Big Data in Genomics: Ethical Challenges and Risks

Genomic information is a class of Big Data in expanding use thanks to technological developments. Here, we review three categories of ethical risks and challenges associated with genomic information: privacy issues, the management of incidental findings, and challenges in data storage and sharing. First, we need to implement strong mechanisms to protect privacy, but genomic data faces specific risks and we need to acknowledge the possibility of re-identification. Proper usage of genomic information has to be regulated, including recommendations on incidental finding management. Also, clear policies for data sharing and explicit efforts to promote central repositories of genomic data should be established. However, technology and new applications of genetic information will develop fast and we should anticipate potential new risks

Autogestió de temàtica, data de presentació i membres de grup: una forma diferent d’utilitzar el recurs WIKI

Assignatura de Psicofisiologia, 2n semestre, Grau de Psicologia UB. 2013-201

Potential signals of natural selection in the top risk loci for coronary artery disease: 9p21 and 10q11

Background: Coronary artery disease (CAD) is a complex disease and the leading cause of death in the world. Populations of different ancestry do not always share the same risk markers. Natural selective processes may be the cause of some of the population differences detected for specific risk mutations. Objective: In this study, 384 single nucleotide polymorphisms (SNPs) located in four genomic regions associated with CAD (1p13, 1q41, 9p21 and 10q11) are analysed in a set of 19 populations from Europe, Middle East and North Africa and also in Asian and African samples from the 1000 Genomes Project. The aim of this survey is to explore for the first time whether the genetic variability in these genomic regions is better explained by demography or by natural selection. Results: The results indicate significant differences in the structure of genetic variation and in the LD patterns among populations that probably explain the population disparities found in markers of susceptibility to CAD. Conclusions: The results are consistent with potential signature of positive selection in the 9p21 region and of balancing selection in the 9p21 and 10q11. Specifically, in Europe three CAD risk markers in the 9p21 region (rs9632884, rs1537371 and rs1333042) show consistent signals of positive selection. The results of this study are consistent with a potential selective role of CAD in the configuration of genetic diversity in current human populations

'Big Data' en genómica: retos y riesgos éticos

La informació genòmica és un tipus de 'Big Data' d'ús creixent a causa de millores tecnològiques. En aquest treball, revisem tres grups de reptes i riscos ètics associats amb aquesta informació: riscos de privadesa, gestió de les troballes incidentals i reptes en l'emmagatzematge i compartició de dades. En primer lloc, hem d'establir mecanismes sòlids per protegir la privadesa, però les dades genòmiques presenten riscos específics i hem d'admetre la possibilitat de reidentificació. Cal regular l'ús adequat de la informació genòmica incloent-hi recomanacions per a la gestió de les troballes incidentals. També cal establir polítiques clares per compartir dades i fomentar l'ús de repositoris de dades genòmiques. No obstant això, hem d'esperar desenvolupaments ràpids a la tecnologia i noves aplicacions de la informació genètica, i hem d'anticipar-nos als riscos potencials futurs.Genomic information is a class of Big Data in expanding use thanks to technological developments. Here, we review three categories of ethical risks and challenges associated with genomic information: privacy issues, the management of incidental findings, and challenges in data storage and sharing. First, we need to implement strong mechanisms to protect privacy, but genomic data faces specific risks and we need to acknowledge the possibility of re-identification. Proper usage of genomic information has to be regulated, including recommendations on incidental finding management. Also, clear policies for data sharing and explicit efforts to promote central repositories of genomic data should be established. However, technology and new applications of genetic information will develop fast and we should anticipate potential new risks.La información genómica es un tipo de 'Big Data' de uso creciente debido a mejoras tecnológicas. En este trabajo, revisamos tres grupos de retos y riesgos éticos asociados con esta información: riesgos de privacidad, gestión de los hallazgos incidentales y retos en el almacenamiento y compartición de datos. En primer lugar, debemos establecer mecanismos sólidos para proteger la privacidad, pero los datos genómicos presentan riesgos específicos y debemos admitir la posibilidad de reidentificación. Hay que regular el uso adecuado de la información genómica incluyendo recomendaciones para la gestión de los hallazgos incidentales. También hay que establecer políticas claras para compartir datos y fomentar el uso de repositorios de datos genómicos. No obstante, debemos esperar desarrollos rápidos en la tecnología y nuevas aplicaciones de la información genética, y debemos anticiparnos a los futuros riesgos potenciales

Involvement of the Serotonin Transporter Gene in Accurate Subcortical Speech Encoding

