In fruit flies, infection results in increased genetic diversity

New research from North Carolina State University and Reed College shows that when fruit flies are attacked by parasites or bacteria they respond by producing offspring with greater genetic variability. This extra genetic variability may give the offspring an increased chance of survival when faced with the same pathogens. These findings demonstrate that parents may purposefully alter the genotypes of their offspring.

The study was led by BRC faculty member Dr. Nadia Singh, and published in the August 14, 2015 issue of Science.

Image credit: Dahlia Nielsen, NCSU

Link: https://news.ncsu.edu/2015/08/singh-fruit-fly/


 

Better, faster, stronger GWAS

BRC faculty member Yi-Hui Zhou, Research Assistant Professor of Biological Sciences, has received a two-year R21 award from the National Human Genome Research Institute to develop new methods to analyze genome-wide association studies (GWAS). Existing methods for genetic association mapping primarily use parametric statistical assumptions. Explains Dr. Zhou, “standard methods can fail, even for large sample sizes, at the extreme significance thresholds required when testing millions of genetic markers.” An alternative approach uses permutation, a kind of data shuffling that provides accurate results, but is computationally intensive. The grant proposes to develop new mathematical approximations to permutation, in order to provide fast and accurate testing with greatly reduced computational burden.


 

David Reif serves on expert Working Group for the World Health Organization’s (WHO) International Agency for Cancer Research (IARC)

David Reif was a member of the Working Group that drew experts from 13 countries to a meeting in Lyon, France in order to evaluate the carcinogenicity of the the insecticides gamma-hexachlorocyclohexane (lindane) and dichlorodiphenyltrichloroethane (DDT) and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D).

Summaries of the final evaluations are available in the official press release and Lancet Oncology article. The detailed assessments will be published as Volume 113 of the IARC Monographs.

New Project Tackles Genetic Switchboard for DNA

It’s 2015, and the link between inherited DNA variation and numerous diseases is well-established. However, an important question remains – how, exactly do these links between genetic variation and disease work? The Genotype-Tissue Expression (GTEx) project, funded by the National Institutes of Health and including a team of researchers from NC State and UNC-Chapel Hill, aims to start answering that question by looking at how genetic variation affects gene expression.

“Important gaps still remain in understanding genetic processes, which vary greatly across the organs and tissues of the human body,” says Fred Wright, professor of statistics and biological sciences at NC State. “We have little understanding of how genetic variants actually cause disease, because we haven’t been able to look at the gene expression part of the equation. GTEx aims to fill the knowledge gap between the DNA you’re born with and actual disease outcomes.”

“You can think of DNA as the controller of a giant genetic switchboard,” explains Wright’s collaborator Andrew Nobel, professor of statistics and operations research at UNC-Chapel Hill. “When DNA switches on a gene, the gene produces proteins with specific functions. In the case of many common diseases, relatively small changes in protein output can have profound effects on disease risk.”

The GTEx project took samples of a large variety of tissues from 175 recently deceased individuals, measuring gene expression in those tissues. First, the researchers established that nearly normal gene activity persists for several hours after death. Then the major task of connecting variation in DNA to expression began. This is where Wright, Nobel and their team came in – to find meaningful correlations among all the “noise.”

“We had data for millions of DNA variants and how each variant was related to gene expression in different tissues,” Wright says. “Since we were looking at multiple tissues, there were gaps and overlaps in the data. We had to come up with a mathematical/statistical model that could assess, for each DNA variant and each gene, the evidence for the variant-gene combination being active for each of the tissues. The data were analyzed all together, but we untangled associations that reflected underlying true biology, versus associations that were happenstance because of sample overlap.”

Initial results were promising. The group found that DNA variants that affect expression tend to do so either in one tissue alone, or in all the examined tissues. Groups within GTEx are now comparing the results of the model to each variant-disease association, helping us further narrow down the genes that the variants affect, and in which tissue. The work may bring us one step closer to personalized therapies for numerous diseases.

The results appear in Science (DOI: 10.1126/science.1262110). NC State co-authors include Yi-Hui Zhou, research assistant professor of biological sciences. Funding was provided by the National Institutes of Mental Health and the NIH Common Fund.

NC State Receives $6.5 Million from NIEHS to Study Effect of Environment on Human Health

Researchers from North Carolina State University’s Center for Human Health and the Environment (CHHE) have received a five-year, $6.5 million grant from the National Institute of Environmental Health Sciences (NIEHS) to investigate the effects of environmental factors on human health.

