[Genetics of sucrose metabolism disorders in different population groups].

The study of the genetic determinants of the disaccharidase activity opens up new prospects for improving diagnostics and choosing medical tactics in gastroenterology. The aim of the study was to systematize the data on the role of the sucrase-isomaltase gene (SI) in regulating sucrose metabolism and the contribution of SI mutations to the prevalence of sucrose malabsorption disorders (sucrase-isomaltase deficiency, SID) and certain forms of enterological pathology in different population groups. Material and methods. A review of the peer-reviewed scientific literature, mainly in the PubMed database (https://pubmed.ncbi.nlm.nih.gov) and eLibrary (https://elibrary.ru), was conducted using key words: carbohydrate malabsorption, sucrase, sucrase-isomaltase deficiency, sucrase-isomaltase SI gene. The search depth was not specified, but particular attention was paid to recent publications. The gnomAD database (https://www.ncbi.nlm. nih.gov/snp/rs781470490) was also used. Results. According to the review results, 37 out of 150 known SI gene mutations have been confirmed to contribute to reduced sucrase activity or restricted sucrase production. The prevalence of point mutations in the SI gene is estimated at 0.0006%, but carrier rates of the SI delAG deletion (rs781470490), manifested as homozygosity in SID, are very high (5-21%) in indigenous populations of Arctic regions in East Asia and America. Medicalgenetic research methods improve the accuracy of differential diagnosis of primary and secondary SID and other forms of disaccharide and polysaccharide malabsorption. The formation of databases on the prevalence of genetic determinants of sucrase-isomaltase insufficiency is a promising way to refine the epidemiology of SID. There is an increased (0.2-2.3%) risk of clinical manifestations of SID in homozygous carriers of the SI delAG mutation in the Chukotka, Kamchatka, and Northern Priochotye populations. Verification of reports on a less pronounced tendency to lipid metabolism disorders in SI delAG carriers compared with the control group is recommended. Conclusion. Manifestations of mutant SI variants in the phenotype are associated with the presence of accompanying carbohydrate malabsorption variants and specific gut microbiota. The SI 15Phe variant (rs9290264) may contribute to the development of irritable bowel syndrome.

[Prevalence of trehalase enzymopathy genetic determinants in Siberian and Russian Far East populations].

To date, it has been established that the patient's genotype plays a significant role in the formation of trehalase enzymopathy: the level of enzyme activity decreases when the G→A allele replacement occurs in the rs2276064 locus of the TREH gene. To assess the prevalence of trehalase deficiency, extensive population-based studies are needed. Clinical observations show that the reduced activity of bowel trehalase is more common in the Arctic than in European populations. The aim of this research was to analyze the frequency of the alleles and variants of trehalase gene (rs2276064 TREH) in the indigenous small-numbered populations of Siberia and the Russian Far East. Material and methods. Using the Infinium iSelect HD Custom BeadChip biochip on the iScan platform and real-time polymerase chain reaction on a Bio-Rad CFX96 Touch amplifier, genotyping of 1068 DNA samples was carried out, of which 711 represent 10 ethnic groups of the indigenous people of the North of Siberia and the Far East of the Russian Federation. Two reference groups of Russians (n=311) and Yakuts (n=46) represented the "Caucasoid" and "Mongoloid" poles of the Russian population. Results. The reduced trehalase activity that the heterozygous GA*TREH genotype determines can manifest itself in 19.8-53.7% of indigenous northerners. An additional 1.0 to 19.7% of the population are carriers of the AA*TREH genotype, which is associated with apparent trehalose malabsorption. The carriers may experience nausea, abdominal pain, and other dyspeptic symptoms after eating trehalose containing foods. The total risk of trehalase enzymopathy among the indigenous northerners in the Asian part of the Russian Federation is very high and can reach 60-70%. There is a gradient in the A*TREH allele frequencies in the small-numbered indigenous northern groups of Russia from the west (Khanty, Mansi, Nenets) to the east (peoples of the Far East). Conclusion. The results are consistent with previously reported data on the higher carriage of the A*TREH mutant allele in Mongoloid populations compared to Caucasoid groups. It was hypothesized that, while the initial A*TREH allele prevalence in Mongoloid groups was moderately high, an adaptation to a low-sugar protein-lipid "high-latitude" diet led to a weaker control over the maintenance of the carriage of the ancestral G allele. Trehalose malabsorption requires special attention of specialists in the field of nutrition, gastroenterology, public health, and medical genetics working in high-latitude regions.

