Use Of Genetic Information Research Articles

Performance of the Use of Genetic Information to Assess the Risk of Colorectal Cancer in the Basque Population.

Simple SummaryThe risk of developing colorectal cancer (CRC) is partially associated with genetics. Different studies have provided valuable genetic information to understand the biology behind CRC and to build models of genetic risk. However, the study of the applicability of such genetic information within the Basque population is limited. Thus, our objectives were to find out if the genetic variants associated with CRC in other populations are the same in the Basque population and to assess the performance of the use of genetic information to calculate the risk of developing CRC. We found that the available genetic information can be applied to the Basque population, although local genetic variation can affect its use. Our findings will help to refine the use of CRC genetic risk calculation in the Basque population, and we expect that our findings could be useful for other populations.Although the genetic contribution to colorectal cancer (CRC) has been studied in various populations, studies on the applicability of available genetic information in the Basque population are scarce. In total, 835 CRC cases and 940 controls from the Basque population were genotyped and genome-wide association studies were carried out. Mendelian Randomization analyses were used to discover the effect of modifiable risk factors and microbiota on CRC. In total, 25 polygenic risk score models were evaluated to assess their performance in CRC risk calculation. Moreover, 492 inflammatory bowel disease cases were used to assess whether that genetic information would not confuse both conditions. Five suggestive (p < 5 × 10−6) loci were associated with CRC risk, where genes previously associated with CRC were located (e.g., ABCA12, ATIC or ERBB4). Moreover, the analyses of CRC locations detected additional genes consistent with the biology of CRC. The possible contribution of cholesterol, BMI, Firmicutes and Cyanobacteria to CRC risk was detected by Mendelian Randomization. Finally, although polygenic risk score models showed variable performance, the best model performed correctly regardless of the location and did not misclassify inflammatory bowel disease cases. Our results are consistent with CRC biology and genetic risk models and could be applied to assess CRC risk in the Basque population.

The Use of Genetic Information to Define Idiopathic Pulmonary Fibrosis in UK Biobank

The Use of Genetic Information to Define Idiopathic Pulmonary Fibrosis in UK Biobank

Teacher and Parent Perspectives on the Use of Genetic Information in Schools

AbstractWhile the predictive power of genetic information is not yet strong enough to apply to individuals in the classroom, this study aimed to explore how genetic information may be received in educational settings as a potentially important source of individual differences in academic achievement and learning difficulties. Focus group discussions with teachers and parents were analyzed using qualitative and linguistic methods. Results showed that teachers and parents had similar knowledge of and questions about genetic information and how it could be used in education; both expressed concerns regarding the ethics of its use and suggested other professionals that should be involved in decisions regarding genetic input in education. Parents' personal struggles to obtain appropriate diagnoses and support for their children with learning difficulties, however, added an emotional edge to their views. Families' direct experiences with educational systems, often adversarial, afford them an authority that should be acknowledged by policymakers.

LEGAL ISSUES OF REGULATION OF THE USE OF GENETIC INFORMATION BY THE NORMS OF THE CURRENT LEGISLATIO

The scientific work is devoted to the issues of improving the national legislation of the Republic of Kazakhstan in the field of legal regulation and protection of personal information of a person, namely in relation to the collection, use and protection of genetic information. The possibilities of modern information carriers and technical innovations require the introduction of provisions into national legislation based on international standards and regulations regarding the preservation of confidentiality and the preservation of restrictions on access to information of a personal nature. Kazakh legislation does not define the concept of "genetic information", at the same time, the concept of genomic information is established by its provisions as personal. Therefore, from a legislative point of view, it is necessary to establish the content and order of use of genetic information. Genetic information in Kazakhstan is entered into an electronic portal and is available to legal entities in the field of public health care, medical personnel, government agencies and employees, an unlimited number of persons who have the opportunity to register, record and other actions through the IIN. On the basis of which it is necessary to have a legally established procedure for implementing the provisions of the current legislation on obtaining the patient's consent to access his personal data in order to eliminate unauthorized access to information, implement various methods of illegal enrichment or other use of data for selfish purposes. The practice of foreign states determines the possibility of creating a non-personalized database for the use of genetic information for scientific purposes, as well as the creation of mechanisms for the digital protection of personal data. National legislation should regulate in detail both the objects of legal protection of personal data, and the mechanism of their use and protection.

