On the MICA deleted‐MICB null, HLA‐B*4801 haplotype

Abstract

A 100-kb deletion including the MICA gene was recently reported in the HLA-B48 (B*4801)-associated haplotype in Japanese. Interestingly, this MICA deletion is accompanied by a MICB null allele, MICB0107N. In order to further investigate the universality of the apparent tight linkage between these two events, we present data on high-resolution deletion mapping of eight HLA-B48-homozygous individuals. Among these, five carried the MICA deletion linked to MICB0107N, as originally reported. Conversely, the remaining three possessed an intact MICA gene of MICA008 or MICA010 allelic variant associated this time with a putative expressed MICB allele, MICB0102. These results may imply that the expression of both MICA and MICB molecules is indispensable to viability through a yet-to-be understood mutual interaction in immune surveillance.

TNFandLTAGene, Allele, and Extended HLA Haplotype Associations with Severe Dengue Virus Infection in Ethnic Thais

“…HLA-B48 occurs predominantly in Oriental and Amerindian populations, but is virtually absent in Africans and Caucasoids (see www.allelefrequencies.net). HLA-B48 is also associated with a gross deletion of the non-classical MHC class I chain related (MIC) gene loci adjacent to HLA-B in the human MHC [31], which encode target ligands for natural killer (NK) cells utilizing the ubiquitous activatory lectin-like receptor NKG2D [32]. NK cells have a variety of immuno-regulatory and antiviral activities, and activation of NK cells is a feature of DENV infection in our ethnic Thai cohort [41].…”

“…DHF disease severity grades 1-3 are defined according to WHO criteria [2]. SNP-defined TNF and LTA haplotype profiles detected only in patients with secondary DHF, and relatively rare HLA alleles and haplotypes associated with null expression of MHC-encoded proteins [31,33], are given in bold. …”

Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence

“…The gorilla, indeed, appears to have only one MIC gene with a strong sequence similarity to the human MICA (25,26). In humans, individuals carrying the HLA-B*4801 allele (rare in Caucasians but more common in Northeast Asians as well as Native Americans) have lost the MICA locus also due to a large 100-kb genomic deletion surrounding and including this locus (albeit the genomic breakpoints are distinct from those observed in chimpanzee) (27,28). All in all, it is quite intriguing that an equal-sized deletion involving this very same region and genes (MICA͞B) has happened at distinct points in time in several different primate species.…”

ERVK9, transposons and the evolution of MHC class I duplicons within the alpha-block of the human and chimpanzee

“…In most humans, the duplicons of category D contain the units HLA-17 pseudogene/ERV16 (P5.8)/MICA and HLA-X pseudogene/ERV16 (P5.1)/MICB and some retrotransposon markers that are different to those of the category A to C duplicons. Surprisingly, the MICA, HLA-X and ERV16 (P5.1) sequences have been lost from some human NE Asian and South American population groups with the haplotype MICAdel/MICBnull/HLA-B48 (Ota et al, 2000;Komatsu-Wakui et al, 2001;Aida et al, 2002) due to a 100-kb genomic deletion by homologous recombination at the 5) and 3) flanking GA repeat sequences (Komatsu-Wakui et al, 1999). Similarly, the Patr-X pseudogene and ERV16 (P5.1) sequences have been lost from the chimpanzee MHC due to a 95-kb deletion resulting in the formation of a chimeric Patr MICA/MICB gene probably due to a homologous recombination between the MICA and MICB genes (Kulski et al, 2002;Anzai et al, 2003).…”

“…In addition, the MICA and MICB genes have been fused into one chimeric Patr MIC gene by a recombination and deletion event within the chimpanzee beta-block at a time after the separation of humans and chimpanzees from a common lineage (Kulski et al, 2002;Anzai et al, 2003). However, the MICA and MICB genes are both noncoding (Komatsu-Wakui et al, 1999) in some human NE Asian and South American population groups (Ota et al, 2000;Komatsu-Wakui et al, 2001;Aida et al, 2002). In contrast to the beta-block, all of the MIC sequences within the alpha-block are fragmented genes and probably non-functional.…”