Genetics Research International The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Does i-T744C P2Y12 Polymorphism Modulate Clopidogrel Response among Moroccan Acute Coronary Syndromes Patients? Sun, 05 Feb 2017 00:00:00 +0000 Background. An interindividual variability in response to Clopidogrel has been widely described in patients with acute coronary syndromes (ACS). The contribution of genetics on modulating this response was widely discussed. The objective of our study was to investigate the potential effect of i-T744C P2Y12 polymorphism on Clopidogrel response in a sample of Moroccan ACS patients. We tried also to determine the frequency of this polymorphism among Moroccan ACS compared to healthy subjects. Methods and Results. 77 ACS patients versus 101 healthy controls were recruited. DNA samples were genotyped by PCR-RFLP method. The VerifyNow assay was used to evaluate platelet function among ACS patients. Our results show that the mutant allele C was more frequent among ACS ST (+) than ST (−) patients (39% versus 19.8%, resp.), when the wild-type allele was more represented in the ACS ST (−) group (80.2%). The C allele frequency was higher among resistant than nonresistant patients (30% versus 20.8%, resp.). Comparison of ACS patients and healthy controls shows higher frequency of mutant C allele among cases compared to controls (22.73% versus 19.31%, resp.); there was a statistically significant association of the recessive and additive transmission models with the ACS development risk (OR [95% CI] = 1.78 [1.58–5.05], and OR [95% CI] = 1.23 [0.74–2.03], , resp.), increasing thus the association of this polymorphism with the pathology. Conclusion. Our results suggest that this polymorphism may have a potential effect on Clopidogrel response among our Moroccan ACS patients and also on ACS development. Hind Hassani Idrissi, Wiam Hmimech, Nada El Khorb, Hafid Akoudad, Rachida Habbal, and Sellama Nadifi Copyright © 2017 Hind Hassani Idrissi et al. All rights reserved. Procaine Induces Epigenetic Changes in HCT116 Colon Cancer Cells Mon, 24 Oct 2016 06:15:55 +0000 Colon cancer is the third most commonly diagnosed cancer in the world, and it is the major cause of morbidity and mortality throughout the world. The present study aimed at treating colon cancer cell line (HCT116) with different chemotherapeutic drug/drug combinations (procaine, vorinostat “SAHA,” sodium phenylbutyrate, erlotinib, and carboplatin). Two different final concentrations were applied: 3 μM and 5 μM. Trypan blue test was performed to assess the viability of the cell before and after being treated with the drugs. The data obtained showed that there was a significant decrease in the viability of cells after applying the chemotherapeutic drugs/drug combinations. Also, DNA fragmentation assay was carried out to study the effect of these drugs on the activation of apoptosis-mediated DNA degradation process. The results indicated that all the drugs/drug combinations had a severe effect on inducing DNA fragmentation. Global DNA methylation quantification was performed to identify the role of these drugs individually or in combination in hypo- or hypermethylating the CpG dinucleotide all over the genome of the HCT116 colon cancer cell line. Data obtained indicated that different combinations had different effects in reducing or increasing the level of methylation, which might indicate the effectiveness of combining drugs in treating colon cancer cells. Hussein Sabit, Mariam B. Samy, Osama A. M. Said, and Mokhtar M. El-Zawahri Copyright © 2016 Hussein Sabit et al. All rights reserved. Screening for Subtelomeric Rearrangements in Thai Patients with Intellectual Disabilities Using FISH and Review of Literature on Subtelomeric FISH in 15,591 Cases with Intellectual Disabilities Sun, 16 Oct 2016 07:36:59 +0000 We utilized fluorescence in situ hybridization (FISH) to screen for subtelomeric rearrangements in 82 Thai patients with unexplained intellectual disability (ID) and detected subtelomeric rearrangements in 5 patients. Here, we reported on a patient with der(20)t(X;20)(p22.3;q13.3) and a patient with der(3)t(X;3)(p22.3;p26.3). These rearrangements have never been described elsewhere. We also reported on a patient with der(10)t(7;10)(p22.3;q26.3), of which the same rearrangement had been reported in one literature. Well-recognized syndromes were detected in two separated patients, including 4p deletion syndrome and 1p36 deletion syndrome. All patients with subtelomeric rearrangements had both ID and multiple congenital anomalies (MCA) and/or dysmorphic features (DF), except the one with der(20)t(X;20), who had ID alone. By using FISH, the detection rate of subtelomeric rearrangements in patients with both ID and MCA/DF was 8.5%, compared to 2.9% of patients with only ID. Literature review found 28 studies on the detection of subtelomeric rearrangements by FISH in patients with ID. Combining data from these studies and our study, 15,591 patients were examined and 473 patients with subtelomeric rearrangements were determined. The frequency of subtelomeric rearrangements detected by FISH in patients with ID was 3%. Terminal deletions were found in 47.7%, while unbalanced derivative chromosomes were found in 47.9% of the rearrangements. Chariyawan Charalsawadi, Jariya Khayman, Verayuth Praphanphoj, and Pornprot Limprasert Copyright © 2016 Chariyawan Charalsawadi et al. All rights reserved. Assessment of Functional EST-SSR Markers (Sugarcane) in Cross-Species Transferability, Genetic Diversity among Poaceae Plants, and Bulk Segregation Analysis Wed, 01 Jun 2016 14:07:02 +0000 Expressed sequence tags (ESTs) are important resource for gene discovery, gene expression and its regulation, molecular marker development, and comparative genomics. We procured 10000 ESTs and analyzed 267 EST-SSRs markers through computational approach. The average density was one SSR/10.45 kb or 6.4% frequency, wherein trinucleotide repeats (66.74%) were the most abundant followed by di- (26.10%), tetra- (4.67%), penta- (1.5%), and hexanucleotide (1.2%) repeats. Functional annotations were done and after-effect newly developed 63 EST-SSRs were used for cross transferability, genetic diversity, and bulk segregation analysis (BSA). Out of 63 EST-SSRs, 42 markers were identified owing to their expansion genetics across 20 different plants which amplified 519 alleles at 180 loci with an average of 2.88 alleles/locus and the polymorphic information content (PIC) ranged from 0.51 to 0.93 with an average of 0.83. The cross transferability ranged from 25% for wheat to 97.22% for Schlerostachya, with an average of 55.86%, and genetic relationships were established based on diversification among them. Moreover, 10 EST-SSRs were recognized as important markers between bulks of pooled DNA of sugarcane cultivars through BSA. This study highlights the employability of the markers in transferability, genetic diversity in grass species, and distinguished sugarcane bulks. Shamshad Ul Haq, Pradeep Kumar, R. K. Singh, Kumar Sambhav Verma, Ritika Bhatt, Meenakshi Sharma, Sumita Kachhwaha, and S. L. Kothari Copyright © 2016 Shamshad Ul Haq et al. All rights reserved. Leveraging Comparative Genomics to Identify and Functionally Characterize Genes Associated with Sperm Phenotypes in Python bivittatus (Burmese Python) Wed, 20 Apr 2016 09:02:33 +0000 Comparative genomics approaches provide a means of leveraging functional genomics information from a highly annotated model organism’s genome (such as the mouse genome) in order to make physiological inferences about the role of genes and proteins in a less characterized organism’s genome (such as the Burmese python). We employed a comparative genomics approach to produce the functional annotation of Python bivittatus genes encoding proteins associated with sperm phenotypes. We identify 129 gene-phenotype relationships in the python which are implicated in 10 specific sperm phenotypes. Results obtained through our systematic analysis identified subsets of python genes exhibiting associations with gene ontology annotation terms. Functional annotation data was represented in a semantic scatter plot. Together, these newly annotated Python bivittatus genome resources provide a high resolution framework from which the biology relating to reptile spermatogenesis, fertility, and reproduction can be further investigated. Applications of our research include (1) production of genetic diagnostics for assessing fertility in domestic and wild reptiles; (2) enhanced assisted reproduction technology for endangered and captive reptiles; and (3) novel molecular targets for biotechnology-based approaches aimed at reducing fertility and reproduction of invasive reptiles. Additional enhancements to reptile genomic resources will further enhance their value. Kristopher J. L. Irizarry and Josep Rutllant Copyright © 2016 Kristopher J. L. Irizarry and Josep Rutllant. All rights reserved. SOD1 Gene +35A/C (exon3/intron3) Polymorphism in Type 2 Diabetes Mellitus among South Indian Population Sun, 17 Apr 2016 12:13:07 +0000 Superoxide dismutase is an antioxidant enzyme that is involved in defence mechanisms against oxidative stress. Cu/Zn SOD is a variant that is located in exon3/intron3 boundary. The aim of the present study was to investigate whether the Cu/Zn SOD (+35A/C) gene polymorphism is associated with the susceptibility to type 2 diabetes mellitus among south Indian population. The study included patients with type 2 diabetes mellitus () and healthy controls (). DNA was isolated from the blood and genotyping of Cu/Zn SOD gene polymorphism was done by polymerase chain reaction based restriction fragment length polymorphism method. Occurrence of different genotypes and normal (A) and mutant (C) allele frequencies were determined. The frequency of the three genotypes of the total subjects was as follows: homozygous wild-type A/A (95%), heterozygous genotype A/C (3%), and homozygous mutant C/C (2%). The mutant (C) allele and the mutant genotypes (AC/CC) were found to be completely absent among the patients with type 2 diabetes mellitus. Absence of mutant genotype (CC) shows that the Cu/Zn SOD gene polymorphism may not be associated with the susceptibility to type 2 diabetes mellitus among south Indian population. K. Nithya, T. Angeline, W. Isabel, and A. J. Asirvatham Copyright © 2016 K. Nithya et al. All rights reserved. Altered Body Weight Regulation in CK1ε Null and tau Mutant Mice on Regular Chow and High Fat Diets Wed, 06 Apr 2016 07:17:15 +0000 Disruption of circadian rhythms results in metabolic dysfunction. Casein kinase 1 epsilon (CK1ε) is a canonical circadian clock gene. Null and tau mutations in CK1ε show distinct effects on circadian period. To investigate the role of CK1ε in body weight regulation under both regular chow (RC) and high fat (HF) diet conditions, we examined body weight on both RC and HF diets in CK1 and CK1 mice on a standard 24 hr light-dark (LD) cycle. Given the abnormal entrainment of CK1 mice on a 24 hr LD cycle, a separate set of CK1 mice were tested under both diet conditions on a 20 hr LD cycle, which more closely matches their endogenous period length. On the RC diet, both CK1 and CK1 