GENETIC DIVERSITY OF THE NKG2/CD94 CLUSTER IN WORLD POPULATIONS

• Grant number: 24/22217-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2025
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Erick da Cruz Castelli
• Grantee: Viviane Aparecida de Oliveira Ciriaco
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The cytotoxic function of NK cells is regulated by the balance of activation and inhibition signals from receptors expressed on the NK surface. These receptors interact with various ligands on the target cells. Among these receptors are those of the NKG2/CD94 cluster, encoded on chromosome 12, with six known members: KLRK1, KLRC1, KLRC2, KLRC3, KLRC4, and KLRD1. These genes originated from duplication events of a common ancestor, resulting in genes with similar sequences. Although these genes exhibit low polymorphism, the sequence similarity and structural variants, such as copy number polymorphisms, jeopardize their analysis using short-read sequencing technologies. Therefore, their genetic diversity might be underestimated in some regions while overestimated in others. Preliminary results show cross-alignments among the KLRC2, KLRC1, and KLRC3 genes and alignment failure for KLRC1 and KLRC4. Therefore, getting reliable genotypes and haplotypes demands computational strategies tailored for these genes. This project aims to develop a bioinformatics pipeline tailored to the NKG2/CD94 cluster to detect SNPs, InDels, and haplotypes. Then, we will apply this pipeline to assess the NKG2/CD94 cluster diversity in 5,347 samples from different populations worldwide, including Brazilian samples.