Author: Bc. Dagmar Bakerová Supervisor: MUDr. Vít Řeháček Charles University, Faculty of Pharmacy in Hradec Králové Title of diploma thesis: RhD antigen screening by molecular genetic methods This thesis deals with the genotyping of weak and partial antigens using molecular genetic methods. The main aim is to evaluate the rate of the representation of individual types of variant and weak RhD antigens in first-time blood donors, patients and pregnant women. Testing took place at the Transfusion Department of University Hospital Hradec Králové between October 2015 and February 2019. The PCR-SSP method was used for RHD genotyping using commercially supplied BAGene SSP kits from BAGene Health Care. The study includes 32 samples from first-time blood donors in the reference period to determine the specific type of RhD antigen, and 188 samples from patients and pregnant women, for whom serological methods could not be used to unequivocally identify the RhD antigen. For all pregnant women, moreover, the genotyping result was a factor in determining whether to administer anti-D immunoglobulin. This RHD genotyping for all serologically ambiguous samples has made it possible to determine a specific type of partial or weak RhD antigen. In the donor group, the weak RhD antigen was detected in 1.12 % of cases...

Depuis l'avènement du Projet de génome humain, les progrès biotechnologiques déboulent à un rythme effréné. Or, les développements en matière de génétique humaine, riches de promesses pour améliorer la santé et le bien-être, pourraient être utilisés à des fins désastreuses, à savoir la possibilité de discrimination fondée sur les caractéristiques génétiques. Dans le domaine de l'emploi, et particulièrement au stade de la pré-embauche, une telle discrimination pourrait se manifester par le refus d'emploi ou l'offre de moins bonnes conditions d'emploi. En conséquence, l'information génétique utilisée à des fins discriminatoires pourrait considérablement ralentir l'acceptation des nouvelles technologies génétiques. Il faut déterminer si l'encadrement actuel est adéquat compte tenu des problématiques soulevées par l'utilisation du test génétique lors de la préembauche. Ce mémoire présente de façon simplifiée les éléments scientifiques liés à la génétique, fournit de l'information sur le Projet de génome humain, expose les applications actuelles du test génétique dans le milieu de travail et examine les enjeux économiques et éthiques soulevés par ce sujet. Par la suite, nous analysons les avantages et les inconvénients des trois approches relatives aux politiques d'encadrement à la discrimination génétique lors du recrutement des futurs employés. Cette analyse est suivie d'un compte rendu de la situation au Québec pour enfin proposer quelques recommandations de manière à encourager l'élaboration d'une politique d'encadrement satisfaisante. / Since the advent of the Ruman Genome Project, discoveries in the field of human genetics have been prolific. As a result of these scientific developments, new genetic tests are now available for a variety of disorders. Although advances in genetic research promise dramatic progress in the treatment and prevention of genetic diseases, they raise concerns about the protection of human rights of individuals such as the possibility of genetic discrimination by employers. With regards to the workplace, genetic information will surely influence hiring praetices. Therefore, such practices will affect public acceptance of new genetic technologies. Considering the issues raised with regards to genetic testing, is the current legislative framework suitable to avoid genetic discrimination in the hiring process? This thesis will attempt to answer this question. We will begin by an overview of genetics and the Ruman Genome Project. We will examine the ethical and legal implications of genetic testing in the workplace. The thesis will focus on three public policy approaches in dealing with genetic discrimination for employment purposes. After outlining the advantages and disadvantages of each approach, we will analyse the state of the law in the province of Québec. At the end of our discussion, we will propose recommendations to deal more efficiently with the increasing fear of genetic discrimination in the workplace and to limit the adverse effects of genetic information in the hiring process. / "Mémoire présenté à la Faculté des études supérieures En vue de l'obtention du grade de maîtrise en droit"

