Next Article in Journal
Translesion DNA Synthesis Across Lesions Induced by Oxidative Products of Pyrimidines: An Insight into the Mechanism by Microscale Thermophoresis
Previous Article in Journal
Control of Arms of Au Stars Size and its Dependent Cytotoxicity and Photosensitizer Effects in Photothermal Anticancer Therapy
Open AccessArticle

Future Preventive Gene Therapy of Polygenic Diseases from a Population Genetics Perspective

1
Centre for Computational Evolution, University of Auckland, Auckland 1010, New Zealand
2
Department of Computer Science, University of Auckland, Auckland 1010, New Zealand
Int. J. Mol. Sci. 2019, 20(20), 5013; https://doi.org/10.3390/ijms20205013
Received: 13 September 2019 / Revised: 1 October 2019 / Accepted: 8 October 2019 / Published: 10 October 2019
(This article belongs to the Section Molecular Genetics and Genomics)
With the accumulation of scientific knowledge of the genetic causes of common diseases and continuous advancement of gene-editing technologies, gene therapies to prevent polygenic diseases may soon become possible. This study endeavored to assess population genetics consequences of such therapies. Computer simulations were used to evaluate the heterogeneity in causal alleles for polygenic diseases that could exist among geographically distinct populations. The results show that although heterogeneity would not be easily detectable by epidemiological studies following population admixture, even significant heterogeneity would not impede the outcomes of preventive gene therapies. Preventive gene therapies designed to correct causal alleles to a naturally-occurring neutral state of nucleotides would lower the prevalence of polygenic early- to middle-age-onset diseases in proportion to the decreased population relative risk attributable to the edited alleles. The outcome would manifest differently for late-onset diseases, for which the therapies would result in a delayed disease onset and decreased lifetime risk; however, the lifetime risk would increase again with prolonging population life expectancy, which is a likely consequence of such therapies. If the preventive heritable gene therapies were to be applied on a large scale, the decreasing frequency of risk alleles in populations would reduce the disease risk or delay the age of onset, even with a fraction of the population receiving such therapies. With ongoing population admixture, all groups would benefit over generations. View Full-Text
Keywords: polygenic risk; polymorphism; heritability; polygenic disease; simulation; gene therapy; gene editing; stratification; lifetime risk; admixture polygenic risk; polymorphism; heritability; polygenic disease; simulation; gene therapy; gene editing; stratification; lifetime risk; admixture
Show Figures

Graphical abstract

MDPI and ACS Style

Oliynyk, R.T. Future Preventive Gene Therapy of Polygenic Diseases from a Population Genetics Perspective. Int. J. Mol. Sci. 2019, 20, 5013.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop