Genes Related to Fat Metabolism in Pigs and Intramuscular Fat Content of Pork: A Focus on Nutrigenetics and Nutrigenomics

Fat metabolism and intramuscular fat (IMF) are qualitative traits in pigs whose development are influenced by several genes and metabolic pathways. Nutrigenetics and nutrigenomics offer prospects in estimating nutrients required by a pig. Application of these emerging fields in nutritional science provides an opportunity for matching nutrients based on the genetic make-up of the pig for trait improvements. Today, integration of high throughput “omics” technologies into nutritional genomic research has revealed many quantitative trait loci (QTLs) and single nucleotide polymorphisms (SNPs) for the mutation(s) of key genes directly or indirectly involved in fat metabolism and IMF deposition in pigs. Nutrient–gene interaction and the underlying molecular mechanisms involved in fatty acid synthesis and marbling in pigs is difficult to unravel. While existing knowledge on QTLs and SNPs of genes related to fat metabolism and IMF development is yet to be harmonized, the scientific explanations behind the nature of the existing correlation between the nutrients, the genes and the environment remain unclear, being inconclusive or lacking precision. This paper aimed to: (1) discuss nutrigenetics, nutrigenomics and epigenetic mechanisms controlling fat metabolism and IMF accretion in pigs; (2) highlight the potentials of these concepts in pig nutritional programming and research.

CRISPR/Cas9 Mediated Genome Editing in Crop Plants

Recently, most genomic research has focused on genome editing methods to develop new technologies that could be easy, reliable, and feasible to edit plant genomes for highly productive agriculture. Genome editing is based on alternating a specific target DNA sequence by adding, replacing, and removing DNA bases. This newest technology called CRISPR/Cas9 seems to be less time-consuming, more effective and used in many research areas of plant genetic research. CRISPR/Cas9 systems have many advantages in comparison with ZFNs and TALENs and has been extensively used for genome editing to many crop plant species. Around 20 crop species are successfully worked out for trait improvements, for example, yield improvement, disease resistance, herbicide tolerance, and biotic and abiotic stress management. This review paper will overview recent advances in CRISPR/Cas genome editing research in detail. The main focus will be on the use of CRISPR/Cas9 technology in plant genome research.

Genome Wide Association Study of Beef Traits in Local Alpine Breed Reveals the Diversity of the Pathways Involved and the Role of Time Stratification

Knowledge of the genetic architecture of key growth and beef traits in livestock species has greatly improved worldwide thanks to genome-wide association studies (GWAS), which allow to link target phenotypes to Single Nucleotide Polymorphisms (SNPs) across the genome. Local dual-purpose breeds have rarely been the focus of such studies; recently, however, their value as a possible alternative to intensively farmed breeds has become clear, especially for their greater adaptability to environmental change and potential for survival in less productive areas. We performed single-step GWAS and post-GWAS analysis for body weight (BW), average daily gain (ADG), carcass fleshiness (CF) and dressing percentage (DP) in 1,690 individuals of local alpine cattle breed, Rendena. This breed is typical of alpine pastures, with a marked dual-purpose attitude and good genetic diversity. Moreover, we considered two of the target phenotypes (BW and ADG) at different times in the individuals’ life, a potentially important aspect in the study of the traits’ genetic architecture. We identified 8 significant and 47 suggestively associated SNPs, located in 14 autosomal chromosomes (BTA). Among the strongest signals, 3 significant and 16 suggestive SNPs were associated with ADG and were located on BTA10 (50–60 Mb), while the hotspot associated with CF and DP was on BTA18 (55–62 MB). Among the significant SNPs some were mapped within genes, such as SLC12A1, CGNL1, PRTG (ADG), LOC513941 (CF), NLRP2 (CF and DP), CDC155 (DP). Pathway analysis showed great diversity in the biological pathways linked to the different traits; several were associated with neurogenesis and synaptic transmission, but actin-related and transmembrane transport pathways were also represented. Time-stratification highlighted how the genetic architectures of the same traits were markedly different between different ages. The results from our GWAS of beef traits in Rendena led to the detection of a variety of genes both well-known and novel. We argue that our results show that expanding genomic research to local breeds can reveal hitherto undetected genetic architectures in livestock worldwide. This could greatly help efforts to map genomic complexity of the traits of interest and to make appropriate breeding decisions.

