Genotypic heterogeneity among Lewis negative individuals

Area of Science:

• Genetics
• Biochemistry
• Immunology

Background:

• The alpha (1,3/1,4) fucosyltransferase III (FT-III) gene is crucial for synthesizing Lewis a and Lewis b blood group antigens.
• Lewis blood group antigens play roles in various biological processes, including immune responses and pathogen binding.

Purpose of the Study:

• To identify genetic variations in the FT-III gene associated with Lewis antigen expression.
• To investigate the functional impact of identified mutations on FT-III enzyme activity and antigen synthesis.

Main Methods:

• DNA sequencing of the FT-III gene coding region.
• Restriction fragment length polymorphism (RFLP) analysis using NlaIII enzyme.
• Genotyping of individuals with known Lewis blood group phenotypes.

Main Results:

• A specific C to T mutation at nucleotide 314 in the FT-III gene was identified.
• This mutation creates a new NlaIII restriction site.
• The mutation was present in homozygous form in 5/18 Lewis negative individuals and absent in 22 Lewis positive individuals.
• Heterozygous individuals for this mutation were found in both Lewis negative (10/18) and Lewis positive (4/22) groups.
• The mutation results in a threonine to methionine amino acid substitution.

Conclusions:

• The identified C to T mutation in the FT-III gene is strongly associated with Lewis negative phenotypes.
• This genetic variation likely impairs the synthesis of Lewis a and b antigens.
• The findings contribute to understanding the genetic basis of Lewis blood group expression and its clinical implications.