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The MICA deletion across different populations
Viviane Aparecida de Oliveira Ciriaco1, Amanda Muniz Rodrigues2, Brenda Caroline da Silva Tibúrcio3
1São Paulo State University (UNESP), Medical School, Botucatu, Brazil.
Abstract:
The MICA gene encodes a glycoprotein upregulated upon cellular stress, particularly in oxidative stress, intracellular infections, and tumorigenesis. This stress-signaling molecule interacts with the activating receptor NKG2D from Natural Killer (NK) and some T lymphocytes, stimulating their cytotoxic activity. MICA is encoded within the human Major Histocompatibility Complex next to the HLA-B locus and is highly polymorphic. MICA might be absent from chromosome 6 due to a large deletion of approximately 100 Kb between HLA-B and MICB. Therefore, some individuals may not produce any isoform of MICA. The distribution of this phenotype may vary among different populations. We evaluated the distribution of the MICA*del and other MICA null alleles in different biogeographic regions and the Linkage Disequilibrium (LD) pattern between this allele and HLA-B. We detected at least two different patterns of deletion, one with full deletion of MICA and surrounding sequences and one partial MICA deletion. The presence of different patterns of deletion suggests independent deletion events. We confirm that the previously described MICA*del allele is mainly associated with B*48 and MICB*009N in Asia and America, but other haplotypes also occur. While most samples with complete or partial MICA deletion are heterozygous and present one functional copy of both MICA and MICB genes, we detected two samples with no functional MICA and one with no functional MIC genes. Therefore, other mechanisms might be in place to compensate for the absence of MIC molecules.
Insights
The MICA gene, crucial for immune response, can be deleted from chromosome 6. This study maps MICA deletion patterns and their association with HLA-B across populations.
Area of Science:
- Immunogenetics
- Human Molecular Genetics
Background:
- The MICA gene encodes a stress-induced glycoprotein that activates Natural Killer (NK) and T lymphocytes via the NKG2D receptor.
- MICA is located within the human Major Histocompatibility Complex (MHC) and is highly polymorphic, with potential absence due to deletions near the HLA-B locus.
Purpose of the Study:
- To investigate the distribution of MICA deletion (MICA*del) and other MICA null alleles across diverse biogeographic regions.
- To analyze the Linkage Disequilibrium (LD) patterns between MICA deletion alleles and the HLA-B locus.
- To characterize the extent of MICA deletions and identify individuals with complete absence of functional MICA or MIC genes.
Main Methods:
- Population-based genetic analysis to determine the frequency of MICA deletion alleles.
- Linkage Disequilibrium (LD) analysis to assess the association between MICA deletion and HLA-B alleles.
- Molecular characterization of deletion patterns (full vs. partial MICA deletion).
Main Results:
- Identified at least two distinct MICA deletion patterns, suggesting independent deletion events.
- Confirmed MICA*del is primarily associated with HLA-B*48 and MICB*009N in Asian and American populations, though other haplotypes exist.
- Observed that most individuals with MICA deletions are heterozygous, possessing at least one functional MICA or MICB gene, but identified rare cases of complete MICA or MIC gene absence.
Conclusions:
- The distribution of MICA null alleles varies geographically, indicating population-specific genetic events.
- The study provides insights into the complex genetic architecture of the MHC region concerning MICA deletions and their associations with HLA-B.
- The existence of individuals lacking functional MICA or MIC genes suggests potential compensatory mechanisms in the immune system.
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