[The influence of environmental factors on the prevalence of «thrifty genotypes¼ as predictors of metabolic disorders].

"Thrifty genotypes" are the risk factors for obesity and lipid and energy metabolism disorders. Hence, it is important to assess the contribution of environmental factors that influenced the thrifty genotypes' population distribution. Aim of the study - systematization and critical analysis of published data on population variability, relationship with climatic and environmental characteristics, association with traditional types of lifestyles, and nutrition for the «thrifty genotypes¼ of APOE, UCP1, UCP3, and FTO genes. Material and methods. The selection of publications from the last 20-25 years presented in the PubMed database (https://pubmed.ncbi.nlm.nih.gov) was carried out by the keywords of the generalizing rank (thrifty genotype, thrifty phenotype, drifty genotype), then narrowed down to the APOE, UCP, FTO. The final set includes publications that consider the association of genotypes with the ecological conditions of the population. Results. Our analysis of publications has confirmed the ethnic and geographical variability in the allele distribution of APOE, UCP1, UCP3, and FTO genes. However, the nature of this variability hasn't been studied sufficiently; the contribution of individual factors of the natural and anthropogenic environment remains unclear. The information on the geographical distribution of the APOE gene alleles is quite complete, while the data on the «thrifty genotypes¼ of UCP and FTO require further study. Conclusion. The frequency of the UCP1 and UCP3 alleles associated with effective non-contractile thermogenesis is increased in populations adapted to low temperatures. However, the population-geographical pattern of the UCP thrifty genotypes' variability as a determinant of increased fat deposition has been studied insufficiently. The carriage of FTO mutant variants increases the adaptability of groups with a traditional lifestyle and diet but is maladaptive in an urbanized environment. The influence of natural and ecological conditions on the formation of the FTO allele geographical distribution requires more attention. The results obtained allow us to propose the included groups' ranking according to the past environmental management and nutrition will facilitate the search for ecological factors that influenced the geographical distribution of genotypes (and, accordingly, populations with different levels of risk of metabolic disorders).

[Genetically determined trehalase deficiency in various population groups of Russia and neighboring countries].

Due to the low specificity and sensitivity of non-invasive clinical tests trehalose malabsorption remained out of sight of gastroenterologists. Therefore, the specialists regard this disorder as rare. Trehalose became widely used in the food industry as a harmless sucrose substitute, sweetener and stabilizer. After the discovery of the trehalase gene (rs2276064 TREH), it was found that the A*TREH allele is the determinant of the disaccharide absorption disorders, and the allele's carriership may be high in some groups. There is not enough information on the A*TREH frequency in the population of Russia. The aim of the study was to analyze the allele and genotype frequencies of the trehalase gene (rs2276064 TREH) in the main population groups of the Russian Federation and neighboring countries. Methods. DNA samples from 1146 unrelated subjects belonging to 21 population groups of Russia, Azerbaijan, Tajikistan and Mongolia were genotyped by the two following methods: 1) using the Infinium iSelect HD Custom Genotyping BeadChip (Illumina, USA) on the iScan platform; 2) by the real time polymer-chain reaction (PCR) method on the Bio-Rad CFX96 Touch amplifier. Results. It has been found that on the territory of the Russian Federation the frequency of the A*TREH allele increases from the west to the east. The frequencies are lowest in the groups of Russians and Finns of the Northwest (0.01-0.03), up to 0.07 in the populations of Central Russia and the Volga region, and even higher toward the Southern Urals (Bashkirs 0.15), in the Transurals and Southern Siberia (0.19 in the Altai people, 0.30 in the Tuvinians and Mongols). Up to 1% of the population of the European part of the Russian Federation have the AA*TREH genotype (i.e. trehalose intolerance in phenotype), and up to 15% (GA*TREH genotype) have a reduced ability to absorb the disaccharide. In the Asian part of the country (Siberia, Altai, Baikal) the genotypes carriers constitute up to 12 and 46% respectively. Conclusion. Trehalose malabsorbtion is an underappreciated problem of particular practical importance for regions with high concentrations of indigenous population (Yakutia-Sakha, Buryatia, Tyva, etc.). It would be feasible to consider food labelling of trehalose.

[Nutritional status of children in rural areas of the Komi Republic and Khanty-Mansi Autonomous Okrug - Yugra by anthropometric data].

