TY - JOUR
T1 - Chasing mendel
T2 - Five questions for personalized medicine
AU - Joyner, Michael J.
AU - Prendergast, Franklyn G.
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/6/1
Y1 - 2014/6/1
N2 - Ideas about personalized medicine are underpinned in part by evolutionary biology's Modern Synthesis. In this essay we link personalized medicine to the efforts of the early statistical investigators who quantified the heritability of human phenotype and then attempted to reconcile their observations with Mendelian genetics. As information about the heritability of common diseases was obtained, similar efforts were directed at understanding the genetic basis of disease phenotypes. These ideas were part of the rationale driving the Human Genome Project and subsequently the personalized medicine movement. In this context, we discuss: (1) the current state of the genotype-phenotype relationship in humans, (2) the common-disease-common-variant hypothesis, (3) the current ability of 'omic' information to inform clinical decision making, (4) emerging ideas about the therapeutic insight available from rare genetic variants, and (5) the social and behavioural barriers to the wider potential success of personalized medicine. There are significant gaps in knowledge as well as conceptual, intellectual, and philosophical limitations in each of these five areas. We then provide specific recommendations to mitigate these limitations and close by asking if it is time for the biomedical research community to 'stop chasing Mendel?' Journal compilation
AB - Ideas about personalized medicine are underpinned in part by evolutionary biology's Modern Synthesis. In this essay we link personalized medicine to the efforts of the early statistical investigators who quantified the heritability of human phenotype and then attempted to reconcile their observations with Mendelian genetics. As information about the heritability of common diseases was obtained, similar efforts were directed at understanding the genetic basis of disease phenotypes. These ideas were part of the rationale driving the Human Genome Project and subsequently the personalized medicine movement. In this context, we discuss: (1) the current state of the genotype-phenotype relationship in humans, (2) the common-disease-common-variant hypothesis, (3) the current ability of 'omic' information to inform clinical decision making, (4) emerging ideas about the therapeutic insight available from rare genetic variants, and (5) the social and behavioural barriers to the wider potential success of personalized medicine. There are significant gaps in knowledge as well as conceptual, intellectual, and philosophical limitations in each of these five areas. We then provide specific recommendations to mitigate these limitations and close by asking if it is time for the biomedical research community to 'stop chasing Mendel?' Journal compilation
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U2 - 10.1113/jphysiol.2014.272336
DO - 10.1113/jphysiol.2014.272336
M3 - Review article
C2 - 24882820
AN - SCOPUS:84901484361
SN - 0022-3751
VL - 592
SP - 2381
EP - 2388
JO - Journal of Physiology
JF - Journal of Physiology
IS - 11
ER -