Hela det mänskliga genomet var sekvenserat i april 2003 och sedan dess har utvecklingen av genetisk testning avancerat snabbt. Sjuksköterskor kan komma att ha en central roll gällande att informera personer kring den genetiska testningen, rådgiva personer som genomgår genetisk testning och hjälpa dem att tolka resultaten. Genom att beskriva personers känslor kring att genomföra genetisk testning kan sjuksköterskor få hjälp till en ökad förståelse. Syftet var därför att beskriva personers känslor kring att genomföra en genetisk testning för genetiskt betingade sjukdomar med en möjlig dödlig utgång. För att få en överblick av det aktuella forskningsläget genomfördes en systematisk sökordsbaserad litteraturöversikt. Totalt tolv artiklar granskades och kodades. Resultatet presenteras i fyra teman: Rädsla och lättnad, som handlar om rädsla för sjukdomen, oro och ångest men också lättnaden när resultatet var negativt; Ovisshet kring hanterandet, där känslor av frustration, chock och orättvisa framkom men även förväntningar inför resultatet; Hopp och hopplöshet, vilket syntes som hopp inför framtiden och personlig kontroll samt en känsla av att vara besegrad, maktlös och förrådd; samt Gemenskap och utanförskap inom familjen, som uppstod i relation till andra där känslan av att vilja dölja samt behov av stöd var framstående. Då hälsa är vårdandets mål diskuteras resultatet utifrån Katie Erikssons hälsokors samt i förhållande till hälsa som rörelse. Ytterligare forskning och utbildning krävs för att sjuksköterskor ska erhålla kunskap om personcentrerat vårdande genom processen av genetisk testning. / The human genome was sequenced in April 2003 and since then genetic testing has developed rapidly. Nurses may come to have a central and significant role regarding informing people about all the potential outcomes of genetic testing, advising people undergoing genetic testing and helping them interpret the results. By describing people's feelings about implementing genetic testing, nurses be helped to a better understanding and ability to perform a person-centered care. The aim was therefore to describe people's feelings about implementing a genetic testing for genetic diseases with possible fatal outcome. To get an overview of the current state of research, a systematic search-terms-based literature review was performed. A total of twelve articles were reviewed and coded, resulted in four themes: Fear and relief, which is about fear of the disease, worry and anxiety but also relief when the result was negative; Uncertainty surrounding the handling, where feelings of frustration, shock and injustice emerged but also expectations for the outcome; Hope and hopelessness, which appeared as a hope for the future and personal control but also a sense of being defeated, powerless and betrayed; and Community and exclusion within the family, which arose in relation to others where feeling of wanting to hide and needs of support were prominent. The goal of caring is health. The result of this study is therefore discussed with reference to Katie Eriksson's health cross and in relation to health as a movement. Further research and education is required for nurses to obtain knowledge about person-centered care through the process of genetic testing.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (p. 121-126).

La dématérialisation de l’accès aux tests génétiques apparaît comme un outil concourant à satisfaire l’ensemble des composantes du droit à la protection de la santé. En effet, en la matière, la spécialisation de la médecine induit une limitation des personnes habilitées à prescrire des tests génétiques. Aussi, la recherche de la meilleure sécurité sanitaire possible pour la réalisation des tests génétiques induit des problématiques d’égal accès aux laboratoires de biologie médicale autorisés à cet effet, mais auxquelles la dématérialisation peut apporter des réponses. Aussi, elle n’apparaît pas être antinomique de l’autonomie des patients, bien qu’elle présente des faiblesses. / The dematerialization of access to genetic testing appears to be a tool to satisfy all the aspects of the right to health protection. Indeed, in this field, the specialization of medicine induces a limitation of the numbers of persons entitled to prescribe genetic tests. The quest for the best quality and health security for the realization of the genetic tests induces problems of equal access to the laboratories of medical biology authorized for this purpose, but to which dematerialization can give answers. Also, dematerialization does not appear to be antinomic of patient autonomy, although it presents weaknesses.

