Increasing diagnostic yield of fast whole genome diagnostics for new borns on the Neonatal Intensive Care Unit (NICU)

Supervisors

Juha Karjalainen and Joeri van der Velde

Introduction

Next Generation Sequencing (NGS) has become a very important tool for geneticists. At the UMCG we recently enrolled in project "5 Genes per Minute (5GpM)" to move this high throughput technology from the research department into the clinic. In 5 GpM we aim to diagnose genetic disease in severely affected new borns on our Neonatal Intensive Care Unit (NICU) by means of whole genome screening. 5 Genes per Minute analysis can be requested for patients when all classic diagnostics failed and speed is essential. We aim for from blood sample to diagnosis in < 48 hours.

Our current bioinformatics analysis only considers single nucleotide variants (SNVs) and short insertion/deletions (InDels). So far we have analysed 10 patients and managed to pin point the causal genetic variant in one. There may be various reasons why we have no diagnosis in the other 9:

• The symptoms are not caused by a genetic disease: something else is going on.
• The genetic variant is part of a region that cannot be reliably sequenced.
• The genetic variant was sequenced, but is not yet called by our bioinformatics pipeline.
• The genetic variant was sequenced and called, but we cannot interpret the effect of the variant correctly.

Variant interpretation is a major challenge in diagnostics.

Projects 6 - Improved variant interpretation

In this student research project we aim to add annotation for less well known genes by predicting their function based on gene networks. We'll add the extra annotation to our analysis pipeline, re-analyse our unsolved cases and test if we can increase the diagnostic yield for this group of patients.