Strong Linkage of the Single Nucleotide Polymorphism rs77308790 with an α0-Thalassemia (– –SEA deletion) Allele and Application for Double-Check Diagnosis of Hb Bart's Hydrops Fetalis Syndrome in Thailand. (3rd September 2019)

• Record Type: Journal Article
• Authors: Jomoui, Wittaya; Tepakhan, Wanicha; Karnpean, Rossarin
• Is Part Of: Hemoglobin. Volume 43:Number 4/5(2019)
• Page Start: 236
• Page End: 240
• Publication Date: 2019-09-03
• Subjects: α0-Thalassemia (α0-thal) (– –SEA deletion) -- single nucleotide polymorphism (SNP) -- rs77308790; Hemoglobinopathy -- Periodicals; Hemoglobin -- Periodicals; Hematology -- Periodicals; Thalassemia -- Periodicals; Blood -- Diseases -- Periodicals; 612.1111
• DOI: 10.1080/03630269.2019.1666720
• Languages: English
• ISSNs: 0363-0269

Abstract

Abstract: The α 0 -thalassemia (α 0 -thal) [– – SEA (Southeast Asian) deletion] is highly prevalent in Southeast Asia and South China. The linkage between the single nucleotide polymorphism (SNP) rs77308790 and the – – SEA deletion was reported in the Chinese population. This study reported the genotype of SNP rs77308790 using the high resolution melting (HRM) curve analysis in the Thai population and the application for double-checking diagnosis of Hb Bart's (γ4) hydrops fetalis syndrome. A total of 202 samples, including α 0 -thal carriers (– – SEA /αα) ( n = 99) and wild-type ( n = 103), was recruited. Minor allele frequency (MAF) of SNP rs77308790 (T allele) represented a significant difference ( p <0.001) between carrier (– – SEA deletion) (MAF 0.455) and wild-type (MAF 0.039). The T allele of SNP rs77308790 showed a strong linkage with the – – SEA deletion allele [correlation coefficient between pairs of loci (D' = 1)] based on constructed random samples (CRSs) in Thais. Moreover, worldwide populations, based on the 1000Genomes database, also found the T allele to be less than 1.0%. For providing a double-checked diagnosis, two SNP (rs3760053, rs77308790) genotypes showed 100.0% concordance with a conventional gap-polymerase chain reaction (gap-PCR) method in nine families at-risk for Hb Bart's hydrops fetalis. The double-checked diagnosis based on the two SNPs (rs3760053, rs77308790) is suitable for implementation in routine diagnosis of Hb Bart's hydrops fetalis syndrome. Furthermore, our HRM analysis system can be amplified with a small amount of fetal DNA and could avoid allele dropouts.