A flourishing line of evidence has highlighted the encoding of speech sounds in the subcortical auditory system as being shaped by acoustic, linguistic, and musical experience and training. And while the heritability of auditory speech as well as nonspeech processing has been suggested, the genetic determinants of subcortical speech processing have not yet been uncovered. Here, we postulated that the serotonin transporter-linked polymorphic region (5-HTTLPR), a common functional polymorphism located in the promoter region of the serotonin transporter gene (SLC6A4), is implicated in speech encoding in the human subcortical auditory pathway. Serotonin has been shown as essential for modulating the brain response to sound both cortically and subcortically, yet the genetic factors regulating this modulation regarding speech sounds have not been disclosed. We recorded the frequency following response, a biomarker of the neural tracking of speech sounds in the subcortical auditory pathway, and cortical evoked potentials in 58 participants elicited to the syllable /ba/, which was presented >2000 times. Participants with low serotonin transporter expression had higher signal-to-noise ratios as well as a higher pitch strength representation of the periodic part of the syllable than participants with medium to high expression, possibly by tuning synaptic activity to the stimulus features and hence a more efficient suppression of noise. These results imply the 5-HTTLPR in subcortical auditory speech encoding and add an important, genetically determined layer to the factors shaping the human subcortical response to speech sounds. SIGNIFICANCE STATEMENT: The accurate encoding of speech sounds in the subcortical auditory nervous system is of paramount relevance for human communication, and it has been shown to be altered in different disorders of speech and auditory processing. Importantly, this encoding is plastic and can therefore be enhanced by language and music experience. Whether genetic factors play a role in speech encoding at the subcortical level remains unresolved. Here we show that a common polymorphism in the serotonin transporter gene relates to an accurate and robust neural tracking of speech stimuli in the subcortical auditory pathway. This indicates that serotonin transporter expression, eventually in combination with other polymorphisms, delimits the extent to which lifetime experience shapes the subcortical encoding of speech

Genetic risk score of NOS gene variants associated with myocardial infarction correlates with coronary incidence across Europe

Coronary artery disease (CAD) mortality and morbidity is present in the European continent in a four-fold gradient across populations, from the South (Spain and France) with the lowest CAD mortality, towards the North (Finland and UK). This observed gradient has not been fully explained by classical or single genetic risk factors, resulting in some cases in the so called Southern European or Mediterranean paradox. Here we approached population genetic risk estimates using genetic risk scores (GRS) constructed with single nucleotide polymorphisms (SNP) from nitric oxide synthases (NOS) genes. These SNPs appeared to be associated with myocardial infarction (MI) in 2165 cases and 2153 controls. The GRSs were computed in 34 general European populations. Although the contribution of these GRS was lower than 1% between cases and controls, the mean GRS per population was positively correlated with coronary incidence explaining 65-85% of the variation among populations (67% in women and 86% in men). This large contribution to CAD incidence variation among populations might be a result of colinearity with several other common genetic and environmental factors. These results are not consistent with the cardiovascular Mediterranean paradox for genetics and support a CAD genetic architecture mainly based on combinations of common genetic polymorphisms. Population genetic risk scores is a promising approach in public health interventions to develop lifestyle programs and prevent intermediate risk factors in certain subpopulations with specific genetic predisposition

The 1000 Genomes Project: new opportunities for research and social challenges

The 1000 Genomes Project, an international collaboration, is sequencing the whole genome of approximately 2,000 individuals from different worldwide populations. The central goal of this project is to describe most of the genetic variation that occurs at a population frequency greater than 1%. The results of this project will allow scientists to identify genetic variation at an unprecedented degree of resolution and will also help improve the imputation methods for determining unobserved genetic variants that are not represented on current genotyping arrays. By identifying novel or rare functional genetic variants, researchers will be able to pinpoint disease-causing genes in genomic regions initially identified by association studies. This level of detailed sequence information will also improve our knowledge of the evolutionary processes and the genomic patterns that have shaped the human species as we know it today. The new data will also lay the foundation for future clinical applications, such as prediction of disease susceptibility and drug response. However, the forthcoming availability of whole genome sequences at affordable prices will raise ethical concerns and pose potential threats to individual privacy. Nevertheless, we believe that these potential risks are outweighed by the benefits in terms of diagnosis and research, so long as rigorous safeguards are kept in place through legislation that prevents discrimination on the basis of the results of genetic testing

Reconstructing native American migrations from whole-genome and whole-exome data.

There is great scientific and popular interest in understanding the genetic history of populations in the Americas. We wish to understand when different regions of the continent were inhabited, where settlers came from, and how current inhabitants relate genetically to earlier populations. Recent studies unraveled parts of the genetic history of the continent using genotyping arrays and uniparental markers. The 1000 Genomes Project provides a unique opportunity for improving our understanding of population genetic history by providing over a hundred sequenced low coverage genomes and exomes from Colombian (CLM), Mexican-American (MXL), and Puerto Rican (PUR) populations. Here, we explore the genomic contributions of African, European, and especially Native American ancestry to these populations. Estimated Native American ancestry is 48% in MXL, 25% in CLM, and 13% in PUR. Native American ancestry in PUR is most closely related to populations surrounding the Orinoco River basin, confirming the Southern American ancestry of the Taíno people of the Caribbean. We present new methods to estimate the allele frequencies in the Native American fraction of the populations, and model their distribution using a demographic model for three ancestral Native American populations. These ancestral populations likely split in close succession: the most likely scenario, based on a peopling of the Americas 16 thousand years ago (kya), supports that the MXL Ancestors split 12.2kya, with a subsequent split of the ancestors to CLM and PUR 11.7kya. The model also features effective populations of 62,000 in Mexico, 8,700 in Colombia, and 1,900 in Puerto Rico. Modeling Identity-by-descent (IBD) and ancestry tract length, we show that post-contact populations also differ markedly in their effective sizes and migration patterns, with Puerto Rico showing the smallest effective size and the earlier migration from Europe. Finally, we compare IBD and ancestry assignments to find evidence for relatedness among European founders to the three populations

