Human Genetics Seminar and Journal Club (HG 282)
This seminar course meets weekly, Friday 1-2:00, Gonda Center 6th Floor Conference Room 6303. The course is linked to the Human Genetics Seminar Series, Monday 11:00-12:00.
Participation in both Friday meeting and Monday seminar is required. On Friday, in Fall and Spring, we will discuss one or two papers related to the topic of the Monday seminar. Each student participating in the class will present one paper. In Winter, Human Genetics graduate students will talk on Friday about their own research project.
We will be limiting the registration for the Human Genetics Journal Club/HG282 to NINE (9) students per quarter so that we have adequate presentation slots for all registered students. As before, registration is not necessary to attend and participate in the journal club discussions - all are welcome!
The instructors for the class in Fall, Winter and Spring is Christina Jamieson.
Esteban Dell'Angelica teaches along with Christina Jamieson in the Winter.
This course satisfies the ACCESS seminar requirements.
Fall Quarter 2009
Fridays 1 pm - 2pm, Gonda Center Conference Room, 6th floor.
Fri, Sept. 25th
Organizational meeting (for registered students): Students sign up for presentations.
Fri, Oct 2
Student's Choice
Fri, Oct 9
Association Studies Involving Rare Variants and Large-Scale DNA Sequence Data Nicholas J. Schork, Ph.D., Director of Biostatistics and Bioinformatics, The Scripps Translational Science Institute, Professor, Molecular and Experimental Medicine, The Scripps Research Institute
Contact & Intro: Marc Suchard, ext 57442
ABSTRACT: The growing availability of efficient DNA sequencing technologies is motivating geneticists to leverage these technologies in association studies focused on the identification of genetic variations that influence phenotypic expression and disease susceptibility. However, making sense of DNA sequence data in the context of association studies is problematic. Statistical methods that are appropriate for the analysis of common genetic variations of the type interrogated in contemporary single nucleotide polymorphism (SNP) genotyping chip-based genome-wide association (GWA) studies are not likely to be appropriate for DNA sequence-based association studies given that rare variations and non-SNP forms of variation must be considered. In fact, the identification and validation of these forms of variation from DNA sequencing runs are themselves problematic and need to be taken into account when analyzed in association studies. In addition, the analysis of rare variations will require genomic annotations (i.e., information about the location of functional elements in the genome) to help put into context their individual and collective biological effects. This talk will outline some general approaches to association analyses involving DNA sequence data, including leveraging local sequence similarity, 'collapsing' collections of rare variations to create 'genetic meta-factors', exploiting sophisticated in silico methods for sequence annotation, and running sophisticated, very high-dimensional regression and related data mining techniques for association testing purposes.
LITERATURE: 1. Malo N, Libiger O, Schork NJ. Accommodating linkage disequilibrium in genetic-association analyses via ridge regression. Am J Hum Genet. 2008 Feb;82(2):375-85. PMID: 18252218 2. Schork NJ, Wessel J, Malo N. DNA sequence-based phenotypic association analysis. Adv Genet. 2008;60:195-217. PMID: 18358322 3. Schork NJ, Murray SS, Frazer KA, Topol EJ. Common vs. rare allele hypotheses for complex diseases. Curr Opin Genet Dev. 2009 Jun;19(3):212-9. Epub 2009 May 28. PMID: 19481926 4. Torkamani A, Kannan N, Taylor SS, Schork NJ. Congenital disease SNPs target lineage specific structural elements in protein kinases. Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9011-6. Epub 2008 Jun 25. PMID: 18579784 5. Torkamani A, Schork NJ. Predicting functional regulatory polymorphisms. Bioinformatics. 2008 Aug 15;24(16):1787-92. Epub 2008 Jun 18. PMID: 18562267
Fri, Oct 16 | Student Presenter: Bridgett vonHoldt
Student's Choice
Mon, Oct 26
11AM Note Special Seminar Gonda First Floor Conference Room
A Systems Genetic Approach for Understanding Cell Responses to Oxidized Phospholipids in Atherosclerosis
Casey Romanoski, UCLA Department of Human Genetics
Contact & Intro: Jake Lusis, ext 51359
ABSTRACT: n/a
LITERATURE: n/a
Fri, Oct 30 | Student Presenter: Jessica Lee
HNF4: New Roles for an Old Nuclear Receptor
Frances Sladek, Ph.D., Professor, Department of Biology and Neuroscience, UC Riverside
Contact & Intro: Christina Jamieson, ext 72469
ABSTRACT: HNF4 is one of the most highly conserved members in the nuclear receptor superfamily. It is essential for early development and plays a major role in the adult gastrointestinal track in the liver, kidney, pancreas and intestine/colon. It is known to regulate hundreds of genes involved in intermediary metabolism, blood coagulation and xenobiotic and drug metabolism. Mutations in HNF4 and its target genes have been linked to human diseases including diabetes, atherosclerosis and hemophilia. We have recently identified the endogenous ligand for HNF4 – linoleic acid, an essential fatty acid – and are uncovering new roles for this ancient receptor in physiology and disease using high throughput genomics and other techniques
LITERATURE: 1. Hwang-Verslues and F.M. Sladek (2008) Nuclear receptor HNF4a1 competes with oncoprotein c-Myc for control of the p21/WAF1 promoter Molecular Endocrinology, 22:78-90 2. Bolotin E, Schnabl J, Sladek F (Updated September, 2009). HNF4A (Homo sapiens). From the Transcription Factor Encyclopedia, http://www.cisreg.ca/tfe 3. Xie, X, H. Liao, H. Dang,, W. Pang, Y. Guan, X. Wang, J. Y-J. Shyy, Y. Zhu, and F. M. Sladek (2009) Down regulation of hepatic HNF4alpha expression during hyperinsulinemia: involvement of SREBPs Molecular Endocrinology 23: 434-443. (contributed equally) 4. Yuan, X., T.C. Ta, M. Lin, J. Evans, Y. Dong, E. Bolotin, M. A. Sherman, B.M. Forman, F.M. Sladek (2009) Identification of an endogenous ligand bound to a native orphan nuclear receptor. PLoS ONE 4:e5609 (contributed equally)
Fri, Nov 06 | Student Presenter: Michael Weinstein
Barry Forman, Ph.D., M.D., Professor and Director, Gene Regulation and Drug Discovery, City of Hope
Contact & Intro: Christina Jamieson, ext 72469
ABSTRACT: n/a
LITERATURE: n/a
Fri, Nov 13
Student's Choice
Fri, Nov 20 | Student Presenter: Princess Gilbert
Mapping QTL to a phylogenetic tree
Karl Broman, Ph.D., Professor, Department of Biostatistics & Medical Informatics, University of Wisconsin, Madison
Contact & Intro: Marc Suchard, ext 57442
ABSTRACT: The joint consideration of multiple crosses between related taxa (whether species or strains) offers the opportunity to identify the origin of a QTL allele on the phylogenetic tree that relates the taxa. We will discuss a formal method for combining multiple crosses to infer the location of a QTL on a tree, and will further discuss various experimental design issues for such endeavors, such as how many crosses are required and which sets of crosses are best.
LITERATURE: n/a
Fri, Nov 27
No Class - Thanksgiving
Fri, Dec 4 | Student Presenter: Mahsa (Huanhuan) He
Molecular Pathways for Schizophrenia: from Genes, Brain Circuitries, to Clinical Applications
Akira Sawa, M.D., Ph.D., Associate Professor of Psychiatry, Director, Program in Molecular Psychiatry, Johns Hopkins University
Contact & Intro: Esteban Dell'Angelica, ext 63749