can more rapidly identify genetic variations influencing disease risk by increasing the statistical power of familial genome sequencing,” Huff says.

This study is a collaboration of several institutions in the United States and one in Europe. Lynn B. Jorde, Ph.D., U of U professor and chair of human genetics and Martin Reese, Ph.D., CEO of Oakland, Calif.-based Omicia Inc., are senior authors. Leroy Hood, M.D., Ph.D., of the Institute for Systems Biology in Seattle, is a co-author as is Stephen L. Guthery, M.D., U of U professor of pediatrics who referred a patient and his family for the study, and Hilary Coon, Ph.D., research professor of psychiatry at the University of Utah School of Medicine.

Media Contacts
Phil Sahm
Office of Public Affairs

Phone: (801) 581-2517
Email: phil.sahm@hsc.utah.edu

Phil Sahm | Eurek Alert!
Further information:
http://healthcare.utah.edu/publicaffairs/news/current/YandellpVAAST52914.php

Further reports about: Disease-Causing ability genomes mutations variations

More articles from Life Sciences:

nachricht Ambush in a petri dish
24.11.2017 | Friedrich-Schiller-Universität Jena

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

IceCube experiment finds Earth can block high-energy particles from nuclear reactions

24.11.2017 | Physics and Astronomy

A 'half-hearted' solution to one-sided heart failure

24.11.2017 | Health and Medicine

Heidelberg Researchers Study Unique Underwater Stalactites

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>