Medical Genetics seminars

Junjie Guo investigates how an intronic nucleotide-repeat expansion in C9orf72 causes familial and some sporadic cases of amyotrophic lateral sclerosis and frontotemporal dementia. The talk presents progress in understanding how the expansion changes gene expression, alongside functional-genomics approaches that identify potential therapeutic targets controlling expression of the pathogenic mutation. It also considers which mechanisms and modifiers extend to other disease-causing repeat expansions. Guo is Associate Professor of Neuroscience at Yale School of Medicine; the seminar is hosted by J. Wren Kim. Online via CUNY ASRC Zoom. Thursday 8 October 2026, 12:00–13:00 EDT (America/New_York; UTC−4). Follow the Zoom link on the official seminar page; meeting details are also supplied in its abstract PDF. Organized by the Advanced Science Research Center at the CUNY Graduate Center, Neuroscience Initiative. This listing advertises remote attendance.

Peter Meikle, Bernie Pope and Tingting Wang present the Australian Cardiovascular disease Data Commons (ACDC). Some heart attacks occur without established risk factors, and repeat events remain common despite optimal treatment. ACDC addresses this gap by securely pooling multi-omics, imaging and longitudinal outcomes from approximately 400,000 people in 18 Australian cohorts. The webinar explains cloud infrastructure, data harmonisation and federated standards based on Gen3; how integrated genomic, multi-omics and imaging cohorts support new risk markers and polygenic risk-score testing; and how the platform can move diagnostic research towards clinical practice. Meikle and Wang are at the Baker Heart and Diabetes Institute; Pope is at Australian BioCommons. Online via Zoom. Wednesday 30 September 2026, 12:00–13:00 AEST (Australia/Melbourne; UTC+10). Free, with advance registration through the official event page. Intended for life scientists, bioinformaticians, cardiovascular clinicians, data custodians and medical data scientists. Parts may be recorded; the Australian BioCommons Code of Conduct applies. Organized by Australian BioCommons.

Shimon Sakaguchi, Mary E. Brunkow and Fred Ramsdell explain how peripheral immune tolerance prevents the immune system from attacking the body. Sakaguchi follows the identification of regulatory T cells, the CD25 marker, and the relationship between central tolerance and active suppression of self-reactive cells. He considers how changing regulatory T-cell activity could support cancer treatment and transplantation. Brunkow describes genetic investigation of scurfy mice, identification of FOXP3, and the connection between mutations in this gene and human IPEX syndrome. The work establishes a molecular basis for the development and function of regulatory T cells. Ramsdell traces the move from these basic discoveries toward therapeutic strategies, including engineering a patient’s regulatory T cells to target inflammation in rheumatoid arthritis. He discusses early clinical investigation and the ambition of restoring immune balance; these approaches are presented as developing treatments rather than established cures.

A hallmark pathological feature of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion of RNA-binding protein TDP-43 from the nucleus of neurons in the brain and spinal cord. A major function of TDP-43 is as a repressor of cryptic exon inclusion during RNA splicing. By re-analyzing RNA-sequencing datasets from human FTD/ALS brains, we discovered dozens of novel cryptic splicing events in important neuronal genes. Single nucleotide polymorphisms in UNC13A are among the strongest hits associated with FTD and ALS in human genome-wide association studies, but how those variants increase risk for disease is unknown. We discovered that TDP-43 represses a cryptic exon-splicing event in UNC13A. Loss of TDP-43 from the nucleus in human brain, neuronal cell lines and motor neurons derived from induced pluripotent stem cells resulted in the inclusion of a cryptic exon in UNC13A mRNA and reduced UNC13A protein expression. The top variants associated with FTD or ALS risk in humans are located in the intron harboring the cryptic exon, and we show that they increase UNC13A cryptic exon splicing in the face of TDP-43 dysfunction. Together, our data provide a direct functional link between one of the strongest genetic risk factors for FTD and ALS (UNC13A genetic variants), and loss of TDP-43 function. Recent analyses have revealed even further changes in TDP-43 target genes, including widespread changes in alternative polyadenylation, impacting expression of disease-relevant genes (e.g., ELP1, NEFL, and TMEM106B) and providing evidence that alternative polyadenylation is a new facet of TDP-43 pathology.

This lecture examines how deletions, duplications and rearrangements of genomic material influence phenotype. Structural variants appear in both clinical and general-population cohorts. Their effects are considered through variable expressivity and through direct or indirect influences on multiple traits.

This lecture examines how genetic predisposition interacts with environmental exposure in disease. It reviews methods for detecting these interactions, the role of large biobanks and examples including obesity. Gene regulation and environmentally influenced epigenetic changes provide possible molecular mechanisms.

