Regional asssignments of the loci AK3, ACONS, and ASS on human chromosome 9.

Experiments are described in which human cells carrying balanced reciprocal translocations involving four different regions of chromosome 9 were fused with a Chinese hamster cell line and the resulting hybrids used to obtain subchromosomal assignments of the loci ASS, AK3, and ACONS. ASS was localized on the distal portion of the long arm of chromosome 9, in the region 9q34 leads to 9qter, and AK3 and ACONS on the short arm, in the region 9pter leads to 9p13.     

Mapping AK1, ACONs, and AK3 to chromosome 9 in man employing and X/9 translocation and somatic cell hybrids.

The adenylate kinase 1 (AK1), adenylate kinase3 (AK3), and aconitaseS (ACONS) genes have been assigned to chromosome 9 in man by employing an X/9 translocation segregating in man-mouse somatic cell hybrids. Segregation was controlled by taking advantage of the HAT/8-azaguanine selection-counterselection strategy directed at the X-linked HPRT locus. Assignment of AK1 to chromosome 9 has suggested the assignment of the ABO blood-group locus and the nail-patella (Np) locus to 9, since both loci are linked to AK1 by family studies.     

Genetic polymorphism of coagulation factor XIII B subunit in the Japanese population: description of three new rare alleles

Polyacrylamide gel isoelectric focusing (PAGIEF) of neuraminidase-treated EDTA plasma samples followed by electroblotting with enzyme immunoassay was performed to further investigate coagulation factor XIII B subunit (FXIII B) polymorphism. In 435 Japanese subjects PAGIEF patterns of FXIII B were classified into five common and three rare allotypes. This suggested that the FXIII B*2 allele existed in the Japanese population in the same manner as in Caucasians. Three new rare allotypes were considered to be controlled by three rare alleles which were designated FXIII B*13, FXIII B*14, and FXIII B*15, respectively. The gene frequencies calculated from 435 Japanese subjects were FXIII B*1 = 0.2977, FXIII B*2 = 0.0184, FXIII B*3 = 0.6805, FXIII B*13 = 0.0011, FXIII B*14 = 0.0011, and FXIII B*15 = 0.0011, respectively.     

Nadeshiko revisited: The situation of women in Japanese research and the measures taken to increase their representation

The Japanese government has enacted measures to increase the representation of women in research; the situation is improving but there is still much to do. Subject Categories: S&S: Careers & Training, S&S: History & Philosophy of Science, S&S: Ethics

Japanese parents are understandably proud that their 15‐year‐old boys and girls do equally well in the Programme for International Student Assessment (PISA). In 2018, Japanese girls ranked second and third in Science and Mathematics, respectively, among the 40 participating countries, and Japanese boys ranked first in both subjects (https://data.oecd.org/japan.htm). However, Japanese boys and girls face different expectations and take different career paths as they grow up. In this commentary, we discuss how this affects the situation of female scientists in Japan. We start with the proportion of women in academic research and describe the problems they currently face. We underscore the tremendous measures developed and administered by the Japanese government to increase the participation and proportion of women in research. Finally, we mention an emerging grassroots initiative that is currently being implemented. We suggest that female empowerment may be one of the most promising strategies to improve the situation of women in the Japanese scientific community.     

C1R subcomponent polymorphism in Japanese: description of a new allele

The polymorphism of C1R was investigated in 570 unrelated Japanese individuals using isoelectric focusing and immunoblotting. A total of 11 different C1R phenotypes including a new pattern designated C1R 11-1 were observed. The allele frequencies were C1R*1 = 0.4561, C1R*2 = 0.3377, C1R*5 = 0.1956, C1R*8 = 0.0088 and C1R*R (C1R*9 and C1R*11) = 0.0018. The population data fitted the Hardy-Weinberg equilibrium. The C1R polymorphism in Japanese was shown to be controlled by 3 common alleles, C1R*1, C1R*2 and C1R*5, as compared to Caucasians where only the former 2 are present commonly. This complement system can be a useful genetic marker for anthropological studies.     

C6 polymorphism in Japanese: typing by agarose gel isoelectric focusing-immunofixation

Agarose gel isoelectric focusing was used to investigate the genetic polymorphism of the sixth component of complement (C6) in Japanese. C6 patterns were visualized by the immunofixation procedure. The allele frequencies calculated from 135 individuals were as follows: C6*A = 0.467, C6*B = 0.481, C6*B2 = 0.037, and C6*B3 = 0.015. It is suggested that C6*B3 is the fourth common allele characterizing the Japanese population.     

