High population frequencies of MICA copy number variations originate from independent recombination events

MICA is a stress-induced ligand of the NKG2D receptor that stimulates NK and T cell responses and was identified as a key determinant of anti-tumor immunity. The gene is located inside the MHC complex and is in strong linkage disequilibrium with . While an -linked deletion-haplotype was previously described in Asian populations, little is known about other copy number variations. Here, we report the genotyping of more than two million individuals revealing high frequencies of duplications (1%) and deletions (0.4%). Their prevalence differs between ethnic groups and can rise to 2.8% (Croatia) and 9.2% (Mexico), respectively. Targeted sequencing of more than 70 samples indicates that these copy number variations originate from independent nonallelic homologous recombination events between segmental duplications upstream of and . Overall, our data warrant further investigation of disease associations and consideration of copy number data in oncological study protocols.