mutants on a 24 hr LD cycle and CK1 mice on a 20 hr LD cycle exhibited significantly lower body weights, despite similar overall food intake and activity levels. On the HF diet, CK1 mice on a 20 hr LD cycle were protected against the development of HF diet-induced excess weight gain. These results provide additional evidence supporting a link between circadian rhythms and energy regulation at the genetic level, particularly highlighting CK1ε involved in the integration of circadian biology and metabolic physiology. Lili Zhou, Keith C. Summa, Christopher Olker, Martha H. Vitaterna, and Fred W. Turek Copyright © 2016 Lili Zhou et al. All rights reserved. Serotonin-Related Gene Polymorphisms and Asymptomatic Neurocognitive Impairment in HIV-Infected Alcohol Abusers Wed, 16 Mar 2016 12:57:30 +0000 HIV-infected individuals continue to experience neurocognitive deterioration despite virologically successful treatments. While the cause remains unclear, evidence suggests that HIV-associated neurocognitive disorders (HAND) may be associated with neurobehavioral dysfunction. Genetic variants have been explored to identify risk markers to determine neuropathogenesis of neurocognitive deterioration. Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life and HIV risk-taking behaviors. Single nucleotide polymorphisms in the SLC6A4, TPH2, and GALM genes may affect the activity of serotonin and increase the risk of HAND. The present study explored the relationship between SLC6A4, TPH2, and GALM genes and neurocognitive impairment in HIV-infected alcohol abusers. A total of 267 individuals were genotyped for polymorphisms in SLC6A4 5-HTTLPR, TPH2 rs4570625, and GALM rs6741892. To assess neurocognitive functions, the Short Category and the Auditory Verbal Learning Tests were used. TPH2 SNP rs4570625 showed a significant association with executive function in African American males (odds ratio 4.8, 95% CI, 1.5–14.8; ). Similarly, GALM SNP rs6741892 showed an increased risk with African American males (odds ratio 2.4, 95% CI, 1.2–4.9; ). This study suggests that TPH2 rs4570625 and GALM rs6741892 polymorphisms may be risk factors for HAND. Karina Villalba, Jessy G. Dévieux, Rhonda Rosenberg, and Jean Lud Cadet Copyright © 2016 Karina Villalba et al. All rights reserved. Molecular Characterization of a Novel Germline VHL Mutation by Extensive In Silico Analysis in an Indian Family with Von Hippel-Lindau Disease Wed, 16 Mar 2016 11:12:46 +0000 Von Hippel-Lindau [VHL] disease, an autosomal dominant hereditary cancer syndrome, is well known for its complex genotype-phenotype correlations. We looked for germline mutations in the VHL gene in an affected multiplex family with Type 1 VHL disease. Real-Time quantitative PCR for deletions and Sanger sequencing of coding regions along with flanking intronic regions were performed in two affected individuals and one related individual. Direct sequencing identified a novel heterozygous single nucleotide base substitution in both the affected members tested, segregating with VHL phenotype in this family. This variant in exon 3, c.473T>A, results in substitution of leucine, a highly conserved acid, to glutamine at position 158 [p.L158Q] and has not been reported thus far as a variant associated with disease causation. Further, this variant was not observed in 50 age and ethnicity matched healthy individuals. Extensive in silico prediction analysis along with molecular dynamics simulation revealed significant deleterious nature of the substitution L158Q on pVHL. The results of this study when collated support the view that the missense variation p.L158Q in the Elongin C binding domain of pVHL may be disease causing. Gautham Arunachal, Divya Pachat, C. George Priya Doss, Sumita Danda, Rekha Pai, and Andrew Ebenazer Copyright © 2016 Gautham Arunachal et al. All rights reserved. Unique AGG Interruption in the CGG Repeats of the FMR1 Gene Exclusively Found in Asians Linked to a Specific SNP Haplotype Wed, 02 Mar 2016 06:23:03 +0000 Fragile X syndrome (FXS) is the most common inherited intellectual disability. It is caused by the occurrence of more than 200 pure CGG repeats in the FMR1 gene. Normal individuals have 6–54 CGG repeats with two or more stabilizing AGG interruptions occurring once every 9- or 10-CGG-repeat blocks in various populations. However, the unique (CGG)6AGG pattern, designated as 6A, has been exclusively reported in Asians. To examine the genetic background of AGG interruptions in the CGG repeats of the FMR1 gene, we studied 8 SNPs near the CGG repeats in 176 unrelated Thai males with 19–56 CGG repeats. Of these 176 samples, we identified AGG interruption patterns from 95 samples using direct DNA sequencing. We found that the common CGG repeat groups (29, 30, and 36) were associated with 3 common haplotypes, GCGGATAA (Hap A), TTCATCGC (Hap C), and GCCGTTAA (Hap B), respectively. The configurations of 9A9A9, 10A9A9, and 9A9A6A9 were commonly found in chromosomes with 29, 30, and 36 CGG repeats, respectively. Almost all chromosomes with Hap B (22/23) carried at least one 6A pattern, suggesting that the 6A pattern is linked to Hap B and may have originally occurred in the ancestors of Asian populations. Pornprot Limprasert, Janpen Thanakitgosate, Kanoot Jaruthamsophon, and Thanya Sripo Copyright © 2016 Pornprot Limprasert et al. All rights reserved. Induced Pluripotent Stem Cell as a New Source for Cancer Immunotherapy Thu, 25 Feb 2016 14:11:12 +0000 The immune system consists of cells, proteins, and other molecules that beside each other have a protective function for the host against foreign pathogens. One