Interaction between Red Meat Intake and NAT2 Genotype in Increasing the Risk of Colorectal Cancer in Japanese and African Americans

Heterocyclic aromatic amines formed in cooked meat may be an underlying mechanism for the red meat-colorectal cancer (CRC) association. These compounds require bioactivaction by N-acetyltransferase 2 (NAT2). An interaction effect between red meat consumption and NAT2 in increasing CRC risk has been inconsistently reported in whites. We investigated this interaction in two populations in which the high-activity rapid NAT2 phenotype is 10- and 2-fold more common than in whites. We meta-analyzed four studies of Japanese (2,217 cases, 3,788 controls) and three studies of African Americans (527 cases, 4,527 controls). NAT2 phenotype was inferred from an optimized seven-SNP genotyping panel. Processed and total red meat intakes were associated with an increased CRC risk in Japanese and in both ethnic groups combined (P’s ≤ 0.002). We observed an interaction between processed meat intake and NAT2 in Japanese (P = 0.04), African Americans (P = 0.02), and in both groups combined (P = 0.006). The association of processed meat with CRC was strongest among individuals with the rapid NAT2 phenotype (combined analysis, OR for highest vs. lowest quartile: 1.62, 95% CI: 1.28–2.05; P_trend = 8.0×10⁻⁵), intermediate among those with the intermediate NAT2 phenotype (1.29, 95% CI: 1.05–1.59; P_trend = 0.05) and null among those with the slow phenotype (P_trend = 0.45). A similar interaction was found for NAT2 and total red meat (P_interaction = 0.03). Our findings support a role for NAT2 in modifying the association between red meat consumption and CRC in Japanese and African Americans.     

Gene-environment association of an ITGB2 sequence variant with obesity in ethnic Japanese

Mice lacking the integrin alphaMbeta2 (Mac-1, CD11b/CD18) develop an obese phenotype on western diet rich in fat. However, no association has been found between variations in the human genes encoding the integrin alphaMbeta2 and obesity. This study was aimed to investigate the association between a single-nucleotide polymorphism (SNP) (rs235326) in the gene encoding human integrin beta2 subunit (ITGB2) with obesity. Our subject cohort comprised 651 people of Japanese ethnicity, of which 274 were Japanese Americans living in Hawaii, and the remaining 377 were native Japanese, two populations in the same genetic background with or without westernized life style. We genotyped the rs235326 polymorphism using a TaqMan assay. In the Japanese-American population, the risk of obesity was found to be 3.29-fold higher (a 95% confidence interval of 1.25-8.67, P = 0.02) in TT homozygotes than in C carriers, using a recessive model and logistic regression analysis that had been adjusted for age. This association was not found in native Japanese individuals. These results indicate that the rs235326 polymorphism in the ITGB2 gene is associated with obesity in Japanese living in the United States whose diet has become "westernized."     

Polymorphism of complement component I in Mongoloid populations: a new genetic variant IF A2

The genetic polymorphism of the complement component I (IF) was investigated in 282 Chinese, 239 Koreans and 198 Japanese. The 3 common IF phenotypes (A, AB and B) and a new rare IF phenotype (BA2) were observed. The obtained allele frequencies are as follows: IF*A = 0.0993 and IF*B = 0.9007 in Chinese; IF*A = 0.0921 and IF*B = 0.9079 in Koreans; IF*A = 0.0985, IF*B = 0.8990 and IF*A2 = 0.0025 in Japanese. These 3 Mongoloid populations showed a much higher degree of IF polymorphism than Caucasian populations.     

Cytochrome P450 2J2*7 polymorphisms in Japanese, Mongolians and Ovambos

Human cytochrome P450 2J2 (CYP2J2) is abundant in cardiovascular tissue and active in the metabolism of arachidonic acid to eicosanoids that have potent vasodilatory properties. Variability of the CYP2J2 gene is highly constrained except for its proximal promoter: there is a relatively common and functionally relevant single nucleotide polymorphism, indicated by -50G > T polymorphism (CYP2J2*7). Although genetic variation is known among ethnic groups, data for allele frequency are limited to a few Caucasian, Asian, and one African populations. In the present study, genotype distribution of CYP2J2*7 polymorphisms was investigated using polymerase chain reaction and restriction fragment length polymorphism assay in Japanese (n = 338), Mongolian (n = 118), and Ovambo (n = 186) populations and the findings compared with other populations. The mutant (CYP2J2*7) frequencies in the Japanese, Mongolians, and Ovambos were 0.0621, 0.0339, and 0.0672, respectively. Except for the Taiwanese, a general uniformity in the polymorphism in the Asian populations was observed. The mutation frequency of Ovambos was relatively lower than that of the African-American population. This study is the first to investigate the distribution of the CYP2J2*7 gene polymorphisms in Japanese, Mongolians, and Ovambos. These data will be informative and facilitate genetic association studies, in Asian and African populations for CYP2J2-related diseases such as cardiovascular disorders.     

