Lars Feuk's research projects – Genetic variation and transcription in human disease

Whole genome sequencing of patients with neurodevelopmental disorders

Jonatan Halvardson, Jin Zhao, Eva Carlström, Lars Feuk

To sequence all the coding regions of a genome in a single experiment is a powerful tool to discover disease genes. In this project, we are mainly focusing on two groups of patients to identify causative mutations. First, in collaboration with the clinical genetics unit, we are investigating patients with severe intellectual disability for de novo mutations by whole genome sequencing of both parents and the patient. The second approach is to use pedigrees with multiple affected individuals to identify mutations in regions of linkage or shared homozygosity. Significant work has been invested into establishing a bioinformatics pipeline for analysis of exome and whole genome sequence data.

Functional characterization of mutations causing intellectual disability

Ammar Zaghlool, Jin Zhao, Mitra Etemadikhah, Lars Feuk

Our exome sequencing projects have led to the discovery of several mutations in genes not previously linked to disease. The most interesting genes have been selected for functional follow-up in order to clarify the role of the gene and the specific mutation in disease. Classic molecular biology (cloning, transfection, RNAi) approaches are combined with high throughput genomics such as RNA-seq and CHiP-seq to characterize the role of the genes and mutations.

Transcriptome analysis

Ammar Zaghlool, Jonatan Halvardson, Mitra Etemadikhah, Adnan Niazi, Eva Carlström, Lars Feuk

Transcriptome sequencing is providing novel insights into the transcriptional landscape of cells and tissues. In this project, we use RNA sequencing to study transcription in human tissue samples. In one project, we are investigating subcellular fractions of RNA in order to characterize specific transcripts that are overrepresented in the nucleus or the cytosol of the cell. In another project, we are investigating gene expression in brain samples from patients with schizophrenia and compare expression profiles with tissue from healthy controls.