Vol 52, No 7 (2016)

The review discusses the causes of multiple failures in cancer treatment, which might primarily result from the excessive variability of cancer genomes. They are capable of changing their spatial and temporal architecture during tumor development. The key reasons of irreproducibility of biomedical data and the presumable means for improvement of therapeutic results aiming at targeting the most stable tumor traits are suggested.

Integration of the methods of contemporary genetics and biotechnology into the breeding process is assessed, and the potential role and efficacy of genome editing as a novel approach is discussed. Use of molecular (DNA) markers for breeding was proposed more than 30 years ago. Nowadays, they are widely used as an accessory tool in order to select plants by mono- and olygogenic traits. Presently, the genomic approaches are actively introduced into the breeding processes owing to automatization of DNA polymorphism analyses and development of comparatively cheap methods of DNA sequencing. These approaches provide effective selection by complex quantitative traits, and are based on the full-genome genotyping of the breeding material. Moreover, biotechnological tools, such as doubled haploids production, which provides fast obtainment of homozygotes, are widely used in plant breeding. Use of genomic and biotechnological approaches makes the development of varieties less time consuming. It also decreases the cultivated areas and financial expenditures required for accomplishment of the breeding process. However, the capacities of modern breeding are not limited to only these advantages. Experiments carried out on plants about 10 years ago provided the first data on genome editing. In the last two years, we have observed a sharp increase in the number of publications that report about successful experiments aimed at plant genome editing owing to the use of the relatively simple and convenient CRISPR/Cas9 system. The goal of some of these experiments was to modify agriculturally valuable genes of cultivated plants, such as potato, cabbage, tomato, maize, rice, wheat, barley, soybean and sorghum. These studies show that it is possible to obtain nontransgenic plants carrying stably inherited, specifically determined mutations using the CRISPR/Cas9 system. This possibility offers the challenge to obtain varieties with predetermined mono- and olygogenic traits.

Horizontal gene transfer (HGT) is widespread in the world of prokaryotes, but the examples of this phenomenon among multicellular animals, particularly insects, are few. This review examines the transfer of genetic material to the nuclear genomes of insects from the mitochondrial genome (intracellular HGT), as well as from the genomes of viruses, bacteria, fungi, and unrelated insects. In most cases, the mechanisms of this transfer are unknown. Many pro- and eukaryotic genes that moved through the HGT are expressed in the insect genome and in some cases can provide the evolutionary innovations that are considered as aromorphoses.

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.

When assessing the combined action of genes on the quantitative or qualitative phenotype we encounter a phenomenon that could be named the “paradox of the risk score summation.” It arises when the search of risk allele and assessment of their combined action are performed with the same single dataset. Too often such methodological error occurs when calculating the so called genetic risk score (GRS), which refers to the total number of alleles associated with the disease. Examples from numerous published genetic association studies are considered in which the claimed statistically significant effects can be attributed to the “risk score summation paradox.” In the second section of the review we discuss the current modifications of multiple regression analysis addressed to the so called “n ≪ p problem” (the number of points is much smaller than the number of possible predictors). Various algorithms for the model selection (searching the significant predictor combinations) are considered, beginning from the common marginal screening of the “top” predictors to LASSO and other modern algorithms of compressed sensing.