Happy New Year!

2011 has been a successful year for CCGS faculty with the publication of over 200 scientific articles and grants support totaling more than $35M, including a newly awarded Clinical Sequencing U01 (See below) .   We are also optimistic about applications the CCGS submitted at the close of the year in response to ENCODE U54 and U01 RFAs. The coming year should be especially interesting for the CCGS.  Highlights will include the opening of the new Genome Sciences Building and Opeining Symposium on October 12, 2012 (save the date!).  We also have a great slate of candidates for our ongoing joint faculty search with Chemistry.   As discussed at our last faculty meeting, we will also be organizing topic-based focus groups to help position our faculty to respond to future RFAs, so stay tuned for that. All the best for a productive 2012-

Jennifer Brennan, Associate Director for Research
Joyce Tan, Program Manager
Jason Lieb, Director

CCGS faculty funded to study genome sequencing in clinical settings
December 6, 2011

Full UNC news release

James EvansCHAPEL HILL, N.C. - The complete sequence of an individual’s genome – all 3 billion DNA building blocks - will soon be affordably available to doctors, patients and even consumers. While knowledge of one’s genome may have important medical benefits, tremendous questions remain regarding an avalanche of such data means and how they should be used. Many clinical, ethical and social issues arise from the evaluation, use and sharing of the data.

To address these issues, UNC scientists have received a four-year $6.4 million grant to establish an effort they have named the North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing (NCGENES). UNC is one of five Clinical Sequencing Exploratory Research projects that will study ways for healthcare professionals to use genome sequencing information in a clinical setting. The grant is funded by the National Human Genome Research Institute, part of the National Institutes of Health.

James P. Evans, MD, PhD, Bryson Distinguished Professor of Genetics in the UNC School of Medicine, is the principal investigator. He says ”We’re thrilled to have the opportunity to investigate how best to use the new technologies of rapid DNA sequencing in patient care. In this effort we will sequence all of the genes in each of about 750 patients to determine how well this technology performs as a diagnostic tool to figure out why these patients are ill.

“We will also carefully investigate how patients and their doctors use this information in both a medical and a non-medical context. For example, sometimes whole exome sequencing will discover things about a person that they might not have wanted to know: being at high risk of an untreatable disease such as dementia. We will investigate how such information is best handled in a way that is sensitive to patient preferences.

“We now have powerful technology that can provide us with much genetic data about an individual.  How do we move this technology into the clinical practice arena and successfully address the technical, logistical, psychosocial and ethical issues that arise from its use?”

Evans leads the Clinical Genetics Program of UNC Lineberger Comprehensive Cancer Center, and is a member of the Carolina Center for Genome Sciences, which will administer the grant.

Whole exome sequencing (WES) will be performed on 750 UNC patients, in whom there is a reasonable suspicion that a discrete genetic error lies at the root of their disorder.  For example, we will focus on individuals with cancer at young ages, those with a strong family history of cancer, and children with developmental disorders.

UNC scientists will evaluate the use and performance of WES as a diagnostic tool, while addressing the impact of the diagnostic WES information on patients and families. WES will also identify what is called “incidental information,” information that may or may not be clinically relevant or medically actionable. Thus, the team will assess how frequently such incidental information is found and whether or how patients want information about these findings, with the goal of developing best practices. The team will implement WES in medically underserved groups and work to identify barriers to recruitment and retention of patients in the study as well as how WES can be expanded to practices beyond UNC.

Other UNC scientists, all CCGS members, leading specific components of the grant are: Jonathan Berg, MD, PhD, assistant professor of genetics; Gail Henderson, PhD, professor and chair of the department of social medicine; Karen Weck-Taylor, MD, PhD, professor of pathology and laboratory medicine and director of the UNC Molecular Genetics Laboratory; and Kirk Wilhelmsen, MD, PhD, professor of genetics and neurology.

Other institutions receiving grants are Baylor College of Medicine, Houston, Texas; Brigham and Women’s Hospital, Boston; Children’s Hospital of Philadelphia, and the University of Washington in Seattle.

NHGRI Press Release
News and Observer Article


Jeff Dangl receives large community sequencing award from DOE Joint Genome Institute
November 3, 2011

Full JGI news release

The JGI 2012 Community Sequencing Program (CSP) invited researchers to submit proposals for projects that advance capabilities in fields such as plant-microbe interactions, microbes involved in carbon capture and greenhouse gas emission, and metagenomics—the characterization of complex collections of microbes from particular environmental niches.  A total of 41 CSP proposals were approved from the 152 submitted, culled from the 188 letters of intent originally received.