Comparative cytogenetics of Chinese and Japanese raccoon dogs, Nyctereutes procyonoides

We investigated the relationships between subspecies of Nyctereutes procyonoides from China (2n = 54 + B chromosomes) and Japan (2n = 38 + B chromosomes). The chromosomes of Chinese and Japanese raccoon dogs were compared by means of conventional staining, G- and C-banding, and silver nitrate staining of NORs. Extensive G-banding homologies revealed karyotype evolution through chromosomal fusion. We believe the reduced diploid number in the Japanese raccoon dogs was achieved by fusion of 16 acrocentrics to form eight metacentric and submetacentric elements. Ten pairs of autosomes appeared to be identical in these subspecies and were presumed to have occurred as such in a common ancestor. G-band patterns of the sex chromosomes were similar in the two subspecies, but differences were noted with other banding and staining techniques. B chromosomes were present in varying numbers and sizes in all animals examined, but the morphology of the B chromosomes differed in the two subspecies. It was concluded from chromosomal and paleontological evidence that the two subspecies were derived from a common mainland ancestor and that the Japanese raccoon dogs is a relatively recent form.     

A prediction equation for total body water from bioelectrical impedance in Japanese children

Total body water (TBW) measured by isotope dilution techniques can be used to assess body composition safely and accurately in children. Unfortunately, this method is not readily available for most research projects, particularly when working with large groups of people, because the equipment is complicated and highly specialized. Bioelectrical impedance (BI) method is a simple, quick, and inexpensive method for the assessment of total body water (TBW). In Japanese child population, however, a lack of prediction equations is a problem to determine TBW. The purpose of this study was to determine the prediction equation for TBW determination in Japanese children using the isotope dilution technique as the reference method. Seventy Japanese children (39 boys, 31 girls) with ages ranging between 3 and 6 years participated in this study. They were randomly divided into the validation group (26 boys, 20 girls) and cross-validation group (13 boys, 11 girls). In a forward stepwise regression analysis, 96% of the variability in TBW measured by deuterium oxide (D(2)O) dilution could be predicted by the following equation: TBW(kg)=0.149 x Resistance Index (Stature(2)/resistance, cm(2)/Omega)+0.244 x Weight(kg)+0.460 x Age(y)+0.501 x Sex (boy=1, girl=0)+1.628, with a root mean square error (RMSE) of 0.440 kg in the validation group. This equation predicted TBW in the cross-validation group with R(2)=0.946 and a pure error (PE)=0.400 kg TBW. Hence, this equation should be applicable for predicting TBW in Japanese children aged 3-6 y.     

Comparative studies on physical characteristics and resting metabolism between young male highlanders of Papua New Guinea and young male Japanese

Anthropometric measurements and measurements of resting metabolism were made on 15 young male highlanders in Beha village at altitudes between 1,500 m and 1,800 m in the Eastern Highland of Papua New Guinea in August in 1978 and 10 young male Japanese in Nishinomiya in September. New Guineans showed significantly lower height, considerably lower body weight than Japanese but heavier body weight for height and significantly greater mean values of Rohrer's index and Brugsch's index than Japanese. Skinfold thicknesses for New Guineans were significantly smaller than those for Japanese. Thus, physically, New Guineans were more muscular and athletic when compared with Japanese. The mean value of resting metabolic rate for New Guineans, 46.35 W/m², at 25°C was considerably lower than that for Japanese, 51.01 W/m². New Guineans showed significantly lower mean value of resting metabolism 47.57 W/m² at 30°C than Japanese 55.16 W/m². The mean values of respiratory quotient for New Guineans (RQ = 0.950 at 25°C and 0.971 at 30°C) were significantly greater than those for Japanese (0.81 at 25°C and 0.81 at 30°C). New Guineans showed considerably lower mean value of heart rate at 30°C (71.1 beats/min) than Japanese (79.2 beats/min). The smaller physique of New Guineans might be the result of lower caloric intake and protein intake as well as of living in a tropical climate.     

