ISRN Genetics The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Association of IL10-1082 and IFN-γ+874 Polymorphisms with Cervical Cancer among Tunisian Women Thu, 06 Feb 2014 11:36:10 +0000 Objective. The aim of this study was to investigate the role of IL10-1082 and IFN-γ+874 polymorphisms in susceptibility to cervical cancer among Tunisian women. Study Design. The IL10-1082 and IFN-γ+874 polymorphisms were analyzed by ARMS-PCR in 160 healthy women and 122 with cervical cancer. The search for associations between those polymorphisms and cervical cancer was based on the test or Fisher's exact test. Results. The IFN-γ+874 polymorphism showed significant increased frequency of T allele in healthy controls compared with patients (OR = 0.71, 95% CI = 0.50–1.01, and ) and individuals with homozygote IFN-γ+874 T/T genotype were at lesser risk of cervical cancer (OR = 0.53, 95% CI = 0.31–0.92, and ). However, carriers of allele have higher risk for developing cervical cancer (OR = 1.88, 95% CI = 1.09–3.24, and ). At the polymorphic nucleotide in position 1082 of the IL10 promoter, no differences were found between patients and controls subjects. Conclusion. Our study shows that the T/T genotype polymorphism of IFN-γ+874 T>A is a protective factor for cervical cancer among Tunisian women. Sabrina Zidi, Yosra Benothmen, Ikram Sghaier, Ezzeddine Ghazoueni, Amel Mezlini, Bouraoui Slimen, and Besma Yacoubi-Loueslati Copyright © 2014 Sabrina Zidi et al. All rights reserved. The Relationship between Polymorphisms in the Vitamin D Receptor Gene and Bone Mineral Density in Postmenopausal Women Thu, 09 Jan 2014 13:46:26 +0000 The objective of this study was to identify, through a systematic review of the literature, Vitamin D receptor gene (VDR) polymorphisms related to osteoporosis and their effects on bone mineral density (BMD). The articles dated between January 2000 and December 2011 in the Scielo and PubMed databases were reviewed. A total of 23 articles that studied the association between the BsmI, ApaI, FokI, and TaqI polymorphisms and bone mineral density in postmenopausal women were selected. We found systematic studies/meta-analysis (level E-I) and case-control/cohort (level E-IV) studies. No definite conclusions can be made regarding the association of BsmI, ApaI, FokI, and TaqI polymorphisms with BMD among postmenopausal women. Larger and more rigorous analytical studies with consideration of gene-gene/environment interactions are needed to further dissect the mechanisms by which VDR alleles influence BMD. Jose M. Moran, Francisco J. Rodriguez-Velasco, Raul Roncero-Martin, Purificación Rey-Sanchez, Mariana Martinez, and Juan D. Pedrera-Zamorano Copyright © 2014 Jose M. Moran et al. All rights reserved. Construction of Genetic Linkage Map and QTL Analysis of Sink-Size Traits in Pearl Millet (Pennisetum glaucum) Tue, 24 Dec 2013 11:09:54 +0000 A linkage map, primarily based on SSCP-SNP markers, was constructed using 188 F2:3 mapping population progenies produced from a cross between two pearl millet inbred lines having diverse parentage. The skeleton linkage map covered 1019 cM and it comprised of 44 markers distributed across the seven linkage groups. Average adjacent-marker intervals ranged from 14 cM on LG1 to 38 cM on LG6, with an overall mean of 23 cM. Using the F2 linkage map and phenotypic data from the F2 and F2:3 generations of the mapping population, a total of 18 putative QTLs were detected for the three sink-size components. Eight QTLs explained 42.7% of observed phenotypic variation for panicle length using the F2:3 data set. For panicle diameter, 5 QTLs explained 45.8% of observed phenotypic variation. Similarly for grain size, 5 QTLs explained 29.6% of phenotypic variation. Genomic regions associated with panicle length, panicle diameter, and grain size were comapped on LG6 between Xpsms88 and Xpsms2270, indicating the existence of a gene or gene cluster. The QTLs for panicle length on LG2 and LG6 ( in both F2 and F2:3 data sets), for panicle diameter on LG2 and LG3 ( in the F2:3 data set), and for grain size on LG3 and LG6 ( in both F2 and F2:3 data sets) were identified as promising candidates for validation prior to possible application in marker-assisted breeding. V. Vengadessan, K. N. Rai, J. R. Kannan Bapu, C. T. Hash, R. Bhattacharjee, S. Senthilvel, M. T. Vinayan, and T. Nepolean Copyright © 2013 V. Vengadessan et al. All rights reserved. Identification of a Novel Ryanodine Receptor Mutation Causing Malignant Hyperthermia Thu, 07 Nov 2013 13:50:14 +0000 Malignant hyperthermia (MH) is a potentially fatal autosomal dominant disorder of the skeletal muscle and is triggered in susceptible individuals by commonly used inhalation anaesthetics and depolarizing muscle relaxants. Around 80% of the affected family are