Project summary
In our project we study neurological syndromes with onset in childhood in order to reveal novel genetic defects and describe the molecular mechanisms involved in the development of disease. We focus on an extremely well selected cohort of very interesting patients: All families have been selected by Prof. Petter Str?mme (Department of Pediatrics, OUS) among the patients he has seen as child neurologist in the past 25 years. All patients have been thoroughly examined clinically and genetically. For all the patients, family history with clinical data and neuroimaging results are recorded in electronic charts, together with photos and videos.
We have performed Whole Exome Sequencing (WES) in more than 70 families with one or more children affected by severe neurological syndromes. In about 50% of the patients the genetic cause of the disease was identified. We have identified seven novel disease entities and so far three of them have been published (1-3).
We have continued our project searching for pathogenic mutations in non-coding regions within WGS data from patients where we did not identify disease causing variants in the exome. In order to understand how the novel disease causing variants affect the brain biology and result in severe neurological syndromes, we perform in vitro and in vivo studies collaborating with Norwegian and international scientists.
Contributions by the student
The student will perform molecular analyses to assess the functional consequences of putative pathogenic mutations detected in our project. The genetic variants will be studied in silico and hypotheses about their molecular consequences will be explored in vitro. This work will include methods such as PCR, analysis of gene expression, molecular cloning, and transfection of reporter constructs in cells established from the patients. This will be performed in collaboration with members of the research group.
Research environment
The project is carried out in Prof. E. Frengen’s research group at Department of Medical Genetics (AMG), a university department located at Oslo University Hospital, Ullev?l.
Frengen’s group currently consists of 1 senior engineer (Doriana Misceo, PhD), 1 research associate (Asbj?rn Holmgren, MSc), 3 PhD students and 1 research medical student/Forskerlinjen. Frengen and Dr. Misceo co-supervise all the students in the group. Frengen has supervised 9 PhD students and 20 MSc students. There are currently 15 Postdocs, 19 PhD students and 5 MSc students at AMG (UiO/OUS). Thus, the group and the department provide an excellent environment for student training.
WES, WGS and RNAseq are carried out at Norwegian Sequencing Centre which is an internationally competitive core facility located at AMG (www.sequencing.uio.no). In addition, we collaborate with world leading experts both nationally and in Europe, USA and Canada.
More information about Frengen’s research group at www.med.uio.no/klinmed/english/people/aca/efrengen/
Feel free to send an E-mail (eirik.frengen@medisin.uio.no) or call (95 88 22 33) if you have questions.
References
- Bar?y et al., (2015). A Novel Type of Rhizomelic Chondrodysplasia Punctata, RCDP5, Is Caused by Loss of the PEX5 Long Isoform. Human Molecular Genetics 24:5845-5854. (PMID: 26220973).
- Gabriele et al., (2017). YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction. American Journal of Human Genetics 100:907-925. (PMID: 28575647).
- Ansar et al., (2017). Biallelic variants in LINGO1 are associated with autosomal recessive intellectual disability, microcephaly, speech and motor delay. Genetics in Medicine, in press.