To kick-off the ASHG 2024 Annual Meeting, ASHG President, Dr. Bruce Gelb will provide a warm welcome to ASHG’s global audience with his Presidential Address and Welcome.

This session highlights cutting-edge research being conducted across the field of human genetics and genomics. This includes examination of natural selection in mosaic chromosomes, meiotic recombination in in vitro fertilized embryos, uniparental disomy in congenital heart disease, long-read sequencing to identify alternative RNA-splicing, the power of combining biobanks together to discover rare variant associations.

Learning Objectives:

1. Summarize the landscape of mosaic chromosomal alterations (mCA’s) across 66,000 individuals from diverse and understudied populations, including how gene expression can reveal evolutionary dynamics of clonal expansion within individuals.
2. State how the use of preimplantation genetic testing (PGT) data from in vitro fertilized (IVF) embryos can elucidate the process of meiotic recombination and its complex genetic architecture.
3. Summarize how uniparental disomy (UPD) events, some of which include variants of uncertain significance (VUS), have been linked to congenital heart disease (CHD) and the related phenotypes observed in zebrafish experiments.
4. Formulate an experiment using a new method, isoLASER, to leverage long-read RNA-seq data to classify splicing events via cis- or trans-directed mechanisms.
5. Generalize findings from rare variant association testing within a global biobank meta-analysis consortium.

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

Biobank scale genetic data resources for studying complex and rare human diseases are introduced in this session, including 100K Genomes of Europe, UAE Genome Program with 43K individuals, Structural variants from the All of US Research Program, and a complete telomere-to-telomere reference pnael of 6K human haplotypes. Updates about diversity in the NHGRI-EBI GWAS Catalog will be shared. A web resource of Mondo harmonizes the world's rare disease knowledge, which will help rare disease diagnosis.

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

Freida Blostein, PhD

Xuanyao Liu, PhD

Anthony Herzig

Michael Olbrich, PhD

Emma Pierce-Hoffman, B.S.

Joseph Lalli, BA

Maria Cerezo, PhD

Jonathan Berg, MD, PhD

While we know have an increased appreciation for the regulatory roles of the non-coding genome, there are still many regions which remain to be defined. This session will leverage cross-species comparisons, epigenetic approaches and machine learning to interpret the non-coding genome. Moreover, massively parallel reporter assays are an increasingly attractive technology for functionally testing the regulatory potential of non-coding DNA at scale, the use of this technology will also be presented.

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

Jacqueline J Harris, PhD

Jeffrey Calhoun, PhD

Brianne Rogers, PhD

Janet Song, PhD

Amber Zimmerman, PhD

William DeGroat

Minhui Chen, PhD

Anusri Pampari, PhD

The challenge of missing heritability is well documented. This session moves beyond standard models of genetic architecture to learn how the complex evolutionary history of a species has shaped different aspects of complex traits.

Learning Objectives:
1. Identify key determinants of gene discovery in Genome Wide Association Studies (GWAS) and Rare Variant Association Studies (RVAS).
2. Examine the influence of admixture in complex diseases.
3. Compare ethnolinguistic, genetic, and geographic data to improve our understanding of genetic variation and ethnolinguistic diversity in eastern and southern African populations and the relationship between them.
4. Identify genetic variants under ongoing natural selection that contribute to disease susceptibilities

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

Charleston Chiang, PhD

Abiodun Olowo, MS

Hakhamanesh Mostafavi, PhD

Michelle Kim, PhD

Mary T. Yohannes, MS

Jing-Lian Chen, MS

Since the origins of the field of human genetics nearly 125 years ago, there have been robust conversations about how to characterize genetic traits and disorders across the range from simple to complex. The intellectual framework has great importance in how human genetics is applied, particularly in an era when population genetic screening for so-called single-gene disorders has become increasingly feasible. The 2024 Presidential Symposium will feature three leaders across aspects of this topic: the history of the intellectual debate over simplicity vs. complexity in human genetics; understanding how genetic complexity modifies a paradigmatic simple genetic trait, sickle cell disease; and how randomness (i.e., stochasticity) contributes to phenotypes.