of the most essential features of the immune system is distinguishability between self- and non-self-cells. This function has an important role in limiting development and progression of cancer cells. In this case, the immune system can detect tumor cell as a foreign pathogen; so, it can be effective in elimination of tumors in their early phases of development. This ability of the immune system resulted in the development of a novel therapeutic field for cancer treatment using host immune components which is called cancer immunotherapy. The main purpose of cancer immunotherapy is stimulation of a strong immune response against the tumor cells that can result from expressing either the immune activator cytokines in the tumor area or gene-modified immune cells. Because of the problems of culturing and manipulating immune cells ex vivo, in recent years, embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) have been used as new sources for generation of modified immune stimulatory cells. In this paper, we reviewed some of the progressions in iPSC technology for cancer immunotherapy. Farzaneh Rami, Halimeh Mollainezhad, and Mansoor Salehi Copyright © 2016 Farzaneh Rami et al. All rights reserved. Association of RBP4 Genotype with Phenotypic Reproductive Traits of Sows Sun, 17 Jan 2016 06:00:52 +0000 PCR-RFLP was applied to a commercial crossbred pig population in order to investigate the association between polymorphism (SNP) of Retinol-binding protein 4 (RBP4) gene and reproductive performance. 400 sows were genotyped and 2000 records of reproductive traits were used in order to retrieve information about the allele frequencies and the association of the RBP4 gene with main reproductive characteristics of the population. A deviation from the Hardy-Weinberg equilibrium was observed as a result of the AB genotype excess. In addition, the AA genotype saw statistically significant higher values of (i) the total number of born piglets (), (ii) the number of piglets born alive (), and (iii) the number of weaned piglets (). The number of the mummified piglets and the number of the piglets born dead did not differ between the various RBP4 genotypes. Interestingly, the AA genotype had a negative impact () on the number of piglets born dead, resulting indirectly in a larger litter size. In conclusion, the AA genotype and in extension the A allele of RBP4 gene are in favor of producing larger litter size, suggesting that the RBP4 gene may be used in Marker-Assisted Selection (MAS) programs for a rapid improvement of the reproductive characteristics in pigs. A. Marantidis, G. P. Laliotis, and M. Avdi Copyright © 2016 A. Marantidis et al. All rights reserved. De Novo Assembly and Transcriptome Characterization of Canine Retina Using High-Throughput Sequencing Wed, 16 Dec 2015 05:57:45 +0000 We performed transcriptome sequencing of canine retinal tissue by 454 GS-FLX and Ion Torrent PGM platforms. RNA-Seq analysis by CLC Genomics Workbench mapped expression of 10,360 genes. Gene ontology analysis of retinal transcriptome revealed abundance of transcripts known to be involved in vision associated processes. The de novo assembly of the sequences using CAP3 generated 29,683 contigs with mean length of 560.9 and N50 of 619 bases. Further analysis of contigs predicted 3,827 full-length cDNAs and 29,481 (99%) open reading frames (ORFs). In addition, 3,782 contigs were assigned to 316 KEGG pathways which included melanogenesis, phototransduction, and retinol metabolism with 33, 15, and 11 contigs, respectively. Among the identified microsatellites, dinucleotide repeats were 68.84%, followed by trinucleotides, tetranucleotides, pentanucleotides, and hexanucleotides in proportions of 25.76, 9.40, 2.52, and 0.96%, respectively. This study will serve as a valuable resource for understanding the biology and function of canine retina. Bhaskar Reddy, Amrutlal K. Patel, Krishna M. Singh, Deepak B. Patil, Pinesh V. Parikh, Divyesh N. Kelawala, Prakash G. Koringa, Vaibhav D. Bhatt, Mandava V. Rao, and Chaitanya G. Joshi Copyright © 2015 Bhaskar Reddy et al. All rights reserved. Study of Cysteine-Rich Protein 61 Genetic Polymorphism in Predisposition to Fracture Nonunion: A Case Control Thu, 10 Dec 2015 07:13:41 +0000 Background. Many factors are responsible for this impaired healing, especially in long bones, but a possible genetic predisposition for the development of this complication remains unknown till now. In the present study, we aim to examine the CYR61 gene polymorphism in fracture nonunion patients and the correlation with clinical findings. Materials and Methods. We performed SNP analysis of the CYR61 gene in 250 fracture nonunion patients and 250 healthy subjects were genotyped in this hospital-based case control study, and 56 cases were further evaluated for mRNA expression of CYR61 by real-time quantitative reverse-transcription PCR. Results. CYR61 gene TT, TG, and GG genotype frequencies of total fracture nonunion cases were 41.6%, 49.2%, and 9.20% and 54.4%, 39.2%, and 6.40% in healthy controls. Heterozygous TG genotype was found statistically significant in fracture nonunion cases compared with that in controls, whereas homozygous mutant GG genotype was not found significant. Moreover, we found that TG + GG genotypes were significantly different in serum expression of CYR61 mRNA when compared with cases (TT genotypes). Conclusions. Our result signifies that genotype of CYR61 affects the mRNA expression and acts as a risk factor that could synergistically increase the susceptibility of a patient to develop fracture nonunion. Sabir Ali, Syed Rizwan