David Geffen School of Medicine at UCLA
Department of Human Genetics

Speaker Series - Winter Quarter 2017

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

Mon, Jan 09
The folding landscape of RNA G-quadruplexes in cells
Junjie U. Guo, PhD, Postdoctoral Fellow, Whitehead Institute / MIT
Contact & Intro: Marc Suchard x 57442
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ABSTRACT: RNA structures play important roles in regulating gene expression. Emerging evidence suggests that some RNAs may adopt different conformations in cells than those in vitro. To investigate the folding of a noncanonical RNA structure known as the G-quadruplex, we developed a suite of high-throughput methods to (1) systematically identify endogenous RNA regions that can form G-quadruplex structures in vitro and (2) quantify their folding state in living cells. Applying these methods to different organisms, we obtained new insights into the cellular regulation of these RNA structures, and provided a framework for further understanding the roles of RNA G-quadruplexes in gene regulation and human diseases.

Tue, Jan 17
Cas9-mediated whole-cell engineering
Alejandro (Alex) Chavez, PhD, Postdoctoral Fellow, Wyss Institute at Harvard University
Contact & Intro: Marc Suchard x 57442
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ABSTRACT: I will present a series of improvements to the RNA-guided endonuclease Cas9 that drastically enhance its ability to induce potent gene expression at genome-wide scales. Furthermore, I will provide simple gRNA design principles that allow users to regulate Cas9 nuclease activity and by doing so, utilize a single Cas9 protein to simultaneously perform targeted gene activation, repression and cutting. Finally, in more recent work we have developed a generalizable method for increasing Cas9 specificity, enabling it to select between two alleles that differ by a single nucleotide polymorphism. Using these tools, I will demonstrate our ability to activate a series of endogenous loci, reprogram iPS cells into neurons, regulate complex transcriptional cascades, and prevent the emergence of undesired point mutations within a population of cells.

Mon, Jan 23
Network biology of cardiometabolic disease - from hairballs to key disease drivers
Johan LM Björkegren, MD, PhD, Professor of Genetics and Genomcis at the Department of Genetics and Genomic Sciences & Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai
Contact & Intro: Jake Lusis, x 41706
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ABSTRACT: Focusing on cardiometabolic disease (CMD), the goal of my research is to use multi-modal big data analysis to create reliable models of gene-regulatory networks in human biology and CMDs. Combined these network models, we believe, have the potential to provide a molecular overview of CMDs that in turn can be used to better predict disease risk, identify new therapeutic targets, and to monitor molecular effects of treatments. To achieve this goal, I have designed and generated a range of large-scale clinical "genetics of gene expression studies" of CMDs that combine detailed clinical characteristics with multi-tissue RNA sequence data.

Mon, Feb 06
LOCATION: Neuroscience Research Building (NRB) Auditorium, Room 132
Overcoming Bias and Batch Effects in High-throughput Biological Data
Rafael Irizarry, PhD, Professor of Applied Statistics, Dana Farber Cancer Institute and Harvard University
Contact & Intro: Jessica Li
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ABSTRACT: In this talk I will demonstrate the presence of bias, systematic error and unwanted variability in next generation sequencing. I will show the substantial downstream effects these have on downstream results and how they can lead to misleading biological conclusions. I will do this using data from the public repositories as well as our own. We will then describe some preliminary solutions to these problems.

Mon, Feb 13
Genome function and evolution through the lens of human genetics
Shamil Sunyaev, PhD, Professor of Biomedical Informatics, Harvard Medical School and Professor of Medicine, Brigham and Women's Hospital, Harvard Medical School
Contact & Intro: Kirk E. Lohmueller, x 57635
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ABSTRACT: Large-scale human genetic data provide a new perspective on genome evolution and function. Sequencing datasets enable estimation of fitness cost of heterozygous loss of function (LoF) alleles. The distribution of LoF alleles in the population is consistent with synergistic epistasis, which has been long suspected on theoretical grounds related to the mutation load argument. For noncoding variants, a combined analysis of dense genotyping and epigenetic data reveals new clues about their functional significance but also brings up new puzzles.

Mon, Feb 27
LOCATION: Neuroscience Research Building (NRB) Auditorium, Room 132
Understanding Rare Diseases: Bringing together basic science and patient care through the Undiagnosed Diseases Network
Drs. Stanley Nelson and Christina Palmer, Principal Investigators of The Undiagnosed Diseases Network (UDN)
Contact & Intro: Christina Palmer x 44796
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ABSTRACT: Special Presentation by:

Stan Nelson, MD, UCLA Department of Human Genetics, Pathology and Laboratory Medicine

Christina Palmer, PhD, UCLA Department of Psychiatry & Biobehavioral Sciences, Human Genetics, and Institute for Society and Genetics

Rare diseases, when considered as a group, can affect up to 10% of the U.S. population and all too often result in diagnostic odysseys for patients. The February 28 Rare Disease Day slogan 'With research, possibilities are limitless' signifies the importance of a team science approach for solving and treating rare diseases. The Undiagnosed Diseases Network (UDN) is a multi-center effort of clinical and basic scientists working together to record the spectrum of phenotypes associated with previously unrecognized diseases and tackle the molecular diagnosis of these ultra-rare disorders in patients who, despite prior extensive clinical and/or genetic workup, have not had the cause(s) of their disease identified. In this presentation, we describe the UCLA Clinical Site’s experience with the team science approach.

Mon, Mar 06
Selective Inference in Genetics
Chiara Sabatti, PhD, Professor of Biomedical Data Science and of Statistics, Stanford University
Contact & Intro: Nelson Freimer x 46427
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ABSTRACT: Geneticists have always been aware that, when looking for signal across the entire genome, one has to be very careful to avoid false discoveries. Contemporary studies often involve a very large number of traits, increasing the challenges of “looking every-where”. I will discuss novel approaches that allow an adaptive exploration of the data, while guaranteeing reproducible results.

Thu, Mar 09
LOCATION: Center for Health Sciences (CHS) Room 13-105; Jointly Sponsored by: Clinical and Translational Science Institute (CTSI) Institute for Precision Health (IPH)
GenomeFIRSTTM a New Paradigm for Return of Genomic Results
Marc S. Williams, MD, FAAP, FACMG, FACMI; Professor and Director Genomic Medicine, Institute Geisinger Health System
Contact & Intro: Daniel Geschwind, x 46570
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ABSTRACT: Objectives: At the end of the presentation attendees should be able to:

• Describe the difference between Phenome first and Genome first medicine • Define what constitutes actionability of a gene and pathogenicity of a variant • Discuss the potential utilities (positive and negative) of a Genome first approach • Understand the importance of familial cascade screening as an integral component of genomic medicine.

Mon, Mar 13
LOCATION: Neuroscience Research Building (NRB) Auditorium, Room 132
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.

Thu, Mar 16
LOCATION: Neuroscience Research Building (NRB) Auditorium, Room 132; Co-sponsored by: UCLA Center for Medieval & Renaissance Studies; Department of Psychiatry and Biobehavioral Sciences; Department of History; and Cotsen Institute of Archaeology
King Richard III: the resolution of a 500 year old cold case
Turi King, PhD, Reader in Genetics and Archaeology, University of Leicester
Contact & Intro: Paivi Pajukanta, x 72011
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ABSTRACT: King Richard III was one of the few English kings for whom the precise location of his grave had been lost. In 2012, during an excavation, his putative remains were found underneath a carpark in Leicester. Dr Turi King led the genetic analysis which led to the identification of the remains as those of King Richard III. Dr Turi King will discuss the case from the very beginning covering the archaeology, osteology, forensics, genealogy, and genetics, through to his identification and reburial in Leicester Cathedral.

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