Jeff DanglOne of single largest projects was awarded to Jeff Dangl at the University of North Carolina and his colleagues and focuses on the rhizosphere, that narrow region where microbes in the soil colonize and interact with plant roots. The importance of rhizosphere microbial communities for plant growth and success cannot be overstated. “The distinctive ‘terroir’ that flavors wine, the yield of maize and other crops, and the productivity of any plant community rely in part on the respective rhizosphere microbiome,” they wrote in their proposal. “The microbiome is most simply viewed as an extension of each plant’s genome; we do not know any plant genome’s full functional capacity until we also know the functional capacity and the drivers governing assembly of its associated microbiome.” The Dangl team will sequence 1-3 Terabases for this project and seeks to apply the genetic and genomic information toward applications in bioenergy and carbon cycling research. They propose to study the rhizosphere microbiomes of maize, Arabidopsis and a mustard relative known commonly as Drummond’s rockcress, as well as potential biofuel crop Miscanthus and wild prairie grasses, to understand the plant genetics involved in determining the microbial communities associated with plant species.

The total allocation for the 2012 CSP portfolio exceeds 30 trillion bases (terabases or Tb), the equivalent of at least 10,000 human genomes in data.

Ethan Lange and colleagues find first major mutation associated with hereditary prostate cancer risk
January 11, 2012

Full UNC News Release

Ethan LangeAfter a 20-year quest to find a genetic driver for prostate cancer that strikes men at younger ages and runs in families, researchers have identified a rare, inherited mutation linked to a significantly higher risk of the disease.

A report on the discovery was published in the January 12, 2012 issue of the New England Journal of Medicine. UNC-Chapel Hill scientist Ethan Lange, PhD, was part of the team of investigators at the Johns Hopkins University School of Medicine, the University of Michigan Health System, Wake Forest University and the Translational Genomics Research Institute.  

Lange is associate professor of genetics and biostatistics and a member of UNC Lineberger Comprehensive Cancer Center and Carolina Center for Genome Sciences. The research team found that men with prostate cancer were 20 times more likely to carry this mutation than screened men without prostate cancer.

Lange explains, “For the first time we have identified an inherited high-risk mutation for prostate cancer. The mutation is significantly more common in men with a family history of prostate cancer that strikes at an earlier age, compared to older patients with no family history. Our findings suggest it could be a valuable early screening tool for men, particularly those with a family history of early-onset disease. The benefit to this population of men could be similar to the benefit of current screening strategies employed for BRCA1 and BRCA2 mutations in women with family history of early-onset breast cancer.

“There is still work to be done regarding understanding the biological function of the mutation and the precise level of absolute risk for carriers of this mutation - a process that took years for the BRCA1 and BRCA2 genes. Still, our results strongly suggest this is the most clinically important mutation identified for prostate cancer to date.”

While accounting for only a small fraction of all prostate cancer cases, the discovery may provide important clues about how this common cancer develops and help to identify a subset of men who might benefit from additional or earlier screening. This year, an estimated 240,000 men in the United States will be diagnosed with prostate cancer.

Lange and Kathleen Cooney, MD, one of two study senior authors, were the first to identify the human chromosome region of interest where the mutation, called HOXB13, was ultimately found. Lange, who has been a collaborator on Dr. Cooney’s University of Michigan Prostate Cancer Genetics Project for 17 years, led the statistical analyses and was actively involved in designing the study and interpreting the findings for the current study.

This particular mutation was found in families of European descent, while two different mutations on the HOXB13 gene were identified in families of African descent. Since only seven of the 94 families studied were of African descent, more research will be required before the significance of those mutations is known. African-American men are more likely to be diagnosed with prostate cancer at younger ages and have a more aggressive form of the disease.

Other UNC authors are: Yunfei Wang, MS, a statistician in the department of genetics, and Chris Bizon, PhD, a senior research scientist with UNC’s Renaissance Computing Institute.

Fernando Pardo Manuel de Villena elected as a fellow of the American Academy for the Advancement of Science
December 15, 2011

Full UNC news release

Fernando Pardo Manel de VillenaSix University of North Carolina at Chapel Hill faculty members have been named fellows of the American Association for the Advancement of Science (AAAS). The association, the world’s largest general scientific society, elects fellows to recognize their efforts toward advancing science applications that are considered scientifically or socially distinguished.
The six new fellows are biochemist Henrik Dohlman, microbiologist William Goldman, geneticist , geneticist Fernando Pardo Manuel de Villena, virologist Nancy Raab-Traub, geneticist Jeff Sekelsky and biochemist Yue Xiong.  In total, 58 Carolina faculty members have been elected fellows of the association.

Pardo-Manuel de Villena was recognized for contributions in the fields of mouse genetics and genomics and the evolution of the mammalian karyotype, which describes the complete set of chromosomes in a species. He is a genetics professor in the School of Medicine and a member of the Lineberger Center.

