Estimating the age of Hb G‐Coushatta [β22(B4)Glu→Ala] mutation by haplotypes of β‐globin gene cluster in Denizli, Turkey

Abstract

BackgroundHb G‐Coushatta variant was reported from various populations’ parts of the world such as Thai, Korea, Algeria, Thailand, China, Japan and Turkey. In our study, we aimed to discuss the possible historical relationships of the Hb G‐Coushatta mutation with the possible migration routes of the world. For this purpose, associated haplotypes were determined using polymorphic loci in the beta globin gene cluster of hemoglobin G‐Coushatta and normal populations in Denizli, Turkey.MethodsWe performed statistical analysis such as haplotype analysis, Hardy–Weinberg equilibrium, measurement of genetic diversity and population differentiation parameters, analysis of molecular variance using F‐statistics, historical‐demographic analyses, mismatch distribution analysis of both populations and applied the test statistics in Arlequin ver. 3.5 software program.ResultsThe diversity of haplotypes has been shown to indicate different genetic origins for two populations. However, AMOVA results, molecular diversity parameters and population demographic expansion times showed that the Hb G‐Coushatta mutation develops on the normal population gene pool. Our estimated τ values showed the average time since the demographic expansion for normal and Hb G‐Coushatta populations ranged from approximately 42,000 to 38,000 ybp, respectively.ConclusionOur data suggest that Hb G‐Coushatta population originate in normal population in Denizli, Turkey. These results support the hypothesis that the multiple origin of Hb G‐Coushatta and indicate that mutation may have been triggered the formation of new variants on beta globin haplotypes.

Protein structure analysis of abnormal hemoglobins; Hb D-Los Angeles, Hb S and Hb G-Coushatta

“…Hb G-Coushatta data associated with the [− + − + + + +] haplotype in Denizli, Türkiye have been published [4,29]. It has been reported that the Hb G-Coushatta cases in this region date back to 38,000 ybp [30]. Similar to Hb D-Los Angeles, individuals with Hb G Coushatta may experience mild hemolytic anemia, but the clinical severity can vary.…”

A novel compound heterozygous of β-thalassemia with HbG-Coushatta: case report of Iran

“…Hemoglobin G-Coushatta with the preferred name NM_000518.4(HBB):c.68A>C (p.Glu23Ala) is an abnormal β-chain structural Hb caused by the substitution of the glutamyl group within residue at position 22 [β22 (B4)Glu →Ala] 3 . This type of Hb variant was identified in various countries, such as Japan, Algeria, Korea, Turkey, and Thailand 3 – 7 .…”

“…HbG-Coushatta has the substitution of the negatively charged glutamyl group with a neutral alanine residue at position 22 3 . This replacement typically affects the distribution of charges and impairs molecular function.…”