July 2009

Facility Manager James Pearson and his colleagues will work with Duke researchers to help them adapt their "favorite assay" for compatibility with the high throughput technology. The development process can take a few months time, but with a robust assay in hand researchers can expect to screen the functions of 22,000 genes almost as easily as they could 100.

"That's when you begin to realize the power of this approach," Pearson said. "A good assay brings a newfound feasibility to whole-genome screens."

As a case in point, Mariano Garcia-Blanco and colleagues recently reported in Nature the results of the first successul whole genome screen to be completed in the facility, which identified dengue virus host factors in insect cells . Stay tuned for news of their first screen done in human cells, that one in search of host factors for yellow fever.

The RNAi facility also offers high-content cell-based imaging and analysis, which enables scoring of rare phenotypes. That technology was critical to the dengue virus work, Pearson said, since only a small percentage of the insect cells were actually infected.

For more information, contact James Pearson at 919-613-5132.

On Malaria Struggle, Baboons and Humans Have Similar Stories to Tell
Greg Wray says that the parallel evolution of a gene that protects against malaria parasites in baboons and humans "is a nice example of how – in the vastness of the genome – the same gene was modified in the same way in two different species to produce the same kind of resistance." Read the original Nature report.

New Cancer Drug Fights Tumors in Those with BRCA Mutation
The discovery that a new drug class can shrink tumors in patients carrying a BRCA mutation show "a really clever understanding of the biology of the cancer," Kelly Marcom says in an ABC News HealthDay report.

Extreme Genomics Update
In Duke Research, an updated version of a story that first appeared in GenomeLIFE reports that David Goldstein's group has now completed the first 10 of 50 HIV-resistant human genomes at high coverage.

Gene Plus Stress Equals Depression Debate
Two new studies in JAMA have sparked debate about whether the short serotonin transporter gene acts as a depression promoter when accompanied by stressful experiences, Science News reports. Avshalom Caspi and Terrie Moffit, who made the original discovery in 2003, say the new meta-analysis underscores the need for more high quality research into gene-by-environment interactions.

The Life-Saving Secrets in Your Family Tree
"For most common diseases, it's more informative to work out your family history" than to get a genetic profile, David Goldstein told the Wall Street Journal.

Life After GWAS: For Some Researchers, Focus Shifts to Rare Variants, CNVs
In a GenomeWeb article, IGSP Member Allen Roses says "GWAS was never meant to substitute for fine genomic sequencing," but rather to identify regions in the genome that warrant further study.

Doubts on Ovarian Cancer Relapse Test
In a New York Times article about early detection of ovarian cancer relapse with a widely used blood test, IGSP Member Andrew Berchuck says some patients "wouldn't dream of not being treated," while others "wouldn't want to go back on chemo unless they absolutely have to."

New Insights, Inroads Against Breast, Ovarian Cancers
In an ABC News article, Kelly Marcom says "We've put that one [CA125 screening] in the grave so many times it has a zombie-like existence."

Yeast Missing Sex Genes Undergo Unexpected Sexual Reproduction
An emerging form of the pathogenic yeast Candida is able to complete a full sexual cycle in a test tube, even though it's missing the genes for reproduction, according to a report by Joe Heitman and colleagues in Nature, which explored eight Candida genomes.

Genomic Features that Predict Allelic Imbalance in Humans Suggest Patterns of Constraint on Gene Expression Variation
In a report in Molecular Biology and Evolution, Jenny Tung, Greg Wray and their colleagues report evidence that the genomic distribution of functional cis-regulatory variants in the human genome is nonrandom, perhaps due to local differences in evolutionary constraint.

Expansion of the Parkinson's Disease-Associated SNCA-Rep1 Allele Up-Regulates Human alpha-Synuclein in Transgenic Mouse Brain
In Human Molecular Genetics, Ornit Chiba-Falek offers new insight into the connection between the alpha-synuclein gene and sporadic Parkinson’s disease.

HLA-B*5701 Genotype is a Major Determinant of Drug-Induced Liver Injury Due to Flucloxacillin
The discovery of a genetic determinant of liver injury caused by a drug used to treat staph infection provides new insights into the mechanism of the condition and has the potential to substantially improve diagnosis of this serious disease, according to a Nature Genetics report co-authored by David Goldstein.

Translating Genomics into Clinical Practice: Applications in Lung Cancer
In a Current Oncology Reports article, Anil Potti and Aubrey Graham say that genomic approaches in non-small cell lung cancer have the potential to advance our understanding of underlying disease biology…ultimately improving survival in patients with NSCLC and providing an opportunity for "personalized medicine."

A Combinatorial Mechanism for Determining the Specificity of E2F Activation and Repression
In the journal Oncogene, Joe Nevins and colleagues propose that the functional E2F element is a module comprising not only the E2F-binding site, but also the adjacent site for the cooperating transcription factor.

Genomic Approached to Outcome Prediction in Prostate Cancer
Phil Febbo reviews in the journal Cancer recent work in genomics approaches and its role in evaluating molecular modifiers of prostate cancer risk and behavior and the development of predictive models that anticipate the risk of developing prostate cancer, prostate cancer progression and the response of prostate cancer to therapy.

Comparative Genome-Wide Screening Identifies a Conserved Doxorubicin Repair Network that is Diploid Specific in Saccharomyces cerevisiae
John Olson and Jeffrey Marks are collaborators on a study reported in PLoS ONE on conserved genes that mediate resistance to the chemotherapeutic drug doxorubicin.

Measuring Spatial Preferences at the Fine-Scale Resolution Identifies Known and Novel cis-Regulatory Element Candidates and Functional Motif-Pair Relationships
Ken Daigoro Yokoyama, Uwe Ohler and Greg Wray report a novel means for predicting sequence elements with a collective role in gene regulation in the journal Nucleic Acids Research.

Anchorage-Independent Cell Growth Signature Identifies Tumors with Metastatic Potential
Joe Nevins and colleagues report in Oncogene the development of a signature of anchorage-independent growth that identifies human tumors with the potential for metastasis.

Erin Heinzen has been appointed Assistant Research Professor in the IGSP and is an Associate Investigator in the IGSP Center for Human Genome Variation. Welcome, Erin!

Julie Horvath, research director for the Duke University Primate Genomics Initiative, is the newest member of the IGSP.

Greenwall Scholar to Examine Use of 'Race' in Medicine
People cannot be classified into distinct races based on their biology, but that hasn't stopped the use of racial categories in clinical research and practice. The question is: how do you both eliminate or reduce health disparities and stay true to the science? says the IGSP's Charmaine Royal, who has been named a Greenwall Faculty Scholar to explore the use of race in medicine by examining the case of BiDil.

Michael Gatza in Joe Nevins' lab has received a one-year fellowship from the National Institutes of Health for a project entitled "Use of Genomic Signatures to Classify Tumors and Direct Chemotherapeutics."

The NIH is soliciting grant applications for a new initiative aimed to address the funding gap – often called the “Valley of Death – that must be crossed to bring promising research and development to the market. The grants are funded by the American Recovery & Reinvestment Act of 2009 and applications are due on September 1.

The National Cancer Institute will fund grants for research to identify non-coding RNA targets for early cancer detection and prevention.

The National Cancer Institute will fund studies aimed at the development of biomarkers for early detection of cancers of the blood.