Consideration of Genetic Structure in the Ecologically or Biologically Significant Marine Areas Criteria: A Review of Convention on Biological Diversity Regional Workshops and A Case Study of Coral Reef Conservation Planning

In this study we reviewed the use of genetic information in the Ecologically or Biologically Significant Marine Areas (EBSA) of Convention on Biological Diversity (CBD). We also evaluated genetic indicators for each criterion of important marine areas. We proposed five genetic indices, mainly based on microsatellite analysis (e.g., private allele frequency and number of cryptic species), then selected EBSAs in tropical and temperate zones of Japan based on eight coral species as a case study. Finally, we compared the results with the findings from conventional species-based EBSAs. In the EBSAs genetic information was mainly used in the Northern Hemisphere, particularly in the Baltic Sea; it was rarely applied in the Southern Hemisphere and Asian regions. Although typically applied to large organisms, genetic information is used to various organisms, including benthic and bacterial communities. Genetic data are used as indicators of diversity and endemism. Genetic indices were available for all seven EBSA criteria, but only five indices of three criteria were used. Examination of important areas of corals in the temperate zone using these indices showed that the indices without genetic indicators extracted a large number of important areas in the tropics; however, the use of genetic indicators identified important locations, including in temperate zones. Comparison with conventional, mainly species-based non-genetic methods showed less than 50% agreement, although particularly important sites in marine protected areas were identified by both methods. While there is still more work to be done, such as consideration of the number of survey sites or target species, one reason is that species-based methods tend to evaluate tropical areas higher. Therefore, these genetic indices are useful for examining important regions, particularly in temperate zones; they revealed cryptic lineages, indicating that many unknown marine taxa should be considered in vulnerable marine areas. Some indicators could be extracted with additional effort, such as population size estimation, immigration, or the use of next-generation sequencing, thus guiding future studies. Because limited genetic information was available in the early stages of EBSA selection, there is a need for systematic surveys and evaluations, particularly in the Southern hemisphere, Asian region, and in small organisms.

A Genomic Information Management System for Maintaining Healthy Genomic States and Application of Genomic Big Data in Clinical Research.

Improvements in next-generation sequencing (NGS) technology and computer systems have enabled personalized therapies based on genomic information. Recently, health management strategies using genomics and big data have been developed for application in medicine and public health science. In this review, I first discuss the development of a genomic information management system (GIMS) to maintain a highly detailed health record and detect diseases by collecting the genomic information of one individual over time. Maintaining a health record and detecting abnormal genomic states are important; thus, the development of a GIMS is necessary. Based on the current research status, open public data, and databases, I discuss the possibility of a GIMS for clinical use. I also discuss how the analysis of genomic information as big data can be applied for clinical and research purposes. Tremendous volumes of genomic information are being generated, and the development of methods for the collection, cleansing, storing, indexing, and serving must progress under legal regulation. Genetic information is a type of personal information and is covered under privacy protection; here, I examine the regulations on the use of genetic information in different countries. This review provides useful insights for scientists and clinicians who wish to use genomic information for healthy aging and personalized medicine.

Parenting in the Context of the Child: Genetic and Social Processes.