Hussain, Ajai Singh, Vineet Kumar, Shah Walliullah, Nazia Rizvi, Manish Yadav, Mohammad Kaleem Ahmad, and Abbas Ali Mahdi Copyright © 2015 Sabir Ali et al. All rights reserved. Frequency Distribution of Mannose Binding Lectin-2 and Vitamin D Receptor Gene Variants: Putative Markers for Tuberculosis Thu, 26 Nov 2015 11:47:18 +0000 Genetic polymorphism in Mannose Binding Lectin-2 (MBL-2) and Vitamin D Receptor (VDR) is known to influence the susceptibility to tuberculosis. The objective of the present study was to evaluate the frequency distribution of the MBL-2 promoter and structural polymorphism (−550 H/L, −221 Y/X, and +4 P/Q; R52C, G54D, and G57F) and VDR polymorphism (FokI, BsmI, TaqI, and ApaI) in healthy individuals of Indian population and comparative analysis with the global population. In Indian population, the frequency of VDR mutant alleles “f” for FokI, “b” for BsmI, “t” for TaqI, and “a” for ApaI was 25%, 54%, 30%, and 61%, respectively. The allelic frequency of MBL-2 promoter polymorphism −550 H/L was H versus L: 32% versus 68%, −221 Y/X was Y versus X: 68% versus 32%, and +4 P/Q was P versus Q: 78% versus 22%. Mutant allelic frequencies of the MBL-2 exon 1 D, B, and C allele were 6%, 11%, and 3%, respectively. Comparative analysis with global populations showed a noteworthy difference for MBL-2 and VDR polymorphism frequency distribution, indicating the ethnic variability of Indians. The study signifies the differential distribution of susceptibility genes in Indian population, which can influence the understanding of the pathophysiology of tuberculosis in Indian population. Anuroopa Gupta and Harish Padh Copyright © 2015 Anuroopa Gupta and Harish Padh. All rights reserved. Association of Polymorphisms of Phase I Metabolizing Genes with Sister Chromatid Exchanges in Occupational Workers Exposed to Toluene Used in Paint Thinners Tue, 24 Nov 2015 09:59:50 +0000 This study investigated genetic damage in paint workers mainly exposed to toluene as it is a major solvent used in paint thinners. Sister chromatid exchange (SCE) assay was used as biomarker of genotoxicity. Blood samples were collected from 30 paint workers and 30 control subjects matched with respect to age and other confounding factors except for exposure to toluene. SCE frequency was found to be significantly higher in paint workers () as compared to control individuals () (). We also investigated influence of polymorphisms of CYP2E1 and CYP1A1m2 genes on SCE frequency. Our results showed that there was significant increase in frequencies of SCE among the mutant genotypes of CYP2E1 and CYP1A1m2 as compared to wild genotypes. Our study indicated that long term exposure of toluene can increase genotoxic risk in paint workers. Kanu Priya, Anita Yadav, Neeraj Kumar, Sachin Gulati, Neeraj Aggarwal, and Ranjan Gupta Copyright © 2015 Kanu Priya et al. All rights reserved. Identification of Proximal and Distal 22q11.2 Microduplications among Patients with Cleft Lip and/or Palate: A Novel Inherited Atypical 0.6 Mb Duplication Thu, 12 Nov 2015 10:46:07 +0000 Misalignments of low-copy repeats (LCRs) located in chromosome 22, particularly band 22q11.2, predispose to rearrangements. A variety of phenotypic features are associated with 22q11.2 microduplication syndrome which makes it challenging for the genetic counselors to recommend appropriate genetic assessment and counseling for the patients. In this study, multiplex ligation probe dependent amplification (MLPA) analysis was performed on 378 patients with cleft lip and/or palate to characterize rearrangements in patients suspected of 22q11.2 microduplication and microdeletion syndromes. Of 378 cases, 15 were diagnosed with a microdeletion with various sizes and 3 with duplications. For the first time in this study an atypical 0.6 Mb duplication is reported. Illustration of the phenotypes associated with the microduplications increases the knowledge of phenotypes reported in the literature. Maryam Sedghi, Hossein Abdali, Mehrdad Memarzadeh, Mansoor Salehi, Narges Nouri, Majid Hosseinzadeh, and Nayereh Nouri Copyright © 2015 Maryam Sedghi et al. All rights reserved. Association Study between Idiopathic Scoliosis and Polymorphic Variants of VDR, IGF-1, and AMPD1 Genes Tue, 25 Aug 2015 13:36:27 +0000 Idiopathic scoliosis (IS) is a complex genetic disorder of the musculoskeletal system, characterized by three-dimensional rotation of the spine with unknown etiology. For the aims of the current study we selected 3 single nucleotide polymorphisms with a low incidence of the polymorphic allele in Bulgarian population, AMPD1 (rs17602729), VDR (rs2228670), and IGF-1 (rs5742612), trying to investigate the association between these genetic polymorphisms and susceptibility to and progression of IS. The polymorphic regions of the genes were amplified by polymerase chain reaction (PCR). The PCR products were cleaved with the appropriate restriction enzymes. The statistical analysis was performed by Pearson’s chi-squared test. A value of was considered to be statistically significant. In conclusion, this case-control study revealed no statistically significant association between the VDR, IGF-1, and AMPD1 polymorphisms and the susceptibility to IS or curve severity in Bulgarian patients. Replication case-control studies will be needed to examine the association between these candidate-genes and IS in different populations. The identification of molecular markers for IS could be useful for early detection and prognosis of the risk for a rapid progression of the curve. That would permit early stage treatment of the patient with the least