The ethics of translating high-throughput science into clinical practice.

Biomedical research is increasingly data intensive and computational, and "big data science" is migrating into the clinical arena. Unfortunately, ethicists, regulators, and policy-makers have barely begun to explore the ethical, legal, and social issues raised by the variety of analytical and computational approaches in use and under development in biology and medicine. Most scholarship concerning big data bioscience has focused on privacy, a vitally important consideration but not the only one. Among the issues raised by new computational technologies are questions about safety and safety assessment, justice, and how to obtain proper informed consent. These technologies also raise a myriad of regulatory issues that could influence the probability of translating new assays or computational tools to the clinical or public health spheres.

[Biomarkers collections: the future or a waste of resources?]. / Biomarkersammlungen: Zukunft oder Ressourcenverschwendung?

Disease biomarkers would aim at a more specific definition of diagnosis or subtype of a certain disease, as well as prognosis definition, including efficacy and side effects of certain therapeutics. Biomarkers could lead to a prognostically optimized definition of remission in the individual patient and thus to a more objective definition of therapeutic efficacy. Is this possible and does it make sense? Or would an extensive analysis of biomarkers to date lead to a costly overestimation of as yet not well established biologic parameters? Although we are currently unable to answer this question, many colleagues argue in favour of more in depth research for a better evaluation of biomarkers in many diseases. This could save money if we were able to predict the efficacy of expensive drugs such as immunobiologics. Biomarkers comprise cytometric information, data on protein expression and secretion, mRNA, microRNA or DNA, including epigenetic variants. Although much of these data already exist in the scientific literature, it is associated with problems in terms of feasibility (for cytometry and RNA analysis only on-site analysis is possible, while for DNA analysis central testing is also possible), costs and reproducibility (ethnic variability!). To date all biomarkers have only limited value in terms of the above-mentioned aims. The present review compiles "PROs and CONs" in a subjective way in order to provoke a discussion on the meaningfulness of biomarkers, while at the same time supporting and encouraging further research in this field.

Collecting biomeasures in the Panel Study of Income Dynamics: ethical and legal concerns.

As social surveys like the Panel Study of Income Dynamics (PSID) consider adding biomeasures to their data collections, they will face complicated ethical, legal, and practical issues. Both fairly and not, research participants are likely to be more concerned about their biomeasures than about their social data. This heightened concern will force investigators to pay more attention to difficult issues such as the research participant's control over subsequent uses of the samples or data, the participant's right to withdraw from the project, protection of the research participant's privacy, return to the participant of important risk information gained through the research, some special issues involving children and families, and the process of informed consent. Investigators can navigate these issues successfully, but the effort will demand time, careful thought, and attention.

Genetic testing for paediatric neurological disorders.

Paediatric neurological disorders encompass a large group of clinically heterogeneous diseases, of which some are known to have a genetic cause. Over the past few years, advances in nosological classifications and in strategies for molecular testing have substantially improved the diagnosis, genetic counselling, and clinical management of many patients, and have facilitated the possibility of prenatal diagnoses for future pregnancies. However, the increasing availability of genetic tests for paediatric neurological disorders is raising important questions with regard to the appropriateness, choice of protocols, interpretation of results, and ethical and social concerns of these services. In this Review, we discuss these topics and how these concerns affect genetic counselling.

Caracterización genética de una población de Ecuador / Genetic characterization of Ecuador population

En los últimos años ha habido un creciente interés por los estudios genéticos en poblaciones latinoamericanas, principalmente con objetivos evolutivos y forenses. En este estudio se ha analizado la distribución de frecuencias de 15 sistemas genéticos STRs autonómicos y de la distribución haplotípica de 12 marcadores STR de cromosoma Y en muestras de los tres grupos étnicos principales de Ecuador (AU)

In the past few years, there has been an increasing interest in genetic studies of Latin-American populations, with evolutionary and forensic purposes. Ecuador’s population is mainly structured in three major ethnic groups: mestizos, Native Americans and Afro-Americans. It is a small country with huge ethnic richness. However, there are few studies about these populations, especially about native Americans and Afro-Americans. In this study the frequency distribution of 15 autosomal STRs, and the haplotipic distribution of 12 Y-STRs have been analysed in samples form the three principal ethnic groups from Ecuador (AU)