The focus on the role of parenting in child development has a long-standing history. When measures of parenting precede changes in child development, researchers typically infer a causal role of parenting practices and attitudes on child development. However, this research is usually conducted with parents raising their own biological offspring. Such research designs cannot account for the effects of genes that are common to parents and children, nor for genetically influenced traits in children that influence how they are parented and how parenting affects them. The aim of this monograph is to provide a clearer view of parenting by synthesizing findings from theEarly Growth and Development Study (EGDS). EGDS is a longitudinal study of adopted children, their birth parents, and their rearing parents studied across infancy and childhood. Families (N = 561) were recruited in the United States through adoption agencies between 2000 and 2010. Data collection began when adoptees were 9 months old (males = 57.2%; White 54.5%, Black 13.2%, Hispanic/Latinx 13.4%, Multiracial 17.8%, other 1.1%). The median child age at adoption placement was 2 days (M = 5.58, SD = 11.32). Adoptive parents were predominantlyin their 30s, White, andcoming from upper-middle- or upper-class backgrounds with high educational attainment (a mode at 4-year college or graduate degree). Mostadoptive parents were heterosexual couples, andweremarried at the beginning of the project. The birth parent sample was more racially and ethnically diverse, but the majority (70%) were White. At the beginning of the study, most birth mothers and fathers were in their 20s, with a mode of educational attainment at high school degree, and few of them were married. We have been following these family members over time, assessing their genetic influences, prenatal environment, rearing environment, and child development. Controlling for effects of genes common to parents and children, we confirmed some previously reported associations between parenting, parent psychopathology, and marital adjustment in relation to child problematic and prosocial behavior. We also observed effects of children's heritable characteristics, characteristics thought to be transmitted from parent to child by genetic means, on their parents and how those effects contributed to subsequent child development. For example, we found that genetically influenced child impulsivity and social withdrawal both elicited harsh parenting, whereas a genetically influenced sunny disposition elicited parental warmth. We found numerous instances of children's genetically influenced characteristics that enhanced positive parental influences on child development or that protected them from harsh parenting. Integrating our findings, we propose a new, genetically informed process model of parenting. We posit that parents implicitly or explicitly detect genetically influenced liabilities and assets in their children. We also suggest future research into factors such as marital adjustment, that favor parents responding with appropriate protection or enhancement. Our findings illustrate a productive use of genetic information in prevention research: helping parents respond effectively to a profile of child strengths and challenges rather than using genetic information simply to identify some children unresponsive to current preventive interventions.

Pharmacogenomics and asthma treatment: acceptability to children, families and healthcare professionals

BackgroundEvidence supporting personalised treatment for asthma based on an individual’s genetics is mounting. The views of children and young people (CYP), parents and healthcare professionals (HCPs) about this evolution of...

Potential threats to the use of genetic technologies and legal ways to resolve them

The object of the study is public relations in the field of the use of genetic technologies and their impact on human and civil rights and freedoms, ensuring the security of society and the state. The subject of the study is the provisions of international law, the legislation of the Russian Federation in the field under consideration, the norms of Russian and international law in the field of criminal law protection of relations that may be jeopardized by the use of genomic technologies. The authors draw attention to the fact that the existing legal system does not fully solve the tasks of ensuring the security of human and civil rights and freedoms, society, the state, environmental protection from dangerous encroachments using advances in the field of genetics. The results of the study are based on formal logical and general scientific methods of scientific cognition, a systematic approach. In addition, private scientific methods: formal legal, comparative legal method of legal interpretation. The main conclusions of the study are the following provisions. Potential threats that pose a danger to human life and health, ensuring the safety of society and the environment have been identified. Potential risks may arise in the field of human genetic research, genome editing technologies of various organisms, illegal collection and use of genetic information about a person, the threat of the development and use of genetic weapons as a type of biological weapon, in the field of regulating the activities of DNA laboratories, the use of genetic material for cloning and the use of human embryonic material. As a solution, it is proposed to use the positive foreign experience indicated in the work, the ideas of domestic authors and also the author's proposals for improving the legal regulation of the sphere in question. The novelty of the study lies in the fact that actual and potential risks are identified that pose a serious danger not only to individuals, but also to society as a whole. Legal solutions for their elimination are proposed.

Liquid Biopsy Using Cell-Free or Circulating Tumor DNA in the Management of Hepatocellular Carcinoma.

