ПОЛИМОРФИЗМ ГЕНА DRD4 У ДЕТЕЙ КОЧЕВЫХ И УРБАНИЗИРОВАННЫХ КОРЕННЫХ ЖИТЕЛЕЙ СЕВЕРА ЗАПАДНОЙ СИБИРИ

Ильинских Н.Н.¹, Ильинских Е.Н.²

¹ORCID: 0000-0003-1014-1096, Доктор биологических наук, профессор,

²ORCID: 0000-0001-7646-6905, доктор медицинских наук, профессор,

Сибирский государственный медицинский университет

Исследование выполнено при поддержке грантов РГНФ 15-06-10190 и РФФИ 16-44-700149

ПОЛИМОРФИЗМ ГЕНА DRD4 У ДЕТЕЙ КОЧЕВЫХ И УРБАНИЗИРОВАННЫХ КОРЕННЫХ ЖИТЕЛЕЙ СЕВЕРА  ЗАПАДНОЙ СИБИРИ

Аннотация

Цель этой работы заключалась в оценке распространенности частот аллелей гена DRD4 у кочевых и городских жителей севера Западной Сибири. Исследование было проведено в школах-интернатах  Пуровского района  Ямало-Ненецкого автономного округа (ЯНАО), где были дети кочевых народов (ДК) и дети, чьи родители постоянно жили (ДО) в поселке. У 178 ДК и 140 ДО были получены образцы клеток буккального эпителия для цепной реакции полимеразы (PCR).  Установлено, что дети кочевых родителей, которые являются оленеводами и городские жители YaNAA, значительно отличаются по частоте DRD4 * 7R аллелей. 

Ключевые слова: DRD4; Cибирь; этнические группы; кочевые популяции. урбанистические популяции.

Ilyinskikh N.N.¹, Ilyinskikh E.N.²

1ORCID: 0000-0003-1014-1096, PhD in Biology, Professor,

2ORCID: 0000-0001-7646-6905, MD, Professor,

Siberian State Medical University

This work was supported by grants RFH 15-06-10190 and RFBR 16-44-700149

DRD4 GENE POLYMORPHISM IN CHILDREN OF NOMADIC AND URBAN INDIGENOUS POPULATIONS IN THE NORTH OF WEST SIBERIA

Abstract

The aim of the work was to assess prevalence of the frequencies of the DRD4 gene alleles in nomadic and urban residents of the north of West Siberia. The study was performed in the boarding schools of Purovsky district of  Yamal-Nenets Autonomous Area (YaNAA) where were both the children of nomadic people (ChNP) and the children whose parents permanently lived (ChPLP) in a settlement. The samples of buccal epithelial cells for the polymerase chain reaction (PCR) were obtained from 178 of the ChNP and 140 of the ChPLP.  Found that the children of the nomadic parents who are reindeer herders and the urban residents of YaNAA are significantly distinguished by the frequency of DRD4*7R allele.

Keywords: DRD4; Siberia; ethnic groups; nomadic population. urban population.

Introduction

Dopaminergic system DRD4 gene are associated with cognitive human activity [10]. Repeat region are found in exon 3 of this gene. The number of repetitions can be from 2 to 11. Particular attention is drawn to a DRD4*7R allele with 7 repeats emerged in humans according to some scientists [7, 12] about 40,000 years ago during the migration of modern man from Africa to Eurasia. A study of Brazilian scientists [11] have demonstrated that this allele is very often present in the genotype of Native American nomadic tribes of "hunter-gatherers" and much less often it is observed in the sedentary Native Americans. Perhaps just such features as "novelty seeking" and "perseverance" which are typical for the "gatherers" with DRD4*7R [8] give them advantage in their nomadic lifestyle. The advantage is likely to disappear when a person moves to a settled way of life and undergoes "selection". However, it was found that the DRD4*7R allele is much less common in the Mongoloid populations than it is observed in European and American populations [6]. Our previous study have shown significant differences the frequency of DRD4*7R allele between the students who came to study from the northern regions of West Siberia [2].

