Complotypes and extended haplotypes in laboratory medicine

Area of Science:

• Immunogenetics
• Human Molecular Genetics

Background:

• The sixth human chromosome region encodes histocompatibility antigens (HLA class I and II) crucial for immune recognition.
• This region also contains class III genes, including complement factors C2, C4, and factor B, located between HLA-B and HLA-DR loci.
• These four complement genes are inherited as a single unit, termed a complotype, without observed crossover.

Purpose of the Study:

• To investigate linkage disequilibrium between HLA alleles and complotypes.
• To identify and characterize extended haplotypes within the human sixth chromosome.
• To explore the implications of extended haplotypes for HLA marker-disease associations and tissue transplantation.

Main Methods:

• Analysis of linkage disequilibrium between HLA-B, HLA-DR alleles, and complotypes.
• Identification of fixed sets of alleles, termed extended or fixed haplotypes.
• Characterization of the genetic makeup of the HLA-B-DR interval.

Main Results:

• Approximately 30% of normal Caucasian chromosomes exhibit fixed extended haplotypes.
• Over a dozen extended haplotypes have been defined by their HLA-B, DR, and complotype alleles.
• Extended haplotypes account for significant linkage disequilibrium and known HLA marker-disease associations.

Conclusions:

• Extended haplotypes represent conserved DNA segments of at least 10^6 base pairs in the HLA-B-DR interval.
• Identical or near-identical extended haplotypes can occur in unrelated individuals.
• The concept of extended haplotypes offers potential for predicting successful tissue transplantation donor-recipient matching.