RESUMEN
Although previous studies have documented a bottleneck in the transmission of mtDNA genomes from mothers to offspring, several aspects remain unclear, including the size and nature of the bottleneck. Here, we analyze the dynamics of mtDNA heteroplasmy transmission in the Genomes of the Netherlands (GoNL) data, which consists of complete mtDNA genome sequences from 228 trios, eight dizygotic (DZ) twin quartets, and 10 monozygotic (MZ) twin quartets. Using a minor allele frequency (MAF) threshold of 2%, we identified 189 heteroplasmies in the trio mothers, of which 59% were transmitted to offspring, and 159 heteroplasmies in the trio offspring, of which 70% were inherited from the mothers. MZ twin pairs exhibited greater similarity in MAF at heteroplasmic sites than DZ twin pairs, suggesting that the heteroplasmy MAF in the oocyte is the major determinant of the heteroplasmy MAF in the offspring. We used a likelihood method to estimate the effective number of mtDNA genomes transmitted to offspring under different bottleneck models; a variable bottleneck size model provided the best fit to the data, with an estimated mean of nine individual mtDNA genomes transmitted. We also found evidence for negative selection during transmission against novel heteroplasmies (in which the minor allele has never been observed in polymorphism data). These novel heteroplasmies are enhanced for tRNA and rRNA genes, and mutations associated with mtDNA diseases frequently occur in these genes. Our results thus suggest that the female germ line is able to recognize and select against deleterious heteroplasmies.
Asunto(s)
ADN Mitocondrial , Familia , Heterogeneidad Genética , Patrón de Herencia , Población Blanca/genética , Alelos , Femenino , Frecuencia de los Genes , Humanos , Masculino , Modelos Genéticos , Modelos Estadísticos , Mutación , Países Bajos , Polimorfismo Genético , Selección Genética , GemelosAsunto(s)
Bancos de Muestras Biológicas/ética , Sistemas de Información Geográfica/ética , Derechos Humanos/psicología , Bancos de Muestras Biológicas/estadística & datos numéricos , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/ética , Monitoreo Epidemiológico , Sistemas de Información Geográfica/estadística & datos numéricos , Humanos , Salud Pública , RiesgoRESUMEN
The aim of this study was to investigate (potential) research participants' (a) information preferences with regard to receiving biobanks' genetic research results, and (b) attitudes towards the duties of researchers to communicate research results. A total group of 1,678 was analyzed, consisting of a sample of the general Dutch population (N=1,163) and patients with asthma, rhinitis, and thrombosis (N=515) who completed a survey including six fictitious genetic research results each presented as aggregate and individual result, varied for treatability and kind of disease. Five questions assessed attitudes towards researchers' duties to communicate research results. Additionally, background characteristics were measured. A majority of the respondents wanted to receive aggregate results as well as individual results. A small majority (59%) held the view that researchers should communicate individual results with no health consequences. One third agreed with an information duty only when treatment is available. A preference for individual results and an attitude in favor of communicating results were both associated with belonging to the general Dutch population rather than being a patient, wanting to learn about own health as the reason for biobank-participation, a monitoring coping style, a general desire for health information, perceived meaningfulness of genetic information and no anticipated anxiousness. A sizable majority of respondents showed a high information preference for individual results, even when it is unclear that treatment is available. Fewer were of the opinion that researchers should make this possible. For their communication policy biobanks should take notice of (potential) participants' high information preferences and expectations.
Asunto(s)
Actitud Frente a la Salud , Enfermedades Genéticas Congénitas/psicología , Investigación Genética , Genómica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Asma/genética , Estudios Transversales , ADN/sangre , ADN/aislamiento & purificación , Escolaridad , Ambiente , Encuestas Epidemiológicas , Humanos , Persona de Mediana Edad , Países Bajos , Rinitis/genética , Saliva/químicaRESUMEN
In 2016, four US cancer patients legally challenged Myriad by claiming full access to all genomic information produced in the course of Myriad's testing of their risks for a variety of cancers. Asserting that Myriad's refusal to provide them with this information violated the HIPAA Privacy Rule, the patients sought a determination of a right to access all their genetic information from testing laboratories. Such access would not only serve their own care, but also enable them to share their genetic data with the scientific community which they alleged Myriad failed to do. A similar case may be brought in Europe under the novel EU GDPR. Specifically, it would put the GDPR right of access to personal data against Myriad's database right under the EU Database Right Directive. The outcome of this case could impact the fate of personalized medicine, which depends on the one hand on patients' having control over their genetic data, and on the other hand on incentives for genetic testing companies to generate these data. We first address the issue of whether the GDPR applies to medical records. We then analyse how GDPR rights could play out in the context of clinical genetic testing and conclude that the GDPR access right stops short of granting unconditional access to all data generated in the process of testing, to the extent that its exercise would result in the violation of medical-professional norms, expose the testing company to potential liability, or compromise normal exploitation of the database of which the personal data form part.
Asunto(s)
Acceso a la Información/legislación & jurisprudencia , Seguridad Computacional/legislación & jurisprudencia , Bases de Datos Genéticas/legislación & jurisprudencia , Pruebas Genéticas/legislación & jurisprudencia , Derechos del Paciente/legislación & jurisprudencia , Europa (Continente) , Pruebas Genéticas/ética , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/psicologíaRESUMEN
A proposal for the development of a dynamic, online, grass roots WIKI+ legal platform for sharing, discussing, validating and issuing authoritative and reliable legal forms and standards to aid the (European) biomedical research community in navigating the legal pathways that govern cross-border, multi-jurisdictional (EU) research (legal platform).
Asunto(s)
Academias e Institutos/legislación & jurisprudencia , Investigación Biomédica/legislación & jurisprudencia , Cooperación Internacional/legislación & jurisprudencia , Sistemas en Línea/estadística & datos numéricos , Europa (Continente)RESUMEN
Eighty Dutch investigators (response 41%) involved in biobank research responded to a web-based survey addressing communication of results of biobank research to individual participants. Questions addressed their opinion towards an obligation to communicate results and related issues such as ownership of blood samples, privacy, therapeutic relationship, costs and implications for participants. Most researchers (74%) indicated that participants only have to be informed when results have implications for treatment or prevention. Researchers were generally not inclined to provide more feedback to patients as compared with healthy participants, nor were they inclined to provide feedback in return for participants' contribution to the biobank. Our results demonstrate major and significant differences in opinion about the feedback of individual results within the community of biobank researchers.