Fiorenzo Facchini

Trading Genes along the Silk Road: mtDNA Sequences and the Origin of Central Asian Populations

Central Asia is a vast region at the crossroads of different habitats, cultures, and trade routes. Little is known about the genetics and the history of the population of this region. We present the analysis of mtDNA control-region sequences in samples of the Kazakh, the Uighurs, the lowland Kirghiz, and the highland Kirghiz, which we have used to address both the population history of the region and the possible selective pressures that high altitude has on mtDNA genes. Central Asian mtDNA sequences present features intermediate between European and eastern Asian sequences, in several parameters-such as the frequencies of certain nucleotides, the levels of nucleotide diversity, mean pairwise differences, and genetic distances. Several hypotheses could explain the intermediate position of central Asia between Europe and eastern Asia, but the most plausible would involve extensive levels of admixture between Europeans and eastern Asians in central Asia, possibly enhanced during the Silk Road trade and clearly after the eastern and western Eurasian human groups had diverged. Lowland and highland Kirghiz mtDNA sequences are very similar, and the analysis of molecular variance has revealed that the fraction of mitochondrial genetic variance due to altitude is not significantly different from zero. Thus, it seems unlikely that altitude has exerted a major selective pressure on mitochondrial genes in central Asian populations.

Sex-specific migration patterns in Central Asian populations, revealed by analysis of Y-chromosome short tandem repeats and mtDNA.

Eight Y-linked short-tandem-repeat polymorphisms (DYS19, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392, and DYS393) were analyzed in four populations of Central Asia, comprising two lowland samples-Uighurs and lowland Kirghiz-and two highland samples-namely, the Kazakhs (altitude 2,500 m above sea level) and highland Kirghiz (altitude 3,200 m above sea level). The results were compared with mtDNA sequence data on the same individuals, to study possible differences in male versus female genetic-variation patterns in these Central Asian populations. Analysis of molecular variance (AMOVA) showed a very high degree of genetic differentiation among the populations tested, in discordance with the results obtained with mtDNA sequences, which showed high homogeneity. Moreover, a dramatic reduction of the haplotype genetic diversity was observed in the villages at high altitude, especially in the highland Kirghiz, when compared with the villages at low altitude, which suggests a male founder effect in the settlement of high-altitude lands. Nonetheless, mtDNA genetic diversity in these highland populations is equivalent to that in the lowland populations. The present results suggest a very different migration pattern in males versus females, in an extended historical frame, with a higher migration rate for females.

Unravelling migrations in the steppe: mitochondrial DNA sequences from ancient central Asians.

This study helps to clarify the debate on the Western and Eastern genetic influences in Central Asia. Thirty–six skeletal remains from Kazakhstan (Central Asia), excavated from different sites dating between the fifteenth century BC to the fifth century AD, have been analysed for the hypervariable control region (HVR–I) and haplogroup diagnostic single nucleotide polymorphisms (SNPs) of the mitochondrial DNA genome. Standard authentication criteria for ancient DNA studies, including multiple extractions, cloning of PCR products and independent replication, have been followed. The distribution of east and west Eurasian lineages through time in the region is concordant with the available archaeological information: prior to the thirteenth–seventh century BC, all Kazakh samples belong to European lineages; while later an arrival of east Eurasian sequences that coexisted with the previous west Eurasian genetic substratum can be detected. The presence of an ancient genetic substratum of European origin in West Asia may be related to the discovery of ancient mummies with European features in Xinjiang and to the existence of an extinct Indo–European language, Tocharian. This study demonstrates the usefulness of the ancient DNA in unravelling complex patterns of past human migrations so as to help decipher the origin of present–day admixed populations.

Lung volume, chest size, and hematological variation in low-, medium-, and high-altitude central Asian populations.

To evaluate adaptive responses to high-altitude environment, we examined three groups of healthy adult males from Central Asia: 94 high-altitude (HA) Kirghiz subjects (3,200 m above sea level); 114 middle-altitude (MA) Kazakh subjects (2,100 m), and 90 low-altitude (LA) Kirghiz subjects (900 m). Data on chest size (chest perimeter and chest diameter), lung volume (forced expiratory volume (FEV) and forced expiratory volume in 1 sec (FEV1)), and hematological parameters (hemoglobin, erythrocytes, hematocrit, and SaO(2)) are discussed. The results show that 1) chest shape is less flat in the samples living at higher altitude. In the HA sample, chest perimeter is lower but chest excursion is high. 2) In the highlanders, forced vital capacity (FVC) and FEV1 are no higher than in the other samples, even when corrected for stature and body weight. The negative correlation between FVC-FEV1 and age decreases with increasing altitude. 3) The HA and MA samples have higher values of hemoglobin, erythrocytes, and hematocrit. The HA sample has lower SaO(2) and higher arterial oxygen content than the LA sample. No association between hematocrit and age was detected in the four samples. The results indicate that the high-altitude Kirghiz present features of developmental acclimatization to hypobaric hypoxia which are also strongly influenced by other major high-altitude environmental stresses.

