David Geffen School of Medicine at UCLA
Department of Human Genetics

Speaker Series - Fall Quarter 2016

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

Thu, Sep 15
Thursday, September 15, 2016 at 12:00PM in 53-105 CHS
Noonan syndrome and related disorders: Voices Heard Along the RASpY Pathway
Bruce Gelb, MD, Director, Cardiovascular Genetics Program, Icahn School of Medicine, Mount Sinai
Contact & Intro: Co- Sponsored by the Jonsson Comprehensive Cancer Center and Signal Transduction and Therapeutics
Mon, Sep 26
Cryptococcus neoformans: from model pathogen to model organism
Hiten Madhani, MD, PhD, Professor, Department of Biochemistry and Biophysics, University of California San Francisco (UCSF)
Contact & Intro: Jingyi (Jessica) Li, x 68375
Mon, Oct 03
Excavating archaic hominin DNA from the genomes of modern humans
Joshua Akey, PhD, Professor, Department of Genome Sciences, University of Washington
Contact & Intro: Kirk Lohmueller, x 57635
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ABSTRACT: Anatomically modern humans overlapped in time and space with archaic hominins, such as Neandertals and Denisovans, and genetic data has revealed that hybridization occurred. We have developed methods to identify archaic hominin sequences that persist in the DNA of modern individuals, and applied it to whole-genome sequences from over 1,500 geographically diverse individuals. We leverage the catalog of surviving archaic sequences to show that admixture occurred multiple times in different non-African populations, characterize genomic regions that are significantly depleted of archaic sequence, and identify signatures of adaptive introgression. These data provide new insights in hominin evolutionary history and genomic regions that may harbor substrates of uniquely modern human phenotypes.

Mon, Oct 10
Integrative analysis of epigenomes illuminates differentiation and diseases of blood cells
Ross Hardison, PhD, Professor, Biochemistry and Molecular Biology, The Pennsylvania State University
Contact & Intro: Jingyi (Jessica) Li, x 68375
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ABSTRACT: The several distinct types of circulating blood cells differ dramatically in abundance, morphology, and function, but all are derived from a common hematopoietic stem cell. We have determined the transcriptomes and chromatin accessibility profiles across the genomes of purified populations of cells at progressive stages of mouse hematopoiesis. We combined these data with published histone modification maps and applied a novel, systematic approach for integrative and discriminative analysis of the epigenome profiles (from Yu Zhang, PSU). Globally, we find that the several stages of multilineage progenitor cells are quite similar to each other, while commitment to the erythroid lineage is accompanied by (or mediated by) substantial changes in chromatin landscape and transcriptional profiles. Importantly, we provide comprehensive, integrated maps showing genomic regions that share features across this differentiation series or that change significantly. Specific aspects of these results are being explored for insights into blood diseases and potential new therapeutic avenues.

Tue, Oct 11
Semel 37-417 NPIH
Deconstructing Bipolar Disorder: Evidence from Community and Family Study Data
Kathleen Ries Merikangas, PhD, Senior Investigator & Chief, Genetic Epidemiology Research Branch; National Institute of Mental Health; Intramural Research Program
Contact & Intro: Nelson Freimer x 46427
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ABSTRACT: This study will describe evidence regarding the symptoms and core features of bipolar disorder based on large scale population based studies of adolescents and adults. Family study data is applied to examine the familial patterns of the core subtypes and features of mania and depression. The application of mobile technologies to examine fluctuation of these symptoms provides insight into subgroups of people with mood disorders that can inform etiology, intervention and prevention efforts.

Mon, Oct 24
Genetic Mapping of Complex Traits in Outbred Mice
Jonathan Flint, MD, Professor-in-Residence, Department of Psychiatry and Biobehavioral Sciences, UCLA
Contact & Intro: Paivi Pajukanta, x 72011
Mon, Oct 31
Discovery and Translation Using a Gene by Medical Phenome Catalog
Nancy Cox, PhD, Professor, Department of Genetics, Vanderbilt University
Contact & Intro: Rita Cantor, x 72440
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ABSTRACT: The opportunity to conduct discovery research using a biobank in which the entire medical phenome is available offers substantial advantages to more traditional research conducted one disease at a time. I will describe here our efforts to construct the first gene by medical phenome catalog at Vanderbilt using the PrediXcan method (Gamazon et al, 2015) to BioVU, the biobank at Vanderbilt University with DNA on more than 218,000 subjects linked to a deidentified and continuously updated image of Vanderbilt's electronic health record (EHR) going back more than 20 years. Our studies highlight new kinds of findings related to how genome variation impacts human phenotypes and provide insights into the nature of polygenic genetic architecture. These studies have also allowed us to better quantify the contribution of Mendelian disease genes to common human disease, offering new possibilities for translation. Finally, using such a catalog can illuminate opportunities for drug repurposing.

