Interpopulation linkage disequilibrium patterns of GABRA2 and GABRG1 genes at the GABA cluster locus on human chromosome 4

GABRA2 and GABRG1, which encode the alpha-2 and gamma-1 subunits, respectively, of the GABA(A) receptor, are located in a cluster on chromosome 4p. The GABRA2 locus has been found to be associated with alcohol dependence in several studies, but no functional variant that can account for this association has been identified. To understand the reported associations, we sought to understand the linkage disequilibrium (LD) patterns and haplotype structures of these genes. With close intergenic distance, approximately 90 kb, it was anticipated that some markers might show intergenic LD. Variation in 13-SNP haplotype block structure was observed in five different populations: European American, African American, Chinese (Han and Thai), Thai, and Hmong. In the Hmong, a 280-kb region of considerably higher LD spans the intergenic region, whereas in other populations, there were two or more LD blocks that cross this region. These findings may aid in understanding the genetic association of this locus with alcohol dependence in several populations.     

Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer

Background

Epstein-Barr virus (EBV) associated nasopharyngeal cancer (NPC) is an important squamous cell cancer endemic in Southeast Asia and the Far East and can be considered a multifactorial genetic disease. This research explores potential associations between nasopharyngeal epithelial EBV receptor and NPC susceptibility. To prove the hypothesis, we evaluated two candidate genes, complement receptor 2 (CR2) and polymeric immunoglobulin receptor (PIGR) by using 4 SNPs, CR2 IVS2-848C→T, PIGR IVS3-156G→T, PIGR 1093G→A and PIGR 1739C→T, to genotype 175 cases and 317 controls, divided into Thai, Chinese and Thai-Chinese based on their respective ethnic origins.

Results

The results obtained indicated that PIGR is an NPC susceptibility gene. The risk association pertaining to each ethnic group was detected for homozygous PIGR 1739C with a significant ethnic group adjusted OR (95%CI) of 2.71(1.72–4.23) and p < 0.00001. Haplotype of the two missense PIGR SNPs, 1093G→A and 1739C→T, and sequence analyses have confirmed the role of the nucleotide PIGR 1739 and excluded possibility of an additional significant nonsynonymous NPC susceptibility SNP.

Conclusions

We present genetic evidence leading to hypothesize a possibility of PIGR to function as the EBV nasopharyngeal epithelium receptor via IgA-EBV complex transcytosis failure. The PIGR 1739C→T is a missense mutation changing alanine to valine near endoproteolytic cleavage site. This variant could alter the efficiency of PIGR to release IgA-EBV complex and consequently increase the susceptibility of populations in endemic areas to develop NPC.

     

Nondisjunction of chromosome 15: origin and recombination.

Thirty-two cases of uniparental disomy (UPD), ascertained from Prader-Willi syndrome patients (N = 27) and Angelman syndrome patients (N = 5), are used to investigate the pattern of recombination associated with nondisjunction of chromosome 15. In addition, the meiotic stage of nondisjunction is inferred by using markers mapping near the centromere. Two basic approaches to the analysis of recombination are utilized. Standard methods of centromere mapping are employed to determine the level of recombination in specific pairwise intervals along the chromosome. This method shows a significant reduction in recombination for two of five intervals examined. Second, the observed frequency of each recombinant class (i.e., zero, one, two, three, or more observable crossovers) is compared with expected values. This is useful for testing whether the reduction in recombination can be attributed solely to a proportion of cases with no recombination at all (because of asynapsis), with the remaining groups showing normal recombination (or even excess recombination), or whether recombination is uniformly reduced. Analysis of maternal UPD(15) data shows a slight reduction in the multiple-recombinant classes, with a corresponding increase in both the zero- and one-recombinant classes over expected values. The majority, more than 82%, of the extra chromosomes in maternal UPD(15) cases are due to meiotic I nondisjunction events. In contrast, most paternal UPD(15) cases so far examined appear to have a postzygotic origin of the extra paternal chromosome.     

A New Apotirucallane from Walsura trichostemon Leaves and Its Antibacterial and α-Glucosidase Inhibitory Activities

Phytochemical investigation of Walsura trichostemon leaves led to the isolation of a new apotirucallane-type triterpenoid, 11,25-dideacetyl-16-hydroxytrichostemonate ( 1 ), along with two known apotirucallane-type triterpenoids ( 2 and 3 ), two known tirucallane-type triterpenes ( 4 and 5 ), and two known steroids ( 6 and 7 ). Their structures were identified by intensive analysis of 1D and 2D nuclear magnetic resonance, infrared, and mass spectrometry data, which were compared with data reported in the literature. Compounds 2 , 3 , and 5 exhibited moderate antibacterial activity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) value: 64 μg/mL), and compound 4 showed weak antibacterial activity against P. aeruginosa (MIC: 128 μg/mL). Furthermore, compound 5 displayed activity against Bacillus cereus (MIC: 64 μg/mL). In addition, compound 4 showed stronger α-glucosidase inhibitory activity than the control, acarbose. The active compound 4 was subjected to molecular docking experiments using AutoDock4 and revealed precise interactions with the active gorge of the enzyme through hydrogen bonding, supporting the in vitro results.     

Morbidity Rate Prediction of Dengue Hemorrhagic Fever (DHF) Using the Support Vector Machine and the Aedes aegypti Infection Rate in Similar Climates and Geographical Areas

BackgroundIn the past few decades, several researchers have proposed highly accurate prediction models that have typically relied on climate parameters. However, climate factors can be unreliable and can lower the effectiveness of prediction when they are applied in locations where climate factors do not differ significantly. The purpose of this study was to improve a dengue surveillance system in areas with similar climate by exploiting the infection rate in the Aedes aegypti mosquito and using the support vector machine (SVM) technique for forecasting the dengue morbidity rate.ConclusionsThe infection rates of the Ae. aegypti female mosquitoes and larvae improved the morbidity rate forecasting efficiency better than the climate parameters used in classical frameworks. We demonstrated that the SVM-R-based model has high generalization performance and obtained the highest prediction performance compared to classical models as measured by the accuracy, sensitivity, specificity, and mean absolute error (MAE).     

