Mithun Sikdar Hemoglobin E in Northeast India Anthropological Review • Vol. 79(3), 241–263 (2016) Hemoglobin E in Northeast India: A review on its origin, distribution, migration and health implication Mithun Sikdar DNA Laboratory Unit, Anthropological Survey of India, Government of India, Western Regional Centre ABSTRACT: A systematic review of the studies on hemoglobin E in Northeast India has been carried out to understand the magnitude of research undertaken on this aspect during the last seven decades. Owing to the high prevalence of hemoglobin E in this part of India different authors have studied this hemoglobin from different perspectives and found conflicting results. However a systematic review of such studies is lacking from a holistic point of view. Most of the epidemiological, in vitro as well as in vivo studies show signatures of selection with this hemoglobin locus. However, how this polymorphism is maintained at dif- ferent rates at different geographical region is still a matter of contention. This review will fill the gap from all perspectives starting from the frequency distribution of hemoglobin E and its spread in different parts of Northeast India, its relationship with malaria hypothesis, the population migration, population affinity and most importantly the health implication arising out of it. A probable origin of hemoglobin E among an Austroasiatic population of Northeast India has been postulated with the help of advance molecular anthropological knowledge like the deep rooted markers of mt DNA and Y-chromosome haplotypes. KEY WORDS: Hemoglobin E, Northeast India, selection, population affinity, health chromosome 11p15.5 is one of the most Introduction intensely studied genetic polymorphism of all human loci. The DNA polymor- It has been estimated that more than phism present in the hemoglobin cluster 70 lakh babies born each year with ei- is also very interesting and it has also ther a congenital abnormality or with been extensively used to examine human a genetic disease (Christianson et al. evolutionary history (Das and Talukdar 2006). Approximately 25% of these ba- 2001). Mutation of β-globin gene causes bies suffer from only five disorders of β-thallasemia and other hemoglobinopa- which two belong to inherited disorders thies of which HbS, HbE, HbD and HbC of hemoglobin (Weatherall 2010). As are most common genetic abnormalities such human β-globin gene located on in the world including India. Spatial dis- Review Article Received: January 3, 2016; Accepted for publication: July 22, 2016 DOI: 10.1515/anre- 2016-00 19 © 2016 Polish Anthropological Society 242 Mithun Sikdar tribution of the deleterious β-globin mu- Materials and methods tations in Indian population is extremely diverse and certain mutations are re- A search of PUBMED, MEDLINE and stricted to particular population groups EMBASE (1950 to January 2016) da- only. Various evolutionary forces such tabases was supplemented by manual as natural selection, mutation, recom- searches of bibliographies of key retrieved bination, migration and genetic drift are articles, reviews of abstracts from scien- known to regulate the frequency of these tific meetings, and contact with experts. deleterious mutations in human popula- The search has been carried out taking tion. Of the various structural hemoglo- into consideration few points in mind bin variants, HbS (Codon 6A-T) variant i.e. peopling of Northeast India, hemo- is widespread among various tribal pop- globin research in Northeast India par- ulations of India (frequency 0–40.0%) ticularly in different states of Northeast where a small frequency has also been India, origin and spread of hemoglobin found among the caste populations (Rao, E, hemoglobin E and malaria hypothesis, 1998). HbD Punjab (Codon 121 G-C) hemoglobin E and health. Further the has an incidence of 2–3% among the Sikh frequency distribution of this particular population of Punjab and is also reported hemoglobin variant in different states of among some other population groups of Northeast India has been supplemented India. On the other hand HbE (Codon 26 in different tables. G-A) is confined exclusively (frequency 0.4–64.5%) among the people originat- Peopling of Northeast India ing from Eastern India, especially North- east India. It has been argued that the Many researchers veered their attention different forms of abnormal hemoglobin to Northeast Indian region due to its originated in different parts of the world considerable variation in ethnic and lin- due to its different survival advantages guistic structure. It is bordered by the and one of such advantages being the Himalayas and the Bay of Bengal in the endemic malarial condition. Because of North and South respectively and it con- conduciveness of abnormal hemoglo- stitutes an exclusively slender passage bin in the malaria endemic areas most that connects the Indian subcontinent of the population groups of Northeast to East Asia and Southeast Asia. Earli- India have