A functional human genome project: integrated research of human congenital disorders.

One of the major challenges in contemporary biomedical research is the annotation of the human genome, i.e. the functional characterisation of all human genes identified through the Human Genome Project. An elegant means to achieve this is the identification of genes underlying human genetic diseases, thus exploiting the effect of naturally occurring genetic mutations and variants on the occurrence of diseases and developmental disorders. However, there are two major limiting factors: (1) access to patients and families with well defined genetic disorders and (2) the technology to identify the causative mutations. Our group, active at the interface between clinical genetics and basic research and with a longstanding expertise in clinical-molecular research of congenital disorders, is well placed to contribute to the functional human genome project. With this proposal, we wish to continue our ongoing efforts and bring it to the next level by implementing the rapidly evolving and continuously generated novel improvements in genetic research. We want to make use of the latest as well as emerging technologies, with the ultimate aim to establish the functional link between genetic alterations and human congenital disorders in a fast and efficient way. This approach, combined with our long-standing clinical expertise and access to often unique patient material, has the advantage that it allows a direct translation of the results to the clinic. We propose a gene identification strategy starting from accurately phenotyped patients and patient cohorts and applying state-of-the-art genetic technologies and methodology in an integrated way to localise and interpret different types of genetic variations. We integrate (1) genome-wide SNP and CNV genotyping , (2) next-generation sequencing technologies, (3) genome-wide epigenetic screens and (4) analysis of (epi)genetic variants according to the current standard in genetic epidemiology.

Keywords:Handicap, Mutation, Syndrome, Genetica

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences, Genetics, Systems biology, Molecular and cell biology, Gynaecology and obstetrics, Morphological sciences, Medical systems biology