Genetic dissection of mammalian ERAD through comparative haploid and CRISPR forward genetic screens

DEFF Research Database (Denmark)

Timms, Richard T.; Menzies, Sam A.; Tchasovnikarova, Iva A.

2016-01-01

The application of forward genetic screens to cultured human cells represents a powerful method to study gene function. The repurposing of the bacterial CRISPR/Cas9 system provides an effective method to disrupt gene function in mammalian cells, and has been applied to genome-wide screens. Here, we...... compare the efficacy of genome-wide CRISPR/Cas9-mediated forward genetic screens versus gene-trap mutagenesis screens in haploid human cells, which represent the existing ‘gold standard’ method. This head-to-head comparison aimed to identify genes required for the endoplasmic reticulum....../3-associated disulphide reductase. Genome-wide CRISPR/Cas9-mediated screens together with haploid genetic screens provide a powerful addition to the forward genetic toolbox....

Technical Update: Preimplantation Genetic Diagnosis and Screening.

Science.gov (United States)

Dahdouh, Elias M; Balayla, Jacques; Audibert, François; Wilson, R Douglas; Audibert, François; Brock, Jo-Ann; Campagnolo, Carla; Carroll, June; Chong, Karen; Gagnon, Alain; Johnson, Jo-Ann; MacDonald, William; Okun, Nanette; Pastuck, Melanie; Vallée-Pouliot, Karine

2015-05-01

To update and review the techniques and indications of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Discussion about the genetic and technical aspects of preimplantation reproductive techniques, particularly those using new cytogenetic technologies and embryo-stage biopsy. Clinical outcomes of reproductive techniques following the use of PGD and PGS are included. This update does not discuss in detail the adverse outcomes that have been recorded in association with assisted reproductive technologies. Published literature was retrieved through searches of The Cochrane Library and Medline in April 2014 using appropriate controlled vocabulary (aneuploidy, blastocyst/physiology, genetic diseases, preimplantation diagnosis/methods, fertilization in vitro) and key words (e.g., preimplantation genetic diagnosis, preimplantation genetic screening, comprehensive chromosome screening, aCGH, SNP microarray, qPCR, and embryo selection). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies published from 1990 to April 2014. There were no language restrictions. Searches were updated on a regular basis and incorporated in the update to January 2015. Additional publications were identified from the bibliographies of retrieved articles. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. (Table 1) BENEFITS, HARMS, AND COSTS: This update will educate readers about new preimplantation genetic concepts, directions, and technologies. The major harms and costs identified are those of assisted reproductive

[Molecular genetic diagnostics and screening of hereditary hemochromatosis].

Science.gov (United States)

Zlocha, J; Kovács, L; Pozgayová, S; Kupcová, V; Durínová, S

2006-06-01

identified through biochemical testing for iron overload using serum transferrin saturation and genetic testing for C282Y homozygosity. DNA analysis is recommended in patients whose transferrin saturation is 45% or more on a repeated test. General population screening has been waived in preference to targeting high-risk groups such as first-degree relatives of affected individuals and those with secondary iron overload, especially patients with chronic liver disorders and chronic anemia. This screening strategy is likely to continue until uncertainties regarding the natural history of the disease, age-related penetrance, and management of asymptomatic individuals are clarified.

Genetic and epigenetic markers in colorectal cancer screening: recent advances.

Science.gov (United States)

Singh, Manish Pratap; Rai, Sandhya; Suyal, Shradha; Singh, Sunil Kumar; Singh, Nand Kumar; Agarwal, Akash; Srivastava, Sameer

2017-07-01

Colorectal cancer (CRC) is a heterogenous disease which develops from benign intraepithelial lesions known as adenomas to malignant carcinomas. Acquired alterations in Wnt signaling, TGFβ, MAPK pathway genes and clonal propagation of altered cells are responsible for this transformation. Detection of adenomas or early stage cancer in asymptomatic patients and better prognostic and predictive markers is important for improving the clinical management of CRC. Area covered: In this review, the authors have evaluated the potential of genetic and epigenetic alterations as markers for early detection, prognosis and therapeutic predictive potential in the context of CRC. We have discussed molecular heterogeneity present in CRC and its correlation to prognosis and response to therapy. Expert commentary: Molecular marker based CRC screening methods still fail to gain trust of clinicians. Invasive screening methods, molecular heterogeneity, chemoresistance and low quality test samples are some key challenges which need to be addressed in the present context. New sequencing technologies and integrated omics data analysis of individual or population cohort results in GWAS. MPE studies following a GWAS could be future line of research to establish accurate correlations between CRC and its risk factors. This strategy would identify most reliable biomarkers for CRC screening and management.

Molecular genetic markers for thyroid FNAB. Established assays and future perspective.

Science.gov (United States)

Musholt, Thomas J; Musholt, P B

2015-01-01

Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18-65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Molecular genetic analysis of FNABs is increasingly performed in Germany

Genetic screens in Caenorhabditis elegans models for neurodegenerative diseases

NARCIS (Netherlands)

Alvarenga Fernandes Sin, Olga; Michels, Helen; Nollen, Ellen A. A.

2014-01-01

Caenorhabditis elegans comprises unique features that make it an attractive model organism in diverse fields of biology. Genetic screens are powerful to identify genes and C. elegans can be customized to forward or reverse genetic screens and to establish gene function. These genetic screens can be

Some legal aspects of genetic screening.

Science.gov (United States)

Abbing, H R

2003-01-01

Screening activities in health care are not always useful and sometimes harmful. The mere offer of a screening test puts the individual's autonomy under constraint. With genetic (predictive and risk assessment) tests, the right to free, informed consent and to protection of privacy and medical confidentiality is even more warranted. Screening evokes many questions from the perspective of the right to health care as well as (in particular with genetic screening) from the perspective of respect for individual human rights. Fear of liability puts pressure on professional restraint not to offer every screening test available. States have to take legislative measures for guaranteeing that only those screening activities become available that can significantly contribute to individual and public health. They also should consider additional rules for protecting individual rights where those that are generally accepted in the "ordinary" medical setting (the individual patient-doctor relationship), offer insufficient protection.

Good laboratory practices for biochemical genetic testing and newborn screening for inherited metabolic disorders.

Science.gov (United States)

2012-04-06

screening laboratories. The recommended practices address the benefits of using a quality management system approach, factors to consider before introducing new tests, establishment and verification of test performance specifications, the total laboratory testing process (which consists of the preanalytic, analytic, and postanalytic phases), confidentiality of patient information and test results, and personnel qualifications and responsibilities for laboratory testing for inherited metabolic diseases. These recommendations are intended for laboratories that perform biochemical genetic testing to improve the quality of laboratory services and for newborn screening laboratories to ensure the quality of laboratory practices for inherited metabolic disorders. These recommendations also are intended as a resource for medical and public health professionals who evaluate laboratory practices, for users of laboratory services to facilitate their collaboration with newborn screening systems and use of biochemical genetic tests, and for standard-setting organizations and professional societies in developing future laboratory quality standards and practice recommendations. This report complements Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions (CDC. Good laboratory practices for molecular genetic testing for heritable diseases and conditions. MMWR 2009;58 [No. RR-6]) to provide guidance for ensuring and improving the quality of genetic laboratory services and public health outcomes. Future recommendations for additional areas of genetic testing will be considered on the basis of continued monitoring and evaluation of laboratory practices, technology advancements, and the development of laboratory standards and guidelines.

Electron screening in molecular fusion reactions

International Nuclear Information System (INIS)

Shoppa, T.D.

1996-01-01

Recent laboratory experiments have measured fusion cross sections at center-of-mass energies low enough for the effects of atomic and molecular electrons to be important. To extract the cross section for bare nuclei from these data (as required for astrophysical applications), it is necessary to understand these screening effects. We study electron screening effects in the low-energy collisions of Z=1 nuclei with hydrogen molecules. Our model is based on a dynamical evolution of the electron wave functions within the TDHF scheme, while the motion of the nuclei is treated classically. We find that at the currently accessible energies the screening effects depend strongly on the molecular orientation. The screening is found to be larger for molecular targets than for atomic targets, due to the reflection symmetry in the latter. The results agree fairly well with data measured for deuteron collisions on molecular deuterium and tritium targets. (orig.)

Molecular genetics

International Nuclear Information System (INIS)

Parkinson, D.R.; Krontiris, T.G.

1986-01-01

In this chapter the authors review new findings concerning the molecular genetics of malignant melanoma in the context of other information obtained from clinical, epidemiologic, and cytogenetic studies in this malignancy. These new molecular approaches promise to provide a more complete understanding of the mechanisms involved in the development of melanoma, thereby suggesting new methods for its treatment and prevention

Preimplantation Genetic Screening and Preimplantation Genetic Diagnosis.

Science.gov (United States)

Sullivan-Pyke, Chantae; Dokras, Anuja

2018-03-01

Preimplantation genetic testing encompasses preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). PGS improves success rates of in vitro fertilization by ensuring the transfer of euploid embryos that have a higher chance of implantation and resulting in a live birth. PGD enables the identification of embryos with specific disease-causing mutations and transfer of unaffected embryos. The development of whole genome amplification and genomic tools, including single nucleotide polymorphism microarrays, comparative genomic hybridization microarrays, and next-generation sequencing, has led to faster, more accurate diagnoses that translate to improved pregnancy and live birth rates. Copyright © 2017 Elsevier Inc. All rights reserved.

CRISPR genetic screens to discover host-virus interactions.

Science.gov (United States)

McDougall, William M; Perreira, Jill M; Reynolds, Erin C; Brass, Abraham L

2018-04-01

Viruses impose an immense burden on human health. With the goal of treating and preventing viral infections, researchers have carried out genetic screens to improve our understanding of viral dependencies and identify potential anti-viral strategies. The emergence of CRISPR genetic screening tools has facilitated this effort by enabling host-virus screens to be undertaken in a more versatile and fidelitous manner than previously possible. Here we review the growing number of CRISPR screens which continue to increase our understanding of host-virus interactions. Copyright © 2018 Elsevier B.V. All rights reserved.

Molecular genetics of breast cancer

International Nuclear Information System (INIS)

Radice, P.; Pierotti, M. A.

1997-01-01

In the last two decades, molecular studies have enlightened the complexity of the genetic alterations that occur in breast cancer cells. To date, more than 40 different genes or loci have been found to be altered in breast carcinomas. Although some of these genes, as for example ERBB2, appear to be mutated in a high proportion of cases, their mechanism of action and their role in the different stages of cancer development are still poorly understood. More recently, two major determinants of the inherited predisposition to breast cancer, BRCA1 and BRCA2, have been isolated. As a consequence, it is now possible to screen families with a positive history of breast carcinomas for the identification of mutations carriers, in order to address these individuals into adequate programs of cancer surveillance and prevention

Screening for genetically modified organisms sequences in food ...

African Journals Online (AJOL)

We used the Allin 2.0 GMO screening system from Biosmart, Switzerland to screen for the presence of genetically modified food sequences in maize meal samples, fresh fruit and vegetables from some retailers around Gaborone, Botswana. The Allin 2.0 is a multiplex PCR system for the detection of genetically modified ...

Molecular Insights into the Genetic Diversity of Garcinia cambogia Germplasm Accessions

Directory of Open Access Journals (Sweden)

C Tharachand

2015-10-01

Full Text Available ABSTRACTIn this work, the genetic relationship among twelveGarcinia cambogia (Gaertn. Desr. accessions were evaluated using Random Amplified Polymorphic DNA markers. The samples were part of the germplasm collected and maintained at NBPGR Regional station, Thrissur, India. Out of thirty RAPD primers used for screening, seven primers produced a total of 128 polymorphic markers in twelve accessions. The Polymorphic Information Content (PIC ranged from 0.28 (OPA18 to 0.37 (OPA9 and Marker Index (MI ranged between 3.61 (OPA12 and 5.93 (OPA3 among the primers used. Jaccard's coefficient of genetic similarity ranged between 0.07 and 0.64. The dendrogram constructed based on the similarity matrix generated from the molecular and morphological data showed the genetic relationship among the sampled accessions. Mantel matrix test showed a positive correlation (r = 0.49 between the cluster analysis of RAPD data and morphological data. The clustering pattern in the molecular dendrogram and Principle Coordinate Analysis (PCoA showed that the genotypes were diverse, which was in congruence with the similarity index values and morphological dendrogram. High frequency of similarity values in the range of 0.11 to 0.17 suggested the existence of high genetic diversity among the accessions. The high level of genetic diversity among the studied accessions ofG.cambogia was also supported by the large variation in the morphological characters observed in the flowers, leaves, fruits and seeds of these sampled accessions. This is the first report for the molecular based genetic diversity studies for these accessions.

Teaching molecular genetics: Chapter 1--Background principles and methods of molecular biology.

NARCIS (Netherlands)

Knoers, N.V.A.M.; Monnens, L.A.H.

2006-01-01

In this first chapter of the series "Teaching molecular genetics," an introduction to molecular genetics is presented. We describe the structure of DNA and genes and explain in detail the central dogma of molecular biology, that is, the flow of genetic information from DNA via RNA to polypeptide

Evaluation of two-year Jewish genetic disease screening program in Atlanta: insight into community genetic screening approaches.

Science.gov (United States)

Shao, Yunru; Liu, Shuling; Grinzaid, Karen

2015-04-01

Improvements in genetic testing technologies have led to the development of expanded carrier screening panels for the Ashkenazi Jewish population; however, there are major inconsistencies in current screening practices. A 2-year pilot program was launched in Atlanta in 2010 to promote and facilitate screening for 19 Jewish genetic diseases. We analyzed data from this program, including participant demographics and outreach efforts. This retrospective analysis is based on a de-identified dataset of 724 screenees. Data were obtained through medical chart review and questionnaires and included demographic information, screening results, response to outreach efforts, and follow-up behavior and preferences. We applied descriptive analysis, chi-square tests, and logistic regression to analyze the data and compare findings with published literature. The majority of participants indicated that they were not pregnant or did not have a partner who was pregnant were affiliated with Jewish organizations and reported 100 % AJ ancestry. Overall, carrier frequency was 1 in 3.9. Friends, rabbis, and family members were the most common influencers of the decision to receive screening. People who were older, had a history of pregnancy, and had been previously screened were more likely to educate others (all p influencers who then encouraged screening in the target population. Educating influencers and increasing overall awareness were the most effective outreach strategies.

Advances in preimplantation genetic diagnosis/screening.

Science.gov (United States)

Yan, LiYing; Wei, Yuan; Huang, Jin; Zhu, XiaoHui; Shi, XiaoDan; Xia, Xi; Yan, Jie; Lu, CuiLing; Lian, Ying; Li, Rong; Liu, Ping; Qiao, Jie

2014-07-01

Preimplantation genetic diagnosis (PGD) gives couples who have a high risk of transmitting genetic disorders to their baby the chance to have a healthy offspring through embryo genetic analysis and selection. Preimplantation genetic screening (PGS) is an effective method to select euploid embryos that may prevent repeated implantation failure or miscarriage. However, how and to whom PGS should be provided is a controversial topic. The first successful case of PGD of a human being was reported in 1990, and there have been tremendous improvements in this technology since then. Both embryo biopsy and genetic technologies have been improved dramatically, which increase the accuracy and expand the indications of PGD/PGS.

Molecular genetic studies on obligate anaerobic bacteria

International Nuclear Information System (INIS)

Woods, D.R.

1982-01-01

Molecular genetic studies on obligate anaerobic bacteria have lagged behind similar studies in aerobes. However, the current interest in biotechnology, the involvement of anaerobes in disease and the emergence of antibioticresistant strains have focused attention on the genetics of anaerobes. This article reviews molecular genetic studies in Bacteroides spp., Clostridium spp. and methanogens. Certain genetic systems in some anaerobes differ from those in aerobes and illustrate the genetic diversity among bacteria

Teaching molecular genetics: Chapter 1--Background principles and methods of molecular biology.

Science.gov (United States)

Knoers, Nine V A M; Monnens, Leo A H

2006-02-01

In this first chapter of the series "Teaching molecular genetics," an introduction to molecular genetics is presented. We describe the structure of DNA and genes and explain in detail the central dogma of molecular biology, that is, the flow of genetic information from DNA via RNA to polypeptide (protein). In addition, several basic and frequently used general molecular tools, such as restriction enzymes, Southern blotting, DNA amplification and sequencing are discussed, in order to lay the foundations for the forthcoming chapters.

Molecular Genetic Identification Of Some Flax Mutants

International Nuclear Information System (INIS)

AMER, I.M.; MOUSTAFA, H.A.M.

2009-01-01

Five flax genotypes (Linum usitatissimum L.) i.e., commercial cultivar Sakha 2, the mother variety Giza 4 and three mutant types induced by gamma rays, were screened for their salinity tolerance in field experiments (salinity concentration was 8600 and 8300 ppm for soil and irrigation water, respectively). Mutation 6 was the most salt tolerant as compared to the other four genotypes.RAPD technique was used to detect some molecular markers associated with salt tolerance in flax (Mut 6), RAPD-PCR results using 12 random primers exhibited 149 amplified fragments; 91.9% of them were polymorphic and twelve molecular markers (8.1%) for salt tolerant (mutant 6) were identified with molecular size ranged from 191 to 4159 bp and only eight primers successes to amplify these specific markers. Concerning the other mutants, Mut 15 and Mut 25 exhibited 4.3% and 16.2% specific markers, respectively. The induced mutants exhibited genetic similarity to the parent variety were about 51%, 58.3% and 61.1% for Mut 25, Mut 6 and Mut 15, respectively. These specific markers (SM) are used for identification of the induced mutations and it is important for new variety registration.

Cystic fibrosis, molecular genetics for all life

Directory of Open Access Journals (Sweden)

Ausilia Elce

2015-10-01

Full Text Available Cystic fibrosis (CF is the most frequent lethal autosomal recessive disorder among Caucasians (incidence: 1:2,500 newborn. In the last two decades CF prognosis considerably improved and many patients well survive into their adulthood. Furthermore, milder CF with a late onset was described. CF is a challenge for laboratory of molecular genetics that greatly contributes to the natural history of the disease since fetal age. Carrier screening and prenatal diagnosis, also by non-invasive analysis of maternal blood fetal DNA, are now available, and many labs offer preimplantation diagnosis. The major criticism in prenatal medicine is the lack of an effective multidisciplinary counseling that helps the couples to plan their reasoned reproductive choice. Most countries offer newborn screening that significantly reduce CF morbidity but different protocols based on blood trypsin, molecular analysis and sweat chloride cause a variable efficiency of the screening programs. Again, laboratory is crucial for CF diagnosis in symptomatic patients: sweat chloride is the diagnostic golden standard, but different methodologies and the lack of quality control in most labs reduce its effectiveness. Molecular analysis contributes to confirm diagnosis in symptomatic subjects; furthermore, it helps to predict the disease outcome on the basis of the mutation (genotype-phenotype correlation and mutations in a myriad of genes, inherited independently by CF transmembrane conductance regulator (CFTR, which may modulate the clinical expression of the disease in each single patient (modifier genes. More recently, the search of the CFTR mutations gained a role in selecting CF patients that may benefit from biological therapy based on correctors and potentiators that are effective in patients bearing specific mutations (personalized therapy. All such applications of molecular diagnostics confirm the “uniqueness” of each CF patient, offering to laboratory medicine the

Molecular genetics: Step by step implementation in maize breeding

Directory of Open Access Journals (Sweden)

Konstantinov Kosana

2007-01-01

Full Text Available Efficiency in plant breeding is determined primarily by the ability to screen for genetic polymorphism, productivity and yield stability early in program. Dependent on the knowledge about the biochemical bases of the trait and nature of its genetic control, trait could be modified either through mutagenesis of genes controlling it or through the transfer of already existing mutant genes, controlling desired trait to different plant genotypes by classic crossing. Objective of this report is to present partly results on the investigation of the possibilities to apply ionizing radiations (fast neutrons, γ -rays and chemical mutagens (EI, iPMS, EMS, ENU to get maize and wheat mutants with increased amount and improved protein quality. Besides this approach in mutation breeding, results on the very early investigation of biochemical background of opaque -2 mutation including use of coupled cell - free RNA and protein synthesis containing components from both wild and opaque - 2 maize genotypes (chromatin, RNA polymerase, microsomall fraction, protein bodies will be presented. Partial results on opaque - 2 gene incorporation in different genetic background are reviewed. Part of report is dealing with different classes of molecular markers (proteins, RFLP, AFLP, RAPD, and SSR application in maize genome polymorphism investigation. Besides application of different molecular markers classes in the investigation of heterosis phenomena they are useful in biochemical pathway of important traits control determination as well. .

[Clinical genealogical and molecular genetic study of patients with mental retardation].

Science.gov (United States)

Hryshchenko, N V; B'ichkova, A M; Lyvshyts, A B; Kravchenko, S A; Pampukha, V N; Solov'ev, A A; Kucherenko, A M; Tatarskiĭ, P F; Afanas'eva, N A; Dubrovskaia, E V; Patskun, Ie Y; Zymak-Zakutnaia, N O; Nykytchina, T V; Lohysh, S Iu; Lyvshyts, L A

2012-01-01

The results of clinical, genealogical, cytogenetic and molecular genetic studies of 113 patients from 96 families with different forms of mental retardation from Ukraine are presented. This study was held as part of the CHERISH project of the 7-th Framework Program. The aim of the project is to improve diagnostics of mental retardation in children in Eastern Europe and Central Asia through detailed analysis of known chromosomal and gene's aberrations and to find the new gene-candidates that cause mental retardation. All patients have normal chromosome number (46XY or 46XX). The cases with fragile-X syndrome were eliminated using molecular genetic methods. Genome rearrangements were found among 28 patients using cytogenetic analysis, multiplex ligation-dependent probe amplification (MLPA analysis) ofsubtelomeric regions and array-based comparative genomic hybridisation (array CGH screening). In 10 cases known pathogenic CNV's were identified, 11 cases are unknown aberrations; their pathogenicity is being determined. The rest cases are known nonpathogenic gene rearrangements. Obtained results show the strong genetic heterogeneity of hereditary forms of mental retardation. The further studies will allow to identificate genes candidates and certain mutations in these genes that may be associated with this pathology.

Stigmatization of carrier status: social implications of heterozygote genetic screening programs.

Science.gov (United States)

Kenen, R H; Schmidt, R M

1978-01-01

Possible latent psychological and social consequences ensuing from genetic screening programs need to be investigated during the planning phase of national genetic screening programs. The relatively few studies which have been performed to determine psychological, social, and economic consequences resulting from a genetic screening program are reviewed. Stigmatization of carrier-status, having major psychosocial implications in heterozygote genetic screening programs, is discussed and related to Erving Goffman's work in the area of stigmatization. Questions are raised regarding the relationship between such variables as religiosity and sex of the individual and acceptance of the status of newly identified carrier of a mutant gene. Severity of the deleterious gene and visibility of the carrier status are two important factors to consider in an estimation of potential stigma. Specific implications are discussed for four genetic diseases: Tay-Sachs, Sickle-Cell Anemia, Huntington's disease and Hemophilia. PMID:152585

Neonatal Screening: Some Ethical Issues of Expanding Spectrum for Genetically Determined Diseases

Directory of Open Access Journals (Sweden)

S. S. Deryabina

2015-01-01

Full Text Available The article considers philosophical questions of neonatal screening technology. The main focus is on ethical and methodological issues that inevitably arise when expanding the number of scanned nosologies and applying genetic research methods. Questions concerning the existing discrepancy between technical capacity and the practical level of healthcare delivery and the probabilistic nature of results obtained by molecular testing are analyzed in terms of methodology. Access to information about the DNA-testing of newborns and the linkage between neonatal screening and prenatal diagnostics are among the most topical ethical problems raised within this article. One of the purposes of this article is to draw the attention of the public — especially it concerns current and prospective parents and volunteer organizations — to these contemporary problems.

Molecular and genetic epidemiology of cancer in low- and medium-income countries.

Science.gov (United States)

Malhotra, Jyoti

2014-01-01

Genetic and molecular factors can play an important role in an individual's cancer susceptibility and response to carcinogen exposure. Cancer susceptibility and response to carcinogen exposure can be either through inheritance of high penetrance but rare germline mutations that constitute heritable cancer syndromes, or it can be inherited as common genetic variations or polymorphisms that are associated with low to moderate risk for development of cancer. These polymorphisms can interact with environmental exposures and can influence an individual's cancer risk through multiple pathways, including affecting the rate of metabolism of carcinogens or the immune response to these toxins. Thus, these genetic polymorphisms can account for some of the geographical differences seen in cancer prevalence between different populations. This review explores the role of molecular epidemiology in the field of cancer prevention and control in low- and medium-income countries. Using data from Human Genome Project and HapMap Project, genome-wide association studies have been able to identify multiple susceptibility loci for different cancers. The field of genetic and molecular epidemiology has been further revolutionized by the discovery of newer, faster, and more efficient DNA-sequencing technologies including next-generation sequencing. The new DNA-sequencing technologies can play an important role in planning and implementation of cancer prevention and screening strategies. More research is needed in this area, especially in investigating new biomarkers and measuring gene-environment interactions. Copyright © 2014 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.

Molecular genetic researches on the radiation genetics of Drosophila in JINR

International Nuclear Information System (INIS)

Afanas'eva, K.P.; Aleksandrova, M.V.; Aleksandrov, I.D.

2016-01-01

Molecular genetic studies of radiation-induced heritable DNA lesions are carried out by the genetic group of Laboratory of nuclear problem in Joint Institute for Nuclear Research. The first results of molecular analysis of γ –ray- and neutron-induced vestigial mutations using PCR and sequencing will be presented. (authors)

Is high pressure liquid chromatography an effective screening tool for characterization of molecular defects in hemoglobinopathies?

Directory of Open Access Journals (Sweden)

Nikhil Moorchung

2013-01-01

Full Text Available Introduction: Hemoglobinopathies constitute entities that are generated by either abnormal hemoglobin or thalassemias. high pressure liquid chromatography (HPLC is one of the best methods for screening and detection of various hemoglobinopathies but it has intrinsic interpretive problems. The study was designed to evaluate the different mutations seen in cases of hemoglobinopathies and compare the same with screening tests. Materials and Methods: 68 patients of hemoglobinopathies were screened by HPLC. Mutation studies in the beta globin gene was performed using the polymerase chain reaction (PCR-based allele-specific Amplification Refractory Mutation System (ARMS. Molecular analysis for the sickle cell mutation was done by standard methods. Results: The IVS 1/5 mutation was the commonest mutation seen and it was seen in 26 (38.23% of the cases. This was followed by the IVS 1/1, codon 41/42, codon 8/9, del 22 mutation, codon 15 mutation and the -619 bp deletion. No mutation was seen in eight cases. There was a 100% concordance between the sickle cell trait as diagnosed by HPLC and genetic testing. Discussion and Conclusion: Our study underlies the importance of molecular testing in all cases of hemoglobinopathies. Although HPLC is a useful screening tool, molecular testing is very useful in accurately diagnosing the mutations. Molecular testing is especially applicable in cases with an abnormal hemoglobin (HbD, HbE and HbS because there may be a concomitant inheritance of a beta thalassemia mutation. Molecular testing is the gold standard when it comes to the diagnosis of hemoglobinopathies.

Toward forward genetic screens in malaria-causing parasites using the piggyBac transposon

Directory of Open Access Journals (Sweden)

de Koning-Ward Tania F

2011-03-01

Full Text Available Abstract The ability to analyze gene function in malaria-causing Plasmodium parasites has received a boost with a recent paper in BMC Genomics that describes a genome-wide mutagenesis system in the rodent malaria species Plasmodium berghei using the transposon piggyBac. This advance holds promise for identifying and validating new targets for intervention against malaria. But further improvements are still needed for the full power of genome-wide molecular genetic screens to be utilized in this organism. See research article: http://www.biomedcentral.com/1471-2164/12/155

Multiplex Polymerase Chain Reaction for Identification of Shigellae and Four Shigella Species Using Novel Genetic Markers Screened by Comparative Genomics.

Science.gov (United States)

Kim, Hyun-Joong; Ryu, Ji-Oh; Song, Ji-Yeon; Kim, Hae-Yeong

2017-07-01

In the detection of Shigella species using molecular biological methods, previously known genetic markers for Shigella species were not sufficient to discriminate between Shigella species and diarrheagenic Escherichia coli. The purposes of this study were to screen for genetic markers of the Shigella genus and four Shigella species through comparative genomics and develop a multiplex polymerase chain reaction (PCR) for the detection of shigellae and Shigella species. A total of seven genomic DNA sequences from Shigella species were subjected to comparative genomics for the screening of genetic markers of shigellae and each Shigella species. The primer sets were designed from the screened genetic markers and evaluated using PCR with genomic DNAs from Shigella and other bacterial strains in Enterobacteriaceae. A novel Shigella quintuplex PCR, designed for the detection of Shigella genus, S. dysenteriae, S. boydii, S. flexneri, and S. sonnei, was developed from the evaluated primer sets, and its performance was demonstrated with specifically amplified results from each Shigella species. This Shigella multiplex PCR is the first to be reported with novel genetic markers developed through comparative genomics and may be a useful tool for the accurate detection of the Shigella genus and species from closely related bacteria in clinical microbiology and food safety.

Pathogenesis of Gastric Cancer: Genetics and Molecular Classification.

Science.gov (United States)

Figueiredo, Ceu; Camargo, M C; Leite, Marina; Fuentes-Pananá, Ezequiel M; Rabkin, Charles S; Machado, José C

Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance. Comprehensive molecular analyses of gastric cancer have disclosed the complex heterogeneity of this disease. In particular, these analyses have confirmed that Epstein-Barr virus (EBV)-positive gastric cancer is a distinct entity. The identification of gastric cancer subtypes characterized by recognizable molecular profiles may pave the way for a more personalized clinical management and to the identification of novel therapeutic targets and biomarkers for screening, prognosis, prediction of response to treatment, and monitoring of gastric cancer progression.

Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy

Science.gov (United States)

2015-10-01

AWARD NUMBER: W81XWH-14-1-0399 TITLE: Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy PRINCIPAL INVESTIGATOR: John F...Include area code) October 2015 Annual Report 30 Sep 2014 - 29 Sep 2015 Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy John... encephalopathy (CTE), but the underlying molecular changes remain unclear. Here, biochemical and genetic studies that deepen our understanding of the

Carrier screening in the era of expanding genetic technology.

Science.gov (United States)

Arjunan, Aishwarya; Litwack, Karen; Collins, Nick; Charrow, Joel

2016-12-01

The Center for Jewish Genetics provides genetic education and carrier screening to individuals of Jewish descent. Carrier screening has traditionally been performed by targeted mutation analysis for founder mutations with an enzyme assay for Tay-Sachs carrier detection. The development of next-generation sequencing (NGS) allows for higher detection rates regardless of ethnicity. Here, we explore differences in carrier detection rates between genotyping and NGS in a primarily Jewish population. Peripheral blood samples or saliva samples were obtained from 506 individuals. All samples were analyzed by sequencing, targeted genotyping, triplet-repeat detection, and copy-number analysis; the analyses were carried out at Counsyl. Of 506 individuals screened, 288 were identified as carriers of at least 1 condition and 8 couples were carriers for the same disorder. A total of 434 pathogenic variants were identified. Three hundred twelve variants would have been detected via genotyping alone. Although no additional mutations were detected by NGS in diseases routinely screened for in the Ashkenazi Jewish population, 26.5% of carrier results and 2 carrier couples would have been missed without NGS in the larger panel. In a primarily Jewish population, NGS reveals a larger number of pathogenic variants and provides individuals with valuable information for family planning.Genet Med 18 12, 1214-1217.

Private and public eugenics: genetic and screening in India

NARCIS (Netherlands)

Gupta, J.A.

2007-01-01

Epidemiologists and geneticists claim that genetics has an increasing role to play in public health policies and programs in the future. Within this perspective, genetic testing and screening are instrumental in avoiding the birth of children with serious, costly or untreatable disorders. This paper

Cellular and molecular modifier pathways in tauopathies: the big picture from screening invertebrate models.

Science.gov (United States)

Hannan, Shabab B; Dräger, Nina M; Rasse, Tobias M; Voigt, Aaron; Jahn, Thomas R

2016-04-01

Abnormal tau accumulations were observed and documented in post-mortem brains of patients affected by Alzheimer's disease (AD) long before the identification of mutations in the Microtubule-associated protein tau (MAPT) gene, encoding the tau protein, in a different neurodegenerative disease called Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). The discovery of mutations in the MAPT gene associated with FTDP-17 highlighted that dysfunctions in tau alone are sufficient to cause neurodegeneration. Invertebrate models have been diligently utilized in investigating tauopathies, contributing to the understanding of cellular and molecular pathways involved in disease etiology. An important discovery came with the demonstration that over-expression of human tau in Drosophila leads to premature mortality and neuronal dysfunction including neurodegeneration, recapitulating some key neuropathological features of the human disease. The simplicity of handling invertebrate models combined with the availability of a diverse range of experimental resources make these models, in particular Drosophila a powerful invertebrate screening tool. Consequently, several large-scale screens have been performed using Drosophila, to identify modifiers of tau toxicity. The screens have revealed not only common cellular and molecular pathways, but in some instances the same modifier has been independently identified in two or more screens suggesting a possible role for these modifiers in regulating tau toxicity. The purpose of this review is to discuss the genetic modifier screens on tauopathies performed in Drosophila and C. elegans models, and to highlight the common cellular and molecular pathways that have emerged from these studies. Here, we summarize results of tau toxicity screens providing mechanistic insights into pathological alterations in tauopathies. Key pathways or modifiers that have been identified are associated with a broad range of processes

Guidelines on the use of molecular genetics in reintroduction programs

Science.gov (United States)

Michael K. Schwartz

2005-01-01

The use of molecular genetics can play a key role in reintroduction efforts. Prior to the introduction of any individuals, molecular genetics can be used to identify the most appropriate source population for the reintroduction, ensure that no relic populations exist in the reintroduction area, and guide captive breeding programs. The use of molecular genetics post-...

Application of molecular genetic tools for forest pathology

Science.gov (United States)

Mee-Sook Kim; John Hanna; Amy Ross-Davis; Ned Klopfenstein

2012-01-01

In recent years, advances in molecular genetics have provided powerful tools to address critical issues in forest pathology to help promote resilient forests. Although molecular genetic tools are initially applied to understand individual components of forest pathosystems, forest pathosystems involve dynamic interactions among biotic and abiotic components of the...

A Report on Molecular Diagnostic Testing for Inherited Retinal Dystrophies by Targeted Genetic Analyses.

Science.gov (United States)

Ramkumar, Hema L; Gudiseva, Harini V; Kishaba, Kameron T; Suk, John J; Verma, Rohan; Tadimeti, Keerti; Thorson, John A; Ayyagari, Radha

2017-02-01

To test the utility of targeted sequencing as a method of clinical molecular testing in patients diagnosed with inherited retinal degeneration (IRD). After genetic counseling, peripheral blood was drawn from 188 probands and 36 carriers of IRD. Single gene testing was performed on each patient in a Clinical Laboratory Improvement Amendment (CLIA) certified laboratory. DNA was isolated, and all exons in the gene of interest were analyzed along with 20 base pairs of flanking intronic sequence. Genetic testing was most often performed on ABCA4, CTRP5, ELOV4, BEST1, CRB1, and PRPH2. Pathogenicity of novel sequence changes was predicted by PolyPhen2 and sorting intolerant from tolerant (SIFT). Of the 225 genetic tests performed, 150 were for recessive IRD, and 75 were for dominant IRD. A positive molecular diagnosis was made in 70 (59%) of probands with recessive IRD and 19 (26%) probands with dominant IRD. Analysis confirmed 12 (34%) of individuals as carriers of familial mutations associated with IRD. Thirty-two novel variants were identified; among these, 17 sequence changes in four genes were predicted to be possibly or probably damaging including: ABCA4 (14), BEST1 (2), PRPH2 (1), and TIMP3 (1). Targeted analysis of clinically suspected genes in 225 subjects resulted in a positive molecular diagnosis in 26% of patients with dominant IRD and 59% of patients with recessive IRD. Novel damaging mutations were identified in four genes. Single gene screening is not an ideal method for diagnostic testing given the phenotypic and genetic heterogeneity among IRD cases. High-throughput sequencing of all genes associated with retinal degeneration may be more efficient for molecular diagnosis.

Preimplantation genetic screening: back to the future

NARCIS (Netherlands)

Mastenbroek, Sebastiaan; Repping, Sjoerd

2014-01-01

All agree that in hindsight the rapid adoption of preimplantation genetic screening (PGS) using cleavage stage biopsy and fluorescence in situ hybridization (FISH) in routine clinical practice without proper evaluation of (cost-)effectiveness basically resulted in couples paying more money for a

Molecular marker systems for Oenothera genetics.

Science.gov (United States)

Rauwolf, Uwe; Golczyk, Hieronim; Meurer, Jörg; Herrmann, Reinhold G; Greiner, Stephan

2008-11-01

The genus Oenothera has an outstanding scientific tradition. It has been a model for studying aspects of chromosome evolution and speciation, including the impact of plastid nuclear co-evolution. A large collection of strains analyzed during a century of experimental work and unique genetic possibilities allow the exchange of genetically definable plastids, individual or multiple chromosomes, and/or entire haploid genomes (Renner complexes) between species. However, molecular genetic approaches for the genus are largely lacking. In this study, we describe the development of efficient PCR-based marker systems for both the nuclear genome and the plastome. They allow distinguishing individual chromosomes, Renner complexes, plastomes, and subplastomes. We demonstrate their application by monitoring interspecific exchanges of genomes, chromosome pairs, and/or plastids during crossing programs, e.g., to produce plastome-genome incompatible hybrids. Using an appropriate partial permanent translocation heterozygous hybrid, linkage group 7 of the molecular map could be assigned to chromosome 9.8 of the classical Oenothera map. Finally, we provide the first direct molecular evidence that homologous recombination and free segregation of chromosomes in permanent translocation heterozygous strains is suppressed.

Counselling considerations for chromosomal mosaicism detected by preimplantation genetic screening.

Science.gov (United States)

Besser, Andria G; Mounts, Emily L

2017-04-01

The evolution of preimplantation genetic screening (PGS) for aneuploidy to blastocyst biopsy and more sensitive 24-chromosome screening techniques has resulted in a new diagnostic category of PGS results: those classified as mosaic. This diagnosis presents significant challenges for clinicians in developing policies regarding transfer and storage of such embryos, as well as in providing genetic counselling for patients prior to and following PGS. Given the high frequency of mosaic PGS results and the wide range of possible associated outcomes, there is an urgent need to understand how to appropriately counsel patients regarding such embryos. This is the first commentary to thoroughly address pre- and post-test genetic counselling recommendations, as well as considerations regarding prenatal screening and diagnosis. Current data on mosaic PGS results are summarized along with embryo selection considerations and potential outcomes of embryos diagnosed as mosaic. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Molecular genetic mutation analysis in Menkes-disease with prenatal diagnosis

DEFF Research Database (Denmark)

László, Aranka; Endreffy, Emoke; Tümer, Zeynep

2010-01-01

Menkes disease (MD) is an X-linked recessive multisystemic lethal, heredodegenerative disorder. Progressive neurodegeneration and connective tissue disturbances with microscopically kinky hair are the main symptoms. Molecular genetic mutation analysis was made at a Hungarian male infant suffering...... from MD and prenatal diagnosis was done in this MD loaded family. METHOD: The 12th exon of ATP7A gene has been analyzed by dideoxy-finger printing (DDF), polymerase chain reaction (PCR), direct sequencing of exon 12. The specific mutation was screened from chorionic villi of the maternal aunt at the 14......th gestational week. RESULTS: In the exon 12th a basic pair substitution with Arg 844 His change was detected leading to very severe fatal missense mutation....

What next for preimplantation genetic screening? A polar body approach!

NARCIS (Netherlands)

Geraedts, Joep; Collins, John; Gianaroli, Luca; Goossens, Veerle; Handyside, Alan; Harper, Joyce; Montag, Markus; Repping, Sjoerd; Schmutzler, Andreas

2010-01-01

Screening of human preimplantation embryos for numerical chromosome abnormalities has been conducted mostly at the preimplantation stage using fluorescence in situ hybridization. However, it is clear that preimplantation genetic screening (PGS) as it is currently practiced does not improve live

Child Development and Molecular Genetics: 14 Years Later

Science.gov (United States)

Plomin, Robert

2013-01-01

Fourteen years ago, the first article on molecular genetics was published in this journal: "Child Development, Molecular Genetics, and What to Do With Genes Once They Are Found" (R. Plomin & M. Rutter, 1998). The goal of the article was to outline what developmentalists can do with genes once they are found. These new directions for developmental…

Changes in screening behaviors and attitudes toward screening from pre-test genetic counseling to post-disclosure in Lynch syndrome families

Science.gov (United States)

Burton-Chase, Allison M.; Hovick, Shelly R.; Peterson, Susan K.; Marani, Salma K.; Vernon, Sally W.; Amos, Christopher I.; Frazier, Marsha L.; Lynch, Patrick M.; Gritz, Ellen R.

2013-01-01

Purpose This study examined colonoscopy adherence and attitudes towards colorectal cancer (CRC) screening in individuals who underwent Lynch syndrome genetic counseling and testing. Methods We evaluated changes in colonoscopy adherence and CRC screening attitudes in 78 cancer-unaffected relatives of Lynch syndrome mutation carriers before pre-test genetic counseling (baseline) and at 6 and 12 months post-disclosure of test results (52 mutation-negative, 26 mutation-positive). Results While both groups were similar at baseline, at 12 months post-disclosure, a greater number of mutation-positive individuals had had a colonoscopy compared with mutation-negative individuals. From baseline to 12 months post-disclosure, the mutation-positive group demonstrated an increase in mean scores on measures of colonoscopy commitment, self-efficacy, and perceived benefits of CRC screening, and a decrease in mean scores for perceived barriers to CRC screening. Mean scores on colonoscopy commitment decreased from baseline to 6 months in the mutation-negative group. Conclusion Adherence to risk-appropriate guidelines for CRC surveillance improved after genetic counseling and testing for Lynch syndrome. Mutation-positive individuals reported increasingly positive attitudes toward CRC screening after receiving genetic test results, potentially reinforcing longer term colonoscopy adherence. PMID:23414081

Integrated screening concept in women with genetic predisposition for breast cancer

International Nuclear Information System (INIS)

Bick, U.

