2.1.1 Classification of MICA 3′UTR types

In previous studies, the classification of MICA 3′UTR types was based on the presence of 9 SNPs; rs9266826 (G/A), rs9266827 (A/G), rs9266828 (G/C), rs9266929 (A/G), rs140390705 (C/T), rs 1880 (C/A), rs113015830 (A/T), rs1131904 (A/G), and rs9266831 (G/A) were grouped into UTR1-UTR7 (Luo et al., 2013). However, in the present study, we introduced a new 3′UTR classification that considers: 1) the introduction of two SNPs, rs9266825(C/A) and rs 1882 (A/G), as they are located in regions with LD with the other 9 SNPs described (from position 1,000 to 1,327 ({"type":"entrez-nucleotide","attrs":{"text":"NM_001177519.3","term_id":"1508736546","term_text":"NM_001177519.3"}}NM_001177519.3)); 2) exclusion of UTR5 and UTR6, which harbor the SNPs rs140390705 allele T and rs113015830 allele A, respectively, as they have a lower global frequency (0.0006 and 0.0044, respectively), and they have not been identified as part of MICA alleles reported in the IPD-IMGT/HLA Database (Table 1); 3) in consideration of a guanine insertion in the transmembrane region at position 952 located in exon 5 (MICA *008), and a deletion of guanine at position 892 in exon 4 (MICA *015, and *017), both of which change the reading frame, resulting in premature stop codons TAA or TGA at positions +997 and +1,035, respectively. The rest of the alleles maintain TAG stop codon at position +1,154. Thus, MICA*008 3′UTR is longer than the 3′UTR from MICA *015, and *017 MICA alleles and the other MICA alleles described to date. MICA alleles reported in the IPD-IMGT/HLA Database are included in Table 1.

Diversity of 3′UTR of the MICA gene and novel classification.

(#): SNPs, with a global frequency lower than 0.005. These SNPs, were excluded for our analysis, resulting in the exclusion of UTR5 and UTR6, which are considered analogous to UTR2 and UTR1 respectively. NA: There are no MICA, alleles reported in the HLA, database.