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 Cancer: Molecularly shutting down cancer cachexia
30.08.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Bringing artificial enzymes closer to nature
30.08.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Streamlining accelerated computing for industry

PyFR code combines high accuracy with flexibility to resolve unsteady turbulence problems

Scientists and engineers striving to create the next machine-age marvel--whether it be a more aerodynamic rocket, a faster race car, or a higher-efficiency jet...

Im Focus: X-ray optics on a chip

Waveguides are widely used for filtering, confining, guiding, coupling or splitting beams of visible light. However, creating waveguides that could do the same for X-rays has posed tremendous challenges in fabrication, so they are still only in an early stage of development.

In the latest issue of Acta Crystallographica Section A: Foundations and Advances , Sarah Hoffmann-Urlaub and Tim Salditt report the fabrication and testing of...

Im Focus: Piggyback battery for microchips: TU Graz researchers develop new battery concept

Electrochemists at TU Graz have managed to use monocrystalline semiconductor silicon as an active storage electrode in lithium batteries. This enables an integrated power supply to be made for microchips with a rechargeable battery.

Small electrical gadgets, such as mobile phones, tablets or notebooks, are indispensable accompaniments of everyday life. Integrated circuits in the interiors...

Im Focus: UCI physicists confirm possible discovery of fifth force of nature

Light particle could be key to understanding dark matter in universe

Recent findings indicating the possible discovery of a previously unknown subatomic particle may be evidence of a fifth fundamental force of nature, according...

Im Focus: Wi-fi from lasers

White light from lasers demonstrates data speeds of up to 2 GB/s

A nanocrystalline material that rapidly makes white light out of blue light has been developed by KAUST researchers.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The energy transition is not possible without Geotechnics

25.08.2016 | Event News

New Ideas for the Shipping Industry

24.08.2016 | Event News

A week of excellence: 22 of the world’s best computer scientists and mathematicians in Heidelberg

12.08.2016 | Event News

 
Latest News

Environmental DNA uncovers biodiversity in rivers

30.08.2016 | Ecology, The Environment and Conservation

Solar houses scientifically evaluated

30.08.2016 | Power and Electrical Engineering

Amazon forests: Biodiversity can help mitigate climate risks

30.08.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>