TY - JOUR
T1 - The continuum of causality in human genetic disorders
AU - Katsanis, Elias Nicholas
N1 - Funding Information:
I thank Erica Davis and Patrick Sullivan for their critical evaluation and assistance in compiling this work and the investigators of the Center for Human Disease Modeling (Duke University Medical Center, NC, USA) for their thoughtful input. This work was supported by grants from the US National Institutes of Health (P50 DK096415, P50 MH094268, and P50 HD028138).
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/11/17
Y1 - 2016/11/17
N2 - Studies of human genetic disorders have traditionally followed a reductionist paradigm. Traits are defined as Mendelian or complex based on family pedigree and population data, whereas alleles are deemed rare, common, benign, or deleterious based on their population frequencies. The availability of exome and genome data, as well as gene and allele discovery for various conditions, is beginning to challenge classic definitions of genetic causality. Here, I discuss recent advances in our understanding of the overlap between rare and complex diseases and the context-dependent effect of both rare and common alleles that underscores the need for revising the traditional categorizations of genetic traits.
AB - Studies of human genetic disorders have traditionally followed a reductionist paradigm. Traits are defined as Mendelian or complex based on family pedigree and population data, whereas alleles are deemed rare, common, benign, or deleterious based on their population frequencies. The availability of exome and genome data, as well as gene and allele discovery for various conditions, is beginning to challenge classic definitions of genetic causality. Here, I discuss recent advances in our understanding of the overlap between rare and complex diseases and the context-dependent effect of both rare and common alleles that underscores the need for revising the traditional categorizations of genetic traits.
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U2 - 10.1186/s13059-016-1107-9
DO - 10.1186/s13059-016-1107-9
M3 - Article
C2 - 27855690
AN - SCOPUS:84997525141
SN - 1474-7596
VL - 17
JO - Genome biology
JF - Genome biology
IS - 1
M1 - 233
ER -