Learning Objectives:
1. Compare simplicity-first (Mendelian) and complexity-first (Weldonian) framings for an elementary genetics curriculum
2. Recognize that sickle cell disease is a monogenic disorder that shows wide variability in clinical outcomes, in part, due to the presence of genetic modifiers
3. Recognize how experiments in gene-edited model organisms can provide insights into the dynamic emergence of developmental defects, focusing on stochastic contributions to partial penetrance

The Trans-Omics in Precision Medicine (TOPMed) project of the National Heart, Lung, and Blood Institute (NHLBI) has supported genomic data generation and harmonization for many U.S. and international-based studies. These include deep whole-genome sequencing (WGS) data and omics datasets. TOPMed is one of the largest resources of WGS and omics (>180,000 WGS, >70,000 funded methylation, RNA-seq, and metabolomics assays, >40,000 proteomics). Importantly, the TOPMed program focuses on data collection from under-studied and under-represented populations such as Hispanic and Latino individuals in the U.S., African, and African American individuals. This session will highlight the 10th anniversary of the TOPMed program and focus on the future use of the TOPMed resource by the broader research community. The session will begin with an “overview of TOPMed” talk by Dr. Gan, the NHLBI program director who oversees TOPMed, describing the vision that motivated TOPMed, highlight major TOPMed milestones, and introduce the vision for the next step of TOPMed. Dr. Gan will also cover the current process for accessing TOPMed data and ideas to improve the process. Four talks will follow highlighting findings enabled by TOPMed: insights into genetic diversity, selection, and population dynamics from large scale sequencing, and findings from integration of omics and genetics. A panel discussion will introduce additional achievements, gaps, and outline to the community how they can use this massive resource.

Learning Objectives:
1. Describe inference and implications of genetic effects at the population levels from ultra-rare genetic variants
2. Identify mechanisms by which trans-eQTLs impact gene expression
3. Examine genetic influences on circulating metabolites with diverse populations via a novel, large multi-ancestry harmonized metabolomics data set
4. State new findings about how proteins causally affect other proteins in human plasma and use of genetic data to infer these relationships

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

Weiniu Gan, PhD

Miguel Guardado

This section will focus on applying novel technologies to access gene regulation networks, understand complex disease mechanism, and deep learning approaches for sequencing data analysis and rare variant interpretation.

Learning Objectives:
1. State the advantages of multimodal single cell sequencing in defining CRISPR induced genetic variation.
2. Identify the gene regulatory mechanisms downstream of neuron-astrocyte interactions.
3. Evaluate the relationship between circRNA function and Alzheimer's disease.
4. Construct an in silico module for comprehensive gene regulatory networks analyses.
5. Design novel methods and deep learning approaches for sequencing data analysis.
6. Define a new approach to interpret rare variants when the goal is to identify a sub-population at low risk of disease

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

Jonathan Berg, MD, PhD

Yuxin Fan, MD, PhD

Yuriy Baglaenko, PhD

Boxun Li, PhD

Feng Wang, PhD

Zechuan Shi

Siying Yang, Master of Science

Alexandre Bolze, PhD

This session showcases state-of-the-art methods for prioritizing causal risk variants in complex trait genetic studies.

Learning Objectives:
1. Identify genetic variants associated with transcription factor binding in liver.
2. Examine using machine learning to predict and prioritize the effects of non-coding variants on diseases, leveraging functional annotations and GWAS data to identify causal variants and gain biological insights.
3. Manage robustness of summary statistics-based methods under LD mismatch.
4. Evaluate whether current genome language and other deep learning models can help pinpoint causal variants in statistical fine-mapping

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

Xihao Li, PhD

Arbel Harpak, PhD

Max Dudek, BS

Siliangyu Cheng, MS

Wenmin Zhang, PhD

Michael Sweeney, MS

This session highlights high scale profiling efforts using different experimental platforms and in different disease settings. This includes heritability analysis in environmental risk and air pollution, methylome and omics (GWAS, TWAS, PWAS) analysis in cancer, global profiling of Cas9 editing sites, and transcriptomics in rare disease.

Learning Objectives:
1. Evaluate several novel strategies for jointly modeling genetic and environmental effects on disease risk using large EHR datasets.
2. Examine how early methylation changes occur and how they interact with other epigenomic shifts.
3. Identify critical pathways in endometriosis pathogenesis using omics approaches.
4. Apply a new sequencing method for targeted pooled and in vivo ribonucleoprotein CRISPR screens in hard-to-transduce cell types and detection of off-target perturbations.
5. Judge a transcriptomics-first method to diagnose rare disease patients by examining transcriptome-wide patterns of minor intron retention events.

