Incidence of the Hb E [β26(B8)Glu→Lys,GAG>AAG] Variant In Totos, One of the Smallest Primitive Tribes in the World

Abstract

Toto is one of the smallest tribes in the world. This primitive sub Himalayan, endogamous tribe lives in a small, isolated village called Totopara in the Jalpaiguri district of West Bengal in India. The tribal communities of West Bengal are vulnerable to various genetic disorders such as β-thalassemia (β-thal). We have studied 443 Totos to define their Hb E [β26(B8)Glu→Lys, GAG>AAG] status. Awareness and screening camps have been organized in various parts of Totopara during the last 2 years. We collected 3 mL peripheral blood from each individual aseptically on which to use the naked eye single tube red cell osmotic fragility test (NESTROFT); complete hemogram and high performance liquid chromatography (HPLC) were done to detect their carrier status. The Hb E variant had been found to be prevalent among the Totos. To confirm the codon 26 (GAG>AAG) mutation in the β-globin gene, amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed. Restriction fragment length polymorphism (RFLP)-PCR was carried out with 44 Hb E alleles to construct the haplotype(s) of the Totos. Our extensive studies have revealed that 49.21% of Totos are Hb E heterozygotes and 19.19% Totos are Hb E homozygotes. The most prevalent haplotype linked with the codon 26 mutation in the Totos is [+ - - - - -] (HincII 5'ϵ, HindIII (G)γ, HindIII (A)γ, HincII 5'ψβ, HincII 3'ψβ and HinfI 3'β). Consanguineous marriages have resulted in a significant increase of the percentages of heterozygotes and homozygotes of Hb E in the Totos. Genetic counseling is essential and important to prevent the spread of this mutation and hence to save them from having any kind of clinically significant hemoglobinopathy in the future.

Hemoglobin E in Northeast India: A review on its origin, distribution, migration and health implication

“…This in turn may increase the genetic load in terms of hemoglobin disorders through reduced level in infant and childhood mortality who will survive until their reproductive period for diagnosis and treatment. Once I hypothesized that together with demographic transition the frequency of the recessive genes like that of hemoglobin E may increase leading to genetic load in a population (Sikdar 2008a) and it became very much implicit with the studies among the Sonowal population of Assam (Barua and Kotal 2008) and Totos of West Bengal (Bhattacharyaa et al 2013). This type of conjuncture can further be established with the help of restudy of different population groups on different abnormal hemoglobin variants over a particular period of time.…”

The Totos of India: Socioeconomic and Demographic Structure of a Particularly Vulnerable Tribe

“…Toto is the smallest, particularly vulnerable tribal group in West Bengal 18 . The Toto population has been distributed in the many pockets of Alipurduar and New Jalpaiguri districts of West Bengal 19 , as well as in the border area of Bhutan 20 , because of their economic activities. Due to the COVID pandemic, the Toto population was getting restricted in a village called Totopara.…”

“…Previous literature has shown that Totos have faced a double burden of different communicable and non-communicable diseases like metabolic syndromes 51 , tuberculosis, malnutrition 52 , malaria, smallpox, and skin problems, like other tribal populations in the hilly terrain of the Himalayan belt 53 . Apart from that burden, the shortfall of healthcare infrastructure was worse than the scarcity.…”

Fannin-Lubbock-I [α2β2119(GLY>ASP)], a rare mutation in the beta-globin gene, has been detected for the first time in a Hindu Brahmin family in West Bengal, India

“…The sequence was compared with the sequence of the Human Genome Mutation Database (HGMD) and the National Centre for Biotechnology Information (NCBI). Haplotype analysis was performed using restriction fragment length polymorphism-PCR (RFLP-PCR) following the standard protocol described in our previous publication [6]. Six restriction endonuclease sites (HindII 5'ε, HindIII G γ, HindIII A γ, HindII 5' Ψβ, HindII 3'Ψβ, and Hinf I 3'β) within the β globin gene cluster were studied to construct the haplotype linked with this mutation.…”