invasive procedures. Svetla Nikolova, Vasil Yablanski, Evgeni Vlaev, Luben Stokov, Alexey Slavkov Savov, and Ivo Marinov Kremensky Copyright © 2015 Svetla Nikolova et al. All rights reserved. Genome-Wide Gene Expression in relation to Age in Large Laboratory Cohorts of Drosophila melanogaster Thu, 21 May 2015 09:08:54 +0000 Aging is a complex process characterized by a steady decline in an organism’s ability to perform life-sustaining tasks. In the present study, two cages of approximately 12,000 mated Drosophila melanogaster females were used as a source of RNA from individuals sampled frequently as a function of age. A linear model for microarray data method was used for the microarray analysis to adjust for the box effect; it identified 1,581 candidate aging genes. Cluster analyses using a self-organizing map algorithm on the 1,581 significant genes identified gene expression patterns across different ages. Genes involved in immune system function and regulation, chorion assembly and function, and metabolism were all significantly differentially expressed as a function of age. The temporal pattern of data indicated that gene expression related to aging is affected relatively early in life span. In addition, the temporal variance in gene expression in immune function genes was compared to a random set of genes. There was an increase in the variance of gene expression within each cohort, which was not observed in the set of random genes. This observation is compatible with the hypothesis that D. melanogaster immune function genes lose control of gene expression as flies age. Kimberly A. Carlson, Kylee Gardner, Anjeza Pashaj, Darby J. Carlson, Fang Yu, James D. Eudy, Chi Zhang, and Lawrence G. Harshman Copyright © 2015 Kimberly A. Carlson et al. All rights reserved. Genetics in Genomic Era Wed, 25 Mar 2015 12:29:12 +0000 Eugenia Poliakov, David N. Cooper, Elena I. Stepchenkova, and Igor B. Rogozin Copyright © 2015 Eugenia Poliakov et al. All rights reserved. Importance of Genetic Diversity Assessment in Crop Plants and Its Recent Advances: An Overview of Its Analytical Perspectives Thu, 19 Mar 2015 12:40:44 +0000 The importance of plant genetic diversity (PGD) is now being recognized as a specific area since exploding population with urbanization and decreasing cultivable lands are the critical factors contributing to food insecurity in developing world. Agricultural scientists realized that PGD can be captured and stored in the form of plant genetic resources (PGR) such as gene bank, DNA library, and so forth, in the biorepository which preserve genetic material for long period. However, conserved PGR must be utilized for crop improvement in order to meet future global challenges in relation to food and nutritional security. This paper comprehensively reviews four important areas; (i) the significance of plant genetic diversity (PGD) and PGR especially on agriculturally important crops (mostly field crops); (ii) risk associated with narrowing the genetic base of current commercial cultivars and climate change; (iii) analysis of existing PGD analytical methods in pregenomic and genomic era; and (iv) modern tools available for PGD analysis in postgenomic era. This discussion benefits the plant scientist community in order to use the new methods and technology for better and rapid assessment, for utilization of germplasm from gene banks to their applied breeding programs. With the advent of new biotechnological techniques, this process of genetic manipulation is now being accelerated and carried out with more precision (neglecting environmental effects) and fast-track manner than the classical breeding techniques. It is also to note that gene banks look into several issues in order to improve levels of germplasm distribution and its utilization, duplication of plant identity, and access to database, for prebreeding activities. Since plant breeding research and cultivar development are integral components of improving food production, therefore, availability of and access to diverse genetic sources will ensure that the global food production network becomes more sustainable. The pros and cons of the basic and advanced statistical tools available for measuring genetic diversity are briefly discussed and their source links (mostly) were provided to get easy access; thus, it improves the understanding of tools and its practical applicability to the researchers. M. Govindaraj, M. Vetriventhan, and M. Srinivasan Copyright © 2015 M. Govindaraj et al. All rights reserved. Unlimited Thirst for Genome Sequencing, Data Interpretation, and Database Usage in Genomic Era: The Road towards Fast-Track Crop Plant Improvement Thu, 19 Mar 2015 11:29:29 +0000 The number of sequenced crop genomes and associated genomic resources is growing rapidly with the advent of inexpensive next generation sequencing methods. Databases have become an integral part of all aspects of science research, including basic and applied plant and animal sciences. The importance of databases keeps increasing as the volume of datasets from direct and indirect genomics, as well as other omics approaches, keeps expanding in recent years. The databases and associated web portals provide at a minimum a uniform set of tools and automated analysis across a wide range of crop plant genomes. This paper reviews some basic terms and considerations in dealing with crop plant databases utilization in advancing genomic era. The utilization of databases for variation analysis with other comparative genomics tools, and data interpretation platforms are well described. The major focus of this review