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

Fernando Scaglia, MD

Marina DiStefano, PhD

Havell Markus

Hayan Lee, PhD

Lindsay Guare

Graham McVicker, PhD

Taylor "Maggie" Margaret Maurer, BA

Genomic sequencing has been used within the clinic for over a decade, yet our understanding of clinically significant genetic variation is largely limited to the protein-coding genome. Although international efforts are underway to systematically interrogate which non-coding genetic variants are clinically significant, translating these findings into clinical medicine remains a challenge. In this session, we will synthesize the literature on hundreds of clinically significant non-coding genetic variants that are known to cause Mendelian conditions via the disruption of gene regulatory elements. In addition, we will discuss the barriers that exist for describing these non-coding variants, as well as ascribing clinical significance to them. Specifically, we will go over challenges that are encountered when assigning nomenclature to regions outside of what is commonly defined as a “gene”. We will then explore challenges with annotating and summarizing the functional impact and clinical significance of non-coding variants within clinically-facing databases like ClinVar. Finally, we will provide examples of syndrome discovery in the Genomics England 100,000 Genomes Project using the recent ACMG/AMP guidelines for interpretation of non-coding variants. The session will end with a panel discussion that will explore how we can overcome these barriers to translate ongoing efforts to annotate the function of the non-coding genome into clinical medicine.

Learning Objectives:
1. Recognize our current knowledge of how non-coding variants contribute to Mendelian conditions
2. Summarize the current naming strategies for elements of the human genome
3. Evaluate how existing guidelines can be adapted for classifying non-coding variation
4. Identify critical data elements to describe functional effects of a variant in a database

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

Wen-Hann Tan

Hope Tanudisastro, BS

Andrew B Stergachis, MD, PhD

Elspeth Bruford, PhD

Melissa Landrum, PhD

Nicola Whiffin, PhD

This session features a collection of abstracts that employ multi-omic data to enhance our understanding of disease susceptibility. It emphasizes analyses involving mitochondrial DNA, leukocyte telomere length, and copy number variations. The abstracts extend beyond genomic data, incorporating various types of omics data to provide a comprehensive view of disease mechanisms. Notably, the session includes innovative approaches to mitochondrial DNA analysis. The speakers contributing to this session are notably diverse, further enriching the breadth of perspectives and expertise presented.

Learning Objectives:
1. Describe the utility of using genetic instruments at scale to disentangle age related disease mechanisms and provide strong support for previously reported relationships between telomere length and human health.
2. Explain the power of deep facial phenotyping and incorporating transcriptomics when analyzing whole genome sequencing data.
3. Recognize genetic factors leading to epistatic relationships of dosage sensitive genes.
4. Identify nuclear genetic loci associated with mitochondrial heteroplasmy.
5. Analyze the role of structural variants in disease.
6. Identify alignment patterns associated with complex genomic rearrangements

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

Satoshi Koyama, MD, PhD

Jennifer Huffman, PhD

Azeez Alade, PhD

Corrine Smolen, MS

Santosh Atanur, PhD

Peter Audano, PhD

This session highlights omics efforts (with a particular focus on sequencing in rare disease cohorts) from different institutions or large-scale projects, including efforts in Germany, the Netherlands, South Africa, and the United States.

Learning Objectives:
1. Summarize how research genomics can impact clinical care.
2. Recognize the challenges and solutions for integration of ultra rapid whole genome sequencing in hospitals.
3. Analyze the clinical utility of HiFi sequencing as a first tier clinical test and how it affects, patient management, and multidisciplinary collaboration.
4. Examine the complex interplay between the gut microbiome and geographical, lifestyle, genetic, and environmental factors in populations from low- and middle-income countries

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

Qiliang (Andy) Ding, PhD

Courtney French, PhD

Luicer Olubayo, PhD

This session will be of interest to researchers and clinicians interested in learning about novel techniques to link large ancient DNA and modern datasets, and a novel technique for resolution of CNVs in complex regions of the genome that had previously been inaccessible. Attendees will then transition from basic science to clinical implementation through talks on how caQTL may help identify a layer of immune response regulation and enhance the prediction of complex disease risk, how genetic variation influences healthcare expenditure. The session will conclude with the results of a prospective pilot study to evaluate sequencing of a targeted set of genes for newborn screening in a diverse population.

