PhD student project: Identifying the molecular causes of inherited blindness by homozygosity mapping in outbred populations 

Background

In approximately half of the patients with inherited blindness the genetic causes are unknown. The classical approach to identify novel disease genes by genetic linkage studies is problematic for autosomal recessive eye diseases which are generally observed in very small families. Homozygosity mapping can be used for the identification of novel genetic defects in consanguineous families, but these are rare in western countries.We have shown that high density SNP microarrays can identify homozygous regions containing causal defects in patients from non-consanguineous families. Congenital blindness (Leber congenital amaurosis - LCA) displays an enormous degree of allelic and genetic heterogeneity and the previously identified defects are very rare. Patients from ethnic groups (French-Canadians, Ashkenazi Jews) and from the Netherlands, were analysed using genome-wide SNP arrays. This enabled us to identify several new leads to identify novel LCA disease genes, and was instrumental to identify the LCA5 gene (see: A.I. den Hollander et al. Nat. Genet. 39, 889-895, 2007). Our results provide proof-of-principle that homozygosity mapping in outbred populations enables the identification of new autosomal recessive disease genes.

Aims

In this study we will further explore homozygosity mapping in non-consanguineous families to identify novel molecular causes for LCA. The function of new LCA genes and their protein products will be studied by various methods. The identification of new LCA genes will lead to new insights in the biochemical and cellular pathways that are involved in the development of the retina, and will be of great importance to understand the pathogenesis of inherited blindness. Moreover, discovery of new LCA genes will improve DNA diagnostics and facilitate the development of gene-specific therapies.

The Department of Human Genetics

Join our research team at the Radboud University Nijmegen Medical Centre in Nijmegen, the Netherlands. Our Department (www.humangenetics.nl) has a longstanding history in the elucidation of the molecular causes of inherited blindness. The project will be supervised by Prof. Dr. Frans P. Cremers and Dr. Anneke I. den Hollander. More information about the project can be requested by e-mail (F.Cremers@antrg.umcn.nl or A.denHollander@antrg.umcn.nl) or telephone (+31-24-3614017).

Candidate requirements

We are looking for a highly motivated candidate who has experience with molecular genetic techniques. The applicant should have completed (or expects to receive) a master’s degree in (Medical) Biology, Molecular Life Sciences or Biomedical Sciences. Experience with microarray techniques would be advantageous. Good communication skills, including proficiency in written and spoken English, are essential.

Please send your motivation and CV, including your strongest technical skills, with two references or letters of recommendation, as one PDF file (filename: “8542_your family name”) by e-mail to mrs. M. Leenders: agsecretariaat@antrg.umcn.nl, before 13 June 2008.

Salary: Gross salary €25.000,- (1st yr) - €35.000,- (4th yr)
Open from: 1 August 2008
Type of employment: Full Time