HLA genes in Macedonians and the sub-Saharan origin of the Greeks

Abstract

HLA alleles have been determined in individuals from the Republic of Macedonia by DNA typing and sequencing. HLA-A, -B, -DR, -DQ allele frequencies and extended haplotypes have been for the first time determined and the results compared to those of other Mediterraneans, particularly with their neighbouring Greeks. Genetic distances, neighbor-joining dendrograms and correspondence analysis have been performed. The following conclusions have been reached: 1) Macedonians belong to the "older" Mediterranean substratum, like Iberians (including Basques), North Africans, Italians, French, Cretans, Jews, Lebanese, Turks (Anatolians), Armenians and Iranians, 2) Macedonians are not related with geographically close Greeks, who do not belong to the "older" Mediterranenan substratum, 3) Greeks are found to have a substantial relatedness to sub-Saharan (Ethiopian) people, which separate them from other Mediterranean groups. Both Greeks and Ethiopians share quasi-specific DRB1 alleles, such as *0305, *0307, *0411, *0413, *0416, *0417, *0420, *1110, *1112, *1304 and *1310. Genetic distances are closer between Greeks and Ethiopian/sub-Saharan groups than to any other Mediterranean group and finally Greeks cluster with Ethiopians/sub-Saharans in both neighbour joining dendrograms and correspondence analyses. The time period when these relationships might have occurred was ancient but uncertain and might be related to the displacement of Egyptian-Ethiopian people living in pharaonic Egypt.

DNA typing of HLA-A, -C, -B, AND -DRB1 in the children with autism in the Republic of Macedonia

“…These haplotypes has not been detected in the healthy Macedonian population, but there is no statistically signifi cant association, probabely because of the small number of investigated persons with autism. The most common alleles in control group were: A*01-C*07-B*08-DRB1*03 (3.1 %), A*02-C*07-B*18-DRB1*11 (2.0 %), A*02-C*06-B*13-DRB1*07 (1.5 %), A*11-C*12-B*52-DRB1*16 (1.5 %), which is different to the other Macedonian antropological study (19). They found increased frequencies of A*02-B*51-DRB1*1601 (3.2 %), and A*03-B*18-DRB1*1601 (2.6 %) (19).…”

“…The most common alleles in control group were: A*01-C*07-B*08-DRB1*03 (3.1 %), A*02-C*07-B*18-DRB1*11 (2.0 %), A*02-C*06-B*13-DRB1*07 (1.5 %), A*11-C*12-B*52-DRB1*16 (1.5 %), which is different to the other Macedonian antropological study (19). They found increased frequencies of A*02-B*51-DRB1*1601 (3.2 %), and A*03-B*18-DRB1*1601 (2.6 %) (19). None of our patients carried alleles or haplotype, which are protective for autism in our population.…”

“…The immunogenetic profi le of the Macedonian population represented by HLA genes is published for HLA-A, -B, -DR, -DQ allele frequencies (19), for HLA-DRB1, DRB3/4/5 and DQB1 polymorphism (20), for HLA-A and HLA-B epidemiology (21), for high-resolution sequence-based method for direct HLA-DRB1 typing (22), for ambiguous allele combinations at the allele group level of HLA-A, -C and -B loci (23), and for HLA-DQB1 typing (24).…”

Immunological and Immunogenetic Changes in Children with Autistic Disorder in Republic of Macedonia

“…If autism is in some cases the result of immune system attack, then particular HLA antigens might be involved as a sufficient or predisposing factor [30]. The immunogenetic profile of the Macedonian population represented by HLA genes is published for HLA-A, -B, -DR, -DQ allele frequencies [31], for HLA-DRB1, DRB3/4/5 and DQB1 polymorphism [32], for HLA-A and HLA-B epidemiology [33], for high-resolution sequence-based method for direct HLA-DRB1 typing [34], for ambiguous allele combinations at the allele group level of HLA-A, -C and -B loci [35], and for HLA-DQB1 typing [36]. Our results showed significantly increased frequencies of HLA-C*03 and HLA-DRB1*01 alleles in autistic patients when compared to the controls.…”

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“…They observed that HLA-A*02,HLA-B*51, and HLA-DRB1*11 are the most frequent HLA alleles in unrelated Turkish individuals. 8 According to the literature, HLA-A*02, HLA-B*51, and HLA-DRB1*11 are found in Armenians and HLA-A( * )02, HLA-B( * )35, and HLA-DRB1( * )11 are found in Brazilian renal transplant candidates. 9,10 When we look at the PRA positivity, we found that A02, A68, A23, B49, B37, B7, DR7, DR14, DR11, DQ9, DQ8, and DQ2 were the most common anti-HLA antibodies.…”