The six are among 539 scientists awarded the honor this year. New fellows will receive certificates and rosette pins at the association’s annual meeting in Vancouver, Canada, in February.

For more information, see http://www.aaas.org/news/releases/2011/1206fellows.shtml and http://www.aaas.org/aboutaaas/fellows/

Full UNC fellows list: http://research.unc.edu/about/facts-rankings/faculty-university-distinctions/CCM3_027316


Praveen Sethupathy recognized as a “rising young investigator” by Genome Technology
December 6, 2011

Praveen SethupathyCongratulations to Praveen Sethupathy, who was selected as a “rising young investigator” by Genome Technology in their sixth annual profile of young PIs recognized for their interesting and thought provoking research in genomics.  Praveen joined the UNC department of genetics and the CCGS as an Assistant Professor in September 2011.  His lab combines computational and experimental genomics to study MIRNA regulation in pancreatic islets to better understand the mechanisms underlying type 2 diabetes.  This is the second year in a row that a CCGS investigator has been recognized.  Last year, Jonathan Berg was cited for “clinical cancer genomics”.


Genome Web Profile for Praveen Sethupathy


UNC Curriculum in Genetics and Molecular Biology PhD program tops rankings of Genetics and Genomics PhD programs in the country

The Genetics and Molecular Biology (GMB) Program at UNC Chapel Hill took the number one spot in a recent survey of large doctoral programs in Genetics and Genomics.  The survey, published by PhDs.org in its latest Graduate School Guide, ranks several different categories and incorporates data from the National Research Council (NRC), The Survey of Earned Doctorates (SED), the Integrated Postsecondary Education Data System (IPEDS) and the Survey of Graduate Students and Postdoctorates in Science and Engineering (GSS).  Users of the Guide can choose the weights assigned to the program characteristics measured by the NRC and others, and rank graduate programs according to their own priorities.  The data was collected from more than 5,000 doctoral programs at 212 universities, covering 62 fields. Included for each program are such characteristics as faculty publications, grants, and awards; student GRE scores, financial support, employment outcomes, program size, time to degree, and faculty composition. Measures of faculty and student diversity are also included.

The interdepartmental GMB program is administered by the CCGS and the Program Director is Bob Duronio.  It supports ~85 students in more than 30 labs in 10 departments on campus.


Upcoming Seminars and Events:
  • January 27, 2012

    CCGS Seminar
    “Potentiating Signal-responsive Transcription: A Dynamic Dance Between Paused Polymerase and Chromatin”
    Karen Adelman
    Principal Investigator
    NIEHS
    Host: Karen Mohlke
    Noon, G100 Bondurant

  • February 2, 2012

    Carolina Systems Genetics Seminar
    “The Plant Immune System:  Discriminating Friend from Foe"
    Jeff Dangl, Ph.D.
    Professor of Biology
    HHMI Investigator
    UNC Chapel Hill
    3pm, Pagano Conference Room LCCC

  • February 21, 2012

    Center for Genomics and Society Interdisciplinary Seminar
    “Ethics and ELSI:  Looking Backwards and Forwards”
    Rebecca Walker
    Department of Social Medicine
    UNC Chapel Hill
    11am, G100 Bondurant

  • February 27, 2012

    CCGS Seminar
    “TBA”
    Nick Grishin, Ph.D.
    Professor of Biochemistry
    HHMI Investigator
    UT Southwestern
    Host:  Nikolay Dokholyan
    Noon, G100 Bondurant

  • March 1, 2012

    Carolina Systems Genetics Seminar
    “TBA"
    Marian Walhout, Ph.D.
    Professor of Molecular Medicine
    University of Massachusetts Medical School
    3pm, Pagano Conference Room LCCC

  • March 2, 2012

    CCGS Seminar
    “TBA”
    Job Dekker, Ph.D.
    Professor of Biochemistry and Molecular Pharmacology
    University of Massachusetts Medical School
    Host:  Jason Lieb
    Noon, G100 Bondurant

  • March 19-21, 2012

    African Genetics International Conference
    The Friday Center
    UNC Chapel Hill
    Featuring talks by Francis Collins, George Church, Carlos Bustamante, Debbie Nickerson and others.

  • March 20, 2012

    Center for Genomics and Society Interdisciplinary Seminar
    “Population-Based Carrier Screening:  Research and Policy in the Coming Years”
    Don Bailey
    Distinguished Fellow
    RTI International
    11am, G010 Bondurant

  • October 12, 2012

    Genome Sciences Building Opening Symposium
    9am-6pm
    Genome Sciences Auditorium
    Save the date!