Mon, Nov 07
Sex-biased genome evolution
Melissa Wilson Sayres, PhD, Assistant Professor, School of Life Sciences, Arizona State University
Contact & Intro: Kirk Lohmueller, x 57635
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ABSTRACT: Tremendous variation exists between the sexes for susceptibility to diseases, and for response to treatments. Sex-biased processes occur on a variety of levels, from the differentiation of our sex chromosomes, to population dynamics, to sex-specific mutation rates and expression. The human sex chromosomes, X and Y, were once an indistinguishable pair of autosomes, but over the past 160 million years have become quite different. As such, studying patterns of genome-wide diversity can provide a unique insight into the history of sex-biased demography, selection, and mutation. I will discuss medical implications of my lab's research to: 1) understand the degradation of the Y, and how this process has affected the X chromosome; and, 2) investigate sex biases in the accumulation of mutations.

Mon, Nov 28
Evolution and developmental control of epigenetic poising in the animal germ line
Bluma J. Lesch, MD, PhD, Senior Research Associate, Whitehead Institute / MIT
Contact & Intro: Marc Suchard x 57442
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ABSTRACT: Germ cells (sperm, egg, and their developmental precursors) carry hereditary information from one generation to the next. In addition to DNA, this information includes regulatory and packaging proteins that control transcription in gametes and can affect gene expression in the embryo following fertilization. I have found that genes central to conserved somatic developmental networks share a specific type of packaging, a state known as epigenetic poising, in the male germ cells of multiple species across mammalian evolution. I hypothesize that poising is an ancient feature of the animal germ line, where it plays a fundamental biological role.

Mon, Dec 05
Of mice, men, and birds: mechanisms and evolution of recombination hotspots
Molly Przeworski, Phd, Professor Department of Genetics and Genomics, Columbia University
Contact & Intro: Jazlyn Mooney
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ABSTRACT: Meiotic recombination is a fundamental genetic process that generates new combinations of alleles on which natural selection can act and, in most sexually-reproducing organisms, ensures the proper alignment and segregation of chromosomes. Recombination events are initiated by double strand breaks deliberately inflicted on the genome during meiosis. In this talk, I’ll present accumulating evidence from my group and others, which suggests two main mechanisms by which the locations of these double strand breaks are specified, with dramatic evolutionary consequences. In apes and mice, recombination events are directed by binding of the gene PRDM9 and hotspots evolve rapidly across populations and species. In species that lack PRDM9, in contrast, recombination events appear to be predominately localized to promoter-like features of the genome and to be evolutionarily stable. These observations sketch the outline of a general pattern whereby the binding specificity of PRDM9 drives rapid turnover, whereas the reliance on accessible, functional genomic features leads to stasis.

Wed, Dec 07
Endogenous retroviruses as catalysts of gene regulatory evolution
Edward B. Chuong, PhD, Postdoctoral fellow, Department of Human Genetics, University of Utah School of Medicine
Contact & Intro: Marc Suchard x 57442
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ABSTRACT: Endogenous retroviruses (ERVs) are genomic parasites that constitute 8-14% of mammalian genomes. Emerging evidence indicates that ERVs exhibit highly regulated transcriptional activity during normal development, but the significance of this activity remains unclear. I will present recent work establishing a beneficial role for ERVs in transcriptionally regulating human innate immune responses. These findings support the idea that ERVs play an important role facilitating the evolution of mammalian gene regulatory networks.

Mon, Dec 12
Causes and consequences of our gut microbial differences
Federico E. Rey, PhD, Assistant Professor, Department of Bacteriology, University of Wisconsin-Madison
Contact & Intro: Jake Lusis, x 41706
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ABSTRACT: The microbial communities that inhabit our intestines exert profound influence on metabolism and metabolic diseases. Diet and host-derived factors modulate the composition of the gut microbiome, which in turn modifies the nutritional value of the food we consume, in part by generating bioactive molecules. I will discuss our efforts aimed at (i) identifyng enviromental and genetic determinants of gut microbiome composition and (ii) understanding how differences in microbiota composition affect metabolism of nutrients and health.

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