linked to the ryanodine receptor (RYR1) gene. More than 300 mutations in RYR1 have been associated with the MH-susceptible phenotype. Here we report the identification by two independent methods of a novel mutation associated with the MH-susceptible phenotype in the RYR1 gene. Iveta Valaskova, Silvie Dudova, Jana Necasova, Edita Ostadalova, Martina Vanaskova, Dagmar Stepankova, Ivana Schröderova, Renata Gaillyova, and Petr Kuglik Copyright © 2013 Iveta Valaskova et al. All rights reserved. No Association of Leptin Receptor Gene Gln223Arg Polymorphism with Capillary Glucose Levels: A Preliminary Population Base Cross-Sectional Study Sun, 25 Aug 2013 09:01:22 +0000 The leptin receptor gene has been reported to associate with insulin and glucose metabolism and adiposity in different study settings and various populations. Therefore, the aim of the study was to investigate the associations of the leptin receptor gene Gln223Arg polymorphism (LEPR Gln223Arg) with high capillary glucose levels. Cross-sectional study with probabilistic sample was carried out in individuals aged ≥18 years in an urban area of Montes Claros, MG, Brazil. The capillary glucose was considered high when ≥140 mg/dL. The genotypes of LEPR Gln223Arg distribution were as the following: 10.43% GG (), 46.81% AG (), and 42.77% AA (), and there were no prevalence differences between genders, (). Multivariate-adjusted models showed that there is no association between the polymorphism LEPR Gln223Arg and capillary high levels of glucose even when adjusted for age, sex, smoking, schooling, and parental history of obesity. In conclusion, no association between the polymorphism LEPR Gln223Arg and elevated blood glucose levels was detected. Geórgia das Graças Pena, Andre Luiz Sena Guimarães, Rosângela Ramos Veloso, Tatiana Carvalho Reis, João Felício Rodrigues Neto, and Gustavo Velasquez-Melendez Copyright © 2013 Geórgia das Graças Pena et al. All rights reserved. Hypermethylation of INS Promoter in the Developing Liver of Cattle Mon, 05 Aug 2013 13:58:01 +0000 Insulin (INS) and insulin-like growth factor 2 (IGF2) are both important for the milk synthesis in human and dairy cattle. Liver is a source of growth factors that play an important role in the regulation of milk synthesis in the mammary gland in influence its composition. Occurrence of common INS-IGF transcript and imprinting regulation in some human tissues suggests close interaction between both genes. Here, we analyzed the DNA methylation pattern of the INS promoter and IGF2 expression at six different pre- and postnatal developmental stages of bovine liver. We found stage-independent DNA hypermethylation (93%) of the INS promoter. In contrast, we observed a 4-fold decrease of the IGF2 expression in 12-month-old adult animals compared to 2-month-old fetuses. We therefore suggest that DNA methylation at the INS promoter does not directly regulate the IGF2 expression in the bovine liver. Pawel Lisowski, Krzysztof Flisikowski, and Lech Zwierzchowski Copyright © 2013 Pawel Lisowski et al. All rights reserved. Functional Interactions in Transcription and Splicing of Ewing’s Sarcoma Mon, 22 Jul 2013 10:19:09 +0000 Ewing’s sarcoma (EWS) protein is a member of the TET (TLS/EWS/TAF15) family of RNA and DNA-binding proteins with unknown cellular role. EWS protein is encoded by the EWS oncogene on chromosome 22q12, a target of chromosomal translocations in Ewing’s sarcoma tumors. The exact mechanism of EWS participation in gene expression and pathogenesis of the resulting cancers is not defined. The binding partners of native EWS and EWS fusion proteins (EFPs) are described schematically in a model, an attempt to link the transcription with the splicing. The experimental data about the partnerships of EWS and EFPs are summarized, which may lead to better understanding of their function. Roumiana Todorova Copyright © 2013 Roumiana Todorova. All rights reserved. Genotyping of CYP2D6 Polymorphisms by MALDI-TOF Mass Spectrometry in Sardinian People Sun, 12 May 2013 17:53:52 +0000 The CYP2D6 enzyme is involved in the metabolism of many commonly prescribed drugs. The presence of CYP2D6 gene SNPs can alter CYP2D6 enzymatic activity with effects ranging considerably within a population. Objectives. In this study, we have developed a genotyping platform able to determine the alleles related to interindividual variability in the CYP2D6 gene. Design and Methods. We used a long PCR strategy coupled to MALDI-TOF mass spectrometry (Sequenom) to develop a SNPs genotyping method. Furthermore, an amplification allele specific was carried out to infer the correct allelic phase. Results. We tested the multiplex platform in 250 DNA Sardinian samples and found it to be 100% concordant with the sequencing results of our previous work. Conclusions. The