Four-locus high-resolution HLA typing in a sample of Mexican Americans

Area of Science:

• Immunogenetics
• Population Genetics
• Hematology

Background:

• Mexican Americans represent a significant minority population in the United States.
• Understanding human leukocyte antigen (HLA) diversity is critical for successful hematopoietic stem cell transplantation (HSCT).
• Previous studies have not fully characterized HLA allele and haplotype frequencies in the Mexican American population.

Purpose of the Study:

• To determine the high-resolution HLA A, C, B, and DRB1 allele and haplotype frequencies in a cohort of Mexican Americans.
• To identify novel HLA alleles within this population.
• To provide foundational data for optimizing the donor pool for HSCT in individuals of Mexican ancestry.

Main Methods:

• High-resolution sequence-based typing (SBT) was employed for HLA loci A, C, B, and DRB1.
• A cohort of 553 bone marrow donor registrants of self-described Mexican ancestry was analyzed.
• Four-locus haplotype frequencies were calculated and analyzed for distribution patterns.

Main Results:

• A total of 47, 34, 76, and 46 distinct alleles were identified at HLA A, C, B, and DRB1, respectively.
• Three novel HLA alleles were discovered.
• The four-locus haplotype frequency distribution was highly skewed, with only 53.9% of chromosomes having more than one estimated copy.
• Haplotypes of Native American origin were detected.

Conclusions:

• The study provides comprehensive HLA typing data for Mexican Americans, revealing significant genetic diversity.
• The identified novel alleles and skewed haplotype frequencies highlight the unique genetic landscape of this population.
• These findings are essential for guiding strategies to build a more representative and effective donor registry for stem cell transplantation.