The primary mission of the CHHE is to understand how human health, of both individuals and populations, is affected by environmental factors and to use this knowledge to prevent or reduce negative environmental impacts on health. Through interdisciplinary research and collaboration, the CHHE wants to construct a complete picture of how environmental stressors interface with pathways, the genome and epigenome.

The grant will be used to further the CHHE’s work by advancing interdisciplinary research in the field of environmental health and supporting community outreach and engagement regarding environmental health issues.

The NIEHS grant will make the CHHE one of 22 centers across the U.S. dedicated to studying environmental health impacts. “Through the purposeful interfacing of different disciplines, CHHE will build on NC State’s unique research and community outreach strengths to make significant contributions to understand and prevent the adverse impacts of environmental factors on human health” says Rob Smart, William Neal Reynolds Distinguished Professor of Biological Science at NC State and director of the CHHE.

The CHHE was founded in 2011 and brings together 70 investigators from 13 departments and six colleges at NC State and as well as investigators from East Carolina University, Brody School of Medicine, North Carolina Central University, NC Department of Health and Human Services, and RTI NIH Eastern Regional Comprehensive Metabolomics Resource Core.

Cross-population Study Links Individuals’ Chemical Sensitivity, Genes

Researchers from North Carolina State University and across the U.S. conducted the first large-scale cell-based screening to test variations in environmental chemical sensitivity across a range of human populations and link those variations to genetic data. The data will improve risk assessment, and shed light on the ways in which our genes interact with certain chemicals.  Testing chemicals for potential human health hazards involves large-scale programs that test hundreds of chemicals in vitro – by exposing a cell culture to differing concentrations of a chemical and recording various responses in hundreds of assays. However, these cell-based tests are usually derived from either rodents or a small sample of humans.

Current NCSU Bioinformatics Research Center Director, Fred Wright and Texas A&M professor of veterinary integrative biosciences Ivan Rusyn, while both on faculty at UNC-Chapel Hill, partnered with the researchers at the National Institute of Environmental Health Sciences and National Center for the Advancement of Translational Sciences to conduct this large-scale experiment. They obtained cell lines from 1,086 individuals who had volunteered their genetic data as part of the 1,000 Genomes Project. The cell lines represented nine different genetic populations spread over five continents. They then exposed cells to 180 different chemicals at eight different concentrations each.

The data revealed that, for some chemicals, the range of sensitivity among individuals was greater than previously thought. The NC State team, including faculty members Alison Motsinger-Reif and Yi-Hui Zhou, was instrumental in discovering several genetic variations that correlated to chemical sensitivity. Most of the genes involved are associated with the way foreign substances get transported across cell membranes.

‘This broad, cross-disciplinary academic-governmental partnership is a model that will fuel important discoveries in environmental health and biomedical sciences,” Rusyn says. “We are very grateful to all who committed time, effort and resources to this important undertaking.”

“This is a great first step,” Wright says, “but ultimately we want to match other biological data and the chemical structures, to find out why genetic differences affect toxicity of some chemicals but not the others. In addition to giving us more personalized information about chemical dangers and helping us determine safe exposure levels for these substances, the data could help us design safer chemicals for everyday use.”

 

Spotlight on the Bioinformatics Consulting and Services Core: The UNC-NCSU Superfund Research Program

The Bioinformatics Consulting and Services Core (BCSC) has received a subcontract to partner with the UNC Superfund Research Program to provide assistance in biostatistics and bioinformatics, starting with the 2014-2015 grant year.  BCSC staff members Elizabeth Scholl, Ph.D., and Allison Dickey, Ph.D., provide consulting assistance to Superfund investigators at UNC-Chapel Hill and NCSU, under the direction of Superfund Bioinformatics leader Fred Wright, Ph.D.  “The BCSC provides important infrastructure to the Superfund Research Program, as well as a combination of expertise in biostatistics and bioinformatics,” says Wright.  Adds Dr. Alison Motsinger-Reif, Director of the BCSC, “this is the sort of partnership that benefits both NCSU and UNC, maximizing efficiency by combining our collective talents.”

The UNC Superfund Research Program (UNC SRP) seeks to understand the human health and environmental risks associated with exposure to toxic chemicals found at hazardous waste sites (sph.unc.edu/superfund-pages/srp/).  Research projects span biomedicine and engineering approaches in environmental sciences, with principal investigators across both institutions.