Alanine in HI: A Silent Mutation Cries Out!

  • J.H. Shah
  • D.J. Maguire
  • T.B. Munce
  • A. Cotterill
Part of the Advances In Experimental Medicine And Biology book series (AEMB, volume 614)


It is a widely held paradigm in molecular biology that a change in the third base of a codon is silent in terms of expression. In this investigation, results are presented that challenge that paradigm, at least in terms of one polymorphism in KCNJ11, which is one of five genes that have been implicated in the disorder Hyperinsulinism of Infancy. In two cohorts of Australian patients, an uneven distribution of KCNJ11 SNP’s was observed. A silent polymorphism at codon 190 was over-represented in the patients who responded well to medical treatment and under-represented in those that required radical surgical intervention. In an attempt to investigate this polymorphism, it was expressed in vitro and western blot analysis showed that there were virtually no bands from the homozygous variant samples, while strong bands were seen in normal controls. The human genome is highly redundant in terms of tRNA species for each amino acids but enigmatically under-represents a number of specific codons. The polymorphism in question occurs within one such codon. We propose that the presence of a base change at the third position of codon that is not represented by a corresponding anti-codon within the human nuclear tRNA leads to a decreased rate of expression of the protein.


Silent Mutation tRNA Molecule Hyperinsulinemic Hypoglycaemia tRNA Species KCNJ11 Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • J.H. Shah
    • 1
  • D.J. Maguire
    • 1
  • T.B. Munce
    • 2
  • A. Cotterill
    • 3
  1. 1.School of Biomolecular and Biophysical Science, Griffith UniversityNathanAustralia
  2. 2.Pathology, Mater Health Services, South Brisbane4101–Metabolic Medicine, Mater Health ServicesSouth Brisbane
  3. 3.Paediatric Endocrinology and Diabetes, Mater Children’s HospitalSouth BrisbaneAustralia

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