Although evidence is currently available for population-based genetic screening and testing of individuals and their family members for certain hereditary chronic disease conditions (Tier 1), few states have integrated these genomic applications into chronic disease prevention programs. State and territorial chronic disease directors (CDDs) could provide the leadership needed to deliver these applications in more states. The purpose of this study was to determine whether an association exists between current chronic disease genomics funding or specific state genomic activities and the level of knowledge and interests in genomics by these directors. Rogers's diffusion of innovations (DIT) theory was used to explain the current climate of state chronic disease genomics and the need for an innovation champion to promote these evidence-based applications both in and out of the state health departments. A nonexperimental, cross-sectional, correlational survey of CDDs (N = 58) was performed using the Chronic Disease Director's Survey and results were analyzed using chi-square, independent t test, ANOVA, logistic regression, and Pearson's correlation coefficient. Results showed CDDs knowledge of genomics is unrelated to current state funding; however, CDD knowledge and interest in genomics was associated with inclusion of genetics in cancer control and cardiovascular health action plans, Tier 1 condition education, privacy and nondiscrimination laws, Behavioral Risk Factor Surveillance System (BRFSS) genomics questions, and frequent collaborations with outside entities. These results provide clear ideas to increase CDDs knowledge and interest in chronic disease genomics and potentially impact Tier 1 genomics implementation in more states.

Indiana University-Purdue University Indianapolis (IUPUI) / This thesis critically evaluates the progress of prenatal genetic testing, and how it, along with concurrent social pressures (such as the goal of having the ideal child) may have altered parental decision-making, autonomy, and attitudes toward children. Distinctive to this thesis is the analysis of prenatal genetic testing with a view of the eugenic history of genetics and public health initiatives in maternal health. This thesis will describe what current genetic screening pursuits may indicate with this historical understanding. I will discuss the dynamics of these subjects, and how they correspond with current social demands for perfection and the growing commodification of children. With this analysis I will attempt to shed greater light upon how our current prenatal screening technologies can modify the parent/child relationship, and what this may mean as medical science and technology advance. This thesis will be organized in a three-chapter format, providing a historical viewpoint and analysis of salient ethical issues.

Genetic test results have important implications for close family members. Indeterminate negative results are the most common outcome of BRCA1/2 mutation testing. Little is known about family members' understanding of indeterminate negative BRCA1/2 test results. The purpose of this qualitative descriptive study was to investigate how daughters and sisters received and understood genetic test results as shared by their mothers or sisters. Participants included 81 women aged 40-74 with mothers or sisters previously diagnosed with breast cancer and who received indeterminate negative BRCA1/2 test results. Participants had never been diagnosed with breast cancer nor received their own genetic testing or counseling. This IRB approved study utilized semi-structured interviews administered via telephone. The research team developed descriptive codes, and NVIVO software was used during qualitative analysis. Participants reported low amounts of information shared with them. Most women described test results as negative and incorrectly interpreted the test to mean there was no genetic component to the pattern of cancer in their families. Only 7 of 81 women accurately described test results consistent with the meaning of an indeterminate negative result — meaning a genetic cause for cancer in their family could still exist. Our findings demonstrate that indeterminate negative genetic test results are not well understood by family members. Lack of understanding may lead to an inability to effectively communicate results to primary care providers and missed opportunities for prevention, screening and further genetic testing. We recommend providing family members letters they can share with their own primary care providers whenever genetic testing is performed.

