An Application to Select Tag Loci by Using Hierarchical Structures of DNA Markers

Makoto Tomita,Koji Kurihara,문승호 한국자료분석학회 2011 Journal of the Korean Data Analysis Society Vol.13 No.6

A domain where recombination does not occur often, yet maintained linkage disequilibrium exists on DNA sequence is known as a ‘haplotype block’ or ‘Linkage Disequilibrium (LD) block’. Many methods are available to identify haplotype blocks using disequilibrium parameters, such as the well-known Gabriel’s method on Haploview, and so on. After identifying hyplotype blocks, we can also select tagging SNPs (single nucleotide polymorphisms) for these hyplotype blocks such as Tagger on Haploview, etc. We considered that Echelon analysis can be applied to identify hyplotype block and to select tagging SNPs, and report herein that the comprehensive method can be applied according to our new method using Echelon analysis. Finally we evaluated about the comparison of results between our method and others, using real data.

Radiosensitivity and the Occurrence of Radiation-related Cataract and Epilation

Tomita, Makoto,Otake, Masanori,Moon, Sung-Ho Korean Data and Information Science Society 2006 한국데이터정보과학회지 Vol.17 No.3

Our purpose is to ascertain, if possible, whether atomic bomb survivors with cataracts and epilation were more radiosensitive than those survivors with cataracts but without epilation. A major ophthalmologic survey was conducted in Hiroshima and Nagasaki in 1963-64. At that time, 2125 individuals were examined. Among these individuals, estimated eye organ doses, based on the DS86 dosimetry system, and information on the occurrence of epilation within the first 60 days following the bombings are available on 1742. In the analysis of these data we have assumed that each individual represents a sample of one from a binomial distribution, and that the occurrence of cataracts and epilation are independent biological phenomena. We got following results. The threshold for cataract induction and its 95% confidence limits have been estimated from data on the occurrence of cataract and epilation. Among the 1742 study subjects, 40 had both cataracts and severe epilation. The estimated threshold based on these cases is 0.98 sievert(Sv), with 95% lower and upper confidence bounds of 0.72, and 1.32 Sv, respectively, and is highly statistically significant. Among the 27 cases of cataracts where severe epilation was not reported, the estimated threshold is 1.74 Sv with 95% lower and upper confidence bounds of 1.21 Sv, and "not estimable". The difference between these two estimates is not statistically significant although the effect of dose is highly significant in both instances. The potential importance of biases in the DS86 dose estimates is discussed. The difference between the threshold estimated from cataract cases with epilation and that from cases without epilation is not statistically significant at the 5% or 10% level, and thus affords no support for the notion of increased radiosensitivity.

Statistical Assessment on Cancer Risks of Ionizing Radiation and Smoking Based on Poisson Models

Tomita, Makoto,Otake, Masanori,Moon, Sung-Ho Korean Data and Information Science Society 2006 한국데이터정보과학회지 Vol.17 No.2

In many epidemiological and medical studies, a number of cancer mortalities in categorical classification may be considered as having Poisson distribution with person-years at risk depending upon time. The cancer mortalities have been evaluated by additive or multiplicative models with regard to background and excess risks based on several covariances such as sex, age at the time of bombings, time at exposure, or ionizing radiation, cigarette smoking habits, duration of smoking habits, etc. An interest herein is to examine an additive, synergistic, or antagonistic relationship between radiation exposures and cigarette smoking habits for cancer mortalities. The results revealed a highly significant antagonistic in uence for cancer mortalities from all non-hematologic findings, lung and respiratory system with negative interaction between radiation exposures and cigarette smoking amounts.

Heritability of Cerebral Palsy Using Structural Equation Modeling

Makoto Tomita,Hiroko Taniai,문승호,Takeshi Nishiyama,Satoshi Sumi 한국자료분석학회 2009 Journal of the Korean Data Analysis Society Vol.11 No.4

Cerebral palsy(CP) is an umbrella term encompassing a group of non- progressive, non-contagious conditions that cause physical disability in human development, however it is unknown etiology with evidence for genetic influences. The current study combined 10 monozygotic twins, 17 dizygotic twins and 1 monozygotic triplets in order to improve statistical power. At least one proband in each pair was diagnosed as having cerebral palsy. An investigation of genetic structure underlying cerebral palsy was performed. We use binary responses for this study. Among all possible values of the parameters, we found the maximum-likelihood estimate(MLE), the value that maximizes the log-likelihood for the model using statistical package "Mx". A best fitting model of influences on cerebral palsy, incorporating additive genetic (A), shared environmental (C) and non-shared environmental influences (E), was generated using this model framework. From the AE or CE model which was the best model by Akaike's information criterion(AIC), however we got a result of the estimated heritability was almost zero for cerebral palsy.

Statistical Assessment on Cancer Risks of Ionizing Radiation and Smoking Based on Poisson Models

Makoto Tomita,Masanori Otake,Sung Ho Moon 한국데이터정보과학회 2006 한국데이터정보과학회지 Vol.17 No.2

Risk Relationship of Cataract and Epilation on Radiation Dose and Smoking Habit

Tomita, Makoto,Otake, Masanori,Moon, Sung-Ho Korean Data and Information Science Society 2006 한국데이터정보과학회지 Vol.17 No.4

An analytic approach that provides explicit estimates of risk on cataract and epilation data is evaluated by reasonableness of conceivable relative risk models regarding a simple, odds, logistic or Gompertz regression method, assuming a binomial distribution. In these analyses, we apply relative risk models with two thresholds between epilators and nonepilators from a highly characteristic lesion of which radiation cataract does not occur around 2 gray for a single acute exposure. The risk models are fitted to the data assuming 10 as a constant relative biological effectiveness of neutron. The likelihood of observing the entire data set in these models fitted is evaluated by an individual binary-response array. Estimation of a threshold with or without severe epilation and the 100 ($1-\alpha$)% confidence limits are derived from the maximum likelihood approach. The relative risk model with two thresholds can be expressed as a formula with structure of Background $\times$ RR, where RR includes threshold models with or without epilation. The radiosensitivity of ionizing radiation to cataracts has been examined for the relationship between epilators and nonepilators.