MALDI-TOF-based multiplexing system allowed simultaneous and efficient genotyping of a set of CYP2D6 SNPs, evidencing its potential use in diagnostic test development to predict drug responses and clinical outcomes. Matteo Falzoi, Luigi Pira, Paolo Lazzari, and Luca Pani Copyright © 2013 Matteo Falzoi et al. All rights reserved. Study Designs in Genetic Epidemiology Sun, 12 May 2013 15:58:06 +0000 Genetic epidemiology, as a relatively new issue, aims to explore the independent role of genetic-environmental determinants of diseases. Genetic epidemiology studies, depending on the objective, encompass the most preliminary surveys from the attempts to find family history in the occurrence of diseases to the most advanced surveys including specific strategies by clinical trials in the prevention of genetic diseases. Different objectives in genetic epidemiology studies require special methods and study designs. In this review, chief designs including familial aggregation, heritability, segregation, linkage, and association are evaluated; likewise, the purpose of diverse kinds of studies and analyses is briefly discussed. The utilization of study designs and related analyses according to the aims are the main issues and necessary in the accurate implementation of the study. Some methodological issues in relation to studies on tuberculosis are also reported. Attention to these issues might be useful in the implementation of these methods in the studies designed for the prevention and treatment of genetic disorders. Leyla Sahebi, Saeed Dastgiri, Khalil Ansarin, Roya Sahebi, and Seyyed Abolghasem Mohammadi Copyright © 2013 Leyla Sahebi et al. All rights reserved. Cuban Adolescents Requesting Presymptomatic Testing for Spinocerebellar Ataxia Type 2 Tue, 30 Apr 2013 11:21:19 +0000 Since 2001 a program for the presymptomatic testing of families affected with SCA2 has been under development in Cuba. According to the initial protocol, access would be given to nonsymptomatic individuals at 50% risk, over 18 years; nevertheless, eleven minors requested their inclusion in the program. A retrospective and descriptive study based on the analysis of the medical records belonging to these individuals was designed. Being aware of how challenging clinical settings of predictive genetic testing for minors are, this paper reviews their profile, the outcome of the carried out studies, as well as the reproductive option chosen by the gene positive consultands. The mean age at the time of testing was 16.2 years. Nine adolescents completed the protocol (three had positive test results) and two withdrew. They had a distinctive profile; all were females, pregnant, motivated by the risk assessment for their descendants, and interested in PND with termination of the gestation were the fetus a carrier. Nevertheless, once the result of the test is known, the gene positive consultands chose discordant reproductive options. Further research is necessary to assess the long-term psychological impact in both gene positive and gene negative participants, as well as in their parents and at-risk relatives. Tania Cruz-Mariño, Luis Velázquez-Pérez, Yanetza González-Zaldivar, Raúl Aguilera-Rodríguez, Miguel Velázquez-Santos, Yaimé Vázquez-Mojena, Annelié Estupiñán-Rodríguez, José Miguel Laffita-Mesa, Rubén Reynaldo-Armiñán, Luis Enrique Almaguer-Mederos, and Milena Paneque Copyright © 2013 Tania Cruz-Mariño et al. All rights reserved. Reference Analysis in a Misclassification Model for the Meiosis I Nondisjunction Fraction in Trisomies Thu, 10 Jan 2013 09:51:54 +0000 The determination of the meiosis I nondisjunction fraction plays an important role in identifying the characteristics of affected individuals and their mothers, which can generate aneuploidies. The number of individuals with one, two, and three peaks pattern is used to obtain the information; however, the data are susceptible to misclassification. We review the misclassification model previously introduced in the literature which considers a common misclassification error. This paper aims to introduce a joint prior distribution for the meiosis I nondisjunction fraction and the misclassification error. We prove that the reference prior is a proper distribution. We analyze a Brazilian Down syndrome dataset and compare the results with those obtained through Bayes-Laplace and beta prior distributions. Rosangela H. Loschi and Vinicius D. Mayrink Copyright © 2013 Rosangela H. Loschi and Vinicius D. Mayrink. All rights reserved. Detection of Fetal Aneuploidies by QF-PCR in Transcervical Cell Samples Sun, 23 Dec 2012 15:54:36 +0000 Objective. To evaluate the accuracy in the diagnosis of aneuploidies of a quantitative fluorescent polymerase chain reaction (QF-PCR) assay on trophoblastic cells recovered from transcervical