Heterogeneity in genetic admixture across different regions of Argentina

The population of Argentina is the result of the intermixing between several groups, including Indigenous American, European and African populations. Despite the commonly held idea that the population of Argentina is of mostly European origin, multiple studies have shown that this process of admixture had an impact in the entire Argentine population. In the present study we characterized the distribution of Indigenous American, European and African ancestry among individuals from different regions of Argentina and evaluated the level of discrepancy between self-reported grandparental origin and genetic ancestry estimates. A set of 99 autosomal ancestry informative markers (AIMs) was genotyped in a sample of 441 Argentine individuals to estimate genetic ancestry. We used non-parametric tests to evaluate statistical significance. The average ancestry for the Argentine sample overall was 65% European (95%CI: 63-68%), 31% Indigenous American (28-33%) and 4% African (3-4%). We observed statistically significant differences in European ancestry across Argentine regions [Buenos Aires province (BA) 76%, 95%CI: 73-79%; Northeast (NEA) 54%, 95%CI: 49-58%; Northwest (NWA) 33%, 95%CI: 21-41%; South 54%, 95%CI: 49-59%; p<0.0001] as well as between the capital and immediate suburbs of Buenos Aires city compared to more distant suburbs [80% (95%CI: 75-86%) versus 68% (95%CI: 58-77%), p = 0.01]. European ancestry among individuals that declared all grandparents born in Europe was 91% (95%CI: 88-94%) compared to 54% (95%CI: 51-57%) among those with no European grandparents (p<0.001). Our results demonstrate the range of variation in genetic ancestry among Argentine individuals from different regions in the country, highlighting the importance of taking this variation into account in genetic association and admixture mapping studies in this population

Desenvolupament transversal de la competència informacional al segon semestre del Grau de Psicologia.

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/66524Buscar, seleccionar i gestionar informació especialitzada de manera estratègica, fent ús de diferents tecnologies i fonts d'informació és una de les competències transversals de la UB. Cinc assignatures del segon semestre de Psicologia van elaborar un pla d’actuació per treballar-la coordinadament. Els estudiants que van seguir aquesta formació van obtenir notables resultats quan s'enfrontaven a exercicis pràctics específics (identificació de paraules clau o factors d'impacte), però van mostrar mancances a l’hora de resoldre tasques que requerien la cerca avançada, l’ús de l'estil APA, la identificació de títols de revistes científiques o el coneixement global dels usos i recursos d'informació. No obstant, els estudiants que van rebre la formació van ser lleugerament més competents que els seus companys de darrer curs del grau (que no havien rebut aquesta formació coordinada, però que se'ls hi suposa experiència en cerca documental, atesa les demandes de les diferents assignatures que han cursat). D’altra banda, l'avaluació de la competència informacional no va resultar independent de la resta de competències avaluades ja que va correlacionar positivament, tant en la tasca de defensa oral, com en la puntuació de l'examen final de continguts bàsics de l'assignatura (valors rxy entre 0,09 i 0,18).Buscar, seleccionar i gestionar informació especialitzada de manera estratègica, fent ús de diferents tecnologies i fonts d'informació és una de les competències transversals de la UB. Cinc assignatures del segon semestre de Psicologia van elaborar un pla d’actuació per treballar-la coordinadament. Els estudiants que van seguir aquesta formació van obtenir notables resultats quan s'enfrontaven a exercicis pràctics específics (identificació de paraules clau o factors d'impacte), però van mostrar mancances a l’hora de resoldre tasques que requerien la cerca avançada, l’ús de l'estil APA, la identificació de títols de revistes científiques o el coneixement global dels usos i recursos d'informació. No obstant, els estudiants que van rebre la formació van ser lleugerament més competents que els seus companys de darrer curs del grau (que no havien rebut aquesta formació coordinada, però que se'ls hi suposa experiència en cerca documental, atesa les demandes de les diferents assignatures que han cursat). D’altra banda, l'avaluació de la competència informacional no va resultar independent de la resta de competències avaluades ja que va correlacionar positivament, tant en la tasca de defensa oral, com en la puntuació de l'examen final de continguts bàsics de l'assignatura (valors rxy entre 0,09 i 0,18)