1997-01-01

Breast cancer is in 5% of cases due to a genetic disposition. BRCA1 and BRCA2 are by far the most common breast cancer susceptibility genes. For a woman with a genetic predisposition, the individual risk of developing breast cancer sometime in her life is between 70 and 90%. Compared to the spontaneous forms of breast cancer, woman with a genetic predisposition often develop breast cancer at a much younger age. This is why conventional screening programs on the basis of mammography alone cannot be applied without modification to this high-risk group. In this article, an integrated screening concept for women with genetic prodisposition for breast cancer using breast self-examination, clinical examination, ultrasound, mammography and magnetic resonance imaging is introduced. (orig.) [de

Genética, biologia molecular e ética: as relações trabalho e saúde Genetics, molecular biology and ethics: work and health connections

Directory of Open Access Journals (Sweden)

Gilka Jorge Figaro Gattás

2002-01-01

Full Text Available O artigo discute o impacto dos avanços da genética e da biologia molecular sobre a prática em saúde ocupacional. O conhecimento atual sobre o genoma humano permite, em certas circunstâncias, identificar fatores individuais de suscetibilidade a doenças em situações de exposição a substâncias químicas ou físicas, ou ainda, a doenças genéticas de manifestação tardia. Estudos epidemiológicos incorporando elementos da genética e da biologia molecular têm sido desenhados para avaliar a interação de variantes metabólicas e exposições ambientais no risco de ocorrência de diferentes doenças. Apesar desta perspectiva, considera-se que as pesquisas nesta área são ainda incipientes. A estratégia para a redução dos danos causados à saúde do trabalhador deve continuar a ter como base, prioritariamente, a modificação e a adequação dos ambientes de trabalho e não a especificação genética da força de trabalho. Introduzir a discussão sobre a necessidade de definir princípios de responsabilidade social no uso de informações genéticas e que possam reger ações éticas em saúde do trabalhador é uma das propostas principais deste artigo.This paper provides a discussion about the increasing development of genetics and molecular biomarkers technologies and consequent impact on practices of occupational health. Genetic analysis could be in specific populations at occupational, pharmacological or environmental exposures. Current knowledge of human genome open up the possibility of individual genetic screening of disease susceptibility among those exposed in workplaces to chemical or physical hazards, or for late onset hereditary disease. Epidemiological studies including genetic and molecular biology approaches have been designed to evaluate the interaction of genetically determined metabolic variants with different environmental exposures on the risk of diseases. The strategy for worker's health promotion must be

Complementary genetic screens identify the E3 ubiquitin ligase CBLC, as a modifier of PARP inhibitor sensitivity

Czech Academy of Sciences Publication Activity Database

Frankum, J.; Moudrý, P.; Brough, R.; Hodný, Zdeněk; Ashworth, A.; Bartek, Jiří; Lord, C.J.

2015-01-01

Roč. 6, č. 13 (2015), s. 10746-10758 ISSN 1949-2553 R&D Projects: GA ČR GA13-17555S EU Projects: European Commission HEALTH-F2-2010-259893 Grant - others:Lundbeck Foundation(DK) R93-A8990; Danish Council for Independent Research(DK) DFF-1331-00262 Institutional support: RVO:68378050 Keywords : DNA damage response * ubiquitin-proteasome system * RNA interference screens * PARP inhibitors * CBLC Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.008, year: 2015

Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.

Directory of Open Access Journals (Sweden)

Mohan Babu

2014-02-01

Full Text Available Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI screens can provide insights into the biological role(s of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.

Rapid recombination mapping for high-throughput genetic screens in Drosophila.

Science.gov (United States)

Sapiro, Anne L; Ihry, Robert J; Buhr, Derek L; Konieczko, Kevin M; Ives, Sarah M; Engstrom, Anna K; Wleklinski, Nicholas P; Kopish, Kristin J; Bashirullah, Arash

2013-12-09

Mutagenesis screens are a staple of classical genetics. Chemical-induced mutations, however, are often difficult and time-consuming to identify. Here, we report that recombination analysis with pairs of dominant visible markers provides a rapid and reliable strategy to map mutations in Drosophila melanogaster. This method requires only two generations and a total of six crosses in vials to estimate the genetic map position of the responsible lesion with high accuracy. This genetic map position can then be reliably used to identify the mutated gene through complementation testing with an average of nine deficiencies and Sanger sequencing. We have used this approach to successfully map a collection of mutations from an ethyl methanesulfonate-based mutagenesis screen on the third chromosome. We propose that this method also may be used in conjunction with whole-genome sequencing, particularly when multiple independent alleles of the mutated locus are not available. By facilitating the rapid identification of mutated genes, our mapping strategy removes a primary obstacle to the widespread use of powerful chemical mutagenesis screens to understand fundamental biological phenomena.

Molecular Genetic Methods Implementation for Phytopathogen Identification in Forest Stands and Nurseries of the Russian Federation

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T. S. Alimova

2014-08-01

Full Text Available The results of the application of molecular genetics methods for the analysis of the plant pathogens present in forest plantations and nurseries of the Russian Federation, including doughnut fungus and annosum root rot are presented. The prospects and benefits of using DNA analysis for early diagnosis of plant diseases without isolation of the pathogen in pure culture, shortening time of analysis, and the possibility of mass screening are discussed.

Advances in genetics. Volume 22: Molecular genetics of plants

International Nuclear Information System (INIS)

Scandalios, J.G.; Caspari, E.W.

1984-01-01

This book contains the following four chapters: Structural Variation in Mitochondrial DNA; The Structure and Expression of Nuclear Genes in Higher Plants; Chromatin Structure and Gene Regulation in Higher Plants; and The Molecular Genetics of Crown Gall Tumorigenesis

The Molecular Genetics of von Willebrand Disease

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Ergül Berber

2012-12-01

Full Text Available Quantitative and/or qualitative deficiency of von Willebrand factor (vWF is associated with the most common inherited bleeding disease von Willebrand disease (vWD. vWD is a complex disease with clinical and genetic heterogeneity. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD also has a complex molecular pathogenesis. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD.

The molecular genetics of von Willebrand disease.

Science.gov (United States)

Berber, Ergül

2012-12-01

Quantitative and/or qualitative deficiency of von Willebrand factor (vWF) is associated with the most common inherited bleeding disease von Willebrand disease (vWD). vWD is a complex disease with clinical and genetic heterogeneity. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD also has a complex molecular pathogenesis. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD. None declared.

Classification of rare missense substitutions, using risk surfaces, with genetic- and molecular-epidemiology applications.

Science.gov (United States)

Tavtigian, Sean V; Byrnes, Graham B; Goldgar, David E; Thomas, Alun

2008-11-01

Many individually rare missense substitutions are encountered during deep resequencing of candidate susceptibility genes and clinical mutation screening of known susceptibility genes. BRCA1 and BRCA2 are among the most resequenced of all genes, and clinical mutation screening of these genes provides an extensive data set for analysis of rare missense substitutions. Align-GVGD is a mathematically simple missense substitution analysis algorithm, based on the Grantham difference, which has already contributed to classification of missense substitutions in BRCA1, BRCA2, and CHEK2. However, the distribution of genetic risk as a function of Align-GVGD's output variables Grantham variation (GV) and Grantham deviation (GD) has not been well characterized. Here, we used data from the Myriad Genetic Laboratories database of nearly 70,000 full-sequence tests plus two risk estimates, one approximating the odds ratio and the other reflecting strength of selection, to display the distribution of risk in the GV-GD plane as a series of surfaces. We abstracted contours from the surfaces and used the contours to define a sequence of missense substitution grades ordered from greatest risk to least risk. The grades were validated internally using a third, personal and family history-based, measure of risk. The Align-GVGD grades defined here are applicable to both the genetic epidemiology problem of classifying rare missense substitutions observed in known susceptibility genes and the molecular epidemiology problem of analyzing rare missense substitutions observed during case-control mutation screening studies of candidate susceptibility genes. (c) 2008 Wiley-Liss, Inc.

Genetic screens to identify new Notch pathway mutants in Drosophila.

Science.gov (United States)

Giagtzoglou, Nikolaos

2014-01-01

Notch signaling controls a wide range of developmental processes, including proliferation, apoptosis, and cell fate specification during both development and adult tissue homeostasis. The functional versatility of the Notch signaling pathway is tightly linked with the complexity of its regulation in different cellular contexts. To unravel the complexity of Notch signaling, it is important to identify the different components of the Notch signaling pathway. A powerful strategy to accomplish this task is based on genetic screens. Given that the developmental context of signaling is important, these screens should be customized to specific cell populations or tissues. Here, I describe how to perform F1 clonal forward genetic screens in Drosophila to identify novel components of the Notch signaling pathway. These screens combine a classical EMS (ethyl methanesulfonate) chemical mutagenesis protocol along with clonal analysis via FRT-mediated mitotic recombination. These F1 clonal screens allow rapid phenotypic screening within clones of mutant cells induced at specific developmental stages and in tissues of interest, bypassing the pleiotropic effects of isolated mutations. More importantly, since EMS mutations have been notoriously difficult to map to specific genes in the past, I briefly discuss mapping methods that allow rapid identification of the causative mutations.

Molecular genetic studies in flax (Linum usitatissimum L.)

NARCIS (Netherlands)

Vromans, J.

2006-01-01

In this thesis five molecular genetic studies on flax ( Linum usitatissimum L.) are described, of which two chapters aim to characterize the genetic structure and the amount of genetic diversity in the primary and secondary gene pool of the crop species. Three chapters describe the development of

Molecular genetics of dyslexia: an overview.

Science.gov (United States)

Carrion-Castillo, Amaia; Franke, Barbara; Fisher, Simon E

2013-11-01

Dyslexia is a highly heritable learning disorder with a complex underlying genetic architecture. Over the past decade, researchers have pinpointed a number of candidate genes that may contribute to dyslexia susceptibility. Here, we provide an overview of the state of the art, describing how studies have moved from mapping potential risk loci, through identification of associated gene variants, to characterization of gene function in cellular and animal model systems. Work thus far has highlighted some intriguing mechanistic pathways, such as neuronal migration, axon guidance, and ciliary biology, but it is clear that we still have much to learn about the molecular networks that are involved. We end the review by highlighting the past, present, and future contributions of the Dutch Dyslexia Programme to studies of genetic factors. In particular, we emphasize the importance of relating genetic information to intermediate neurobiological measures, as well as the value of incorporating longitudinal and developmental data into molecular designs. Copyright © 2013 John Wiley & Sons, Ltd.

Assessing Date Palm Genetic Diversity Using Different Molecular Markers.

Science.gov (United States)

Atia, Mohamed A M; Sakr, Mahmoud M; Adawy, Sami S

2017-01-01

Molecular marker technologies which rely on DNA analysis provide powerful tools to assess biodiversity at different levels, i.e., among and within species. A range of different molecular marker techniques have been developed and extensively applied for detecting variability in date palm at the DNA level. Recently, the employment of gene-targeting molecular marker approaches to study biodiversity and genetic variations in many plant species has increased the attention of researchers interested in date palm to carry out phylogenetic studies using these novel marker systems. Molecular markers are good indicators of genetic distances among accessions, because DNA-based markers are neutral in the face of selection. Here we describe the employment of multidisciplinary molecular marker approaches: amplified fragment length polymorphism (AFLP), start codon targeted (SCoT) polymorphism, conserved DNA-derived polymorphism (CDDP), intron-targeted amplified polymorphism (ITAP), simple sequence repeats (SSR), and random amplified polymorphic DNA (RAPD) to assess genetic diversity in date palm.

Medical and lay attitudes towards genetic screening and testing in Finland

DEFF Research Database (Denmark)

Toiviainen, Hanna; Jallinoja, Piia; Aro, Arja R

2003-01-01

The purpose of this study was to compare physicians', midwives' and lay people's attitudes towards genetic screening and testing to find out whether medical education and experience influence attitudes of genetic screening and testing. The study was based on comparison of answers to joint questions...... in three different cross-sectional postal surveys between October 1996 and April 1998 in Finland. Target groups were physicians (study base n=772, response rate 74%, including gynaecologists, paediatricians, general practitioners and clinical geneticists), midwives and public health nurses (collectively...

Molecular characterization and assessment of genetic diversity of ...

African Journals Online (AJOL)

R Madhusudhana

genetic diversity available at molecular level among a set of phenotypically different ... allele matching and cluster analysis based on unweighted neighbor- joining (Gascuel, 1997) ..... on isozyme data-a simulation study. Theor. Appl. Genet.

Evaluating genetic ancestry and self-reported ethnicity in the context of carrier screening.

Science.gov (United States)

Shraga, Roman; Yarnall, Sarah; Elango, Sonya; Manoharan, Arun; Rodriguez, Sally Ann; Bristow, Sara L; Kumar, Neha; Niknazar, Mohammad; Hoffman, David; Ghadir, Shahin; Vassena, Rita; Chen, Serena H; Hershlag, Avner; Grifo, Jamie; Puig, Oscar

2017-11-28

Current professional society guidelines recommend genetic carrier screening be offered on the basis of ethnicity, or when using expanded carrier screening panels, they recommend to compute residual risk based on ethnicity. We investigated the reliability of self-reported ethnicity in 9138 subjects referred to carrier screening. Self-reported ethnicity gathered from test requisition forms and during post-test genetic counseling, and genetic ancestry predicted by a statistical model, were compared for concordance. We identified several discrepancies between the two sources of self-reported ethnicity and genetic ancestry. Only 30.3% of individuals who indicated Mediterranean ancestry during consultation self-reported this on requisition forms. Additionally, the proportion of individuals who reported Southeast Asian but were estimated to have a different genetic ancestry was found to depend on the source of self-report. Finally, individuals who reported Latin American demonstrated a high degree of ancestral admixture. As a result, carrier rates and residual risks provided for patient decision-making are impacted if using self-reported ethnicity. Our analysis highlights the unreliability of ethnicity classification based on patient self-reports. We recommend the routine use of pan-ethnic carrier screening panels in reproductive medicine. Furthermore, the use of an ancestry model would allow better estimation of carrier rates and residual risks.

Rapid Recombination Mapping for High-Throughput Genetic Screens in Drosophila

OpenAIRE

Sapiro, Anne L.; Ihry, Robert J.; Buhr, Derek L.; Konieczko, Kevin M.; Ives, Sarah M.; Engstrom, Anna K.; Wleklinski, Nicholas P.; Kopish, Kristin J.; Bashirullah, Arash

2013-01-01

Mutagenesis screens are a staple of classical genetics. Chemical-induced mutations, however, are often difficult and time-consuming to identify. Here, we report that recombination analysis with pairs of dominant visible markers provides a rapid and reliable strategy to map mutations in Drosophila melanogaster. This method requires only two generations and a total of six crosses in vials to estimate the genetic map position of the responsible lesion with high accuracy. This genetic map positio...

Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies

Directory of Open Access Journals (Sweden)

Serena Catarzi

2013-01-01

Full Text Available Medium-chain acyl-CoA dehydrogenase deficiency (MCADD is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS were confirmed by molecular analysis of the medium-chain acyl-CoA dehydrogenase (ACADM gene. Out of 324.000 newborns screened, we identified 14 MCADD patients, in whom, by molecular analysis, we found a new nonsense c.823G>T (p.Gly275* and two new missense mutations: c.253G>C (p.Gly85Arg and c.356T>A (p.Val119Asp. Bioinformatics predictions based on both phylogenetic conservation and functional/structural software were used to characterize the new identified variants. Our findings confirm the rising incidence of MCADD whose existence is increasingly recognized due to the efficacy of an expanded newborn screening panel by LC-MS/MS making possible early specific therapies that can prevent possible crises in at-risk infants. We noticed that the “common” p.Lys329Glu mutation only accounted for 32% of the defective alleles, while, in clinically diagnosed patients, this mutation accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs are especially critical when considering screening programs. The functional and pathogenic characterization of genetic variants presented here is required to predict their medical consequences in newborns.

Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies

Science.gov (United States)

Catarzi, Serena; Caciotti, Anna; Thusberg, Janita; Tonin, Rodolfo; Malvagia, Sabrina; la Marca, Giancarlo; Pasquini, Elisabetta; Cavicchi, Catia; Ferri, Lorenzo; Donati, Maria A.; Baronio, Federico; Guerrini, Renzo; Mooney, Sean D.; Morrone, Amelia

2013-01-01

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were confirmed by molecular analysis of the medium-chain acyl-CoA dehydrogenase (ACADM) gene. Out of 324.000 newborns screened, we identified 14 MCADD patients, in whom, by molecular analysis, we found a new nonsense c.823G>T (p.Gly275∗) and two new missense mutations: c.253G>C (p.Gly85Arg) and c.356T>A (p.Val119Asp). Bioinformatics predictions based on both phylogenetic conservation and functional/structural software were used to characterize the new identified variants. Our findings confirm the rising incidence of MCADD whose existence is increasingly recognized due to the efficacy of an expanded newborn screening panel by LC-MS/MS making possible early specific therapies that can prevent possible crises in at-risk infants. We noticed that the “common” p.Lys329Glu mutation only accounted for 32% of the defective alleles, while, in clinically diagnosed patients, this mutation accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs) are especially critical when considering screening programs. The functional and pathogenic characterization of genetic variants presented here is required to predict their medical consequences in newborns. PMID:24294134

Improving Molecular Genetic Test Utilization through Order Restriction, Test Review, and Guidance.

Science.gov (United States)

Riley, Jacquelyn D; Procop, Gary W; Kottke-Marchant, Kandice; Wyllie, Robert; Lacbawan, Felicitas L

2015-05-01

The ordering of molecular genetic tests by health providers not well trained in genetics may have a variety of untoward effects. These include the selection of inappropriate tests, the ordering of panels when the assessment of individual or fewer genes would be more appropriate, inaccurate result interpretation and inappropriate patient guidance, and significant unwarranted cost expenditure. We sought to improve the utilization of molecular genetic tests by requiring providers without specialty training in genetics to use genetic counselors and molecular genetic pathologists to assist in test selection. We used a genetic and genomic test review process wherein the laboratory-based genetic counselor performed the preanalytic assessment of test orders and test triage. Test indication and clinical findings were evaluated against the test panel composition, methods, and test limitations under the supervision of the molecular genetic pathologist. These test utilization management efforts resulted in a decrease in genetic test ordering and a gross cost savings of $1,531,913 since the inception of these programs in September 2011 through December 2013. The combination of limiting the availability of complex genetic tests and providing guidance regarding appropriate test strategies is an effective way to improve genetic tests, contributing to judicious use of limited health care resources. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Intelligent DNA-based molecular diagnostics using linked genetic markers

Energy Technology Data Exchange (ETDEWEB)

Pathak, D.K.; Perlin, M.W.; Hoffman, E.P.

1994-12-31

This paper describes a knowledge-based system for molecular diagnostics, and its application to fully automated diagnosis of X-linked genetic disorders. Molecular diagnostic information is used in clinical practice for determining genetic risks, such as carrier determination and prenatal diagnosis. Initially, blood samples are obtained from related individuals, and PCR amplification is performed. Linkage-based molecular diagnosis then entails three data analysis steps. First, for every individual, the alleles (i.e., DNA composition) are determined at specified chromosomal locations. Second, the flow of genetic material among the individuals is established. Third, the probability that a given individual is either a carrier of the disease or affected by the disease is determined. The current practice is to perform each of these three steps manually, which is costly, time consuming, labor-intensive, and error-prone. As such, the knowledge-intensive data analysis and interpretation supersede the actual experimentation effort as the major bottleneck in molecular diagnostics. By examining the human problem solving for the task, we have designed and implemented a prototype knowledge-based system capable of fully automating linkage-based molecular diagnostics in X-linked genetic disorders, including Duchenne Muscular Dystrophy (DMD). Our system uses knowledge-based interpretation of gel electrophoresis images to determine individual DNA marker labels, a constraint satisfaction search for consistent genetic flow among individuals, and a blackboard-style problem solver for risk assessment. We describe the system`s successful diagnosis of DMD carrier and affected individuals from raw clinical data.

Genetic screening for infertility: When should it be done?

Directory of Open Access Journals (Sweden)

Elda Kara

2010-07-01

Primary amenorrhea should be investigated by karyotype analysis and selected mutation screening according to the patient's clinical features. Karyotype analyses and FMR1 gene screening is recommended in cases of POF. At present the infertility of patients with POF cannot be restored if the diagnosis is made after complete follicular depletion, but in some cases, early diagnosis by genetic investigation may instead lead to the advice of early conception or oocyte harvesting and preservation. In addition, the accumulation and annotation of array comparative genomic hybridization data might, in the near future, lead to the identification of pathogenetic copy number variations and genes involved in POF. Karyotype analysis of both partners is recommended in all couples with recurrent pregnancy loss. No routine genetic test can be recommended so far in patients with PCOS.

Cancer Screening and Genetics: A Tale of Two Paradigms

OpenAIRE

Hamilton, Jada G.; Edwards, Heather M.; Khoury, Muin J.; Taplin, Stephen H.

2014-01-01

The long-standing medical tradition to “first do no harm” is reflected in population-wide evidence-based recommendations for cancer screening tests that focus primarily on reducing morbidity and mortality. The conventional cancer screening process is predicated on finding early-stage disease that can be treated effectively; yet emerging genetic and genomic testing technologies have moved the target earlier in the disease development process to identify a probabilistic predisposition to diseas...

Molecular marker screening of peanut ( Arachis hypogaea L ...

African Journals Online (AJOL)

Molecular marker screening of peanut (Arachis hypogaea L.) germplasm for Meloidogyne arenaria resistance. V Carpentieri-Pipolo, M Gallo-Meagher, DW Dickson, DW Gorbet, M de Lurdes Mendes, SG Hulse de Souza ...

Genarris: Random generation of molecular crystal structures and fast screening with a Harris approximation

Science.gov (United States)

Li, Xiayue; Curtis, Farren S.; Rose, Timothy; Schober, Christoph; Vazquez-Mayagoitia, Alvaro; Reuter, Karsten; Oberhofer, Harald; Marom, Noa

2018-06-01

We present Genarris, a Python package that performs configuration space screening for molecular crystals of rigid molecules by random sampling with physical constraints. For fast energy evaluations, Genarris employs a Harris approximation, whereby the total density of a molecular crystal is constructed via superposition of single molecule densities. Dispersion-inclusive density functional theory is then used for the Harris density without performing a self-consistency cycle. Genarris uses machine learning for clustering, based on a relative coordinate descriptor developed specifically for molecular crystals, which is shown to be robust in identifying packing motif similarity. In addition to random structure generation, Genarris offers three workflows based on different sequences of successive clustering and selection steps: the "Rigorous" workflow is an exhaustive exploration of the potential energy landscape, the "Energy" workflow produces a set of low energy structures, and the "Diverse" workflow produces a maximally diverse set of structures. The latter is recommended for generating initial populations for genetic algorithms. Here, the implementation of Genarris is reported and its application is demonstrated for three test cases.

Molecular screening of antibiotic-resistant determinants among ...

African Journals Online (AJOL)

Background: Globally, and particularly in developing countries, the menace of anti-microbial resistance is an accelerating problem. In Nigeria, increase in bacterial resistance has been phenotypically established but due to high cost, few molecular studies have been reported. Objectives: This study screened for presence of ...

NEW MOLECULAR TECHNOLOGIES IN GENETIC DIAGNOSIS OF MALE INFERTILITY

Directory of Open Access Journals (Sweden)

V. B. Chernykh

2017-01-01

Full Text Available In recent years, the accelerated development of technologies in the field of molecular genetics and cytogenetics has led to significant opportunities of the research and diagnosis of mutations and variations of the genome. This article provides a brief review of new molecular technology, also as the results of their use in reproductive medicine and their perspectives in the genetic diagnosis of male infertility. 

Molecular diversity and genetic relationships in Secale

Indian Academy of Sciences (India)

Molecular diversity and genetic relationships in Secale. E. Santos, M. Matos, P. Silva, A. M. Figueiras, C. Benito and O. Pinto-Carnide. J. Genet. 95, 273–281. Table 1. RAPD and ISSR primers used in this study. Primer. 5 –3. Primer. 5 –3. RAPDs (Operon). A1. CAGGCCCTTC. C5. CATGACCGCC. A4. AATCGGGCTG. C6.

MOLECULAR GENETIC MARKERS AND METHODS OF THEIR IDENTIFICATION IN MODERN FISH-FARMING

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I. Hrytsyniak

2014-03-01

Full Text Available Purpose. The application of molecular genetic markers has been widely used in modern experimental fish-farming in recent years. This methodology is currently presented by a differentiated approach with individual mechanisms and clearly defined possibilities. Numerous publications in the scientific literature that are dedicated to molecular genetic markers for the most part offer purely practical data. Thus, the synthesis and analysis of existing information on the general principles of action and the limits of the main methods of using molecular genetic markers is an actual problem. In particular, such a description will make it possible to plan more effectively the experiment and to obtain the desired results with high reliability. Findings. The main types of variable parts of DNA that can be used as molecular genetic markers in determining the level of stock hybridization, conducting genetic inventory of population and solving other problems in modern fish-farming are described in this paper. Also, the article provides an overview of principal modern methods that can be used to identify molecular genetic markers. Originality. This work is a generalization of modern ideas about the mechanisms of experiments with molecular genetic markers in fish-farming. Information is provided in the form of consistent presentation of the principles and purpose of each method, as well as significant advances during their practical application. Practical value. The proposed review of classic and modern literature data on molecular genetic markers can be used for planning, modernization and correction of research activity in modern fish-farming.

Population genetic structure of rare and endangered plants using molecular markers

Science.gov (United States)

Raji, Jennifer; Atkinson, Carter T.

2013-01-01

This study was initiated to assess the levels of genetic diversity and differentiation in the remaining populations of Phyllostegia stachyoides and Melicope zahlbruckneri in Hawai`i Volcanoes National Park and determine the extent of gene flow to identify genetically distinct individuals or groups for conservation purposes. Thirty-six Amplified Fragment Length Polymorphic (AFLP) primer combinations generated a total of 3,242 polymorphic deoxyribonucleic acid (DNA) fragments in the P. stachyoides population with a percentage of polymorphic bands (PPB) ranging from 39.3 to 65.7% and 2,780 for the M. zahlbruckneri population with a PPB of 18.8 to 64.6%. Population differentiation (Fst) of AFLP loci between subpopulations of P. stachyoides was low (0.043) across populations. Analysis of molecular variance of P. stachyoides showed that 4% of the observed genetic differentiation occurred between populations in different kīpuka and 96% when individuals were pooled from all kīpuka. Moderate genetic diversity was detected within the M. zahlbruckneri population. Bayesian and multivariate analyses both classified the P. stachyoides and M. zahlbruckneri populations into genetic groups with considerable sub-structuring detected in the P. stachyoides population. The proportion of genetic differentiation among populations explained by geographical distance was estimated by Mantel tests. No spatial correlation was found between genetic and geographic distances in both populations. Finally, a moderate but significant gene flow that could be attributed to insect or bird-mediated dispersal of pollen across the different kīpuka was observed. The results of this study highlight the utility of a multi-allelic DNA-based marker in screening a large number of polymorphic loci in small and closely related endangered populations and revealed the presence of genetically unique groups of individuals in both M. zahlbruckneri and P. stachyoides populations. Based on these findings

Molecular phylogeny of Toxoplasmatinae: comparison between inferences based on mitochondrial and apicoplast genetic sequences

Directory of Open Access Journals (Sweden)

Michelle Klein Sercundes

2016-03-01

Full Text Available Abstract Phylogenies within Toxoplasmatinae have been widely investigated with different molecular markers. Here, we studied molecular phylogenies of the Toxoplasmatinae subfamily based on apicoplast and mitochondrial genes. Partial sequences of apicoplast genes coding for caseinolytic protease (clpC and beta subunit of RNA polymerase (rpoB, and mitochondrial gene coding for cytochrome B (cytB were analyzed. Laboratory-adapted strains of the closely related parasites Sarcocystis falcatula and Sarcocystis neurona were investigated, along with Neospora caninum, Neospora hughesi, Toxoplasma gondii (strains RH, CTG and PTG, Besnoitia akodoni, Hammondia hammondiand two genetically divergent lineages of Hammondia heydorni. The molecular analysis based on organellar genes did not clearly differentiate between N. caninum and N. hughesi, but the two lineages of H. heydorni were confirmed. Slight differences between the strains of S. falcatula and S. neurona were encountered in all markers. In conclusion, congruent phylogenies were inferred from the three different genes and they might be used for screening undescribed sarcocystid parasites in order to ascertain their phylogenetic relationships with organisms of the family Sarcocystidae. The evolutionary studies based on organelar genes confirm that the genusHammondia is paraphyletic. The primers used for amplification of clpC and rpoB were able to amplify genetic sequences of organisms of the genus Sarcocystisand organisms of the subfamily Toxoplasmatinae as well.

Virtual Screening of Receptor Sites for Molecularly Imprinted Polymers.

Science.gov (United States)

Bates, Ferdia; Cela-Pérez, María Concepción; Karim, Kal; Piletsky, Sergey; López-Vilariño, José Manuel

2016-08-01

Molecularly Imprinted Polymers (MIPs) are highly advantageous in the field of analytical chemistry. However, interference from secondary molecules can also impede capture of a target by a MIP receptor. This greatly complicates the design process and often requires extensive laboratory screening which is time consuming, costly, and creates substantial waste products. Herein, is presented a new technique for screening of "virtually imprinted receptors" for rebinding of the molecular template as well as secondary structures, correlating the virtual predictions with experimentally acquired data in three case studies. This novel technique is particularly applicable to the evaluation and prediction of MIP receptor specificity and efficiency in complex aqueous systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

RESEARCH NOTE Molecular genetic analysis of consanguineous ...

Indian Academy of Sciences (India)

Navya

Molecular genetic analysis of consanguineous families with primary microcephaly ... Translational Research Institute, Academic Health System, Hamad Medical ..... bridging the gap between homozygosity mapping and deep sequencing.

Genetic dissimilarity among sweet potato genotypes using morphological and molecular descriptors

Directory of Open Access Journals (Sweden)

Elisângela Knoblauch Viega de Andrade

2017-08-01

Full Text Available This study aimed to evaluate the genetic dissimilarity among sweet potato genotypes using morphological and molecular descriptors. The experiment was conducted in the Olericulture Sector at Federal University of Jequitinhonha and Mucuri Valleys (UFVJM and evaluated 60 sweet potato genotypes. For morphological characterization, 24 descriptors were used. For molecular characterization, 11 microsatellite primers specific for sweet potatoes were used, obtaining 210 polymorphic bands. Morphological and molecular diversity was obtained by dissimilarity matrices based on the coefficient of simple matching and the Jaccard index for morphological and molecular data, respectively. From these matrices, dendrograms were built. There is a large amount of genetic variability among sweet potato genotypes of the germplasm bank at UFVJM based on morphological and molecular characterizations. There was no duplicate suspicion or strong association between morphological and molecular analyses. Divergent accessions have been identified by molecular and morphological analyses, which can be used as parents in breeding programmes to produce progenies with high genetic variability.

Molecular research and genetic engineering of resistance to ...

African Journals Online (AJOL)

This paper reviews the recent research progress on genetic methods of resistance, the status and existing problems, traditional breeding, the main resistance mechanism, molecular markers and genetic engineering of resistance genes. It is hoped that new breeding methods and new varieties resistant to Verticillium wilt will ...

Molecular Genetic Studies of Some Eye Diseases Affecting the ...

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. Molecular Genetic Studies of Some Eye Diseases Affecting the Indian Population. Single gene disorders. Complex eye diseases. Genotype-phenotype correlation. Molecular diagnostics.

Molecular and Genetic Determinants of Glioma Cell Invasion

Directory of Open Access Journals (Sweden)

Kenta Masui

2017-12-01

Full Text Available A diffusely invasive nature is a major obstacle in treating a malignant brain tumor, “diffuse glioma”, which prevents neurooncologists from surgically removing the tumor cells even in combination with chemotherapy and radiation. Recently updated classification of diffuse gliomas based on distinct genetic and epigenetic features has culminated in a multilayered diagnostic approach to combine histologic phenotypes and molecular genotypes in an integrated diagnosis. However, it is still a work in progress to decipher how the genetic aberrations contribute to the aggressive nature of gliomas including their highly invasive capacity. Here we depict a set of recent discoveries involving molecular genetic determinants of the infiltrating nature of glioma cells, especially focusing on genetic mutations in receptor tyrosine kinase pathways and metabolic reprogramming downstream of common cancer mutations. The specific biology of glioma cell invasion provides an opportunity to explore the genotype-phenotype correlation in cancer and develop novel glioma-specific therapeutic strategies for this devastating disease.

Molecular characterization of genetic diversity in some durum wheat ...

African Journals Online (AJOL)

Molecular characterization of genetic diversity in some durum wheat ... African Journal of Biotechnology ... Thus, RAPD offer a potentially simple, rapid and reliable method to evaluate genetic variation and relatedness among ten wheat ...

Micropropagation, genetic engineering, and molecular biology of Populus

Science.gov (United States)

N. B. Klopfenstein; Y. W. Chun; M. -S. Kim; M. A. Ahuja; M. C. Dillon; R. C. Carman; L. G. Eskew

1997-01-01

Thirty-four Populus biotechnology chapters, written by 85 authors, are comprised in 5 sections: 1) in vitro culture (micropropagation, somatic embryogenesis, protoplasts, somaclonal variation, and germplasm preservation); 2) transformation and foreign gene expression; 3) molecular biology (molecular/genetic characterization); 4) biotic and abiotic resistance (disease,...

Molecular Darwinism: The Contingency of Spontaneous Genetic Variation

OpenAIRE

Arber, Werner

2011-01-01

The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign...

Current and future role of genetic screening in gynecologic malignancies.

Science.gov (United States)

Ring, Kari L; Garcia, Christine; Thomas, Martha H; Modesitt, Susan C

2017-11-01

The world of hereditary cancers has seen exponential growth in recent years. While hereditary breast and ovarian cancer and Lynch syndrome account for the majority of mutations encountered by gynecologists, newly identified deleterious genetic mutations continue to be unearthed with their associated risks of malignancies. However, these advances in genetic cancer predispositions then force practitioners and their patients to confront the uncertainties of these less commonly identified mutations and the fact that there is limited evidence to guide them in expected cancer risk and appropriate risk-reduction strategies. Given the speed of information, it is imperative to involve cancer genetics experts when counseling these patients. In addition, coordination of screening and care in conjunction with specialty high-risk clinics, if available, allows for patients to have centralized management for multiple cancer risks under the guidance of physicians with experience counseling these patients. The objective of this review is to present the current literature regarding genetic mutations associated with gynecologic malignancies as well to propose screening and risk-reduction options for these high-risk patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Preimplantation genetic diagnosis and screening by array comparative genomic hybridisation: experience of more than 100 cases in a single centre.

Science.gov (United States)

Chow, J Fc; Yeung, W Sb; Lee, V Cy; Lau, E Yl; Ho, P C; Ng, E Hy

2017-04-01

Preimplantation genetic screening has been proposed to improve the in-vitro fertilisation outcome by screening for aneuploid embryos or blastocysts. This study aimed to report the outcome of 133 cycles of preimplantation genetic diagnosis and screening by array comparative genomic hybridisation. This study of case series was conducted in a tertiary assisted reproductive centre in Hong Kong. Patients who underwent preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening between 1 April 2012 and 30 June 2015 were included. They underwent in-vitro fertilisation and intracytoplasmic sperm injection. An embryo biopsy was performed on day-3 embryos and the blastomere was subject to array comparative genomic hybridisation. Embryos with normal copy numbers were replaced. The ongoing pregnancy rate, implantation rate, and miscarriage rate were studied. During the study period, 133 cycles of preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening were initiated in 94 patients. Overall, 112 cycles proceeded to embryo biopsy and 65 cycles had embryo transfer. The ongoing pregnancy rate per transfer cycle after preimplantation genetic screening was 50.0% and that after preimplantation genetic diagnosis was 34.9%. The implantation rates after preimplantation genetic screening and diagnosis were 45.7% and 41.1%, respectively and the miscarriage rates were 8.3% and 28.6%, respectively. There were 26 frozen-thawed embryo transfer cycles, in which vitrified and biopsied genetically transferrable embryos were replaced, resulting in an ongoing pregnancy rate of 36.4% in the screening group and 60.0% in the diagnosis group. The clinical outcomes of preimplantation genetic diagnosis and screening using comparative genomic hybridisation in our unit were comparable to those reported internationally. Genetically transferrable embryos replaced in a natural cycle may improve the ongoing pregnancy rate

[Molecular genetic analysis and clinical aspects of patients with hereditary hemochromatosis].

Science.gov (United States)

Lange, U; Teichmann, J; Dischereit, G

2014-08-01

The purpose of the study was to perform a molecular genetic analysis and to document clinical aspects in patients with hereditary hemochromatosis. The study included 33 outpatients (23 males average age 50.6 years and 10 females average age 60.6 years) with a disorder of iron metabolism (transferrin saturation > 75 %) as confirmation of hemochromatosis who were subjected to molecular genetic and clinical analyses. A homozygous mutation of the hemochromatosis (HFE) gene (C282YY) was detected in 63.6 %, a compound heterozygous mutation (C282Y/H63D) in 30.3% and no mutation of the HFE gene was detected in 6.1 %. The following organ manifestations could be objectified: arthralgia (78.8 %), liver disease (39.9 %), skin hyperpigmentation (30.3 %), osteoporosis (24.2 %), diabetes mellitus (24.2 %) and cardiomyopathy (12.1 %). Comparison between patients with heterozygous and homozygous hemochromatosis revealed the following differences: compound heterozygote patients presented less frequently with osteoarthritis of the metacarpophalangeal (MCP) joints and hands (85.7 %/71.4 % homozygotes vs. 60 %/60 % heterozygotes). Osteoarthritis of the shoulder joints and osteoporosis as well as hypothyroidism were more frequent in compound heterozygote patients, whereas osteoarthritis of the knee and hip joints as well as liver disease were more common in homozygote patients. No differences between both groups were seen with respect to the clinical manifestations of cardiomyopathy and diabetes mellitus. Prevalent causes of death in hereditary hemochromatosis are heart failure, liver disease (cirrhosis and hepatocellular carcinoma) and portal hypertension. Therefore, an early diagnosis, adequate therapy and genetic screening of family members are of great importance. Medicinal treatment will only effectively prevent deleterious organ involvement and subsequent complications if initiated at an early stage. Furthermore, an overview of the current data is given.

Plant genetic and molecular responses to water deficit

Directory of Open Access Journals (Sweden)

Silvio Salvi

2011-02-01

Full Text Available Plant productivity is severely affected by unfavourable environmental conditions (biotic and abiotic stresses. Among others, water deficit is the plant stress condition which mostly limits the quality and the quantity of plant products. Tolerance to water deficit is a polygenic trait strictly dependent on the coordinated expression of a large set of genes coding for proteins directly involved in stress-induced protection/repair mechanisms (dehydrins, chaperonins, enzymes for the synthesis of osmoprotectants and detoxifying compounds, and others as well as genes involved in transducing the stress signal and regulating gene expression (transcription factors, kinases, phosphatases. Recently, research activities in the field evolved from the study of single genes directly involved in cellular stress tolerance (functional genes to the identification and characterization of key regulatory genes involved in stress perception and transduction and able to rapidly and efficiently activate the complex gene network involved in the response to stress. The complexity of the events occurring in response to stress have been recently approached by genomics tools; in fact the analysis of transcriptome, proteome and metabolome of a plant tissue/cell in response to stress already allowed to have a global view of the cellular and molecular events occurring in response to water deficit, by the identification of genes activated and co-regulated by the stress conditions and the characterization of new signalling pathways. Moreover the recent application of forward and reverse genetic approaches, trough mutant collection development, screening and characterization, is giving a tremendous impulse to the identification of gene functions with key role in stress tolerance. The integration of data obtained by high-throughput genomic approaches, by means of powerful informatic tools, is allowing nowadays to rapidly identify of major genes/QTLs involved in stress tolerance

Genetic Breeding and Diversity of the Genus Passiflora: Progress and Perspectives in Molecular and Genetic Studies

Directory of Open Access Journals (Sweden)

Carlos Bernard M. Cerqueira-Silva

2014-08-01

Full Text Available Despite the ecological and economic importance of passion fruit (Passiflora spp., molecular markers have only recently been utilized in genetic studies of this genus. In addition, both basic genetic researches related to population studies and pre-breeding programs of passion fruit remain scarce for most Passiflora species. Considering the number of Passiflora species and the increasing use of these species as a resource for ornamental, medicinal, and food purposes, the aims of this review are the following: (i to present the current condition of the passion fruit crop; (ii to quantify the applications and effects of using molecular markers in studies of Passiflora; (iii to present the contributions of genetic engineering for passion fruit culture; and (iv to discuss the progress and perspectives of this research. Thus, the present review aims to summarize and discuss the relationship between historical and current progress on the culture, breeding, and molecular genetics of passion fruit.

Genetics and molecular biology of breast cancer

Energy Technology Data Exchange (ETDEWEB)

King, M.C. [California Univ., Berkeley, CA (United States); Lippman, M. [Georgetown Univ. Medical Center, Washington, DC (United States)] [comps.

1992-12-31

This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

Employment discrimination implications of genetic screening in the workplace under Title VII and the Rehabilitation Act.

Science.gov (United States)

Canter, E F

1984-01-01

The emergence of genetic screening techniques will permit employers to exclude hypersusceptible individuals from potentially hazardous workplace environments. The denial of employment opportunities to these individuals, however, may constitute discrimination. This Note analyzes genetic screening cases with respect to currently available remedies contained in Title VII of the Civil Rights Act of 1964 and the Rehabilitation Act of 1973. The Note concludes that Title VII claims may succeed but only in limited circumstances and that Rehabilitation Act claims will encounter numerous obstacles to relief. Additionally, the Note discusses some of the implications of the use of genetic screening in the workplace.

Molecular markers: a potential resource for ginger genetic diversity studies.

Science.gov (United States)

Ismail, Nor Asiah; Rafii, M Y; Mahmud, T M M; Hanafi, M M; Miah, Gous

2016-12-01

Ginger is an economically important and valuable plant around the world. Ginger is used as a food, spice, condiment, medicine and ornament. There is available information on biochemical aspects of ginger, but few studies have been reported on its molecular aspects. The main objective of this review is to accumulate the available molecular marker information and its application in diverse ginger studies. This review article was prepared by combing material from published articles and our own research. Molecular markers allow the identification and characterization of plant genotypes through direct access to hereditary material. In crop species, molecular markers are applied in different aspects and are useful in breeding programs. In ginger, molecular markers are commonly used to identify genetic variation and classify the relatedness among varieties, accessions, and species. Consequently, it provides important input in determining resourceful management strategies for ginger improvement programs. Alternatively, a molecular marker could function as a harmonizing tool for documenting species. This review highlights the application of molecular markers (isozyme, RAPD, AFLP, SSR, ISSR and others such as RFLP, SCAR, NBS and SNP) in genetic diversity studies of ginger species. Some insights on the advantages of the markers are discussed. The detection of genetic variation among promising cultivars of ginger has significance for ginger improvement programs. This update of recent literature will help researchers and students select the appropriate molecular markers for ginger-related research.

Supplementary data: Molecular assessment of genetic diversity in ...

Indian Academy of Sciences (India)

Molecular assessment of genetic diversity in cluster bean. (Cyamopsis tetragonoloba) genotypes. Rakesh Pathak, S. K. Singh, Manjit Singh and A. Henry. J. Genet. 89, 243–246. Figure 1. RAPD profile of 1–16 Cyamopsis tetragonoloba genotypes amplified with arbitrary primer OPA-16. Figure 2. RAPD profile of 17–32 ...

The molecular genetic architecture of self-employment.

Science.gov (United States)

van der Loos, Matthijs J H M; Rietveld, Cornelius A; Eklund, Niina; Koellinger, Philipp D; Rivadeneira, Fernando; Abecasis, Gonçalo R; Ankra-Badu, Georgina A; Baumeister, Sebastian E; Benjamin, Daniel J; Biffar, Reiner; Blankenberg, Stefan; Boomsma, Dorret I; Cesarini, David; Cucca, Francesco; de Geus, Eco J C; Dedoussis, George; Deloukas, Panos; Dimitriou, Maria; Eiriksdottir, Guðny; Eriksson, Johan; Gieger, Christian; Gudnason, Vilmundur; Höhne, Birgit; Holle, Rolf; Hottenga, Jouke-Jan; Isaacs, Aaron; Järvelin, Marjo-Riitta; Johannesson, Magnus; Kaakinen, Marika; Kähönen, Mika; Kanoni, Stavroula; Laaksonen, Maarit A; Lahti, Jari; Launer, Lenore J; Lehtimäki, Terho; Loitfelder, Marisa; Magnusson, Patrik K E; Naitza, Silvia; Oostra, Ben A; Perola, Markus; Petrovic, Katja; Quaye, Lydia; Raitakari, Olli; Ripatti, Samuli; Scheet, Paul; Schlessinger, David; Schmidt, Carsten O; Schmidt, Helena; Schmidt, Reinhold; Senft, Andrea; Smith, Albert V; Spector, Timothy D; Surakka, Ida; Svento, Rauli; Terracciano, Antonio; Tikkanen, Emmi; van Duijn, Cornelia M; Viikari, Jorma; Völzke, Henry; Wichmann, H-Erich; Wild, Philipp S; Willems, Sara M; Willemsen, Gonneke; van Rooij, Frank J A; Groenen, Patrick J F; Uitterlinden, André G; Hofman, Albert; Thurik, A Roy

2013-01-01

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σ(g)(2)/σ(P)(2) = 25%, h(2) = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with pself-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases.