Liver cancer (hepatocellular carcinoma [HCC]) is a fatal cancer worldwide and often is detected at an advanced stage when treatment options are very limited. This drives the development of techniques and platforms for early detection of HCC. In recent years, liquid biopsy has provided a means of noninvasive detection of cancers. By detecting plasma circulating tumor DNA (ctDNA) released from dying cancer cells, the presence of HCC can be detected in a noninvasive manner. In this review, we discuss the molecular characteristics of ctDNA and its various molecular landscapes in HCC. These include the mutational landscape, single-nucleotide variations, copy number variations, methylation landscape, end motif/coordinate preference, hepatitis B virus integration, and mitochondrial DNA mutations. The consistency between the plasma ctDNA and the tumor tissue genomic DNA mutational profile is pivotal for the clinical utility of ctDNA in the clinical management of HCC. With strategic use of genetic information provided from plasma ctDNA profiling and procedure standardization to facilitate implementation in clinical practice, better clinical management would become permissible through more efficient detection and diagnosis of HCC, better prognostication, precision-matched treatment guidance, and more reliable disease monitoring.

Gene-diet interaction in plasma lipid response to plant sterols and stanols: A review of clinical trials

• PS reduce plasma LDL-C levels by 6–12%. • LDL-C response to PS intake modulated by variants in cholesterol metabolism genes. • Only CYP7A1 c. −204C > A variant offered an hypocholesterolemic effect. • Standardization of clinical trials evaluating gene-diet interaction is necessary. Plant sterols and stanols (PS) are well known for their cholesterol-lowering effect by reducing intestinal absorption of cholesterol. However, genetic factors modulate the low-density lipoprotein cholesterol (LDL-C) response to PS therapy. This review examines clinical trials evaluating the impact of the main genes associated with response of plasma lipid concentrations to PS intake: APOE, CYP7A1, ABCG5/G8, NPC1L1, CETP, APOA4/A5, SCARBI, HMGCR, PPARα, LIPC, MTHFR and LPA. Evidence indicates that carriers of mutant allele of the CYP7A1 c. −204 A > C variant experience a greater plasma cholesterol reduction after PS intake, although there is discrepancy for the rest of genetic variants studied. Thus, it is necessary to standardize the design of these studies to validate the use of genetic information as a predictor marker of the response to the intervention with PS, to scientifically validate the use of these data in the personalized dietary advice.

Genetic testing in ambulatory cardiology clinics reveals high rate of findings with clinical management implications

Cardiovascular disease (CVD) is the leading cause of death in adults in the United States, yet the benefits of genetic testing are not universally accepted. We developed the "HeartCare" panel of genes associated with CVD, evaluating high-penetrance Mendelian conditions, coronary artery disease (CAD) polygenic risk, LPA gene polymorphisms, and specific pharmacogenetic (PGx) variants. We enrolled 709 individuals from cardiology clinics at Baylor College of Medicine, and samples were analyzed in a CAP/CLIA-certified laboratory. Results were returned to the ordering physician and uploaded to the electronic medical record. Notably, 32% of patients had a genetic finding with clinical management implications, even after excluding PGx results, including 9% who were molecularly diagnosed with a Mendelian condition. Among surveyed physicians, 84% reported medical management changes based on these results, including specialist referrals, cardiac tests, and medication changes. LPA polymorphisms and high polygenic risk of CAD were found in 20% and 9% of patients, respectively, leading to diet, lifestyle, and other changes. Warfarin and simvastatin pharmacogenetic variants were present in roughly half of the cohort. Our results support the use of genetic information in routine cardiovascular health management and provide a roadmap for accompanying research.

Genetic testing and insurance implications: Surveying the US general population about discrimination concerns and knowledge of the Genetic Information Nondiscrimination Act (GINA).

Globally, due to public concerns of genetic discrimination, some countries and insurance industries have adopted policies restricting insurer use of genetic information, such as the US Genetic Information Nondiscrimination Act (GINA). This study reports on combined analysis of two surveys assessing public knowledge of GINA and concerns of genetic discrimination in a diverse U.S. sample (N=1616). We focus on whether occupation, genetic testing history, and insurance status are correlated with knowledge of GINA or concerns of discrimination. While bivariate analysis identified some populations with higher subjective/objective knowledge and concern relative to counterparts, multivariable regression identified very few significant associations with outcomes of interest. Overall, this study highlights lack of awareness and understanding of GINA, even among subpopulations hypothesized to have greater knowledge of the law. These findings have implications for the broader debate around insurer use of genetic information.