cells samples (TCCs) collected by intrauterine lavage (IUL). Study Design. DNA analysis was performed on cells of seemingly trophoblastic origin isolated from IUL samples collected prior to first trimester termination of pregnancy. The analysis was performed by multiplex QF-PCR, using a panel of 29 polymorphic short tandem repeats (STRs) for the chromosomes X, Y, 21, 13, and 18. Results. The QF-PCR analysis on placental samples revealed that among the three cases studied there were two cases of trisomy 21 and one case of monosomy X; the comparison of peak profiles obtained from IUL, placental, and maternal samples confirmed the diagnosis of aneuploidy in all three cases. Conclusion. This study suggests that the detection of chromosomal aneuploidies in micromanipulated TCC samples can be achieved by QF-PCR amplification of selected highly polymorphic and chromosome specific markers. With respect to standard karyotype, QF-PCR analysis has the limitation that only numerical abnormalities of selected chromosomes can be detected but retains the advantages of being quicker, less expensive, and less lab demanding. Riccardo Cioni, Cecilia Bussani, and Mariarosaria Di Tommaso Copyright © 2013 Riccardo Cioni et al. All rights reserved. Mutation Screening of Elongation Factor 2 in Shwachman-Diamond Syndrome Patients Lacking Mutations in the SBDS Gene Mon, 03 Dec 2012 08:27:08 +0000 Shwachman-Diamond syndrome is an autosomal recessive disorder characterized by bone marrow failure, pancreatic insufficiency, and skeletal abnormalities. Mutations in SBDS gene explain, by literature, 90% of SDS cases. The Italian experience shows that only the 5% of individuals diagnosed as affected by SDS on clinical and hematological grounds lack mutations in the SBDS gene. It is well established that SBDS protein is essential for the assembly of mature ribosomes. The yeast SBDS ortholog functions within a pathway containing elongation factor-like 1, homologous to human GTPase elongation factor-2, to promote the release and recycling of the nucleolar shuttling factor Tif6 from cytoplasmic pre-60S subunits in a cascade targeted to form the active ribosome. We considered that mutations of genes that disrupt pathways shared by SBDS may result in disease with comparable clinical features. EEF2 was evaluated as a candidate gene by mutation screening in clinically defined SDS which lack mutations in the SBDS gene. To date, no deleterious mutations were found in EEF2 in four Italian patients without SBDS mutations, but with a clinical diagnosis of SDS. Elena Nicolis and Marco Cipolli Copyright © 2013 Elena Nicolis and Marco Cipolli. All rights reserved. Analysis of CYP2D6 Allele Frequencies and Identification of Novel SNPs and Sequence Variations in Sardinians Mon, 05 Nov 2012 16:08:34 +0000 The CYP2D6 enzyme is involved in the metabolism of many commonly prescribed drugs. The presence of polymorphisms in the CYP2D6 gene may modulate the enzyme level and activity affecting individual responses, to pharmacological treatment in drug level, response and adverse reactions. Aims. This study aimed to analyze the determination of allele frequencies in Sardinians and the comparison to frequencies found in the Caucasian Population. Methods and Materials. We used a Long PCR strategy coupled to direct genomic DNA sequencing analysis. An amplification allele-specific was carried out to infer the correct allelic phase. The TaqMan Gene Copy Number Assay (Applied Biosystems) was used to verify the presence of gene deletions/multiplications. Results and Conclusions. Our results indicated that CYP2D6 allele frequencies in Sardinians differed from those previously detected in the Caucasian Population. Moreover, three new SNPs and four novel haplotypes were identified. Matteo Falzoi, Luigi Pira, Paolo Lazzari, and Luca Pani Copyright © 2013 Matteo Falzoi et al. All rights reserved. Perspectives for the Use of Quantitative Genetics in Breeding of Autogamous Plants Thu, 01 Nov 2012 15:57:48 +0000 With the increased demand for food, the use of methods and alternatives that increase efficiency in selection of inbred lines is necessary. The use of quantitative genetics plays an important role in this respect, especially when the pedigree method is used in autogamous plants. This study proposes the inclusion of relationship information among progenies using the best linear unbiased predictor (BLUP) to obtain the breeding values of greater accuracy and, consequently, increase genetic gains from the selection. A strategy is proposed that aims to accelerate the program of obtaining perennial plant inbreds and use the greatest amount of information possible in selection so as to attain maximum accuracy. In that way, it would be possible to make inbreds available which are better than the existing