Restos biológicos de interés forense: extracción de ADN a partir de muestras comunes / Biological remains of forensic interest: DNA extraction from non complex samples

En el presente artículo se realiza una revisión de los diferentes métodos de extracción de ADN a partir de muestras biológicas comunes: sangre, semen y saliva. El objetivo de este trabajo es comparar las ventajas e inconvenientes de los diversos procedimientos de extracción, para poder evaluar qué métodos son los más adecuados en las distintas investigaciones forenses. La sangre, el semen y la saliva son evidencias biológicas muy comunes en investigaciones médico-legales, especialmente en crímenes violentos. La sangre y la saliva son excelentes fuentes de ADN, que no presentan grandes dificultades en el proceso de extracción de ADN. Por eso, este tipo de evidencias se utilizan como muestras indubitadas para obtener el perfil genético de las personas implicadas en la investigación. En cambio, la extracción de ADN a partir de muestras de semen puede resultar problemática, ya que es habitual hallar mezclar de semen con células epiteliales vaginales u otros fluidos biológicos procedentes de la víctima. Esto dará lugar a una mezcla de perfiles genéticos en el genotipado de las muestras, por lo que será necesaria la separación de los diferentes tipos celulares para poder discriminar el perfil genético masculino del femenino

We have reviewed the different methods for DNA extraction from common biological samples: blood, semen and saliva. The advantages and disadvantages of the extraction methods have been considered, so that the most adequate techniques in the different forensic investigations can be avaluated. Blood, semen and saliva are very common biological evidences in medical legal investigations, especially in violent assaults. Blood and saliva are excellent DNA sources, which do not present many problems in the DNA extraction process. For this reason, these kinds of evidence are used as reference samples to obtain genetic profiles. Otherwise, the DNA extraction form sperm could be problematic, since it´s usual to find mixtures of sperm and female vaginal cells. In such cases the female DNA could mask the genetic profile of the male component, and it would be necessary to separate the different cell types, so individual DNA profiles can be obtained

Ethical considerations in testing workers for the -Glu69 marker of genetic susceptibility to chronic beryllium disease.

OBJECTIVE: The most compelling real-world example of genetic testing for susceptibility to a workplace exposure involves those industries that process or fabricate beryllium. We examined ethical issues associated with testing for susceptibility to chronic beryllium disease. METHODS: Using ethical and clinical criteria, we examined voluntary employer-sponsored testing programs in which individual results are reported directly to workers in a confidential manner. RESULTS: Under reasonable assumptions, the longitudinal positive predictive value of the HLA-DPB1-Glu69 marker of susceptibility to beryllium disease is 12%. Interpretive challenges further limit the utility of the test and may inadvertently suggest a false sense of safety among workers. Concerns about confidential participation and pressures to be tested also must be addressed. CONCLUSIONS: Difficulties surrounding the interpretation of the HLA-DPB1-Glu69 marker, lack of assurance regarding the protection of worker confidentiality, and the potential lowering of social barriers to the implementation of mandatory worker screening combine to make testing beryllium workers inappropriate at this time.

The CYP3A4*1B variant is related to the onset of puberty, a known risk factor for the development of breast cancer.

Breast development, one of the first signs of puberty, is closely associated with age at menarche; and early menarche is in turn a well-established risk factor for female breast cancer. We examined the relationships between the onset of puberty and gene variants for certain enzymes that regulate hormone metabolism among 137 healthy nine-year-old girls from two pediatric clinics. High-activity CYP17 alleles, involved in estrogen formation, and high-activity CYP1A2 and CYP1B1 alleles, whose gene products metabolize estradiol, were not associated with pubertal stage. High activity CYP3A4, but not CYP3A5, which primarily metabolizes testosterone, showed a striking association with the onset of puberty (adjusted odds ratio, 3.21; 95% confidence interval, 1.62-6.89 for the genotype 0-1-2 rapid alleles). Of the homozygous CYP3A4*1B/1B girls, 90% had reached puberty; whereas, for the low-activity homozygous CYP3A4*1A/1A individuals, only 40% had done so. In heterozygotes, 56% had reached puberty. CYP1B1, CYP3A4, and CYP3A5 rapid variants were more common in African-American than in Hispanic or Caucasian girls.