PROBLEMS OF THE USE OF GENETIC INFORMATION IN CIVIL PROCEEDINGS1*

In the presented article, the author analyzes the features of the use of genetic information obtained as a result of the study of human DNA (Deoxyribonucleic acid) in civil proceedings, which, until recently, was considered as one of the most reliable evidence in the case. However, the examples from practice given in the work show the vulnerability of the approach when any of the evidence is recognized as having the greatest value, compared to the rest. The cases considered indicate that, despite the high reliability of the genetic information obtained as a result of the study of the DNA profile, nevertheless, the result of the examination may be erroneous due to cross-contamination of samples with other genetic material, mixing of DNA samples belonging to different persons in forensic medicine laboratories, including due to mislabelling and, finally, the minimal, but existing possibility, the overlap of DNA profiles in different subjects. The presented article substantiates the conclusion that the value and significance of the results of DNA research for the purpose of providing genetic information about one of the parties to the trial will largely depend on its analysis in conjunction with other available evidence in the case. Given that genetic tests in legal proceedings can certainly be useful and necessary, the court should use an individual approach when deciding whether to order a genetic examination. The widespread use of genetic tests in civil proceedings can have far-reaching implications not only for judicial practice and legal doctrine, but for the whole society as a whole, and can affect public attitudes towards responsibility, privacy and justice.

Investigating perceived heritability of mental health disorders and attitudes toward genetic testing in the United States, United Kingdom, and Australia.

Our beliefs about the heritability of psychiatric traits may influence how we respond to the use of genetic information in this area. In the present study, we aim to inform future education campaigns as well as genetic counseling interventions by exploring common fears and misunderstandings associated with learning about genetic predispositions for mental health disorders. We surveyed 3,646 genetic research participants from Australia, and 960 members of the public from the United Kingdom, and the United States, and evaluated attitudes toward psychiatric genetic testing. Participants were asked hypothetical questions about their interest in psychiatric genetic testing, perceived usefulness of psychiatric genetic testing, and beliefs about malleability of behavior, among others. We also asked them to estimate the heritability of alcohol dependence, schizophrenia, and major depression. We found a high interest in psychiatric genetic testing. In most cases, more than a third of the participants showed serious concerns related to learning about personal genetic predisposition, such as not wanting to have children if they knew they had a high genetic predisposition, or not wanting to choose a partner with a high genetic predisposition for a mental health problem. Finally, we found a significant association between most participants' attitudes and their lay estimates of heritability, which highlights the complexity of educating the public about genetics.

Colonization history and human translocations explain the population genetic structure of the noble crayfish (Astacus astacus) in Fennoscandia: Implications for the management of a critically endangered species

Abstract The noble crayfish (Astacus astacus) is an endangered freshwater species in Europe. The main threat is from lethal crayfish plague, caused by the oomycete Aphanomyces astaci that has been spread over Europe by introduced North American crayfish species, acting as chronic carriers of the disease. Most of the remaining noble crayfish populations are found in the Baltic Sea area, and there is an urgent need to implement conservation actions to slow down or halt the extinction rate in this region. However, limited knowledge about the genetic structure of populations in this area has so far precluded the development of conservation strategies that take genetic aspects into consideration. Key objectives of this large‐scale genetic study, covering 77 locations mainly from northern Europe, were to describe the contemporary population genetic structure of the noble crayfish in the Fennoscandian peninsula (Sweden, Norway, and Finland), taking postglacial colonization history into account, and to evaluate how human activities such as stocking have affected the genetic structure of the populations. Analyses of 15 microsatellite markers revealed three main genetic clusters corresponding to populations in northern, middle, and southern Fennoscandia, with measures of genetic diversity being markedly higher within populations in the southern cluster. The observed genetic structure probably mirrors two main colonizations of the Baltic Sea basin after the last glaciation period. At the same time, several deviations from this pattern were observed, reflecting past human translocations of noble crayfish. The results are discussed in relation to the conservation and management of this critically endangered species. In particular, we recommend increased efforts to protect the few remaining noble crayfish populations in southern Fennoscandia and the use of genetic information when planning stocking activities, such as reintroductions following local extinctions.

