KIR2DL4 variability and haplotypes in a Brazilian population sample from the State of São Paulo.

Author(s)

Emiliana Weiss

• Document type: Master's Dissertation
• Press: Botucatu. 2019-05-23.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2019-03-11
• Advisor: Erick da Cruz Castelli

Abstract

KIR2DL4 is the most unusual Killer Cell Immunoglobulin-Like receptor (KIR) family member in terms of structure, expression, and signaling properties. The only known KIR2DL4 ligand is HLA-G, and polymorphisms might disrupt this interaction. KIR2DL4 variability is not well explored in admixed populations. Here we explored KIR2DL4 exon variability in 157 individuals from the State of São Paulo/Brazil. Because of sequence similarity with other KIR genes, it is expected genotyping errors when using secondgeneration sequencing. We developed an approach to score each read based on known KIR sequences, addressing them to the most likely locus. We evaluated the SNPforID 34-plex panel to assess ancestry. The methodology was applied to survey the variability of a very admixed population, such as Brazilian, counting with 157 samples of São Paulo State. Considering a segment of about 13-kb, KIR2DL4 gene was conserved with few different and frequent sequences. Overall, 152 variable sites were detected, arranged in 32 haplotypes codifying 13 protein. We found 11 promoter haplotypes, 8 with a frequency greater than 1%. In the coding region we detected 70 haplotypes, four of which correspond to 50% of the coding sequences (KIR2DL4 * 0080204, * 008105, * 001, * 005). In the 3'UTR region, 14 haplotypes were identified with MAF greater than 1%. The KIR2DL4 coding region was the most variable segment. We observed that KIR2DL4 variability is strongly influenced by the sample ancestry background. KIR2DL4 is highly conserved at both the DNA and protein levels. (AU)

• FAPESP's process: 17/05042-4 - KIR2DL4 variability and haplotypes in a Brazilian population sample from the State of São Paulo.
• Grantee: Emiliana Weiss
• Support Opportunities: Scholarships in Brazil - Master