LAUSR

Aim There is a strong linkage disequilibrium between HLA-C and -B due to their genome proximity. The purpose of this study is to identify the associations between HLA-C∗07:01 and C∗07:02 allelic variations and HLA-B alleles in a Brazilian sample. Methods Third generation sequencing HLA typing (PacBio, Histogenetics) was performed on 155 DNA samples from Brazilian Bone Marrow Donor Registry (REDOME) with known high resolution HLA typing by sanger sequencing method (SeCore, Life Techology). Results Three allelic variations were identified in the 46 individuals previously typed as HLA-C∗07:01P group: HLA-C∗07:01:01:01 (n = 36, 78%), -C∗07:01:02 (n = 5, 11%) and -C∗07:18 (n = 5, 11%). In the C∗07:02P group (n = 23) only two allelic variations were identified: HLA-C∗07:02:01:03 (n = 15, 65%) and C∗07:02:01:01 (n = 8, 35%). Four different HLA-C/B haplotypes were observed in 33 individuals caring C∗07:01:01:01. The most frequently association was HLA-C∗07:01:01:01/ B∗08:01:01 (n = 17, 47%) followed by B∗49:01:01 (n = 11, 30%), B∗51:01:01:01 (n = 3, 8%) and B∗57:01:01 (n = 2, 6%). HLA-C∗07:18 was observed in 100% of the individuals caring B∗58:01:01 (n = 5, 100%) while no significant association was found among HLA-C∗07:01:02 and HLA-B alleles. In regard to the C∗07:02P group, a strong linkage disequilibrium was found between HLA-C∗07:02:01:03/B∗07:02:01 haplotypes (n = 15, 100%). HLA-C∗07:02:01:01/B∗07:02:01 haplotype were observed in 3/8 individuals (37%). Nevertheless others associations were found with C∗07:02:01:01 in individuals carrying B∗39 allelic variants (B∗39:03, B∗39:06, B∗39:09 and B∗39:13). Conclusions The identification of allelic variations by NGS allowing an extended gene coverage can demonstrate that specific haplotype combinations can be found in the different populations in stronger associations than expected.