been studied during the last er the entire Northeastern part of India few decades either singly or in combina- was referred to as Assam but after the tion to have the distributional pattern of Independence of India in 1947 new ter- hemoglobinopathies in different popula- ritories and states were came into being. tion groups. It is very important to have Now the region is composed of seven ad- a sum up of most of the works on he- ministrative units and is the homeland moglobin E in Northeast India to have of different ethnic communities with its trend of research and to gear up new diverse linguistic and sociocultural tra- possibilities of research in this particular ditions. In 2002 the state of Sikkim was domain. also included as the eight administrative part of Northeast India. It is said that the diverge population came to this main- land India from different directions and Hemoglobin E in Northeast India 243 at different times through various routes represented by the Indid Assamese, the like the Northern passage which opens at major inhabitants of Brahmaputra val- Bhutan and Tibet, the Eastern route of ley. Tibeto-Burmese populations are the Assam-Myanmar and from the Western earliest inhabitants of this land. One of route which constitutes the Ganges and the subdivisions of Tibeto-Burman i.e. Brahmaputra valley. North-Assam group of languages are The extensive linguistic diversity of spoken by most of the tribes of Aruna- Northeast India is represented by three chal Pradesh as well as Assam and Ma- major linguistic families: Austro-Asiat- nipur. Another subdivision known as As- ic, Indo-European and Tibeto-Burman. sam-Burma group is spoken by the Bodo The Austro-Asiatic group has a linguis- group of tribes of Assam, Meghalaya and tic relation with the Mon-Khmer people Tripura; Karbis of Assam; Nagas of Na- of mainland Burma as well as Thailand galand; Mizo-kukis of Mizoram; Meities and its main representative is the Kha- of Manipur etc. Besides, there is anoth- sis of Meghalaya. The Khasis practice er linguistic group i.e. Siamese-Chinese, matriarchy unlike the other tribal popu- which is spoken by a limited number of lation of Northeast India. It is believed population groups. Tai which is one of that the Indo-European group migrated the sub divisions of Siamese Chinese to this particular land from the West and is spoken by Aiton, Turung, Khamti, Fig. 1. Map of Northeast India showing different regions. 244 Mithun Sikdar Khamyang and Phakials of Assam and an Assamese caste population of Low- Arunachal Pradesh. Once, Tai was also er Assam as a base for comparison. The the original language of the Ahom, a ma- first publication (Das et al. 1971) of this jor population group of Assam. A more study showed a high frequency of HbE recent addition to the population of (0.2 19) among the Khasi, and a higher Northeast India is the tribal people of frequency (0.359) among the Ahom. The Orissa and Chotonagpur most of which second publication of the survey (Flatz are from the Kolarian linguistic group et al. 1972) also validates the earlier and were brought to this mainland as findings. The high frequency of the gene workers in the tea gardens of Assam. among the Khasis was consistent with the hypothesis of a correlation between Hemoglobin E research Austro-Asiatic linguistic affiliations with HbE. in Northeast India At that time the high prevalence of HbE gene among the Ahom led to much Research on hemoglobin E started in speculation. Since Flatz et al. (1965) Northeast India when Chatterjea (1959) did not find HbE genotype among the reported some sporadic cases of HbE in Thai population from South-West Chi- Assamese population. A few years latter na they argued that it was not likely that Chaudhuri et al. (1962) reported a rel- the Ahom descended directly from the atively high percentage of HbE (0.099) Thai population of South-West China. among the Totos, a Tibeto-Burman pop- On the other hand historical records in- ulation of Totopara in the Assam-West dicate a process which they interpreted Bengal border. With these few investi- as ‘Thaization’ of Austro-Asiatic groups gations it became an interesting area of throughout South-East Asia during the research in Northeast India just within early centuries of Thai migration (Wood a decade of its discovery (Chernoff et al. 1961). The process was evident in the 1954; Itano et al. 1954). Shan of Burma, who were Thai speak- Initially a strong relationship be- ers with considerable prevalence of HbE tween HbE and Austro-Asiatic linguistic (Than-Batu and Hla-Pe 1971). It was groups of Southeast Asia was pointed highlighted that the Ahoms were once out by Flatz (1967) and he hypothesized a sub division of the Shan, they specu- that high frequency of HbE could also lated that it was quite possible that their be expected in the population groups of genetic structure was predominantly Northeast India which have ethnic rela- Austro-Asiatic inspite of their prevalent tion with Southeast Asia.