Lude Frank, PhD
Professor of Functional Genomics
University of Groningen
Reconciling germline and somatic variation through regulatory network integration
Germline and somatic genetic variation is known to cause many different diseases, but the genetic architecture differs tremendously between different types of disease. In the last few years many germline variants have been found that either cause Mendelian disease or are associated to complex diseases – yet most Mendelian diseases appear to be caused by coding mutations, whereas complex diseases are mostly due to non-coding variants.
We recently obtained proof-of-concept that these complex-disease-associated, non-coding germline variants show regulatory effects that converge downstream onto genes that cause Mendelian forms of these traits, indicating a clear relationship between these two seemingly disparate classes of disease. For instance, various loci associated to systemic lupus erythematosus show converging trans-eQTL effects on type 1 interferon response genes, and genes within loci associated to height show strong co-regulation with genes that cause Mendelian forms of extreme skeletal deformities
