[Migration as the main factor of the Russia's urban population dynamics].

This review summarizes the results of the long-term studies performed at the Institute of General Genetics, Russian Academy of Sciences, in the field of genetic demography of migration processes in Russia and its capital. The main population-genetic parameters of migration and their dynamics in Moscow over a hundred years are given. Sociodemographic and population-genetic implications of migration processes are considered. A model predicting the population gene pool dynamics under migration pressure for genes of different localization (autosomal, sex-linked, and mitochondrial), exemplified by predicting the allele frequency dynamics in the Moscow population of some gene markers, including genes accounting for monogenic pathology and genes associated with resistance to socially significant diseases, are presented. The paper discusses the selective character of migration processes, in particular, processes of emigration, with respect to some genetically significant ethnodemographic traits; the problem of adaptation of migrants; and adaptive strategies of consolidation of ethnoconfessional groups in the megalopolis (compact settlement over the urban territory and positive assortative mating with respect to demographic traits). It was shown that, owing to the intense influx of migrants and gene flows between ethnic groups, the population of the megalopolis is of mixed origin in terms of ethnic, anthropologic, and genetic aspects. The results of the study suggest the necessity to develop a specific strategy of genetic database formation for the population of megalopolises for the purposes of medical genetics and forensic medicine.

[Genetic demography of populations of three megalopolises in relation to the problem of creating genetic databases].

Based on data collected from urban residents by questionnaire, the basic parameters of the genetic-demographic structure of populations of the three megalopolises, i.e., Moscow, Kharkov, and Minsk, have been calculated, including the migration coefficients and their dynamics in generations, the radius of the cities migration attraction, the parameters of marriage structure (the proportion ofinterethnic marriages, the level of intraethnic assortative mating, the marital distances), and the gene flow between the ethnic groups. It is shown that the representatives of the most numerous ethnic groups in each megalopolis have considerable amount of admixture. For Russians of Moscow, Ukrainians of Kharkov, and Belarusians of Minsk, the proportion of individuals whose ancestors were all born in the given city for at least three generations and belonged to the same nationality turned out to be very low (4.75% in Moscow, 1.83% in Kharkov, and 3.13% in Minsk). This finding questions the formation of a reference population in the megalopolis as a sampling of aboriginals of certain ethnic origins. In the paper, we justify principles of creating genetic databases for the population of the megalopolis taking into account the complexity and dynamism of its population structure.

[Variation of morphophysiological and genetic demographic traits in children with congenital cleft lip and palate].

Medical records and questionnaire data have been used to analyze morphophysiological (the birth weight and length) and genetic demographic (maternal age and marriage structure) traits in a sample of children with orofacial malformations (OMs, cleft palate and/or cleft lip) living in Krasnodar krai, Russia. The sample of children with malformations (including premature infants) differs from the control group in lower birth weight and length and a lower proportion of children with morphophysiological values close to the population average values, as well as a higher family exogamy level estimated on the basis of marriage structure in the parental and preceding generations. The risk of congenital cleft palate and/or cleft lip is considerably increased if the material age is over 35 years or, to a lower degree, if it is under 20 years.

[Population genetic study of Russian cosmonauts and test subjects: genetic demographic parameters and immunogenetic markers].

Genetic demographic characteristics and immunogenetic markers (blood groups ABO, Rhesus, MNSs, P, Duffy, Kidd, and Kell) have been studied in a group of 132 Russian cosmonauts and test subjects (CTSG). Analysis of pedigrees has shown a high exogamy in the preceding generations: almost half of the subjects have mixed ethnic background. According to the results of genetic demographic analysis, a sample from the Moscow population was used as control group (CG). Comparison between the CTSG and CG has demonstrated significant differences in genotype frequencies for several blood group systems. The CTSG is characterized by a decreased proportion of rare interlocus genotypic combinations and an increased man heterozygosity. Analysis of the distributions of individual heterozygosity for loci with codominant expression of alleles has shown that highly heterozygous loci are more frequent in the CTSG. Taking into account that the CTSG has been thoroughly selected from the general population, it is concluded that heterozygosity is related to successful adaptation to a space flight.