The aim of the work was to assess prevalence of the frequencies of the DRD4 alleles in nomadic and urban residents of Yamal-Nenets Autonomous Area (YaNAA) of Tyumen Region belonging to different ethnic groups.

Material and methods

We examined schoolchildren belonging to different indigenous ethnic groups including Nenets, Selkups, and Khanty whose parents either resided in the local settlements or lead a nomadic way of life rearing their reindeer herds in YaNAA of Tyumen Region. The study was performed in the boarding schools of Purovsky district of YaNAA where were both the children of nomadic people (ChNP) and the children whose parents permanently lived (ChPLP) in a settlement. The samples of buccal epithelial cells for the polymerase chain reaction (PCR) were obtained from 178 of the ChNP and 140 of the ChPLP. Informed consents were received from the children’s parents or their guardians to carry out this research. The schoolchildren were also divided into subgroups based on ethnicity (Nenets, Selkups, and Khanty). The samples of DNA were extracted from the buccal epithelial cells by means of reagents and a technique developed by PrepFiler Automated Forensic DNA Extraction Kit (USA). Amplification of the DNA loci studied was performed by PCR using thermocycler "Tertsik" ("OOO DNA technology", Moscow. Russia).

To determine the DRD4 alleles used the technique described earlier [5]. The differences between the frequencies of prevalence of these gene alleles in the groups was assessed by the criterion χ² using the program «Statistica 6.0». Statistically significant difference between the samples was considered in p <0.05.

Results and discussion

Except for nomadic Khanty, the most of the schoolchildren had DRD4*4R allele (Table 1). Some investigators believe that all alleles of this cluster are derived from the ancestral variant DRD4*4R allele and therefore this allele is found in the most of the human population more frequently than the others [8].

Table 1 – Prevalence of the frequencies of DRD4 alleles in different ethnic groups of schoolchildren in Yamal-Nenets Autonomous Area

DRD4 allele	Frequencies of DRD4 alleles in different ethnic groups
	Selkups % (val.)			Nenets % (val.)			Khanty % (val.)
	Nomadic n=56	Settled n=50	P	Nomadic n=51	Settled n=43	P	Nomadic n=24	Settled n=47	P
*2R	8.9 (5)	6.0 (3)	0.08	13.7 (7)	6.9 (3)	0.02	16.7 (5)	8.5 (4)	0.04
*3R	3.6 (2)	4.0 (2)	0.56	5.9 (3)	9.3 (4)	0.06	0	6.4 (3)
*4R	48.2 (27)	64.0 (32)	0.04	52.9 (27)	58.1 (25)	0.23	12.5 (3)	70.2 (33)	0.01
*5R	12.5 (7)	12.0 (6)	0.89	7.8 (4)	9.3 (4)	0.36	41.7 (10)	6.4 (3)	0.01
*6R	5.4 (3)	4.0 (2)	0.62	3.9 (2)	6.9 (3)	0.12	4.2 (1)	4.3 (2)	0.56
*7R	19.6 (11)	6.0 (3)	0.02	13.7 (7)	4.7 (2)	0.03	29.2 (7)	4.3 (2)	0.01
*8R	1.8 (1)	4.0 (2)	0.06	2.0 (1)	4.7 (2)	0.09	0	0

Among the nomadic Khanty, there is a significant increase in the frequencies of prevalence of the DRD4*2R (p<0.04), DRD4*5R (p<0.01), and DRD4*7R (p<0.01) alleles, while the frequency of the individuals with the DRD4*4R allele (p <0.01) is significantly reduced. The DRD4*7R allele are found almost in every 4^th individual of the nomadic Khanty, in every 5th of the nomadic Selkups, and in every 7^th of the nomadic Nenets.

For comparison, among the urbanized ethnic subgroups, the frequency of prevalence of this allele is significantly lower: 24 % of the settled Khanty, 22 % of the settled Nenets, and 17 % of the settled Selkups. Among the nomadic Nenets, there was a significant increase in the frequency of persons with DRD4*2R allele (13.7% in ChNP and 6.9% in ChPLP; p<0.02).

