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Abstract

Abstract

Psoriasis is a chronic inflammatory skin disease posing a considerable world-wide health problem due to its high prevalence, associated morbidity and high health-care costs. It is a multifactorial “complex” disorder, with compelling evidence for a genetic predisposition.

Majeed syndrome is a Mendelian disorder with a consistent phenotype and its causative gene can be examined for its role in the more common bone and skin inflammatory disorders of complex etiology. Majeed syndrome is caused by mutations in LPIN2.

Many observations have implicated LPIN2 in the genetic etiology of psoriasis. Based on these observations, we hypothesize that variations in LPIN2 play a role in the susceptibility to development of psoriasis and that LPIN2 is the psoriasis susceptibility locus on 18p.

In our previous study, we identified 6 coding variants that may be associated with psoriasis due to the fact that they change evolutionary conserved amino acids and they are present in the general population at a very low allele frequency. However, the ultimate evidence of their causation of the phenotype is to prove that there is a change in protein properties or function with the molecular variations. One of the aims of the current work is to shed light on whether each identified LPIN2 mutation has an effect on the integrity of the properties of the Lipin2 protein and therefore its function.

The wide type and six different cDNA LPIN2 clones, each harboring one of the six described variations were successfully synthesised after codon optimisation for maximum expression in yeast.

The LPIN2 gene and two mutants were excised from its original construct and inserted into similarly digested pYES2. The newly formed constructs were transformed into competent cells of Saccharomyces cerevisiae for protein expression. Our preliminary analyses using SDS gel electrophoresis and Western blot indicate that the wild type and the two mutants are expressed in S. cerevisiae but at a low level. Optimization of the expression as well as expression of these genes in different expression system is being carried out. The recombinant protein of the wild type LPIN2 and the two mutants will be subjected to circular dichroism and fluorescence measurements to study the effect of each mutant on the folding and therefore the function of the protein.

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/content/papers/10.5339/qfarf.2010.BMP13
2010-12-13
2020-11-24
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References

  1. M. Osman, G. Sayed, J. Alami, H. El Shanti, Characterization of the LPIN2 gene and its protein and examination of its role in psoriasis, QFARF Proceedings, 2010, BMP13.
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