β-globin gene cluster haplotypes in ethnic minority populations of southwest China

Abstract

The genetic diversity and relationships among ethnic minority populations of southwest China were investigated using seven polymorphic restriction enzyme sites in the β-globin gene cluster. The haplotypes of 1392 chromosomes from ten ethnic populations living in southwest China were determined. Linkage equilibrium and recombination hotspot were found between the 5′ sites and 3′ sites of the β-globin gene cluster. 5′ haplotypes 2 (+−−−), 6 (−++−+), 9 (−++++) and 3′ haplotype FW3 (−+) were the predominant haplotypes. Notably, haplotype 9 frequency was significantly high in the southwest populations, indicating their difference with other Chinese. The interpopulation differentiation of southwest Chinese minority populations is less than those in populations of northern China and other continents. Phylogenetic analysis shows that populations sharing same ethnic origin or language clustered to each other, indicating current β-globin cluster diversity in the Chinese populations reflects their ethnic origin and linguistic affiliations to a great extent. This study characterizes β-globin gene cluster haplotypes in southwest Chinese minorities for the first time, and reveals the genetic variability and affinity of these populations using β-globin cluster haplotype frequencies. The results suggest that ethnic origin plays an important role in shaping variations of the β-globin gene cluster in the southwestern ethnic populations of China.

Interactions of unstable hemoglobin Rush with thalassemia and hemoglobin E result in thalassemia intermedia

“…Moreover, the Hb Rush variant in the different Chinese families was linked to a common β-globin gene cluster haplotype [+----+-], thus suggesting a common origin of the variant in the populations of Southwest China, presumably owing to a founder effect. However, the haplotype [+----+-] is a prevalent haplotype that is associated with thalassemia and normal β-globins in the region [22], it may be generated by recombination and gene conversion events [23]. Therefore, our findings do not exclude the possibility that the unstable Hb Rush variant might have arisen more than once in Chinese populations.…”

Genetics background of β‐thalassemia (3.5 kb deletion) in Southern Thailand: Haplotype analysis using novel reverse dot blot hybridization

“…The β 3.5 kb deletion chromosome was found to be closely related to haplotype H2, with only one change (rs77526129 ( Hinc II‐5′ε)) from the ancestral haplotype. For comparison of the β A haplotype, previously reported information was also listed, as shown in Table 3 (Aggarwal et al., 2013; Callegari‐Jacques et al., 2007; Chan et al., 1986; Fucharoen et al., 2002; Long et al., 1990; Shimizu et al., 2004; Shimizu et al., 2008; Shimizu et al., 2006; Sun et al., 2017). The result showed that haplotype H2 is the most frequent haplotype in Thai, Chinese, Indians, other Asian, European, and American Indian populations, except in the African population.…”

“… 3 a Data from Fucharoen et al, 2002; b data from Aggarwal et al, 2013; c data from Chan et al, 1986; d data from Shimizu et al, 2008; e data from Sun et al, 2017; f data from Shimizu et al, 2006; g data from Shimizu et al, 2004; h data from Long, Chakravarti, Boehm, Antonarakis, & Kazazian, 1990; i data from Callegari‐Jacques et al, 2007. The symbols (‐ or +) indicate the absent (‐) or present (+) of each polymorphic site, respectively.…”

“…The haplotype analysis has been explored to determine the clinical relationship, the evolutionary study and the origin of mutation (Jomoui et al, 2017;Jomoui et al, 2019;Steinberg, 2005). For haplotype analysis of the β-globin gene cluster, seven polymorphic sites are commonly used, including five polymorphic 5′-haplotype sites (HincII-5′ε, HindIII-G γ, HindIII-A γ, HincII-5′ψβ, and HincII-3′ψβ) and two polymorphic 3′-haplotype sites (AvaII-β and HinfI-3′β) (Sun et al, 2017). β-thal (3.5 kb deletion) was found to be caused by a 3,490 bp deletion of the promoter and whole β-globin gene (Lynch et al, 1991 sequences were not homologous at upstream and downstream of the breakpoint region.…”

“…Previously, many haplotype studies have tended to use the PCR‐RFLP method (Aggarwal et al., 2013; Chan et al., 1986; Shimizu et al., 2008; Sun et al., 2017). However, this method is laborious, expensive, and time‐consuming.…”