Impact of preimplantation genetic screening on donor oocyte-recipient cycles in the United States.

Science.gov (United States)

Barad, David H; Darmon, Sarah K; Kushnir, Vitaly A; Albertini, David F; Gleicher, Norbert

2017-11-01

Our objective was to estimate the contribution of preimplantation genetic screening to in vitro fertilization pregnancy outcomes in donor oocyte-recipient cycles. This was a retrospective cross-sectional study of US national data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System between 2005 and 2013. Society for Assisted Reproductive Technology Clinic Outcome Reporting relies on voluntarily annual reports by more than 90% of US in vitro fertilization centers. We evaluated pregnancy and live birth rates in donor oocyte-recipient cycles after the first embryo transfer with day 5/6 embryos. Statistical models, adjusted for patient and donor ages, number of embryos transferred, race, infertility diagnosis, and cycle year were created to compare live birth rates in 392 preimplantation genetic screening and 20,616 control cycles. Overall, pregnancy and live birth rates were significantly lower in preimplantation genetic screening cycles than in control cycles. Adjusted odds of live birth for preimplantation genetic screening cycles were reduced by 35% (odds ratio, 0.65, 95% confidence interval, 0.53-0.80; P cycles over the past 9 years, has not been associated with improved odds of live birth or reduction in miscarriage rates. Copyright © 2017 Elsevier Inc. All rights reserved.

Advances in molecular genetic studies of primary dystonia

Directory of Open Access Journals (Sweden)

MA Ling-yan

2013-07-01

Full Text Available Dystonias are heterogeneous hyperkinetic movement disorders characterized by involuntary muscle contractions which result in twisting, repetitive movements and abnormal postures. In recent years, there was a great advance in molecular genetic studies of primary dystonia. This paper will review the clinical characteristics and molecular genetic studies of primary dystonia, including early-onset generalized torsion dystonia (DYT1, whispering dysphonia (DYT4, dopa-responsive dystonia (DYT5, mixed-type dystonia (DYT6, paroxysmal kinesigenic dyskinesia (DYT10, myoclonus-dystonia syndrome (DYT11, rapid-onset dystonia parkinsonism (DYT12, adult-onset cervical dystonia (DYT23, craniocervical dystonia (DYT24 and primary torsion dystonia (DYT25.

A practical approach to screen for authorised and unauthorised genetically modified plants.

Science.gov (United States)

Waiblinger, Hans-Ulrich; Grohmann, Lutz; Mankertz, Joachim; Engelbert, Dirk; Pietsch, Klaus

2010-03-01

In routine analysis, screening methods based on real-time PCR are most commonly used for the detection of genetically modified (GM) plant material in food and feed. In this paper, it is shown that the combination of five DNA target sequences can be used as a universal screening approach for at least 81 GM plant events authorised or unauthorised for placing on the market and described in publicly available databases. Except for maize event LY038, soybean events DP-305423 and BPS-CV127-9 and cotton event 281-24-236 x 3006-210-23, at least one of the five genetic elements has been inserted in these GM plants and is targeted by this screening approach. For the detection of these sequences, fully validated real-time PCR methods have been selected. A screening table is presented that describes the presence or absence of the target sequences for most of the listed GM plants. These data have been verified either theoretically according to available databases or experimentally using available reference materials. The screening table will be updated regularly by a network of German enforcement laboratories.

The Molecular Genetic Architecture of Self-Employment

Science.gov (United States)

van der Loos, Matthijs J. H. M.; Rietveld, Cornelius A.; Eklund, Niina; Koellinger, Philipp D.; Rivadeneira, Fernando; Abecasis, Gonçalo R.; Ankra-Badu, Georgina A.; Baumeister, Sebastian E.; Benjamin, Daniel J.; Biffar, Reiner; Blankenberg, Stefan; Boomsma, Dorret I.; Cesarini, David; Cucca, Francesco; de Geus, Eco J. C.; Dedoussis, George; Deloukas, Panos; Dimitriou, Maria; Eiriksdottir, Guðny; Eriksson, Johan; Gieger, Christian; Gudnason, Vilmundur; Höhne, Birgit; Holle, Rolf; Hottenga, Jouke-Jan; Isaacs, Aaron; Järvelin, Marjo-Riitta; Johannesson, Magnus; Kaakinen, Marika; Kähönen, Mika; Kanoni, Stavroula; Laaksonen, Maarit A.; Lahti, Jari; Launer, Lenore J.; Lehtimäki, Terho; Loitfelder, Marisa; Magnusson, Patrik K. E.; Naitza, Silvia; Oostra, Ben A.; Perola, Markus; Petrovic, Katja; Quaye, Lydia; Raitakari, Olli; Ripatti, Samuli; Scheet, Paul; Schlessinger, David; Schmidt, Carsten O.; Schmidt, Helena; Schmidt, Reinhold; Senft, Andrea; Smith, Albert V.; Spector, Timothy D.; Surakka, Ida; Svento, Rauli; Terracciano, Antonio; Tikkanen, Emmi; van Duijn, Cornelia M.; Viikari, Jorma; Völzke, Henry; Wichmann, H. -Erich; Wild, Philipp S.; Willems, Sara M.; Willemsen, Gonneke; van Rooij, Frank J. A.; Groenen, Patrick J. F.; Uitterlinden, André G.; Hofman, Albert; Thurik, A. Roy

2013-01-01

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable–entrepreneurship–that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σg 2/σP 2 = 25%, h 2 = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with pentrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases. PMID:23593239

Recent advances in preimplantation genetic diagnosis and screening.

Science.gov (United States)

Lu, Lina; Lv, Bo; Huang, Kevin; Xue, Zhigang; Zhu, Xianmin; Fan, Guoping

2016-09-01

Preimplantation genetic diagnosis/screening (PGD/PGS) aims to help couples lower the risks of transmitting genetic defects to their offspring, implantation failure, and/or miscarriage during in vitro fertilization (IVF) cycles. However, it is still being debated with regard to the practicality and diagnostic accuracy of PGD/PGS due to the concern of invasive biopsy and the potential mosaicism of embryos. Recently, several non-invasive and high-throughput assays have been developed to help overcome the challenges encountered in the conventional invasive biopsy and low-throughput analysis in PGD/PGS. In this mini-review, we will summarize the recent progresses of these new methods for PGD/PGS and discuss their potential applications in IVF clinics.

Genetic high throughput screening in Retinitis Pigmentosa based on high resolution melting (HRM) analysis.

Science.gov (United States)

Anasagasti, Ander; Barandika, Olatz; Irigoyen, Cristina; Benitez, Bruno A; Cooper, Breanna; Cruchaga, Carlos; López de Munain, Adolfo; Ruiz-Ederra, Javier

2013-11-01

Retinitis Pigmentosa (RP) involves a group of genetically determined retinal diseases caused by a large number of mutations that result in rod photoreceptor cell death followed by gradual death of cone cells. Most cases of RP are monogenic, with more than 80 associated genes identified so far. The high number of genes and variants involved in RP, among other factors, is making the molecular characterization of RP a real challenge for many patients. Although HRM has been used for the analysis of isolated variants or single RP genes, as far as we are concerned, this is the first study that uses HRM analysis for a high-throughput screening of several RP genes. Our main goal was to test the suitability of HRM analysis as a genetic screening technique in RP, and to compare its performance with two of the most widely used NGS platforms, Illumina and PGM-Ion Torrent technologies. RP patients (n = 96) were clinically diagnosed at the Ophthalmology Department of Donostia University Hospital, Spain. We analyzed a total of 16 RP genes that meet the following inclusion criteria: 1) size: genes with transcripts of less than 4 kb; 2) number of exons: genes with up to 22 exons; and 3) prevalence: genes reported to account for, at least, 0.4% of total RP cases worldwide. For comparison purposes, RHO gene was also sequenced with Illumina (GAII; Illumina), Ion semiconductor technologies (PGM; Life Technologies) and Sanger sequencing (ABI 3130xl platform; Applied Biosystems). Detected variants were confirmed in all cases by Sanger sequencing and tested for co-segregation in the family of affected probands. We identified a total of 65 genetic variants, 15 of which (23%) were novel, in 49 out of 96 patients. Among them, 14 (4 novel) are probable disease-causing genetic variants in 7 RP genes, affecting 15 patients. Our HRM analysis-based study, proved to be a cost-effective and rapid method that provides an accurate identification of genetic RP variants. This approach is effective for

[Colorectal cancer (CCR): genetic and molecular alterations].

Science.gov (United States)

Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

2014-01-01

The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

Science.gov (United States)

Lynch, HT; Lynch, PM; Lanspa, SJ; Snyder, CL; Lynch, JF; Boland, CR

2010-01-01

More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (~30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC’s proximal occurrence (70–80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40–60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/carcinomas (Muir-Torre variant). LS explains only 10–25% of familial CRC. PMID:19659756

Molecular – genetic variance of RH blood group system within human population of Bosnia and Herzegovina

Directory of Open Access Journals (Sweden)

Lejla Lasić

2013-02-01

Full Text Available There are two major theories for inheritance of Rh blood group system: Fisher - Race theory and Wiener theory. Aim of this study was identifying frequency of RHDCE alleles in Bosnian - Herzegovinian population and introduction of this method in screening for Rh phenotype in B&H since this type of analysis was not used for blood typing in B&H before. Rh blood group was typed by Polymerase Chain Reaction, using the protocols and primers previously established by other authors, then carrying out electrophoresis in 2-3% agarose gel. Percentage of Rh positive individuals in our sample is 84.48%, while the percentage of Rh negative individuals is 15.52%. Inter-rater agreement statistic showed perfect agreement (K=1 between the results of Rh blood system detection based on serological and molecular-genetics methods. In conclusion, molecular - genetic methods are suitable for prenatal genotyping and specific cases while standard serological method is suitable for high-throughput of samples.

Genetic diversity of popcorn genotypes using molecular analysis.

Science.gov (United States)

Resh, F S; Scapim, C A; Mangolin, C A; Machado, M F P S; do Amaral, A T; Ramos, H C C; Vivas, M

2015-08-19

In this study, we analyzed dominant molecular markers to estimate the genetic divergence of 26 popcorn genotypes and evaluate whether using various dissimilarity coefficients with these dominant markers influences the results of cluster analysis. Fifteen random amplification of polymorphic DNA primers produced 157 amplified fragments, of which 65 were monomorphic and 92 were polymorphic. To calculate the genetic distances among the 26 genotypes, the complements of the Jaccard, Dice, and Rogers and Tanimoto similarity coefficients were used. A matrix of Dij values (dissimilarity matrix) was constructed, from which the genetic distances among genotypes were represented in a more simplified manner as a dendrogram generated using the unweighted pair-group method with arithmetic average. Clusters determined by molecular analysis generally did not group material from the same parental origin together. The largest genetic distance was between varieties 17 (UNB-2) and 18 (PA-091). In the identification of genotypes with the smallest genetic distance, the 3 coefficients showed no agreement. The 3 dissimilarity coefficients showed no major differences among their grouping patterns because agreement in determining the genotypes with large, medium, and small genetic distances was high. The largest genetic distances were observed for the Rogers and Tanimoto dissimilarity coefficient (0.74), followed by the Jaccard coefficient (0.65) and the Dice coefficient (0.48). The 3 coefficients showed similar estimations for the cophenetic correlation coefficient. Correlations among the matrices generated using the 3 coefficients were positive and had high magnitudes, reflecting strong agreement among the results obtained using the 3 evaluated dissimilarity coefficients.

Toward a generalized and high-throughput enzyme screening system based on artificial genetic circuits.

Science.gov (United States)

Choi, Su-Lim; Rha, Eugene; Lee, Sang Jun; Kim, Haseong; Kwon, Kilkoang; Jeong, Young-Su; Rhee, Young Ha; Song, Jae Jun; Kim, Hak-Sung; Lee, Seung-Goo

2014-03-21

Large-scale screening of enzyme libraries is essential for the development of cost-effective biological processes, which will be indispensable for the production of sustainable biobased chemicals. Here, we introduce a genetic circuit termed the Genetic Enzyme Screening System that is highly useful for high-throughput enzyme screening from diverse microbial metagenomes. The circuit consists of two AND logics. The first AND logic, the two inputs of which are the target enzyme and its substrate, is responsible for the accumulation of a phenol compound in cell. Then, the phenol compound and its inducible transcription factor, whose activation turns on the expression of a reporter gene, interact in the other logic gate. We confirmed that an individual cell harboring this genetic circuit can present approximately a 100-fold higher cellular fluorescence than the negative control and can be easily quantified by flow cytometry depending on the amounts of phenolic derivatives. The high sensitivity of the genetic circuit enables the rapid discovery of novel enzymes from metagenomic libraries, even for genes that show marginal activities in a host system. The crucial feature of this approach is that this single system can be used to screen a variety of enzymes that produce a phenol compound from respective synthetic phenyl-substrates, including cellulase, lipase, alkaline phosphatase, tyrosine phenol-lyase, and methyl parathion hydrolase. Consequently, the highly sensitive and quantitative nature of this genetic circuit along with flow cytometry techniques could provide a widely applicable toolkit for discovering and engineering novel enzymes at a single cell level.

Comprehensive Molecular Screening in Chinese Usher Syndrome Patients.

Science.gov (United States)

Sun, Tengyang; Xu, Ke; Ren, Yanfan; Xie, Yue; Zhang, Xiaohui; Tian, Lu; Li, Yang

2018-03-01

Usher syndrome (USH) refers to a group of autosomal recessive disorders causing deafness and blindness. The objectives of this study were to determine the mutation spectrum in a cohort of Chinese patients with USH and to describe the clinical features of the patients with mutations. A total of 119 probands who were clinically diagnosed with USH were recruited for genetic analysis. All probands underwent ophthalmic examinations. A combination of molecular screening methods, including targeted next-generation sequencing, Sanger-DNA sequencing, and multiplex ligation probe amplification assay, was used to detect mutations. We found biallelic mutations in 92 probands (77.3%), monoallelic mutations in 5 patients (4.2%), and 1 hemizygous mutation in 1 patient (0.8%), resulting in an overall mutation detection rate of 78.2%. Overall, 132 distinct disease-causing mutations involving seven USH (ABHD12, CDH23, GPR98, MYO7A, PCDH15, USH1C, and USH2A) genes; 5 other retinal degeneration genes (CHM, CNGA1, EYS, PDE6B, and TULP1); and 1 nonsyndromic hearing loss gene (MYO15A) were identified, and 78 were novel. Mutations of MYOA7 were responsible for 60% of USH1 families, followed by PCDH15 (20%) and USH1C (10%). Mutations of USH2A accounted for 67.7% of USH2 families, and mutation c.8559-2A>G was the most frequent one, accounting for 19.1% of the identified USH2A alleles. Our results confirm that the mutation spectrum for each USH gene in Chinese patients differs from those of other populations. The formation of the mutation profile for the Chinese population will enable a precise genetic diagnosis for USH patients in the future.

Molecular evaluation of genetic diversity and association studies in ...

Indian Academy of Sciences (India)

Molecular evaluation of genetic diversity and association studies in rice. (Oryza sativa L.) C. Vanniarajan, K. K. Vinod and Andy Pereira. J. Genet. 91, 9–19. Table 1. Chromosome-wise distribution of SSR alleles and their number (k), polymorphic information content (PIC) and allele discrimination index (Dm). Chromosome.

Empirical Refinements of a Molecular Genetics Learning Progression: The Molecular Constructs

Science.gov (United States)

Todd, Amber; Kenyon, Lisa

2016-01-01

This article describes revisions to four of the eight constructs of the Duncan molecular genetics learning progression [Duncan, Rogat, & Yarden, (2009)]. As learning progressions remain hypothetical models until validated by multiple rounds of empirical studies, these revisions are an important step toward validating the progression. Our…

Genetic screening of prospective parents and of workers: some scientific and social issues.

Science.gov (United States)

Hubbard, R; Henifin, M S

1985-01-01

Genetic screening programs are based on assumptions and values that reflect the history of racial and social eugenics in the United States and Europe. They stigmatize individuals by shifting the focus from social, economic, and political decisions that affect the health of prospective parents, newborns, and workers to "bad genes," that is, intrapersonal factors that are given the status of "causes" of disease. Prenatal screening, at best, can help the relatively few individuals who know that their future children are at risk for a particular inherited disease or disability; it has little positive value for the average person. Workplace genetic screening has not been shown to reduce occupational disease, but it has led to employment discrimination and has drawn attention away from controlling exposures to toxic chemicals in the workplace.

Primer on molecular genetics. DOE Human Genome Program

Energy Technology Data Exchange (ETDEWEB)

1992-04-01

This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

EMQN/CMGS best practice guidelines for the molecular genetic testing of Huntington disease.

Science.gov (United States)

Losekoot, Monique; van Belzen, Martine J; Seneca, Sara; Bauer, Peter; Stenhouse, Susan A R; Barton, David E

2013-05-01

Huntington disease (HD) is caused by the expansion of an unstable polymorphic trinucleotide (CAG)n repeat in exon 1 of the HTT gene, which translates into an extended polyglutamine tract in the protein. Laboratory diagnosis of HD involves estimation of the number of CAG repeats. Molecular genetic testing for HD is offered in a wide range of laboratories both within and outside the European community. In order to measure the quality and raise the standard of molecular genetic testing in these laboratories, the European Molecular Genetics Quality Network has organized a yearly external quality assessment (EQA) scheme for molecular genetic testing of HD for over 10 years. EQA compares a laboratory's output with a fixed standard both for genotyping and reporting of the results to the referring physicians. In general, the standard of genotyping is very high but the clarity of interpretation and reporting of the test result varies more widely. This emphasizes the need for best practice guidelines for this disorder. We have therefore developed these best practice guidelines for genetic testing for HD to assist in testing and reporting of results. The analytical methods and the potential pitfalls of molecular genetic testing are highlighted and the implications of the different test outcomes for the consultand and his or her family members are discussed.

Medulloblastoma: Molecular Genetics and Animal Models

Directory of Open Access Journals (Sweden)

Corey Raffel

2004-07-01

Full Text Available Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.

Creation of a National, At-home Model for Ashkenazi Jewish Carrier Screening.

Science.gov (United States)

Grinzaid, Karen Arnovitz; Page, Patricia Zartman; Denton, Jessica Johnson; Ginsberg, Jessica

2015-06-01

Ethnicity-based carrier screening for the Ashkenazi Jewish population has been available and encouraged by advocacy and community groups since the early 1970's. Both the American College of Medical Genetics and the American Congress of Obstetricians and Gynecologists recommend carrier screening for this population (Obstetrics and Gynecology, 114(4), 950-953, 2009; Genetics in Medicine, 10(1), 55-56, 2008). While many physicians inquire about ethnic background and offer appropriate carrier screening, studies show that a gap remains in implementing recommendations (Genetic testing and molecular biomarkers, 2011). In addition, education and outreach efforts targeting Jewish communities have had limited success in reaching this at-risk population. Despite efforts by the medical and Jewish communities, many Jews of reproductive age are not aware of screening, and remain at risk for having children with preventable diseases. Reaching this population, preferably pre-conception, and facilitating access to screening is critically important. To address this need, genetic counselors at Emory University developed JScreen, a national Jewish genetic disease screening program. The program includes a national marketing and PR campaign, online education, at-home saliva-based screening, post-test genetic counseling via telephone or secure video conferencing, and referrals for face-to-face genetic counseling as needed. Our goals are to create a successful education and screening program for this population and to develop a model that could potentially be used for other at-risk populations.

Screening Chinese soybean genotypes for Agrobacterium-mediated genetic transformation suitability*

Science.gov (United States)

Song, Zhang-yue; Tian, Jing-luan; Fu, Wei-zhe; Li, Lin; Lu, Ling-hong; Zhou, Lian; Shan, Zhi-hui; Tang, Gui-xiang; Shou, Hui-xia

2013-01-01

The Agrobacterium-mediated transformation system is the most commonly used method in soybean transformation. Screening of soybean genotypes favorable for Agrobacterium-infection and tissue regeneration is the most important step to establish an efficient genetic transformation system. In this study, twenty soybean genotypes that originated from different soybean production regions in China were screened for transient infection, regeneration capacity, and stable transgenic efficiency. Three genotypes, Yuechun 04-5, Yuechun 03-3, and Tianlong 1, showed comparable stable transgenic efficiencies with that of the previously reported American genotypes Williams 82 and Jack in our experimental system. For the Tianlong 1, the average stable transformation efficiency is 4.59%, higher than that of control genotypes (Jack and Williams 82), which is enough for further genomic research and genetic engineering. While polymerase chain reaction (PCR), LibertyLink strips, and β-glucuronidase (GUS) staining assays were used to detect the insertion and expression of the transgene, leaves painted with 135 mg/L Basta could efficiently identify the transformants. PMID:23549846

Forward Genetic Screening Using Behavioral Tests in Zebrafish: A Proof of Concept Analysis of Mutants.

Science.gov (United States)

Gerlai, Robert; Poshusta, Tanya L; Rampersad, Mindy; Fernandes, Yohaan; Greenwood, Tammy M; Cousin, Margot A; Klee, Eric W; Clark, Karl J

2017-01-01

The zebrafish enjoys several advantages over other model organisms. It is small, easy to maintain, prolific, and numerous genetic tools are available for it. For example, forward genetic screens have allowed investigators to identify important genes potentially involved in a variety of functions from embryogenesis to cancer. However, despite its sophisticated behavioral repertoire, behavioral methods have rarely been utilized in forward genetic screens. Here, we employ a two-tiered strategy, a proof of concept study, to explore the feasibility of behavioral screens. We generated mutant lines using transposon-based insertional mutagenesis, allowing us to bias mutant selection with target genes expressed within the brain. Furthermore, we employed an efficient and fast behavioral pre-selection in which we investigated the locomotory response of 5-day post-fertilization old larval fish to hyperosmotic shock. Based on this assay, we selected five lines for our lower throughput secondary adult behavioral screen. The latter screen utilized tests in which computer animated image presentation and video-tracking-based automated quantification of behavior allowed us to compare heterozygous zebrafish with their wild-type siblings on their responses to a variety of stimuli. We found significant mutation induced adult behavioral alterations in 4 out of the 5 lines analyzed, including changes in response to social or fear inducing stimuli, to handling and novelty, or in habituation to novelty. We discuss the pros and cons of behavioral phenotyping and of the use of different forward genetic methods in biomedical research with zebrafish.

A molecular genetic toolbox for Yarrowia lipolytica

DEFF Research Database (Denmark)

Bredeweg, Erin L.; Pomraning, Kyle R.; Dai, Ziyu

2017-01-01

used these tools to build the "Yarrowia lipolytica Cell Atlas," a collection of strains with endogenous fluorescently tagged organelles in the same genetic background, in order to define organelle morphology in live cells. Conclusions: These molecular and isogenetic tools are useful for live assessment...

DataGenno: building a new tool to bridge molecular and clinical genetics

Directory of Open Access Journals (Sweden)

Fabricio F Costa

2011-03-01

Full Text Available Fabricio F Costa1,2, Luciano S Foly1, Marcelo P Coutinho11DataGenno Interactive Research Ltd., Itaperuna, Rio de Janeiro, Brazil; 2Cancer Biology and Epigenomics Program, Children's Memorial Research Center, Northwestern University's Feinberg School of Medicine, Chicago, IL, USAAbstract: Clinical genetics is one of the most challenging fields in medicine, with thousands of children born every year with congenital defects that have no satisfactory diagnosis. There are more than 6,000 known single-gene disorders that can cause birth defects or diseases in approximately 1 in every 200 births. Clinical and molecular information on genetic diseases and syndromes are widespread in the literature, and there are few databases combining this information. Therefore, it is very challenging for health care professionals and researchers to translate the latest advances in science and medicine into effective clinical interventions and new treatments. In order to overcome this obstacle and promote networking, we are building DataGenno, an online medical and scientific portal. DataGenno has been developed to be a source of information on genetic diseases and syndromes for the needs of all heath care professionals and researchers. Our database will be able to integrate both clinical and molecular aspects of genetic diseases in a fully interactive environment. DataGenno’s system already contains clinical and molecular information for 300 diseases, with approximately 6,000 signs and symptoms of these diseases in a database combined with a search engine. Our main goal is to cover all genetic diseases described to date, providing not only clinical information such as morphological and anatomical features but also the most comprehensive molecular genetics/genomics features and available testing information. We are also developing ways to connect DataGenno’s portal with Electronic Health Records in order to improve the efficiency of patient care. Additionally

Genetic variability of hull-less barley accessions based on molecular and quantitative data

Directory of Open Access Journals (Sweden)

Ricardo Meneses Sayd

2015-02-01

Full Text Available The objective of this work was to characterize and quantify the genetic, molecular, and agronomic variability of hull-less barley genotypes, for the selection of parents and identification of genotypes adapted to the irrigated production system in the Brazilian Cerrado. Eighteen hull-less barley accessions were evaluated, and three covered barley accessions served as reference. The characterization was based on 157 RAPD molecular markers and ten agronomic traits. Genetic distance matrices were obtained based on molecular markers and quantitative traits. Graphic grouping and dispersion analyses were performed. Genetic, molecular, and agronomic variability was high among genotypes. Ethiopian accessions were genetically more similar, and the Brazilian ones were genetically more distant. For agronomic traits, two more consistent groupings were obtained, one with the most two-rowed materials, and the other with six-rowed materials. The more diverging materials were the two-rowed CI 13453, CN Cerrado 5, CN Cerrado 1, and CN Cerrado 2. The PI 356466, CN Cerrado 1, PI 370799, and CI 13453 genotypes show agronomic traits of interest and, as genetically different genotypes, they are indicated for crossing, in breeding programs.

ESHRE Task Force on Ethics and Law 21: genetic screening of gamete donors: ethical issues.

Science.gov (United States)

Dondorp, W; De Wert, G; Pennings, G; Shenfield, F; Devroey, P; Tarlatzis, B; Barri, P; Diedrich, K; Eichenlaub-Ritter, U; Tüttelmann, F; Provoost, V

2014-07-01

This Task Force document explores the ethical issues involved in the debate about the scope of genetic screening of gamete donors. Calls for expanded donor screening arise against the background of both occasional findings of serious but rare genetic conditions in donors or donor offspring that were not detected through present screening procedures and the advent of new genomic technologies promising affordable testing of donors for a wide range of conditions. Ethical principles require that all stakeholders' interests are taken into account, including those of candidate donors. The message of the profession should be that avoiding all risks is impossible and that testing should remain proportional.

Genetics Home Reference: autosomal recessive primary microcephaly

Science.gov (United States)

... microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings. Am J Hum Genet. 2005 May;76( ... genome editing and CRISPR-Cas9? What is precision medicine? What is newborn screening? New Pages Alopecia areata ...

Phenotypic and molecular genetic analysis of Pyruvate Kinase ...

African Journals Online (AJOL)

Phenotypic and molecular genetic analysis of Pyruvate Kinase deficiency in a Tunisian family. Jaouani Mouna, Hamdi Nadia, Chaouch Leila, Kalai Miniar, Mellouli Fethi, Darragi Imen, Boudriga Imen, Chaouachi Dorra, Bejaoui Mohamed, Abbes Salem ...

Forward genetic screen for auxin-deficient mutants by cytokinin

Czech Academy of Sciences Publication Activity Database

Wu, L.; Luo, P.; Di, D.W.; Wang, L.; Wang, M.; Lu, C.K.; Wei, S.D.; Zhang, L.; Zhang, T.Z.; Amakorová, Petra; Strnad, Miroslav; Novák, Ondřej; Guo, G.Q.

2015-01-01

Roč. 5, JUL 6 (2015) ISSN 2045-2322 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : ETHYLENE-INSENSITIVE MUTANTS * YUCCA FLAVIN MONOOXYGENASES * ARABIDOPSIS-THALIANA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.228, year: 2015

Molecular screening in galactosemia

Energy Technology Data Exchange (ETDEWEB)

Elsas, L.J.; Singh, R.; Fernhoff, P.M. [Emory Univ., Atlanta, GA (United States)] [and others

1994-09-01

Classical galactosemia (G/G) is caused by the absence of galactose-1-phosphate uridyl transferase (GALT) activity while the Duarte allele produces partial impairment and a specific biochemical phenotype. Cloning and sequencing of the human GALT gene has enabled the identification of prevalent mutations for both Classical and Duarte alleles. The G allele is caused by a Q188R codon mutation in exon 6 in 70% of a Caucasian population while the D allele is caused by an N134D codon mutation in exon 10. Since the Q188R sequence creates a new Hpa II site and the N314D sequence creates a new Sin I site, it is relatively easy to screen for both mutations by multiplex PCR and restriction digest. Here we describe a method for detection of new mutations producing impaired GALT. Patient DNAs are subjected to SSCP (single strand conformational polymorphism) analysis of their 11 GALT exons. Direct sequencing of the exons targeted by SSCP has revealed many codon changes: IVSC 956 (a splice acceptor site loss), S135L, V151A, E203K, A320T, and Y323D. Two of these codon changes, V151A and S135L, have been confirmed as mutations by finding impaired GALT activity in a yeast expression system. We conclude that molecular screening of GALT DNA will clarify the structural biology of GALT and the pathophysiology of galactosemia.

Vitrified/warmed single blastocyst transfer in preimplantation genetic diagnosis/preimplantation genetic screening cycles.

Science.gov (United States)

Huang, Jin; Li, Rong; Lian, Ying; Chen, Lixue; Shi, Xiaodan; Qiao, Jie; Liu, Ping

2015-01-01

To investigate the single blastocyst transfer in preimplantation genetic diagnosis (PGD)/preimplantation genetic screening (PGS) cycles. 80 PGD/PGS cycles undergoing blastocyst biopsy were studied. There were 88 warming cycles during the study period. Only one warmed blastocyst was transferred per cycle. The outcomes were followed up to the infants were born. The embryo implantation rate was 54.55% (48/88). The clinical pregnancy rate was 54.55% (48/88) per transfer cycle and 60% (48/80) per initial PGD/PGS cycle. There was no multi-pregnant in this study. The live birth rate was 42.05% (37/88) per transfer cycle and 46.25% (37/80) per initial PGD/PGS cycle. In PGD/PGS cycles, single blastocyst transfer reduces the multiple pregnancy rate without affecting the clinical outcomes.

The attitudes of Dutch fertility specialists towards the addition of genetic testing in screening of tubal factor infertility.

Science.gov (United States)

Malogajski, Jelena; Jansen, Marleen E; Ouburg, Sander; Ambrosino, Elena; Terwee, Caroline B; Morré, Servaas A

2017-06-01

This study aims to identify elements perceived by Dutch fertility specialists as barriers and facilitators for the introduction of genetic testing, and their attitudes towards the use of genetic information. The genetic test would be implemented in routine screening for tubal pathology and identifies SNPs relevant for the immune response causing tubal pathology. Experienced reproductive specialists working in Dutch Academic Hospitals were interviewed. Based on the results of four interviews a questionnaire was developed and used to survey medical doctors in six out of eight Dutch Academic hospitals. 60.4% (n=91) stated that the addition of genetic markers to the Chlamydia trachomatis antibody test (CAT) in screening for tubal pathology would increase screening accuracy. 68.2% (n=90) agreed they would require additional training on clinical genetics. Clinical utility (91.2%, n=91) and cost-effectiveness (95.6%, n=91) were recognized by the respondents as important factors in gaining support for the new screening strategy. In summary, respondents showed a positive attitude towards the implementation of a genetic test combined with CAT for tubal factor infertility (TFI) screening. To gain their support the majority of respondents agreed that clinical utility, specifically cost-effectiveness, is an important factor. Comprehensive research about economic implications and utility regarding the introduction of genomic markers should be the next step in the implementation strategy. Furthermore, education and training would need to be developed and offered to fertility care professionals about genetic markers, their interpretation, and implications for clinical decision-making. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of molecular genetics and historical records to reconstruct the ...

African Journals Online (AJOL)

Recent advances in molecular genetics made the inference of past demographic events through the analysis of gene pools from modern populations possible. The technology uses genetic markers to provide previously unavailable resolution into questions of human evolution, migration and the historical relationship of ...

Genetic factors and molecular mechanisms in dry eye disease.

Science.gov (United States)

Lee, Ling; Garrett, Qian; Flanagan, Judith; Chakrabarti, Subhabrata; Papas, Eric

2018-04-01

Dry eye disease (DED) is a complex condition with a multifactorial etiology that can be difficult to manage successfully. While external factors are modifiable, treatment success is limited if genetic factors contribute to the disease. The purpose of this review is to compile research describing normal and abnormal ocular surface function on a molecular level, appraise genetic studies involving DED or DED-associated diseases, and introduce the basic methods used for conducting genetic epidemiology studies. Copyright © 2018 Elsevier Inc. All rights reserved.

Molecular species identification and population genetics of ...

African Journals Online (AJOL)

Molecular genetic techniques, such as DNA barcoding and genotyping, are increasingly being used to assist with the conservation and management of chondrichthyans worldwide. Southern Africa is a shark biodiversity hotspot, with a large number of endemic species. According to the IUCN Red List, a quarter of South ...

Molecular diversity and genetic relationships in Secale

Indian Academy of Sciences (India)

The objective of this study was to quantify the molecular diversity and to determine the genetic relationships amongSecalespp. and among cultivars ofSecale ... Faculty of Sciences, Campo Grande, Lisboa, Portugal; Departamento de Genética, Facultad de Biologia, Universidad Complutense, C/ José Antonio Novais, 12, ...

[Towards a molecular psychiatry].

Science.gov (United States)

de la Fuente, J R

1988-06-01

Recent research data from psychopharmacology, brain imaging and molecular genetics support the notion of a new psychiatric frontier: that of molecular psychiatry. Identification of different subtypes of neurotransmitter receptors and their changes in density and sensitivity in response to endogenous ligands and/or psychotropic drugs may account for the clinical expression of various behavioral phenomena, including some psychiatric disorders. Brain imaging, in particular positron-emission tomographic evaluations, are likely to change psychiatric nosology. New diagnostic elements derived from these scanners will allow to associate psychotic states to neuroreceptor changes. Molecular genetics has shown that bipolar affective disorder can be caused by a single gene. A strong linkage seems to exist between a gene locus on chromosome 11 and bipolar illness. An amyloid gene located on chromosome 21 has also been shown to be strongly related to familial Alzheimer's disease. While genetic heterogeneity limits the screening value of these findings, the powerful techniques of molecular biology have entered the field of psychiatry. Ethical issues regarding DNA immortality, gene cloning and gene therapy will strengthen this relationship.

Molecular Genetic of Atopic dermatitis: An Update

Science.gov (United States)

Al-Shobaili, Hani A.; Ahmed, Ahmed A.; Alnomair, Naief; Alobead, Zeiad Abdulaziz; Rasheed, Zafar

2016-01-01

Atopic dermatitis (AD) is a chronic multifactorial inflammatory skin disease. The pathogenesis of AD remains unclear, but the disease results from dysfunctions of skin barrier and immune response, where both genetic and environmental factors play a key role. Recent studies demonstrate the substantial evidences that show a strong genetic association with AD. As for example, AD patients have a positive family history and have a concordance rate in twins. Moreover, several candidate genes have now been suspected that play a central role in the genetic background of AD. In last decade advanced procedures similar to genome-wide association (GWA) and single nucleotide polymorphism (SNP) have been applied on different population and now it has been clarified that AD is significantly associated with genes of innate/adaptive immune systems, human leukocyte antigens (HLA), cytokines, chemokines, drug-metabolizing genes or various other genes. In this review, we will highlight the recent advancements in the molecular genetics of AD, especially on possible functional relevance of genetic variants discovered to date. PMID:27004062

Validation and application of a novel integrated genetic screening method to a cohort of 1,112 men with idiopathic azoospermia or severe oligozoospermia.

Science.gov (United States)

Oud, Manon S; Ramos, Liliana; O'Bryan, Moira K; McLachlan, Robert I; Okutman, Özlem; Viville, Stephane; de Vries, Petra F; Smeets, Dominique F C M; Lugtenberg, Dorien; Hehir-Kwa, Jayne Y; Gilissen, Christian; van de Vorst, Maartje; Vissers, Lisenka E L M; Hoischen, Alexander; Meijerink, Aukje M; Fleischer, Kathrin; Veltman, Joris A; Noordam, Michiel J

2017-11-01

Microdeletions of the Y chromosome (YCMs), Klinefelter syndrome (47,XXY), and CFTR mutations are known genetic causes of severe male infertility, but the majority of cases remain idiopathic. Here, we describe a novel method using single molecule Molecular Inversion Probes (smMIPs), to screen infertile men for mutations and copy number variations affecting known disease genes. We designed a set of 4,525 smMIPs targeting the coding regions of causal (n = 6) and candidate (n = 101) male infertility genes. After extensive validation, we screened 1,112 idiopathic infertile men with non-obstructive azoospermia or severe oligozoospermia. In addition to five chromosome YCMs and six other sex chromosomal anomalies, we identified five patients with rare recessive mutations in CFTR as well as a patient with a rare heterozygous frameshift mutation in SYCP3 that may be of clinical relevance. This results in a genetic diagnosis in 11-17 patients (1%-1.5%), a yield that may increase significantly when more genes are confidently linked to male infertility. In conclusion, we developed a flexible and scalable method to reliably detect genetic causes of male infertility. The assay consolidates the detection of different types of genetic variation while increasing the diagnostic yield and detection precision at the same or lower price compared with currently used methods. © 2017 Wiley Periodicals, Inc.

Molecular markers unravel intraspecific and interspecific genetic ...

Indian Academy of Sciences (India)

[Kotwal S., Dhar M. K., Kour B., Raj K. and Kaul S. 2013 Molecular markers unravel intraspecific and interspecific genetic variability in ... of bowel problems including chronic constipation, amoebic ..... while to select parents from accessions, Pov80 and Pov79 ... nology (DBT), Govt. of India, for financial assistance in the form.

Molecular screening and isolation of Newcastle disease virus from ...

African Journals Online (AJOL)

Molecular screening and isolation of Newcastle disease virus from live poultry markets and chickens from commercial poultry farms in Zaria, Kaduna state, Nigeria. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader).

Molecular Genetics of Beauveria bassiana Infection of Insects.

Science.gov (United States)

Ortiz-Urquiza, A; Keyhani, N O

2016-01-01

Research on the insect pathogenic filamentous fungus, Beauveria bassiana has witnessed significant growth in recent years from mainly physiological studies related to its insect biological control potential, to addressing fundamental questions regarding the underlying molecular mechanisms of fungal development and virulence. This has been in part due to a confluence of robust genetic tools and genomic resources for the fungus, and recognition of expanded ecological interactions with which the fungus engages. Beauveria bassiana is a broad host range insect pathogen that has the ability to form intimate symbiotic relationships with plants. Indeed, there is an increasing realization that the latter may be the predominant environmental interaction in which the fungus participates, and that insect parasitism may be an opportunist lifestyle evolved due to the carbon- and nitrogen-rich resources present in insect bodies. Here, we will review progress on the molecular genetics of B. bassiana, which has largely been directed toward identifying genetic pathways involved in stress response and virulence assumed to have practical applications in improving the insect control potential of the fungus. Important strides have also been made in understanding aspects of B. bassiana development. Finally, although increasingly apparent in a number of studies, there is a need for progressing beyond phenotypic mutant characterization to sufficiently investigate the molecular mechanisms underlying B. bassiana's unique and diverse lifestyles as saprophyte, insect pathogen, and plant mutualist. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular and genetic mechanisms of environmental mutagens

International Nuclear Information System (INIS)

Kubitschek, H.E.; Derstine, P.L.; Griego, V.M.; Matsushita, T.; Peak, J.G.; Peak, M.J.; Reynolds, P.R.; Webb, R.B.; Williams-Hill, D.

1981-01-01

This program is primarily concerned with elucidation of the nature of DNA lesions produced by environmental and energy related mutagens, their mechanisms of action, and their repair. The main focus is on actions of chemical mutagens and electromagnetic radiations. Synergistic interactions between mutagens and the mutational processes that lead to synergism are being investigated. Mutagens are chosen for study on the basis of their potential for analysis of mutation (as genetic probes), for development of procedures for reducing mutational damage, for their potential importance to risk assessment, and for development of improved mutagen testing systems. Bacterial cells are used because of the rapidity and clarity of scientific results that can be obtained, the detailed genetic maps, and the many well-defined mutand strains available. The conventional tools of microbial and molecular genetics are used, along with intercomparison of genetically related strains. Advantage is taken of tcollective dose commitment will result in more attention being paid to potential releases of radionuclides at relatively short times after disposal

Genetic characterization, species differentiation and detection of Fasciola spp. by molecular approaches.

Science.gov (United States)

Ai, Lin; Chen, Mu-Xin; Alasaad, Samer; Elsheikha, Hany M; Li, Juan; Li, Hai-Long; Lin, Rui-Qing; Zou, Feng-Cai; Zhu, Xing-Quan; Chen, Jia-Xu

2011-06-10

Liver flukes belonging to the genus Fasciola are among the causes of foodborne diseases of parasitic etiology. These parasites cause significant public health problems and substantial economic losses to the livestock industry. Therefore, it is important to definitively characterize the Fasciola species. Current phenotypic techniques fail to reflect the full extent of the diversity of Fasciola spp. In this respect, the use of molecular techniques to identify and differentiate Fasciola spp. offer considerable advantages. The advent of a variety of molecular genetic techniques also provides a powerful method to elucidate many aspects of Fasciola biology, epidemiology, and genetics. However, the discriminatory power of these molecular methods varies, as does the speed and ease of performance and cost. There is a need for the development of new methods to identify the mechanisms underpinning the origin and maintenance of genetic variation within and among Fasciola populations. The increasing application of the current and new methods will yield a much improved understanding of Fasciola epidemiology and evolution as well as more effective means of parasite control. Herein, we provide an overview of the molecular techniques that are being used for the genetic characterization, detection and genotyping of Fasciola spp..

Genetic Diversity Analysis in 27 Tomato Accessions Using Morphological and Molecular Markers

Directory of Open Access Journals (Sweden)

Catur Herison

2018-02-01

Full Text Available Genetic diversity is the most important aspect in tomato breeding activities. Better assessment on the diversity of the collected accessions will come up with better result of the cultivar development. This study aimed at analyzing the genetic diversity of 27 tomato accessions by morphological and molecular markers. Twenty seven accessions collected from various regions of Indonesia were planted in the field and evaluated for their morphological traits, and RAPD analyzed for their molecular markers. The UPGMA clustering analyzes, elaborating the combination of morphological and molecular data, indicated that the tomato accessions could be grouped into 5 major groups with 70 % genetic similarity levels. Current study indicated that although many accessions came from different locations, they congregated into the same group. Cherry, Kudamati 1 and Lombok 3 were the farthest genetic distant accessions to the others. Those three genotypes will be the most valuable accessions, when they were crossed with other accessions, for designing a prospective breeding program in the future.

