Age-dependent HLA profiles of the Israeli population: impact on hematopoietic cell donor recruitment and availability

Abstract

Approximately three million people have immigrated to the state of Israel since it was founded. Consequently, the immunogenetic profile of the younger generation may consist of a genetic mixture of formerly distinct population groups. We aimed to investigate whether HLA profiles in the Israeli population are age dependent and how this influences representation of various age groups in local donor registries. We determined HLA-A*, HLA-B*, and HLA-DRB1* low-resolution phenotypes of three age groups (n = 4,169 in each): (1) cord blood units collected between 2009 and 2013 (BABIES) and adult registry donors (2) aged 18-28 years (YOUNG) and (3) aged 49-60 years (OLD). We compared the results with virtual groups that simulate the offspring of the actual study groups. None of the three actual age groups were in Hardy-Weinberg equilibrium. The YOUNG presented four HLA-B alleles that were absent in the OLD and BABIES. A significantly higher percentage among the OLD and BABIES had a "matched" individual within their group in comparison to the YOUNG. In the YOUNG, the 10 most common haplotypes account for 16.7 % of the population, in comparison to 18.2 % in the OLD or 19.8 % in the BABIES group. The BABIES group was genetically remote from all other groups. Further disparities were found between the actual and the corresponding virtual groups. We conclude that discrete age groups in Israel present distinct immunogenetic profiles, where the younger generation is more heterogeneous. The population dynamics of the age-dependent HLA profile is multifactorial: gradual intersubgroup admixture, nonrandom mating, and entry of new alleles.

East Meets West—Impact of Ethnicity on Donor Match Rates in the Ezer Mizion Bone Marrow Donor Registry

“…As such, models assuming HWE might not be valid. The results of subethnic admixture in contemporary Israeli society are already apparent in the lower numbers of fully HLA MUDs actually found for children as compared with adult transplant recipients in Israel [14]. Exploring haplotype frequencies and match rates for the growing multi-ethnic population base in the EM BMDR will set the foundation for elaborating strategies for recruitment and expansion of the registry, and will highlight the value added to the international community through the contributions of multiethnic donors in an increasingly globalized community.…”

“…Israel is a home to the entire genetic spectrum of the Jewish Diaspora, as well as to large minorities composed of non-Jewish ethnic groups, leading to substantial ethnic diversity in a country of only 8 million individuals. As second-generation Israelis start marrying outside of their ancestral subethnicities, an additional layer of diversity has been introduced into the HLA landscape in Israel, leading to immunogenetic intergenerational differences within the Israeli population [14].…”