[An attempt at the historical reconstruction of the genetic demographic structure of the Moscow population at the turn of the 20th century]. / Opyt istoricheskoi rekonstruktsii genetiko-demograficheskoi struktury moskovskoi populiatsii na rubeze XIX-XX vekov.

The genetic demographic structure of the Moscow population at the turn of the 20th century was studied based on the data from parish books and census records. The main sources of population gene pool replenishment were analyzed, and migration coefficients and the main parameters of the model of isolation by distance were estimated. Data on so-called quasigenetic markers (ethnicity and birthplace) were used to reveal intrapopulation heterogeneity, which facilitates the adaptation of migrants to a new ethnic and cultural environment. The spatial subdivision was analyzed with the use of GST statistics. Muscovites exhibited a considerable positive assortative mating with respect to birthplace. The results of this study provide the necessary historical perspective for predicting the current genetic demographic trends in the Moscow population. It was shown that the co-efficients of marriage migration were almost the same (0.7 < m < 0.8) in the late 19th and mid-20th centuries; however, these values were two times greater than in the late 20th century. This decrease in marriage migration was accompanied by a threefold increase in the radius of centripetal migration and a threefold decrease in the level of isolation by distance. It was determined that the increase in the ethnic and genetic diversity of the Moscow population in the 20th century had started in the 1860s.

[Genetic-demographic processes in the Moscow population in the mid 1990's. Analysis of ethnogeographic migration parameters (isolation by distance)]. / Genetiko-demograficheskie protsessy v moskovskoi populiatsii v seredine 90-x godov. Analiz étnogeograficheskikh parametrov migratsii: izoliatsiia rasstoianiem.

Geographic parameters of migration were analyzed on the basis of data on birthplaces of individuals who contracted marriages in Moscow 1955, 1980, and 1994 to 1995. It was shown that the relationship between the migration rate and distance significantly changed in the 1990s. Investigation of ethnic composition of migrants demonstrated that an increase of migration activity of residents of Transcaucasia and North Caucasus recorded in 1990s was associated with an increase in migration to Moscow of representatives of indigenous populations of these regions rather than with repatriation of Russians. Analysis of migration with the use of the Malecot's model of isolation by distance showed that genetically effective migration accounted for 1/7, 1/3, and 1/4 of the total marital migration rate in 1995, 1980, and 1990, respectively. An increase in mean migration distance in 1995 to 1980 is explained mainly by a decrease in the proportion of short-range migration. The level of isolation by distance was extremely low and showed a trend to further decrease during the 40-year time interval. Parameters of the model indicated that at present the population of the central part of the Moscow oblast in the 80-km zone from the city center should be assigned to the Moscow population.

[Genetic-demographic processes in the Muscovite population in the mid-1990s. Migration and emigration as a factor for changing the genetic diversity of the population]. / Genetiko-demograficheski protsessy v Moskovskoi populiatsii v seredine 1990-x godov. Migratsiia i émigratsiia kak faktora izmeneniia geneticheskogo raznoobraziia populiatsii.

On the basis of official migration statistics and marriage records, the genetic parameters of migration in the Moscow population over the past 120 years were determined. Although the number of officially registered migrants decreased, the coefficient of marriage migration in the mid-1990s was higher than in the mid-1980s (m = 0.4). The in-migrants considerably differed from Moscow-born residents with respect to their age at marriage, ethnicity, level of education, and speciality. The emigration of the Moscow residents to foreign countries was selective with respect to the educational level and adversely affected the labor, intellectual, and cultural resources of Moscow (the "braindrain"). In the long run, the observed ethnic differences between in-migrants and emigrants may considerably influence the ethnic composition and, hence, genetic diversity of the Moscow population.

