Increased heterozygosity for MHC class II lineages in newborn males

Area of Science:

• Genetics
• Immunology
• Evolutionary Biology

Background:

• Genetic compatibility systems are crucial for offspring diversity in many species.
• The Major Histocompatibility Complex (MHC), including human leukocyte antigen (HLA), is implicated as a vertebrate compatibility system.
• HLA class II haplotypes, specifically DRB loci (DRB3, DRB4, DRB5), are associated with ancestral lineages and genetic diversity.

Purpose of the Study:

• To investigate sex-specific prenatal selection events related to HLA class II haplotypes.
• To analyze heterozygosity rates and haplotype diversity in newborns concerning sex.

Main Methods:

• Analysis of 415 newborns using Polymerase Chain Reaction (PCR).
• Examination of all expressed DRB loci, including DRB1, DRB3, DRB4, and DRB5.
• Comparison of heterozygosity rates and haplotype combinations between male and female newborns.

Main Results:

• No significant difference in DRB1 heterozygosity between sexes.
• A significantly higher proportion of males carried two DRB1 specificities from different ancestral lineages (53.7% vs. 39.3%).
• The most phylogenetically distinct haplotypes (DRB3 and DRB4) showed the most striking sex difference in genotype combinations (P = 0.007).

Conclusions:

• Results suggest a prenatal advantage for male conceptuses heterozygous for specific supertypical HLA haplotypes.
• This heterozygosity may ensure functional diversity at the MHC class II locus and other MHC loci.
• Findings align with existing data on male heterozygote advantage in other species and could explain human sex ratio patterns.