Development of a qualitative, multiplex real-time PCR kit for screening of genetically modified organisms (GMOs).

Science.gov (United States)

Dörries, Hans-Henno; Remus, Ivonne; Grönewald, Astrid; Grönewald, Cordt; Berghof-Jäger, Kornelia

2010-03-01

The number of commercially available genetically modified organisms (GMOs) and therefore the diversity of possible target sequences for molecular detection techniques are constantly increasing. As a result, GMO laboratories and the food production industry currently are forced to apply many different methods to reliably test raw material and complex processed food products. Screening methods have become more and more relevant to minimize the analytical effort and to make a preselection for further analysis (e.g., specific identification or quantification of the GMO). A multiplex real-time PCR kit was developed to detect the 35S promoter of the cauliflower mosaic virus, the terminator of the nopaline synthase gene of Agrobacterium tumefaciens, the 35S promoter from the figwort mosaic virus, and the bar gene of the soil bacterium Streptomyces hygroscopicus as the most widely used sequences in GMOs. The kit contains a second assay for the detection of plant-derived DNA to control the quality of the often processed and refined sample material. Additionally, the plant-specific assay comprises a homologous internal amplification control for inhibition control. The determined limits of detection for the five assays were 10 target copies/reaction. No amplification products were observed with DNAs of 26 bacterial species, 25 yeasts, 13 molds, and 41 not genetically modified plants. The specificity of the assays was further demonstrated to be 100% by the specific amplification of DNA derived from reference material from 22 genetically modified crops. The applicability of the kit in routine laboratory use was verified by testing of 50 spiked and unspiked food products. The herein described kit represents a simple and sensitive GMO screening method for the reliable detection of multiple GMO-specific target sequences in a multiplex real-time PCR reaction.

Molecular genetic gene-environment studies using candidate genes in schizophrenia: a systematic review.

Science.gov (United States)

Modinos, Gemma; Iyegbe, Conrad; Prata, Diana; Rivera, Margarita; Kempton, Matthew J; Valmaggia, Lucia R; Sham, Pak C; van Os, Jim; McGuire, Philip

2013-11-01

The relatively high heritability of schizophrenia suggests that genetic factors play an important role in the etiology of the disorder. On the other hand, a number of environmental factors significantly influence its incidence. As few direct genetic effects have been demonstrated, and there is considerable inter-individual heterogeneity in the response to the known environmental factors, interactions between genetic and environmental factors may be important in determining whether an individual develops the disorder. To date, a considerable number of studies of gene-environment interactions (G×E) in schizophrenia have employed a hypothesis-based molecular genetic approach using candidate genes, which have led to a range of different findings. This systematic review aims to summarize the results from molecular genetic candidate studies and to review challenges and opportunities of this approach in psychosis research. Finally, we discuss the potential of future prospects, such as new studies that combine hypothesis-based molecular genetic candidate approaches with agnostic genome-wide association studies in determining schizophrenia risk. © 2013 Elsevier B.V. All rights reserved.

Recharging of a screened ion on the molecular ion

International Nuclear Information System (INIS)

Karbovanets, M.I.; Lazur, V.Yu.; Yudin, G.L.; Gosudarstvennyj Komitet po Ispol'zovaniyu Atomnoj Ehnergii SSSR, Obninsk. Fiziko-Ehnergeticheskij Inst.)

1987-01-01

Charge exchange of a screened ion on a molecular ion is studied in the Oppenheimer-Brinkman-Cramers approximation. To calculate ion exchange probabilities and cross sections summed over the final degenerated electron states method of Green functions analogous to that applied earlier in the direct Coulomb excitation theory and atomic ionization is developed

Genetic diversity in cultivated carioca common beans based on molecular marker analysis

Directory of Open Access Journals (Sweden)

Juliana Morini Küpper Cardoso Perseguini

2011-01-01

Full Text Available A wide array of molecular markers has been used to investigate the genetic diversity among common bean species. However, the best combination of markers for studying such diversity among common bean cultivars has yet to be determined. Few reports have examined the genetic diversity of the carioca bean, commercially one of the most important common beans in Brazil. In this study, we examined the usefulness of two molecular marker systems (simple sequence repeats - SSRs and amplified fragment length polymorphisms - AFLPs for assessing the genetic diversity of carioca beans. The amount of information provided by Roger's modified genetic distance was used to analyze SSR data and Jaccards similarity coefficient was used for AFLP data. Seventy SSRs were polymorphic and 20 AFLP primer combinations produced 635 polymorphic bands. Molecular analysis showed that carioca genotypes were quite diverse. AFLPs revealed greater genetic differentiation and variation within the carioca genotypes (Gst = 98% and Fst = 0.83, respectively than SSRs and provided better resolution for clustering the carioca genotypes. SSRs and AFLPs were both suitable for assessing the genetic diversity of Brazilian carioca genotypes since the number of markers used in each system provided a low coefficient of variation. However, fingerprint profiles were generated faster with AFLPs, making them a better choice for assessing genetic diversity in the carioca germplasm.

[The development of molecular human genetics and its significance for perspectives of modern medicine].

Science.gov (United States)

Coutelle, C; Speer, A; Grade, K; Rosenthal, A; Hunger, H D

1989-01-01

The introduction of molecular human genetics has become a paradigma for the application of genetic engineering in medicine. The main principles of this technology are the isolation of molecular probes, their application in hybridization reactions, specific gene-amplification by the polymerase chain reaction, and DNA sequencing reactions. These methods are used for the analysis of monogenic diseases by linkage studies and the elucidation of the molecular defect causing these conditions, respectively. They are also the basis for genomic diagnosis of monogenic diseases, introduced into the health care system of the GDR by a national project on Duchenne/Becker muscular dystrophy, Cystic Fibrosis and Phenylketonuria. The rapid development of basic research on the molecular analysis of the human genome and genomic diagnosis indicates, that human molecular genetics is becoming a decisive basic discipline of modern medicine.

Fast screening of ketamine in biological samples based on molecularly imprinted photonic hydrogels

International Nuclear Information System (INIS)

Meng, Liang; Meng, Pinjia; Zhang, Qingqing; Wang, Yanji

2013-01-01

Graphical abstract: A novel label-free colorimetric chemosensor: with the increase in the concentration of ketamine, the Bragg diffraction peak of MIPHs gradually shifted to the longer wavelength region. Accompanying the peak shift, the color change of MIPHs was also observed obviously: from green to red. Highlights: ► We developed the label-free colorimetric MIPHs for handy and fast screening of ketamine. ► The obvious color change of MIPHs was observed upon ketamine. ► The MIPHs exhibited good sensing abilities in an aqueous environment. ► The sensing mechanisms of the water-compatible MIPHs were investigated. ► The MIPHs were employed to screening ketamine in real biological samples. -- Abstract: A novel label-free colorimetric chemosensor was developed for handy and fast screening of ketamine with high sensitivity and specificity based on molecularly imprinted photonic hydrogels (MIPHs) that combined the colloidal-crystal with molecular imprinting technique. The unique inverse opal arrays with a thin polymer wall in which the imprinted nanocavities of ketamine moleculars distributed allowed high sensitive, quick responsive, specific detection of the target analyte, and good regenerating ability in an aqueous environment. Due to the hierarchical inverse opal structural characteristics, the specific ketamine molecular recognition process can induce obvious swelling of the MIPHs to be directly transferred into visually perceptible optical signal (change in color) which can be detected by the naked eye through Bragg diffractive shifts of ordered macroporous arrays. In order to enhance the recognition ability in aqueous environments, the MIPHs were designed as water-compatible and synthesized in a water–methanol system. The molecular recognition mechanisms were investigated. The proposed MIPHs were successfully employed to screen trace level ketamine in human urine and saliva samples, exhibiting high sensitivity, rapid response, and specificity in the

Fast screening of ketamine in biological samples based on molecularly imprinted photonic hydrogels

Energy Technology Data Exchange (ETDEWEB)

Meng, Liang [Department of Forensic Science, People' s Public Security University of China, Beijing (China); Meng, Pinjia, E-mail: mengpinjia@163.com [Department of Forensic Science, People' s Public Security University of China, Beijing (China); Zhang, Qingqing; Wang, Yanji [Department of Forensic Science, People' s Public Security University of China, Beijing (China)

2013-04-10

Graphical abstract: A novel label-free colorimetric chemosensor: with the increase in the concentration of ketamine, the Bragg diffraction peak of MIPHs gradually shifted to the longer wavelength region. Accompanying the peak shift, the color change of MIPHs was also observed obviously: from green to red. Highlights: ► We developed the label-free colorimetric MIPHs for handy and fast screening of ketamine. ► The obvious color change of MIPHs was observed upon ketamine. ► The MIPHs exhibited good sensing abilities in an aqueous environment. ► The sensing mechanisms of the water-compatible MIPHs were investigated. ► The MIPHs were employed to screening ketamine in real biological samples. -- Abstract: A novel label-free colorimetric chemosensor was developed for handy and fast screening of ketamine with high sensitivity and specificity based on molecularly imprinted photonic hydrogels (MIPHs) that combined the colloidal-crystal with molecular imprinting technique. The unique inverse opal arrays with a thin polymer wall in which the imprinted nanocavities of ketamine moleculars distributed allowed high sensitive, quick responsive, specific detection of the target analyte, and good regenerating ability in an aqueous environment. Due to the hierarchical inverse opal structural characteristics, the specific ketamine molecular recognition process can induce obvious swelling of the MIPHs to be directly transferred into visually perceptible optical signal (change in color) which can be detected by the naked eye through Bragg diffractive shifts of ordered macroporous arrays. In order to enhance the recognition ability in aqueous environments, the MIPHs were designed as water-compatible and synthesized in a water–methanol system. The molecular recognition mechanisms were investigated. The proposed MIPHs were successfully employed to screen trace level ketamine in human urine and saliva samples, exhibiting high sensitivity, rapid response, and specificity in the

Molecular genetics and genomics generate new insights into invertebrate pest invasions.

Science.gov (United States)

Kirk, Heather; Dorn, Silvia; Mazzi, Dominique

2013-07-01

Invertebrate pest invasions and outbreaks are associated with high social, economic, and ecological costs, and their significance will intensify with an increasing pressure on agricultural productivity as a result of human population growth and climate change. New molecular genetic and genomic techniques are available and accessible, but have been grossly underutilized in studies of invertebrate pest invasions, despite that they are useful tools for applied pest management and for understanding fundamental features of pest invasions including pest population demographics and adaptation of pests to novel and/or changing environments. Here, we review current applications of molecular genetics and genomics in the study of invertebrate pest invasions and outbreaks, and we highlight shortcomings from the current body of research. We then discuss recent conceptual and methodological advances in the areas of molecular genetics/genomics and data analysis, and we highlight how these advances will further our understanding of the demographic, ecological, and evolutionary features of invertebrate pest invasions. We are now well equipped to use molecular data to understand invertebrate dispersal and adaptation, and this knowledge has valuable applications in agriculture at a time when these are critically required.

Molecular Darwinism: the contingency of spontaneous genetic variation.

Science.gov (United States)

Arber, Werner

2011-01-01

The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions.

Using the Drosophila Melanogaster Genetics Reference Panel to Identify Toxicity Pathways for Toluene

Science.gov (United States)

Mechanistic information is needed to link effects of chemicals at molecular targets in high­ throughput screening assays to adverse outcomes in whole organisms. This study was designed to use the Drosophila Genetic Reference Panel (DGRP), a set of genetically well...

Molecular and genetic basis for partial resistance of western white pine against Cronartium ribicola.

Science.gov (United States)

Jun-Jun Liu; Arezoo Zamany; Richard. Sniezko

2012-01-01

Western white pine (Pinus monticola Douglas ex D. Don) is an important forest species in North America. Forest genetics programs have been breeding for durable genetic resistance against white pine blister rust (WPBR) caused by Cronartium ribicola in the past few decades. As various genetic resistance resources are screened and...

Genetic characterization, species differentiation and detection of Fasciola spp. by molecular approaches

Directory of Open Access Journals (Sweden)

Li Hai-Long

2011-06-01

Full Text Available Abstract Liver flukes belonging to the genus Fasciola are among the causes of foodborne diseases of parasitic etiology. These parasites cause significant public health problems and substantial economic losses to the livestock industry. Therefore, it is important to definitively characterize the Fasciola species. Current phenotypic techniques fail to reflect the full extent of the diversity of Fasciola spp. In this respect, the use of molecular techniques to identify and differentiate Fasciola spp. offer considerable advantages. The advent of a variety of molecular genetic techniques also provides a powerful method to elucidate many aspects of Fasciola biology, epidemiology, and genetics. However, the discriminatory power of these molecular methods varies, as does the speed and ease of performance and cost. There is a need for the development of new methods to identify the mechanisms underpinning the origin and maintenance of genetic variation within and among Fasciola populations. The increasing application of the current and new methods will yield a much improved understanding of Fasciola epidemiology and evolution as well as more effective means of parasite control. Herein, we provide an overview of the molecular techniques that are being used for the genetic characterization, detection and genotyping of Fasciola spp..

Position statement on opportunistic genomic screening from the Association of Genetic Nurses and Counsellors (UK and Ireland)

OpenAIRE

Middleton, Anna; Patch, Chris; Wiggins, Jennifer; Barnes, Kathy; Crawford, Gill; Benjamin, Caroline; Bruce, Anita

2014-01-01

The American College of Medical Genetics and Genomics released recommendations for reporting incidental findings (IFs) in clinical exome and genome sequencing. These suggest ‘opportunistic genomic screening' should be available to both adults and children each time a sequence is done and would be undertaken without seeking preferences from the patient first. Should opportunistic genomic screening be implemented in the United Kingdom, the Association of Genetic Nurses and Counsellors (AGNC), w...

Position statement on opportunistic genomic screening from the Association of Genetic Nurses and Counsellors (UK and Ireland).

Science.gov (United States)

Middleton, Anna; Patch, Chris; Wiggins, Jennifer; Barnes, Kathy; Crawford, Gill; Benjamin, Caroline; Bruce, Anita

2014-08-01

The American College of Medical Genetics and Genomics released recommendations for reporting incidental findings (IFs) in clinical exome and genome sequencing. These suggest 'opportunistic genomic screening' should be available to both adults and children each time a sequence is done and would be undertaken without seeking preferences from the patient first. Should opportunistic genomic screening be implemented in the United Kingdom, the Association of Genetic Nurses and Counsellors (AGNC), which represents British and Irish genetic counsellors and nurses, feels strongly that the following must be considered (see article for complete list): (1) Following appropriate genetic counselling, patients should be allowed to consent to or opt out of opportunistic genomic screening. (2) If true IFs are discovered the AGNC are guided by the report from the Joint Committee on Medical Genetics about the sharing of genetic testing results. (3) Children should not be routinely tested for adult-onset conditions. (4) The formation of a list of variants should involve a representative from the AGNC as well as a patient support group. (5) The variants should be for serious or life-threatening conditions for which there are treatments or preventative strategies available. (6) There needs to be robust evidence that the benefits of opportunistic screening outweigh the potential harms. (7) The clinical validity and utility of variants should be known. (8) There must be a quality assurance framework that operates to International standards for laboratory testing. (9) Psychosocial research is urgently needed in this area to understand the impact on patients.

Genetic screening of EXT1 and EXT2 in Cypriot families with ...

Indian Academy of Sciences (India)

RESEARCH NOTE. Genetic screening of EXT1 and EXT2 in Cypriot families with hereditary .... on samples from the HMO patient's parents in an attempt to establish .... Intragenic deletions involving single or multiple EXT1 or. EXT2 exons are ...

Genetic diversity analysis of common beans based on molecular markers

Directory of Open Access Journals (Sweden)

Homar R. Gill-Langarica

2011-01-01

Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

Genetic diversity analysis of common beans based on molecular markers

Directory of Open Access Journals (Sweden)

Homar R. Gill-Langarica

Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

Genetic diversity analysis of common beans based on molecular markers.

Science.gov (United States)

Gill-Langarica, Homar R; Muruaga-Martínez, José S; Vargas-Vázquez, M L Patricia; Rosales-Serna, Rigoberto; Mayek-Pérez, Netzahualcoyotl

2011-10-01

A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement

Science.gov (United States)

Prasad, Megana K; Geoffroy, Véronique; Vicaire, Serge; Jost, Bernard; Dumas, Michael; Le Gras, Stéphanie; Switala, Marzena; Gasse, Barbara; Laugel-Haushalter, Virginie; Paschaki, Marie; Leheup, Bruno; Droz, Dominique; Dalstein, Amelie; Loing, Adeline; Grollemund, Bruno; Muller-Bolla, Michèle; Lopez-Cazaux, Séréna; Minoux, Maryline; Jung, Sophie; Obry, Frédéric; Vogt, Vincent; Davideau, Jean-Luc; Davit-Beal, Tiphaine; Kaiser, Anne-Sophie; Moog, Ute; Richard, Béatrice; Morrier, Jean-Jacques; Duprez, Jean-Pierre; Odent, Sylvie; Bailleul-Forestier, Isabelle; Rousset, Monique Marie; Merametdijan, Laure; Toutain, Annick; Joseph, Clara; Giuliano, Fabienne; Dahlet, Jean-Christophe; Courval, Aymeric; El Alloussi, Mustapha; Laouina, Samir; Soskin, Sylvie; Guffon, Nathalie; Dieux, Anne; Doray, Bérénice; Feierabend, Stephanie; Ginglinger, Emmanuelle; Fournier, Benjamin; de la Dure Molla, Muriel; Alembik, Yves; Tardieu, Corinne; Clauss, François; Berdal, Ariane; Stoetzel, Corinne; Manière, Marie Cécile; Dollfus, Hélène; Bloch-Zupan, Agnès

2016-01-01

Background Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. Methods We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. Results We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. Conclusions We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. Trial registration numbers NCT01746121 and NCT02397824. PMID:26502894

The molecular genetic basis of age-related macular degeneration ...

Indian Academy of Sciences (India)

2009-12-10

Dec 10, 2009 ... this review, we have provided an overview on the underlying molecular genetic mechanisms in AMD worldwide and highlight ..... eases like diabetes (Scott et al. ...... 2006 Systematic review and meta-analysis of.

A genetic analysis of segregation distortion revealed by molecular ...

Indian Academy of Sciences (India)

Journal of Genetics, Vol. 90, No. ... Segregation analysis was based on 64 molecular markers, including 26 .... FHB of RIL populations was controlled by quantitative trait ... The authors acknowledge financial support by the National Basic.

A Baseline Algorithm for Molecular Diagnosis of Genetic Eye Diseases: Ophthalmologist’s Perspective

Directory of Open Access Journals (Sweden)

Hande Taylan Şekeroğlu

2016-12-01

microscopically visible abnormalities in chromosome number and structure, as well as translocations and large indels, and is appropriate as the first-tier test in multisystemic congenital abnormalities. Although conventional cytogenetic analysis may be considered as a screening test in such patients, microscopic diagnosis sometimes requires preliminary clinical diagnosis, designed in order to unveil specific deletions or duplications. A classic example is the small 11p interstitial deletion in Wilms tumor and aniridia, which could only be shown via fluorescence in situ hybridization or multiplex ligation-dependent probe amplification. Array comparative genomic hybridization methods are preferred for genetic eye diseases involving copy number variations. One such example is congenital cataract, which has a very complicated phenotype-genotype correlation and shows clinical heterogeneity. Responsible mutations in crystallins, transcription factors and membrane proteins have been reported.3 Furthermore, single nucleotide polymorphism array may enable the detection of disease predisposition or drug resistance (e.g. age-related macular degeneration. Next generation sequencing is the most current technology allowing parallel sequencing of many genes and may cover either a spectrum of known genes or all exons of all genes, allowing the discovery of new causative genes. The latter is called whole exome sequencing, and is a popular and practical investigation tool for developmental diseases.1 Genetic testing, theoretically, can also reveal the underlying ocular problem in cases with subnormal vision but otherwise normal ophthalmological examination (i.e. inherited retinal dystrophies, or it can define the high-risk group for an ocular disease and factors that prevent/delay any poor prognosis (i.e. early-onset glaucoma.4 The ultimate aim is to treat the condition. This is crucial in genetic disorders, in which modern treatment suggestions involve replacement of the missing molecular element

Quantifying the advantages and disadvantages of pre-placement genetic screening.

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Palmer, K T; Poole, J; Rawbone, R G; Coggon, D

2004-05-01

Tests of genotype may enable workers at unusual risk of future ill-health to be identified. Using them to select for employment, however, entails gains and losses to employers and employees. Ensuring a fair balance between the rights and obligations of each group requires a value judgement, but the advantages and disadvantages to interested parties must first be quantified in a meaningful way. The purposes of pre-employment screening are reviewed, and several simple measures relevant to the separate interests of employers and job applicants proposed-number screened to prevent a single adverse outcome; number excluded to prevent a case; expected incidence of the adverse outcome in those excluded; and preventable fraction. The derivation of these measures is illustrated, and the factors that influence them (the prevalence of the prognostic trait, the relative risk that it carries for an adverse outcome, and the overall incidence of disease) are related algebraically and graphically, to aid judgement on the utility of screening under different circumstances. In sensitive areas such as genetic testing the onus should be on the employer to justify plans for pre-placement screening. Several quantitative measures can be used to inform the ethical and economic debate about screening and to evaluate alternative strategies for prevention.

Journal of Genetics, Volume 86, 2007

Indian Academy of Sciences (India)

phalipoproteinemia in a Moroccan family (Research note) 159 dog. Isolation, characterization and genetic analysis of canine GATA4 gene in a family of Doberman Pinschers with an atrial septal de- fect. 241. Isolation, characterization and molecular screening of canine. SLC26A2 (sulphate transporter) in German Shepherd ...

Management of insect pests: Nuclear and related molecular and genetic techniques

International Nuclear Information System (INIS)

1993-01-01

The conference was organized in eight sessions: opening, genetic engineering and molecular biology, genetics, operational programmes, F 1 sterility and insect behaviour, biocontrol, research and development on the tsetse fly, and quarantine. The 64 individual contributions have been indexed separately for INIS. Refs, figs and tabs

The Molecular Epidemiology and Genetic Environment of Carbapenemases Detected in Africa.

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Sekyere, John Osei; Govinden, Usha; Essack, Sabiha

2016-01-01

Research articles describing carbapenemases and their genetic environments in Gram-negative bacteria were reviewed to determine the molecular epidemiology of carbapenemases in Africa. The emergence of resistance to the carbapenems, the last resort antibiotic for difficult to treat bacterial infections, affords clinicians few therapeutic options, with a resulting increase in morbidities, mortalities, and healthcare costs. However, the molecular epidemiology of carbapenemases throughout Africa is less described. Research articles and conference proceedings describing the genetic environment and molecular epidemiology of carbapenemases in Africa were retrieved from Google Scholar, Scifinder, Pubmed, Web of Science, and Science Direct databases. Predominant carbapenemase genes so far described in Africa include the blaOXA-48 type, blaIMP, blaVIM, and blaNDM in Acinetobacter baumannii, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter spp., and Escherichia coli carried on various plasmid types and sizes, transposons, and integrons. Class D and class B carbapenemases, mainly prevalent in A. baumannii, K. pneumoniae, E. cloacae, Citrobacter spp., and E. coli were the commonest carbapenemases. Carbapenemases are mainly reported in North and South Africa as under-resourced laboratories, lack of awareness and funding preclude the detection and reporting of carbapenemase-mediated resistance. Consequently, the true molecular epidemiology of carbapenemases and their genetic environment in Africa is still unknown.

Relative profile analysis of molecular markers for identification and genetic discrimination of loaches (Pisces, Nemacheilidae).

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Patil, Tejas Suresh; Tamboli, Asif Shabodin; Patil, Swapnil Mahadeo; Bhosale, Amrut Ravindra; Govindwar, Sanjay Prabhu; Muley, Dipak Vishwanathrao

2016-01-01

Genus Nemacheilus, Nemachilichthys and Schistura belong to the family Nemacheilidae of the order Cypriniformes. The present investigation was undertaken to observe genetic diversity, phylogenetic relationship and to develop a molecular-based tool for taxonomic identification. For this purpose, four different types of molecular markers were utilized in which 29 random amplified polymorphic DNA (RAPD), 25 inter-simple sequence repeat (ISSR) markers, and 10 amplified fragment length polymorphism (AFLP) marker sets were screened and mitochondrial COI gene was sequenced. This study added COI barcodes for the identification of Nemacheilus anguilla, Nemachilichthys rueppelli and Schistura denisoni. RAPD showed higher polymorphism (100%) than the ISSR (93.75-100%) and AFLP (93.86-98.96%). The polymorphic information content (PIC), heterozygosity, multiplex ratio, and gene diversity was observed highest for AFLP primers, whereas the major allele frequency was observed higher for RAPD (0.5556) and lowest for AFLP (0.1667). The COI region of all individuals was successfully amplified and sequenced, which gave a 100% species resolution. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Progress in cancer genetics: lessons from pancreatic cancer

NARCIS (Netherlands)

Goggins, M.; Kern, S. E.; Offerhaus, J. A.; Hruban, R. H.

1999-01-01

In the near future advances in the molecular basis of cancer are expected to facilitate cancer diagnosis, to rationalize treatment, to facilitate screening, and to identify individuals requiring cancer prevention strategies. The literature was reviewed concerning the genetic alterations that

76 FR 18227 - Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of...

Science.gov (United States)

2011-04-01

...] Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of Meeting... comment period for the notice announcing a meeting of the Molecular and Clinical Genetics Panel (the panel... Clinical Genetics Panel of the Medical Devices Advisory Committee, and the opening of a public docket to...

Frequency of Usher syndrome in two pediatric populations: Implications for genetic screening of deaf and hard of hearing children.

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Kimberling, William J; Hildebrand, Michael S; Shearer, A Eliot; Jensen, Maren L; Halder, Jennifer A; Trzupek, Karmen; Cohn, Edward S; Weleber, Richard G; Stone, Edwin M; Smith, Richard J H

2010-08-01

Usher syndrome is a major cause of genetic deafness and blindness. The hearing loss is usually congenital and the retinitis pigmentosa is progressive and first noticed in early childhood to the middle teenage years. Its frequency may be underestimated. Newly developed molecular technologies can detect the underlying gene mutation of this disorder early in life providing estimation of its prevalence in at risk pediatric populations and laying a foundation for its incorporation as an adjunct to newborn hearing screening programs. A total of 133 children from two deaf and hard of hearing pediatric populations were genotyped first for GJB2/6 and, if negative, then for Usher syndrome. Children were scored as positive if the test revealed > or =1 pathogenic mutations in any Usher gene. Fifteen children carried pathogenic mutations in one of the Usher genes; the number of deaf and hard of hearing children carrying Usher syndrome mutations was 15/133 (11.3%). The population prevalence was estimated to be 1/6000. Usher syndrome is more prevalent than has been reported before the genome project era. Early diagnosis of Usher syndrome has important positive implications for childhood safety, educational planning, genetic counseling, and treatment. The results demonstrate that DNA testing for Usher syndrome is feasible and may be a useful addition to newborn hearing screening programs.

Molecular approaches for genetic improvement of seed quality and characterization of genetic diversity in soybean: a critical review.

Science.gov (United States)

Tripathi, Niraj; Khare, Dhirendra

2016-10-01

Soybean is an economically important leguminous crop. Genetic improvements of soybeans have focused on enhancement of seed and oil yield, development of varieties suited to different cropping systems, and breeding resistant/tolerant varieties for various biotic and abiotic stresses. Plant breeders have used conventional breeding techniques for the improvement of these traits in soybean. The conventional breeding process can be greatly accelerated through the application of molecular and genomic approaches. Molecular markers have proved to be a new tool in soybean breeding by enhancing selection efficiency in a rapid and time-bound manner. An overview of molecular approaches for the genetic improvement of soybean seed quality parameters, considering recent applications of marker-assisted selection and 'omics' research, is provided in this article.

Panel 4: Recent Advances in Otitis Media in Molecular Biology, Biochemistry, Genetics, and Animal Models

Science.gov (United States)

Li, Jian-Dong; Hermansson, Ann; Ryan, Allen F.; Bakaletz, Lauren O.; Brown, Steve D.; Cheeseman, Michael T.; Juhn, Steven K.; Jung, Timothy T. K.; Lim, David J.; Lim, Jae Hyang; Lin, Jizhen; Moon, Sung-Kyun; Post, J. Christopher

2014-01-01

Background Otitis media (OM) is the most common childhood bacterial infection and also the leading cause of conductive hearing loss in children. Currently, there is an urgent need for developing novel therapeutic agents for treating OM based on full understanding of molecular pathogenesis in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Objective To provide a state-of-the-art review concerning recent advances in OM in the areas of molecular biology, biochemistry, genetics, and animal model studies and to discuss the future directions of OM studies in these areas. Data Sources and Review Methods A structured search of the current literature (since June 2007). The authors searched PubMed for published literature in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Results Over the past 4 years, significant progress has been made in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. These studies brought new insights into our understanding of the molecular and biochemical mechanisms underlying the molecular pathogenesis of OM and helped identify novel therapeutic targets for OM. Conclusions and Implications for Practice Our understanding of the molecular pathogenesis of OM has been significantly advanced, particularly in the areas of inflammation, innate immunity, mucus overproduction, mucosal hyperplasia, middle ear and inner ear interaction, genetics, genome sequencing, and animal model studies. Although these studies are still in their experimental stages, they help identify new potential therapeutic targets. Future preclinical and clinical studies will help to translate these exciting experimental research findings into clinical applications. PMID:23536532

Molecular research on the genetic diversity of Tunisian date palm ...

African Journals Online (AJOL)

Molecular research on the genetic diversity of Tunisian date palm ( Phoenix dactylifera L.) using the random amplified microsatellite polymorphism (RAMPO) and amplified fragment length polymorphism (AFLP) methods.

A comprehensive platform for highly multiplexed mammalian functional genetic screens

Directory of Open Access Journals (Sweden)

Cheung-Ong Kahlin

2011-05-01

Full Text Available Abstract Background Genome-wide screening in human and mouse cells using RNA interference and open reading frame over-expression libraries is rapidly becoming a viable experimental approach for many research labs. There are a variety of gene expression modulation libraries commercially available, however, detailed and validated protocols as well as the reagents necessary for deconvolving genome-scale gene screens using these libraries are lacking. As a solution, we designed a comprehensive platform for highly multiplexed functional genetic screens in human, mouse and yeast cells using popular, commercially available gene modulation libraries. The Gene Modulation Array Platform (GMAP is a single microarray-based detection solution for deconvolution of loss and gain-of-function pooled screens. Results Experiments with specially constructed lentiviral-based plasmid pools containing ~78,000 shRNAs demonstrated that the GMAP is capable of deconvolving genome-wide shRNA "dropout" screens. Further experiments with a larger, ~90,000 shRNA pool demonstrate that equivalent results are obtained from plasmid pools and from genomic DNA derived from lentivirus infected cells. Parallel testing of large shRNA pools using GMAP and next-generation sequencing methods revealed that the two methods provide valid and complementary approaches to deconvolution of genome-wide shRNA screens. Additional experiments demonstrated that GMAP is equivalent to similar microarray-based products when used for deconvolution of open reading frame over-expression screens. Conclusion Herein, we demonstrate four major applications for the GMAP resource, including deconvolution of pooled RNAi screens in cells with at least 90,000 distinct shRNAs. We also provide detailed methodologies for pooled shRNA screen readout using GMAP and compare next-generation sequencing to GMAP (i.e. microarray based deconvolution methods.

Molecular genetic diversity in populations of the stingless bee Plebeia remota: A case study

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Flávio de Oliveira Francisco

2013-01-01

Full Text Available Genetic diversity is a major component of the biological diversity of an ecosystem. The survival of a population may be seriously threatened if its genetic diversity values are low. In this work, we measured the genetic diversity of the stingless bee Plebeia remota based on molecular data obtained by analyzing 15 microsatellite loci and sequencing two mitochondrial genes. Population structure and genetic diversity differed depending on the molecular marker analyzed: microsatellites showed low population structure and moderate to high genetic diversity, while mitochondrial DNA (mtDNA showed high population structure and low diversity in three populations. Queen philopatry and male dispersal behavior are discussed as the main reasons for these findings.

[Psychological distress in applicants for genetic screening for colorectal cancer].

Science.gov (United States)

Fantini, C; Pedinielli, J-L; Manouvrier, S

2007-01-01

Introduction. The development of a DNA based diagnostic test has allowed for the genetic screening of many hereditary diseases. In addition to the identification of the deleterious gene, this screening process has led to the recognition of developing illnesses at high risk. In recent years, a number of genes predisposing to an inherited cancer syndrome have been identified. Our purpose in this study was to determine whether subjects at risk who test for inherited colorectal cancer, are likely to develop a higher level of psychological distress than the norm, taking into consideration the particular history of this familial disease. The demographic and psychosocial aspects of our population was described using: 1) the State Trait Anxiety Inventory (STAI), 2) the Center for Epidemiologic Studies Depression (CES-D), 3) a perceived risk for the gene carrier, 4) subjective perception of personal vulnerability and 5) the role of the medical status (affected or not), which places the subject in either predisposition or predictive testing. Results show that our population had a higher predisposition for depressive disorders (chi2=9,3. p=0.002) and a significantly higher state of anxiety (chi2=9,3. p=0.002), prior to genetic counselling, compared with other populations. We found no evidence in the medical status, nor the perceived risk. However, the assessment of one's own personal vulnerability is related to psychological distress. These results highlight the particular vulnerability of subjects undergoing genetic testing as well as showing the pertinence of proposing psychological help throughout the process of these new specific diagnoses.

Enhancing genetic gain in the era of molecular breeding.

Science.gov (United States)

Xu, Yunbi; Li, Ping; Zou, Cheng; Lu, Yanli; Xie, Chuanxiao; Zhang, Xuecai; Prasanna, Boddupalli M; Olsen, Michael S

2017-05-17

As one of the important concepts in conventional quantitative genetics and breeding, genetic gain can be defined as the amount of increase in performance that is achieved annually through artificial selection. To develop pro ducts that meet the increasing demand of mankind, especially for food and feed, in addition to various industrial uses, breeders are challenged to enhance the potential of genetic gain continuously, at ever higher rates, while they close the gaps that remain between the yield potential in breeders' demonstration trials and the actual yield in farmers' fields. Factors affecting genetic gain include genetic variation available in breeding materials, heritability for traits of interest, selection intensity, and the time required to complete a breeding cycle. Genetic gain can be improved through enhancing the potential and closing the gaps, which has been evolving and complemented with modern breeding techniques and platforms, mainly driven by molecular and genomic tools, combined with improved agronomic practice. Several key strategies are reviewed in this article. Favorable genetic variation can be unlocked and created through molecular and genomic approaches including mutation, gene mapping and discovery, and transgene and genome editing. Estimation of heritability can be improved by refining field experiments through well-controlled and precisely assayed environmental factors or envirotyping, particularly for understanding and controlling spatial heterogeneity at the field level. Selection intensity can be significantly heightened through improvements in the scale and precision of genotyping and phenotyping. The breeding cycle time can be shortened by accelerating breeding procedures through integrated breeding approaches such as marker-assisted selection and doubled haploid development. All the strategies can be integrated with other widely used conventional approaches in breeding programs to enhance genetic gain. More transdisciplinary

Congenital heart disease and genetic syndromes: new insights into molecular mechanisms.

Science.gov (United States)

Calcagni, Giulio; Unolt, Marta; Digilio, Maria Cristina; Baban, Anwar; Versacci, Paolo; Tartaglia, Marco; Baldini, Antonio; Marino, Bruno

2017-09-01

Advances in genetics allowed a better definition of the role of specific genetic background in the etiology of syndromic congenital heart defects (CHDs). The identification of a number of disease genes responsible for different syndromes have led to the identification of several transcriptional regulators and signaling transducers and modulators that are critical for heart morphogenesis. Understanding the genetic background of syndromic CHDs allowed a better characterization of the genetic basis of non-syndromic CHDs. In this sense, the well-known association of typical CHDs in Down syndrome, 22q11.2 microdeletion and Noonan syndrome represent paradigms as chromosomal aneuploidy, chromosomal microdeletion and intragenic mutation, respectively. Area covered: For each syndrome the anatomical features, distinctive cardiac phenotype and molecular mechanisms are discussed. Moreover, the authors include recent genetic findings that may shed light on some aspects of still unclear molecular mechanisms of these syndromes. Expert commentary: Further investigations are needed to enhance the translational approach in the field of genetics of CHDs. When there is a well-established definition of genotype-phenotype (reverse medicine) and genotype-prognosis (predictive and personalized medicine) correlations, hopefully preventive medicine will make its way in this field. Subsequently a reduction will be achieved in the morbidity and mortality of children with CHDs.

Update on the Cytogenetics and Molecular Genetics of Chordoma

Directory of Open Access Journals (Sweden)

Larizza Lidia

2005-02-01

Full Text Available Abstract Chordoma is a rare mesenchymal tumour of complex biology for which only histologic and immunohistochemical criteria have been defined, but no biomarkers predicting the clinical outcome and response to treatment have yet been recognised. We herein review the interdisciplinary information achieved by epidemiologists, neurosurgeons and basic scientists on chordoma, usually a sporadic tumour, which also includes a small fraction of familial cases. Main focus is on the current knowledge of the genetic alterations which might pinpoint candidate genes and molecular mechanisms shared by sporadic and familiar chordomas. Due to the scarcity of the investigated tumour specimens and the multiple chromosome abnormalities found in tumours with aberrant karyotypes, conventional cytogenetics and Fluorescence In Situ Hybridization failed to detect recurrent chordoma-specific chromosomal rearrangements. Genome-wide approaches such as Comparative Genomic Hybridization (CGH are yet at an initial stage of application and should be implemented using BAC arrays either genome-wide or targeting selected genomic regions, disclosed by Loss of Heterozygosity (LOH studies. An LOH region was shown by a systematic study on a consistent number of chordomas to encompass 1p36, a genomic interval where a candidate gene was suggested to reside. Despite the rarity of multiplex families with chordoma impaired linkage studies, a chordoma locus could be mapped to chromosome 7q33 by positive lod score in three independent families. The role in chordomagenesis of the Tuberous Sclerosis Complex (TSC genes has been proved, but the extent of involvement of TSC1 and TSC2 oncosuppressors in chordoma remains to be assessed. In spite of the scarce knowledge on the genetics and molecular biology of chordoma, recent initiation of clinical trials using molecular-targeted therapy, should validate new molecular targets and predict the efficacy of a given therapy. Comparative genetic and

Pooled-matrix protein interaction screens using Barcode Fusion Genetics.

Science.gov (United States)

Yachie, Nozomu; Petsalaki, Evangelia; Mellor, Joseph C; Weile, Jochen; Jacob, Yves; Verby, Marta; Ozturk, Sedide B; Li, Siyang; Cote, Atina G; Mosca, Roberto; Knapp, Jennifer J; Ko, Minjeong; Yu, Analyn; Gebbia, Marinella; Sahni, Nidhi; Yi, Song; Tyagi, Tanya; Sheykhkarimli, Dayag; Roth, Jonathan F; Wong, Cassandra; Musa, Louai; Snider, Jamie; Liu, Yi-Chun; Yu, Haiyuan; Braun, Pascal; Stagljar, Igor; Hao, Tong; Calderwood, Michael A; Pelletier, Laurence; Aloy, Patrick; Hill, David E; Vidal, Marc; Roth, Frederick P

2016-04-22

High-throughput binary protein interaction mapping is continuing to extend our understanding of cellular function and disease mechanisms. However, we remain one or two orders of magnitude away from a complete interaction map for humans and other major model organisms. Completion will require screening at substantially larger scales with many complementary assays, requiring further efficiency gains in proteome-scale interaction mapping. Here, we report Barcode Fusion Genetics-Yeast Two-Hybrid (BFG-Y2H), by which a full matrix of protein pairs can be screened in a single multiplexed strain pool. BFG-Y2H uses Cre recombination to fuse DNA barcodes from distinct plasmids, generating chimeric protein-pair barcodes that can be quantified via next-generation sequencing. We applied BFG-Y2H to four different matrices ranging in scale from ~25 K to 2.5 M protein pairs. The results show that BFG-Y2H increases the efficiency of protein matrix screening, with quality that is on par with state-of-the-art Y2H methods. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Molecular genetics of hemophilia A: Clinical perspectives | Tantawy ...

African Journals Online (AJOL)

Since the publication of the sequence of the factor VIII (F8) gene in 1984, a large number of mutations that cause hemophilia A have been identified and a significant progress has been made in translating this knowledge for clinical diagnostic and therapeutic purposes. Molecular genetic testing is used to determine the ...

Nasopharyngeal angiofibroma: review of the genetic and molecular aspects

Directory of Open Access Journals (Sweden)

Oliveira, Viviane Boaventura de

2008-09-01

Full Text Available Introduction: Juvenile nasopharyngeal angiofibroma (JNA is a rare fibrovascular tumor of unknown etiology, with few studies analyzing its pathogenesis. Objective: Reviewing JNA's pathogenesis, emphasizing genetic and molecular aspects. Method: All the relevant articles indexed in PUBMED and LILACS, besides reference book chapters, published between 1959 and 2007 were reviewed. Results: The sex selectivity seen in JNA may be explained by intranuclear accumulation of androgen receptor and beta-catenin, a co-activator which increases the tumor sensitivity to androgynous. The genetic alterations seen in JNA are most frequently located in sexual chromosomes. A number of growth factors seem to be related to the tumor pathogenesis. The insulin-like growth factor II is highly expressed while the vascular endothelial growth factor and the transforming growth factor beta are released by stromal cells and may influence the JNA's growth and vascularization. Conclusion: In spite of the scarce data describing the JNA etiology and pathogenesis, genetic and molecular factors seem to collaborate to the understanding of the disease's many clinical and morphological features. Knowledge regarding these specific issues could contribute for the establishment of potential therapeutic targets in the future.

[Genetics of congenital heart diseases].

Science.gov (United States)

Bonnet, Damien

2017-06-01

Developmental genetics of congenital heart diseases has evolved from analysis of serial slices in embryos towards molecular genetics of cardiac morphogenesis with a dynamic view of cardiac development. Genetics of congenital heart diseases has also changed from formal genetic analysis of familial recurrences or population-based analysis to screening for mutations in candidates genes identified in animal models. Close cooperation between molecular embryologists, pathologists involved in heart development and pediatric cardiologists is crucial for further increase of knowledge in the field of cardiac morphogenesis and genetics of cardiac defects. The genetic model for congenital heart disease has to be revised to favor a polygenic origin rather than a monogenic one. The main mechanism is altered genic dosage that can account for heart diseases in chromosomal anomalies as well as in point mutations in syndromic and isolated congenital heart diseases. The use of big data grouping information from cardiac development, interactions between genes and proteins, epigenetic factors such as chromatin remodeling or DNA methylation is the current source for improving our knowledge in the field and to give clues for future therapies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Preimplantation genetic diagnosis and screening: Current status and future challenges

Directory of Open Access Journals (Sweden)

Hsin-Fu Chen

2018-02-01

Full Text Available Preimplantation genetic diagnosis (PGD is a clinically feasible technology to prevent the transmission of monogenic inherited disorders in families afflicted the diseases to the future offsprings. The major technical hurdle is it does not have a general formula for all mutations, thus different gene locus needs individualized, customized design to make the diagnosis accurate enough to be applied on PGD, in which the quantity of DNA is scarce, whereas timely result is sometimes requested if fresh embryo transfer is desired. On the other hand, preimplantation genetic screening (PGS screens embryo with aneuploidy and was also known as PGD-A (A denotes aneuploidy in order to enhance the implantation rates as well as livebirth rates. In contrasts to PGD, PGS is still under ferocious debate, especially recent reports found that euploid babies were born after transferring the aneuploid embryos diagnosed by PGS back to the womb and only very few randomized trials of PGS are available in the literature. We have been doing PGD and/or PGS for more than 10 years as one of the core PGD/PGS laboratories in Taiwan. Here we provide a concise review of PGD/PGS regarding its current status, both domestically and globally, as well as its future challenges.