New and Notable Publications from CCGS Colleagues                            
(November 2011- January 2012):

 

  • Karen Mohlke

    Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. Cho YS, Chen CH, Hu C, Long J, Hee Ong RT, Sim X, Takeuchi F, Wu Y, Go MJ, Yamauchi T, Chang YC, Kwak SH, Ma RC, Yamamoto K, Adair LS, Aung T, Cai Q, Chang LC, Chen YT, Gao Y, Hu FB, Kim HL, Kim S, Kim YJ, Lee JJ, Lee NR, Li Y, Liu JJ, Lu W, Nakamura J, Nakashima E, Ng DP, Tay WT, Tsai FJ, Wong TY, Yokota M, Zheng W, Zhang R, Wang C, So WY, Ohnaka K, Ikegami H, Hara K, Cho YM, Cho NH, Chang TJ, Bao Y, Hedman AK, Morris AP, McCarthy MI; DIAGRAM Consortium; MuTHER Consortium, Takayanagi R, Park KS, Jia W, Chuang LM, Chan JC, Maeda S, Kadowaki T, Lee JY, Wu JY, Teo YY, Tai ES, Shu XO, Mohlke KL, Kato N, Han BG, Seielstad M.
    Nat Genet. 2011 Dec 11;44(1):67-72. doi: 10.1038/ng.1019.

    Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. Kilpeläinen TO, Qi L, Brage S, Sharp SJ, Sonestedt E, Demerath E, Ahmad T, Mora S, Kaakinen M, Sandholt CH, Holzapfel C, Autenrieth CS, Hyppönen E, Cauchi S, He M, Kutalik Z, Kumari M, Stančáková A, Meidtner K, Balkau B, Tan JT, Mangino M, Timpson NJ, Song Y, Zillikens MC, Jablonski KA, Garcia ME, Johansson S, Bragg-Gresham JL, Wu Y, van Vliet-Ostaptchouk JV, Onland-Moret NC, Zimmermann E, Rivera NV, Tanaka T, Stringham HM, Silbernagel G, Kanoni S, Feitosa MF, Snitker S, Ruiz JR, Metter J, Larrad MT, Atalay M, Hakanen M, Amin N, Cavalcanti-Proença C, Grøntved A, Hallmans G, Jansson JO, Kuusisto J, Kähönen M, Lutsey PL, Nolan JJ, Palla L, Pedersen O, Pérusse L, Renström F, Scott RA, Shungin D, Sovio U, Tammelin TH, Rönnemaa T, Lakka TA, Uusitupa M, Rios MS, Ferrucci L, Bouchard C, Meirhaeghe A, Fu M, Walker M, Borecki IB, Dedoussis GV, Fritsche A, Ohlsson C, Boehnke M, Bandinelli S, van Duijn CM, Ebrahim S, Lawlor DA, Gudnason V, Harris TB, Sørensen TI, Mohlke KL, Hofman A, Uitterlinden AG, Tuomilehto J, Lehtimäki T, Raitakari O, Isomaa B, Njølstad PR, Florez JC, Liu S, Ness A, Spector TD, Tai ES, Froguel P, Boeing H, Laakso M, Marmot M, Bergmann S, Power C, Khaw KT, Chasman D, Ridker P, Hansen T, Monda KL, Illig T, Järvelin MR, Wareham NJ, Hu FB, Groop LC, Orho-Melander M, Ekelund U, Franks PW, Loos RJ. PLoS Med. 2011 Nov;8(11):e1001116. Epub 2011 Nov 1.

  • Joe Muenzer

    Overview of the mucopolysaccharidoses. Muenzer J. Rheumatology (Oxford). 2011 Dec;50 Suppl 5:v4-v12.

    The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus.
    Muenzer J, Bodamer O, Burton B, Clarke L, Frenking GS, Giugliani R, Jones S, Rojas MV, Scarpa M, Beck M, Harmatz P. Eur J Pediatr. 2012 Jan;171(1):181-8.

  • Dan Nelson

    Research participants' perspectives on genotype-driven research recruitment. Beskow LM, Namey EE, Cadigan RJ, Brazg T, Crouch J, Henderson GE, Michie M, Nelson DK, Tabor HK, Wilfond BS. J Empir Res Hum Res Ethics. 2011 Dec;6(4):3-20.

  • Cindy Powell

    Genotype-phenotype correlation in interstitial 6q deletions: a report of 12 new cases. Rosenfeld JA, Amrom D, Andermann E, Andermann F, Veilleux M, Curry C, Fisher J, Deputy S, Aylsworth AS, Powell CM, Manickam K, Heese B, Maisenbacher M, Stevens C, Ellison JW, Upton S, Moeschler J, Torres-Martinez W, Stevens A, Marion R, Pereira EM, Babcock M, Morrow B, Sahoo T, Lamb AN, Ballif BC, Paciorkowski AR, Shaffer LG. Neurogenetics. 2012 Jan 5.