Webinar 2: April 8th, 2024
Please note that this video has been edited to remove pauses due to technical difficulties
First talk:- Beyond the exome: Solving the unsolved rare diseases
Speaker: Prof. Dr. med. Olaf Riess (University of Tübingen)
Abstract: About 80% of all rare diseases are caused by genetic changes in the genome. Wit the best standard of care, which is not widely implemented throughout Europe yet, whole exome diagnostic is applied to find these genetic causes. However, diagnostic sensitivity is barely above 40% of all patients analysed, even if clear family information indicated a genetic cause of the underlying disease. Thus, other disease mechanisms have to be considered “beyond the exome” which need to be implemented into the diagnostic process. First step in this direction is the sequencing of the entire genome in diagnostics, but despite of lack of knowledge and due to limited bioinformatic tools we increase diagnostic sensitivity only by about 6% in total. Complementary transcriptome sequencing by RNASeq further delivers data sets to identify potential genetic alterations. With my talk I will give an overview on sequencing several thousand RD patients in the diagnostic setting and provide examples of solving cases. Also, I will cover advantages of long read sequencing in clinical care.
Second talk:- cis-eQTL mapping of TB-T2D comorbidity elucidates the involvement of African ancestry in TB susceptibility.
Speaker: Dr. Yolandi Swart (Stellenbosch University)
Abstract: The validation of genome-wide association signals for tuberculosis (TB) susceptibility as well as the development of type 2 diabetes (T2D) across diverse populations are ongoing challenges. Identifying ancestry-specific expression quantitative trait loci (eQTLs) can aid in distinguishing the most probable disease-causing variants for population-specific therapeutic interventions. Therefore, cis-eQTL mapping was conducted in healthy controls, T2D-, TB- and TB-T2D patients. Both genotyping (Infinium H3A array with ~2.3 M markers) and RNA sequencing data of 96 complex multi-way admixed South Africans were used. Unique gene-variant pairs were associated with TB-T2D on chromosome 7p22 whilst adjusting for Bantu-speaking African ancestry and Khoe-San ancestry . In addition, IFITM3(a biomarker for the development of TB) was associated with three eSNPs on chromosome 11p15 while adjusting for Khoe-San ancestry. Our results also indicated that the upregulation of the NLRP6 inflammasome is strongly associated with people with TB-T2D while adjusting for Khoe-San ancestry. Two African-specific eGenes (IFITM3 and PRKAR1B) would therefore have been missed if local ancestry adjustment was not conducted. The incorporation of local ancestry in cis-eQTL mapping lead to the discovery of ancestry-specific eQTLs in a five-way admixed southern African TB-T2D cohort.
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