is to provide knowledge on platforms and databases for genome-based investigations of agriculturally important crop plants. The utilization of these databases in applied crop improvement program is still being achieved widely; otherwise, the end for sequencing is not far away. Arun Prabhu Dhanapal and Mahalingam Govindaraj Copyright © 2015 Arun Prabhu Dhanapal and Mahalingam Govindaraj. All rights reserved. Caspase Activation and Aberrant Cell Growth in a p53+/+ Cell Line from a Li-Fraumeni Syndrome Family Wed, 18 Mar 2015 14:01:51 +0000 Wild-type p53 is well known to induce cell cycle arrest and apoptosis to block aberrant cell growth. However, p53’s unique role in apoptosis and cell proliferation in Li-Fraumeni Syndrome (LFS) has not been well elucidated. The aim of this study is to characterize the activity of wild-type p53 protein in LFS family dominated by a germline negative mutant p53. As expected, etoposide-treated wild-type p53-containing cell lines, LFS 2852 and control Jurkat, showed a greater rate of caspase- and annexin V-induced apoptotic cell death compared to the p53-mutant LFS 2673 cell line although mitochondrial and nuclear assays could not detect apoptosis in these organelles. The most intriguing part of the observation was the abnormal proliferation rate of the wild-type p53-containing cell line, which grew twice as fast as 2673 and Jurkat cells. This is important because apoptosis inducers acting through the mitochondrial death pathway are emerging as promising drugs against tumors where the role of p53 is not only to target gene regulation but also to block cell proliferation. This study casts a long shadow on the possible dysregulation of p53 mediators that enable cell proliferation. The deregulation of proliferation pathways represents an important anticancer therapeutic strategy for patients with the LFS phenotype. Zaki A. Sherif Copyright © 2015 Zaki A. Sherif. All rights reserved. Inheritance Pattern of Temephos Resistance, an Organophosphate Insecticide, in Aedes aegypti (L.) Mon, 16 Mar 2015 11:31:15 +0000 The present paper reports the mode of inheritance of resistance in laboratory induced temephos resistant and susceptible strains of Ae. aegypti. Homozygous resistant and susceptible strains of Ae. aegypti were generated by selective inbreeding at a diagnostic dose of 0.02 mg/L of temephos. Genetic crosses were carried out between these strains to determine the inheritance pattern of temephos resistance. The log-dosage probit mortality relationships and degree of dominance (D) were calculated. The dosage-mortality (d-m) line of the F1 generation was nearer to the resistant parent than the susceptible one. The “D” value was calculated as 0.15 indicating that the temephos resistant gene is incompletely dominant. The d-m lines of the F2 generation and progeny from the backcross exhibited clear plateaus of mortality across a range of doses indicating that temephos resistance is controlled by a single gene. Comparison of the mortality data with the theoretical expectations using the test revealed no significant difference, confirming a monogenic pattern of inheritance. In conclusion, the study provides evidence that the temephos resistance in Ae. aegypti follows an incompletely dominant and monogenic mode of inheritance. Vinaya Shetty, Deepak Sanil, and N. J. Shetty Copyright © 2015 Vinaya Shetty et al. All rights reserved. Genetic Variant in the CYP19A1 Gene Associated with Coronary Artery Disease Mon, 16 Mar 2015 10:39:23 +0000 The CYP19A1 gene encodes the enzyme aromatase, which is responsible for the biosynthesis of estrogens. The rs10046 polymorphism of CYP19A1 gene has been investigated in two studies on the occurrence of hypertension, but there are no studies on its correlation with coronary artery disease (CAD). We investigated 189 subjects who were hospitalized at “KAT” General Hospital of Athens and underwent coronary angiography. Of these, 123 were found with CAD with an average age of 60 years and constituted the patients group and 66 subjects with an average age of 58 years without damage in the coronary vessels and constituted the control group (healthy). The frequencies of genotypes CC, CT, and TT of rs10046 polymorphism are significantly different between the group of CAD patients and the control group (0.34, 0.48, and 0.18 versus 0.20, 0.48, and 0.32, resp., ) as the frequency of C allele (0.58 versus 0.44, resp., OR = 1.771 and ). We found similar results for men, but not for women (small sample). The results of this study show that the rs10046 (C/T) polymorphism of CYP19A1 gene exhibits correlation with CAD and that patients with C allele have an increased probability of manifesting the disease. Konstantina Bampali, Charalampos Grassos, Angeliki Mouzarou, Charalampos Liakos, Georgios Mertzanos, Klea Lamnissou, and Dimitrios Babalis Copyright © 2015 Konstantina Bampali et al. All rights reserved. An Introspective Update on the Influence of miRNAs in Breast Carcinoma and Neuroblastoma Chemoresistance Thu, 04 Dec 2014 00:10:00 +0000 Chemoresistance to conventional cytotoxic drugs may occur in any type of cancer and this can either be inherent or develop through time. Studies have linked this acquired resistance to the abnormal expression of microRNAs (miRNAs) that normally silence genes. At abnormal levels, miRNAs can either gain ability to silence tumour suppressor genes or else lose ability to silence oncogenes. miRNAs can also affect pathways that are involved in drug metabolism, such as drug efflux pumps, resulting in a resistant phenotype. The scope of this review is to provide an introspective