Comprehensive preimplantation genetic screening and sperm deoxyribonucleic acid fragmentation from three males carrying balanced chromosome rearrangements.

Science.gov (United States)

Ramos, Laia; Daina, Gemma; Del Rey, Javier; Ribas-Maynou, Jordi; Fernández-Encinas, Alba; Martinez-Passarell, Olga; Boada, Montserrat; Benet, Jordi; Navarro, Joaquima

2015-09-01

To assess whether preimplantation genetic screening can successfully identify cytogenetically normal embryos in couples carrying balanced chromosome rearrangements in addition to increased sperm DNA fragmentation. Comprehensive preimplantation genetic screening was performed on three couples carrying chromosome rearrangements. Sperm DNA fragmentation was assessed for each patient. Academic center. One couple with the male partner carrying a chromosome 2 pericentric inversion and two couples with the male partners carrying a Robertsonian translocation (13:14 and 14:21, respectively). A single blastomere from each of the 18 cleavage-stage embryos obtained was analysed by metaphase comparative genomic hybridization. Single- and double-strand sperm DNA fragmentation was determined by the alkaline and neutral Comet assays. Single- and double-strand sperm DNA fragmentation values and incidence of chromosome imbalances in the blastomeres were analyzed. The obtained values of single-strand sperm DNA fragmentation were between 47% and 59%, and the double-strand sperm DNA fragmentation values were between 43% and 54%. No euploid embryos were observed in the couple showing the highest single-strand sperm DNA fragmentation. However, euploid embryos were observed in the other two couples: embryo transfer was performed, and pregnancy was achieved by the couple showing the lowest sperm DNA fragmentation values. Preimplantation genetic screening enables the detection of euploid embryos in couples affected by balanced chromosome rearrangements and increased sperm DNA fragmentation. Even though sperm DNA fragmentation may potentially have clinical consequences on fertility, comprehensive preimplantation genetic screening allows for the identification and transfer of euploid embryos. Copyright © 2015. Published by Elsevier Inc.

Molecular Markers for Genetic Diversity Studies of European Hare (Lepus europaeus Pallas, 1778 Populations

Directory of Open Access Journals (Sweden)

Noémi Soós

2015-05-01

Full Text Available The purpose of this article is to give an overview of different molecular techniques which have been used in studies concerning population genetic issues of Lepus species and specifically of L. europaeus. The importance of these researches is ever-growing as the European populations of the brown hare have suffered several falloffs as a consequent upon both natural and anthropogenic effects. With developing tools and techniques molecular genetics have become the centrepiece of population genetics and conservation biology. Nucleic acid methods based on both bi- and uniparentally inherited DNA (allozymes, microsatellites, Y chromosome, mtDNA are often used to study genetic structure, diversity and phylogeography of different species’ populations due to their effectiveness in identifying genetic variability

Construction of intergeneric conjugal transfer for molecular genetic ...

African Journals Online (AJOL)

SAM

2014-03-26

Mar 26, 2014 ... The attB integration site in the S. mobaraensis genome was detected as a single attB ... present study, to promote the molecular genetic study of. S. mobaraensis .... further increase in the number of E. coli donor cells. (≥1.25 × 108) (Choi et .... rational mutagenesis and random mutagenesis. Appl. Microbiol.

Hamartomatous polyps - a clinical and molecular genetic study

DEFF Research Database (Denmark)

Jelsig, Anne Marie

2016-01-01

the knowledge on clinical course and molecular genetics in patients with HPs and HPS, and to investigate research participants' attitude towards the results of extensive genetic testing. Paper I: In the first paper we investigated the occurrence, anatomic distribution, and other demographics of juvenile polyps...... appearance. Patients with one or a few juvenile polyps are usually not offered clinical follow-up as the polyp(s) are considered not to harbour any malignant potential. Nevertheless, it is important to note that juvenile polyps and HPs are also found in patients with hereditary hamartomatous polyposis......-Jeghers syndrome, and the PTEN hamartoma tumour syndrome. Currently, the HPS diagnoses are based on clinical criteria and are often assisted with genetic testing as candidate genes have been described for each syndrome. This thesis is based on six scientific papers. The overall aim of the studies was to expand...

Frequency of chromosomal aneuploidy in high quality embryos from young couples using preimplantation genetic screening

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Farzaneh Fesahat

2017-09-01

Full Text Available Background: Selection of the best embryo for transfer is very important in assisted reproductive technology (ART. Using morphological assessment for this selection demonstrated that the correlation between embryo morphology and implantation potential is relatively weak. On the other hand, aneuploidy is a key genetic factor that can influence human reproductive success in ART. Objective: The aim of this lab trial study was to evaluate the incidence of aneuploidies in five chromosomes in the morphologically high-quality embryos from young patients undergoing ART for sex selection. Materials and Methods: A total of 97 high quality embryos from 23 women at the age of 37or younger years that had previously undergone preimplantation genetic screening for sex selection were included in this study. After washing, the slides of blastomeres from embryos of patients were reanalyzed by fluorescence in-situ hybridization for chromosomes 13, 18 and 21. Results: There was a significant rate of aneuploidy determination in the embryos using preimplantation genetic screening for both sex and three evaluated autosomal chromosomes compared to preimplantation genetic screening for only sex chromosomes (62.9% vs. 24.7%, p=0.000. The most frequent detected chromosomal aneuploidy was trisomy or monosomy of chromosome 13. Conclusion: There is considerable numbers of chromosomal abnormalities in embryos generated in vitro which cause in vitro fertilization failure and it seems that morphological characterization of embryos is not a suitable method for choosing the embryos without these abnormalities

Implementation of molecular karyotyping in clinical genetics

Directory of Open Access Journals (Sweden)

Luca Lovrecic

2013-11-01

Full Text Available Rapid development of technologies for the study of the human genome is an expected step after the discovery and sequencing of the entire human genome. Chromosomal microarrays, which allow us to perform tens of thousands of previously individual experiments simultaneously, are being utilized in all areas of human genetics and genomics. Initially, this was applicable only for research purposes, but in the last few years their clinical diagnostic purposes are becoming more and more relevant. Using molecular karyotyping (also chromosomal microarray, comparative genomic hybridization with microarray, aCGH, one can analyze microdeletions / microduplications in the whole human genome at once. It is a first-tier cytogenetic diagnostic test instead of G-banded karyotyping in patients with developmental delay and/or congenital anomalies. Molecular karyotyping is used as a diagnostic test in patients with unexplained developmental delay and/or idiopathic intellectual disability and/or dysmorphic features and/or multiple congenital anomalies (DD/ID/DF/MCA. In addition, the method is used in prenatal diagnostics and in some centres also in preimplantation genetic diagnosis.The aim of this paper is to inform the professional community in the field about this new diagnostic method and its implementation in Slovenia, and to define the clinical situations where the method is appropriate.

Initiation of universal tumor screening for Lynch syndrome in colorectal cancer patients as a model for the implementation of genetic information into clinical oncology practice.

Science.gov (United States)

Cohen, Stacey A; Laurino, Mercy; Bowen, Deborah J; Upton, Melissa P; Pritchard, Colin; Hisama, Fuki; Jarvik, Gail; Fichera, Alessandro; Sjoding, Britta; Bennett, Robin L; Naylor, Lorraine; Jacobson, Angela; Burke, Wylie; Grady, William M

2016-02-01

Lynch syndrome confers a hereditary predisposition to colorectal and other cancers. Universal tumor screening (UTS) for Lynch syndrome is recommended by several professional societies, but the implementation can be complex. This article describes the evaluation, process development, and initiation of Lynch syndrome UTS at a tertiary referral cancer center. A multidisciplinary team developed the new process design. Issues in 5 themes were noted: timing, funding, second-opinion patients, result processing, and the role of genetics providers. A committee approach was used to examine each issue for process-improvement development. The issues related to testing were addressed individually for the successful implementation of UTS at the institutional level. In the conventional-care period, 9 of 30 cases (30%) received Lynch syndrome screening, and 4 cases were referred to medical genetics. During the 6 months following the implementation of UTS, 32 of 44 patients (73%) received Lynch syndrome screening. The 13 unscreened patients all had identified reasons for nonscreening (eg, financial limitations). Ten patients were referred to medical genetics, which identified no new cases of Lynch syndrome, but a low-risk adenomatous polyposis coli (APC) variant was detected in 1 individual. The implementation of effective Lynch syndrome UTS can feasibly alter practice at the institutional level. This experience with the assessment and management of issues relevant to the successful implementation of a new clinical care paradigm based on emerging technology has implications for the uptake of advances across molecular oncology into clinical practice, and this is highly relevant in the current era of rapidly evolving genomic technology. © 2015 American Cancer Society.

GAPscreener: An automatic tool for screening human genetic association literature in PubMed using the support vector machine technique

Directory of Open Access Journals (Sweden)

Khoury Muin J

2008-04-01

Full Text Available Abstract Background Synthesis of data from published human genetic association studies is a critical step in the translation of human genome discoveries into health applications. Although genetic association studies account for a substantial proportion of the abstracts in PubMed, identifying them with standard queries is not always accurate or efficient. Further automating the literature-screening process can reduce the burden of a labor-intensive and time-consuming traditional literature search. The Support Vector Machine (SVM, a well-established machine learning technique, has been successful in classifying text, including biomedical literature. The GAPscreener, a free SVM-based software tool, can be used to assist in screening PubMed abstracts for human genetic association studies. Results The data source for this research was the HuGE Navigator, formerly known as the HuGE Pub Lit database. Weighted SVM feature selection based on a keyword list obtained by the two-way z score method demonstrated the best screening performance, achieving 97.5% recall, 98.3% specificity and 31.9% precision in performance testing. Compared with the traditional screening process based on a complex PubMed query, the SVM tool reduced by about 90% the number of abstracts requiring individual review by the database curator. The tool also ascertained 47 articles that were missed by the traditional literature screening process during the 4-week test period. We examined the literature on genetic associations with preterm birth as an example. Compared with the traditional, manual process, the GAPscreener both reduced effort and improved accuracy. Conclusion GAPscreener is the first free SVM-based application available for screening the human genetic association literature in PubMed with high recall and specificity. The user-friendly graphical user interface makes this a practical, stand-alone application. The software can be downloaded at no charge.

Strengthening molecular genetics and training in craniosynostosis: The need of the hour

Science.gov (United States)

Barik, Mayadhar; Bajpai, Minu; Panda, Shasanka Shekhar; Malhotra, Arun; Samantaray, Jyotish Chandra; Dwivedi, Sada Nanda

2014-01-01

Craniosynostosis (CS) is premature fusion of skull. It is divided into two groups: Syndromic craniosynostosis (SCS) and non-syndromic craniosynostosis (NSC). Its incidence in Indian population is 1:1000 live births where as in the USA it is 1:2500 live births. Its incidence varies from country to country. Molecular genetics having great interest and relevance in medical students, faculty, scientist, pediatric neurosurgeon and staff nurses, our objective was to educate the medical students, residents, researchers, clinicians, pediatric neurosurgeon, anesthetists, pediatricians, staff nurses and paramedics. We summarized here including with diagnosis, investigations, surgical therapy, induction therapy, and molecular therapy. Molecular genetics training is needed to know the information regarding development of skull, cranial connective tissue, craniofacial dysplasia, frame work, network of receptors and its etiopathogenesis. The important part is clinically with molecular therapy (MT) how to manage CS in rural sector and metropolitan cities need a special attention. PMID:25288859

Strengthening molecular genetics and training in craniosynostosis: The need of the hour

Directory of Open Access Journals (Sweden)

Mayadhar Barik

2014-01-01

Full Text Available Craniosynostosis (CS is premature fusion of skull. It is divided into two groups: Syndromic craniosynostosis (SCS and non-syndromic craniosynostosis (NSC. Its incidence in Indian population is 1:1000 live births where as in the USA it is 1:2500 live births. Its incidence varies from country to country. Molecular genetics having great interest and relevance in medical students, faculty, scientist, pediatric neurosurgeon and staff nurses, our objective was to educate the medical students, residents, researchers, clinicians, pediatric neurosurgeon, anesthetists, pediatricians, staff nurses and paramedics. We summarized here including with diagnosis, investigations, surgical therapy, induction therapy, and molecular therapy. Molecular genetics training is needed to know the information regarding development of skull, cranial connective tissue, craniofacial dysplasia, frame work, network of receptors and its etiopathogenesis. The important part is clinically with molecular therapy (MT how to manage CS in rural sector and metropolitan cities need a special attention.

Molecular genetics and livestock selection. Approaches, opportunities and risks

International Nuclear Information System (INIS)

Williams, J.L.

2005-01-01

Following domestication, livestock were selected both naturally through adaptation to their environments and by man so that they would fulfil a particular use. As selection methods have become more sophisticated, rapid progress has been made in improving those traits that are easily measured. However, selection has also resulted in decreased diversity. In some cases, improved breeds have replaced local breeds, risking the loss of important survival traits. The advent of molecular genetics provides the opportunity to identify the genes that control particular traits by a gene mapping approach. However, as with selection, the early mapping studies focused on traits that are easy to measure. Where molecular genetics can play a valuable role in livestock production is by providing the means to select effectively for traits that are difficult to measure. Identifying the genes underpinning particular traits requires a population in which these traits are segregating. Fortunately, several experimental populations have been created that have allowed a wide range of traits to be studied. Gene mapping work in these populations has shown that the role of particular genes in controlling variation in a given trait can depend on the genetic background. A second finding is that the most favourable alleles for a trait may in fact. be present in animals that perform poorly for the trait. In the long term, knowledge of -the genes controlling particular traits, and the way they interact with the genetic background, will allow introgression between breeds and the assembly of genotypes that are best suited to particular environments, producing animals with the desired characteristics. If used wisely, this approach will maintain genetic diversity while improving performance over a wide range of desired traits. (author)

Genetic screening: programs, principles, and research--thirty years later. Reviewing the recommendations of the Committee for the Study of Inborn Errors of Metabolism (SIEM).

Science.gov (United States)

Simopoulos, A P

2009-01-01

Screening programs for genetic diseases and characteristics have multiplied in the last 50 years. 'Genetic Screening: Programs, Principles, and Research' is the report of the Committee for the Study of Inborn Errors of Metabolism (SIEM Committee) commissioned by the Division of Medical Sciences of the National Research Council at the National Academy of Sciences in Washington, DC, published in 1975. The report is considered a classic in the field worldwide, therefore it was thought appropriate 30 years later to present the Committee's modus operandi and bring the Committee's recommendations to the attention of those involved in genetics, including organizational, educational, legal, and research aspects of genetic screening. The Committee's report anticipated many of the legal, ethical, economic, social, medical, and policy aspects of genetic screening. The recommendations are current, and future committees should be familiar with them. In 1975 the Committee stated: 'As new screening tests are devised, they should be carefully reviewed. If the experimental rate of discovery of new genetic characteristics means an accelerating rate of appearance of new screening tests, now is the time to develop the medical and social apparatus to accommodate what later on may otherwise turn out to be unmanageable growth.' What a prophetic statement that was. If the Committee's recommendations had been implemented on time, there would be today a federal agency in existence, responsive and responsible to carry out the programs and support research on various aspects of genetic screening, including implementation of a federal law that protects consumers from discrimination by their employers and the insurance industry on the basis of genetic information. Copyright 2008 S. Karger AG, Basel.

Best practice guidelines for the molecular genetic diagnosis of Type 1 (HFE-related hereditary haemochromatosis

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Barton David E

2006-11-01

Full Text Available Abstract Background Hereditary haemochromatosis (HH is a recessively-inherited disorder of iron over-absorption prevalent in Caucasian populations. Affected individuals for Type 1 HH are usually either homozygous for a cysteine to tyrosine amino acid substitution at position 282 (C282Y of the HFE gene, or compound heterozygotes for C282Y and for a histidine to aspartic acid change at position 63 (H63D. Molecular genetic testing for these two mutations has become widespread in recent years. With diverse testing methods and reporting practices in use, there was a clear need for agreed guidelines for haemochromatosis genetic testing. The UK Clinical Molecular Genetics Society has elaborated a consensus process for the development of disease-specific best practice guidelines for genetic testing. Methods A survey of current practice in the molecular diagnosis of haemochromatosis was conducted. Based on the results of this survey, draft guidelines were prepared using the template developed by UK Clinical Molecular Genetics Society. A workshop was held to develop the draft into a consensus document. The consensus document was then posted on the Clinical Molecular Genetics Society website for broader consultation and amendment. Results Consensus or near-consensus was achieved on all points in the draft guidelines. The consensus and consultation processes worked well, and outstanding issues were documented in an appendix to the guidelines. Conclusion An agreed set of best practice guidelines were developed for diagnostic, predictive and carrier testing for hereditary haemochromatosis and for reporting the results of such testing.

Molecular Genetic and Gene Therapy Studies of the Musculoskeletal System

National Research Council Canada - National Science Library

Baylink, David

2004-01-01

The primary goal of the proposed work is to apply several state of the art molecular genetic and gene therapy technologies to address fundamental questions in bone biology with a particular emphasis on attempting: l...

A systematic review on screening for Fabry disease: prevalence of individuals with genetic variants of unknown significance

NARCIS (Netherlands)

van der Tol, L.; Smid, B. E.; Poorthuis, B. J. H. M.; Biegstraaten, M.; Deprez, R. H. Lekanne; Linthorst, G. E.; Hollak, C. E. M.

2014-01-01

Screening for Fabry disease (FD) reveals a high prevalence of individuals with α-galactosidase A (GLA) genetic variants of unknown significance (GVUS). These individuals often do not express characteristic features of FD. A systematic review on FD screening studies was performed to interpret the

Molecular and genetic insights into an infantile epileptic encephalopathy-CDKL5 disorder

Institute of Scientific and Technical Information of China (English)

Ailing Zhou; Song Han; Zhaolan Joe Zhou

2017-01-01

BACKGROUND:The discovery that mutations in cyclin-dependent kinase-like 5 (CDKL5) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder.Given the large number of literature published thus far,this review aims to summarize current genetic studies,draw a consensus on proposed molecular functions,and point to gaps of knowledge in CDKL5 research.METHODS:A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years.We analyzed these publications and summarized the findings into four sections:genetic studies,CDKL5 expression pattems,molecular functions,and animal models.We also discussed challenges and future directions in each section.RESULTS:On the clinical side,CDKL5 disorder is characterized by early onset epileptic seizures,intellectual disability,and stereotypical behaviors.On the research side,a series of molecular and genetic studies in human patients,cell cultures and animal models have established the causality of CDKL5 to the infantile epileptic encephalopathy,and pointed to a key role for CDKL5 in regulating neuronal function in the brain.Mouse models of CDKL5 disorder have also been developed,and notably,manifest behavioral phenotypes,mimicking numerous clinical symptoms of CDKL5 disorder and advancing CDKL5 research to the preclinical stage.CONCLUSIONS:Given what we have leamed thus far,future identification of robust,quantitative,and sensitive outcome measures would be the key in animal model studies,particularly in heterozygous females.In the meantime,molecular and cellular studies of CDKL5 should focus on mechanism-based investigation and aim to uncover druggable targets that offer the potential to rescue or ameliorate CDKL5 disorder-related phenotypes.

Molecular and genetic insights into an infantile epileptic encephalopathy - CDKL5 disorder.

Science.gov (United States)

Zhou, Ailing; Han, Song; Zhou, Zhaolan Joe

2017-02-01

The discovery that mutations in cyclin-dependent kinase-like 5 ( CDKL5 ) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder. Given the large number of literature published thus far, this review aims to summarize current genetic studies, draw a consensus on proposed molecular functions, and point to gaps of knowledge in CDKL5 research. A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years. We analyzed these publications and summarized the findings into four sections: genetic studies, CDKL5 expression patterns, molecular functions, and animal models. We also discussed challenges and future directions in each section. On the clinical side, CDKL5 disorder is characterized by early onset epileptic seizures, intellectual disability, and stereotypical behaviors. On the research side, a series of molecular and genetic studies in human patients, cell cultures and animal models have established the causality of CDKL5 to the infantile epileptic encephalopathy, and pointed to a key role for CDKL5 in regulating neuronal function in the brain. Mouse models of CDKL5 disorder have also been developed, and notably, manifest behavioral phenotypes, mimicking numerous clinical symptoms of CDKL5 disorder and advancing CDKL5 research to the preclinical stage. Given what we have learned thus far, future identification of robust, quantitative, and sensitive outcome measures would be the key in animal model studies, particularly in heterozygous females. In the meantime, molecular and cellular studies of CDKL5 should focus on mechanism-based investigation and aim to uncover druggable targets that offer the potential to rescue or ameliorate CDKL5 disorder-related phenotypes.

Nephronophthisis: A Genetically Diverse Ciliopathy

Directory of Open Access Journals (Sweden)

Roslyn J. Simms

2011-01-01

Full Text Available Nephronophthisis (NPHP is an autosomal recessive cystic kidney disease and a leading genetic cause of established renal failure (ERF in children and young adults. Early presenting symptoms in children with NPHP include polyuria, nocturia, or secondary enuresis, pointing to a urinary concentrating defect. Renal ultrasound typically shows normal kidney size with increased echogenicity and corticomedullary cysts. Importantly, NPHP is associated with extra renal manifestations in 10–15% of patients. The most frequent extrarenal association is retinal degeneration, leading to blindness. Increasingly, molecular genetic testing is being utilised to diagnose NPHP and avoid the need for a renal biopsy. In this paper, we discuss the latest understanding in the molecular and cellular pathogenesis of NPHP. We suggest an appropriate clinical management plan and screening programme for individuals with NPHP and their families.

EMQN/CMGS best practice guidelines for the molecular genetic testing of Huntington disease

OpenAIRE

Losekoot, Monique; van Belzen, Martine J; Seneca, Sara; Bauer, Peter; Stenhouse, Susan A R; Barton, David E

2012-01-01

Huntington disease (HD) is caused by the expansion of an unstable polymorphic trinucleotide (CAG)n repeat in exon 1 of the HTT gene, which translates into an extended polyglutamine tract in the protein. Laboratory diagnosis of HD involves estimation of the number of CAG repeats. Molecular genetic testing for HD is offered in a wide range of laboratories both within and outside the European community. In order to measure the quality and raise the standard of molecular genetic testing in these ...

Molecular markers for genetic diversity and phylogeny research of ...

African Journals Online (AJOL)

Brazilian sheep descended from several breeds brought to the New World by Portuguese and Spanish colonists, and they have evolved and adapted to local climatic variations and acquired tolerance or resistance to many diseases. Molecular markers are widely used in analyzing genetic variability, and markers such as ...

Cytogenetics and molecular genetics of Wilms' tumor of childhood

NARCIS (Netherlands)

Slater, R. M.; Mannens, M. M.

1992-01-01

We describe the way in which application of cytogenetic and molecular genetic techniques to the study of Wilms' tumor (WT) of the kidney and the associated congenital disorders, such as sporadic aniridia and the Beckwith-Wiedemann syndrome, has led to identification of two regions on the short arm

MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms.

Science.gov (United States)

Kumar, Sudhir; Stecher, Glen; Li, Michael; Knyaz, Christina; Tamura, Koichiro

2018-06-01

The Molecular Evolutionary Genetics Analysis (Mega) software implements many analytical methods and tools for phylogenomics and phylomedicine. Here, we report a transformation of Mega to enable cross-platform use on Microsoft Windows and Linux operating systems. Mega X does not require virtualization or emulation software and provides a uniform user experience across platforms. Mega X has additionally been upgraded to use multiple computing cores for many molecular evolutionary analyses. Mega X is available in two interfaces (graphical and command line) and can be downloaded from www.megasoftware.net free of charge.

Genética molecular: avanços e problemas Molecular genetics: advances and problems

Directory of Open Access Journals (Sweden)

Eloi S. Garcia

1996-03-01

Full Text Available Este artigo traz a discussão sobre genética molecular em saúde ao campo da saúde pública. Com a revolução produzida pela chegada da engenharia genética, é importante discutir alguns dos avanços e problemas desta tecnologia para a sociedade. Está na hora de se fazer uma avaliação clara e bem informada acerca do que já se conseguiu e do que ainda podemos conseguir através desta tecnologia. A sociedade precisa compreender as implicações éticas e práticas de uma tecnologia capaz de produzir drogas milagrosas, dagnósticos modernos e a cura de todas as doenças. Alguns pontos particularmente delicados pertinentes às questões sociais ligadas à biologia molecular e ao projeto genoma humano são discutidos.This article is an attempt to draw the discussion on molecular genetics in health into the public health domain. Now that the genetic engineering revolution has arrived, it is important to point out the advances and problems this technology poses for society. It is time for a clear, informed assessment of what we have already achieved and may soon achieve using this technology. Clearly, society needs to understand the ethical and practical implications of a technology which can produce miracle drugs and modern diagnoses and cure virtually every disease. Important points from sensitive social issues raised by molecular biology and the human genome project are discussed.

New Advances of Preimplantation and Prenatal Genetic Screening and Noninvasive Testing as a Potential Predictor of Health Status of Babies

Directory of Open Access Journals (Sweden)

Tanya Milachich

2014-01-01

Full Text Available The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF embryos. Preimplantation genetic diagnosis (PGD or screening (PGS involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future.

New Advances of Preimplantation and Prenatal Genetic Screening and Noninvasive Testing as a Potential Predictor of Health Status of Babies

Science.gov (United States)

2014-01-01

The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF) embryos. Preimplantation genetic diagnosis (PGD) or screening (PGS) involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND) require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future. PMID:24783200

Isolation and molecular genetic characterization of a yeast strain ...

African Journals Online (AJOL)

The yeast was identified by molecular genetics technique based on sequence analysis of the variable D1/D2 domain of the large subunit (26S) ribosomal DNA. Subsequent 26S rRNA gene sequencing showed 100% base sequence homology and it was identified as Candida viswanathii. The degradation of PAHs

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

Out of the 40 primers screened, seven primers generated 174 amplification products with an average of 24.85 bands per primer. The RAPD profiles were analysed for Jaccard's similarity coefficients that was found to be in the range from 0 to 0.48, indicating the presence of wide range of genetic diversity at molecular level.

Business and Breakthrough: Framing (Expanded) Genetic Carrier Screening for the Public.

Science.gov (United States)

Holton, Avery E; Canary, Heather E; Wong, Bob

2017-09-01

A growing body of research has given attention to issues surrounding genetic testing, including expanded carrier screening (ECS), an elective medical test that allows planning or expecting parents to consider the potential occurrence of genetic diseases and disorders in their children. These studies have noted the role of the mass media in driving public perceptions about such testing, giving particular attention to ways in which coverage of genetics and genetic testing broadly may drive public attitudes and choices concerning the morality, legality, ethics, and parental well-being involved in genetic technologies. However, few studies have explored how mass media are covering the newer test, ECS. Drawing on health-related framing studies that have shown in varying degrees the impact particular frames such as gain/loss and thematic/episodic can have on the public, this study examines the frame selection employed by online media in its coverage of ECS. This analysis-combined with an analysis of the sources and topics used in such coverage and how they relate to selected frames-helps to clarify how mass media are covering an increasingly important medical test and offers considerations of how such coverage may inform mass media scholarship as well as health-related practices.

Phenylketonuria Genetic Screening Simulation

Science.gov (United States)

Erickson, Patti

2012-01-01

After agreeing to host over 200 students on a daylong genetics field trip, the author needed an easy-to-prepare genetics experiment to accompany the DNA-necklace and gel-electrophoresis activities already planned. One of the student's mothers is a pediatric physician at the local hospital, and she suggested exploring genetic-disease screening…

The molecular genetics of inflammatory, autoimmune, and infectious diseases of the sinonasal tract: a review.

Science.gov (United States)

Montone, Kathleen T

2014-06-01

The sinonasal tract is frequently affected by a variety of nonneoplastic inflammatory disease processes that are often multifactorial in their etiology but commonly have a molecular genetic component. To review the molecular genetics of a variety of nonneoplastic inflammatory diseases of the sinonasal tract. Inflammatory lesions of the sinonasal tract can be divided into 3 main categories: (1) chronic rhinosinusitis, (2) infectious diseases, and (3) autoimmune diseases/vasculitides. The molecular diagnosis and pathways of a variety of these inflammatory lesions are currently being elucidated and will shed light on disease pathogenesis and treatment. The sinonasal tract is frequently affected by inflammatory lesions that arise through complex interactions of environmental, infectious, and genetic factors. Because these lesions are all inflammatory in nature, the molecular pathology surrounding them is most commonly due to upregulation and down-regulation of genes that affect inflammatory responses and immune regulation.

Genetic Diversity Analysis of Tagetes Species Using PCR Based Molecular Markers

International Nuclear Information System (INIS)

Shahzadi, I.; Ahmad, R.; Waheed, U.; Shah, M. F.

2016-01-01

Tagetes is a genus of medicinally important wild and cultivated plants containing several chemical compounds. Lack of information on variation at molecular level present in Tagetes species is paramount to understand the genetic basis of medicinally important compounds. Current study aims at finding genetic variability in Tagetes species using random and specific molecular markers. Two primer systems including 25 RAPD and 3 STS (limonene gene) were used to ascertain genetic diversity of 15 Tagetes genotypes belonging to different species. We found that 20 of the 25 tested RAPD primers generated stable band patterns with 167 loci of amplification products. The proportion of polymorphic bands was 95.21 percent for RAPD primers. Three STS primers generated a total of 29 amplification products, of which 96.55 percent were polymorphic. Homology of genotypes was 53.18 percent and 51.11 percent with RAPD and STS primers respectively. The dendrogram obtained revealed that the range of overall genetic distances estimated was 22 percent to 100 percent through RAPD and 9 percent to 100 percent through STS markers. The findings help to establish that PCR-based assay such as RAPD and STS could be used successfully for estimation of genetic diversity of different genotypes of Tagetes that can be used for selection of parents for improvement of the species. (author)

Newborn Screening for Primary Immunodeficiency Diseases: The Past, the Present and the Future

Directory of Open Access Journals (Sweden)

Jovanka King

2017-08-01

Full Text Available Primary immunodeficiency diseases (PID are a heterogeneous group of disorders caused by inborn errors of immunity, with affected children presenting with severe, recurrent or unusual infections. Over 300 distinct genetic molecular abnormalities resulting in PID have been identified, and this number continues to rise. Newborn screening for PID has been established in many countries, with the majority of centers using a PCR-based T cell receptor excision circle (TREC assay to screen for severe combined immunodeficiency (SCID and other forms of T cell lymphopenia. Multiplexed screening including quantitation of kappa-recombining exclusion circles (KREC has also been described, offering advantages over TREC screening alone. Screening technologies are also expanding to include protein-based assays to identify complement deficiencies and granulocyte disorders. Given the rapid advances in genomic medicine, a potential future direction is the application of next-generation sequencing (NGS technologies to screen infants for a panel of genetic mutations, which would enable identification of a wide range of diseases. However, several ethical and economic issues must be considered before moving towards this screening strategy.

Molecular genetic identification of some wheat cultivars in the sudan

International Nuclear Information System (INIS)

Mekki, I. I; El Amin, H. B.

2002-01-01

Four wheat (Triticum aestivum L.) cultivars, namely condor, El-Nellene, Wadi El Neil and Debeira were characterized on biochemical and molecular bases. The biochemical ones were protein-banding patterns, using sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and isozymes to identify the biochemical genetic fingerprint of the four cultivars. Water-soluble protein-banding pattern showed no polymorphisms among the tested cultivars. The data from starch gel electrophoresis of enzymes, malate dehydrogenase (MDH), esterase (EST) and acid phosphate (ACPH) showed that the cultivars are monomorphic. Further trials to identify the molecular genetic fingerprints of the studied cultivars were carried out using RAPD-PCR twenty-five primers were tested to perform. RAPD-PCR analysis. From the PCR products, a phylogenetic map, i.e, dendrogram, was constructed for the studied cultivars which depicted tow groups. The first group contained Wadi El Neil and Deberia with 48.4% similarity, and the second group contained Condor and El Neileen with 100% similarity. There was no similarity between Condor and Debeira (100% dissimilarity). Therefor, these data can be used subsequently for genetic engineering research and for wheat breeding programmes in the Sudan.(Author)

Quality control in mutation analysis: the European Molecular Genetics Quality Network (EMQN).

Science.gov (United States)

Müller, C R

2001-08-01

The demand for clinical molecular genetics testing has steadily grown since its introduction in the 1980s. In order to reach and maintain the agreed quality standards of laboratory medicine, the same internal and external quality assurance (IQA/EQA) criteria have to be applied as for "conventional" clinical chemistry or pathology. In 1996 the European Molecular Genetics Quality Network (EMQN) was established in order to spread QA standards across Europe and to harmonise the existing national activities. EMQN is operated by a central co-ordinator and 17 national partners from 15 EU countries; since 1998 it is being funded by the EU commission for a 3-year period. EMQN promotes QA by two tools: by providing disease-specific best practice meetings (BPM) and EQA schemes. A typical BPM is focussed on one disease or group of related disorders. International experts report on the latest news of gene characterisation and function and the state-of-the-art techniques for mutation detection. Disease-specific EQA schemes are provided by experts in the field. DNA samples are sent out together with mock clinical referrals and a diagnostic question is asked. Written reports must be returned which are marked for genotyping and interpretation. So far, three BPMs have been held and six EQA schemes are in operation at various stages. Although mutation types and diagnostic techniques varied considerably between schemes, the overall technical performance showed a high diagnostic standard. Nevertheless, serious genotyping errors have been occurred in some schemes which underline the necessity of quality assurance efforts. The European Molecular Genetics Quality Network provides a necessary platform for the internal and external quality assurance of molecular genetic testing.

Oral Administration and Detection of a Near-Infrared Molecular Imaging Agent in an Orthotopic Mouse Model for Breast Cancer Screening.

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Bhatnagar, Sumit; Verma, Kirti Dhingra; Hu, Yongjun; Khera, Eshita; Priluck, Aaron; Smith, David E; Thurber, Greg M

2018-05-07

Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical imaging can achieve. However, the high cost and risks of ionizing radiation for several molecular imaging modalities have prevented a feasible and scalable approach for screening. Clinical studies have demonstrated the ability to detect breast tumors using nonspecific probes such as indocyanine green, but the lack of molecular information and required intravenous contrast agent does not provide a significant benefit over current noninvasive imaging techniques. Here we demonstrate that negatively charged sulfate groups, commonly used to improve solubility of near-infrared fluorophores, enable sufficient oral absorption and targeting of fluorescent molecular imaging agents for completely noninvasive detection of diseased tissue such as breast cancer. These functional groups improve the pharmacokinetic properties of affinity ligands to achieve targeting efficiencies compatible with clinical imaging devices using safe, nonionizing radiation (near-infrared light). Together, this enables development of a "disease screening pill" capable of oral absorption and systemic availability, target binding, background clearance, and imaging at clinically relevant depths for breast cancer screening. This approach should be adaptable to other molecular targets and diseases for use as a new class of screening agents.

Classification of genetic variation for cadmium tolerance in Bermudagrass [Cynodon dactylon (L.) Pers.] using physiological traits and molecular markers.

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Xie, Yan; Luo, Hongji; Hu, Longxing; Sun, Xiaoyan; Lou, Yanhong; Fu, Jinmin

2014-08-01

Cadmium (Cd) is one of the most toxic pollutants that caused severe threats to animal and human health. Bermudagrass is a dominant species in Cd contaminated soils, which can prevent Cd flow and spread. The objectives of this study were to determine the genetic variations in major physiological traits related to Cd tolerance in six populations of Bermudagrass collected from China, and to examine the genetic diversity and relationships among these accessions that vary in Cd tolerance using molecular markers. Plants of 120 accessions (116 natural accessions and 4 commercial cultivars) were exposed to 0 (i.e. control) or 1.5 mM CdSO4·8/3H2O for 3 weeks in hydroponic culture. Turf quality, transpiration rate, chlorophyll content, leaf water content and growth rate showed wide phenotypic variation. The membership function method was used to comprehensively evaluate Cd-tolerance. According to the average subordinate function value, four accessions were classified as the most tolerant genotypes and four accessions as Cd-sensitive genotypes. The trend of Cd tolerance among the six studied populations was as follows: Hunan > South China > North China > Central China > West South China and Xinjiang population. Phylogenetic analysis revealed that the majority of accessions from the same or adjacent regions were clustered into the same groups or subgroups, and the accessions with similar cadmium tolerance displayed a close phylogenetic relationship. Screening genetically diverse germplasm by combining the physiological traits and molecular markers could prove useful in developing Cd-tolerant Bermudagrass for the remediation of mill tailings and heavy metal polluted soils.

Reliable prediction of adsorption isotherms via genetic algorithm molecular simulation.

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LoftiKatooli, L; Shahsavand, A

2017-01-01

Conventional molecular simulation techniques such as grand canonical Monte Carlo (GCMC) strictly rely on purely random search inside the simulation box for predicting the adsorption isotherms. This blind search is usually extremely time demanding for providing a faithful approximation of the real isotherm and in some cases may lead to non-optimal solutions. A novel approach is presented in this article which does not use any of the classical steps of the standard GCMC method, such as displacement, insertation, and removal. The new approach is based on the well-known genetic algorithm to find the optimal configuration for adsorption of any adsorbate on a structured adsorbent under prevailing pressure and temperature. The proposed approach considers the molecular simulation problem as a global optimization challenge. A detailed flow chart of our so-called genetic algorithm molecular simulation (GAMS) method is presented, which is entirely different from traditions molecular simulation approaches. Three real case studies (for adsorption of CO 2 and H 2 over various zeolites) are borrowed from literature to clearly illustrate the superior performances of the proposed method over the standard GCMC technique. For the present method, the average absolute values of percentage errors are around 11% (RHO-H 2 ), 5% (CHA-CO 2 ), and 16% (BEA-CO 2 ), while they were about 70%, 15%, and 40% for the standard GCMC technique, respectively.

The impact of advances in human molecular biology on radiation genetic risk estimation in man

International Nuclear Information System (INIS)

Sankaranarayanan, K.

1996-01-01

This paper provides an overview of the conceptual framework, the data base, methods and assumptions used thus far to assess the genetic risks of exposure of human populations to ionising radiation. These are then re-examined in the contemporary context of the rapidly expanding knowledge of the molecular biology of human mendelian diseases. This re-examination reveals that (i) many of the assumptions used thus far in radiation genetic risk estimation may not be fully valid and (ii) the current genetic risk estimates are probably conservative, but provide an adequate margin of safety for radiological protection. The view is expressed that further advances in the field of genetic risk estimation will be largely driven by advances in the molecular biology of human genetic diseases. (author). 37 refs., 5 tabs

Dual gene activation and knockout screen reveals directional dependencies in genetic networks. | Office of Cancer Genomics

Science.gov (United States)

Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair.

Impact of transition from microscopy to molecular screening for detection of intestinal protozoa in Dutch patients.

Science.gov (United States)

Svraka-Latifovic, S; Bouter, S; Naus, H; Bakker, L J; Timmerman, C P; Dorigo-Zetsma, J W

2014-11-01

Detection of intestinal protozoa by PCR methods has been described as being sensitive and specific, and as improving the diagnostic yield. Here we present the outcome of the transition from microscopy to molecular screening for detection of a select group of intestinal protozoa in faeces in our laboratory. Introduction of molecular screening for intestinal protozoa resulted in higher sensitivity, reduced hands-on-time, reduced time-to-results, leading to improved diagnostic efficiency. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

[Genetic diagnostics of pathogenic splicing abnormalities in the clinical laboratory--pitfalls and screening approaches].

Science.gov (United States)

Niimi, Hideki; Ogawa, Tomomi; Note, Rhougou; Hayashi, Shirou; Ueno, Tomohiro; Harada, Kenu; Uji, Yoshinori; Kitajima, Isao

2010-12-01

In recent years, genetic diagnostics of pathogenic splicing abnormalities are increasingly recognized as critically important in the clinical genetic diagnostics. It is reported that approximately 10% of pathogenic mutations causing human inherited diseases are splicing mutations. Nonetheless, it is still difficult to identify splicing abnormalities in routine genetic diagnostic settings. Here, we studied two different kinds of cases with splicing abnormalities. The first case is a protein S deficiency. Nucleotide analyses revealed that the proband had a previously reported G to C substitution in the invariant AG dinucleotide at the splicing acceptor site of intronl/exon2, which produces multiple splicing abnormalities resulting in protein S deficiency. The second case is an antithrombin (AT) deficiency. This proband had a previously reported G to A substitution, at nucleotide position 9788 in intron 4, 14 bp in front of exon 5, which created a de novo exon 5 splice site and resulted in AT deficiency. From a practical standpoint, we discussed the pitfalls, attentions, and screening approaches in genetic diagnostics of pathogenic splicing abnormalities. Due to the difficulty with full-length sequence analysis of introns, and the lack of RNA samples, splicing mutations may escape identification. Although current genetic testing remains to be improved, to screen for splicing abnormalities more efficiently, it is significant to use an appropriate combination of various approaches such as DNA and/or RNA samples, splicing mutation databases, bioinformatic tools to detect splice sites and cis-regulatory elements, and in vitro and/or in vivo experimentally methods as needed.

76 FR 6623 - Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of Meeting

Science.gov (United States)

2011-02-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0066] Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY... public. Name of Committee: Molecular and Clinical Genetics Panel of the Medical Devices Advisory...

Genetics and molecular biology of hypotension

Science.gov (United States)

Robertson, D.

1994-01-01

Major strides in the molecular biology of essential hypertension are currently underway. This has tended to obscure the fact that a number of inherited disorders associated with low blood pressure exist and that these diseases may have milder and underrecognized phenotypes that contribute importantly to blood pressure variation in the general population. This review highlights some of the gene products that, if abnormal, could cause hypotension in some individuals. Diseases due to abnormalities in the catecholamine enzymes are discussed in detail. It is likely that genetic abnormalities with hypotensive phenotypes will be as interesting and diverse as those that give rise to hypertensive disorders.

Molecular and genetic insights into an infantile epileptic encephalopathy – CDKL5 disorder

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Zhou, Ailing; Han, Song

2017-01-01

Background The discovery that mutations in cyclin-dependent kinase-like 5 (CDKL5) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder. Given the large number of literature published thus far, this review aims to summarize current genetic studies, draw a consensus on proposed molecular functions, and point to gaps of knowledge in CDKL5 research. Methods A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years. We analyzed these publications and summarized the findings into four sections: genetic studies, CDKL5 expression patterns, molecular functions, and animal models. We also discussed challenges and future directions in each section. Results On the clinical side, CDKL5 disorder is characterized by early onset epileptic seizures, intellectual disability, and stereotypical behaviors. On the research side, a series of molecular and genetic studies in human patients, cell cultures and animal models have established the causality of CDKL5 to the infantile epileptic encephalopathy, and pointed to a key role for CDKL5 in regulating neuronal function in the brain. Mouse models of CDKL5 disorder have also been developed, and notably, manifest behavioral phenotypes, mimicking numerous clinical symptoms of CDKL5 disorder and advancing CDKL5 research to the preclinical stage. Conclusions Given what we have learned thus far, future identification of robust, quantitative, and sensitive outcome measures would be the key in animal model studies, particularly in heterozygous females. In the meantime, molecular and cellular studies of CDKL5 should focus on mechanism-based investigation and aim to uncover druggable targets that offer the potential to rescue or ameliorate CDKL5 disorder-related phenotypes. PMID:28580010

Electrochemical sensor for multiplex screening of genetically modified DNA: identification of biotech crops by logic-based biomolecular analysis.

