4 September 2017

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.”

Publication: link

Related news items


4,8 million euros for prevention of tuberculosis among people with diabetes in Africa

16 July 2019

Reinout van Crevel and Lindsey te Brake have received European funding of 4.8 million euros to lead an international consortium to screen thousands of people with diabetes in Uganda and Tanzania for TB, and investigate the effect and costs of 3 months preventive treatment for TB.

read more

50.000 grant for Paul de Jonge and Harry Dolstra

15 July 2019

Paul de Jonge and Harry Dolstra, theme Cancer development and immune defense, received a €50.000,- (NWA-IDG) grant for their project regarding cancer immunotherapy.

read more

Handbook of biomarkers and precision medicine a new publication by Alain van Gool

12 July 2019

Alain van Gool published a new handbook on biomarkers and applications in (pre)clinical drug development for precision medicine.

read more

The real impact of menstrual complaints on work and school productivity

8 July 2019

Menstrual period symptoms may be linked to nearly nine days of lost productivity every year, through presenteeism, suggests the largest study of its kind, published in the journal BMJ Open. But the real impact on women and society is underestimated and poorly appreciated, say the researchers.

read more

Successful Summer School by CMBI, TML and Human Genetics

8 July 2019

CMBI, TML and Human Genetics organized a successful Summer School on 'Integrative X-omics Analyses Empowering Personalized Healthcare'.

read more

Walking for science Research by Radboud university medical center and Radboud University during the Vierdaagse (Four Day Marches)

5 July 2019

The Vierdaagse is a unique opportunity to conduct research into physical activity and healthy lifestyle.

read more