Identification of novel genetic modifiers in ß-thalassemia

Final Report Abstract

The understanding of the phenotypic variability of genetically homogenous disorders represents a major challenge. In ß-thalassaemia the ß-globin gene is affected by a variety of mutations. The group of patients to be analyzed here is homozygous for a splice site mutation that is common in the Middle East. In contrast to this genetic homogeneity the spectrum of the clinical phenotype ranges from mild anaemia to most severe, transfusion-dependent anaemia. We aim at an understanding of this perplexing clinical variability by using a genetic linkage approach to identify modifying factors and by analyzing the efficiency of an mRNA surveillance mechanism that is referred to as nonsense-mediated decay and represents a candidate genetic modifier of ß-thalassaemia and other genetic disorders.

Publications

• Exon-junction components specify distinct routes of nonsense-mediated mRNA decay with differential co-factor requirements. Molecular Cell 20: 65-75 (2005)
  Gehring, N., J. B. Kunz, G. Neu-Yilik, S. Breit, M. H. Viegas, M. W. Hentze, A. E. Kulozik
  
• The abundance of RNPS1, a protein component of the exon junction complex, can determine the 5 variability in efficiency of the Nonsense Mediated Decay Pathway. Nucleic Acids Research 35:4542-4551 (2007)
  Viegas, M.H., N.H. Gehring, S. Breit, M. W. Hentze, A.E. Kulozik