Science.gov (United States)

Liao, Wei-Ching; Chuang, Min-Chieh; Ho, Ja-An Annie

2013-12-15

Genetically modified (GM) technique, one of the modern biomolecular engineering technologies, has been deemed as profitable strategy to fight against global starvation. Yet rapid and reliable analytical method is deficient to evaluate the quality and potential risk of such resulting GM products. We herein present a biomolecular analytical system constructed with distinct biochemical activities to expedite the computational detection of genetically modified organisms (GMOs). The computational mechanism provides an alternative to the complex procedures commonly involved in the screening of GMOs. Given that the bioanalytical system is capable of processing promoter, coding and species genes, affirmative interpretations succeed to identify specified GM event in terms of both electrochemical and optical fashions. The biomolecular computational assay exhibits detection capability of genetically modified DNA below sub-nanomolar level and is found interference-free by abundant coexistence of non-GM DNA. This bioanalytical system, furthermore, sophisticates in array fashion operating multiplex screening against variable GM events. Such a biomolecular computational assay and biosensor holds great promise for rapid, cost-effective, and high-fidelity screening of GMO. Copyright © 2013 Elsevier B.V. All rights reserved.

Fluorescence-based high-throughput screening of dicer cleavage activity

Czech Academy of Sciences Publication Activity Database

Podolská, Kateřina; Sedlák, David; Bartůněk, Petr; Svoboda, Petr

2014-01-01

Roč. 19, č. 3 (2014), s. 417-426 ISSN 1087-0571 R&D Projects: GA ČR GA13-29531S; GA MŠk(CZ) LC06077; GA MŠk LM2011022 Grant - others:EMBO(DE) 1483 Institutional support: RVO:68378050 Keywords : Dicer * siRNA * high-throughput screening Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.423, year: 2014

Genetic diversity and structure of tea plant in Qinba area in China by three types of molecular markers.

Science.gov (United States)

Zhang, Yu; Zhang, Xiaojuan; Chen, Xi; Sun, Wang; Li, Jiao

2018-01-01

advantages in terms of NPB, PPB, Rp, EMR, and MI. Nevertheless, the values of PIC showed different trends, with the highest values generated with EST-SSR, followed by SCoT and SRAP. The average band informativeness showed similar trends. Correlation between genetic distances produced by three different molecular markers were very small, thus it is not recommended to use a single marker to evaluate genetic diversity and population structure. It is hence suggested that combining of different types of molecular markers should be used to evaluate the genetic diversity and population structure. It also seems crucial to screen out, for each type of molecular markers, core markers of Camellia sinensis . This study revealed that genes of exotic plant varieties have been constantly integrated into the gene pool of Qinba area tea. A low level of genetic diversity was observed; this is shown by an average coefficient of genetic similarity of 0.74.

The Genetics of Aortopathies in Clinical Cardiology

Directory of Open Access Journals (Sweden)

Amit Goyal

2017-05-01

Full Text Available Aortopathies pose a significant healthcare burden due to excess early mortality, increasing incidence, and underdiagnosis. Understanding the underlying genetic causes, early diagnosis, timely surveillance, prophylactic repair, and family screening are keys to addressing these diseases. Next-generation sequencing continues to expand our understanding of the genetic causes of heritable aortopathies, rapidly clarifying their underlying molecular pathophysiology and suggesting new potential therapeutic targets. This review will summarize the pathogenetic mechanisms and management of heritable genetic aortopathies with attention to specific forms of both syndromic and nonsyndromic disorders, including Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, and familial thoracic aortic aneurysm and dissection.

Rapid screening for targeted genetic variants via high-resolution melting curve analysis.

Science.gov (United States)

Chambliss, Allison B; Resnick, Molly; Petrides, Athena K; Clarke, William A; Marzinke, Mark A

2017-03-01

Current methods for the detection of single nucleotide polymorphisms (SNPs) associated with aberrant drug-metabolizing enzyme function are hindered by long turnaround times and specialized techniques and instrumentation. In this study, we describe the development and validation of a high-resolution melting (HRM) curve assay for the rapid screening of variant genotypes for targeted genetic polymorphisms in the cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP3A5. Sequence-specific primers were custom-designed to flank nine SNPs within the genetic regions of aforementioned drug metabolizing enzymes. PCR amplification was performed followed by amplicon denaturation by precise temperature ramping in order to distinguish genotypes by melting temperature (Tm). A standardized software algorithm was used to assign amplicons as 'reference' or 'variant' as compared to duplicate reference sequence DNA controls for each SNP. Intra-assay (n=5) precision of Tms for all SNPs was ≤0.19%, while inter-assay (n=20) precision ranged from 0.04% to 0.21%. When compared to a reference method of Sanger sequencing, the HRM assay produced no false negative results, and overcall frequency ranged from 0% to 26%, depending on the SNP. Furthermore, HRM genotyping displayed accuracy over input DNA concentrations ranging from 10 to 200 ng/μL. The presented assay provides a rapid method for the screening for genetic variants in targeted CYP450 regions with a result of 'reference' or 'variant' available within 2 h from receipt of extracted DNA. The method can serve as a screening approach to rapidly identify individuals with variant sequences who should be further investigated by reflexed confirmatory testing for aberrant cytochrome P450 enzymatic activity. Rapid knowledge of variant status may aid in the avoidance of adverse clinical events by allowing for dosing of normal metabolizer patients immediately while identifying the need to wait for confirmatory testing in those patients who are

Genetic influences on attention deficit hyperactivity disorder symptoms from age 2 to 3: A quantitative and molecular genetic investigation

Directory of Open Access Journals (Sweden)

Saudino Kimberly J

2010-12-01

Full Text Available Abstract Background A twin study design was used to assess the degree to which additive genetic variance influences ADHD symptom scores across two ages during infancy. A further objective in the study was to observe whether genetic association with a number of candidate markers reflects results from the quantitative genetic analysis. Method We have studied 312 twin pairs at two time-points, age 2 and age 3. A composite measure of ADHD symptoms from two parent-rating scales: The Child Behavior Checklist/1.5 - 5 years (CBCL hyperactivity scale and the Revised Rutter Parent Scale for Preschool Children (RRPSPC was used for both quantitative and molecular genetic analyses. Results At ages 2 and 3 ADHD symptoms are highly heritable (h2 = 0.79 and 0.78, respectively with a high level of genetic stability across these ages. However, we also observe a significant level of genetic change from age 2 to age 3. There are modest influences of non-shared environment at each age independently (e2 = 0.22 and 0.21, respectively, with these influences being largely age-specific. In addition, we find modest association signals in DAT1 and NET1 at both ages, along with suggestive specific effects of 5-HTT and DRD4 at age 3. Conclusions ADHD symptoms are heritable at ages 2 and 3. Additive genetic variance is largely shared across these ages, although there are significant new effects emerging at age 3. Results from our genetic association analysis reflect these levels of stability and change and, more generally, suggest a requirement for consideration of age-specific genotypic effects in future molecular studies.

Screening of Potential Lead Molecule as Novel MurE Inhibitor: Virtual Screening, Molecular Dynamics and In Vitro Studies.

Science.gov (United States)

Zaveri, Kunal; Kiranmayi, Patnala

2017-01-01

The prevalence of multi-drug resistance S. aureus is one of the most challenging tasks for the treatment of nosocomial infections. Proteins and enzymes of peptidoglycan biosynthesis pathway are one among the well-studied targets, but many of the enzymes are unexplored as targets. MurE is one such enzyme featured to be a promising target. As MurE plays an important role in ligating the L-lys to stem peptide at third position that is crucial for peptidoglycan synthesis. To screen the potential MurE inhibitor by in silico approach and evaluate the best potential lead molecule by in vitro methods. In the current study, we have employed structure based virtual screening targeting the active site of MurE, followed by Molecular dynamics and in vitro studies. Virtual screening resulted in successful screening of potential lead molecule ((2R)-2-[[1-[(2R)- 2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan). The molecular dynamics of the MurE and Lead molecule complex emphasizes that lead molecule has shown stable interactions with active site residues Asp 406 and with Glu 460. In vitro studies demonstrate that the lead molecule shows antibacterial activity close to standard antibiotic Vancomycin and higher than that of Ampicillin, Streptomycin and Rifampicin. The MIC of lead molecule at 50μg/mL was observed to be 3.75 μg/mL, MBC being bactericidal with value of 6.25 μg/mL, cytotoxicity showing 34.44% and IC50 of 40.06μg/mL. These results suggest ((2R)-2-[[1-[(2R)-2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan) as a promising lead molecule for developing a MurE inhibitor against treatment of S. aureus infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Molecular analysis for diagnosis of Marfan syndrome and Marfan-associated disorders

Institute of Scientific and Technical Information of China (English)

GAO Ling-gen; YAO Xiu-ping; ZHANG Lin; HUI Ru-tai; ZHOU Xian-liang

2011-01-01

Marfan syndrome is a systemic disorder of connective tissue, caused by mutations in the FBN1, TGFBR1 or TGFBR2 genes. This syndrome is characterized by involvement of three major systems, skeletal, ocular, and cardiovascular. The continuing improvements in molecular biology and increasing availability of molecular diagnosis in clinical practice allow recognition of Marfan syndrome in patients with incomplete phenotypes. Additionally, molecular analyses could also be used for preimplantation genetic diagnosis. The identification of a mutation allows for early diagnosis, prognosis, genetic counseling, preventive management of carriers and reassurance for unaffected relatives. The importance of knowing in advance the location of the putative family mutation is highlighted by its straightforward application to prenatal and postnatal screening.

Genetic studies and a search for molecular markers that are linked ...

African Journals Online (AJOL)

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Instead, linkage analysis resulted in the construction of a molecular marker linkage map consisting of 45 ..... This limits the application of this marker type, particularly in ... primer design when one uses RAPDs. .... Concepts of Genetics. Fourth.

Generation of Mouse Haploid Somatic Cells by Small Molecules for Genome-wide Genetic Screening

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Zheng-Quan He

2017-08-01

Full Text Available The recent success of derivation of mammalian haploid embryonic stem cells (haESCs has provided a powerful tool for large-scale functional analysis of the mammalian genome. However, haESCs rapidly become diploidized after differentiation, posing challenges for genetic analysis. Here, we show that the spontaneous diploidization of haESCs happens in metaphase due to mitotic slippage. Diploidization can be suppressed by small-molecule-mediated inhibition of CDK1 and ROCK. Through ROCK inhibition, we can generate haploid somatic cells of all three germ layers from haESCs, including terminally differentiated neurons. Using piggyBac transposon-based insertional mutagenesis, we generated a haploid neural cell library harboring genome-wide mutations for genetic screening. As a proof of concept, we screened for Mn2+-mediated toxicity and identified the Park2 gene. Our findings expand the applications of mouse haploid cell technology to somatic cell types and may also shed light on the mechanisms of ploidy maintenance.

The Effects of Using Touch-Screen Devices on Students' Molecular Visualization and Representational Competence Skills

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McCollum, Brett M.; Regier, Lisa; Leong, Jaque; Simpson, Sarah; Sterner, Shayne

2014-01-01

The impact of touch-screen technology on spatial cognitive skills as related to molecular geometries was assessed through 102 one-on-one interviews with undergraduate students. Participants were provided with either printed 2D ball-and-stick images of molecules or manipulable projections of 3D molecular structures on an iPad. Following a brief…

Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing.

Science.gov (United States)

Kauffman, Tia L; Wilfond, Benjamin S; Jarvik, Gail P; Leo, Michael C; Lynch, Frances L; Reiss, Jacob A; Richards, C Sue; McMullen, Carmit; Nickerson, Deborah; Dorschner, Michael O; Goddard, Katrina A B

2017-02-01

Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results are placed into the medical record for use by healthcare providers. Through quantitative and qualitative measures, including baseline and post result disclosure surveys, post result disclosure interviews, 1-2year follow-up interviews, and team journaling, we are obtaining data about the clinical and personal utility of genomic carrier screening in this population. Key outcomes include the number of reportable carrier and additional findings, and the comparative cost, utilization, and psychosocial impacts of usual care vs. genomic carrier screening. As the study progresses, we will compare the costs of genome sequencing and usual care as well as the cost of screening, pattern of use of genetic or mental health counseling services, number of outpatient visits, and total healthcare costs. This project includes novel investigation into human reactions and responses from would-be parents who are learning information that could both affect a future pregnancy and their own health. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment

Science.gov (United States)

Willis, Rudolph E.

2016-01-01

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis. PMID:27649156

Prenatal screening for chromosomal abnormalities in IVF patients that opted for preimplantation genetic screening/diagnosis (PGS/D): a need for revised algorithms in the era of personalized medicine.

Science.gov (United States)

Takyi, Afua; Santolaya-Forgas, Joaquin

2017-06-01

Obstetricians offer prenatal screening for most common chromosomal abnormalities to all pregnant women including those that had in vitro fertilization (IVF) and preimplantation genetic screening/diagnosis (PGS/D). We propose that free fetal DNA in maternal circulation together with the second trimester maternal serum alfa feto protein (MSAFP) and ultrasound imaging is the best prenatal screening test for chromosomal abnormalities and congenital anomalies in IVF-PGD/S patients because risk estimations from all other prenatal screening algorithms for chromosomal abnormalities depend heavily on maternal age which is irrelevant in PGS/D patients.

A genetic screen for increasing metabolic flux in the isoprenoid pathway of Saccharomyces cerevisiae: Isolation of SPT15 mutants using the screen

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M. Wadhwa

2016-12-01

Full Text Available A genetic screen to identify mutants that can increase flux in the isoprenoid pathway of yeast has been lacking. We describe a carotenoid-based visual screen built with the core carotenogenic enzymes from the red yeast Rhodosporidium toruloides. Enzymes from this yeast displayed the required, higher capacity in the carotenoid pathway. The development also included the identification of the metabolic bottlenecks, primarily phytoene dehydrogenase, that was subjected to a directed evolution strategy to yield more active mutants. To further limit phytoene pools, a less efficient version of GGPP synthase was employed. The screen was validated with a known flux increasing gene, tHMG1. New mutants in the TATA binding protein SPT15 were isolated using this screen that increased the yield of carotenoids, and an alternate isoprenoid, α-Farnesene confirming increase in overall flux. The findings indicate the presence of previously unknown links to the isoprenoid pathway that can be uncovered using this screen. Keywords: Metabolic engineering, Carotenoids, Isoprenoids, α-Farnesene, Rhodosporidium toruloides, SPT15

Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series

International Nuclear Information System (INIS)

Crispo, Anna; Esposito, Emanuela; Amore, Alfonso; Di Bonito, Maurizio; Botti, Gerardo; Montella, Maurizio; Barba, Maddalena; D’Aiuto, Giuseppe; De Laurentiis, Michelino; Grimaldi, Maria; Rinaldo, Massimo; Caolo, Giuseppina; D’Aiuto, Massimiliano; Capasso, Immacolata

2013-01-01

Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit. In a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes. Screen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05). Molecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially. Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology

[Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

Science.gov (United States)

Maroto Rey, José Pablo; Cillán Narvaez, Elena

2013-06-01

There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

Molecular marker studies in riverine buffaloes, for characterization and diagnosis of genetic defects

International Nuclear Information System (INIS)

Yadav, B.R.

2005-01-01

The buffalo is probably the last livestock species to have been domesticated, with many genetic, physiological and behavioural traits not yet well understood. Molecular markers have been used for characterizing animals and breeds, diagnosing diseases and identifying anatomical and physiological anomalies. RFLP studies showed low heterozygosity, but genomic and oligonucleotide probes showed species-specific bands useful for identification of carcass or other unknown samples. Use of RAPD revealed band frequencies, band sharing frequencies, genetic distances, and genetic and identity indexes in different breeds. Bovine microsatellite primers indicate that 70.9% of bovine loci were conserved in buffalo. Allele numbers, sizes, frequencies, heterozygosity and polymorphism information content showed breed-specific patterns. Different marker types - genomic and oligonucleotide probes, RAPD and microsatellites - are useful in parent identification. Individual specific DNA fingerprinting techniques were applied with twin-born animal (XX/XY) chimerism, sex identification, anatomically defective and XO individuals. Molecular markers are a potential tool for geneticists and breeders to evaluate existing germplasm and to manipulate it to develop character-specific strains and to provide the basis for effective genetic conservation. (author)

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 December 2012 - 31 January 2013

Czech Academy of Sciences Publication Activity Database

Mendel, Jan; Urbánková, Soňa; Vyskočilová, M.

2013-01-01

Roč. 13, č. 3 (2013), s. 546-549 ISSN 1755-098X Institutional support: RVO:68081766 Keywords : genetic database * microsatellite marker loci Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.626, year: 2013

Impact of Professional Learning on Teachers' Representational Strategies and Students' Cognitive Engagement with Molecular Genetics Concepts

Science.gov (United States)

Nichols, Kim

2018-01-01

A variety of practices and specialised representational systems are required to understand, communicate and construct molecular genetics knowledge. This study describes teachers' use of multimodal representations of molecular genetics concepts and how their strategies and choice of resources were interpreted, understood and used by students to…

Genetic screening and testing in an episode-based payment model: preserving patient autonomy.

Science.gov (United States)

Sutherland, Sharon; Farrell, Ruth M; Lockwood, Charles

2014-11-01

The State of Ohio is implementing an episode-based payment model for perinatal care. All costs of care will be tabulated for each live birth and assigned to the delivering provider, creating a three-tiered model for reimbursement for care. Providers will be reimbursed as usual for care that is average in cost and quality, while instituting rewards or penalties for those outside the expected range in either domain. There are few exclusions, and all methods of genetic screening and diagnostic testing are included in the episode cost calculation as proposed. Prenatal ultrasonography, genetic screening, and diagnostic testing are critical components of the delivery of high-quality, evidence-based prenatal care. These tests provide pregnant women with key information about the pregnancy, which, in turn, allows them to work closely with their health care provider to determine optimal prenatal care. The concepts of informed consent and decision-making, cornerstones of the ethical practice of medicine, are founded on the principles of autonomy and respect for persons. These principles recognize that patients' rights to make choices and take actions are based on their personal beliefs and values. Given the personal nature of such decisions, it is critical that patients have unbarred access to prenatal genetic tests if they elect to use them as part of their prenatal care. The proposed restructuring of reimbursement creates a clear conflict between patient autonomy and physician financial incentives.

Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of Tuberous Sclerosis

Science.gov (United States)

2016-07-01

tsc1 and tsc2 loss of function mutations in Schizosaccharomyces pombe. Northeast Regional Yeast Meeting, June 16-17, University at Buffalo, The State...AWARD NUMBER: W81XWH-14-1-0169 TITLE: Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of...SUBTITLE Using Genetic Buffering Relationships Identified in Fission 5a. CONTRACT NUMBER W81XWH-14-1-0169 Yeast to Elucidate the Molecular Pathology

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli.

Science.gov (United States)

Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex K; Hacohen, Nir; Amit, Ido; Regev, Aviv

2013-04-01

Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative trait loci or reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant responds as an activator of the antiviral response; using RNA interference, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli.

Psychological impact of von Hippel-Lindau genetic screening in patients with a previous history of hemangioblastoma of the central nervous system.

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Rochette, Claire; Baumstarck, Karine; Canoni-Zattara, Hélène; Abdullah, Ahmad Esmaeel; Figarella-Branger, Dominique; Pertuit, Morgane; Barlier, Anne; Castinetti, Frédéric; Pacak, Karel; Metellus, Philippe; Taïeb, David

2018-05-15

Von Hippel-Lindau (VHL) syndrome is a hereditary cancer syndrome characterized by a high risk of developing benign and malignant tumors, including central nervous system hemangioblastomas (CNS HBs). For an early diagnosis of VHL, before the occurrence of cancers (especially renal cell carcinoma), it is of huge importance to initiate VHL genetic testing in at-risk patients. The aim of the study was to assess the psychological impact of VHL genetic testing in patients previously diagnosed with a CNS HB. From 1999 until 2015, 55 patients underwent surgery for CNS HBs. Eleven patients were already screened for VHL mutations and 3 patients deceased before the start of the study. From the remaining 42 patients, 24 were accepted to be enrolled in the study. Assessment of psychological impact of VHL genetic testing was performed by measuring anxiety levels, mood disorders, quality of life, and psychological consequences of genetic screening. Twenty-one of the enrolled 24 patients underwent VHL genetic testing and 12 patients came back for the communication of positive genetic results. The baseline psychological status did not differ between these 2 groups. Patients who attended the visit of communication of genetic results had similar anxiety levels compared to those who had not. Furthermore, they also experienced an improvement in the level of anxiety and two QoL dimension scores compared to their baseline status. In summary, there is no evidence of a negative psychosocial impact of VHL genetic testing in patients with a previous history of CNS HB. We, therefore, recommend the recall of patients who have not been previously screened.

Pharmacophore-based virtual screening, molecular docking, molecular dynamics simulation, and biological evaluation for the discovery of novel BRD4 inhibitors.

Science.gov (United States)

Yan, Guoyi; Hou, Manzhou; Luo, Jiang; Pu, Chunlan; Hou, Xueyan; Lan, Suke; Li, Rui

2018-02-01

Bromodomain is a recognition module in the signal transduction of acetylated histone. BRD4, one of the bromodomain members, is emerging as an attractive therapeutic target for several types of cancer. Therefore, in this study, an attempt has been made to screen compounds from an integrated database containing 5.5 million compounds for BRD4 inhibitors using pharmacophore-based virtual screening, molecular docking, and molecular dynamics simulations. As a result, two molecules of twelve hits were found to be active in bioactivity tests. Among the molecules, compound 5 exhibited potent anticancer activity, and the IC 50 values against human cancer cell lines MV4-11, A375, and HeLa were 4.2, 7.1, and 11.6 μm, respectively. After that, colony formation assay, cell cycle, apoptosis analysis, wound-healing migration assay, and Western blotting were carried out to learn the bioactivity of compound 5. © 2017 John Wiley & Sons A/S.

Molecular profiling techniques as tools to detect potential unintended effects in genetically engineered maize

CSIR Research Space (South Africa)

Barros, E

2010-05-01

Full Text Available Molecular Profiling Techniques as Tools to Detect Potential Unintended Effects in Genetically Engineered Maize Eugenia Barros Introduction In the early stages of production and commercialization of foods derived from genetically engineered (GE) plants... systems. In a recent paper published in Plant Biotechnology Journal,4 we compared two transgenic white maize lines with the non-transgenic counterpart to investigate two possible sources of variation: genetic engineering and environmental variation...

Identification of critical chemical features for Aurora kinase-B inhibitors using Hip-Hop, virtual screening and molecular docking

Science.gov (United States)

Sakkiah, Sugunadevi; Thangapandian, Sundarapandian; John, Shalini; Lee, Keun Woo

2011-01-01

This study was performed to find the selective chemical features for Aurora kinase-B inhibitors using the potent methods like Hip-Hop, virtual screening, homology modeling, molecular dynamics and docking. The best hypothesis, Hypo1 was validated toward a wide range of test set containing the selective inhibitors of Aurora kinase-B. Homology modeling and molecular dynamics studies were carried out to perform the molecular docking studies. The best hypothesis Hypo1 was used as a 3D query to screen the chemical databases. The screened molecules from the databases were sorted based on ADME and drug like properties. The selective hit compounds were docked and the hydrogen bond interactions with the critical amino acids present in Aurora kinase-B were compared with the chemical features present in the Hypo1. Finally, we suggest that the chemical features present in the Hypo1 are vital for a molecule to inhibit the Aurora kinase-B activity.

A strategy for molecular diagnostics of Fanconi anemia in Brazilian patients.

Science.gov (United States)

Pilonetto, Daniela V; Pereira, Noemi F; Bonfim, Carmem M S; Ribeiro, Lisandro L; Bitencourt, Marco A; Kerkhoven, Lianne; Floor, Karijn; Ameziane, Najim; Joenje, Hans; Gille, Johan J P; Pasquini, Ricardo

2017-07-01

Fanconi anemia (FA) is a predominantly autosomal recessive disease with wide genetic heterogeneity resulting from mutations in several DNA repair pathway genes. To date, 21 genetic subtypes have been identified. We aimed to identify the FA genetic subtypes in the Brazilian population and to develop a strategy for molecular diagnosis applicable to routine clinical use. We screened 255 patients from Hospital de Clínicas, Universidade Federal do Paraná for 11 common FA gene mutations. Further analysis by multiplex ligation-dependent probe amplification (MLPA) for FANCA and Sanger sequencing of all coding exons of FANCA , -C , and - G was performed in cases who harbored a single gene mutation. We identified biallelic mutations in 128/255 patients (50.2%): 89, 11, and 28 carried FANCA , FANCC , and FANCG mutations, respectively. Of these, 71 harbored homozygous mutations, whereas 57 had compound heterozygous mutations. In 4/57 heterozygous patients, both mutations were identified by the initial screening, in 51/57 additional analyses was required for classification, and in 2/57 the second mutation remained unidentified. We found 52 different mutations of which 22 were novel. The proposed method allowed genetic subtyping of 126/255 (49.4%) patients at a significantly reduced time and cost, which makes molecular diagnosis of FA Brazilian patients feasible.

Reno-endocrinal disorders: A basic understanding of the molecular genetics

Directory of Open Access Journals (Sweden)

Sukhminder Jit Singh Bajwa

2012-01-01

Full Text Available The successful management of endocrine diseases is greatly helped by the complete understanding of the underlying pathology. The knowledge about the molecular genetics contributes immensely in the appropriate identification of the causative factors of the diseases and their subsequent management. The fields of nephrology and endocrinology are also interrelated to a large extent. Besides performing the secretory functions, the renal tissue also acts as target organ for many hormones such as antidiuretic hormone (ADH, atrial natriuretic peptides (ANP, and aldosterone. Understanding the molecular genetics of these hormones is important because the therapeutic interventions in many of these conditions is related to shared renal and endocrine functions, including the anemia of renal disease, chronic kidney disease, mineral bone disorders, and hypertension related to chronic kidney disease. Their understanding and in-depth knowledge is very essential in designing and formulating the therapeutic plans and innovating new management strategies. However, we still have to go a long way in order to completely understand the various confounding causative relationships between the pathology and disease of these reno-endocrinal manifestations.

Incorporating personalized gene sequence variants, molecular genetics knowledge, and health knowledge into an EHR prototype based on the Continuity of Care Record standard

Science.gov (United States)

Jing, Xia; Kay, Stephen; Marley, Tom; Hardiker, Nicholas R.; Cimino, James J.

2011-01-01

Summary Objectives The current volume and complexity of genetic tests, and the molecular genetics knowledge and health knowledge related to interpretation of the results of those tests, are rapidly outstripping the ability of individual clinicians to recall, understand and convey to their patients information relevant to their care. The tailoring of molecular genetics knowledge and health knowledge in clinical settings is important both for the provision of personalized medicine and to reduce clinician information overload. In this paper we describe the incorporation, customization and demonstration of molecular genetic data (mainly sequence variants), molecular genetics knowledge and health knowledge into a standards-based electronic health record (EHR) prototype developed specifically for this study. Methods We extended the CCR (Continuity of Care Record), an existing EHR standard for representing clinical data, to include molecular genetic data. An EHR prototype was built based on the extended CCR and designed to display relevant molecular genetics knowledge and health knowledge from an existing knowledge base for cystic fibrosis (OntoKBCF). We reconstructed test records from published case reports and represented them in the CCR schema. We then used the EHR to dynamically filter molecular genetics knowledge and health knowledge from OntoKBCF using molecular genetic data and clinical data from the test cases. Results The molecular genetic data were successfully incorporated in the CCR by creating a category of laboratory results called “Molecular Genetics ” and specifying a particular class of test (“Gene Mutation Test”) in this category. Unlike other laboratory tests reported in the CCR, results of tests in this class required additional attributes (“Molecular Structure” and “Molecular Position”) to support interpretation by clinicians. These results, along with clinical data (age, sex, ethnicity, diagnostic procedures, and therapies) were used

piggyBac transposon somatic mutagenesis with an activated reporter and tracker (PB-SMART for genetic screens in mice.

Directory of Open Access Journals (Sweden)

Sean F Landrette

Full Text Available Somatic forward genetic screens have the power to interrogate thousands of genes in a single animal. Retroviral and transposon mutagenesis systems in mice have been designed and deployed in somatic tissues for surveying hematopoietic and solid tumor formation. In the context of cancer, the ability to visually mark mutant cells would present tremendous advantages for identifying tumor formation, monitoring tumor growth over time, and tracking tumor infiltrations and metastases into wild-type tissues. Furthermore, locating mutant clones is a prerequisite for screening and analyzing most other somatic phenotypes. For this purpose, we developed a system using the piggyBac (PB transposon for somatic mutagenesis with an activated reporter and tracker, called PB-SMART. The PB-SMART mouse genetic screening system can simultaneously induce somatic mutations and mark mutated cells using bioluminescence or fluorescence. The marking of mutant cells enable analyses that are not possible with current somatic mutagenesis systems, such as tracking cell proliferation and tumor growth, detecting tumor cell infiltrations, and reporting tissue mutagenesis levels by a simple ex vivo visual readout. We demonstrate that PB-SMART is highly mutagenic, capable of tumor induction with low copy transposons, which facilitates the mapping and identification of causative insertions. We further integrated a conditional transposase with the PB-SMART system, permitting tissue-specific mutagenesis with a single cross to any available Cre line. Targeting the germline, the system could also be used to conduct F1 screens. With these features, PB-SMART provides an integrated platform for individual investigators to harness the power of somatic mutagenesis and phenotypic screens to decipher the genetic basis of mammalian biology and disease.

Towards a systematic nationwide screening strategy for MODY.

Science.gov (United States)

Shields, Beverley; Colclough, Kevin

2017-04-01

MODY is an early-onset monogenic form of diabetes. Correctly identifying MODY is of considerable importance as diagnosing the specific genetic subtype can inform the optimal treatment, with many patients being able to discontinue unnecessary insulin treatment. Diagnostic molecular genetic testing to confirm MODY is expensive, so screening strategies are required to identify the most appropriate patients for testing. In this issue of Diabetologia, Johansson and colleagues (DOI 10.1007/s00125-016-4167-1 ) describe a nationwide systematic screening approach to identify individuals with MODY in the paediatric age range. They focused testing on patients negative for both GAD and islet antigen 2 (IA-2) islet autoantibodies, thereby ruling out those with markers of type 1 diabetes, the most common form of diabetes in this age group. This commentary discusses the advantages and limitations of the approach, and the caution required when interpreting variants of uncertain pathogenicity identified from testing whole populations rather than targeting only patients with a strong MODY phenotype.

Catecholaminergic systems in stress: structural and molecular genetic approaches.

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Kvetnansky, Richard; Sabban, Esther L; Palkovits, Miklos

2009-04-01

Stressful stimuli evoke complex endocrine, autonomic, and behavioral responses that are extremely variable and specific depending on the type and nature of the stressors. We first provide a short overview of physiology, biochemistry, and molecular genetics of sympatho-adrenomedullary, sympatho-neural, and brain catecholaminergic systems. Important processes of catecholamine biosynthesis, storage, release, secretion, uptake, reuptake, degradation, and transporters in acutely or chronically stressed organisms are described. We emphasize the structural variability of catecholamine systems and the molecular genetics of enzymes involved in biosynthesis and degradation of catecholamines and transporters. Characterization of enzyme gene promoters, transcriptional and posttranscriptional mechanisms, transcription factors, gene expression and protein translation, as well as different phases of stress-activated transcription and quantitative determination of mRNA levels in stressed organisms are discussed. Data from catecholamine enzyme gene knockout mice are shown. Interaction of catecholaminergic systems with other neurotransmitter and hormonal systems are discussed. We describe the effects of homotypic and heterotypic stressors, adaptation and maladaptation of the organism, and the specificity of stressors (physical, emotional, metabolic, etc.) on activation of catecholaminergic systems at all levels from plasma catecholamines to gene expression of catecholamine enzymes. We also discuss cross-adaptation and the effect of novel heterotypic stressors on organisms adapted to long-term monotypic stressors. The extra-adrenal nonneuronal adrenergic system is described. Stress-related central neuronal regulatory circuits and central organization of responses to various stressors are presented with selected examples of regulatory molecular mechanisms. Data summarized here indicate that catecholaminergic systems are activated in different ways following exposure to distinct

Classical and molecular genetics of malignant melanoma and dysplastic naevi

International Nuclear Information System (INIS)

Traupe, H.; Macher, E.

1988-01-01

The authors conclude that the prevailing concept of monogenic autosomaldominant inheritance of dysplastic naevi and familial melanoma is not compatible with the principles of formal (Mendelian) genetics. The concept of polygenic inheritance offers instead a sound basis to explain familial aggregation of dysplastic naevi and melanoma. The various genes involved have not yet been identified at the molecular level. The recent advances made possible by modern DNA technology have given us a new view of carcinogenesis. In human malignant melanoma, chromosomes 1, 6, 7 are of particular interest and oncogenes located on these chromosomes may be involved with the initiation, promotion and progression of melanoma. Carcinogenesis is viewed as a multistep process and even tumour initiation requires the input of at least two independent oncogenes. Molecular genetics thus adds an important argument for the existence of a polygenic predisposition to melanoma. The concept of polygenic inheritance is not restricted to familial melanoma, but implies that all melanomas basically share the same predisposition and are due to similar genetic mechanisms. In some patients an inherited genetic predisposition is of great importance, whereas in others (the majority) environmental factors (e.g. UV-light-induced mutations) will be the cause of initial steps in the malignant transformation. The concept of polygenic inheritance has consequences for the management of our patients. In contrast to simple Mendelian inheritance, the risk for dysplastic naevi and melanoma is not constantly 50%, but increases with the number of family members already affected. Persons belonging to families with more that 2 affected close relatives should be considered at high risk regardless of the dysplastic naevus status. Strict surveillance of this patient group is warranted for melanoma prevention

Joint SOGC-CCMG Opinion for Reproductive Genetic Carrier Screening: An Update for All Canadian Providers of Maternity and Reproductive Healthcare in the Era of Direct-to-Consumer Testing.

Science.gov (United States)

Wilson, R Douglas; De Bie, Isabelle; Armour, Christine M; Brown, Richard N; Campagnolo, Carla; Carroll, June C; Okun, Nan; Nelson, Tanya; Zwingerman, Rhonda; Audibert, Francois; Brock, Jo-Ann; Brown, Richard N; Campagnolo, Carla; Carroll, June C; De Bie, Isabelle; Johnson, Jo-Ann; Okun, Nan; Pastruck, Melanie; Vallée-Pouliot, Karine; Wilson, R Douglas; Zwingerman, Rhonda; Armour, Christine; Chitayat, David; De Bie, Isabelle; Fernandez, Sara; Kim, Raymond; Lavoie, Josee; Leonard, Norma; Nelson, Tanya; Taylor, Sherry; Van Allen, Margot; Van Karnebeek, Clara

2016-08-01

This guideline was written to update Canadian maternity care and reproductive healthcare providers on pre- and postconceptional reproductive carrier screening for women or couples who may be at risk of being carriers for autosomal recessive (AR), autosomal dominant (AD), or X-linked (XL) conditions, with risk of transmission to the fetus. Four previous SOGC- Canadian College of Medical Geneticists (CCMG) guidelines are updated and merged into the current document. All maternity care (most responsible health provider [MRHP]) and paediatric providers; maternity nursing; nurse practitioner; provincial maternity care administrator; medical student; and postgraduate resident year 1-7. Fertile, sexually active females and their fertile, sexually active male partners who are either planning a pregnancy or are pregnant (preferably in the first trimester of pregnancy, but any gestational age is acceptable). Women and their partners will be able to obtain appropriate genetic carrier screening information and possible diagnosis of AR, AD, or XL disorders (preferably pre-conception), thereby allowing an informed choice regarding genetic carrier screening and reproductive options (e.g., prenatal diagnosis, preimplantation genetic diagnosis, egg or sperm donation, or adoption). Informed reproductive decisions related to genetic carrier screening and reproductive outcomes based on family history, ethnic background, past obstetrical history, known carrier status, or genetic diagnosis. SOGC REPRODUCTIVE CARRIER SCREENING SUMMARY STATEMENT (2016): Pre-conception or prenatal education and counselling for reproductive carrier screening requires a discussion about testing within the three perinatal genetic carrier screening/diagnosis time periods, which include pre-conception, prenatal, and neonatal for conditions currently being screened for and diagnosed. This new information should be added to the standard reproductive carrier screening protocols that are already being utilized by

Molecular genetics made simple

Directory of Open Access Journals (Sweden)

Heba Sh. Kassem

2012-07-01

Full Text Available Genetics have undoubtedly become an integral part of biomedical science and clinical practice, with important implications in deciphering disease pathogenesis and progression, identifying diagnostic and prognostic markers, as well as designing better targeted treatments. The exponential growth of our understanding of different genetic concepts is paralleled by a growing list of genetic terminology that can easily intimidate the unfamiliar reader. Rendering genetics incomprehensible to the clinician however, defeats the very essence of genetic research: its utilization for combating disease and improving quality of life. Herein we attempt to correct this notion by presenting the basic genetic concepts along with their usefulness in the cardiology clinic. Bringing genetics closer to the clinician will enable its harmonious incorporation into clinical care, thus not only restoring our perception of its simple and elegant nature, but importantly ensuring the maximal benefit for our patients.

Molecular genetics made simple

Science.gov (United States)

Kassem, Heba Sh.; Girolami, Francesca; Sanoudou, Despina

2012-01-01

Abstract Genetics have undoubtedly become an integral part of biomedical science and clinical practice, with important implications in deciphering disease pathogenesis and progression, identifying diagnostic and prognostic markers, as well as designing better targeted treatments. The exponential growth of our understanding of different genetic concepts is paralleled by a growing list of genetic terminology that can easily intimidate the unfamiliar reader. Rendering genetics incomprehensible to the clinician however, defeats the very essence of genetic research: its utilization for combating disease and improving quality of life. Herein we attempt to correct this notion by presenting the basic genetic concepts along with their usefulness in the cardiology clinic. Bringing genetics closer to the clinician will enable its harmonious incorporation into clinical care, thus not only restoring our perception of its simple and elegant nature, but importantly ensuring the maximal benefit for our patients. PMID:25610837

Progress in the molecular and genetic modification breeding of beef cattle in China.

Science.gov (United States)

Tong, Bin; Zhang, Li; Li, Guang-Peng

2017-11-20

The studies of beef cattle breeding in China have been greatly improved with the rapid development of the international beef cattle industrialization. The beef cattle breeding technologies have rapidly transformed from traditional breeding to molecular marker-assisted breeding, genomic selection and genetic modification breeding. Hundreds of candidate genes and molecular markers associated with growth, meat quality, reproduction performance and diseases resistance have been identified, and some of them have already been used in cattle breeding. Genes and molecular markers associated with growth and development are focused on the growth hormone, muscle regulatory factors, myostatin and insulin-like growth factors. Meat quality is mediated by fatty acid transport and deposition related signals, calpains and calpain system, muscle regulatory factors and muscle growth regulation pathways. Reproduction performance is regulated by GnRH-FSH-LH, growth differentiation factor 9, prolactin receptor and forkhead box protein O1. Disease resistance is modulated by the major histocompatibility complex gene family, toll-like receptors, mannose-binding lectin and interferon gene signals. In this review, we summarize the most recent progress in beef cattle breeding in marker-assisted selection, genome-wide selection and genetic modification breeding, aiming to provide a reference for further genetic breeding research of beef cattle in China.

Association of Screening and Treatment With Breast Cancer Mortality by Molecular Subtype in US Women, 2000-2012.

Science.gov (United States)

Plevritis, Sylvia K; Munoz, Diego; Kurian, Allison W; Stout, Natasha K; Alagoz, Oguzhan; Near, Aimee M; Lee, Sandra J; van den Broek, Jeroen J; Huang, Xuelin; Schechter, Clyde B; Sprague, Brian L; Song, Juhee; de Koning, Harry J; Trentham-Dietz, Amy; van Ravesteyn, Nicolien T; Gangnon, Ronald; Chandler, Young; Li, Yisheng; Xu, Cong; Ergun, Mehmet Ali; Huang, Hui; Berry, Donald A; Mandelblatt, Jeanne S

2018-01-09

Given recent advances in screening mammography and adjuvant therapy (treatment), quantifying their separate and combined effects on US breast cancer mortality reductions by molecular subtype could guide future decisions to reduce disease burden. To evaluate the contributions associated with screening and treatment to breast cancer mortality reductions by molecular subtype based on estrogen-receptor (ER) and human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu). Six Cancer Intervention and Surveillance Network (CISNET) models simulated US breast cancer mortality from 2000 to 2012 using national data on plain-film and digital mammography patterns and performance, dissemination and efficacy of ER/ERBB2-specific treatment, and competing mortality. Multiple US birth cohorts were simulated. Screening mammography and treatment. The models compared age-adjusted, overall, and ER/ERBB2-specific breast cancer mortality rates from 2000 to 2012 for women aged 30 to 79 years relative to the estimated mortality rate in the absence of screening and treatment (baseline rate); mortality reductions were apportioned to screening and treatment. In 2000, the estimated reduction in overall breast cancer mortality rate was 37% (model range, 27%-42%) relative to the estimated baseline rate in 2000 of 64 deaths (model range, 56-73) per 100 000 women: 44% (model range, 35%-60%) of this reduction was associated with screening and 56% (model range, 40%-65%) with treatment. In 2012, the estimated reduction in overall breast cancer mortality rate was 49% (model range, 39%-58%) relative to the estimated baseline rate in 2012 of 63 deaths (model range, 54-73) per 100 000 women: 37% (model range, 26%-51%) of this reduction was associated with screening and 63% (model range, 49%-74%) with treatment. Of the 63% associated with treatment, 31% (model range, 22%-37%) was associated with chemotherapy, 27% (model range, 18%-36%) with hormone therapy, and 4% (model range, 1

Genetic diversity and molecular characterization of Saccharomyces cerevisiae strains from winemaking environments

OpenAIRE

Schuller, Dorit Elisabeth

2004-01-01

Tese de doutoramento em Ciências The principal aim of the present work is to assess the genetic diversity of fermenting Saccharomyces cerevisiae strains found in vineyards belonging to the Vinho Verde Region in order to create a strain collection representing the region’s biodiversity wealth as a basis for future strain selection and improvement programs. Validation of molecular techniques for accurate genotyping is an indispensable prerequisite for biogeographical surveys. Molecular ty...

Toxoplasmosis: Seroprevalence in pregnant women, and serological and molecular screening in neonatal umbilical cord blood.

