The principle of utility comes to the fore to justify and legislate new diagnostic and treatment methods, in particular human genome editing. The article examines the main ethical and legal trends in this area through the prism of utilitarianism. Editing a portion of human germline DNA using CRISPR/Cas technology has generated much debate regarding the possible benefits and risks for individuals and society. On the one hand, significant social groups get a chance to get rid of the disease in future generations, on the other hand, future children will be exposed to risks associated with specific and nonspecific changes in the genome, without their consent. Another important problem that is considered in the article from the perspective of utilitarianism is the social consequences of genome editing, such as social discrimination, if the technology is used to human enhancement. The object of the study is one of the most discussed and controversial issues in bioethics – genome editing of human embryos. The article provides an ethical and philosophical analysis of the legal aspects of editing the genome of a human embryo from the point of view of hygienic treatment.

PIK3CA is one of the three most frequently mutated oncogenes in human cancers. The highest rate of mutations is found in breast cancer, endometrial cancer, bladder cancer and some other tumors. Due to integration of PI3K inhibitors in clinical practice, PIK3CA testing is necessary for developing treatment strategies for HR-positive HER2-negative patients. However, PIK3CA testing may play an important role in understanding and treatment of HER2-positive and triple-negative subtypes as well. We hereby discuss clinical significance of PIK3CA mutations in different molecular breast cancer subtypes and possible genetic testing challenges. The article also presents a frequency analysis of different PIK3CA mutations in a study of 118 patients.

Preconception carrier screening (PS) is a set of measures aimed at preventing the birth of children with genetic diseases and identifying high-risk groups. As part of preconception genetic screening programs, studies of biomaterial samples of future parents are carried out, which usually includes a cytogenetic study to exclude chromosome abnormalities, as well as analysis of the heterozygous carriage of monogenic autosomal recessive or X-linked diseases. PS is the most important tool for assessing the risk of hereditary pathology in families at the stage of pregnancy planning, which allows potential parents to increase awareness of hereditary factors associated with pregnancy, as well as to formulate timely strategy for planning and managing pregnancy to prevent the birth of a sick child. The article reviews the strategies, approaches, and methods that are currently used in preconception genetic screening, and discusses the impact of the carrier screening programs in the world.

Genomic imprinting is an epigenetic mechanism that determines and regulates expression of homologous alleles of genes of different parental origin. Disturbances in this mechanism lead to imprinting disorders (IDs). Imprinting is regulated not only within closely located gene clusters, but also through interactions in imprinted gene networks (IGNs). These interactions may explain some of the observed differences in the phenotypes of various ImpDis and MLID (multilocus imprinting disturbances, in which multiple methylation abnormalities of imprinted regions and genes are observed), where the correlation between the epigenotype and the phenotype is not always obvious. To date, at least 20 IDs have been described in humans, both with independent and with overlapping clinical signs, including minor developmental anomalies, congenital malformations, metabolic disorders, features of intellectual, motor, and physical development. More often, in an individual with a specific ID, one specific imprinted locus is affected, but there are increasing reports of patients with MLID. The causes of MLID are pathogenic variants in genes encoding oocyte and zygotic embryo development factors, 

such as NLRP2, NLRP5, NLRP7, KHDC3L, OOEP, PADI6, TLE6, UHRF1, ZFP57, ARID4A, ZAR1, ZNF445, TRIM28. Pathogenic variants of these

genes exhibit a distinct mode of inheritance in that they become functionally significant only in female carriers. They do not affect the health of the carrier herself, but her reproductive prognosis. When providing genetic counseling, it should be taken into account that the phenotype caused by disturbances in the genes for oocyte and zygotic factors of embryo development appears only when the carriers are women. Thus, the variant can be passed on through the father’s side without causing reproductive problems.

MLID is an actively studied problem in clinical and molecular genetics. Due to the possible similarity of the clinical picture of classical ID and MLID, it is advisable for patients with suspected ID to undergo analysis for MLID to establish additional methylation patterns of imprinted DMRs, since in families of patients with MLID it is necessary to conduct medical genetic counseling with a further search for genetic variants in MLID-associated genes, to establish the risk of recurrent birth of children with ID. Also, the study of MLID-associated genes may be relevant for patients with recurrent miscarriage, recurrent hydatidiform mole, and for the study of abortive material, in the absence of chromosomal abnormalities identified in it, to determine the causes of termination and competent planning of a subsequent pregnancy.

