PIONEERING SCIENCE
EFFICIENT MANIPULATION OF GENE DOSAGE IN HUMAN IPSCS USING CRISPR/CAS9 NICKASES
Publish on Nature Communications Biology (2021)
Abstract (Partial)
The dysregulation of gene dosage due to duplication or haploinsufficiency is a major cause of autosomal dominant diseases such as Alzheimer’s disease. However, there is currently no rapid and efficient method for manipulating gene dosage in a human model system such as human induced pluripotent stem cells (iPSCs). Here, we demonstrate a simple and precise method to simultaneously generate iPSC lines with different gene dosages using paired Cas9 nickases. Our method described herein can be a useful model system for investigating disease mechanisms and therapeutic development.
GENETIC AND POLYGENIC RISK SCORE ANALYSIS FOR ALZHEIMER'S DISEASE IN THE CHINESE POPULATION
Published on
The Journal of Alzheimer's Association (2020)
Abstract (Partial)
Dozens of Alzheimer's disease (AD)-associated loci have been identified in European-descent populations, but their effects have not been thoroughly investigated in the Hong Kong Chinese population. SORL1 is associated with AD in the Hong Kong Chinese population. Meta-analysis corroborates the AD-protective effect of the SORL1 rs11218343 C allele. The PRS is developed and associated with AD risk, cognitive status, and AD-related endophenotypes. TREM2 H157Y might influence the amyloid beta 42/40 ratio and levels of immune-associated proteins in plasma. SORL1 is associated with AD in the Hong Kong Chinese population. The PRS model can predict AD risk and cognitive status in this population.