Autism-associated variation ranges from individual genetic changes to the combined influence of many variants. This seminar examines how implicated genes affect synaptic number and function, connecting genetic diversity with brain connectivity. It also considers research conducted with autistic people and families, and how that participation can inform care, education, inclusion and efforts to reduce stigma.

This lecture examines how regulatory DNA contacts its target genes through both CTCF-dependent and other mechanisms. It then considers diseases caused by disrupted enhancer function, ranging from missing elements to genomic rearrangements that alter regulatory contacts. Transposable elements are discussed as contributors to the evolution of gene regulation.

This lecture examines traits and diseases influenced by many genetic variants. It introduces genome-wide association studies, pleiotropy and polygenic risk scores, then considers their use in precision medicine. Outstanding limitations include unexplained heritability and the uneven representation of human populations in genomic research.

Inherited differences help explain why infections affect individuals differently. This seminar follows the route from genomic discovery and data analysis to more individualized infectious-disease care. HIV and hepatitis C illustrate how human genetic variation can reveal disease mechanisms and guide translational research.

This lecture reviews genetic explanations for single-gene disorders through Mendelian inheritance and examples such as achondroplasia. Whole-genome sequencing helps identify causal variants, while comparisons of rare and common mutations illuminate disease mechanisms. The discussion also considers what transcriptomic and proteomic measurements add to clinical genetic investigation.

This seminar examines genetic contributions to obesity and type 2 diabetes alongside their major health consequences. It challenges explanations based solely on personal behaviour and discusses how genetic studies can inform individualised care. The presentation also considers the discovery of treatment targets through research on disease-associated variants.

Studies of families with inherited breast-cancer risk led to BRCA1 and subsequently many other susceptibility genes. This seminar examines how large-scale sequencing and population studies have refined tumour associations and penetrance estimates. It moves from a simple dominant-inheritance model toward multifactorial risk, considering genetic and environmental modifiers that could support individualized surveillance and management.

Pluripotent cells, including embryonic stem (ES) and induced pluripotent stem (iPS) cells, are used to investigate the genetic and epigenetic underpinnings of human diseases such as Parkinson’s, Alzheimer’s, autism, and cancer. Mechanisms of somatic cell reprogramming to an embryonic pluripotent state are explored, utilizing patient-specific pluripotent cells to model and analyze neurodegenerative diseases.

The development of the iPS cell technology has revolutionized our ability to study development and diseases in defined in vitro cell culture systems. The talk will focus on Rett Syndrome and discuss two topics: (i) the use of gene editing as an approach to therapy and (ii) the role of MECP2 in gene expression (i) The mutation of the X-linked MECP2 gene is causative for the disease. In a female patient, every cell has a wt copy that is, however, in 50% of the cells located on the inactive X chromosome. We have used epigenetic gene editing tools to activate the wt MECP2 allele on the inactive X chromosome. (ii) MECP2 is thought to act as repressor of gene expression. I will present data which show that MECP2 binds to Pol II and acts as an activator for thousands of genes. The target genes are significantly enriched for Autism related genes. Our data challenge the established model of MECP2’s role in gene expression and suggest novel therapeutic approaches.

Neurodevelopmental disorders (NDDs) impose a global burden, affecting an increasing number of individuals. While some causative genes have been identified, understanding the human-specific mechanisms involved in these disorders remains limited. Traditional gene-driven approaches for modeling brain diseases have failed to capture the diverse and convergent mechanisms at play. Centrosomes and cilia act as intermediaries between environmental and intrinsic signals, regulating cellular behavior. Mutations or dosage variations disrupting their function have been linked to brain formation deficits, highlighting their importance, yet their precise contributions remain largely unknown. Hence, we aim to investigate whether the centrosome/cilia axis is crucial for brain development and serves as a hub for human-specific mechanisms disrupted in NDDs. Towards this direction, we first demonstrated species-specific and cell-type-specific differences in the cilia-genes expression during mouse and human corticogenesis. Then, to dissect their role, we provoked their ectopic overexpression or silencing in the developing mouse cortex or in human brain organoids. Our findings suggest that cilia genes manipulation alters both the numbers and the position of NPCs and neurons in the developing cortex. Interestingly, primary cilium morphology is disrupted, as we find changes in their length, orientation and number that lead to disruption of the apical belt and altered delamination profiles during development. Our results give insight into the role of primary cilia in human cortical development and address fundamental questions regarding the diversity and convergence of gene function in development and disease manifestation. It has the potential to uncover novel pharmacological targets, facilitate personalized medicine, and improve the lives of individuals affected by NDDs through targeted cilia-based therapies.