Risk Relationship of Cataract and Epilation on Radiation Dose and Smoking Habit

Makoto Tomita,Masanori Otake,Sung Ho Moon 한국데이터정보과학회 2006 한국데이터정보과학회지 Vol.17 No.4

Radiosensitivity and the Occurrence of Radiation-related Cataract and Epilation

Makoto Tomita,Masanori Otake,문승호 한국데이터정보과학회 2006 한국데이터정보과학회지 Vol.17 No.3

Our purpose is to ascertain, if possible, whether atomic bomb survivors with cataracts and epilation were more radiosensitive than those survivors with cataracts but without epilation. A major ophthalmologic survey was conducted in Hiroshima and Nagasaki in 1963-64. At that time, 2125 individuals were examined. Among these individuals, estimated eye organ doses, based on the DS86 dosimetry system, and information on the occurrence of epilation within the first 60 days following the bombings are available on 1742. In the analysis of these data we have assumed that each individual represents a sample of one from a binomial distribution, and that the occurrence of cataracts and epilation are independent biological phenomena. We got following results. The threshold for cataract induction and its 95% confidence limits have been estimated from data on the occurrence of cataract and epilation. Among the 1742 study subjects, 40 had both cataracts and severe epilation. The estimated threshold based on these cases is 0.98 sievert(Sv), with 95% lower and upper confidence bounds of 0.72, and 1.32 Sv, respectively, and is highly statistically significant. Among the 27 cases of cataracts where severe epilation was not reported, the estimated threshold is 1.74 Sv with 95% lower and upper confidence bounds of 1.21 Sv, and “not estimable”. The difference between these two estimates is not statistically significant although the effect of dose is highly significant in both instances. The potential importance of biases in the DS86 dose estimates is discussed. The difference between the threshold estimated from cataract cases with epilation and that from cases without epilation is not statistically significant at the 5% or 10% level, and thus affords no support for the notion of increased radiosensitivity.

Genetic Investigation of Some Behaviors and Impairments with Autism Spectrum Disorders Using Structural Equation Modeling

Makoto Tomita,Takeshi Nishiyama,Hiroko Taniai,Taishi Miyachi,Satoshi Sumi,문승호 한국자료분석학회 2009 Journal of the Korean Data Analysis Society Vol.11 No.3

Autism is a severe developmental disorder of unknown etiology but with evidence for genetic influences. The current study combined 47 twins in order to improve statistical power. At least one proband in each pair was diagnosed as having autism spectrum disorder(ASD), using the DSM-IV category of pervasive developmental disorder. An investigation of genetic structure underlying autistic traits was performed. We use bivariate coefficient for this study. Among all possible values of the parameters, we found the maximum-likelihood estimate(MLE), the value that maximizes the log-likelihood for the model. A best fitting model of influences on autistic traits, incorporating additive genetic (A), shared environmental (C) and non-shared environmental influences (E), was generated using this model framework. We got the AE model as the best model by Akaike's information criterion(AIC), then the estimated heritability was 0.74 for restricted and repetitive behaviors and interests(RRBI), whereas for social impairments(SI) it was 0.96. They are very high values of heritability, respectively.

Structural Insights into the CotB2-Catalyzed Cyclization of Geranylgeranyl Diphosphate to the Diterpene Cyclooctat-9-en-7-ol

Tomita, Takeo,Kim, Seung-Young,Teramoto, Kazuya,Meguro, Ayuko,Ozaki, Taro,Yoshida, Ayako,Motoyoshi, Yudai,Mori, Naoki,Ishigami, Ken,Watanabe, Hidenori,Nishiyama, Makoto,Kuzuyama, Tomohisa AMERICAN CHEMICAL SOCIETY 2017 ACS CHEMICAL BIOLOGY Vol.12 No.6

<P>The diterpene cyclase CotB2 catalyzes the cyclization of geranylgeranyl diphosphate (GGPP) to the tricyclic cyclooctat-9-en-7-ol, which is characterized by a 5-8-5-fused ring skeleton. We have previously proposed a cyclization cascade involving a unique carbon-carbon bond rearrangement combined with multiple hydride shifts, all occurring at a single active site. Here, we report the first high-resolution X-ray crystal structure of CotB2 with bound substrate analog geranylgeranyl thiodiphosphate (GGSPP). In the GGSPP-bound form, GGSPP folds into a unique S-shaped conformation that probably reflects the substrate-bound state prior to ionization of the substrate GGPP. The folded framework of GGSPP is surrounded by hydrophobic residues and several aromatic and asparagine residues that are well-positioned to stabilize a series of reactive carbocation intermediates through a combination of cation−π and dipole charge interactions. The combined crystal structures and mutagenesis-based biochemical assays provide a structural basis for exquisite control of ring formation and stereochemistry during CotB2 catalysis.</P> [FIG OMISSION]</BR>