Science.gov (United States)

Shieh, Mahshad; Didehdar, Mojtaba; Hajihossein, Reza; Ahmadi, Farzam; Eslamirad, Zahra

2017-10-01

Toxoplasmosis is a common zoonotic disease that can also be transmitted from the mother to the embryo, with the risk of congenital infection varying around the world. The aim of this study was to screen pregnant women and their neonates for toxoplasmosis by serologic and molecular methods and assess the impact of risk factors associated with toxoplasmosis on the rate of congenital infection. This study was conducted at a regional maternity hospital in Arak, the capital of the Markazi Province in Iran, during a period of six months. All selected pregnant women (n=261) and the corresponding cord blood samples were serologically screened for toxoplasmosis, with seropositive samples also undergoing molecular testing. Demographic data, as well as information related to the risk factors associated with the transmission of the disease, were collected from mothers and their neonates. The detection of anti-Toxoplasma antibodies and the extraction of DNA from blood samples were conducted using commercial kits. Results showed that the sera of 87 maternal blood samples (33.3%) and 40 cord blood samples (15.3%) were positive for anti-Toxoplasma antibodies (IgG and/or IgM). Molecular screening of the seropositive samples only identified one positive cord blood sample. In other words, the diagnosis of congenital toxoplasmosis was definitive in only one neonate. There was no significant association between the risk of parasite transmission and neonatal seropositivity (p >0.05). Therefore, the results showed that the prevalence of congenital toxoplasmosis in the studied area was consistent with the global rate and suggest that the implementation of newborn screening and follow-up testing could help reduce the disease risk. Copyright © 2017 Elsevier B.V. All rights reserved.

FieldChopper, a new tool for automatic model generation and virtual screening based on molecular fields.

Science.gov (United States)

Kalliokoski, Tuomo; Ronkko, Toni; Poso, Antti

2008-06-01

Algorithms were developed for ligand-based virtual screening of molecular databases. FieldChopper (FC) is based on the discretization of the electrostatic and van der Waals field into three classes. A model is built from a set of superimposed active molecules. The similarity of the compounds in the database to the model is then calculated using matrices that define scores for comparing field values of different categories. The method was validated using 12 publicly available data sets by comparing the method to the electrostatic similarity comparison program EON. The results suggest that FC is competitive with more complex descriptors and could be used as a molecular sieve in virtual screening experiments when multiple active ligands are known.

A genetic screen for mutations affecting embryonic development in medaka fish (Oryzias latipes).

Science.gov (United States)

Loosli, F; Köster, R W; Carl, M; Kühnlein, R; Henrich, T; Mücke, M; Krone, A; Wittbrodt, J

2000-10-01

In a pilot screen, we assayed the efficiency of ethylnitrosourea (ENU) as a chemical mutagen to induce mutations that lead to early embryonic and larval lethal phenotypes in the Japanese medaka fish, Oryzias latipes. ENU acts as a very efficient mutagen inducing mutations at high rates in germ cells. Three repeated treatments of male fish in 3 mM ENU for 1 h results in locus specific mutation rates of 1.1-1.95 x10(-3). Mutagenized males were outcrossed to wild type females and the F1 offspring was used to establish F2 families. F2 siblings were intercrossed and the F3 progeny was scored 24, 48 and 72 h after fertilization for morphological alterations affecting eye development. The presented mutant phenotypes were identified using morphological criteria and occur during early developmental stages of medaka. They are stably inherited in a Mendelian fashion. The high efficiency of ENU to induce mutations in this pilot screen indicates that chemical mutagenesis and screening for morphologically visible phenotypes in medaka fish allows the genetic analysis of specific aspects of vertebrate development complementing the screens performed in other vertebrate model systems.

Genetic and clinical characteristics of primary and secondary glioblastoma is associated with differential molecular subtype distribution

OpenAIRE

Li, Rui; Li, Hailin; Yan, Wei; Yang, Pei; Bao, Zhaoshi; Zhang, Chuanbao; Jiang, Tao; You, Yongping

2015-01-01

Glioblastoma multiforme (GBM) is classified into primary (pGBM) or secondary (sGBM) based on clinical progression. However, there are some limits to this classification for insight into genetically and clinically distinction between pGBM and sGBM. The aim of this study is to characterize pGBM and sGBM associating with differential molecular subtype distribution. Whole transcriptome sequencing data was used to assess the distribution of molecular subtypes and genetic alterations in 88 pGBM and...

In vivo quantification of fluorescent molecular markers in real-time by ratio Imaging for diagnostic screening and image-guided surgery

NARCIS (Netherlands)

Bogaards, A.; Sterenborg, H. J. C. M.; Trachtenberg, J.; Wilson, B. C.; Lilge, L.

2007-01-01

Future applications of "molecular diagnostic screening" and "molecular image-guided surgery" will demand images of molecular markers with high resolution and high throughput (similar to >= 30 frames/second). MRI, SPECT, PET, optical fluorescence tomography, hyper-spectral fluorescence imaging, and

Phenotypic and genetic characterization of Paecilomyces lilacinus strains with biocontrol activity against root-knot nematodes.

Science.gov (United States)

Gunasekera, T S; Holland, R J; Gillings, M R; Briscoe, D A; Neethling, D C; Williams, K L; Nevalainen, K M

2000-09-01

Efficient selection of fungi for biological control of nematodes requires a series of screening assays. Assessment of genetic diversity in the candidate species maximizes the variety of the isolates tested and permits the assignment of a particular genotype with high nematophagous potential using a rapid novel assay. Molecular analyses also facilitate separation between isolates, allowing the identification of proprietary strains and trace biocontrol strains in the environment. The resistance of propagules to UV radiation is an important factor in the survival of a biocontrol agent. We have analyzed 15 strains of the nematophagous fungus Paecilomyces lilacinus using these principles. Arbitrarily primed DNA and allozyme assays were applied to place the isolates into genetic clusters, and demonstrated that some genetically related P. lilacinus strains exhibit widespread geographic distributions. When exposed to UV radiation, some weakly nematophagous strains were generally more susceptible than effective isolates. A microtitre tray-based assay used to screen the pathogenic activity of each isolate to Meloidogyne javanica egg masses revealed that the nematophagous ability varied between 37%-100%. However, there was no clear relationship between nematophagous ability and genetic clusters. Molecular characterizations revealed sufficient diversity to allow tracking of strains released into the environment.

the genetic and molecular basis of bacterial invasion of epithelial cells

African Journals Online (AJOL)

DR. AMINU

The pathogenic species of bacteria are of great medical importance as causative agents of infectious diseases. Moreover, as the condition of human existence have changed, so have the bacterial species that produce diseases. It is against this background that molecular genetics have now entered the field of microbial ...

[Malignant Melanoma - from Classical Histology towards Molecular Genetic Testing].

Science.gov (United States)

Ryška, A; Horký, O; Berkovcová, J; Tichá, I; Kalinová, M; Matějčková, M; Bóday, Á; Drábek, J; Martínek, P; Šimová, J; Sieglová, K; Vošmiková, H

Malignant melanoma is - in comparison with other skin tumors - a relatively rare malignant neoplasm with highly aggressive biologic behavior and variable prognosis. Recent data in pathology and molecular diagnostics indicate that malignant melanoma is in fact not a single entity but a group of different neoplasms with variable etiopathogenesis, biologic behavior and prognosis. New therapeutic options using targeted treatment blocking MAPK signaling pathway require testing of BRAF gene mutation status. This helps to select patients with highest probability of benefit from this treatment. This article summarizes information on the correlation of morphological findings with genetic changes, discusses the representation of individual genetic types in various morphological subgroups and deals with the newly proposed genetic classification of melanoma and the current possibilities, pitfalls and challenges in BRAF testing of malignant melanoma. It also describes the current testing situation in the Czech Republic - the methods used, the representation of BRAF mutations in the tested population and the future of testing. It also shows the limitations of the BRAF and MEK targeted treatment concept resulting from the heterogeneity of the tumor population. Mechanisms of acquired resistance to MAPK pathway inhibitors, possibilities of their detection, and issues of combination of targeted therapy and immunotherapy are discussed.Key words: malignant melanoma - BRAF - mutation - molecular targeted therapy - tumor microenvironment - tumor heterogeneity This work was supported by projects PROGRES Q40/11, BBMRICZ LM2015089, SVV 260398 and GACR 17-10331S. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 28. 3. 2017Accepted: 16. 5. 2017.

Permanent genetic resources added to molecular ecology resources database 1 February 2013-31 March 2013

Czech Academy of Sciences Publication Activity Database

Arias, M. C.; Atteke, C.; Augusto, S. C.; Bailey, J.; Bazaga, P.; Beheregaray, L. B.; Benoit, L.; Blatrix, R.; Born, C.; Brito, R. M.; Chen, H.-K.; Covarrubias, S.; de Vega, C.; Djiéto-Lordon, C.; Dubois, M.-P.; Francisco, F. O.; García, C.; Concalves, P. H. P.; González, C.; Gutiérrez-Rodríguez, C.; Hammer, M. P.; Herrera, C. M.; Itoh, H.; Kamimura, S.; Karaoglu, H.; Kojima, S.; Li, S.-L.; Ling, H. J.; Matos Maravi, Pavel F.; McKey, D.; Mezui-M’Eko, J.; Ornelas, J. F.; Park, R. F.; Pozo, M. I.; Ramula, S.; Rigueiro, C.; Sandoval-Castillo, J.; Santiago, L. R.; Seino, M. M.; Song, C.-B.; Takeshima, H.; Vasemägi, A.; Wellings, C. R.; Yan, J.; Du, Y.-Z.; Zhang, C.-R.; Zhang, T.-Y.

2013-01-01

Roč. 13, č. 4 (2013), s. 760-762 ISSN 1755-098X Institutional support: RVO:60077344 Keywords : molecular ecology Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.626, year: 2013 http://onlinelibrary.wiley.com/doi/10.1111/1755-0998.12121/pdf

Molecular evaluation of genetic variability of wheat elite breeding material

Directory of Open Access Journals (Sweden)

Brbaklić Ljiljana

2009-01-01

Full Text Available Estimation of genetic variability of breeding material is essential for yield improvement in wheat cultivars. Modern techniques based on molecular markers application are more efficient and precise in genetic variability evaluation then conventional methods. Variability of 96 wheat cultivars and lines was analyzed using four microsatellite markers (Gwm11, Gwm428, Psp3200, Psp3071. The markers were chosen according to their potential association with important agronomical traits indicated in the literature. Total of 31 alleles were detected with maximum number of alleles (11 in Xgwm11 locus. The highest polymorphism information content (PIC value (0,831 was found in the locus Xpsp3071. The genotypes were grouped into three subpopulations based on their similarity in the analyzed loci. The results have indicated wide genetic variability of the studied material and possibility of its application in further breeding process after validation of marker-trait association. .

GENETICS AND MOLECULAR BIOLOGY AND PIG MEAT QUALITY IMPROVEMENT

Directory of Open Access Journals (Sweden)

J. BULLA

2007-05-01

Full Text Available The main goals in pig breeding have for many years been to improve growth rate, feedconversion and carcass composition. There have been less efforts to improve meat qualityparameters (WHC, pH, tenderness, colour etc. but the main contribution has been areduction of stress susceptibility and PSE meat. Unfortunately, the quantitative geneticapproach has yielded few clues regarding the fundamental genetic changes that accompaniedthe selection of animal for superior carcass attributes. While mapping efforts are makingsignificant major effects on carcass and his quality composition DNA test would be availableto detect some positive or negative alleles. There are clear breed effects on meat quality,which in some cases are fully related to the presence of a single gene with major effect (RYR1,MYF4, H-FABP, LEPR, IGF2. Molecular biology methods provides excellent opportunitiesto improve meat quality in selection schemes within breeds and lines. Selection on majorgenes will not only increase average levels of quality but also decrease variability (ei increaseuniformity. The aim of this paper is to discuss there genetic and non-genetic opportunities.

GENETICS AND MOLECULAR BIOLOGY AND PIG MEAT QUALITY IMPROVEMENT

Directory of Open Access Journals (Sweden)

BULLA, J.

2007-01-01

Full Text Available The main goals in pig breeding have for many years been to improve growth rate, feedconversion and carcass composition. There have been less efforts to improve meat qualityparameters (WHC, pH, tenderness, colour etc. but the main contribution has been areduction of stress susceptibility and PSE meat. Unfortunately, the quantitative geneticapproach has yielded few clues regarding the fundamental genetic changes that accompaniedthe selection of animal for superior carcass attributes. While mapping efforts are makingsignificant major effects on carcass and his quality composition DNA test would be availableto detect some positive or negative alleles. There are clear breed effects on meat quality,which in some cases are fully related to the presence of a single gene with major effect (RYR1,MYF4, H-FABP, LEPR, IGF2. Molecular biology methods provides excellent opportunitiesto improve meat quality in selection schemes within breeds and lines. Selection on majorgenes will not only increase average levels of quality but also decrease variability (ei increaseuniformity. The aim of this paper is to discuss there genetic and non-genetic opportunities.

["Screening" in special situations. Assessing predictive genetic screening for hereditary breast and colorectal cancer].

Science.gov (United States)

Jonas, Susanna; Wild, Claudia; Schamberger, Chantal

2003-02-01

mastectomy (PM) reduces the relative breast cancer risk by approximately 90%. The question is if PM has an impact on mortality. The acceptance of PM is culture-dependent. Colectomy can be used as a prophylactic (FAP) and therapeutic method. After surgery, the cancer risk remains high and so early detection examinations are still necessary. EVIDENCE-BASED STATEMENTS: The evidence is often fragmentary and of limited quality. For objective test result presentation information about sensitivity, specificity, positive predictive value, and number needed to screen and treat, respectively, are necessary. New identification of mutations and demand will lead to an increase of predictive genetic counselling and testing. There is a gap between predictive genetic diagnosis and prediction, prevention, early detection and surgical interventions. These circumstances require a basic strategy. Since predictive genetic diagnosis is a very sensitive issue it is important to deal with it carefully in order to avoid inappropriate hopes. Thus, media, experts and politicians need to consider opportunities and limitations in their daily decision-making processes.

A molecular, genetic and physiological analysis of plant aluminum tolerance (abstract)

International Nuclear Information System (INIS)

Pineros, M.

2005-01-01

Aluminum (Al) toxicity is an important agronomic trait, limiting crop production on acid soils that comprise up to 50% of the world's potentially arable lands. A significant genetic variation in Al tolerance exists in both crop plants and Arabidopsis. The exploitation of this genetic variation to breed crops with increased Al tolerance has been a productive and active area of research, however, the underlying molecular, genetic and physiological bases are still not well understood. Only very recently was the first Al tolerance gene, ALMT1, isolated in wheat and shown to be a novel Al-activated malate transporter. Work in our laboratory has focused on using integrated genomic (gene and protein expression profiling), molecular genetic and physiological approaches to identify novel Al tolerance genes and the physiological mechanisms they control in the cereal crops maize and sorghum, and also in arabidopsis. In sorghum we had previously shown that Al tolerance is the result of a single locus, Alt/sub SB/ which maps to the top of sorghum chromosome 3 in a region totally distinct from where the major Al tolerance maps in wheat and other related members of the Triticeae. Very recently, we have used map-based cloning techniques in sorghum to clone Alt/sub SB/ and have found it is a novel Al tolerance gene. Here we will present a molecular characterization of the Alt/sub SB/ gene and also the physiological mechanism of sorghum Al tolerance it controls. In arabidopsis, we have previously shown that Al tolerance is a quantitative trait and have identified two major Al tolerance QTL on chromosomes 1 and 5. These genes function to confer tolerance via Al via activated root malate release. We found that a member of the arabidopsis gene family that is a close homolog to wheat ALMT1 maps near the largest tolerance QTL on chromosome 1 and have also found this gene encodes the Al-activated malate transport involved in arabidopsis Al tolerance. However, we have clear molecular

Molecular mechanisms of the genetic risk factors in pathogenesis of Alzheimer disease.

Science.gov (United States)

Kanatsu, Kunihiko; Tomita, Taisuke

2017-01-01

Alzheimer disease (AD) is a neurodegenerative disease characterized by the extensive deposition of senile plaques and neurofibrillary tangles. Until recently, only the APOE gene had been known as a genetic risk factor for late-onset AD (LOAD), which accounts for more than 95% of all AD cases. However, in addition to this well-established genetic risk factor, genome-wide association studies have identified several single nucleotide polymorphisms as genetic risk factors of LOAD, such as PICALM and BIN1 . In addition, whole genome sequencing and exome sequencing have identified rare variants associated with LOAD, including TREM2 . We review the recent findings related to the molecular mechanisms by which these genetic risk factors contribute to AD, and our perspectives regarding the etiology of AD for the development of therapeutic agents.

Molecular genetics of early-onset Alzheimer's disease revisited.

Science.gov (United States)

Cacace, Rita; Sleegers, Kristel; Van Broeckhoven, Christine

2016-06-01

As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Skin Cancer Screening

Science.gov (United States)

... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease ...

"Am I carrier?" The patient's lived experience of thrombophilia genetic screening and its outcome.

Science.gov (United States)

Graffigna, Guendalina; Leone, Daniela; Vegni, Elena

2014-01-01

How do patients with thrombophilia experience a physician's request to undergo a genetic test? How do they experience the test outcome? To answer these questions, we conducted an interpretative phenomenological analysis study, based on 10 in-depth interviews with patients who underwent genetic testing for thrombophilia in Italy, half with positive and half with negative results. The experience of undergoing genetic screening for thrombophilia plays an important role in reconfiguring patients' signification of their illness experience. A positive outcome becomes a cue to reorganize in a more adaptive way the illness meaning at the cognitive and emotive levels, whereas a negative outcome appears more distressing and confusing. As a clinical implication of the study, clinicians should consider communicating carefully with the patients regardless from the positive/negative test results and they should explore the patient's specific reaction and understanding of test result.

Revealing molecular mechanisms by integrating high-dimensional functional screens with protein interaction data.

Directory of Open Access Journals (Sweden)

Angela Simeone

2014-09-01

Full Text Available Functional genomics screens using multi-parametric assays are powerful approaches for identifying genes involved in particular cellular processes. However, they suffer from problems like noise, and often provide little insight into molecular mechanisms. A bottleneck for addressing these issues is the lack of computational methods for the systematic integration of multi-parametric phenotypic datasets with molecular interactions. Here, we present Integrative Multi Profile Analysis of Cellular Traits (IMPACT. The main goal of IMPACT is to identify the most consistent phenotypic profile among interacting genes. This approach utilizes two types of external information: sets of related genes (IMPACT-sets and network information (IMPACT-modules. Based on the notion that interacting genes are more likely to be involved in similar functions than non-interacting genes, this data is used as a prior to inform the filtering of phenotypic profiles that are similar among interacting genes. IMPACT-sets selects the most frequent profile among a set of related genes. IMPACT-modules identifies sub-networks containing genes with similar phenotype profiles. The statistical significance of these selections is subsequently quantified via permutations of the data. IMPACT (1 handles multiple profiles per gene, (2 rescues genes with weak phenotypes and (3 accounts for multiple biases e.g. caused by the network topology. Application to a genome-wide RNAi screen on endocytosis showed that IMPACT improved the recovery of known endocytosis-related genes, decreased off-target effects, and detected consistent phenotypes. Those findings were confirmed by rescreening 468 genes. Additionally we validated an unexpected influence of the IGF-receptor on EGF-endocytosis. IMPACT facilitates the selection of high-quality phenotypic profiles using different types of independent information, thereby supporting the molecular interpretation of functional screens.

Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing

OpenAIRE

Kauffman, Tia L.; Wilfond, Benjamin S.; Jarvik, Gail P.; Leo, Michael C.; Lynch, Frances L.; Reiss, Jacob A.; Richards, C. Sue; McMullen, Carmit; Nickerson, Deborah; Dorschner, Michael O.; Goddard, Katrina A.B.

2016-01-01

Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results...

Pharmacophore modeling, virtual screening and molecular docking of ATPase inhibitors of HSP70.

Science.gov (United States)

Sangeetha, K; Sasikala, R P; Meena, K S

2017-10-01

Heat shock protein 70 is an effective anticancer target as it influences many signaling pathways. Hence the study investigated the important pharmacophore feature required for ATPase inhibitors of HSP70 by generating a ligand based pharmacophore model followed by virtual based screening and subsequent validation by molecular docking in Discovery studio V4.0. The most extrapolative pharmacophore model (hypotheses 8) consisted of four hydrogen bond acceptors. Further validation by external test set prediction identified 200 hits from Mini Maybridge, Drug Diverse, SCPDB compounds and Phytochemicals. Consequently, the screened compounds were refined by rule of five, ADMET and molecular docking to retain the best competitive hits. Finally Phytochemical compounds Muricatetrocin B, Diacetylphiladelphicalactone C, Eleutheroside B and 5-(3-{[1-(benzylsulfonyl)piperidin-4-yl]amino}phenyl)- 4-bromo-3-(carboxymethoxy)thiophene-2-carboxylic acid were obtained as leads to inhibit the ATPase activity of HSP70 in our findings and thus can be proposed for further in vitro and in vivo evaluation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and validation of duplex, triplex, and pentaplex real-time PCR screening assays for the detection of genetically modified organisms in food and feed.

Science.gov (United States)

Huber, Ingrid; Block, Annette; Sebah, Daniela; Debode, Frédéric; Morisset, Dany; Grohmann, Lutz; Berben, Gilbert; Stebih, Dejan; Milavec, Mojca; Zel, Jana; Busch, Ulrich

2013-10-30

Worldwide, qualitative methods based on PCR are most commonly used as screening tools for genetically modified material in food and feed. However, the increasing number and diversity of genetically modified organisms (GMO) require effective methods for simultaneously detecting several genetic elements marking the presence of transgenic events. Herein we describe the development and validation of a pentaplex, as well as complementary triplex and duplex real-time PCR assays, for the detection of the most common screening elements found in commercialized GMOs: P-35S, T-nos, ctp2-cp4-epsps, bar, and pat. The use of these screening assays allows the coverage of many GMO events globally approved for commercialization. Each multiplex real-time PCR assay shows high specificity and sensitivity with an absolute limit of detection below 20 copies for the targeted sequences. We demonstrate by intra- and interlaboratory tests that the assays are robust as well as cost- and time-effective for GMO screening if applied in routine GMO analysis.

Use of preimplantation genetic diagnosis and preimplantation genetic screening in the United States: a Society for Assisted Reproductive Technology Writing Group paper.

Science.gov (United States)

Ginsburg, Elizabeth S; Baker, Valerie L; Racowsky, Catherine; Wantman, Ethan; Goldfarb, James; Stern, Judy E

2011-10-01

To comprehensively report Society for Assisted Reproductive Technology (SART) member program usage of preimplantation genetic testing (PGT), preimplantation genetic diagnosis (PGD) for diagnosis of specific conditions, and preimplantation genetic screening for aneuploidy (PGS). Retrospective study. United States SART cohort data. Women undergoing a PGT cycle in which at least one embryo underwent biopsy. PGT. PGT use, indications, and delivery rates. Of 190,260 fresh, nondonor assisted reproductive technology (ART) cycles reported to SART CORS in 2007-2008, 8,337 included PGT. Of 6,971 cycles with a defined indication, 1,382 cycles were for genetic diagnosis, 3,645 for aneuploidy screening (PGS), 527 for translocation, and 1,417 for elective sex election. Although the total number of fresh, autologous cycles increased by 3.6% from 2007 to 2008, the percentage of cycles with PGT decreased by 5.8% (4,293 in 2007 and 4,044 in 2008). As a percentage of fresh, nondonor ART cycles, use dropped from 4.6% (4,293/93,433) in 2007 to 4.2% (4,044/96,827) in 2008. The primary indication for PGT was PGS: cycles performed for this indication decreased (-8.0%). PGD use for single-gene defects (+3.2%), elective sex selection (+5.3%), and translocation analysis (+0.5%) increased. PGT usage varied significantly by geographical region. PGT usage in the United States decreased between 2007 and 2008 owing to a decrease in PGS. Use of elective sex selection increased. High transfer cancellation rates correlated with reduced live-birth rates for some PGT indications. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Colorectal Cancer Screening

Science.gov (United States)

... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

Clinical, Endocrine, and Molecular Genetic Analysis of a Large Cohort of Saudi Arabian Patients with Laron Syndrome.

Science.gov (United States)

Al-Ashwal, Abdullah A; Al-Sagheir, Afaf; Ramzan, Khushnooda; Al-Owain, Mohammed; Allam, Rabab; Qari, Alya; Al-Numair, Nouf S; Imtiaz, Faiqa

2017-01-01

Laron syndrome (LS) is an autosomal recessive disease characterized by marked short stature and very low serum IGF-1 and IGFBP-3 levels. This study assessed the clinical and endocrine features alongside determining the growth hormone receptor gene (GHR) mutation in Saudi Arabian patients with LS in order to establish whether or not a genotype/phenotype correlation is evident in this large cohort. A total of 40 Saudi Arabian patients with a suspected diagnosis of LS were recruited and subjected to a full clinical and endocrine investigation together with direct sequencing of the coding regions of the GHR gene. GHR mutations were identified in 34 patients from 22 separate nuclear families. All 34 molecularly confirmed patients had the typical clinical and endocrinological manifestations of LS. Eleven different mutations (9 previously unreported) were detected in this cohort of patients, all inherited in an autosomal recessive homozygous form. No genotype/phenotype correlation was apparent. The identification of pathogenic mutations causing LS will be of tremendous use for the molecular diagnosis of patients in Saudi Arabia and the region in general, with respect to prevention of this disease in the forms of future carrier testing, prenatal testing, premarital screening and preimplantation genetic diagnosis. © 2017 S. Karger AG, Basel.

Chemical Genetics — A Versatile Method to Combine Science and Higher Level Teaching in Molecular Genetics

Directory of Open Access Journals (Sweden)

Björn Sandrock

2012-10-01

Full Text Available Phosphorylation is a key event in many cellular processes like cell cycle, transformation of environmental signals to transcriptional activation or polar growth. The chemical genetics approach can be used to analyse the effect of highly specific inhibition in vivo and is a promising method to screen for kinase targets. We have used this approach to study the role of the germinal centre kinase Don3 during the cell division in the phytopathogenic fungus Ustilago maydis. Due to the easy determination of the don3 phenotype we have chosen this approach for a genetic course for M.Sc. students and for IMPRS (International Max-Planck research school students. According to the principle of “problem-based learning” the aim of this two-week course is to transfer knowledge about the broad spectrum of kinases to the students and that the students acquire the ability to design their own analog-sensitive kinase of interest. In addition to these training goals, we benefit from these annual courses the synthesis of basic constructs for genetic modification of several kinases in our model system U. maydis.

Clinical and molecular characterization of Chilean patients with Léri-Weill dyschondrosteosis.

Science.gov (United States)

Rodríguez, Fernando Adrián; Unanue, Nancy; Hernandez, María Isabel; Basaure, Javiera; Heath, Karen Elise; Cassorla, Fernando

2013-01-01

Léri-Weill dyschondrosteosis (LWD) is a mesomelic dysplasia with disproportionate short stature associated with short stature homeobox-containing gene (SHOX) haploinsufficiency. The objective of this study was to improve the diagnosis of patients with suspected LWD through molecular analysis. Twelve patients from 11 families with a clinical diagnosis of LWD were analyzed with multiplex ligation-dependent probe amplification to detect deletions and duplications of SHOX and its enhancer regions. High resolution melting and sequencing was employed to screen for mutations in SHOX coding exons. The molecular-based screening strategy applied in these patients allowed detection of five SHOX deletions and two previously unreported SHOX missense mutations. Molecular studies confirmed the clinical diagnosis of LWD in seven out of 12 patients, which provided support for therapeutic decisions and improved genetic counseling in their families.

Molecular characterization and genetic diversity of different genotypes of Oryza sativa and Oryza glaberrima

Directory of Open Access Journals (Sweden)

Caijin Chen

2017-11-01

Conclusions: Genetic diversity studies revealed that 50 rice types were clustered into different subpopulations whereas three genotypes were admixtures. Molecular fingerprinting and 10 specific markers were obtained to identify the 53 rice genotypes. These results can facilitate the potential utilization of sibling species in rice breeding and molecular classification of O. sativa and O. glaberrima germplasms.

Molecular genetics of follicular cell thyroid carcinoma

Directory of Open Access Journals (Sweden)

Valentina D. Yakushina

2016-09-01

Full Text Available Thyroid cancer is the most frequent endocrine malignancy. In the most cases thyroid cancer arises from follicular cells. Diagnosis of the cancer is based on the cytological analysis of fine needle aspiration biopsy of thyroid nodes. But the accuracy of the cytological diagnosis is about 80% that leads to the false positive and false negative cases and wrong strategy of treatment. Identification of genetic and epigenetic markers in the biopsies will allow to improve diagnostic accuracy. This article describes mutations, aberrant DNA methylation and abnormal microRNA expression constituting the core of molecular genetics of follicular cell thyroid cancer. The mutations given in the article includes point mutations, fusions and copy number variation. Besides frequent and well described driver mutations in genes of МАРK, PI3K/Akt and Wnt signaling pathways, as well as TP53 and TERT genes, we introduce here less frequent mutations appeared in the literature during the past two years. In addition the article contains examples of diagnostic panels applying these markers.

Successful application of virtual screening and molecular dynamics simulations against antimalarial molecular targets

Directory of Open Access Journals (Sweden)

Renata Rachide Nunes

Full Text Available The main challenge in the control of malaria has been the emergence of drug-resistant parasites. The presence of drug-resistant Plasmodium sp. has raised the need for new antimalarial drugs. Molecular modelling techniques have been used as tools to develop new drugs. In this study, we employed virtual screening of a pyrazol derivative (Tx001 against four malaria targets: plasmepsin-IV, plasmepsin-II, falcipain-II, and PfATP6. The receiver operating characteristic curves and area under the curve (AUC were established for each molecular target. The AUC values obtained for plasmepsin-IV, plasmepsin-II, and falcipain-II were 0.64, 0.92, and 0.94, respectively. All docking simulations were carried out using AutoDock Vina software. The ligand Tx001 exhibited a better interaction with PfATP6 than with the reference compound (-12.2 versus -6.8 Kcal/mol. The Tx001-PfATP6 complex was submitted to molecular dynamics simulations in vacuum implemented on an NAMD program. The ligand Tx001 docked at the same binding site as thapsigargin, which is a natural inhibitor of PfATP6. Compound TX001 was evaluated in vitro with a P. falciparum strain (W2 and a human cell line (WI-26VA4. Tx001 was discovered to be active against P. falciparum (IC50 = 8.2 µM and inactive against WI-26VA4 (IC50 > 200 µM. Further ligand optimisation cycles generated new prospects for docking and biological assays.

Molecular genetics of aging in the fly: is this the end of the beginning?

Science.gov (United States)

Helfand, Stephen L; Rogina, Blanka

2003-02-01

How we age and what we can do about it have been uppermost in human thought since antiquity. The many false starts have frustrated experimentalists and theoretical arguments pronouncing the inevitability of the process have created a nihilistic climate among scientists and the public. The identification of single gene alterations that substantially extend life span in nematodes and flies however, have begun to reinvigorate the field. Drosophila's long history of contributions to aging research, rich storehouse of genetic information, and powerful molecular techniques make it an excellent system for studying the molecular mechanisms underlying the process of aging. In recent years, Drosophila has been used to test current theories on aging and explore new directions of potential importance to the biology of aging. One such example is the surprising finding that, as opposed to the commonly held assumption that adult life is a period of random passive decline in which all things are thought to fall apart, the molecular life of the adult fly appears to be a state of dynamic well-regulated change. In the fly, the level of expression of many different genes changes in an invariant, often age-dependent, manner. These as well as other molecular genetic studies and demographic analyses using the fly have begun to challenge widely held ideas about aging providing evidence that aging may be a much more dynamic and malleable process than anticipated. With the enormous success that Drosophila molecular genetics has demonstrated in helping understand complex biological phenomena such as development there is much optimism that similar approaches can be adapted to assist in understanding the process of aging. Copyright 2003 Wiley Periodicals, Inc.

Human fertility, molecular genetics, and natural selection in modern societies.

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Felix C Tropf

Full Text Available Research on genetic influences on human fertility outcomes such as number of children ever born (NEB or the age at first childbirth (AFB has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758, results show significant additive genetic effects on both traits explaining 10% (SE = 5 of the variance in the NEB and 15% (SE = 4 in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of -0.62 (SE = 0.27, p-value = 0.02. This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size.

Validation of Version 3.0 of the Breast Cancer Genetics Referral Screening Tool (B-RST™).

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Bellcross, Cecelia; Hermstad, April; Tallo, Christine; Stanislaw, Christine

2018-05-08

Despite increased awareness of hereditary breast and ovarian cancer among clinicians and the public, many BRCA1/2 mutation carriers remain unaware of their risk status. The Breast Cancer Genetics Referral Screening Tool (B-RST™) was created and validated to easily identify individuals at increased risk for hereditary breast and ovarian cancer for referral to cancer genetics services. The purpose of this study was to revise B-RST™ to maximize sensitivity against BRCA1/2 mutation status. We analyzed pedigrees of 277 individuals who had undergone BRCA1/2 testing to determine modifications to the B-RST™ 2.0 algorithm that would maximize sensitivity for mutations, while maintaining simplicity. We used McNemar's chi-square test to compare validation measures between the revised version (3.0) and the 2.0 version. Algorithmic changes made to B-RST™ 2.0 increased the sensitivity against BRCA1/2 mutation analysis from 71.1 to 94.0% (P 3.0 demonstrates high sensitivity for BRCA1/2 mutations, yet remains a simple and quick screening tool for at-risk individuals.

Genetic determinants of heart failure: facts and numbers.

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Czepluch, Frauke S; Wollnik, Bernd; Hasenfuß, Gerd

2018-06-01

The relevance of gene mutations leading to heart diseases and hence heart failure has become evident. The risk for and the course of heart failure depends on genomic variants and mutations underlying the so-called genetic predisposition. Genetic contribution to heart failure is highly heterogenous and complex. For any patient with a likely inherited heart failure syndrome, genetic counselling is recommended and important. In the last few years, novel sequencing technologies (named next-generation sequencing - NGS) have dramatically improved the availability of molecular testing, the efficiency of genetic analyses, and moreover reduced the cost for genetic testing. Due to this development, genetic testing has become increasingly accessible and NGS-based sequencing is now applied in clinical routine diagnostics. One of the most common reasons of heart failure are cardiomyopathies such as the dilated or the hypertrophic cardiomyopathy. Nearly 100 disease-associated genes have been identified for cardiomyopathies. The knowledge of a pathogenic mutation can be used for genetic counselling, risk and prognosis determination, therapy guidance and hence for a more effective treatment. Besides, family cascade screening for a known familial, pathogenic mutation can lead to an early diagnosis in affected individuals. At that timepoint, a preventative intervention could be used to avoid or delay disease onset or delay disease progression. Understanding the cellular basis of genetic heart failure syndromes in more detail may provide new insights into the molecular biology of physiological and impaired cardiac (cell) function. As our understanding of the molecular and genetic pathophysiology of heart failure will increase, this might help to identify novel therapeutic targets and may lead to the development of new and specific treatment options in patients with heart failure. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European

Genetic diversity assessment of sesame core collection in China by phenotype and molecular markers and extraction of a mini-core collection

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Zhang Yanxin

2012-11-01

Full Text Available Abstract Background Sesame (Sesamum indicum L. is one of the four major oil crops in China. A sesame core collection (CC was established in China in 2000, but no complete study on its genetic diversity has been carried out at either the phenotypic or molecular level. To provide technical guidance, a theoretical basis for further collection, effective protection, reasonable application, and a complete analysis of sesame genetic resources, a genetic diversity assessment of the sesame CC in China was conducted using phenotypic and molecular data and by extracting a sesame mini-core collection (MC. Results Results from a genetic diversity assessment of sesame CC in China were significantly inconsistent at the phenotypic and molecular levels. A Mantel test revealed the insignificant correlation between phenotype and molecular marker information (r = 0.0043, t = 0.1320, P = 0.5525. The Shannon-Weaver diversity index (I and Nei genetic diversity index (h were higher (I = 0.9537, h = 0.5490 when calculated using phenotypic data from the CC than when using molecular data (I = 0.3467, h = 0.2218. A mini-core collection (MC containing 184 accessions was extracted based on both phenotypic and molecular data, with a low mean difference percentage (MD, 1.64%, low variance difference percentage (VD, 22.58%, large variable rate of coefficient of variance (VR, 114.86%, and large coincidence rate of range (CR, 95.76%. For molecular data, the diversity indices and the polymorphism information content (PIC for the MC were significantly higher than for the CC. Compared to an alternative random sampling strategy, the advantages of capturing genetic diversity and validation by extracting a MC using an advanced maximization strategy were proven. Conclusions This study provides a comprehensive characterization of the phenotypic and molecular genetic diversities of the sesame CC in China. A MC was extracted using both phenotypic and molecular data. Low MD% and VD%, and

Genetic diversity assessment of sesame core collection in China by phenotype and molecular markers and extraction of a mini-core collection

Science.gov (United States)

2012-01-01

Background Sesame (Sesamum indicum L.) is one of the four major oil crops in China. A sesame core collection (CC) was established in China in 2000, but no complete study on its genetic diversity has been carried out at either the phenotypic or molecular level. To provide technical guidance, a theoretical basis for further collection, effective protection, reasonable application, and a complete analysis of sesame genetic resources, a genetic diversity assessment of the sesame CC in China was conducted using phenotypic and molecular data and by extracting a sesame mini-core collection (MC). Results Results from a genetic diversity assessment of sesame CC in China were significantly inconsistent at the phenotypic and molecular levels. A Mantel test revealed the insignificant correlation between phenotype and molecular marker information (r = 0.0043, t = 0.1320, P = 0.5525). The Shannon-Weaver diversity index (I) and Nei genetic diversity index (h) were higher (I = 0.9537, h = 0.5490) when calculated using phenotypic data from the CC than when using molecular data (I = 0.3467, h = 0.2218). A mini-core collection (MC) containing 184 accessions was extracted based on both phenotypic and molecular data, with a low mean difference percentage (MD, 1.64%), low variance difference percentage (VD, 22.58%), large variable rate of coefficient of variance (VR, 114.86%), and large coincidence rate of range (CR, 95.76%). For molecular data, the diversity indices and the polymorphism information content (PIC) for the MC were significantly higher than for the CC. Compared to an alternative random sampling strategy, the advantages of capturing genetic diversity and validation by extracting a MC using an advanced maximization strategy were proven. Conclusions This study provides a comprehensive characterization of the phenotypic and molecular genetic diversities of the sesame CC in China. A MC was extracted using both phenotypic and molecular data. Low MD% and VD%, and large VR% and CR

Chondrosarcoma: With Updates on Molecular Genetics

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Mi-Jung Kim

2011-01-01

Full Text Available Chondrosarcoma (CHS is a malignant cartilage-forming tumor and usually occurs within the medullary canal of long bones and pelvic bones. Based on the morphologic feature alone, a correct diangosis of CHS may be difficult, Therefore, correlation of radiological and clinicopathological features is mandatory in the diagnosis of CHS. The prognosis of CHS is closely related to histologic grading, however, histologic grading may be subjective with high inter-observer variability. In this paper, we present histologic grading system and clinicopathological and radiological findings of conventional CHS. Subtypes of CHSs, such as dedifferentiated, mesenchymal, and clear cell CHSs are also presented. In addition, we introduce updated cytogenetic and molecular genetic findings to expand our understanding of CHS biology. New markers of cell differentiation, proliferation, and cell signaling might offer important therapeutic and prognostic information in near future.

Proof of concept: preimplantation genetic screening without embryo biopsy through analysis of cell-free DNA in spent embryo culture media.

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Shamonki, Mousa I; Jin, Helen; Haimowitz, Zachary; Liu, Lian

2016-11-01

To assess whether preimplantation genetic screening (PGS) is possible by testing for free embryonic DNA in spent IVF media from embryos undergoing trophectoderm biopsy. Prospective cohort analysis. Academic fertility center. Seven patients undergoing IVF and 57 embryos undergoing trophectoderm biopsy for PGS. On day 3 of development, each embryo was placed in a separate media droplet. All biopsied embryos received a PGS result by array comparative genomic hybridization. Preimplantation genetic screening was performed on amplified DNA extracted from media and results were compared with PGS results for the corresponding biopsy. [1] Presence of DNA in spent IVF culture media. [2] Correlation between genetic screening result from spent media and corresponding biopsy. Fifty-five samples had detectable DNA ranging from 2-642 ng/μL after a 2-hour amplification. Six samples with the highest DNA levels underwent PGS, rendering one result with a derivative log ratio SD (DLRSD) of media and a result that is consistent with trophectoderm biopsy. Improvements in DNA collection, amplification, and testing may allow for PGS without biopsy in the future. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

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Tia DiTommaso

2014-10-01

Full Text Available The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP. A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1, while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1. The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.

A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction

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Bell, Richard L.; Hauser, Sheketha; Rodd, Zachary A.; Liang, Tiebing; Sari, Youssef; McClintick, Jeanette; Rahman, Shafiqur; Engleman, Eric A.

2016-01-01

The purpose of this review is to present up-to-date pharmacological, genetic and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein we sought to place the P rat’s behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this paper discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general. PMID:27055615

Current and future molecular diagnostics in colorectal cancer and colorectal adenoma.

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Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

2014-04-14

Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma.

Molecular profiling of cancer--the future of personalized cancer medicine: a primer on cancer biology and the tools necessary to bring molecular testing to the clinic.

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Stricker, Thomas; Catenacci, Daniel V T; Seiwert, Tanguy Y

2011-04-01

Cancers arise as a result of an accumulation of genetic aberrations that are either acquired or inborn. Virtually every cancer has its unique set of molecular changes. Technologies have been developed to study cancers and derive molecular characteristics that increasingly have implications for clinical care. Indeed, the identification of key genetic aberrations (molecular drivers) may ultimately translate into dramatic benefit for patients through the development of highly targeted therapies. With the increasing availability of newer, more powerful, and cheaper technologies such as multiplex mutational screening, next generation sequencing, array-based approaches that can determine gene copy numbers, methylation, expression, and others, as well as more sophisticated interpretation of high-throughput molecular information using bioinformatics tools like signatures and predictive algorithms, cancers will routinely be characterized in the near future. This review examines the background information and technologies that clinicians and physician-scientists will need to interpret in order to develop better, personalized treatment strategies. Copyright © 2011 Elsevier Inc. All rights reserved.

A Novel Forward Genetic Screen for Identifying Mutations Affecting Larval Neuronal Dendrite Development in Drosophila melanogaster

OpenAIRE

Medina, Paul Mark B.; Swick, Lance L.; Andersen, Ryan; Blalock, Zachary; Brenman, Jay E.

2006-01-01

Vertebrate and invertebrate dendrites are information-processing compartments that can be found on both central and peripheral neurons. Elucidating the molecular underpinnings of information processing in the nervous system ultimately requires an understanding of the genetic pathways that regulate dendrite formation and maintenance. Despite the importance of dendrite development, few forward genetic approaches have been used to analyze the latest stages of dendrite development, including the ...

[Genetic polymorphism of flax Linum usitatissimum based on use of molecular cytogenetic markers].

