David Geffen School of Medicine at UCLA
Department of Human Genetics

Speaker Series - Spring Quarter 2017

Mondays, 11am - 12pm, Gonda Building First Floor Conference Room, 1357

Mon, Apr 03
An assessment of the population genetic evidence for selection across twenty brain related phenotypes
Barbara Stranger, PhD, Assistant Professor, Section of Genetic Medicine, Dept of Medicine, Institute for Genomics and Systems Biology, Center for Data Intensive Science, University of Chicago
Contact & Intro: Eleazar Eskin x 51322
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ABSTRACT: Inter-individual variation in neuropsychiatric traits is present across diverse human populations, has persisted through recorded history, and has been shown to have a genetic basis primarily accounted for by common single nucleotide polymorphisms. Motivated by recent observations that SNPs with high minor allele frequency (MAF) contribute disproportionately to some neuropsychiatric phenotypes, we tested the hypothesis that common susceptibility variants for neuropsychiatric phenotypes have experienced selection over the course of human history.

Mon, Apr 10
Analysis of Genome, Exposome and Phenome
Xihong Lin, PhD, Chair and Henry Pickering Walcott Professor of Biostatistics; Harvard T.H. Chan School of Public Health
Contact & Intro: Jessica Li
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ABSTRACT: This talk will discuss analysis of massive genome, exposome, and phenome data. Specific topics include rare variant analysis of whole-genome sequencing association studies; analysis of multiple phenotypes (pleiotropy), and integrative analysis of different types of genetic and genomic, environmental data using mediation analysis. Connection between mediation analysis and Mendelian Randomization will be discussed.

Mon, Apr 17
Estimating heritable components of drug side-effects and other complex traits in model organisms using diallels
William Valdar, PhD, Associate Professor, Department of Genetics, University of North Carolina at Chapel Hill
Contact & Intro: Jonathan Flint
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ABSTRACT: It is well known that vulnerability to drug side-effects has a heritable component. But because vulnerability is itself a response to an applied treatment, its heritable nature is hard to estimate precisely in humans, and even in model organisms requires careful experimental design. Here I describe a model organism approach to decomposing different types of heritable effects using a novel Bayesian analysis of one of the old genetic designs, the diallel. Defined as a set of inbred strains and all possible F1 hybrid offspring, I show how diallels can reveal signals of additive genetics, dominance, parent-of-origin, epistasis and sex-specific versions thereof; how they can be applied to study the heritability of treatment response; and how they can be used to guide selection of follow-up studies using derivative populations of those same inbred strains. In particular, I describe a diallel study of haloperidol side-effects using the founder strains of the mouse resource, the Collaborative Cross (CC), and how this can guide follow-up in the CC and related populations. Implications for defining heritability of genetic by treatment effects are also discussed.

Mon, Apr 24
Epigenetic fine-mapping of cardiovascular disease loci
Christopher Brown, PhD, Assistant Professor, Department Genetics and Institute for Biomedical Informatics, University of Pennsylvania
Contact & Intro: Eleazar Eskin x 51322
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ABSTRACT: I will present our recent research that aims to characterize the mechanisms that underlie cardiovascular disease loci. To identify the specific variants and genes that affect CVD risk, we have deeply phenotyped liver biopsies and iPSC derived hepatocytes form more than 400 donors, collecting RNA-seq along with histone modification and transcription factor ChIP-seq data. We have used these data to identify thousands of genetic variants associated with allele-specific transcription factor binding, histone modification, gene expression, and splicing. Using a combination of massively parallel reporter assays, genome-edited stem cells, CRISPR interference, and in vivo mouse models, we establish rs2277862-CPNE1, rs10889356-ANGPTL3, rs10889356-DOCK7, and rs10872142-FRK as causal SNP-gene sets for CVD. These results demonstrate that a molecular trait mapping framework can rapidly identify causal genes and variants contributing to complex human traits and demonstrates that, at many GWAS loci, candidate genes have been falsely implicated based on proximity to the lead SNP.

Mon, May 15
Jeffrey Leek, PhD, Associate Professor, Department of Biostatistics, Johns Hopkins University
Contact & Intro: Eleazar Eskin x 51322
Mon, May 22
Hua Tang, PhD, Professor, Department of Genetics, Stanford University
Contact & Intro: Jessica Li x 68375
Mon, Jun 05
Noah Zaitlen, PhD, Assistant Professor, Department of Medicine in Human Genetics, University of California San Francisco
Contact & Intro: Eleazar Eskin x 51322
Mon, Jun 12
Causes and Consequences of Human Genomic Variation
Sohini Ramachandran, PhD, Manning Assistant Professor, Ecology and Evolutionary Biology, Brown University
Contact & Intro: Jazlyn Mooney
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ABSTRACT: Determining the genomic elements underlying adaptive evolution and diseases in a species is essential for connecting genetic variation to phenotypes and fitness, but current statistical methods overlook the confounding effect population histories have on the identification and localization of adaptive and disease-associated mutations. I'll discuss two methods developed in my laboratory that (i) model the complex interaction between various modes of selection and population histories; and (ii) accurately identify and localize mutations, genes, and pathways underlying adaptive traits and disease for further experimental validation. These methods can be extended and applied to existing and emerging genome-wide polymorphism and next-generation sequencing datasets for humans and a range of other organisms. Our goal is to yield new insight into the interaction between selection and dynamic population histories in generating human genetic diversity and the human phenotype.

Mon, Jun 26
LOCATION: Neuroscience Research Building (NRB) Auditorium, Room 132
Bradley Bernstein, MD, PhD, Department of Pathology, Massachusetts General Hospital, Harvard, Medical School and Broad Institute
Contact & Intro: Jason Ernst x 53658

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