Determination of HLA-A, -B, and -DRB1 Allele and Haplotype Frequencies in the Croatian Population Based on a Family Study

HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 allele and haplotype frequencies defined by next generation sequencing in a population of East Croatia blood donors

“…Greater differences in frequency rate between general and east Croatian population were, however, noticed among HLA-B allelic variants. The HLA-B*51:01 allelic group was the most frequent in both general and east Croatian cohort, but the frequency rank of the remaining HLA-B allelic variants was different, which was particularly evident for our 6 th ranking B*18:01 allele group, previously reported as the 2 nd most frequent allelic variant in the CBMDR (8.16%) 17 and one Croatian family study (8.27%) 18 . Among five different B*18 alleles detected in the Croats so far 28 , we observed only two, the B*18:01:01 (5.14%) and the B*18:03 (0.90%), resulting in a B*18:01 distribution closer to those reported in Armenians 29 , Germans 30 , Austrian and the Turkish minority in Germany 20 , Bulgarian Roma individuals 31 , and Iranian Kurds 32 .…”

“…Among 181 six-loci haplotypes (Supplementary Table 8), 10 appeared in three or more copies (Table 5), and the most frequent was the ancestral haplotype A*01:01:01:01~C*07:01:01~B*08:01:01~DRB1*03:01:01:01~ DQA1*05:01:01:02~DQB1*02:01:01 (3.6%). Three six-loci combinations (A*02:01:01~C*07:01:0 1~B*18:01:01~ DRB1*11:04:01~DQA1*05:05:01:09~DQB1*03:01:01:03, A*03:01:01:01~C*07:02:01~ B*07:02:01~DRB1*16:01:01~DQA1*01:02:02~DQB1*05:02:01:01, and A*11:01:01:01~ C*04:01:01:01~ B*35:01:01~DRB1*16:01:01~DQA1*01:02:02~DQB1*05:02:01:01), which have already been reported in Italian population 27 , Turkish minority in Germany 20 , and Croatian families 18 , were also commonly (1.8%) observed. Haplotypes characteristic for South European populations of Slavic background or admixture were also found 17 , namely A*02:01:01~C*02:02:02~B*27:02:01:01~DRB1*16:01:02~ DQA1*01:02:02~DQB1*05:02:01:01 (1.8%), and even more unique A*02:01:01~C*02:02:02~B*27:05:02~DRB1*01:01:01~DQA1*01:01:01:03~DQB1*05:02:01:01 (0.45%), A*02:01:01~C*07:02:01~B*27:05:02~DRB1*01:01:01~ DQA1*01:01:01:01~DQB1*05:01:01:03 (0.45%) and A*02:01:01~C*07:02:01~ B*27:05:02~DRB1*01:01:01~ DQA1*01:01:01:03~ DQB1*03:01:01:03 (0.45%).…”

“…Up to date, HLA allelic and haplotype diversity of a general Croatian population, irrespective of specific geographical preferences, was estimated in several large cohorts originating from Croatia [16][17][18][19] and emigrant population in Germany 20 , as well as few, more isolated populations from particular geographical locations such as island Krk 21 , island Hvar 22 , Istrian city of Rijeka 23 and Gorski Kotar 24 . Moreover, several non-frequent, rare and very rare HLA-A, -B and -DRB1 alleles and haplotypes have been characterized among the unrelated volunteer donors from the Croatian Bone Marrow Donor Registry (CBMDR) 25 .…”

Identification of the novel HLA‐B*18:37:02 allele in a Croatian individual

“…A further step was sequence-based typing (SBT) method for HLA-B locus using a commercial Olerup SBT Resolver kit (CareDx Pty Ltd, Fremantle Western Australia, Australia) with standard HLA-B locus-specific primers for exons 1 to The exact HLA haplotype could not be deduced due to the lack of samples from the family members of the donor. According to data from the family study and the frequency of HLA-A~B~DRB1 haplotypes among donors from CBMDR, 3,4 the second most common haplotype in Croatia is HLA*02:01~B*18:01~DRB1*11:04 (1.57% and 1.48%), while the rank seven belongs to haplotype HLA*25:01~B*18:01~DRB1*15:01 (0.93% and 0.53%). Therefore, based on the data from the Croatian population and linkage disequilibrium (regarding HLA-B~C and HLA-DR~DQ loci), the proposed haplotype is HLA*25:01~B*18:37:02~C*12:03~DRB1*15:01~DQB1* 06:02~DQA1*01:02.…”

HLA allele and haplotype diversity in the Croatian population: State of the art

“…Because of Croatia's specific geographical position and various influences of different populations throughout history, the HLA profile of the Croatian population is complex and intriguing. For that reason, the population studies about HLA diversity among Croats have been ongoing for many years, even in the “molecular era” of HLA …”