A characteristic feature of the "global obesity epidemic" in recent decades is the rapid spread of overweight among the rural population. However, there is a lack of objective data on how this process is unfolding in the northern and Arctic regions of the Russian Federation. The aim of the work was to analyze the prevalence of malnutrition and rates of overweight and obesity in children living in Khanty-Mansi Autonomous Okrug - Yugra (KhMAO) and the Komi Republic (KR). Material and methods. We conducted a study of the nutritional status of rural children in the northern regions of the Russian Federation in 2018-2019. The subjects of the study were children aged 3-17 years of KhMAO, ethnic Khanty, Mansi and of various non-indigenous descent in small remote settlements (n=302) and 956 children in the administrative center of the northern district, a town-type residency. We also examined 7-17-year-old children (n=628) in large settlements of the KR, over 90% of them were ethnic Komi. For each individual, body mass index values (BMI) were calculated. The nutritional status was assessed by comparing the individual BMI with the age and sex specific standards set by the Ministry of Health of the Russian Federation (2017). Results and discussion. 74.4% of children aged 3-6 in KhMAO, and 70% of the 7-17-year-old children of KR and KhMAO meet the standards for their age-sex groups; 6.1% of children aged 3-17 are underweight and 19.5% are overweight. Among the 7-17-year-olds, the ratio of the underweight and overweight (including obese) differs significantly in the settlement dwellers of the KR from that in the living in small settlements of KhMAO (p=0.004), as well as in the group of town residents of KhMAO (p=0.017). The children of the KR have slightly higher percentage of the overweight and obese (26.6 vs 25.7 and 24.8% in the town and settlements of KhMAO, respectively), but significantly lower percentage of those who are underweight (1.9 vs 5.0 and 6.8%). The proportion of obese schoolchildren in small remote settlements of KhMAO is higher than that in the large settlements of KhMAO and in large settlements of the KR (13.1, 7.7 and 9.2%, respectively). Conclusion. There were no differences found between ethnic groups, however the role of social and anthropological factors in the formation of the nutritional status differences between the indigenous and non-indigenous children in Western Siberia calls for further investigation.

[Anthropometric indicators of physical development and nutritional status employed in hygiene practice in Russia].

In the current review, we consider the main working methods of Russian hygienists to assess anthropometric indices using a) regional data on (populational) variability of the concerning measurements and b) unified reference data applicable in most regions. An analysis showed that in most cases, the regional standards are based on average values and variabilities derived from a local sample, which can not serve as a working normative. As a result, these so called "standards" do not provide information on how healthy children should develop, and the assessments inferred are difficult to integrate to draw a picture for the whole country. In 2017, the Ministry of Health of the Russian Federation recommended the use of the WHO Child Growth Standards and the WHO Growth Reference for the purpose of medical screenings in children and adolescents. These data sets reflect the conditions, that healthy children should attain growing in supportive environment, with adequate nutrition and care. The single set of criteria will allow unifying the data collected in different regions, which is a necessity in communal hygiene and medical statistics. However, additional research is needed to check the validity of the WHO standards and reference to assess physical development and nutritional status in highly anthropologically specific populations, in particular in those indigenous and long-ago adapted to the sharply continental or Arctic climate.

[Carbohydrate-related nutritional and genetic risks of obesity for indigenous northerners].