analysis on the specific niches of breast carcinoma and neuroblastoma research. Alessia Carta, Rachel Chetcuti, and Duncan Ayers Copyright © 2014 Alessia Carta et al. All rights reserved. MTHFR Gene C677T Polymorphism in Autism Spectrum Disorders Thu, 06 Nov 2014 07:03:26 +0000 Aim. Autism is a subgroup of autism spectrum disorders, classified as a heterogeneous neurodevelopmental disorder and symptoms occur in the first three years of life. The etiology of autism is largely unknown, but it has been accepted that genetic and environmental factors may both be responsible for the disease. Recent studies have revealed that the genes involved in the folate/homocysteine pathway may be risk factors for autistic children. In particular, C677T polymorphism in the MTHFR gene as a possible risk factor for autism is still controversial. We aimed to investigate the possible effect of C677T polymorphism in a Turkish cohort. Methods. Autism patients were diagnosed by child psychiatrists according to DSM-IV and DSM-V criteria. A total of 98 children diagnosed as autistic and 70 age and sex-matched children who are nonautistic were tested for C677T polymorphism. This polymorphism was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Results. MTHFR 677T-allele frequency was found to be higher in autistic children compared with nonautistic children (29% versus 24%), but it was not found statistically significant. Conclusions. We conclude that other MTHFR polymorphisms such as A1298C or other folate/homocysteine pathway genes may be studied to show their possible role in autism. Elif Funda Sener, Didem Behice Oztop, and Yusuf Ozkul Copyright © 2014 Elif Funda Sener et al. All rights reserved. Clinical Presentation and Microarray Analysis of Peruvian Children with Atypical Development and/or Aberrant Behavior Mon, 20 Oct 2014 12:28:09 +0000 We report our experience with high resolution microarray analysis in infants and young children with developmental disability and/or aberrant behavior enrolled at the Centro Ann Sullivan del Peru in Lima, Peru, a low income country. Buccal cells were collected with cotton swabs from 233 participants for later DNA isolation and identification of copy number variation (deletions/duplications) and regions of homozygosity (ROH) for estimating consanguinity status in 15 infants and young children (12 males, 3 females; mean age ± SD = 28.1 m  m; age range 14 m–41 m) randomly selected for microarray analysis. An adequate DNA yield was found in about one-half of the enrolled participants. Ten participants showed deletions or duplications containing candidate genes reported to impact behavior or cognitive development. Five children had ROHs which could have harbored recessive gene alleles contributing to their clinical presentation. The coefficient of inbreeding was calculated and three participants showed first-second cousin relationships, indicating consanguinity. Our preliminary study showed that DNA isolated from buccal cells using cotton swabs was suboptimal, but yet in a subset of participants the yield was adequate for high resolution microarray analysis and several genes were found that impact development and behavior and ROHs identified to determine consanguinity status. Merlin G. Butler, Kelly Usrey, Jennifer L. Roberts, Stephen R. Schroeder, and Ann M. Manzardo Copyright © 2014 Merlin G. Butler et al. All rights reserved. Power Estimation for Gene-Longevity Association Analysis Using Concordant Twins Tue, 16 Sep 2014 00:00:00 +0000 Statistical power is one of the major concerns in genetic association studies. Related individuals such as twins are valuable samples for genetic studies because of their genetic relatedness. Phenotype similarity in twin pairs provides evidence of genetic control over the phenotype variation in a population. The genetic association study on human longevity, a complex trait that is under control of both genetic and environmental factors, has been confronted by the small sample sizes of longevity subjects which limit statistical power. Twin pairs concordant for longevity have increased probability for carrying beneficial genes and thus are useful samples for gene-longevity association analysis. We conducted a computer simulation to estimate the power of association study using longevity concordant twin pairs. We observed remarkable power increases in using singletons from longevity concordant twin pairs as cases in comparison with cases of sporadic proband. A similar power would require doubled sample sizes for fraternal twins than for identical twins who are concordant for longevity suggesting that longevity concordant identical twins are more efficient samples than fraternal twins. We also observed an approximate of 2- to 3-fold increase in sample sizes needed for longevity cutoff at age 90 as compared with that at age 95. Overall, our results showed high value of twins in genetic association studies on human longevity. Qihua Tan, Jing Hua Zhao, Torben Kruse, and Kaare Christensen Copyright © 2014 Qihua Tan et al. All rights reserved. Modulation at Age of Onset in Tunisian Huntington Disease Patients: Implication of New Modifier Genes Mon, 01 Sep 2014 00:00:00 +0000 Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO) of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population. Dorra Hmida-Ben Brahim, Marwa Chourabi, Sana Ben Amor, Imed Harrabi, Saoussen Trabelsi, Marwa Haddaji-Mastouri, Moez Gribaa, Sihem Sassi, Fatma Ezzahra Gahbiche, Turkia Lamouchi, Soumaya Mougou-Zereli, Sofiane Ben Ammou, and Ali Saad Copyright © 2014 Dorra Hmida-Ben Brahim et al. All rights reserved.