Genetic Origin of Hb D-Los Angeles [β121(GH4)Glu→Gln,GAA→CAA] According to the β-Globin Gene Cluster Haplotypes

Abstract

Hb D-Los Angeles (also known as D-Punjab, D-North Carolina, D-Portugal, D-Chicago and Oak Ridge) is an abnormal hemoglobin (Hb) with an amino acid substitution of glutamine for glutamic acid at codon 121 of the beta-globin gene. The origin and spread of Hb D-Los Angeles is not known. This is due to lack of information and remains to be elucidated. According to published reports, the Hb D-Los Angeles mutation is mostly linked with Mediterranean haplotype I [+ - - - - + +]. Besides the Mediterranean haplotype, a novel haplotype was also reported from Thailand [- - + + - - + + +]. Here we report a new haplotype from Turkey [- + -- + + +] that has not been described before. These results suggest that the Hb D-Los Angeles mutation has at least three different genetic origins.

Does Elevated Hemoglobin F Modulate the Phenotype in Hb SD-Los Angeles?

“…At alkaline pH, its electrophoretic mobility is similar to Hb S, but separates easily on anion or cation exchange chromatography [1]. It is most prevalent in the Indian subcontinent but is seen sporadically in other ethnic groups [2,3,4,5]. Recent β-globin gene cluster haplotype studies have shown that the β 121 GAA→CAA mutation might have originated on at least four different occasions in different parts of the world, which would explain its wide distribution [5,6].…”

Analysis of the population genetic structure of Hb D‐Los Angeles [β121 (GH4) Glu→Gln GAA→CAA] in Denizli, Turkey; genetic diversity, historical demography and estimation of the mutation rates based on haplotype variation

“…Hb D‐Los Angeles is one of the most commonly observed abnormal hemoglobin (Hb) variants worldwide, including Italy, Belgium, Austria, and Turkey (Atalay, ). Distribution of Hb D‐Los Angeles in the observed populations led to the hypothesis that this mutation arose in Central Asia and then spread to other countries.…”

“…Although data on the β‐globin gene cluster haplotypes are limited for the Asian cases (especially from China and India; Patel et al, ), there are two β‐globin gene cluster haplotypes reported in association with the Hb D‐Los Angeles cases as Mediterranean haplotype I [+ − − − − + +] from Mexico (Perea, ), Italy (Fioretti, ), Iran (Rahimi, ) and the previously undescribed haplotype from Thailand [− + + − + + +] (Fucharoen, ). Additionally, two different haplotypes were also observed in association with Hb D‐Los Angeles from the Denizli Province in the Aegean region of Turkey (Atalay, ). Most of the cases were found to be in association with the Mediterranean haplotype I [+ − − − − + +] and linked with the newly reported Turkish haplotype [− + − − + + +] (Atalay, ).…”

Clinical, hematological and genetic data of a cohort of children with hemoglobin SD

“…Haplotype I is the commonest type of D-Punjab allele in almost all ethnic populations so far described 6, 14, 15, 30. The exception is Thailand, where haplotype II was found in nine patients from five families 31 .…”