Feasibility of melting fingerprint obtained from ISSR-HRM curves for marine mammal species identification.

Currently, species identification of stranded marine mammals mostly relies on morphological features, which has inherent challenges. The use of genetic information for marine mammal species identification remains limited, therefore, new approaches that can contribute to a better monitoring of stranded species are needed. In that context, the ISSR-HRM method we have proposed offers a new approach for marine mammal species identification. Consequently, new approaches need to be developed to identify individuals at the species level. Eight primers of the ISSR markers were chosen for HRM analysis resulting in ranges of accuracy of 56.78–75.50% and 52.14–75.93% in terms of precision, while a degree of sensitivity of more than 80% was recorded when each single primer was used. The ISSR-HRM primer combinations revealed a success rate of 100% in terms of discrimination for all marine mammals included in this study. Furthermore, ISSR-HRM analysis was successfully employed in determining marine mammal discrimination among varying marine mammal species. Thus, ISSR-HRM analysis could serve as an effective alternative tool in the species identification process. This option would offer researchers a heightened level of convenience in terms of its performance and success rate. It would also offer field practice to veterinarians, biologists and other field-related people a greater degree of ease with which they could interpret results when effectively classifying stranded marine mammals. However, further studies with more samples and with a broader geographical scope will be required involving distinct populations to account for the high degree of intraspecific variability in cetaceans and to demonstrate the range of applications of this approach.

Population Genetics of the Invasive Red Fox, Vulpes vulpes, in South-Eastern Australia.

The use of genetic information in conservation biology has become more widespread with genetic information more readily available for non-model organisms. It has also been recognized that genetic information from invasive species can inform their management and control. The red fox poses a significant threat to Australian native fauna and the agricultural industry. Despite this, there are few recently published studies investigating the population genetics of foxes in Australia. This study investigated the population genetics of 94 foxes across the Illawarra and Shoalhaven regions of New South Wales, Australia. Diversity Array sequencing technology was used to genotype a large number of single nucleotide polymorphisms (N = 33,375). Moderate genetic diversity and relatedness were observed across the foxes sampled. Low to moderate levels of inbreeding, high-levels of identity-by-state values, as well as high identity-by-descent values were also found. There was limited evidence for population genetic structure among the foxes across the landscape sampled, supporting the presence of a single population across the study area. This indicates that there may be no barriers hindering fox dispersal across the landscape.

Using Pharmacogenetics of Direct Oral Anticoagulants to Predict Changes in Their Pharmacokinetics and the Risk of Adverse Drug Reactions.

Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.

Pharmacoepidemiology: A time for a new multidisciplinary approach to precision medicine.

The advent of the genomic age has created a rapid increase in complexity for the development and selection of drug treatments. A key component of precision medicine is the use of genetic information to improve therapeutic effectiveness of drugs and prevent potential adverse drug reactions. Pharmacoepidemiology, as a field, uses observational methods to evaluate the safety and effectiveness of drug treatments in populations. Pharmacoepidemiology by virtue of its focus, tradition, and research orientation can provide appropriate study designs and analysis methods for precision medicine. The objective of this manuscript is to demonstrate how pharmacoepidemiology can impact and shape precision medicine and serve as a reference for pharmacoepidemiologists interested in contributing to the science of precision medicine. This paper depicts the state of the science with respect to the need for pharmacoepidemiology and pharmacoepidemiological methods, tools and approaches for precision medicine; the need for and how pharmacoepidemiologists use their skills to engage with the precision medicine community; and recommendations for moving the science of precision medicine pharmacoepidemiology forward. We propose a new integrated multidisciplinary approach dedicated to the emerging science of precision medicine pharmacoepidemiology.