Patterns and Possible Roles of LINE-1 Methylation Changes in Smoke-Exposed Epithelia

Tobacco smoking and reduced methylation of long interspersed element-1 (LINE-1) are crucial in oral carcinogenesis. 5′UTR of human LINE-1 sequence contains several CpG dinucleotides which are methylated in various proportions (0–100%). Methylation levels of many LINE-1s in cancer were reduced, hypomethylated. The hypomethylation of each LINE-1 locus can promote instability of genome and repress expression of a gene located on that same chromosome. This study investigated if cigarette smoking influences LINE-1 methylation of oral mucosal cells. The methylation of human LINE-1 in clinically normal oral mucosa of current smokers was compared to non-smokers. By using the combined bisulphite restriction analysis, each LINE-1 sequence was categorised into 4 patterns depending on the methylation status and location of the two 18-bp successive CpG from 5′ to 3′ including ^mC^mC, ^uC^uC, ^mC^uC and ^uC^mC. Of these, ^mC and ^uC represent methylated and unmethylated CpG, respectively. The DNA bisulphite sequence demonstrated that most CpGs of ^mC^mC and ^uC^uC were methylated and unmethylated, respectively. Nevertheless, some CpGs of each ^mC^uC or ^uC^mC allele were methylated. Imaging of the digestion products was used to generate %methylation value. No significant difference in the overall LINE-1 methylation level but the differences in percentages of some methylation patterns were discovered. The %^mC^mC and %^uC^uC increased, while the %^mC^uC decreased in current smokers (p = 0.002, 0.015, and <0.0001, respectively). Additionally, the lower %^mC^uC still persisted in persons who had stopped smoking for over 1 year (p = 0.001). The %^mC^uC also decreased in the higher pack-year smokers (p = 0.028). Smoking possibly altered ^mC^uC to ^mC^mC and ^uC^uC forms, and changes ^uC^mC to ^uC^uC forms. In conclusion, smoking changes methylation levels of partial methylated LINE-1s and increased the number of hypo- and hypermethylated loci. These hypomethylated LINE-1s may possess carcinogenesis potential. Moreover, LINE-1 methylation patterns may be useful for monitoring oral carcinogenesis in smokers.     

Evaluation of attractants and egg-laying substrate preference for oviposition by Aedes albopictus (Diptera: Culicidae).

Evaluation of oviposition attractants and substrate preferences of Aedes albopictus was carried out under laboratory and field conditions. To obtain candidate oviposition substances we used a water rinse of 3 mollusk species: blood cockle (Anadara granosa), carpet shell (Paphia undulata), and sea mussel (Mytilus smaragdinus), and the giant tiger prawn (Penaeus monodon). The rinse water of carpet shell and giant tiger prawn showed higher attractiveness for ovipostion than the other candidate attractants. The filter paper substrate received fewer eggs than the other two substrates. There was no significant difference between the mean number of eggs laid on hardboard paddles and sponge sheets. The hatching rate of Ae. albopictus eggs laid on hardboard paddles was higher than those from the filter papers and sponge sheets. The sponge had lethal effects on Ae. albopictus eggs, and very few eggs laid on sponge hatched. In field experiments, evaluation of attractiveness of carpet shell rinse in ovitraps lined with sponge sheet as egg-laying substrate was carried out in various habitats and different areas of Thailand. The mean number of eggs in traps containing carpet shell rinse was significantly higher than those laid in rainwater traps. These studies reveal that the carpet shell and giant tiger prawn rinses are sources of oviposition attractant for Ae. albopictus under both laboratory and field conditions and could possibly be used as an attractant in surveillance and control.     

Characteristics of replication-independent endogenous double-strand breaks in Saccharomyces cerevisiae

Background

Replication-independent endogenous double-strand breaks (RIND-EDSBs) occur in both humans and yeast in the absence of inductive agents and DNA replication. In human cells, RIND-EDSBs are hypermethylated, preferentially retained in the heterochromatin and unbound by γ-H2AX. In single gene deletion yeast strains, the RIND-EDSB levels are altered; the number of RIND-EDSBs is higher in strains with deletions of histone deacetylase, endonucleases, topoisomerase, or DNA repair regulators, but lower in strains with deletions of the high-mobility group box proteins or Sir2. In summary, RIND-EDSBs are different from pathologic DSBs in terms of their causes and consequences. In this study, we identified the nucleotide sequences surrounding RIND-EDSBs and investigated the features of these sequences as well as their break locations.

Results

In recent work, we detected RIND-EDSBs using ligation mediated PCR. In this study, we sequenced RIND-EDSB PCR products of resting state Saccharomyces cerevisiae using next-generation sequencing to analyze RIND-EDSB sequences. We found that the break locations are scattered across a number of chromosomes. The number of breaks correlated with the size of the chromosomes. Most importantly, the break occurrences had sequence pattern specificity. Specifically, the majority of the breaks occurred immediately after the sequence “ACGT” (P = 2.2E-156). Because the “ACGT” sequence does not occur primarily in the yeast genome, this specificity of the “ACGT” sequence cannot be attributed to chance.

Conclusions

RIND-EDSBs occur non-randomly; that is, they are produced and retained by specific mechanisms. Because these particular mechanisms regulate their generation and they possess potentially specific functions, RIND-EDSBs could be epigenetic marks.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-750) contains supplementary material, which is available to authorized users.