The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform

Jan P Dumanski - One of the best experts on this subject based on the ideXlab platform.

  • republished non Heritable genetics of human Disease spotlight on post zygotic genetic variation acquired during lifetime
    Postgraduate Medical Journal, 2013
    Co-Authors: Lars Forsberg, Devin Absher, Jan P Dumanski
    Abstract:

    The heritability of most common, multifactorial Diseases is rather modest and known genetic effects account for a small part of it. The remaining portion of Disease aetiology has been conventionally ascribed to environmental effects, with an unknown part being stochastic. This review focuses on recent studies highlighting stochastic events of potentially great importance in human Disease—the accumulation of post-zygotic structural aberrations with age in phenotypically normal humans. These findings are in agreement with a substantial mutational load predicted to occur during lifetime within the human soma. A major consequence of these results is that the genetic profile of a single tissue collected at one time point should be used with caution as a faithful portrait of other tissues from the same subject or the same tissue throughout life. Thus, the design of studies in human genetics interrogating a single sample per subject or applying lymphoblastoid cell lines may come into question. Sporadic disorders are common in medicine. We wish to stress the non-Heritable genetic variation as a potentially important factor behind the development of sporadic Diseases. Moreover, associations between post-zygotic mutations, clonal cell expansions and their relation to cancer predisposition are central in this context. Post-zygotic mutations are amenable to robust examination and are likely to explain a sizable part of non-Heritable Disease causality, which has routinely been thought of as synonymous with environmental factors. In view of the widespread accumulation of genetic aberrations with age and strong predictions of Disease risk from such analyses, studies of post-zygotic mutations may be a fruitful approach for delineation of variants that are causative for common human disorders.

  • non Heritable genetics of human Disease spotlight on post zygotic genetic variation acquired during lifetime
    Journal of Medical Genetics, 2013
    Co-Authors: Lars Forsberg, Devin Absher, Jan P Dumanski
    Abstract:

    The heritability of most common, multifactorial Diseases is rather modest and known genetic effects account for a small part of it. The remaining portion of Disease aetiology has been conventionally ascribed to environmental effects, with an unknown part being stochastic. This review focuses on recent studies highlighting stochastic events of potentially great importance in human Disease—the accumulation of post-zygotic structural aberrations with age in phenotypically normal humans. These findings are in agreement with a substantial mutational load predicted to occur during lifetime within the human soma. A major consequence of these results is that the genetic profile of a single tissue collected at one time point should be used with caution as a faithful portrait of other tissues from the same subject or the same tissue throughout life. Thus, the design of studies in human genetics interrogating a single sample per subject or applying lymphoblastoid cell lines may come into question. Sporadic disorders are common in medicine. We wish to stress the non-Heritable genetic variation as a potentially important factor behind the development of sporadic Diseases. Moreover, associations between post-zygotic mutations, clonal cell expansions and their relation to cancer predisposition are central in this context. Post-zygotic mutations are amenable to robust examination and are likely to explain a sizable part of non-Heritable Disease causality, which has routinely been thought of as synonymous with environmental factors. In view of the widespread accumulation of genetic aberrations with age and strong predictions of Disease risk from such analyses, studies of post-zygotic mutations may be a fruitful approach for delineation of variants that are causative for common human disorders.

David M Demarini - One of the best experts on this subject based on the ideXlab platform.

  • Harnessing genomics to identify environmental determinants of Heritable Disease
    Mutation research, 2012
    Co-Authors: Carole L. Yauk, David M Demarini, J. Lucas Argueso, Scott S. Auerbach, Philip Awadalla, Sean Davis, George R. Douglas, Yuri E. Dubrova, Rosalie K. Elespuru, Thomas W. Glover
    Abstract:

    Next-generation sequencing technologies can now be used to directly measure Heritable de novo DNA sequence mutations in humans. However, these techniques have not been used to examine environmental factors that induce such mutations and their associated Diseases. To address this issue, a working group on environmentally induced germline mutation analysis (ENIGMA) met in October 2011 to propose the necessary foundational studies, which include sequencing of parent–offspring trios from highly exposed human populations, and controlled dose–response experiments in animals. These studies will establish background levels of variability in germline mutation rates and identify environmental agents that influence these rates and Heritable Disease. Guidance for the types of exposures to examine come from rodent studies that have identified agents such as cancer chemotherapeutic drugs, ionizing radiation, cigarette smoke, and air pollution as germ-cell mutagens. Research is urgently needed to establish the health consequences of parental exposures on subsequent generations.

  • declaring the existence of human germ cell mutagens
    Environmental and Molecular Mutagenesis, 2012
    Co-Authors: David M Demarini
    Abstract:

    After more than 80 years of searching for human germ-cell mutagens, I think that sufficient evidence already exists for a number of agents to be so considered, and definitive confirmation seems imminent due to the application of recently developed genomic techniques. In preparation for this, an assessment panel of internationally recognized experts in germ-cell biology and genomics is required to consider either the current evidence now, or impending genomic evidence later, to declare whether an agent is a human germ-cell mutagen. I propose that such a panel be organized under the aegis of the World Health Organization and constructed similarly to the working groups assembled by the International Agency for Research on Cancer for the evaluation of human carcinogens. Support from prominent national and international organizations would be important. Many regulatory agencies already have procedures in place for assessing potential human germ-cell mutagens, and the time is approaching when definitive genomic data in humans will obligate such evaluations. In my view, application of an IARC-type of assessment using available evidence leads to the conclusion that ionizing radiation, cancer chemotherapy, cigarette smoking, and air pollution are “Group 1” human germ-cell mutagens. Consideration of the potential adverse health effects to the unexposed offspring of an exposed parent will usher in an entirely new realm of environmental health assessment. I suggest that the long search for human germ-cell mutagens is about to end, and a demonstration of the much-anticipated linkage between Heritable Disease and environmental factors is poised to begin. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.

