A study titled "Aggregation of population-based genetic variation over protein domain homologues and its potential use in genetic diagnostics" was recently accepted for publication in Human Mutation.
his work was a collaborative effort between Christian Gilissen, Department of Human Genetics, and Gert Vriend, Centre for Molecular and Biomolecular Informatics.
This publication is part of the PhD project of Laurens van de Wiel and shows how homologous protein domain relations may be used to interpret normal and pathogenic variation at a much finer scale than previously possible.
“We developed a framework that maps population variation and known pathogenic mutations onto 2,750 “meta-domains.” These meta-domains consist of 30,853 homologous Pfam protein domain instances that cover 36% of all human protein coding sequences. We find that genetic tolerance is consistent across protein domain homologues, and that patterns of genetic tolerance faithfully mimic patterns of evolutionary conservation. Furthermore, for a significant fraction (68%) of the meta-domains high-frequency population variation re-occurs at the same positions across domain homologues more often than expected. In addition, we observe that the presence of pathogenic missense variants at an aligned homologous domain position is often paired with the absence of population variation and vice versa.”
Related news items
Jong KNCV organizes a Pitch competition for PhD candidates13 August 2020
Are you a PhD candidate and would you like to win 500 euros with a pitch about your research? Young KNCV gives you that chance! During the KNCV Chemistry 2020 Evening on October 8th.read more
Collective invasion induced by autocrine purinergic loop through connexin-43 hemichannels13 August 2020
Peter Friedl and Paul Span show in Journal of Cell Biology that breastcancer cells release purines into the extracellular space via connexin-43 hemichannels to control collective invasion.read more
TP53 allelic state is critical for diagnostic and prognostic precision in blood cancer12 August 2020
An international study, in which Joop Jansen participated, shows that a double mutaton in TP53 gene deteriotes the prognosis of a rare form of blood cancer. If there is only one mutation or no mutation, then the prognosis is better.read more
BCG vaccine is safe with no increased risk of COVID-19 symptoms says Mihai Netea11 August 2020
The BCG vaccine has a general stimulatory effect on the immune system and is therefore effective against multiple infectious diseases - possibly also against COVID-19.read more
650,000 Euro funding for research into the phasing out of medication for leukaemia patients30 July 2020
With a 650,000 euro funding from ZonMw, researchers from the Haematology and Pharmacy departments can develop a medication phasing out strategy for patients with chronic myeloid leukaemia. This strategy will be tested in practice.read more
Increased role of patients after bowel cancer treatment30 July 2020
Approximately 14,000 patients get colorectal cancer every year. Almost all patients are operated on and monitored afterwards (follow-up). In 2019 Radboudumc started a new approach to follow-up research after the treatment of stage II/III colorectal cancer.read more