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Project
Breakpoint variability as an explanation for phenotypical variation in 22q11DS.
The 22q11 deletion syndrome is a genomic aberration characterized by a recurrent microdeletion. The estimated prevalence is 1 in 4000 live births. Clinical features include congenital cardiac anomalies, a typical facial expression, immunological defects, mental retardation and psychiatric conditions like schizophrenia. The latter occurs in 30% of the patients, making 22q11DS the only known genetic factor with a high penetrance for the disorder.
The majority (90%) of patients have a hemizygous deletion of 3 megabases on the long arm of chromosome 22. It is caused by non-allelic homologous recombination between large duplicationsegments in the region and contains at least 40 known genes. Several association studies attempted to correlate schizophrenia to these genes, but remained without success.
Our hypothesis is that variable rearrangements within the duplication segments can result in differentgene compositions between patients. Alternatively the copy number of a critical element can depend on the position of the deletion. If the copynumber of this segment drops below a critical limit, patients could develop schizophrenia.
With this project we will develop new methods to characterize the breakpoints. A new strategy has applications in diagnostics and could possibly lead to new therapeutic insight in schizophrenia.
The majority (90%) of patients have a hemizygous deletion of 3 megabases on the long arm of chromosome 22. It is caused by non-allelic homologous recombination between large duplicationsegments in the region and contains at least 40 known genes. Several association studies attempted to correlate schizophrenia to these genes, but remained without success.
Our hypothesis is that variable rearrangements within the duplication segments can result in differentgene compositions between patients. Alternatively the copy number of a critical element can depend on the position of the deletion. If the copynumber of this segment drops below a critical limit, patients could develop schizophrenia.
With this project we will develop new methods to characterize the breakpoints. A new strategy has applications in diagnostics and could possibly lead to new therapeutic insight in schizophrenia.
Date:1 Aug 2013 → 11 Jun 2020
Keywords:Diagnostics, DNA sequencing, DNA amplification, Chromosome Microdissection, Schizophrenia, 22Q11 Deletion Syndrome
Disciplines:Genetics, Systems biology, Molecular and cell biology, Diagnostics, Laboratory medicine, Medicinal products, Psychiatry and psychotherapy, Nursing, Other paramedical sciences, Clinical and counselling psychology, Other psychology and cognitive sciences
Project type:PhD project