Bioinformatic Analysis of Pathogenic Missense Mutations of MLH1

Abstract: MLH1 gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). It is a human mismatch repair gene. The nature of amino acid substitutions in invariant sites will condition the effect on protein structure, while variable positions can be analysed for residues that can be exchanged without detrimental effects.Here we analyse three SNP to find their pathogenic effect. Each mutant were compared with the corresponding wild-type structures. 1) rs63750792NM_001258271.1:c.83C> T XP_005265218.1:p.Pro28Leu 2) rs63750823 NM_000249.3:c.67G> A, XP_005265218.1:p.Glu23Ter 3) rs63751012 NM_000249.3:c.109G> A XP_005265218.1:p.Glu37Ter In rs63750792 Proline, changed to Leucine. In the wild type proline has 2 bond with Alanine (A) in position 31, but in the mutated form the bond are different. The replaced amino acid, has a bond to Isoleusine (I) 32 and a bond with Alanine (A) 31. This SNP is related to Lynch syndrome and hereditary cancer-predisposing syndrome.In rs63750823 Glutamine, changed to Threonine. In the wild type Glutamine has one bond with Glutamine (Q) 26, Isoleucine (I) 19, and Alanine (A) 20. In mutated form, Threonine has a bond with Glutamine (Q) 26 and Alanine (A) 20, but it has two bonds with Isoleucine (I) 19.This SNP is associated with Lynch syndrome and HNPCC.In rs63751012 amino acid in the wild type, Glutamine (E) has a bond with aspartic acid (D) 41 and two bonds with Lysine (K) 33. The mutated form has same bonds as wild type, but it causes alteration in protein structure. This alteration maybe a reason of causing HNPCC.

Keywords:

HNPCC , Mutation , Pathogen , Analyze