Classical HLA Allele and Haplotype Frequency Estimates in US Populations

Area of Science:

• Immunogenetics
• Population Genetics
• Transplantation Science

Background:

• The human leukocyte antigen (HLA) system is critical for transplantation compatibility and immune response.
• Understanding HLA diversity is essential for advancing HCT, solid organ transplantation, and disease research.

Purpose of the Study:

• To characterize nine-locus classical HLA allele and haplotype frequencies across diverse US populations.
• To provide comprehensive HLA data for clinical decision-making and research in immunogenetics and transplantation.

Main Methods:

• Utilized targeted genotyping by DNA-based methods for 9,671,082 US donors.
• Employed an expectation-maximization (EM) framework for frequency estimation with mixed-resolution HLA data.
• Leveraged next-generation sequencing for extensive HLA genotyping, particularly for HLA class II.

Main Results:

• Presented HLA allele and haplotype frequency estimates for five broad and 21 detailed US populations.
• Identified predominantly population-specific high-resolution haplotypes, with few shared across major groups.
• Observed the greatest nine-locus haplotypic diversity in Black populations, irrespective of sample size.

Conclusions:

• The study provides the largest US cohort-derived HLA frequencies to date.
• Findings support clinical practice and research in histocompatibility and transplantation.
• Publicly available data expands knowledge of MHC complex diversity, especially for HLA class II.