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Comprehensive analyses of point mutations in coagulation factors: correlation to severity of hemophilia diseases

Thursday, October 11, 2012 — Poster Session III

10:00 a.m. – Noon

Natcher Conference Center, Building 45




  • N.H. Katagiri
  • R Salari
  • V.L. Simhadri
  • S.C. Tseng
  • E Needlman
  • N.C. Edwards
  • N Nelson
  • M Katz
  • J Lee
  • Z.E. Sauna
  • V Grigoryan
  • A.A. Komar
  • T.M. Przytycka
  • C Kimchi-Sarfaty


Hemophilia A and B are X-linked recessive disorders caused by deficiency of functional coagulation factor VIII and IX, respectively, which result almost exclusively from mutations in the F8 or F9 genes, respectively. We sought to determine features which could distinguish between mutations that cause severe disease symptoms from those that cause non-severe disease symptoms. Toward this objective, we have performed a statistical analysis of qualities in reported point mutations in these genes such as potential local changes in mRNA free energy, codon usage, charge and type of mutated amino acid, location on the protein secondary structure and functional domain, and amino acids’ evolutionary conservation scores. For both diseases, we found significant differences between severe and non-severe disease causing mutations and evolutionarily conserved amino acids. Other correlations such as information at the mRNA level and codon usage with severity will be discussed further in the presentation. This study demonstrates that computational tools may be used to characterize the severity of hemophilia associated with point mutations and suggests their utility in predicting the outcome of sequence changes in recombinant proteins.

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