Diagnostic Biomarkers and Immune Infiltration in Patients With T Cell-Mediated Rejection After Kidney Transplantation

T cell-mediated rejection (TCMR) is an important rejection type in kidney transplantation, characterized by T cells and macrophages infiltration. The application of bioinformatic analysis in genomic research has been widely used. In the present study, Microarray data was analyzed to identify the potential diagnostic markers of TCMR in kidney transplantation. Cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT) was performed to determine the distribution of immune cell infiltration in the pathology. Totally 129 upregulated differently expressed genes (DEGs) and 378 downregulated DEGs were identified. The GO and KEGG results demonstrated that DEGs were mainly associated with pathways and diseases involved in immune response. The intersection of the two algorithms (PPI network and LASSO) contains three overlapping genes (CXCR6, CXCL13 and FCGR1A). After verification in GSE69677, only CXCR6 and CXCL13 were selected. Immune cells Infiltration analysis demonstrated that CXCR6 and CXCL13 were positively correlated with gamma delta T cells (p < 0.001), CD4+ memory activated T cells (p < 0.001), CD8+ T cells (p < 0.001) and M1 macrophages (p = 0.006), and negatively correlated with M2 macrophages (p < 0.001) and regulatory T cells (p < 0.001). Immunohistochemical staining and image analysis confirmed the overexpression of CXCR6 and CXCL13 in human allograft TCMR samples. CXCR6 and CXCL13 could be diagnostic biomarkers of TCMR and potential targets for immunotherapy in patients with TCMR.

Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes

Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.

BIOLOGICAL SESSION“THE IMPORTANCE OF G. GAMOW'S IDEAS FOR BIOLOGY OF THE 21st CENTURY” AT THE XXI GAMOW INTERNATIONAL ASTRONOMICAL CONFERENCE-SCHOOL IN ODESSA (15-21 AUGUST, 2021)

Третій рік поспіль в межах Гамовської конференції працює Біологічна секція: «Важливість ідей Г.А. Гамова для біології 21-ого століття», організація якої викликана великою повагою до особистості вченого Георгія Антоновича Гамова, наукові інтереси якого об’єднали астрофізику, космологію та молекулярну біологію. Цього року Біологічна секція працювала в режимі on-line 17.08.2021. Роботу секції розпочали з виступу професора Тобіуса Дельбрюка (Institute of Neuroinformatics – ETH and University of Zurich, Zurich, Switzerland), сина видатного фізика, Нобелевського лауреата Макса Дельбрюка (в певний період товариша Г.А. Гамова). Професор Тобіус Дельбрюк назвав свою доповідь – "Out of this world: Recounting Max's Delbruck memories of George Gamow”. Ця доповідь, присвячена феноменальній особистості Г.А. Гамова, придала засіданню біологічної секції емоційну атмосферу наближення до великих ідей, що надали і зараз надають поштовх для розвитку молекулярної біології. Значну зацікавленість учасників секції викликала доповідь Dr. V.N. Korzun (KWS SAAT SE & Co. KGaA (м. Айнбек, Німеччина) «Applications of genetic and genomic research in cereals», що продемонструвала впровадження в селекційний процес сучасних молекулярно-генетичних технологій. З доповіддю «DNA-protein interactions as a tool of synthetic biology», що присвячена високо технологічним розробкам зі створення біосенсорів науково-виробничою фіромою Explogen LLC (EXG) (м. Львів, Україна) виступив к.б.н. Ю. Ребець. Наступна пленарна доповідь «Using the G.A. Gamow’s ideas for molecular genetic diagnostics of infectious and somatic human diseases at the current stage of medical development» була представлена білоруськими вченими, а саме професор С.А. Касцьюк розповіла про молекулярно-генетичні дослідження, що виконуються в Білоруській медичній академії післядипломної освіти. Dr. Yu. Monchak з McGill University (м. Монреаль, Канада) також представив доповідь присвячену впровадженню ДНК-технологій в діагностику патології людини ˗ «Targeted therapy, DNA sequence and the race against neoplasia». Ця доповідь викликала велику зацікавленість учасників біологічної секції. Молоді науковці Іщенко О.О., Жарікова Д.О., Роман І.І., Доля Б., Рошка Н.М., Чубик І.Ю., Попович Ю.А., Топораш М.К., Пидюра М.О. – доктори філософії з біології, кандидати наук, аспіранти, що займаються дослідженнями в галузі молекулярної біології представили дев’ять доповідей, що відбивають результати виконаних досліджень у низці провідних університетів нашої країни, а саме у Львівському національному університеті ім. І. Франка, у Одеському національному університеті імені І.І. Мечникова, у Чернівецькому національному університеті ім. Юрія Федьковича та ДУ «Інституті харчової біотехнології та Геноміки» (м. Київ). Представлені доповіді викликали жвавий інтерес, а формат on-line дозволів об’єднати у роботі секції понад 35 учасників з різних країн ˗ України, Білорусі, Швейцарії, Німеччини, Канади і Казахстану.