By the end of the 2010-s the prevalence of obesity among the indigenous people of the North approached to the all-Russia one and the speed of the spread of other metabolic disorders exceeded the average all-country levels. Aim of this review is to analyze data on the increase in consumption and variety of sugars coupled with a genetic specificity of regulation of saccharidase activity and their possible impact on the matters. Results. It have been shown that the traditional protein-lipid-based northern type diet has substantially changed and now contains a high proportion of carbohydrates. The carbohydrate per capita consumption among the indigenous people of the North has reached the all-Russia average level (40 kg per year) which exceeds the European average of 36.2 kg per year. The variety of food disaccharides has also considerably increased. The daily consumption of sucrose, at the beginning of the 20th century it was the only sugar contained in the store-bought foods, increased from 30 g in the 1930s to 63-65 g in the 1990s. In addition, the proportion of sucrose dropped to 60-70 per cent, while the contribution of other disaccharides (lactose, trehalose) reached 30-40 per cent. Daily starch consumption has also increased and got close to the national average (males 228.5 g, females 157.5 g per day). Such a diet in itself increases the risk of metabolic disorders and obesity. The high prevalence of the genotypes that determine reduced levels or inability to produce sucrase-isomaltase, lactase, trehalase, salivary and pancreatic amylases among northerners becomes a negative cofactor. The evolutionary driven and embodied in genotype reduced ability of the indigenous Arctic people to digest complex carbohydrates is in a conflict with the growing consumption of sugars and starchy foods in modern conditions. The northern people have a high proportion of carriers of the AG deletion in SI gene (3.5-14.3% against 0.05-0.2% among Europeans) which determines malabsorption of sucrose. The CC/LCT genotype (96.6% in northerners, 36-49% in Russians) presumes lactose intolerance and is associated with the risk of childhood obesity. The occurrence of A allele in the rs2276064 locus of TREH gene (trehalose intolerance; 31.3-58.9% in northerners, 1.9% in Europeans) increases the probability of the onset of type 2 diabetes mellitus. According to preliminary estimates, 28-52% of the northerners completely lost AMY gene that precludes or drastically reduces the ability to digest starch. A reduction in the number of copies of AMY gene (the average number of copies AMY2A - 4, in, in northerners it is 1.0-1.4) is associated with overweight and obesity. Conclusion. The analysis shows that, in the case of the modern indigenous northerners, nutritional and genetic risks of metabolic disorders accumulate.

[Differences in self-assessment of health and psychological wellbeing between healthy and unhealthy young adults].

Self-assessment of health is the one out of the most important characteristics, which gives an idea about the health of the respondent as a psychophysiological continuum. The purpose of this study is to establish the relationship between indices of self-rated health and characteristics of the psychological well-being. Sample 344 young adults - students at an average age of 20.9 ± 1.6 years. Methods. "Self-assessment of health" questionnaire was used; MOSSF36 questionnaire and "Psychological wellbeing scale" developed by K. Riff. Respondents were divided into groups: (1) without chronic diseases; (2) having one or more chronic diseases of any etiology. Results. The presence of chronic diseases was shown to negatively effect on the self-estimation of physical and psychological state. The significant positive correlation (p <0,001) between the perceived health and subjective well-being was found. Healthy individuals perceive the state of their own physical health and psychological wellbeing as unrelated to each other characteristics. In contrast, in cases with even mild chronic health problems there is pronounced the relationship between somatic and psychological health, which forms a complex of physical and psychological factors determining the general state of a person.

[Cortisol as a marker of stress].

The role of cortisol (Crt), dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) in stress responses were shown. The fluctuations in concentration of Crt, DHEA and DHEA-S depending on age, sex and time of the day in norm and under acute and chronic stress were quoted. The main techniques of assessment of serum, urine and saliva Crt concentrations were discussed. A special attention had been paid to the use of Crt concentration in anthropological and psychological research. Bibliography comprises 181 works.

[Vitamin D status in population of the perm territory and Komi and Udmurtia Republics].

Seasonal and geographical variability in blood serum concentration of 25-OHD3 among the residents of the Perm Territory, Komi and Udmurtia Republics (327 subjects in total) were investigated. The mean values of serum 25-OHD3 concentrations in 13-16 years old adolescents vary from 31.1 to 49.6 nmol/l, in adults from 39.7 to 47.7 nmol/l. They are within the range of variation reported in other groups in Russian Federation and North-Western Europe. Seasonal fluctuations of vitamin D content are more expressed in adolescents. The geographical distribution of the measures does not agree with the conventional notion that it has a latitudinal (South-North) variability gradient.

[Blood serum concentration of lipids and lipoproteins and body composition].

The purpose of this study is the analysis of the relationship of blood serum apolipoprotein E (apoE), total cholesterol (TC), triglycerides (TG) and high-density and low-density lipoproteins (HDL, LDL), with body mass index (BMI), relative body surface area (RBSA) and body muscle (BM) and body fat (BF). The subjects are males and females aged 14-16 (adolescent age group 1: n1M = 141, n1F = 151) and 18-25 (young adult group 2, n2M = 16, n2F = 46). Significant correlations of serum TG and HDL with somatometric indicators were not observed. In the female samples, TC content directly correlates (p < 0.05) with BF (r1 = 0.164; r2 = 0.418) and negatively correlates with BM (r1 = -0.165; r2 = -0.352). The blood serum concentration of apoE is significantly correlated with body composition in adolescent females (for BF r1 = -0.168; for BM r1 = 0.266; p < 0.05); in males 14-16 years old, the both correlations have a significance level p < 0.06. In young adult females TC and LDL content negatively correlates with RBSA (r2 = -0.386 and -0.377 respectively; p < 0.05) and positively correlates with BMI (r2 = 0.413 and 0.415 respectively; p < 0.05). Adolescent females and young adult females have opposite relationships between FC and apoE concentration. In females 14-15 years old apoE concentration decreases as FC increases. In females 16-17 the correlation disappears, and in older females apoE concentration and FC increase together.

