Seminar: The search for autosomal recessive genes
Speaker: Prof. Stylianos Emmanuel Antonarakis
Professor Emeritus (active), University of Geneva Medical School, Geneva Switzerland
Honorary Member, Swiss Academy of Medical Sciences
Member of the Academy of Athens, Greece
Host: Prof. Lina Ma
Time: 10:30－11:30, May 11th, 2026
Location: The first floor conference room, CNCB
Abstract:
Consanguineous unions, while increasing the risk of recessive disorders, provide a powerful genetic paradigm for gene discovery. Offspring from consanguineous parents inherit large, identical-by-descent genomic segments, effectively acting as natural in vivo experiments that unmask homozygous pathogenic variants. This homozygosity mapping strategy, particularly when integrated with genomic sequencing exploration, has proven highly effective in characterizing the molecular basis of numerous rare diseases. We estimated that more than 7000 autosomal recessive disorders in humans are still unknown. We have focused on consanguineous populations with the phenotypes of intellectual disability or visual impairment and used genomic analyses to pinpoint causative variants within shared regions of homozygosity to identify new disease genes. This approach has led to the identification of more than 65 novel disease genes across these phenotypic spectra. Functional validation using model organisms such as Drosophila, zebrafish and mice confirms the pathogenicity of identified variants. Ultimately, the systematic study of consanguineous families not only elucidates the genetic architecture of autosomal recessive conditions but also directly informs genetic counseling and bridges the critical gap between genotype and rare disease phenotypes. In some cases, immediate therapeutic strategies can be implemented based on the pathophysiology of a specific molecular defect. Examples of new fundamental insights into disease mechanisms (CIZ1 gene), and therapeutic applications (SLC6A6 gene) will be presented.
Speaker introduction：
Stylianos Emmanuel Antonarakis is Professor Emeritus at the University of Geneva Medical School, Switzerland, an Honorary Member of the Swiss Academy of Medical Sciences, and a Member of the Academy of Athens, Greece. The primary objective of his research is to elucidate how genetic variation drives phenotypic diversity. His work encompasses the molecular characterization of single-gene disorders (including thalassemias and hemophilias), the application of DNA polymorphisms in clinical medicine, the molecular predisposition to Down syndrome and mechanisms of non-disjunction, and the study of apolipoprotein genes in premature coronary artery disease. He has made pioneering contributions to the understanding of the molecular mechanisms of Down syndrome, the genetics of hemophilia, and the Human Genome Project. Dr. Antonarakis has authored over 750 scientific papers, which have garnered more than 160,000 citations, resulting in an H-index of 169. He previously served as President of the Human Genome Organization (HUGO) and is the recipient of numerous prestigious awards, including the William Allan Award from the American Society of Human Genetics.
