ABSTRACT
[This corrects the article DOI: 10.31662/jmaj.2018-0005.].
ABSTRACT
Induced pluripotent stem cells (iPSCs) describe somatic cells that have been reprogrammed to the pluripotent state. From a scientific perspective, their discovery has provided a molecular roadmap for turning on and off cell identities, effectively allowing any cell type to have its identity changed into any other cell type. They also act as a human model for understanding the development of every cell and organ in the body. In addition, because they can be prepared from patients, iPSCs offer a unique human model for studying disease development, including many diseases that are generally diagnosed at a late stage of their development. These models have provided new insights on the pathogenesis and new targets to prevent or reverse the disease development process. Indeed, clinical studies on compounds based on drug screening hits in human iPSC disease models have begun. Because of their proliferation and differentiation capacity, iPSCs can also be used to prepare cells for transplantations, and related clinical studies using iPSC-based cell therapies are ongoing. The combination of iPSCs with other technologies or therapeutic strategies is expected to expand their medical benefits. In this review, we consider medical accomplishments based on iPSC research and future ones that can be anticipated.
ABSTRACT
Tuberculosis (TB) is a complex disease, and both genetic and environmental factors contribute to disease progression. A previous genome-wide linkage study in Thailand determined that chromosome 20p13-12.3 may contain risk factors for young-onset disease. The present study aimed to identify novel susceptibility genes for young-onset TB within a 1-Mbp target region adjacent to the top-ranking risk marker in Chr.20p13-12.3. We performed next-generation sequencing (NGS) of the region in 13 young patients from multi-case families in Thailand. We then selected the functionally interesting single-nucleotide polymorphisms as candidates for subsequent analyses. The detected candidates rs13830 and rs1127354 in ITPA showed an association with young (<45 years old) TB patients. However, there was no association in old (⩾45 years old) patients. These findings confirm that stratifying patients based on age of TB onset can be important for identifying genetic risk factors for TB susceptibility. In addition, in silico expression quantitative trait loci analyses indicated that ITPA expression was associated with rs13830 genotype. This is the first study to use NGS resequencing to gain insight into host genetic factors associated with TB and to report a significant association for ITPA with host susceptibility in young-onset TB. The study also demonstrated the effectiveness of NGS in identifying susceptibility genes in common diseases.