Public health screening plays an important role in the overall healthcare system. As an example, consider newborn screening, a state-level initiative that screens newborns for life-threatening genetic disorders for which early treatment can substantially improve health outcomes. Another topical example is in the realm of infectious disease screening, e.g., screening for COVID-19. The common features of both public health screening problems include large testing populations and resource limitations that inhibit screening efforts. Cost is a major barrier to the inclusion of genetic disorders in newborn screening, and thus screening must be both highly accurate and efficient; and for COVID-19, limited testing kits, and other shortages, have been major barriers to screening efforts. Further, for both newborn screening and infectious disease screening, equity (reducing health disparities among different sub-populations) is an important consideration. We study the testing process design for newborn screening for genetic diseases, considering cystic fibrosis as a model disorder. Our optimization-based models take into account disease-related parameters, subject risk factors, test characteristics, parameter uncertainty, and limited testing resources so as to design equitable, accurate, and robust screening processes that classify newborns as positive or negative for cystic fibrosis. Our models explicitly consider the trade-off between false-negatives, which lead to missed diagnoses, and the required testing resources; and the trade-off between the accuracy and equity of screening. We also study the testing process design for infectious disease screening, considering COVID-19 as a model disease. Our optimization-based models account for key subject risk factors that are important to consider, including the likelihood of being disease-positive, and the potential harm that could be averted through testing and the subsequent interventions. Our objectives include the minimization of harm (through detection and mitigation) or maximization of testing coverage. These are complex problems. We develop novel mathematical models and characterize key structural properties of optimal solutions. This, in turn, allows the development of effective and efficient algorithms that exploit these structural properties. These algorithms are either polynomial- or pseudo-polynomial-time algorithms, and are able to solve realistic-sized problems efficiently. Our case studies on cystic fibrosis screening and COVID-19 screening, based on realistic data, underscore the value of the proposed optimization-based approaches for public health screening, compared to current practices. Our findings have important implications for public policy. / Doctor of Philosophy / Public health screening plays an important role in the overall healthcare system. As an example, consider newborn screening, a state-level initiative that screens newborns for life-threatening genetic disorders for which early treatment can substantially improve health outcomes. Another topical example is in the realm of infectious disease screening, e.g., screening for COVID-19. The common features of both public health screening problems include large testing populations and resource limitations that inhibit screening efforts. Cost is a major barrier to the inclusion of genetic disorders in newborn screening, and thus screening must be both highly accurate and efficient; and for COVID-19, limited testing kits, and other shortages, have been major barriers to screening efforts. Further, for both newborn screening and infectious disease screening, equity (reducing health disparities among different sub-populations) is an important consideration. We study the testing process design for newborn screening for genetic diseases, considering cystic fibrosis as a model disorder. Our optimization-based models take into account disease-related parameters, subject risk factors, test characteristics, parameter uncertainty, and limited testing resources so as to design screening processes that classify newborns as positive or negative for cystic fibrosis. Our models explicitly consider the trade-off between false-negatives, which lead to missed diagnoses, and the required testing resources; and the trade-off between the accuracy and equity of screening. We also study the testing process design for infectious disease screening, considering COVID-19 as a model disease. Our optimization-based models account for key subject risk factors that are important to consider, including the likelihood of being disease-positive, and the potential harm that could be averted through testing and the subsequent interventions. Our objectives include the minimization of harm (through detection and mitigation) or maximization of testing coverage. These are complex problems. We develop novel mathematical models and characterize key structural properties of optimal solutions. This, in turn, allows the development of effective and efficient algorithms that exploit these structural properties. Our case studies on cystic fibrosis screening and COVID-19 screening, based on realistic data, underscore the value of the proposed optimization-based approaches for public health screening, compared to current practices. Our findings have important implications for public policy.

Positive identification of a deceased individual is one of the major aspects of modem forensic death investigations. Incomplete or fragmented skeletal remains pose a problem for identification because the normal methods forensic anthropologists employ for compiling a biological profile of the decedent are of no use. Ancestry is an important aspect of the biological profile that, when known, can help narrow the focus of investigations by excluding many individuals from the search scope. This thesis describes molecular genetic methods which can be used to estimate ancestry in order to aid in forensic identification when other methods fail. The Y chromosome is one aspect of the genome shown to contain markers which are associated with the geographical origins of its possessor. The laboratory aspect of this research involved taking bone samples from humerii, extracting DNA from these samples and then sequencing a number of Y-SNPs in order to predict the biogeographical origins of each sample. Performing this research demonstrated the steps involved in this type of genetic ancestral analysis. At present, anthropology can only distinguish between major population groups. However, as research continues to be performed, the discriminatory power of molecular genetic ancestral analyses such as this has the potential to be further refined so that sub-populations may be distinguished between. This could be of great value if introduced into the forensic community.