[Vitamin D level in the indigenous populations of Russia European North].

The aim of our research was to investigate the level of 25-OH vitamin D3 in blood plasma of indigenous inhabitants of Russia European North. The study showed that there was wide spreading of vitamin D deficiency among northerners especially in teenager. The significant reduction of level of 25-OH vitamin D3 was revealed in the inhabitants of Far North in March.

[Changes in the anthropometric characteristics of neonatal infants and in the reproductive behavior of the indigenous population of Chukotka].

The anthropometric characteristics of neonatal infants from the Chukotka indigenous population, age of onset of sexual behavior, and maternal age at first birth were assessed from the records available in 257 labor histories. According to the WHO criteria, physical development was rated as satisfactory in a 2000-2003 neonatal cohort. Birth weight and head and chest circumferences in the neonates were significantly lower than those in a 1967-1970 one. The proportion of babies who had birth weight less than 2500 was 97 per thousand, which was higher than the average value in the Russian Federation and than that of the indigenous population of Alaska and Canada. By the early 2000s versus 1990, reproductive behavioral changes in the native women of Chukotka were exhibited by an average 17-month decrease in age of onset of sexual behavior to 16.9 and 17.26 years in females living in the settlements and villages, respectively. In the meantime, the mean female age at first birth did not differ from that for a group of traditional lifestyle (18-19 years), but the dispersion of the indicator was on the rise. As a result, the proportion of parturients among the Chukchi girls aged 17 years or younger was 2-4 times (according to the place of residence) greater than the total Russian value.

[Polymorphism of the apolipoprotein E gene (APOE) in the populations of Russia and neighboring countries].

Allele and genotype frequencies for the locus encoding apolipoprotein E, involved in the regulation of lipid metabolism (APOE), were evaluated in 16 populations representing 12 ethnic groups (a total of 1103 subjects) from Russia and neighboring countries. In the populations examined, the frequencies of allele epsilon4, which is the risk factor of Alzheimer's disease and coronary heart disease, varied from less than 5 to more than 20%, while the variation of the major epsilon3 allele in these populations ranged from less than 75 to 95%. The frequencies of alleles epsilon3 and epsilon4 were 0.714 and 0.205 in Saami, 0.734 and 0.149 in Maris, 0.841 and 0.122 in Evenks, 0.788 and 0.163 in Buryats, 0.764 and 0.202 in Chukchi, 0.875 and 0.075 in Iranians, 0.956 and 0.044 in mountain-dwellers of the Pamirs, 0.771 and 0.094 in Ukrainians, and 0.795 and 0.091 in Belarussians, respectively. In Russians from different regions of the country, the frequencies of these alleles were 0.728 and 0.139 (Kostroma), 0.795 and 0.105 (Moscow), 0.857 and 0.092 (Rostov-on-Don), and 0.824 and 0.083 (Krasnodar), respectively. The latitudinal distribution of the APOE epsilon3 and epsilon4 allele frequencies in the populations examined was comparable to the frequency distribution pattern of these alleles in other populations of Eurasia.

[Molecular diagnosis and frequencies of primary hypolactasia in populations of RUSSIA and neighboring countries].

The digestion of the milk sugar (lactose) is observed every normal child but not in every adult. The decreased lactase synthesis in some adults results in problems with digestion of the whole milk (primary hypolactasy). An association of lactase activity in adults with carrying of the allele T within the polymorphism C/T-13910 located upstream of the lactase gene and 100% association of hypolactasy with the genotype C/C has recently been shown for a Finnish sample. In the present work we determined the LCT* C/T_13910 genotypes and allele frequencies in populations from Russia. The genotype C/C frequencies varied from 36.6% for Russians to 88.2% for Chukchi and were close to the published medical and epidemiological data on hypolactasy frequencies in respective populations. Genotyping was performed by three different methods to identify the optimal one. Our results have shown that the studied locus is the key determinant for the primary hypolactasy development in various human populations. Consequently, the DNA diagnostics of the C/C genotype carrying is a promising predictive test to detect the primary hypolactasy long before its clinical development. Practical application of this type of diagnostics would be a step towards the individual-oriented medicine.