Currently, the study of mitochondrial genome in male and female gametes is one of the actively investigated topics in reproductive genetics. A number of authors argue that there is an association between mtDNA copy number, quality of gametes, and fertility potential. Male fertility depends on a large extent on seminal fluid parameters, in particular on the quantity and quality of spermatozoa, which are influenced by many genetic and non-genetic factors. Some of the genetic factors of decreased sperm motility are mitochondrial dysfunction, mitochondrial DNA (mtDNA) abnormalities in male germ cells. This article presents a brief review of the results of studies related to the mitochondrial DNA content in normal sperm parameters and various forms of pathozoospermia.

We assessed the level of genetic diversity, power of discrimination, power of exclusion of 43 autosomal STRs (D3S1358, TH01, D12S391, D5S818, TPOX, D13S317, FGA, D22S1045, D18S51, D16S539 , D8S1179, CSF1PO, D6S1043, vWA, D21S11, SE33, D10S1248, D1S1656, D19S433, D2S1338, D20S1082, D6S474, D12ATA63, D4S2666, D1S1677, D11S4463, D9S1 122, D2S1776, D10S1435, D3S3053, D5S2500, D1S1627, D3S4529, D2S1360, D17S974 , D3S1744, D9S2157, D17S1301, D8S1132, Penta D, D21S2050, D7S1517, Penta E) in Avar populations from three regions of Dagestan: Shamilsky district, Tlyaratinsky district, Untsukulsky district. The results emphasized the need to take into account the geographic origin of the individual, and not just his nationality, when choosing reference data during genetic examination in the populations of Dagestan.

Background. Karyotyping of induced pluripotent stem cells (iPSCs) is a generally accepted stage of characterization of the genetic stability of cell lines, necessary for their registration and further scientific and medical use. Recurrent karyotype anomalies can be also detected by targeted methods (FISH, qPCR), however, the laboratory-specific peculiarities of cell handling protocols can influence the pattern of aberrations.
Aim. Identification of karyotype abnormalities in iPSC lines obtained from Russian donors and their comparison with recurrent aberrations known from literature data.
Methods. Karyotyping of iPSC cultures was carried out on passage 7-28, FISH with centromeric probes was used in specific cases to clarify the frequency of trisomy detected during karyotype analysis.
Results. We analyzed karyotypes of 34 iPSC lines obtained from 19 donors. Two lines with numerical chromosomal abnormalities (+8 and +20), three lines with large structural chromosomal rearrangements (duplication in 2q and two duplications in 1q) and one line with spontaneous non-clonal chromatid breaks were revealed. Additional FISH analysis with centromeric probes of a line with mosaic trisomy 8 and an autologous line with a normal karyotype revealed the presence of an abnormal clone in both lines. Thus, the frequency of karyotype abnormalities in the analyzed iPSC lines corresponds to the literature data. Chromosomal aberrations in two of the seven abnormal lines are not described as frequent recurrent genetic anomalies in iPSCs used for targeted methods for monitoring the genetic stability of cells.
Conclusions. Our study clarifies the frequency and structure of karyotype anomalies in iPSCs obtained from Russian donors and substantiates the rationality of combining genome-wide and targeted methods for assessing the genetic stability of these cells. The presented data can be used to develop recommendations for assessing the quality of iPSC.

A family case of hereditary transthyretin amyloidosis is described. A clinical examination and molecular genetic testing of a 50-year- old patient, his 44-year-old brother and his 30-year-old son with symptoms of polyneuropathy, indigestion and urination were carried out. All three patients had a pathogenic variant of the nucleotide sequence c.199G>C (p.(Gly67Arg), p.(G67R) in exon 2 of the TTR gene in the heterozygous state. This variant was described in hereditary transthyretin familial amyloidosis. Еstablishing an accurate diagnosis for patients with symptoms of polyneuropathy of unclear genesis will allow effective preventive measures, minimize the risk of complications and conduct timely medical and genetic counseling for family.