The prediction of extracellular and total body water from bioelectric impedance in a non-Caucasian population from Central Asia

The availability of only a small number of studies on bioelectric impedance analysis (BIA) in non-Caucasian ethnic groups appears to limit reliable utilization of this method in anthropological field studies. In this study, 28 male Turkish-Mongolian subjects native of Kazakhstan (Central Asia) underwent total body water (TBW) and extracellular water (ECW) assessment by deuterium oxide (D2O) and sodium bromide (NaBr) dilution respectively. Bioelectric impedance (BI) was recorded at multiple frequencies. ECW and TBW were calculated from BI at 1 and 100 kHz respectively by applying formulae developed on a sample of Caucasian subjects with a hydration status similar to that of the study population. TBW predicted from BI at 1 and 100 kHz (37.5 +/- 3.31) was highly correlated and not significantly different from that obtained by D2O dilution (39.0 +/- 4.11, r = 0.894, p < 0.0001, SEE = 1.91). Similarly, ECW predicted from BI at 1 kHz (15.1 +/- 1.21) was highly correlated and not significantly different from that obtained by NaBr dilution (15.0 +/- 1.61, r = 0.847, p < 0.0001, SEE = 0.81). It is concluded that selected predictive formulae developed on Caucasian subjects may provide a precise and accurate assessment of ECW and TBW in Turkish-Mongolian populations.

Puberty in modernizing Kazakhstan: A comparison of rural and urban children

Background: Data on puberty development are available for several countries but not for Central Asia. Aim: Using data collected during the Kazakhstan Health and Nutrition Survey (KHA-ES), we evaluated the relationship between the living environment (rural vs. urban), ethnicity (Russians vs. Kazakhs) and pubertal status in children living in Kazakhstan. Subjects and methods: Genital (G1–G5), breast (B1–B5) and pubic hair (PH1–PH5) development were evaluated in a sample of 2389 boys and 2416 girls using Tanners criteria. Age at menarche was evaluated using the ‘status quo’ and ‘recall’ methods. Results: Rural children were older than urban children at stages ≥G2 for males and ≥B2 for females, and this difference was more evident for Russian males. Differences levelled out at later stages of development in Kazakh males and in the pooled girls. The living environment was slightly but significantly associated with median age at menarche (12.89 years for urban Kazakhs to 13.43 years for rural Kazakhs). Male and female Kazakhs were older than Russians at stages 4 and 5, especially in the urban area. Conclusion: A relationship between pubertal status and the living environment was present in a rapidly modernizing country such as Kazakhstan.

Body composition in Central Asia populations: Fat patterning variation in the Kazakhs of the Tien Shan mountains and the Uighurs of Semericia

Eleven anthropometric variables related to fat patterning were analyzed in two populations of Central Asia, the Kazakhs of the Tien Shan mountains (2100 m) and the Uighurs of the Semericia plains. Subjects were healthy unrelated males, 122 Kazakhs and 79 Uighurs, 19–65 years. Comparisons were done with a preliminary analysis of variance and then by covariance analysis, taking into account the influence of age. The Uighurs, independently of age, show higher values than Kazakhs for all of the characteristics related to fat patterning, but principal components analysis suggests a similar somatic structure in the two samples. The presence of lower adiposity in the Kazakhs than in the Uighurs could be related to stress, probably associated with nutrition and lifestyle in a mountain environment. Am. J. Hum. Biol. 10:241–247, 1998.

Digital and palmar dermatoglyphics and the population structure of the Upper Bologna Apennine

Analysis of digital and palmar dermatoglyphics in an Italian mountain population was carried out. Dermatoglyphic variability was particularly investigated in samples from four different valleys. Microgeographical differences in qualitative and quantitative traits among valleys were found. The relationship between degree of endogamy and dermatoglyphic differences is discussed. The biological repercussion of isolation in the history of this Apennine population is also pointed out by means of comparisons with a nearby plains population characterized by low inbreeding.

Biological age in Italian adults: Influence of social and behavioural factors

This study investigated changes with age in biological characters in a sample of 571 Italian males aged between 25 and 64 years. The influence of environmental factors on inter-individual variation in physical efficiency was examined by biological age determination. Data on somatometric, physiometric, haematological variables, personal background and lifestyle, were collected. Principal-component analysis was used to study the patterns of relationship in these characters. Over 45% of the total variance is explained by the ageing process, but the secular trend also affects the variation of height and of height-related characters. Changes with age were investigated clustering the sample in eight 5-year classes: results are in agreement with previous findings in Western populations. Ten selected variables were transformed into biological age scores reflecting a mans status relative to his chronological age peers (Borkan and Norris 1980a). Biological age scores of subsamples characterized by different social and behavioural situations were compared. Occupation, educational level and physical activity seem to have the greatest influence on biological age status. The intensity or duration of some habits can induce a clear trend in biological age scores. Results suggest that the environmental influence could be related to the interindividual differences in physical efficiency and to the increase in variability with age observed for some characters.

Spirometric reference values for children and adolescents from Kazakhstan

Background: Spirometric parameters are influenced by several factors and many reference data are available in the literature. However, no spirometric data are available for children and adolescents from Central Asia. Aim: The study aimed to calculate spirometric reference curves on the basis of anthropometry, ethnicity (Kazakh vs. Russian) and living environment (urban vs. rural). Subjects and methods: Spirometry (FEV1, FVC and FEF25–75%) was performed and anthropometric measurements taken for 1926 male and 1967 female Kazakh children aged 7–18 years. Results: Height explained almost all the variance of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) for both sexes, while age and inspiratory circumference contributed slightly to the prediction. Moreover, FVC and FEV1 were greater in Russians than in Kazakhs and ethnicity did enter the prediction model for these parameters. The living environment had a marginal effect on spirometry. In fact, forced expiratory flow 25–75% (FEF25–75%) was slightly higher in urban than in rural females, FVC was slightly higher in rural than in urban males, while FEV1 was not affected. Finally, among several spirometric equations available in the literature, those performing better in our children were obtained in developed countries. Conclusion: Anthropometry was the most important predictor of spirometry. Age and ethnicity were also predictors, while the contribution of the living environment was more limited.