Dana H. Bovbjerg - One of the best experts on this subject based on the ideXlab platform.

  • A Model of Disease-Specific Worry in Heritable Disease: The Influence of Family History, Perceived Risk and Worry About Other Illnesses
    Journal of Behavioral Medicine, 2006
    Co-Authors: Terry A. Dilorenzo, Julie Schnur, Guy H. Montgomery, Joel Erblich, Gary Winkel, Dana H. Bovbjerg
    Abstract:

    Disease-related worry is associated with family history and perceived risk of that Disease; however, the influences of general risk perceptions and tendencies to worry about Diseases have been neglected in the literature. This study investigates a model of Disease-specific worry which includes family history, Disease-specific perceived risk, and perceived risk for and worry about other Diseases. Participants completed a survey assessing these variables in relation to several Heritable Diseases. Structural equation modeling found that family history predicted Disease-specific perceived risk but not perceived risk for other Diseases. Disease-specific perceived risk predicted Disease-specific worry and worry about other Diseases. Perceived risk for other Diseases predicted worry about other Diseases and Disease-specific perceived risk but not Disease-specific worry. Disease-specific worry predicted worry about other Diseases. This model was supported across several Diseases and indicates that Disease-specific and general considerations of risk influence worry about a Disease and should be considered in interventions.

Sharon Cresci - One of the best experts on this subject based on the ideXlab platform.

Lars Forsberg - One of the best experts on this subject based on the ideXlab platform.

  • republished non Heritable genetics of human Disease spotlight on post zygotic genetic variation acquired during lifetime
    Postgraduate Medical Journal, 2013
    Co-Authors: Lars Forsberg, Devin Absher, Jan P Dumanski
    Abstract:

    The heritability of most common, multifactorial Diseases is rather modest and known genetic effects account for a small part of it. The remaining portion of Disease aetiology has been conventionally ascribed to environmental effects, with an unknown part being stochastic. This review focuses on recent studies highlighting stochastic events of potentially great importance in human Disease—the accumulation of post-zygotic structural aberrations with age in phenotypically normal humans. These findings are in agreement with a substantial mutational load predicted to occur during lifetime within the human soma. A major consequence of these results is that the genetic profile of a single tissue collected at one time point should be used with caution as a faithful portrait of other tissues from the same subject or the same tissue throughout life. Thus, the design of studies in human genetics interrogating a single sample per subject or applying lymphoblastoid cell lines may come into question. Sporadic disorders are common in medicine. We wish to stress the non-Heritable genetic variation as a potentially important factor behind the development of sporadic Diseases. Moreover, associations between post-zygotic mutations, clonal cell expansions and their relation to cancer predisposition are central in this context. Post-zygotic mutations are amenable to robust examination and are likely to explain a sizable part of non-Heritable Disease causality, which has routinely been thought of as synonymous with environmental factors. In view of the widespread accumulation of genetic aberrations with age and strong predictions of Disease risk from such analyses, studies of post-zygotic mutations may be a fruitful approach for delineation of variants that are causative for common human disorders.

  • non Heritable genetics of human Disease spotlight on post zygotic genetic variation acquired during lifetime
    Journal of Medical Genetics, 2013
    Co-Authors: Lars Forsberg, Devin Absher, Jan P Dumanski
    Abstract:

    The heritability of most common, multifactorial Diseases is rather modest and known genetic effects account for a small part of it. The remaining portion of Disease aetiology has been conventionally ascribed to environmental effects, with an unknown part being stochastic. This review focuses on recent studies highlighting stochastic events of potentially great importance in human Disease—the accumulation of post-zygotic structural aberrations with age in phenotypically normal humans. These findings are in agreement with a substantial mutational load predicted to occur during lifetime within the human soma. A major consequence of these results is that the genetic profile of a single tissue collected at one time point should be used with caution as a faithful portrait of other tissues from the same subject or the same tissue throughout life. Thus, the design of studies in human genetics interrogating a single sample per subject or applying lymphoblastoid cell lines may come into question. Sporadic disorders are common in medicine. We wish to stress the non-Heritable genetic variation as a potentially important factor behind the development of sporadic Diseases. Moreover, associations between post-zygotic mutations, clonal cell expansions and their relation to cancer predisposition are central in this context. Post-zygotic mutations are amenable to robust examination and are likely to explain a sizable part of non-Heritable Disease causality, which has routinely been thought of as synonymous with environmental factors. In view of the widespread accumulation of genetic aberrations with age and strong predictions of Disease risk from such analyses, studies of post-zygotic mutations may be a fruitful approach for delineation of variants that are causative for common human disorders.