It is known that the sign of "novelty seeking" in some Mongoloid groups is found in the individuals with DRD4*2R allele, which is prevalent among these populations, but is not in the ones with DRD4*7R allele [12]. Among the nomadic Nenets, 13.7% of the 51 schoolchildren have both DRD4*2R and DRD4*7R alleles.

    When psychological testing, the majority of Europeans with a higher index of "novelty seeking" have the allele DRD4*7R, while, by contrast, in the Finnish population, this sign is found in the individuals with DRD4*2R and DRD4*5R alleles [9]. Perhaps, this association pertains to the nomadic Khanty who, as it is known, are related to the Finno-Ugric peoples.

Among the ethnic groups of the north of West Siberia, the Khanty are the most urbanized group. As a result of the active migration of a significant number of male population to YaNAA from the European part of Russia and the CIS countries, who are mainly occupied in oil and gas production, there is hybridization between the indigenous and migrant populations. This effect is the most clearly manifested in the Khanty [3]. The same may be said of Selkups [4].

Other associations in mate choice occurs in the Nenets. They are not prohibited marriages between close relatives. Therefore, in the Forest Nenets, there are more common individuals who are homozygous for a significant number of loci [1]. These features of assortative marriage, there appears to have effect on the prevalence of allele frequencies among ethnically different groups of the schoolchildren. It is presumed that the allele DRD4*2R occurred in the Mongoloid race as a result of recombination between the DRD4*4R and DRD4*7R alleles. Therefore, the DRD4*2R allele plays a role of the DRD4*7R allele in Asian populations [12].

Conclusion

Thus, the results suggest that there are significant differences of DRD4 gene allele frequency among the schoolchildren of YaNAA belonging to different ethnic groups. The children of the nomadic parents who are reindeer herders and the urban residents of YaNAA are significantly distinguished by the frequency of DRD4*7R allele. The Nenets schoolchildren are also characterized by the higher frequency of DRD4*2R allele.

Список литературы / References

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Список литературы на английском языке / References in English

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5. Benjamin J., Ebstein R., Belmaker H. Molecular genetics and human personality. ed. R. Ebstein. Washington: American Psychiatric Publishing Inc.; 2002.
6. Chang F. M., Kidd J. R., Livak K. J. The world-wide distribution of allele frequencies at the human dopamine D4 receptor locus// Hum. Genet.- 1996.- Vol.98, №1.- P. 91-101.
7. Ding Y. C., Chi H. C., Grady D. L. Evidence of positive selection acting at the human dopamine receptor D4 gene locus// Proc Natl Acad Sci USA.- 2002.- Vol. 99, №1.- P. 309-314.
8. Ebstein R. P. Saga of an adventure gene: novelty seeking, substance abuse and the dopamine D4 receptor exon III repeat polymorphism// Моl. Psychiatry.- 1997. Vol. 2.- P. 381-384.
9. Ekelund J., Lichtermann D., Jarvelin M. R. Association between novelty seeking and the type 4 dopamine receptor gene in a large Finnish cohort sample//  J. Psychiatry.-1999.- Vol 156, №9.- P.1453-1455.
10. Seaman M. L, Fisher J. B., Chang F. Tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4)// Am J Med Genet.- 1999.- Vol. 88,№ 6.- P. 705-709.
11. Tovo‐Rodrigues S. M., Callegari‐Jacques M. L., Petzl‐Erler L. Dopamine Receptor D4 Allele Distribution in Amerindians: A Reflection of Past Behavior Differences? // Amer. J of Physical Anthrop.- 2010.- Vol. 143, №3.- P.458-464.
12. Wang E., Ding Y. C., Flodman P. The genetic architecture of selection at the human dopamine receptor D4 (DRD4) gene locus// Am J Hum Genet.- 2004.- Vol. 74, №5.- P. 931-944.