The population dynamics and changes in the sex and age structure of the Shor populations of four rural district municipalities of Tashtagolskii raion of Kemerovo oblast (Kyzyl-Shorskii, Ust-Anzasskii, Ust-Kolzasskii, and Ust-Kabyrzinsskii) with time have been analyzed. The Shor populations have been found to have contained a high proportion of people under 18 years of age during two periods, 1940–1955 and 1970–1975 (38.12–46.38 and 40.98–54.97%, respectively). However, the population reproduction pattern changed into the “reduced” one in all the municipalities studied by the early 2000s. Although there are some regional variations, a common trend towards rural population aging has formed: the man age in the Tashtagolskii raion population has increased by 7.52 and 6.94 years for men and women, respectively, during two generations; the natural sex ratio has been disturbed in both the prereproductive and reproductive populations. The total population size and effective reproductive size have decreased in three out of the four rural subpopulations studied.

Представлены результаты анализа динамики численности и половозрастной структуры шорского населения четырех сельских территориальных управлений Таштагольского района Кемеровской области – Кызыл-Шорского, Усть-Анзасского, Усть-Колзасского, Усть-Кабырзинского. Для шорских популяций показана высокая доля лиц в возрасте до 18 лет в двух временных периодах – 1940–55 гг. и 1970–75 гг. (38.12–46.38% и 40.98–54.97% соответственно), но к началу 2000-х годов наблюдается смена типа воспроизводства на “суженный” в населении всех изученных территориальных управлений. Несмотря на территориальные вариации, наметилась общая тенденция – старение сельского населения: средний возраст в целом по району за два поколения увеличивается у мужчин на 7.52, у женщин на 6.94 года; нарушено естественное соотношение полов в дорепродуктивной и репродуктивной части популяции. В трех из четырех исследованных сельских субпопуляций показано снижение общей численности и эффективно-репродуктивного объема.

A simulation model has been developed for predicting the distribution of trinucleotide repeat expansion diseases in human populations. The interface of the software used to run this model presents the options for simulating natural reproduction of a population, with the population demographic parameters taken into account, and for simulating the appearance of a dynamic mutation in populations, transmission of the mutant gene from parents to offspring, and the effect of the phenotypic expression of the disease (the patients’ life expectancy and birthrate) on the transmission of the mutant allele in the patients’ families and its accumulation in the population.

Разработана имитационная модель для прогнозирования распространения заболеваний экспансии тринуклеотидных повторов в популяциях человека. Интерфейс компьютерной программы, реализующей данную модель, включает в себя как моделирование естественного воспроизводства населения с учетом демографических параметров конкретной популяции, так и имитацию появления динамической мутации в популяции, передачу мутантного гена от родителей потомкам и влияние фенотипического проявления заболевания (продолжительности жизни больных и уровня рождаемости) на передачу мутантного аллеля в семьях больных и накопление его в популяции.

Marriage structure has been analyzed in the populations of the administrative centers of five uluses of the Republic of Sakha (Yakutia). The populations studied differ from one another with respect to ethnic composition, namely in the ratio between the indigenous and immigrant populations (the indigenous populations are larger in three uluses), in the proportions of representatives of indigenous ethnic groups among men and women contracting marriages, and in the frequencies of monoethnic and interethnic marriages. Positive assortative marriage among persons of the same ethnic group has been demonstrated. The total inbreeding estimated by isonymy (Fit) varies from 0 to 0.007576.

Приведены результаты анализа брачной структуры населения из административных центров пяти улусов Республики Саха (Якутия). Обследованные популяции различаются между собой по национальному составу как в соотношении коренного и пришлого населения (в трех улусах преобладает коренное население), так и по составу представителей коренных этнических групп среди женихов и невест; по распространенности одно- и межнациональных браков. Показана положительная брачная ассортативность по национальной принадлежности супругов. Величина тотального инбридинга по изонимии Fit варьирует от 0 до 0.007576.

The marriage structure of the population of Ulan Ude, the capital of Buryat Republic, which is characterized by a mixed ethnic composition, has been studied. Differences between Ulan Ude districts in a number of genetic demographic parameters have been found. In ethnic terms, the city district populations differ from one another in the number of ethnic groups and the proportions of the largest groups (Russians and Buryats). In the total Ulan Ude population, the proportions of Russian men and women among persons contracting marriages are 71.44 and 73.79%, respectively; those of Buryat men and women are 23.36 and 22.79%, respectively. The total proportion of all other ethnic groups among both men and women contracting marriages is no more than 5.2%. The mean ages at first marriage in both indigenous and immigrant populations of Ulan Ude are relatively old; these values are 25.9 and 24.72 years for Buryat men and women and 24.86 and 22.69 for non-indigenous men and women, respectively.

Проведено изучение брачной структуры столицы Бурятии, характеризующейся смешанным этническим составом. Установлены различия по ряду генетико-демографических параметров между районами Улан-Удэ. Национальный состав районов города отличается по числу этносов и доле основных национальностей – русских и бурят. В целом по Улан-Удэ доля женихов и невест русской национальности наблюдалась на уровне 71.44 и 73.79%, женихов-бурят и невест-буряток – 23.36 и 22.79% соответственно. Суммарная численность лиц других национальностей в населении Улан-Удэ не превышает 5.2% как среди невест, так и женихов. Средний возраст вступления в первый брак у представителей коренного и пришлого населения, проживающего в Улан-Удэ, имеет высокие значения – для мужчин и женщин бурятской национальности 25.9 и 24.72 лет соответственно, 24.86 и 22.69 лет для некоренного населения, соответственно.