Legal aspects of using genetic evidence on the example of US judicial practice

Advances in genomic research, biobanking and DNA identification technologies are expanding the use of biological and genetic evidence in litigation. The discovery of DNA and one of its functions to transmit hereditary information made it possible to look differently at the theory of a genetic predisposition to deviant behavior. The relevance of the study is due to the fact that the availability and increase of genetic research allows, along with the traditional use of genetic expertise in litigation (search and identification of a criminal, establishment of paternity), to expand the possibility of using the achievements of genetics by the parties to prove other circumstances in court. In this article, the authors analyze the US jurisprudence regarding the possibility of a party using the protection of genetic evidence in order to present a position in justification of the mitigation of punishment for an accused due to her genetic predisposition to criminal behavior. The authors also paid attention to the consideration of the issue of using the results of genetic testing in civil proceedings in order to prove the fact of the influence of the inherited gene on deviant behavior. In carrying out this study, the authors used a significant number of Russian and foreign sources of scientific literature. General and specific scientific methods of cognition, including the formal legal and comparative legal method, were used as research methods

Self-Regulation of genetic studies in Russia: search for the optimal model

The article is devoted to the general analysis of self-regulatory practices of genetic research in Russia (conducted by public research institutions and commercial companies). Selfregulation is a special type of regulation, performed by organizations providing genetic research and their associations as well as by relevant professional and scientific community; it is regulated by local acts, agreements, memoranda, professional standards, codes of ethics, etc. and is aimed at establishing relationships in the field of organization, provision and use of results of genetic studies. Basically, selfregulation is especially critical in various aspects of organization and conducting genetic research in the worldwide perspective. The analysis provided by this article allows concluding that self-regulation practice in Russia is applied in several public research institutions, but rather fragmentarily. Moreover, the development of such form of regulation goes slowly. At the same time non-public genomic institutions are trying to evade any significant self-regulation of their activities; they do not provide for any expanded rules or standards of their practices (or they just confine themselves to references and general provisions which are not in line with the specifics of the mentioned activities). On the other hand, it is important to keep in mind that the current Russian legislation is full of gaps in terms of regulating genetic research process. Analysis of several websites of Russian private companies providing genetic profiling services revealed that those organizations almost never place complex information guides on their information portals; they neither provide the standards for performing genetic research in an intelligible form. The websites do not contain any information on possible risks or threats to health connected with application of medical procedures, while the issue of disclosure the gathered genomic information to third parties (e.g., enforcement agencies) is often ignored. More than that, there are hardly any published standards for conducting genomic research or documents on protecting patients rights, etc. Thus, we are forced to acknowledge that the institute of self-regulation in the field of genetic studies is not developed well enough in Russia. The current fragmented nature of legal regulation and selfregulation concerning genetic research may contribute to violation of rights and legitimate interests of patients in terms of confidentiality and safeguarding genetic information, gathered in the process of research. The state therefore should within the established goals of intensive genetic technological development provide all the necessary conditions (including of legal character). However, it is still not clear how the issues of legal regulation of status of genetic research participants, protection of genetic data, incentives for providing genetic research, etc. should be handled. We assume that one of the possible ways of tackling the aforementioned challenges is developing relevant complex legal regulation (including departmental acts) and/or investing the frontline public research institutions with special functions (i.e., within a special council, commission, or association). Such powers will contribute to regulating certain aspects of administering and conducting genetic research and using its results in the framework of legal regulation, which should be mandatory, including for non-public organizations, offering genetic services in the territory of the Russian Federation.

International Legal Regulation of Genetic Research and Implementation of International Legal Standards in this sphere into Russian Legislation

The article analyzes the topical issues of international legal regulation of genetic research; it provides a comparative analysis of two groups of international acts regulating relations related to genetic research and application of their results on creation, use and circulation of genetically modified organisms (except humans), on the study of human genome and application of their results. The article deals with the issues of objects and methods of genetic research regulation, balance of interests as the basis for legal regulation of public relations in the field of genomic research. It also considers approaches to ensuring a balance of private, group and common (public) interests. Criticism of certain provisions of the Convention on Human Rights and Biomedicine is given, the question of the inadmissibility of legal opposition between the protection of human rights and the interests of science and society as a whole is raised. The authors put forward proposals on the implementation of a number of international norms in Russian legislation and its further improvement, as well as on the use of blockchain technology in genetic research.