A novel nonsense mutation found in the CD177 gene of Thai individuals with the HNA‐2 null phenotype
| Autor: | Oytip Nathalang, Sawang Petvises, Jeeraphong Thanongsaksrikul, Kamphon Intharanut, Kanokpol Siriphanthong |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Isoantigens Nonsense mutation Blood Donors Receptors Cell Surface Single-nucleotide polymorphism 030204 cardiovascular system & hematology Biology GPI-Linked Proteins Polymorphism Single Nucleotide 03 medical and health sciences Exon 0302 clinical medicine Genotype Humans Gene Genetics Homozygote Heterozygote advantage Exons Hematology Thailand Codon Nonsense Mutation (genetic algorithm) Female Primer (molecular biology) 030215 immunology |
| Zdroj: | Transfusion Medicine. 30:30-36 |
| ISSN: | 1365-3148 0958-7578 |
| DOI: | 10.1111/tme.12650 |
| Popis: | Objectives The aim of this study is to explore the molecular basis and to develop a simple sequence-specific primer polymerase chain reaction (PCR-SSP) technique for screening genotypes associated with the human neutrophil antigen-2 (HNA-2) null phenotype among Thai blood donors. Background Single-nucleotide polymorphisms (SNPs) c.787A>T of the CD177 gene is well known to be primarily demonstrated as a genetic determinant for HNA-2 deficiency. Methods The SNPs in the CD177 gene (exons 7 and 9) of 49 Thai blood donors with the known percentage of CD177 expression by flow cytometry including 48 HNA-2 positive and 1 HNA-2 null individuals were identified by long-range PCR amplification and sequencing. Moreover, screening for the c.1254G>A mutation was developed using an in-house PCR-SSP technique and tested among 771 unrelated donor samples. Results A HNA-2 null sample from the first cohort was heterozygous for c.787A/T and homozygous for c.1291G/G, namely, a 787A-1291G/787T-1291G (AG/TG) genotype. Interestingly, we could identify SNP c.1254G>A (rs188387562, p. Trp418Ter) that caused a nonsense mutation of the CD177 gene in exon 9. This individual might have the 787A-1254A-1291G/787T-1254G-1291G genotype. From the second cohort (771 unrelated donors), the 1254GG homozygote was the most common (96.37%), followed by the 1254GA heterozygote (3.50%) and 1254AA homozygote (0.13%). Blood samples of two individuals with 787AT-1254GA-1291GG and 787AA-1254AA-1291GG genotypes were tested and the HNA-2 antigen expressions were 0.03% and 0.16% in rank. Conclusions The c.787A>T is a primary genetic hallmark to determine the HNA-2 null phenotype. Additional screening of the novel c.1254G>A in combination with c.787A>T is a suitable, convenient and effective diagnosis among Thais. |
| Databáze: | OpenAIRE |
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