Common (syntropic) genes of allergic diseases (ADs) HLA-DQB1, HLA-DRB1, IL4, IL4RA, MS4A2, HLA-DQA1, LTC4S, IL13, IL10, and TGFB1 have been identified on the basis of information from the HuGENet internet database. The functional realm of these genes is associated mainly with the initiation and regulation of an immune response and inflammation. Importance of these processes in the development of ADs is underlined. The results of cluster analysis of allergic diseases obtained using the data on common genes predisposing to their development are presented. Genetic clusterization of ADs confirms their accepted clinical classification.

На основании информации интернет-базы данных HuGENet выделены общие (синтропные) гены аллергических заболеваний (АЗ): HLA-DQB1, HLA-DRB1, IL4, IL4RA, MS4A2, HLA-DQA1, LTC4S, IL13, IL10, TGFB1. Функциональная сфера компетенции этих генов лежит главным образом в области инициации и регуляции иммунного ответа и воспаления. Подчеркивается важность этих процессов в развитии АЗ. Представлены результаты анализа кластеризации АЗ на основе данных об общности предрасполагающих к их развитию генов. Установлено, что генетическая кластеризация АЗ подтверждает принятую в клинике классификацию аллергических заболеваний.

We propose a novel universal methodology, Short Oligonucleotide Tandem Ligation Assay (SOTLA), for SNP genotyping. SOTLA is based on using a tandem of short oligonucleotide (TSO) probes consisting of three fragments: the core oligonucleotide and two flanking oligomers, one of which is immobilized onto a solid support and another one contains the biotin label. TSO is self-associated on a complementary DNA template, forms the complex containing two nicks, which are efficiently ligated with DNA ligase giving biotinylated oligonucleotide covalently bound to polymer beads. No ligation of TSO on an imperfect DNA template bearing the base substitution in the core binding site is occurred. We used SOTLA for the highly selective SNP analysis in different DNA fragments of human Y chromosome. Comparison of SOTLA results with those of PCR-RFLP and allele-specific PCR techniques demonstrates that SOTLA ensures the univocal reliable SNP analysis in different PCR fragments varying in length and base composition. The fundamental difference between SOTLA and well known OLA approaches while using T4 DNA ligase is that the accuracy of SNP analysis in OLA is ensured only by the specificity of ligase while that in SOTLA is provided by the specificity of both ligation and hybridization of TSO probes.

Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae and remains endemic in many parts of the world. Despite several major studies on susceptibility to leprosy, few genomic loci have been replicated independently. We have conducted an association analysis of more than 1,500 individuals from different case-control and family studies, and observed consistent associations between genetic variants in both TLR1 and the HLA-DRB1/DQA1 regions with susceptibility to leprosy (TLR1 I602S, case-control P = 5.7 x 10(-8), OR = 0.31, 95% CI = 0.20-0.48, and HLA-DQA1 rs1071630, case-control P = 4.9 x 10(-14), OR = 0.43, 95% CI = 0.35-0.54). The effect sizes of these associations suggest that TLR1 and HLA-DRB1/DQA1 are major susceptibility genes in susceptibility to leprosy. Further population differentiation analysis shows that the TLR1 locus is extremely differentiated. The protective dysfunctional 602S allele is rare in Africa but expands to become the dominant allele among individuals of European descent. This supports the hypothesis that this locus may be under selection from mycobacteria or other pathogens that are recognized by TLR1 and its co-receptors. These observations provide insight into the long standing host-pathogen relationship between human and mycobacteria and highlight the key role of the TLR pathway in infectious diseases.

Allele frequencies for 15 STRs (CSF1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, Penta D, Penta E, THO1, TPOX, and vWA) in the PowerPlex 16 System (Promega Corporation) were assessed in 386 individuals from five Russian urban populations. No significant between-population differences in frequencies and molecular variance of 15 microsatellites were revealed. For all 15 loci, the combined matching probability is 3.19 x 10(-18) and the power of exclusion is 99.99989%.

The concept of syntropic diseases was proposed at the beginning of the last century to emphasize the phenomenon of nonrandom co-occurrence of human disorders. Common genes underlying specific syntropic diseases were called syntropic genes. The application of this concept to contemporary genomic studies will facilitate the understanding of the molecular basis of complex diseases, provide future direction for discovering new targets for therapy and prognosis, and may even lead to the reassessment of disease classification for the practice of more precise personalized medicine. With the acceptance of the syntropic genes theory, new genetic tests, focused on markers pointing to a set of pathogenetically linked diseases rather than to a single nosology, can be developed.

Many new genetic tests for common multifactorial disorders are becoming available to individuals, including direct-to-consumer genotyping services. Typically, studies of public attitudes reveal a high level of interest for individual genotyping. In a Russian urban population, 85% of 2000 respondents answered positively to a question about their own willingness to undergo predictive genetic testing for preventable health conditions. Gender, age and health status significantly influenced response. Multivariate discriminant analyses revealed that wanting to know about probable future diseases, readiness to improve lifestyles and an interest in learning about individual genome characteristics are the most important predictors for wanting to be tested. Along with the high level of interest, highly overestimated expectations were encountered in many studies. With the low predictive abilities of currently available genetic tests for common disorders, proper interpretation of the data and genetic counseling are essential. There is a need for prospective validation of genetic panels for risk assessments, and for efforts to measure the effects of genetic information disclosure and how this information might contribute to lifestyle changes.