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1.  Identification of an Interaction between VWF rs7965413 and Platelet Count as a Novel Risk Marker for Metabolic Syndrome: An Extensive Search of Candidate Polymorphisms in a Case-Control Study 
PLoS ONE  2015;10(2):e0117591.
Although many single nucleotide polymorphisms (SNPs) have been identified to be associated with metabolic syndrome (MetS), there was only a slight improvement in the ability to predict future MetS by the simply addition of SNPs to clinical risk markers. To improve the ability to predict future MetS, combinational effects, such as SNP—SNP interaction, SNP—environment interaction, and SNP—clinical parameter (SNP × CP) interaction should be also considered. We performed a case-control study to explore novel SNP × CP interactions as risk markers for MetS based on health check-up data of Japanese male employees. We selected 99 SNPs that were previously reported to be associated with MetS and components of MetS; subsequently, we genotyped these SNPs from 360 cases and 1983 control subjects. First, we performed logistic regression analyses to assess the association of each SNP with MetS. Of these SNPs, five SNPs were significantly associated with MetS (P < 0.05): LRP2 rs2544390, rs1800592 between UCP1 and TBC1D9, APOA5 rs662799, VWF rs7965413, and rs1411766 between MYO16 and IRS2. Furthermore, we performed multiple logistic regression analyses, including an SNP term, a CP term, and an SNP × CP interaction term for each CP and SNP that was significantly associated with MetS. We identified a novel SNP × CP interaction between rs7965413 and platelet count that was significantly associated with MetS [SNP term: odds ratio (OR) = 0.78, P = 0.004; SNP × CP interaction term: OR = 1.33, P = 0.001]. This association of the SNP × CP interaction with MetS remained nominally significant in multiple logistic regression analysis after adjustment for either the number of MetS components or MetS components excluding obesity. Our results reveal new insight into platelet count as a risk marker for MetS.
doi:10.1371/journal.pone.0117591
PMCID: PMC4315519  PMID: 25646961
2.  Genetic analyses of agronomic traits in Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.) 
Breeding Science  2012;62(4):303-309.
The consumption of products made from Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.) has increased in recent years in Japan. Increased consumer demand has led to recognition of the need for early varieties of this crop with high and stable yields. In order to accomplish this, more information is needed on the genetic mechanisms affecting earliness and yield. We conducted genetic analysis of 3 agronomic traits (days to flowering, plant height and total seed weight per plant) to segregate F2 and F3 populations derived from a cross between Tartary buckwheat cultivars ‘Hokuriku No. 4’ and ‘Ishisoba’. Broad-sense heritability estimates for days to flowering, plant height and total seed weight were 0.70, 0.62 and 0.75, respectively, in F3 population. Narrow-sense heritability for total seed weight (0.51) was highest, followed by heritability for days to flowering (0.37), with heritability for plant height (0.26) lowest. Later flowering was associated with increased plant height and higher yields. From the F4 generation, we identified twelve candidate plants with earlier maturity and reduced plant height compared to ‘Hokuriku No. 4’, but almost the same total seed weight. These results suggest that hybridization breeding using the single seed descent (SSD) method is an effective approach for improving agronomic characteristics of Tartary buckwheat.
doi:10.1270/jsbbs.62.303
PMCID: PMC3528326  PMID: 23341743
Tartary buckwheat; segregating generation; genetic parameter; heritability; genetic correlation; phenotypic correlation; hybridization breeding
3.  Combinational risk factors of metabolic syndrome identified by fuzzy neural network analysis of health-check data 
Background
Lifestyle-related diseases represented by metabolic syndrome develop as results of complex interaction. By using health check-up data from two large studies collected during a long-term follow-up, we searched for risk factors associated with the development of metabolic syndrome.
Methods
In our original study, we selected 77 case subjects who developed metabolic syndrome during the follow-up and 152 healthy control subjects who were free of lifestyle-related risk components from among 1803 Japanese male employees. In a replication study, we selected 2196 case subjects and 2196 healthy control subjects from among 31343 other Japanese male employees. By means of a bioinformatics approach using a fuzzy neural network (FNN), we searched any significant combinations that are associated with MetS. To ensure that the risk combination selected by FNN analysis was statistically reliable, we performed logistic regression analysis including adjustment.
Results
We selected a combination of an elevated level of γ-glutamyltranspeptidase (γ-GTP) and an elevated white blood cell (WBC) count as the most significant combination of risk factors for the development of metabolic syndrome. The FNN also identified the same tendency in a replication study. The clinical characteristics of γ-GTP level and WBC count were statistically significant even after adjustment, confirming that the results obtained from the fuzzy neural network are reasonable. Correlation ratio showed that an elevated level of γ-GTP is associated with habitual drinking of alcohol and a high WBC count is associated with habitual smoking.