No association between INSIG2 Gene rs7566605 polymorphism and being overweight in Japanese population

Obesity is a complex trait reflecting numerous genetic and environmental factors. Recently, a common genetic polymorphism (rs7566605) associated with a higher BMI was found in proximity to the insulin induced protein 2 (INSIG2 ) gene, with replication in four unrelated populations living in Western countries. We investigated the susceptibility to the polymorphism amongst the general Japanese population (n = 1976). The frequency of appearance of the single-nucleotide polymorphism (SNP) in the Japanese (G allele; 0.652, C allele; 0.348) was not different from that found in subjects of European origin as reported previously. However, the BMI levels in each of these genotypes did not differ significantly (GG; 23 +/- 3, GC; 24 +/- 3, CC; 24 +/- 3 kg/m(2), P = 0.906). In a separate analysis according to sex (male; P = 0.462, female; P = 0.879), age decade (40s; P = 0.057, 50s; P = 0.998, 60s; P = 0.622, 70s; 0.425, respectively), and tertiles of the BMI (1st; P = 0.409, 2nd; P = 0.088, 3rd; P = 0.780), the differences did not achieve statistical significance. The frequency of obesity did not differ among the genotypes (25 kg/m(2); 30.3, 30.8, 28.2%, P = 0.729, 30 kg/m(2); 2.9, 3.8, 2.8%, P = 0.549). No associations were also observed for related plasma markers; high-molecular weight (HMW) adiponectin (P = 0.510), high-sensitive C-reactive protein (P = 0.788), resistin (P = 0.937) and homeostasis of minimal assessment of insulin resistance (P = 0.634). These results indicate a lack of association between SNP rs7566605 and being overweight among the Japanese (in the middle-aged and elderly population).     

Japanese Lifestyle during Childhood Prevents the Future Development of Obesity among Japanese-Americans

Objective

To evaluate whether a Japanese lifestyle during childhood could protect against the future development of obesity-associated metabolic diseases by comparing native Japanese with Japanese-Americans in whom genetic factors are the same.

Methods

Study subjects were 516 native Japanese and 781 Japanese-Americans who underwent medical examinations between 2007 and 2010. Japanese-Americans were divided into 444 first-generation immigrants (JA-1), who were born in Japan, and 337 second- or later-generation descendants (JA-2), who were born in the United States. The JA-2 group was then divided into the kibei subgroup (N = 79), who had moved to Japan before the age of 18 years and later returned to the United States, and the non-kibei subgroup (N = 258), who had never lived in Japan.

Results

The JA-2 group had the highest percentages of obesity, metabolic syndrome, and type 2 diabetes compared with native Japanese and JA-1. Furthermore, among JA-2, the prevalence of obesity and metabolic syndrome in the kibei subgroup was significantly lower than that in the non-kibei subgroup. The prevalence of diabetes in the kibei subgroup also tended to be lower than in the non-kibei subgroup.

Conclusions

The prevalence of obesity and metabolic diseases differed with residence in Japan during childhood among Japanese-Americans. These findings indicate the possibility that Japanese lifestyle during childhood could reduce the future risks for obesity-associated metabolic diseases.     

Soluble TNF receptors and albuminuria in non-obese Japanese type 2 diabetic patients.

The aim of this study was to investigate the relationships between albuminuria and tumor necrosis factor (TNF)-alpha or soluble TNF receptors (sTNF-R1, sTNF-R2) in eighty-eight non-obese Japanese type 2 diabetic patients stratified into two groups according to albuminuria status-microalbuminuria or normoalbuminuria. Patients with microalbuminuria were older and had significantly higher concentrations of sTNF-R1 and sTNF-R2 than those with normoalbuminuria. There was, however, no significant difference in sex, diabetes duration, smoking, BMI, systolic and diastolic blood pressure, HbA (1c), serum creatinine, and lipid profile between the two groups. Although serum TNF-alpha was positively correlated to serum sTNF-R1 and sTNF-R2, serum TNF-alpha level did not differ with respect to albuminuria. Univariate regression analysis showed that urinary albumin concentration was positively correlated to age (r=0.380, p<0.001), serum creatinine (r=0.214, p<0.05) and concentrations of sTNF-R1 (r=0.364, p<0.001) and sTNF-R2 (r=0.342, p<0.005). Other variables, including TNF-alpha, were not associated with albuminuria. Multiple regression analyses showed that urinary albumin concentration was independently predicted by the level of sTNF-R1 (F=32.1), which explained 26.3% of the variability of urinary albumin concentration. From these results, it can be concluded that serum soluble TNF receptor is an important independent factor associated with albuminuria in non-obese Japanese type 2 diabetic patients.     