ones, with greater frequency, meeting the agribusiness demand involved in production of perennial plants. Magno Antonio Patto Ramalho, Bruna Line Carvalho, and José Airton Rodrigues Nunes Copyright © 2013 Magno Antonio Patto Ramalho et al. All rights reserved. Genetic Divergence in Indigenous Wild and Cultivated Rice Species of Manipur Valley Thu, 01 Nov 2012 14:27:24 +0000 Genetic divergence of 32 indigenous rice germplasms and five wild rice of which three from Manipur and two wild rice procured from IRRI, Philippines was investigated using Mahalanobis, statistic. Based on twelve agromorphological characters, the thirty-seven germplasms both wild and cultivated were grouped into five clusters based on the relative magnitudes of values following Tocher's method of cluster formation. Based on the rank totals, the characters which contributed maximum towards genetic divergence in the present studies were grain yield/plant, spikelet/panicle, 100 grain weight, grain length, days to 50% flowering, ear bearing tillers/plant, and flag leaf length. In the present study, maximum intercluster distance was estimated between cluster III and () which was closed followed by clusters II and V (). On the basis of their greater intercluster distance, high value of cluster mean according to the character to be improved and performance of the individual germplasms for the character, the germplasms could be used in hybridization programme for improvement of different plant characters in the rice germplasms of Manipur. K. Medhabati, K. Rajiv Das, M. Rohinikumar, H. Sunitibala, and Th. Dikash Singh Copyright © 2013 K. Medhabati et al. All rights reserved. Molecular and Chromosomal Markers for Evolutionary Considerations in Torpediniformes (Chondrichthyes, Batoidea) Tue, 25 Sep 2012 16:11:27 +0000 Due to their basal position in the vertebrate phylogenetic tree, the study on elasmobranch genetics and cytogenetics can provide remarkable information on the mechanisms underlying the evolution of all vertebrates. In recent years, different molecular approaches have been used to study the relationships between the different taxonomic groups of cartilaginous fish, among them are the physical mapping of specific nucleotide sequences on chromosomes. However, these are controversial, particularly in Torpediniformes in which the species have different karyological parameters. The purpose of this paper is to gather the molecular markers so far present in literature that were used to reconstruct the phylogenetic position of Torpediniformes with respect to the other Batoidea and to discriminate between the various chromosome pairs in the endemic species in the Mediterranean Sea, Torpedo torpedo, T. marmorata and T. nobiliana. The 5S and 18S ribosomal DNA, the HpaI and Alu SINE, the telomeric (TTAGGG)n and the spermatogenesis-related SPATA 16, SPATA 18, and UTY sequences were particularly useful. These last genomic segments were also able to differentiate between the male and the female karyotypes. Moreover, the torpedoes showed a particular genomic organization, especially Torpedo torpedo, in which large quantities of highly repeated DNA and a characteristic distribution of heterochromatin, which is never centromeric, were observed. Lucia Rocco Copyright © 2013 Lucia Rocco. All rights reserved. Fetal Nucleic Acids in Maternal Circulation: A Genetic Resource for Noninvasive Prenatal Diagnosis Thu, 20 Sep 2012 16:12:00 +0000 Invasive prenatal diagnosis (PND) holds a multitude of psychological considerations for women, their partners, family and community as a whole. Earlier, the non-invasive screening methods for certain disorders were serum analytes or ultrasound with low sensitivity and high false positivity. The discovery of fetal DNA in maternal plasma has opened up an approach for noninvasive PND (NIPD). Presence of fetal cells and cell-free fetal DNA (cffDNA) in the blood of pregnant women has been accepted universally and constant efforts are being made to enrich fetal DNA from maternal blood/plasma. Real-time quantitative polymerase chain reaction (qrt-PCR) has enabled fetal DNA to serve as a marker for chromosomal abnormalities, for example, trisomy 21, preterm labor, and preeclampsia. In India, PND is provided in few centers since invasive methods require trained gynecologists, this limits investigation and therefore NIPD with cffDNA from mother's blood will revolutionize fetal medicine. The present paper deals with the latest developments in procurement of cffDNA, the probable source and enrichment of fetal DNA in maternal plasma, and the current status of its detection methodologies, applications, and its potential to be used as a powerful diagnostic tool. Monisha Banerjee and Deepika Misra Copyright © 2013 Monisha Banerjee and Deepika Misra. All rights reserved.