[Detection of the adaptive significance of human blood group polymorphism by analyzing a series of loci. Level of heterozygosity and variety of phenotypes in two generations]. / Vyiavlenie adaptivnogo znacheniia polimorfizma grupp krovi cheloveka putem analiza sovokurnosti lokusov. Urovni geterozigotnosti i raznoobrazie fenotipov v dvukh pokoleniiakh.

Phenotypes of the blood group systems AB0, Rhesus, MNSs, and P are determined, and the levels of individual heterozygosity are estimated for a set of loci studied in representative samples of newborns and their mothers, representing two generations of the Moscow population. Mothers are shown to differ from their offspring by higher average heterozygosity, lower phenotypic diversity, and a reduced frequency of the "rare" interlocus phenotypic combinations. An optimal heterozygosity level, which provides maximum fitness for a large class of genotypes, is revealed in the reproductive part of the population, while the average population heterozygosity level is two-thirds of the optimal level.

Secular growth trend in two generations of the Russian population.

A retrospective sample survey of birth certificates from a Moscow maternity hospital over a 40-year period has revealed secular growth changes (involving mothers' stature, age at menarche, and four anthropometric traits in newborns) in two consecutive generations. Cohorts of mothers born in the period 1930-1949 showed high rates of acceleration. Age at menarche decreased in these cohorts at a rate of 12.5 months per 10 years, and a parallel gain in stature averaged 1.8 cm per 10 years; both rates were significantly higher than those for Western Europe. In later birth cohorts the acceleration in the maternal generation apparently ended. Anthropometric traits at birth (weight, body length, head and chest circumferences) show different patterns of secular changes from 1950 to 1990. According to multiple regression analysis, a temporal trend in the neonate body size might be mainly due to the parallel increase in mother's stature. The contribution of socioeconomic factors to the observed secular growth changes is discussed.

[Genetic-demographic study of mountain populations from Dagestan and their migrants to the lowlands. Comparison of basic parameters of fitness]. / Genetiko-demograficheskoe issledovanie gorskikh populiatsii Dagestana i migrantov iz nikh na ravninu. Sravnenie osnovnykh prarametrov prisposoblennosti.

Results of a total genetic demography study of females of postreproductive age from both parts of "splits" highland isolates of Dagestan, highlanders, and migrants to lowlands are described. The components of natural selection that were related to differential mortality and differential fertility were estimated in the highlanders and the migrants using Crow indices. Offsprings of female migrants were characterized by a higher prenatal (spontaneous abortions and still-births) and a lower prereproductive mortality. These differences may be accounted for by two mechanisms: (1) the effects of changing marital structure (female migrants are more exogamous) and (2) better medical care for the children of migrants compared to those living in highland auls (settlements), which are still difficult to access. It was demonstrated that mortality of probands' children before reproductive age, as well as the proportion of their close genetic relatives that died within five years after resettling, increased with an increase in the level of individual inbreeding in women examined (probands). These data allow us to suggest that the drastic increase revealed in mortality of the highlanders during the first years after resettling may be partially attributed to high levels of inbreeding and heterozygosity; these, in turn, decrease the individual's nonspecific resistance to new ecological factors. Fertility and prenatal mortality appeared to increase and decrease, respectively, with an increase in the inbreeding level.

[Genetic aspects of chronologic dynamics of variability of morphophysiologic characteristics in newborns and their mothers]. / Geneticheskie aspekty vremennoi dinamiki izmenchivosti morfofiziologicheskikh priznakov novorozdennykh i ikh materei.

