期刊论文详细信息
International Journal of Molecular Sciences
Future Preventive Gene Therapy of Polygenic Diseases from a Population Genetics Perspective
RomanTeo Oliynyk1 
[1] Centre for Computational Evolution, University of Auckland, Auckland 1010, New Zealand;
关键词: polygenic risk;    polymorphism;    heritability;    polygenic disease;    simulation;    gene therapy;    gene editing;    stratification;    lifetime risk;    admixture;   
DOI  :  10.3390/ijms20205013
来源: DOAJ
【 摘 要 】

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.

【 授权许可】

Unknown   

  文献评价指标  
  下载次数:0次 浏览次数:0次