Learning Objectives:
1. Recognize the genetic contribution to healthcare cost and poor health.
2. Illustrate a new computational tool for inferring genealogical relationships in modern and ancient DNA.
3. Resolving the remaining dark regions of the human genome.
4. Investigate the opportunities, challenges, and feasibility of DNA sequencing-based newborn screening.
5. Assess the contribution of chromatin accessibility differences to transcriptional immune variation across healthy individuals

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

A major goal of human genetics and genomics research is to understand, treat, and correct genetic diseases and alleviate patient suffering. However, moving discoveries from the bench to the bedside can be both daunting and lengthy. The 2024 Distinguished Speakers Symposium will feature leaders who have made important basic science discoveries and navigated the journey from discovery to drug development, clinical trials, and implementation of new therapies. Their work has given hope to patients and framed the ethics, policy, and communication around ground-breaking genetics and genomics research.

Gillian Hooker, PhD, ScM, CGC

David Goldstein, PhD

Heather Hampel, MS, CGC

David Altshuler, MD, PhD

Crystal Lumpkins, PhD, MA, FSBM

Lizeth Tamayo, PhD

Interested in learning more about self-advocacy or negotiating and transitioning into a new role? Attend the Career Development Committee’s Annual Meeting Event, How to Set Yourself Apart. During this lunchtime panel, you will hear from 3 experienced panelists who have knowledge across academia and industry on personal branding, self-advocacy, and making a career transition. Learn how to be your best advocate by combining skills you already have and using them to negotiate your next step or transition to a new job.

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

During this session, a range of stakeholders will participate in a panel discussion to highlight the role of Artificial Intelligence and Machine Learning in accelerating genetic research by examining policy frameworks for risk as well as other considerations for responsible use.

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

ASHG Professional Practice and Social Implications (PPSI) committee-led discussion with a speaker panel and audience engagement on a topic related to the committee's ongoing work in the ethical, legal, and social implications of human genetics research.

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

The UCSC Genome Browser is a widely used tool for both clinical genetics and in the research lab. A visualization tool that combines data from a host of projects in an easy-to-use graphical interface, the Browser allows scientists to explore a wide variety of data types, using their own intuition to guide the configuration of the data. To keep the Browser interface from becoming overwhelming, it has been necessary to make only a subset of features obvious to the user. Based on years of experience in workshops, we know that many of the most interesting features have not been discovered by even experienced users. 

This workshop will begin with a demonstration of these features, including and especially, recently released user-controlled options. Workshop participants will use these features in service of solving problems. Interactive elements will include exercises designed to put the new features into practice. Participants will create, save and share their sessions with each other. The workshop is designed for the new generation of geneticists who have not grown up with the Browser during its 24 years of development, highlighting data sets that are used most frequently in interpreting variants, both CNVs and SNVs. Participants will learn how to use the highlight tool enhance their Browser view, how to save and share sessions and how to export high-resolution images for publication. Participants should bring a fully charged laptop and expect to participate.

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.

The NIH's All of Us data is a significant source of biomedical and genomic data with 245,400 short-read whole genome sequences (WGS), 1,040 long-read WGS, 11,400 short-read WGS with structural variant calls, and 312,940 genotyping arrays. The genomic data are from participants who have also shared phenotypic data, including from electronic health records, drug exposures, procedures, physical measurements, Fitbits, and surveys. New data are released every year with ongoing engagement of one million participants planned. Researchers from institutions with Data Use and Registration Agreements (DURAs) access and analyze the data on the online platform, the All of Us Researcher Workbench. This workshop will take attendees through interactive exercises to become familiar with the All of Us data and begin research with it. First, attendees will perform a data quest on the All of Us Research Hub to browse and query the available data and to examine current projects. Then attendees will complete an exercise to learn the unique tools of the Researcher Workbench and how they are used to access and analyze the data. We will demonstrate a GWAS in interactive Jupyter Notebooks using Hail, a cloud-compatible genomic data analytic tool with efficiency and scalability to handle the large dataset. Example notebooks will be provided to the attendees. We will also address importing external (local or cloud-based) data in the Researcher Workbench. The close of the workshop will be a Q&A session.

Please note: This item is only available as part of the ASHG 2024 Annual Meeting Digital Pass.