Temporal dynamics of morphophysiological characteristics variability in generations of newborn children and their mothers living in Moscow is considered in this work. The study is based on histories of newborn children and histories of delivery in 1950, 1955, 1960, 1965, 1970, 1975, and 1980. High rate of acceleration was exposed for women born since 1930. Decrease of menarche age in this age cohorts was 12.5 months per decade and three times exceed correspondent index of European countries. Average increase of body length in the age cohorts was 1.9 cm per decade and twice exceeded analogous index of European countries. Variability of four anthropometric characteristics (body weight, body length, circumference of head and chest) of natural time delivered newborn children was studied. The characteristic values were shown to increase from 1950 to 1980. According to the data of analysis, the temporal dynamics in newborn children was not connected with improvement of environmental conditions during the period of pregnancy but caused by epochal changes in maternal generation. A possible connection between the temporal dynamics of morphophysiological characteristics in newborn children and their mothers and changes in genofond of outbred population of the European territory of Russia is discussed.

[Adaptive norm and stabilizing selection for anthropometric characters at birth]. / Adaptivnaia norma i stabiliziruiushchii otbor po antropometricheskim priznakam pri rozhdenii.

Analysis carried out on medical documentation containing data on several thousand healthy and affected babies has revealed patterns of differential mortality and differential morbidity for newborns and infants which allow to estimate relative risk as a function of birth weight and body length. Adaptive norm for anthropometric traits at birth was defined as the weight or length interval in which mortality/morbidity rates were lower than the overall population level. The intensity of stabilizing selection associated with birth weight calculated from these data is several times higher in the neonatal period than for the age interval 1-12 months. Neonatal mortality in more than 50% cases can be attributed to the effects of stabilizing selection associated with birth weight.

[Significance of indices of potential selection for residents of the USSR]. / Znachenie indeksov potentsial'nogo otbora dlia naseleniia SSSR.

Crow's indices of the opportunity for selection and their components connected with differential mortality (Im) and differential fertility (If) were estimated for populations of Soviet Union republics and for a number of USSR ethnic groups on the basis of demographic statistics. More than 10-fold decrease in the Im value was revealed in the total population of the USSR during 1926-1987. At present, the Im values in republics vary from 0.020 to 0.094 for urban population and from 0.030 to 0.121 in rural population, the ratio of perinatal mortality in the whole structure of prereproductive mortality being higher in the republics with lower values of the Im. The range of the If values for different peoples (0.148-0.643) is wider than for the populations of the republics (0.326-0.578). Interethnic differences contribute 47% of the variance in fertility. The structure of Crow's indices is given for urban and rural populations of the republics. Genetic implications of the data presented are discussed with respect to possible manifestation of the effects of inter-group selection.

Genetic demography of the Moscow population: migration, outbreeding and assortative mating.

Using marriage records, census data, and other statistical sources, some demographic parameters of Moscow population in 1955 and 1980 have been studied, such as age at marriage, birthplace, nationality and profession of permanent residents. Migration has been shown to be the main factor of Moscow population dynamics. Genetically significant, quantitative and geographic parameters of this process have been obtained (migration rates, migration and marital distances, proportion of interethnic marriages). During the past two centuries the mean distance travelled by migrants, arriving in Moscow, increased by several times, the genetic contribution from eastern and southern parts of the country being especially marked. In the period of maximum migration rates the percentage share of marriages between Moscow-born people was only 10%. The percentage share of interethnic marriages was 14.75% in 1955 and 16.53% in 1980. The degree of isolation by distance, predicted by Malécot's model, appeared to be quite low. Positive assortative mating for nationality, birthplace, age and profession was characterized as a factor, counteracting outbreeding. While the deleterious effects of isolation and inbreeding are well known, the genetic consequences of alternative state are still obscure.

[The problem of the adaptive norm in human populations]. / Problema adaptivnoi normy v populiatsiiakh cheloveka.

The results of some investigations recently fulfilled in the framework of population-genetics approach to the problem of adaptive norm in human populations are summarized in this review. The main items considered are: methods of identification of morphologically "average" phenotypes, the role of stabilizing selection in maintaining the population adaptive norm, the problem of joint variation of monogenic and polygenic traits ant its relevance to "norm" and pathology. The significance of the concept of adaptive norm for preventive medicine and genetic monitoring is discussed.

