Aim: The First Nations of Quebec are under-represented in Hema-Quebec’s stem cell donor Registry and their HLA is poorly understood. This could carry heavy clinical consequences for patients from the First Nations. The following objectives were defined in a project drafted in collaboration with several First Nations: Identify frequent and rare alleles and haplotypes in the Wendat First Nations; Determine the presence of differences between First Nations and the population of Québec; and Determine whether it is possible, with the generated data, to improve or inform on the chances of finding compatible donors for patients originating from the First Nations.
Method: HLA typing was performed by NGS on DNA extracted from buccal swabs, using NGSgo-AmpX v2 typing kits from GenDX (Utrecht, The Netherlands) and acquired on a MiSeq system from Illumina (San Diego, CA, USA). HLA data were analysed with the GENE[RATE] tools to estimate the allele and haplotype frequencies and test for Hardy-Weinberg Equilibrium (HWE) and linkage disequilibrium. The genetic diversity between regions was assessed by pairwise FST.
Results: For 63 individuals from the Wendat Nation that enrolled in the project, we were able to determine the HLA allele typing. Moreover, from the 28 individuals admissible to register to the stem cell donor Registry, 20 (71%) enrolled in the Registry. From the HLA typing of individuals, the allele frequencies were determined for the Wendat Nation. Among the most frequently observed alleles, a large proportion is more frequent than in the general population of Québec. Also, certain alleles in the Wendat Nation are less frequent. There is thus a dissimilarity in the HLA allele frequency between the Wendat Nation and the Quebecers. When considering the most frequent haplotypes of the Wendat Nation, differences can be observed with the population of Québec. Very few of the most frequent Wendat haplotypes can be found in the population of Québec. By comparing the genetic distance, we can observe that Wendats are distant from the population of all the regions of Québec, although the regions themselves are variable among each other.
Conclusion: The Wendat First Nation individuals have an HLA composition different from the general population of Québec. Increasing the number of donors belonging to the Wendat First Nations within the stem cell donor Registry would greatly improve the likelihood of finding suitable donors for this Nation.
