Studies on Understanding Individual Willingness to Disclose Genetic Information to Public and Private Stakeholders

While technologies for genetic sequencing have increased the promise of personalized medicine, they simultaneously pose threats to personal privacy. The public’s desire to protect itself from unauthorized access to information may limit the uses of this valuable resource. To date, there is limited understanding about the public’s attitudes toward the regulation and sharing of such information. We sought to understand the drivers of individuals’ decisions to disclose genetic information to a third party in a setting where disclosure potentially creates both private and social benefits, but also carries the risk of potential misuse of private information. We conducted two separate but related studies. First, we administered surveys to college students and parents, to determine individual attitudes toward and inter-generational influences on the disclosure decision. Second, we conducted a game-theory based experiment that assessed how participants’ decisions to disclose genetic information are influenced by societal and health factors. Key survey findings indicate that concerns about genetic information privacy negatively impact the likelihood of disclosure while the perceived benefits of disclosure and trust in the institution receiving the information have a positive influence. The experiment results also show that the risk of discrimination negatively affects the likelihood of disclosure, while the positive impact that disclosure has on the probability of finding a cure and the presence of a monetary incentive to disclose, increase the likelihood. We also study the determinants of individuals’ decision to be informed of findings about their health, and how information about health status is used for financial decisions.

Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery.

Intratumoral B lymphocytes are an integral part of the lung tumor microenvironment. Interrogation of the antibodies they express may improve our understanding of the host response to cancer and could be useful in elucidating novel molecular targets. We used two strategies to explore the repertoire of intratumoral B cell antibodies. First, we cloned VH and VL genes from single intratumoral B lymphocytes isolated from one lung tumor, expressed the genes as recombinant mAbs, and used the mAbs to identify the cognate tumor antigens. The Igs derived from intratumoral B cells demonstrated class switching, with a mean VH mutation frequency of 4%. Although there was no evidence for clonal expansion, these data are consistent with antigen-driven somatic hypermutation. Individual recombinant antibodies were polyreactive, although one clone demonstrated preferential immunoreactivity with tropomyosin 4 (TPM4). We found that higher levels of TPM4 antibodies were more common in cancer patients, but measurement of TPM4 antibody levels was not a sensitive test for detecting cancer. Second, in an effort to focus our recombinant antibody expression efforts on those B cells that displayed evidence of clonal expansion driven by antigen stimulation, we performed deep sequencing of the Ig genes of B cells collected from seven different tumors. Deep sequencing demonstrated somatic hypermutation but no dominant clones. These strategies may be useful for the study of B cell antibody expression, although identification of a dominant clone and unique therapeutic targets may require extensive investigation.

ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide.

In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date - of schizophrenia and major depression - ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others(1), ENIGMA's genomic screens - now numbering over 30,000 MRI scans - have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants - and genetic variants in general - may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures - from tens of thousands of people - that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.

Por qué cae la productividad de los rodales forestales? : influencia de la dominancia de crecimiento del rodal y la eficiencia de crecimiento individual

Un patrón reconocido del desarrollo de los bosques (naturales o implantados) es la caída en su tasa de crecimiento luego de alcanzar un máximo. En el presente estudio se evaluó el efecto de los cambios en la estructura del rodal, caracterizados por la dominancia de crecimiento, sobre el crecimiento del rodal, la eficiencia de crecimiento del rodal y la eficiencia de crecimiento de árboles de distinto tamaño en parcelas raleadas y sin ralear de Pinus taeda. De acuerdo a la hipótesis planteada, la caída en el crecimiento del rodal estaría relacionada con la disminución en la eficiencia de crecimiento de los individuos de menor tamaño de un rodal debido al establecimiento de la dominancia de crecimiento. La dominancia de crecimiento en las parcelas sin ralear aumentó en forma continua con la edad, aunque siempre manteniendo valores bajos. En las parcelas raleadas los niveles de dominancia de crecimiento fueron aun menores y no se observó un patrón sistemático con la edad. Esta menor dominancia de crecimiento no resultó en una mayor eficiencia de crecimiento del rodal. Por otro lado, en las parcelas sin ralear los árboles de mayor tamaño siempre fueron más eficientes que los de menor tamaño, mientras que en las parcelas raleadas esto dependió del año. En contra de la hipótesis planteada, y al igual que la eficiencia de crecimiento de los árboles más chicos, la eficiencia de los árboles dominantes también disminuyó con la edad. De acuerdo a los bajos niveles de dominancia de crecimiento encontrados (en comparación a otros géneros) se concluye que ésta no es responsable de la caída de la eficiencia de crecimiento de los individuos más pequeños ni de la tasa de crecimiento del rodal en su conjunto. Asimismo, se propone que es la diferencia en eficiencia entre individuos la que conduce al desarrollo de la dominancia de crecimiento y no al revés.