Role of Lung Function Genes in the Development of Asthma

Although our previous GWAS failed to identify SNPs associated with pulmonary function at the level of genomewide significance, it did show that the heritability for FEV₁/FVC was 41.6% in a Japanese population, suggesting that the heritability of pulmonary function traits can be explained by the additive effects of multiple common SNPs. In addition, our previous study indicated that pulmonary function genes identified in previous GWASs in non-Japanese populations accounted for 4.3% to 12.0% of the entire estimated heritability of FEV₁/FVC in a Japanese population. Therefore, given that many loci with individual weak effects may contribute to asthma risk, in this study, we created a quantitative score of genetic load based on 16 SNPs implicated in lower lung function in both Japanese and non-Japanese populations. This genetic risk score (GRS) for lower FEV₁/FVC was consistently associated with the onset of asthma (P = 9.6 × 10⁻⁴) in 2 independent Japanese populations as well as with the onset of COPD (P = 0.042). Clustering of asthma patients based on GRS levels indicated that an increased GRS may be responsible for the development of a particular phenotype of asthma characterized by early onset, atopy, and severer airflow obstruction.     

Placental glucose dehydrogenase polymorphism in Japanese

The polymorphism of glucose dehydrogenase (GDH) was investigated in 516 Japanese placentae. The allele frequencies were GDH*1 = 0.510, GDH*2 = 0.488 and GDH*3 = 0.002. GDH*3 appears to increase from Japan via Southeast Asia and India to Europe.     

Phenotypic and genetic characterizations of Streptococcus dysgalactiae strains isolated from fish collected in Japan and other Asian countries

Lancefield group C Streptococcus dysgalactiae is an emerging fish pathogen, which was first isolated in 2002 in Japan. Streptococcus dysgalactiae isolates collected from diseased fish in Japan ( n =12), Taiwan ( n =12), China ( n =2), Malaysia ( n =3), and Indonesia ( n =1) were characterized using biased sinusoidal field gel electrophoresis (BSFGE), sodA gene sequence analysis, and antimicrobial susceptibility. These isolates exhibited high phenotypic homogeneity irrespective of the countries from where the strains were collected. Seventeen isolates were found to be resistant to oxytetracycline and carried the tet (M) gene, except for the strains collected in Taiwan and the PP1564 strain collected in China. The sodA gene sequence analysis revealed that 23 isolates were identical, except for one Japanese isolate (KNH07902), in which a single nucleotide differed from that of the other isolates. Based on BSFGE typing by ApaI macrorestriction, the isolates – including the Japanese, Taiwanese, and Chinese isolates – could be grouped into one main cluster at a 70% similarity level. However, the macrorestriction genotypes of some isolates were apparently distinct from those of the main cluster.     

Somatic Copy Number Alterations Associated with Japanese or Endometriosis in Ovarian Clear Cell Adenocarcinoma

When compared with other epithelial ovarian cancers, the clinical characteristics of ovarian clear cell adenocarcinoma (CCC) include 1) a higher incidence among Japanese, 2) an association with endometriosis, 3) poor prognosis in advanced stages, and 4) a higher incidence of thrombosis as a complication. We used high resolution comparative genomic hybridization (CGH) to identify somatic copy number alterations (SCNAs) associated with each of these clinical characteristics of CCC. The Human Genome CGH 244A Oligo Microarray was used to examine 144 samples obtained from 120 Japanese, 15 Korean, and nine German patients with CCC. The entire 8q chromosome (minimum corrected p-value: q = 0.0001) and chromosome 20q13.2 including the ZNF217 locus (q = 0.0078) were amplified significantly more in Japanese than in Korean or German samples. This copy number amplification of the ZNF217 gene was confirmed by quantitative real-time polymerase chain reaction (Q-PCR). ZNF217 RNA levels were also higher in Japanese tumor samples than in non-Japanese samples (P = 0.027). Moreover, endometriosis was associated with amplification of EGFR gene (q = 0.047), which was again confirmed by Q-PCR and correlated with EGFR RNA expression. However, no SCNAs were significantly associated with prognosis or thrombosis. These results indicated that there may be an association between CCC and ZNF217 amplification among Japanese patients as well as between endometriosis and EGFR gene amplifications.