[The role of migration processes in the formation of marriage structure of Moscow population. II. Assortative mating for the age, birthplace and nationality]. / Rol' migratsionnykh protsessov v formirovanii brachnoi struktury moskovskoi populiatsii. Soobshchenie II. Brachnaia assortativnost' v otnoshenii vozrasta, mest rozhdeniia i natsional'nosti suprugov.

Positive assortative mating for age at marriage, birthplace and nationality has been revealed by means of sample analysis of couples married in Moscow in 1955 and 1980. The correlation coefficient between mates for age at marriage was r = 0.81 in 1955 and r = 0.88 in 1980; the age difference between spouses had a mean of 1.55 and 2.21 years, respectively. The determinative role of migration in forming Moscow population marriage structure accounts for the fact that the greater part of marriages registered in the capital are between migrants from various regions of the USSR or between the Moscow-born and the migrants. The proportion of marriages between individuals born in Moscow has increased over 25 years from 10 to 38%, these values being significantly higher than those expected under random mating between the migrants and the Moscow-born. The contingency coefficient measuring the association between the birthplaces of husband and wife was K = 0.16 in 1955 and K = 0.11 in 1980, the preferential marriage between mates born in the same region being still significant even when marriages are registered in Moscow. The highest degrees of assortative mating were observed for nationality character: K = 0.37 in 1955 and K = 0.28 in 1980. The decrease in these values over the past 25 years has resulted in a slight growth of the proportion of international marriages (from 14.75 to 16.53%) which has not yet reached the level expected under panmixia (about 21%).

[The role of migration processes in the formation of the marriage structure of Moscow population. III. Assortative mating as a factor counteracting the outbreeding]. / Rol' migratsionnykh protsessov v formirovanii brachnoi struktury moskovskoi populiatsii. Soobshchenie III. Brachnaia assortativnost' kak faktor, protivodeistvuiushchii autbridingu.

The genetic consequence of positive assortative mating for the demographic characters in the megapolis population is being discussed.

[Population genetic study of differential fertility in man (illustrated by habitual abortion). IV. Distribution of blood groups and frequency of incompatible marriages]. / Populiatsionno-geneticheskoe izuchenie differentsial'noi plodovitosticheloveka (na primere privychnogo nevynashivaniia beremennosti). Soobshchenie IV. Raspredelenie grupp krovi i chastota nesovmestimykh brakov.

Hereditary variation of 5 immunological systems coded by 8 loci was compared in 148 couples and 100 women with repeated spontaneous abortions in anamnesis (experimental group) and 141 couples and 100 women with normal fertility (control group). Marked differences in distributions of genotypes and frequencies of 3 systems (MNSs, Rhesus, Duffy) and frequency of AB0-incompatible couples were found between control and experimental groups. An average value of observed heterozygosity in experimental group was lower, as compared to the expected value. Possible influence of immunological factors on recurrent fetal wastage is discussed.

[Population-genetical study of differential fertility in humans (based on an example of habitual abortion). I. Approach to the problem and analysis of morpho-physiological and demographic traits]. / Populiatsionno-geneticheskoe izuchenie differentsial'noi plodovitosticheloveka (na primere privychnogo nevynashivaniia beremennosti. Soobshchenie I. Obosnovanie podkhoda i analiz mofofiziologicheskikh i demograficheskikh priznakov.

It was shown that women from the studied group of married couples, suffering from repeated spontaneous abortions (the main group), have earlier menarche and their husbands are taller, as compared with the control group of couples with normal reproductive performance. The degree of similarity between mates in age and stature appeared to be lower in the main group than in the control group. The variation of the characters under study is supposed to provide an auxiliary criterion in selecting couples at high risk of repeated spontaneous abortions.