Conclusions
This result obtained by fuzzy neural network analysis of health check-up data from large long-term studies can be useful in providing a personalized novel diagnostic and therapeutic method involving the γ-GTP level and the WBC count.
doi:10.1186/1472-6947-12-80
PMCID: PMC3469424  PMID: 22853735
Data mining; Combinational risk factor; Fuzzy neural network; Glutamyltranspeptidase; Lifestyle disease; Personalized diagnostic method; White blood cell
4.  QTL analysis of heterostyly in Primula sieboldii and its application for morph identification in wild populations 
Annals of Botany  2011;108(1):133-142.
Background and Aims
Primula sieboldii is a perennial clonal herb that is distributed around the Sea of Japan and is endangered in Japan. Its breeding system is characterized by heteromorphic self-incompatibility, and the morph ratio within a population is very important for reproductive success. The aims of this study were to construct a linkage map, map the S locus as a qualitative trait and quantitative trait loci (QTLs) for floral morphological traits related to heterostyly, and predict the morph type in wild populations by using molecular markers for devising a conservation strategy.
Methods
A linkage map was constructed with 126 markers. The QTLs for four floral traits and the S locus were mapped. Using the genotypes of loci that were located near both the S locus and the QTLs with large effects, morphs of 59 wild genets were predicted.
Key Results
The linkage map consisted of 14 linkage groups (LGs). The S locus was mapped to LG 7. Major QTLs for stigma and anther heights were detected in the same region as the S locus. These QTLs exhibited high logarithm of the odds scores and explained a high percentage of the phenotypic variance (>85 %). By analysing these two traits within each morph, additional QTLs for each trait were detected. Using the four loci linked to the S locus, the morphs of 43 genets in three wild populations could be predicted.
Conclusions
This is the first report of a linkage map and QTL analysis for floral morphology related to heterostyly in P. sieboldii. Floral morphologies related to heterostyly are controlled by the S locus in LG 7 and by several QTLs in other LGs. Additionally, this study showed that molecular markers are effective tools for investigating morph ratios in a population containing the non-flowering individuals or during the non-flowering seasons.
doi:10.1093/aob/mcr117
PMCID: PMC3119624  PMID: 21693668
Heterostyly; floral morphology; QTL analysis; Primula sieboldii; morph identification; monitoring of morph ratio
5.  Direct immobilization of DNA oligomers onto the amine-functionalized glass surface for DNA microarray fabrication through the activation-free reaction of oxanine 
Nucleic Acids Research  2007;35(17):e110.
Oxanine having an O-acylisourea structure was explored to see if its reactivity with amino group is useful in DNA microarray fabrication. By the chemical synthesis, a nucleotide unit of oxanine (Oxa-N) was incorporated into the 5′-end of probe DNA with or without the -(CH2)n- spacers (n = 3 and 12) and found to immobilize the probe DNA covalently onto the NH2-functionalized glass slide by one-pot reaction, producing the high efficiency of the target hybridization. The methylene spacer, particularly the longer one, generated higher efficiency of the target recognition although there was little effect on the amount of the immobilized DNA oligomers. The post-spotting treatment was also carried out under the mild conditions (at 25 or 42°C) and the efficiencies of the immobilization and the target recognition were evaluated similarly, and analogous trends were obtained. It has also been determined under the mild conditions that the humidity and time of the post-spotting treatment, pH of the spotting solution and the synergistic effects with UV-irradiation largely contribute to the desired immobilization and resulting target recognition. Immobilization of DNA oligomer by use of Oxa-N on the NH2-functionalized surface without any activation step would be employed as one of the advanced methods for generating DNA-conjugated solid surface.
doi:10.1093/nar/gkm619
PMCID: PMC2034461  PMID: 17715142
6.  Simulating hemispatial neglect with virtual reality 
Background
Hemispatial neglect is a cognitive disorder defined as a lack of attention for stimuli contra-lateral to the brain lesion. The assessment is traditionally done with basic pencil and paper tests and the rehabilitation programs are generally not well adapted. We propose a virtual reality system featuring an eye-tracking device for a better characterization of the neglect that will lead to new rehabilitation techniques.
Methods
This paper presents a comparison of eye-gaze patterns of healthy subjects, patients and healthy simulated patients on a virtual line bisection test. The task was also executed with a reduced visual field condition hoping that fewer stimuli would limit the neglect.
Results
We found that patients and healthy simulated patients had similar eye-gaze patterns. However, while the reduced visual field condition had no effect on the healthy simulated patients, it actually had a negative impact on the patients. We discuss the reasons for these differences and how they relate to the limitations of the neglect simulation.
Conclusion
We argue that with some improvements the technique could be used to determine the potential of new rehabilitation techniques and also help the rehabilitation staff or the patient's relatives to better understand the neglect condition.
doi:10.1186/1743-0003-4-27
PMCID: PMC1965467  PMID: 17640377

Results 1-6 (6)