Biology subjects

Tsuboi, Y.

Publications and source records attributed to Tsuboi, Y..

2 recordsLinked to original sources

bioRxiv2020

Association between the extent of DNA methylation at the CpG sites of HIF3A and parameters of obesity in the general Japanese population

Obesity is a major public health problem worldwide owing to the substantial increase in risk of metabolic diseases. Hypoxia-inducible factors (HIFs) regulate transcriptional responses to hypoxic stress. DNA methylation in the CpG sites of intron 1 of HIF3A is associated with body mass index in the whole blood and adipose tissue. This study investigates the correlation between DNA methylation of HIF3A and parameters of obesity, including thickness of visceral (VAT) and subcutaneous adipose tissues, in the general Japanese population. Participants (220 men and 253 women) who underwent medical examination were enrolled in this cross-sectional study. We used pyrosequencing to quantify DNA methylation (CpG sites of cg16672562, cg22891070, and cg27146050) in HIF3A. DNA methylation of HIF3A was only different in women. Multiple regression analysis showed that DNA methylation level at cg27146050 was associated with thickness of VAT in women. DNA methylation level at cg27146050 also correlated with body mass index and percentage of body fat in women after excluding smokers and non-smokers who quit smoking with the last 5 years. DNA methylation in the CpG site (cg27146050) of HIF3A correlated with parameters of obesity in Japanese women.

biochemistry↗

bioRxiv2019

Long-read sequencing identifies GGC repeat expansion in human-specific NOTCH2NLC associated with neuronal intranuclear inclusion disease

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in neuronal and somatic cells. The wide range of clinical manifestations in NIID makes ante-mortem diagnosis difficult 1-8, but skin biopsy realized its ante-mortem diagnosis 9,10 and many NIID cases have been diagnosed by skin biopsy11,12. Most cases of NIID are sporadic, but several familial cases are known. Using a large NIID family, we conducted linkage mapping, found a 58.1-Mb linked-region at 1p22.1-q21.3 with a maximum logarithm of odds (LOD) score of 4.21, and successfully identified a GGC repeat expansion in the 5 portion of NOTCH2NLC in all affected members by long-read sequencing, but not in unaffected members. We further found the similar expansions in additional 8 unrelated families with NIID as well as 39 sporadic NIID patients. Repeat-primed PCR consistently detected the GGC repeat expansion in all the familial and sporadic patients diagnosed by skin biopsy, but never in unaffected family members nor 200 controls. This shows that pathogenic changes in a human-specific gene evolutionarily generated by segmental duplication indeed causes a human disease.

genetics↗