Y chromosomal haplogroup J as a signature of the post-neolithic colonization of Europe.

In order to attain a finer reconstruction of the peopling of southern and central-eastern Europe from the Levant, we determined the frequencies of eight lineages internal to the Y chromosomal haplogroup J, defined by biallelic markers, in 22 population samples obtained with a fine-grained sampling scheme. Our results partially resolve a major multifurcation of lineages within the haplogroup. Analyses of molecular variance show that the area covered by haplogroup J dispersal is characterized by a significant degree of molecular radiation for unique event polymorphisms within the haplogroup, with a higher incidence of the most derived sub-haplogroups on the northern Mediterranean coast, from Turkey westward; here, J diversity is not simply a subset of that present in the area in which this haplogroup first originated. Dating estimates, based on simple tandem repeat loci (STR) diversity within each lineage, confirmed the presence of a major population structuring at the time of spread of haplogroup J in Europe and a punctuation in the peopling of this continent in the post-Neolithic, compatible with the expansion of the Greek world. We also present here, for the first time, a novel method for comparative dating of lineages, free of assumptions of STR mutation rates.

A multistep process for the dispersal of a Y chromosomal lineage in the Mediterranean area.

In this work we focus on a microsatellite-defined Y-chromosomal lineage (network 1.2) identified by us and reported in previous studies, whose geographic distribution and antiquity appear to be compatible with the Neolithic spread of farmers. Here, we set network 1.2 in the Y-chromosomal phylogenetic tree, date it with respect to other lineages associated with the same movements by other authors, examine its diversity by means of tri- and tetranucleotide loci and discuss the implications in reconstructing the spread of this group of chromosomes in the Mediterranean area. Our results define a tripartite phylogeny within HG 9 (Rosser et al. 2000), with the deepest branching defined by alleles T (Haplogroup Eu10) or G (Haplogroup Eu9) at M172 (Semino et al. 2000), and a subsequent branching within Eu9 defined by network 1.2. Population distributions of HG 9 and network 1.2 show that their occurrence in the surveyed area is not due to the spread of people from a single parental population but, rather, to a process punctuated by at least two phases. Our data identify the wide area of the Balkans, Aegean and Anatolia as the possible homeland harbouring the largest variation within network 1.2. The use of recently proposed tests based on the stepwise mutation model suggests that its spread was associated to a population expansion, with a high rate of male gene flow in the Turkish-Greek area.

Lactase haplotype diversity in the Old World.

Lactase persistence, the genetic trait in which intestinal lactase activity persists at childhood levels into adulthood, varies in frequency in different human populations, being most frequent in northern Europeans and certain African and Arabian nomadic tribes, who have a history of drinking fresh milk. Selection is likely to have played an important role in establishing these different frequencies since the development of agricultural pastoralism approximately 9,000 years ago. We have previously shown that the element responsible for the lactase persistence/nonpersistence polymorphism in humans is cis-acting to the lactase gene and that lactase persistence is associated, in Europeans, with the most common 70-kb lactase haplotype, A. We report here a study of the 11-site haplotype in 1,338 chromosomes from 11 populations that differ in lactase persistence frequency. Our data show that haplotype diversity was generated both by point mutations and recombinations. The four globally common haplotypes (A, B, C, and U) are not closely related and have different distributions; the A haplotype is at high frequencies only in northern Europeans, where lactase persistence is common; and the U haplotype is virtually absent from Indo-European populations. Much more diversity is seen in sub-Saharan Africans than in non-Africans, consistent with an "Out of Africa" model for peopling of the Old World. Analysis of recent recombinant haplotypes by allele-specific PCR, along with deduction of the root haplotype from chimpanzee sequence, allowed construction of a haplotype network that assisted in evaluation of the relative roles of drift and selection in establishing the haplotype frequencies in the different populations. We suggest that genetic drift was important in shaping the general pattern of non-African haplotype diversity, with recent directional selection in northern Europeans for the haplotype associated with lactase persistence.