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Rachinskaia, O A; Lemesh, V A; Muravenko, O V; Iurkevich, O Iu; Guzenko, E V; Bol'sheva, N L; Bogdanova, M V; Samatadze, T E; Popov, K V; Malyshev, S V; Shostak, N G; Heller, K; Khotyleva, L V; Zelenin, A V

2011-01-01

Using a set of approaches based on the use of molecular cytogenetic markers (DAPI/C-banding, estimation of the total area of DAPI-positive regions in prophase nuclei, FISH with 26S and 5S rDNA probes) and the microsatellite (SSR-PCR) assay, we studied genomic polymorphism in 15 flax (Linum usitatissimum L.) varieties from different geographic regions belonging to three directions of selection (oil, fiber, and intermediate flaxes) and in the k-37 x Viking hybrid. All individual chromosomes have been identified in the karyotypes of these varieties on the basis of the patterns of differential DAPI/C-banding and the distribution of 26S and 5S rDNA, and idiograms of the chromosomes have been generated. Unlike the oil flax varieties, the chromosomes in the karyotypes of the fiber flax varieties have, as a rule, pericentromeric and telomeric DAPI-positive bands of smaller size, but contain larger intercalary regions. Two chromosomal rearrangements (chromosome 3 inversions) were discovered in the variety Luna and in the k-37 x Viking hybrid. In both these forms, no colocalization of 26S rDNA and 5S rDNA on the satellite chromosome was detected. The SSR assay with the use of 20 polymorphic pairs of primers revealed 22 polymorphic loci. Based on the SSR data, we analyzed genetic similarity of the flax forms studied and constructed a genetic similarity dendrogram. The genotypes studied here form three clusters. The oil varieties comprise an independent cluster. The genetically related fiber flax varieties Vita and Luna, as well as the landrace Lipinska XIII belonging to the intermediate type, proved to be closer to the oil varieties than the remaining fiber flax varieties. The results of the molecular chromosomal analysis in the fiber and oil flaxes confirm their very close genetic similarity. In spite of this, the combined use of the chromosomal and molecular markers has opened up unique possibilities for describing the genotypes of flax varieties and creating their genetic

Molecular genetic analysis of a cattle population to reconstitute the extinct Algarvia breed

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Rangel-Figueiredo Teresa

2010-06-01

Full Text Available Abstract Background Decisions to initiate conservation programmes need to account for extant variability, diversity loss and cultural and economic aspects. Molecular markers were used to investigate if putative Algarvia animals could be identified for use as progenitors in a breeding programme to recover this nearly extinct breed. Methods 46 individuals phenotypically representative of Algarvia cattle were genotyped for 27 microsatellite loci and compared with 11 Portuguese autochthonous and three imported breeds. Genetic distances and factorial correspondence analyses (FCA were performed to investigate the relationship among Algarvia and related breeds. Assignment tests were done to identify representative individuals of the breed. Y chromosome and mtDNA analyses were used to further characterize Algarvia animals. Gene- and allelic-based conservation analyses were used to determine breed contributions to overall genetic diversity. Results Genetic distance and FCA results confirmed the close relationship between Algarvia and southern Portuguese breeds. Assignment tests without breed information classified 17 Algarvia animals in this cluster with a high probability (q > 0.95. With breed information, 30 cows and three bulls were identified (q > 0.95 that could be used to reconstitute the Algarvia breed. Molecular and morphological results were concordant. These animals showed intermediate levels of genetic diversity (MNA = 6.0 ± 1.6, Rt = 5.7 ± 1.4, Ho = 0.63 ± 0.19 and He = 0.69 ± 0.10 relative to other Portuguese breeds. Evidence of inbreeding was also detected (Fis = 0.083, P st = 0.028, P > 0.05. Algarvia cattle provide an intermediate contribution (CB = 6.18, CW = -0.06 and D1 = 0.50 to the overall gene diversity of Portuguese cattle. Algarvia and seven other autochthonous breeds made no contribution to the overall allelic diversity. Conclusions Molecular analyses complemented previous morphological findings to identify 33 animals that

A Molecular Genetic Lab to Generate Inclusive and Exclusive Forensic Evidence: Two Suspects, a Victim, and a Bloodstained T-Shirt

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Smit, Julie; Heath, Daniel D.; Walter, Ryan P.

2014-01-01

Molecular genetic laboratory exercises can be ineffective due the student's lack of connection to the complex and sequential protocols. In this inquiry-based molecular genetic laboratory exercise, we harness students' fascination with human forensics and provide a real-life scenario using biomolecular techniques to identify "whose…

Studying Human Disease Genes in "Caenorhabditis Elegans": A Molecular Genetics Laboratory Project

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Cox-Paulson, Elisabeth A.; Grana, Theresa M.; Harris, Michelle A.; Batzli, Janet M.

2012-01-01

Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifically, students investigated whether "Caenorhabditis elegans" can be a useful model system for studying genes…

Molecular and genetic aspects of odontogenic tumors: a review.

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Garg, Kavita; Chandra, Shaleen; Raj, Vineet; Fareed, Wamiq; Zafar, Muhammad

2015-06-01

Odontogenic tumors contain a heterogeneous collection of lesions that are categorized from hamartomas to benign and malignant neoplasms of inconstant aggressiveness. Odontogenic tumors are usually extraordinary with assessed frequency of short of 0.5 cases/100,000 population for every year. The lesions such as odontogenic tumors are inferred from the components of the tooth-structuring contraption. They are discovered solely inside the maxillary and mandibular bones. This audit speaks to experiences and cooperation of the molecular and genetic variations connected to the development and movement of odontogenic tumors which incorporate oncogenes, tumor-silencer genes, APC gene, retinoblastoma genes, DNA repair genes, onco-viruses, development components, telomerase, cell cycle controllers, apoptosis-related elements, and regulators/conttrollers of tooth development. The reasonable and better understanding of the molecular components may prompt new ideas for their detection and administrating a better prognosis of odontogenic tumors.

Testicular germ cell tumors: Molecular genetic and clinicomorphological aspects

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M. V. Nemtsova

2015-03-01

Full Text Available Testicular tumors are the most common form of solid cancer in young men. According to the 2004 WHO classification, testicular germ cell tumors (TGCT may present with different histological types. Embryonic cells of varying grade may be a source of TGCT and the occurrence of this type of tumors is directly related to the formation of a pool of male sex cells and gametogenesis. The paper gives information on mo- lecular stages for the process of formation of male sex cells in health, as well as ways of their impairments leading to TGCT. An investigation of the profiles of gene expression and the spectrum of molecular damages revealed genes responsible for a predisposition to the sporadic and hereditary forms of TGCT. The paper presents the current molecular genetic and clinicomorphological characteristics of TGCT. 

Candidate gene molecular markers as tools for analyzing genetic susceptibility to morbillivirus infection in stranded Cetaceans

Czech Academy of Sciences Publication Activity Database

Stejskalová, K.; Bayerova, Z.; Futas, J.; Hrazdilová, K.; Klumplerova, M.; Oppelt, J.; Šplíchalová, P.; Di Guardo, G.; Mazzariol, S.; Di Francesco, C. E.; Di Francesco, G.; Terracciano, G.; Paiu, R.M.; Ursache, T. D.; Modrý, David; Horin, P.

2017-01-01

Roč. 90, č. 6 (2017), s. 343-353 ISSN 2059-2302 Institutional support: RVO:60077344 Keywords : Cetacea * haplotype * immunity * innate * mhc-dqb * Phocoena phocoena * polymorphism * single nucleotide * Stenella coeruleoalba Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology

Genetic basis of arrhythmogenic cardiomyopathy.

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Karmouch, Jennifer; Protonotarios, Alexandros; Syrris, Petros

2018-05-01

To date 16 genes have been associated with arrhythmogenic cardiomyopathy (ACM). Mutations in these genes can lead to a broad spectrum of phenotypic expression ranging from disease affecting predominantly the right or left ventricle, to biventricular subtypes. Understanding the genetic causes of ACM is important in diagnosis and management of the disorder. This review summarizes recent advances in molecular genetics and discusses the application of next-generation sequencing technology in genetic testing in ACM. Use of next-generation sequencing methods has resulted in the identification of novel causative variants and genes for ACM. The involvement of filamin C in ACM demonstrates the genetic overlap between ACM and other types of cardiomyopathy. Putative pathogenic variants have been detected in cadherin 2 gene, a protein involved in cell adhesion. Large genomic rearrangements in desmosome genes have been systematically investigated in a cohort of ACM patients. Recent studies have identified novel causes of ACM providing new insights into the genetic spectrum of the disease and highlighting an overlapping phenotype between ACM and dilated cardiomyopathy. Next-generation sequencing is a useful tool for research and genetic diagnostic screening but interpretation of identified sequence variants requires caution and should be performed in specialized centres.

Genetic diversity analyses of Lasiodiplodia theobromae on Morus alba and Agave sisalana based on RAPD and ISSR molecular markers

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Hong-hui Xie

2016-10-01

Full Text Available Genetic diversity of 23 Lasiodiplodia theobromae isolates on Morus alba and 6 isolates on Agave sisalana in Guangxi province, China, was studied by using random amplified polymorphic DNA and inter-simple sequence repeat molecular markers. Results of two molecular markers showed that the average percentage of polymorphic loci of all isolates was more than 93%. Both dendrograms of two molecular markers showed obvious relationship between groups and the geographical locations where those strains were collected, among which, the 23 isolates on M. alba were divided into 4 populations and the 6 isolates on A. sisalana were separated as a independent population. The average genetic identity and genetic distance of 5 populations were 0.7215, 0.3284 and 0.7915, 0.2347, respectively, which indicated that the genetic identity was high and the genetic distance was short in the 5 populations. Average value of the gene diversity index (H and the Shannon’s information index (I of 29 isolates were significantly higher than 5 populations which showed that genetic diversity of those isolates was richer than the populations and the degree of genetic differentiation of the isolates was higher. The Gst and Nm of 29 isolates were 0.4411, 0.6335 and 0.4756, 0.5513, respectively, which showed that the genetic diversity was rich in those isolates.

DNA Re-EvolutioN: a game for learning molecular genetics and evolution.

Science.gov (United States)

Miralles, Laura; Moran, Paloma; Dopico, Eduardo; Garcia-Vazquez, Eva

2013-01-01

Evolution is a main concept in biology, but not many students understand how it works. In this article we introduce the game DNA Re-EvolutioN as an active learning tool that uses genetic concepts (DNA structure, transcription and translation, mutations, natural selection, etc.) as playing rules. Students will learn about molecular evolution while playing a game that mixes up theory and entertainment. The game can be easily adapted to different educational levels. The main goal of this play is to arrive at the end of the game with the longest protein. Students play with pawns and dices, a board containing hypothetical events (mutations, selection) that happen to molecules, "Evolution cards" with indications for DNA mutations, prototypes of a DNA and a mRNA chain with colored "nucleotides" (plasticine balls), and small pieces simulating t-RNA with aminoacids that will serve to construct a "protein" based on the DNA chain. Students will understand how changes in DNA affect the final protein product and may be subjected to positive or negative selection, using a didactic tool funnier than classical theory lectures and easier than molecular laboratory experiments: a flexible and feasible game to learn and enjoy molecular evolution at no-cost. The game was tested by majors and non-majors in genetics from 13 different countries and evaluated with pre- and post-tests obtaining very positive results. © 2013 by The International Union of Biochemistry and Molecular Biology.

Development and interlaboratory validation of quantitative polymerase chain reaction method for screening analysis of genetically modified soybeans.

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Takabatake, Reona; Onishi, Mari; Koiwa, Tomohiro; Futo, Satoshi; Minegishi, Yasutaka; Akiyama, Hiroshi; Teshima, Reiko; Kurashima, Takeyo; Mano, Junichi; Furui, Satoshi; Kitta, Kazumi

2013-01-01

A novel real-time polymerase chain reaction (PCR)-based quantitative screening method was developed for three genetically modified soybeans: RRS, A2704-12, and MON89788. The 35S promoter (P35S) of cauliflower mosaic virus is introduced into RRS and A2704-12 but not MON89788. We then designed a screening method comprised of the combination of the quantification of P35S and the event-specific quantification of MON89788. The conversion factor (Cf) required to convert the amount of a genetically modified organism (GMO) from a copy number ratio to a weight ratio was determined experimentally. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDR), respectively. The determined RSDR values for the method were less than 25% for both targets. We consider that the developed method would be suitable for the simple detection and approximate quantification of GMO.

Application of molecular imaging combined with genetic screening in diagnosing MELAS, diabetes and recurrent pancreatitis.

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Zhiping, W; Quwen, L; Hai, Z; Jian, Z; Peiyi, G

2016-01-01

We report molecular imaging combined with gene diagnosis in a family with 7 members who carried an A3243G mutation in mitochondrial tRNA and p.Thr 137 Met in cationic trypsinogen (PRSS1) gene presented with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), diabetes, and recurrent pancreatitis. DNA sequencing was used to detect and validate mitochondrial DNA and PRSS1. We also verified that mitochondrial heterozygous mutations and c.410 C>T mutation causing p.Thr 137 Met could be detected in oral epithelial cells or in urine sediment cells. In addition, molecular imaging was carried out in the affected family members. In this pedigree, MELAS syndrome accompanied by pancreatitis was an important clinical feature, followed by diabetes. Heteroplasmy of the mtDNA A3243G and c.410 C>T mutation of PRSS1 was found in all tissue samples of these patients, but no mutations were found in 520 normal control and normal individuals of the family. However, based on molecular imaging observations, patients with relatively higher lactate/pyruvate levels had more typical and more severe symptoms, particularly those of pancreatic disease (diabetes or pancreatitis). MELAS syndrome may be associated with pancreatitis. For the diagnosis, it is more reasonable to perform molecular imaging combined with gene diagnosis.

Design of efficient molecular organic light-emitting diodes by a high-throughput virtual screening and experimental approach

Science.gov (United States)

Gómez-Bombarelli, Rafael; Aguilera-Iparraguirre, Jorge; Hirzel, Timothy D.; Duvenaud, David; MacLaurin, Dougal; Blood-Forsythe, Martin A.; Chae, Hyun Sik; Einzinger, Markus; Ha, Dong-Gwang; Wu, Tony; Markopoulos, Georgios; Jeon, Soonok; Kang, Hosuk; Miyazaki, Hiroshi; Numata, Masaki; Kim, Sunghan; Huang, Wenliang; Hong, Seong Ik; Baldo, Marc; Adams, Ryan P.; Aspuru-Guzik, Alán

2016-10-01

Virtual screening is becoming a ground-breaking tool for molecular discovery due to the exponential growth of available computer time and constant improvement of simulation and machine learning techniques. We report an integrated organic functional material design process that incorporates theoretical insight, quantum chemistry, cheminformatics, machine learning, industrial expertise, organic synthesis, molecular characterization, device fabrication and optoelectronic testing. After exploring a search space of 1.6 million molecules and screening over 400,000 of them using time-dependent density functional theory, we identified thousands of promising novel organic light-emitting diode molecules across the visible spectrum. Our team collaboratively selected the best candidates from this set. The experimentally determined external quantum efficiencies for these synthesized candidates were as large as 22%.

Values of molecular markers in the differential diagnosis of thyroid abnormalities.

Science.gov (United States)

Tennakoon, T M P B; Rushdhi, M; Ranasinghe, A D C U; Dassanayake, R S

2017-06-01

Thyroid cancer (TC), follicular adenoma (FA) and Hashimoto's thyroiditis (HT) are three of the most frequently reported abnormalities that affect the thyroid gland. A frequent co-occurrence along with similar histopathological features is observed between TC and FA as well as between TC and HT. The conventional diagnostic methods such as histochemical analysis present complications in differential diagnosis when these abnormalities occur simultaneously. Hence, the authors recognize novel methods based on screening genetic defects of thyroid abnormalities as viable diagnostic and prognostic methods that could complement the conventional methods. We have extensively reviewed the existing literature on TC, FA and HT and also on three genes, namely braf, nras and ret/ptc, that could be used to differentially diagnose the three abnormalities. Emphasis was also given to the screening methods available to detect the said molecular markers. It can be conferred from the analysis of the available data that the utilization of braf, nras and ret/ptc as markers for the therapeutic evaluation of FA and HT is debatable. However, molecular screening for braf, nras and ret/ptc mutations proves to be a conclusive method that could be employed to differentially diagnose TC from HT and FA in the instance of a suspected co-occurrence. Thyroid cancer patients can be highly benefited from the screening for the said genetic markers, especially the braf gene due to its diagnostic value as well as due to the availability of personalized medicine targeted specifically for braf mutants.

An effective HIV-1 integrase inhibitor screening platform: Rationality validation of drug screening, conformational mobility and molecular recognition analysis for PFV integrase complex with viral DNA.

Science.gov (United States)

Du, Wenyi; Zuo, Ke; Sun, Xin; Liu, Wei; Yan, Xiao; Liang, Li; Wan, Hua; Chen, Fengzheng; Hu, Jianping

2017-11-01

As an important target for the development of novel anti-AIDS drugs, HIV-1 integrase (IN) has been widely concerned. However, the lack of a complete accurate crystal structure of HIV-1 IN greatly blocks the discovery of novel inhibitors. In this work, an effective HIV-1 IN inhibitor screening platform, namely PFV IN, was filtered from all species of INs. Next, the 40.8% similarity with HIV-1 IN, as well as the high efficiency of virtual screening and the good agreement between calculated binding free energies and experimental ones all proved PFV IN is a promising screening platform for HIV-1 IN inhibitors. Then, the molecular recognition mechanism of PFV IN by its substrate viral DNA and six naphthyridine derivatives (NRDs) inhibitors was investigated through molecular docking, molecular dynamics simulations and water-mediated interactions analyses. The functional partition of NRDs IN inhibitors could be divided into hydrophobic and hydrophilic ones, and the Mg 2+ ions, water molecules and conserved DDE motif residues all interacted with the hydrophilic partition, while the bases in viral DNA and residues like Tyr212, Pro214 interacted with the hydrophobic one. Finally, the free energy landscape (FEL) and cluster analyses were performed to explore the molecular motion of PFV IN-DNA system. It is found that the association with NRDs inhibitors would obviously decrease the motion amplitude of PFV IN-DNA, which may be one of the most potential mechanisms of IN inhibitors. This work will provide a theoretical basis for the inhibitor design based on the structure of HIV-1 IN. Copyright © 2017 Elsevier Inc. All rights reserved.

Joint analysis of phenotypic and molecular diversity provides new insights on the genetic variability of the Brazilian physic nut germplasm bank.

Science.gov (United States)

Alves, Alexandre Alonso; Bhering, Leonardo Lopes; Rosado, Tatiana Barbosa; Laviola, Bruno Galvêas; Formighieri, Eduardo Fernandes; Cruz, Cosme Damião

2013-09-01

The genetic variability of the Brazilian physic nut (Jatropha curcas) germplasm bank (117 accessions) was assessed using a combination of phenotypic and molecular data. The joint dissimilarity matrix showed moderate correlation with the original matrices of phenotypic and molecular data. However, the correlation between the phenotypic dissimilarity matrix and the genotypic dissimilarity matrix was low. This finding indicated that molecular markers (RAPD and SSR) did not adequately sample the genomic regions that were relevant for phenotypic differentiation of the accessions. The dissimilarity values of the joint dissimilarity matrix were used to measure phenotypic + molecular diversity. This diversity varied from 0 to 1.29 among the 117 accessions, with an average dissimilarity among genotypes of 0.51. Joint analysis of phenotypic and molecular diversity indicated that the genetic diversity of the physic nut germplasm was 156% and 64% higher than the diversity estimated from phenotypic and molecular data, respectively. These results show that Jatropha genetic variability in Brazil is not as limited as previously thought.

Genetic basis of prune belly syndrome: screening for HNF1β gene.

Science.gov (United States)

Granberg, Candace F; Harrison, Steven M; Dajusta, Daniel; Zhang, Shaohua; Hajarnis, Sachin; Igarashi, Peter; Baker, Linda A

2012-01-01

Although the cause of prune belly syndrome is unknown, familial evidence suggests a genetic component. Recently 2 nonfamilial cases of prune belly syndrome with chromosome 17q12 deletions encompassing the HNF1β gene have made this a candidate gene for prune belly syndrome. To date, there has been no large-scale screening of patients with prune belly syndrome for HNF1β mutations. We assessed the role of HNF1β in prune belly syndrome by screening for genomic mutations with functional characterization of any detected mutations. We studied patients with prune belly syndrome who were prospectively enrolled in our Pediatric Genitourinary DNA Repository since 2001. DNA from patient samples was amplified by polymerase chain reaction, sequenced for coding and splice regions of the HNF1β gene, and compared to control databases. We performed functional assay testing of the ability of mutant HNF1β to activate a luciferase construct with an HNF1β DNA binding site. From 32 prune belly syndrome probands (30 males, 2 females) HNF1β sequencing detected a missense mutation (V61G) in 1 child with prune belly syndrome. Absent in control databases, V61G was previously reported in 2 patients without prune belly syndrome who had congenital genitourinary anomalies. Functional testing showed similar luciferase activity compared to wild-type HNF1β, suggesting the V61G substitution does not disturb HNF1β function. One genomic HNF1β mutation was detected in 3% of patients with prune belly syndrome but found to be functionally normal. Thus, functionally significant HNF1β mutations are uncommon in prune belly syndrome, despite case reports of HNF1β deletions. Further genetic study is necessary, as identification of the genetic basis of prune belly syndrome may ultimately lead to prevention and improved treatments for this rare but severe syndrome. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Molecular and genetic aspects of odontogenic tumors: a review

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Kavita Garg

2015-06-01

Full Text Available Odontogenic tumors contain a heterogeneous collection of lesions that are categorized from hamartomas to benign and malignant neoplasms of inconstant aggressiveness. Odontogenic tumors are usually extraordinary with assessed frequency of short of 0.5 cases/100,000 population for every year. The lesions such as odontogenic tumors are inferred from the components of the tooth-structuring contraption. They are discovered solely inside the maxillary and mandibular bones. This audit speaks to experiences and cooperation of the molecular and genetic variations connected to the development and movement of odontogenic tumors which incorporate oncogenes, tumor-silencer genes, APC gene, retinoblastoma genes, DNA repair genes, onco-viruses, development components, telomerase, cell cycle controllers, apoptosis-related elements, and regulators/controllers of tooth development. The reasonable and better understanding of the molecular components may prompt new ideas for their detection and administrating a better prognosis of odontogenic tumors.

Genetics of Gigantism and Acromegaly

Science.gov (United States)

Hannah-Shmouni, Fady; Trivellin, Giampaolo; Stratakis, Constantine A.

2016-01-01

Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and genetic etiologies of pituitary gigantism and acromegaly yielded several genetic causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The early diagnosis of these conditions helps guide early intervention, screening, and genetic counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the genetics of gigantism and acromegaly. PMID:27657986

Genetics of gigantism and acromegaly.

Science.gov (United States)

Hannah-Shmouni, Fady; Trivellin, Giampaolo; Stratakis, Constantine A

Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and genetic etiologies of pituitary gigantism and acromegaly yielded several genetic causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The early diagnosis of these conditions helps guide early intervention, screening, and genetic counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the genetics of gigantism and acromegaly. Published by Elsevier Ltd.

SSR Analysis of Genetic Diversity Among 192 Diploid Potato Cultivars

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Xiaoyan Song

2016-05-01

Full Text Available In potato breeding, it is difficult to improve the traits of interest at the tetraploid level due to the tetrasomic inheritance. A promising alternative is diploid breeding. Thus it is necessary to assess the genetic diversity of diploid potato germplasm for efficient exploration and deployment of desirable traits. In this study, we used SSR markers to evaluate the genetic diversity of diploid potato cultivars. To screen polymorphic SSR markers, 55 pairs of SSR primers were employed to amplify 39 cultivars with relatively distant genetic relationships. Among them, 12 SSR markers with high polymorphism located at 12 chromosomes were chosen to evaluate the genetic diversity of 192 diploid potato cultivars. The primers produced 6 to 18 bands with an average of 8.2 bands per primer. In total, 98 bands were amplified from 192 cultivars, and 97 of them were polymorphic. Cluster analysis using UPGMA showed the genetic relationships of all accessions tested: 186 of the 192 accessions could be distinguished by only 12 pairs of SSR primers, and the 192 diploid cultivars were divided into 11 groups, and 83.3% constituted the first group. Clustering results showed relatively low genetic diversity among 192 diploid cultivars, with closer relationship at the molecular level. The results can provide molecular basis for diploid potato breeding.

Characterization of some bread wheat genotypes using molecular markers for drought tolerance.

Science.gov (United States)

Ateş Sönmezoğlu, Özlem; Terzi, Begüm

2018-02-01

Because of its wide geographical adaptation and importance in human nutrition, wheat is one of the most important crops in the world. However, wheat yield has reduced due to drought stress posing threat to sustainability and world food security in agricultural production. The first stage of drought tolerant variety breeding occurs on the molecular and biochemical characterization and classification of wheat genotypes. The aim of the present study is characterization of widely grown bread wheat cultivars and breeding lines for drought tolerance so as to be adapted to different regions in Turkey. The genotypes were screened with molecular markers for the presence of QTLs mapped to different chromosomes. Results of the molecular studies identified and detected 15 polymorphic SSR markers which gave the clearest PCR bands among the control genotypes. At the end of the research, bread wheat genotypes which were classified for tolerance or sensitivity to drought and the genetic similarity within control varieties were determined by molecular markers. According to SSR based dendrogram, two main groups were obtained for drought tolerance. At end of the molecular screening with SSR primers, genetic similarity coefficients were obtained that ranged from 0.14 to 0.71. The ones numbered 8 and 11 were the closest genotypes to drought tolerant cultivar Gerek 79 and the furthest genotypes from this cultivar were number 16 and to drought sensitive cultivar Sultan 95. The genotypes as drought tolerance due to their SSR markers scores are expected to provide useful information for drought related molecular breeding studies.

Is preimplantation genetic diagnosis the ideal embryo selection method in aneuploidy screening?

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Levent Sahin

2014-10-01

Full Text Available To select cytogenetically normal embryos, preimplantation genetic diagnosis (PGD aneuploidy screening (AS is used in numerous centers around the world. Chromosomal abnormalities lead to developmental problems, implantation failure, and early abortion of embryos. The usefulness of PGD in identifying single-gene diseases, human leukocyte antigen typing, X-linked diseases, and specific genetic diseases is well-known. In this review, preimplantation embryo genetics, PGD research studies, and the European Society of Human Reproduction and Embryology PGD Consortium studies and reports are examined. In addition, criteria for embryo selection, technical aspects of PGD-AS, and potential noninvasive embryo selection methods are described. Indications for PGD and possible causes of discordant PGD results between the centers are discussed. The limitations of fluorescence in situ hybridization, and the advantages of the array comparative genomic hybridization are included in this review. Although PGD-AS for patients of advanced maternal age has been shown to improve in vitro fertilization outcomes in some studies, to our knowledge, there is not sufficient evidence to use advanced maternal age as the sole indication for PGD-AS. PGD-AS might be harmful and may not increase the success rates of in vitro fertilization. At the same time PGD, is not recommended for recurrent implantation failure and unexplained recurrent pregnancy loss.

Molecular markers to assess genetic diversity and mutant identifications in Jatropha curcas

International Nuclear Information System (INIS)

Azhar Mohamad; Yie Min Kwan; Fatin Mastura Derani; Abdul Rahim Harun

2010-01-01

Jatropha curcas (Linnaeus) belongs to the Euphorbiaceae family, is a multipurpose use, drought resistant and perennial plant. It is an economic important crop, which generates wide interest in understanding the genetic diversity of the species towards selection and breeding of superior genotypes. Jatropha accessions are closely related family species. Thus, better understanding of the effectiveness of the different DNA-based markers is an important step towards plant germplasm characterization and evaluation. It is becoming a prerequisite for more effective application of marker techniques in breeding programs. Inter-simple sequence repeats (ISSRs) has shown rapid, simple, reproducible and inexpensive means in molecular taxonomy, conservation breeding and genetic diversity analysis. These markers were used to understand diversity and differentiate amongst accessions of Jatropha population and mutant lines generated by acute gamma radiation. The ISSR for marker applications are essential to facilitate management, conservation and genetic improvement programs towards improvement of bio-diesel production and medication substances. A total of 62 ISSR primers were optimized for polymorphism evaluations on five foreign accessions (Africa, India, Myanmar, Indonesia, Thailand), nine local accessions and two mutants of Jatropha. Optimization was resulted 54 ISSR primers affirmative for the polymorphism evaluation study, which encountered 12 ISSR primers, showed significance polymorphism amongst the accessions and mutants. Marker derived from ISSR profiling is a powerful method for identification and molecular classification of Jatropha from accession to generated mutant varieties. (author)

Flow Cytometry Enables Multiplexed Measurements of Genetically Encoded Intramolecular FRET Sensors Suitable for Screening.

Science.gov (United States)

Doucette, Jaimee; Zhao, Ziyan; Geyer, Rory J; Barra, Melanie M; Balunas, Marcy J; Zweifach, Adam

2016-07-01

Genetically encoded sensors based on intramolecular FRET between CFP and YFP are used extensively in cell biology research. Flow cytometry has been shown to offer a means to measure CFP-YFP FRET; we suspected it would provide a unique way to conduct multiplexed measurements from cells expressing different FRET sensors, which is difficult to do with microscopy, and that this could be used for screening. We confirmed that flow cytometry accurately measures FRET signals using cells transiently transfected with an ERK activity reporter, comparing responses measured with imaging and cytometry. We created polyclonal long-term transfectant lines, each expressing a different intramolecular FRET sensor, and devised a way to bar-code four distinct populations of cells. We demonstrated the feasibility of multiplexed measurements and determined that robust multiplexed measurements can be conducted in plate format. To validate the suitability of the method for screening, we measured responses from a plate of bacterial extracts that in unrelated experiments we had determined contained the protein kinase C (PKC)-activating compound teleocidin A-1. The multiplexed assay correctly identifying the teleocidin A-1-containing well. We propose that multiplexed cytometric FRET measurements will be useful for analyzing cellular function and for screening compound collections. © 2016 Society for Laboratory Automation and Screening.

[The clinical and molecular genetic characteristics of phenylketonuria patients in the Republic of Crimea].

Science.gov (United States)

Afanas'eva, N A; Bychkova, A M; Livshits, L A; Bariliak, I R

1998-01-01

The clinical and genetical characteristics of patients with phenylketonuria in the Crimean population is done in the present work. The comparison of clinical peculiarities of 28 patients, revealed by means of neonatal screening and that of 24 patients, the treatment of which was started late is presented. The prenatal diagnostics of 4 families with high phenylketonuria risk is conducted.

Applying theological developments to bioethical issues such as genetic screening.

Science.gov (United States)

Mallia, Pierre; ten Have, Henk

2005-01-01

Catholic movements within the centre of Roman Catholic doctrine recently have discussed Trinitarian theology as applied to sciences, arts, economics, health and other social areas. We explore the possibilities Trinitarian theology offers to bioethical debate, concentrating particularly on genetic screening and testing. It is important therefore to analyse the philosophical implications of this approach onto the bioethical world, where much disagreement occurs on fundamental issues. It is Catholic basic teaching to recognize and see God's hand in plurality, not merely as a cliche and then doing what we feel is right, but to recognize how to live in a pluralistic world. We recognize, in agreement with these theologians, that in order for a Trinitarian mode of understanding to be used by those doing bioethical debate, there is a need to depart from fundamentalism.

Genetic characterization, molecular epidemiology, and phylogenetic relationships of insect-specific viruses in the taxon Negevirus.

Science.gov (United States)

Nunes, Marcio R T; Contreras-Gutierrez, María Angélica; Guzman, Hilda; Martins, Livia C; Barbirato, Mayla Feitoza; Savit, Chelsea; Balta, Victoria; Uribe, Sandra; Vivero, Rafael; Suaza, Juan David; Oliveira, Hamilton; Nunes Neto, Joaquin P; Carvalho, Valeria L; da Silva, Sandro Patroca; Cardoso, Jedson F; de Oliveira, Rodrigo Santo; da Silva Lemos, Poliana; Wood, Thomas G; Widen, Steven G; Vasconcelos, Pedro F C; Fish, Durland; Vasilakis, Nikos; Tesh, Robert B

2017-04-01

The recently described taxon Negevirus is comprised of a diverse group of insect-specific viruses isolated from mosquitoes and phlebotomine sandflies. In this study, a comprehensive genetic characterization, molecular, epidemiological and evolutionary analyses were conducted on nearly full-length sequences of 91 new negevirus isolates obtained in Brazil, Colombia, Peru, Panama, USA and Nepal. We demonstrated that these arthropod restricted viruses are clustered in two major phylogenetic groups with origins related to three plant virus genera (Cilevirus, Higrevirus and Blunevirus). Molecular analyses demonstrated that specific host correlations are not present with most negeviruses; instead, high genetic variability, wide host-range, and cross-species transmission were noted. The data presented here also revealed the existence of five novel insect-specific viruses falling into two arthropod-restrictive virus taxa, previously proposed as distinct genera, designated Nelorpivirus and Sandewavirus. Our results provide a better understanding of the molecular epidemiology, evolution, taxonomy and stability of this group of insect-restricted viruses. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic Confirmation of Mungbean (Vigna radiata) and Mashbean (Vigna mungo) Interspecific Recombinants using Molecular Markers.

Science.gov (United States)

Abbas, Ghulam; Hameed, Amjad; Rizwan, Muhammad; Ahsan, Muhammad; Asghar, Muhammad J; Iqbal, Nayyer

2015-01-01

Molecular confirmation of interspecific recombinants is essential to overcome the issues like self-pollination, environmental influence, and inadequacy of morphological characteristics during interspecific hybridization. The present study was conducted for genetic confirmation of mungbean (female) and mashbean (male) interspecific crosses using molecular markers. Initially, polymorphic random amplified polymorphic DNA (RAPD), universal rice primers (URP), and simple sequence repeats (SSR) markers differentiating parent genotypes were identified. Recombination in hybrids was confirmed using these polymorphic DNA markers. The NM 2006 × Mash 88 was most successful interspecific cross. Most of true recombinants confirmed by molecular markers were from this cross combination. SSR markers were efficient in detecting genetic variability and recombination with reference to specific chromosomes and particular loci. SSR (RIS) and RAPD identified variability dispersed throughout the genome. In conclusion, DNA based marker assisted selection (MAS) efficiently confirmed the interspecific recombinants. The results provided evidence that MAS can enhance the authenticity of selection in mungbean improvement program.

Genetic and molecular analysis of radon-induced rat lung tumours

International Nuclear Information System (INIS)

Guilly, M.N.; Joubert, Ch.; Levalois, C.; Dano, L.; Chevillard, S.

2002-01-01

We have a model of radon-induced rat lung tumours, which allow us to analyse the cytogenetic and molecular alterations of the tumours. The aim is to better understand the mechanisms of radio-induced carcinogenesis and to define if it exists a specificity of radio-induced genetic alterations as compared to the genetic alterations found in the sporadic tumours. We have started our analysis by developing global cytogenetic and molecular approaches. We have shown that some alterations are recurrent. The genes that are potentially involved are the oncogene MET and the tumour suppressor Bene p16, which are also frequently altered in human lung tumours. Simultaneously, we have focussed our analysis by targeting the search of mutation in the tumour suppressor gene TP3. We have found that 8 of 39 tumours were mutated by deletion in the coding sequence of TP53. This high frequency of deletion, which is not observed in the human p53 mutation database could constitute a signature of radio-induced alterations. On this assumption, this type of alteration should not be only found on TP53 Bene but also in other suppressor genes which are inactivated by a mutation such as p16 for example. The work we are carrying out on radio-induced tumours among humans and animals is directed to this end. (author)

Fanconi anaemia: genetics, molecular biology, and cancer – implications for clinical management in children and adults.

Science.gov (United States)

Schneider, M; Chandler, K; Tischkowitz, M; Meyer, S

2015-07-01

Fanconi anaemia (FA) is an inherited disease with congenital and developmental abnormalities, cross-linker hypersensitivity and extreme cancer predisposition. With better understanding of the genetic and molecular basis of the disease, and improved clinical management, FA has been transformed from a life-limiting paediatric disease to an uncommon chronic condition that needs lifelong multidisciplinary management, and a paradigm condition for the understanding of the gene-environment interaction in the aetiology of congenital anomalies, haematopoiesis and cancer development. Here we review genetic, molecular and clinical aspects of FA, and discuss current controversies and future prospects. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synovial sarcoma with radiological appearances of primitive neuroectodermal tumour/Ewing sarcoma: differentiation by molecular genetic studies

International Nuclear Information System (INIS)

O'Donnell, P.; Diss, T.C.; Whelan, J.; Flanagan, A.M.

2006-01-01

Synovial sarcoma (SS) arises in soft tissues but may invade adjacent bone. We describe a case of SS presenting as aggressive lysis of the proximal ulna, the imaging of which suggested a primary bone lesion. Needle biopsy showed a 'small round blue cell tumour', and a primitive neuroectodermal tumour (PNET)/Ewing sarcoma was suggested on the basis of the imaging appearances. The definitive diagnosis of synovial sarcoma was made following molecular genetic studies, which demonstrated a fusion product incorporating the genes SYT and SSX1. The importance of correct diagnosis to guide appropriate management, and, therefore, the necessity for molecular genetic studies, is discussed. (orig.)

Screening for thalassemia and other hemoglobinopathies in a tertiary care hospital of West Bengal: Implications for population screening

OpenAIRE

Bhawna Bhutoria Jain; Rabindra Nath Roy; Sulekha Ghosh; Tapan Ghosh; Uma Banerjee; Subodh Kumar Bhattacharya

2012-01-01

Hemoglobinopathies are common genetic disorders of hemoglobin, which can be prevented by population screening and offering genetic counseling. In absence of population-based screening for hemoglobinopathies, the hospital-based diagnosis register provide idea about the extent of problem in the community. The present study was undertaken to find out the burden of hemoglobinopathies and spectrum of this disorders among the population who were screened in the hospital-based screening program. A r...

MODY in Siberia – molecular genetics and clinical characteristics

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Alla Konstantinovna Ovsyannikova

2017-05-01

Full Text Available The diagnosis of maturity onset diabetes of the young (MODY has high clinical significance in young patients (no absolute need for exogenous insulin; normoglycaemia in most patients achieved by dieting or taking oral hypoglycaemic agents and their relatives (high probability of first-degree relatives being carriers of mutations, which requires a thorough collection of family history and determination of the parameters of carbohydrate metabolism. Aim. This study aimed was to determine the clinical characteristics of different subtypes of MODY in a Siberian region. Materials and Methods. We performed an examination, biochemical and hormonal blood tests, ultrasound and molecular genetic testing of 20 patients with a clinical diagnosis of MODY. Results. Four subtypes of MODY were verified: MODY2 in 11 patients, MODY3 in two, MODY8 in one and MODY12 in two. Eleven patients (69% exhibited no clinical manifestations of carbohydrate metabolism disorders, and one patient showed weight loss during early stage of the disease. Comorbidities included dyslipidemia, thyroid gland disorders and arterial hypertension. One patient (6% exhibited diabetic nephropathy; two (13%, diabetic retinopathy and three (19%, peripheral neuropathy of lower legs. All patients achieved the target carbohydrate metabolism; the level of C-peptide was within the reference range. Conclusion. Four different subtypes of MODY (2, 3, 8, 12 were diagnosed in the present study, which differed in their clinical characteristics, presence of complications and treatment strategies. Our knowledge of monogenic forms of diabetes is expanding with the development in molecular genetics, but several aspects related to them require further study.

A Genomewide Screen for Tolerance to Cationic Drugs Reveals Genes Important for Potassium Homeostasis in Saccharomyces cerevisiae

Czech Academy of Sciences Publication Activity Database

Barreto, L.; Canadell, D.; Petrezsélyová, Silvia; Navarrete, C.; Marešová, Lydie; Peréz-Valle, J.; Herrera, R.; Olier, I.; Giraldo, J.; Sychrová, Hana; Yenush, L.; Ramos, J.; Ariňo, J.

2011-01-01

Roč. 10, č. 9 (2011), s. 1241-1250 ISSN 1535-9778 R&D Projects: GA MŠk(CZ) LC531; GA AV ČR(CZ) IAA500110801 Institutional research plan: CEZ:AV0Z50110509 Keywords : Potassium homeostasis * Saccharomyces cerevisiae * genomewide screen Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.604, year: 2011

Molecular genetic analysis of activation-tagged transcription factors thought to be involved in photomorphogenesis

Energy Technology Data Exchange (ETDEWEB)

Neff, Michael M.

2011-06-23

This is a final report for Department of Energy Grant No. DE-FG02-08ER15927 entitled “Molecular Genetic Analysis of Activation-Tagged Transcription Factors Thought to be Involved in Photomorphogenesis”. Based on our preliminary photobiological and genetic analysis of the sob1-D mutant, we hypothesized that OBP3 is a transcription factor involved in both phytochrome and cryptochrome-mediated signal transduction. In addition, we hypothesized that OBP3 is involved in auxin signaling and root development. Based on our preliminary photobiological and genetic analysis of the sob2-D mutant, we also hypothesized that a related gene, LEP, is involved in hormone signaling and seedling development.

["A decision meaning a new foundation...": from the Kaiser Wilhelm Institute for Anthropology, Human Genetics and Eugenics to the Max Planck Institute for Molecular Genetics].

Science.gov (United States)

Sachse, Carola

2011-01-01

The Max Planck Institute for Molecular Genetics (MPIMG) in Berlin-Dahlem dates its establishment to 1964. Its homepage makes no mention of its predecessor institutes, the Kaiser Wilhelm Institute for Anthropology, Human Genetics and Eugenics (KWIA) and the subsequent MPI for Comparative Genetics and Hereditary Pathology (MPIVEE). This article traces the two critical phases of transition regarding the constellations of academic staff, institutional and epistemic ruptures and continuities specific to the era. Only one of the five department heads from the final war years, Hans Nachtsheim, remained a researcher within the Max Planck Society (MPG); he nevertheless continued to advocate the pre-war and wartime eugenic agenda in the life sciences and social policy. The generational change of 1959/60 became a massive struggle within the institute, in which microbial genetics (with Fritz Kaudewitz) was pitted against human genetics (with Friedrich Vogel) and managed to establish itself after a fresh change in personnel in 1964/65. For the Dahlem institute, this involved a far-reaching reorientation of its research, but for the genetically oriented life sciences in the Max Planck Society as a whole it only meant that molecular biology, which was already being pursued in the West German institutes, gained an additional facility. With this realignment of research traditions, the Society was able to draw a line under the Nazi past without having to address it head-on.

Genetic and molecular dosimetry of HZE radiation (US-1 RADIAT)

Science.gov (United States)

Nelson, Gregory A.; Schubert, W. W.; Kazarians, G. A.; Richards, G. F.; Benton, E. V.; Benton, E. R.; Henke, R. P.

1995-01-01

In order to estimate radiation exposure in space, experiments were conducted during the 1st International Microgravity Laboratory (IML-1) mission in order to isolate genetic changes in animal cells caused by cosmic rays. The space measurements were evaluated against results from synthetic cosmic rays produced by particle accelerators on the ground. The biological material used was the tiny soil nematode, Caenorhabditis elegans. The measurements were made by thermoluminescent detectors and plastic nuclear track detectors. The development and the chromosome mechanics in microgravity were studied, and the mutagenesis induced by radiation exposure was analyzed. The results showed that there are no obvious differences in the development, behavior and chromosome mechanics, as a function of gravity unloading (reproduction, self-fertilization and mating of males with hermaphrodites, gross anatomy, symmetry and gametogenesis, pairing, disjoining and recombination of chromosomes). A variety of mutants were isolated, and it was noted that mutants isolated from regions of identified high particles were more severely affected than those isolated by random screening. Linear energy transfer particles seem to favor large scale genetic lesions.

New STS molecular markers for assessment of genetic diversity and DNA fingerprinting in hop (Humulus lupulus L.)

Czech Academy of Sciences Publication Activity Database

Patzak, J.; Vrba, Lukáš; Matoušek, Jaroslav

2007-01-01

Roč. 50, č. 1 (2007), s. 15-25 ISSN 0831-2796 R&D Projects: GA ČR GA521/03/0072 Institutional research plan: CEZ:AV0Z50510513 Keywords : hop (Humulus lupulus L.) * genetic diversity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.785, year: 2007

A forward genetic screen reveals essential and non-essential RNAi factors in Paramecium tetraurelia

Science.gov (United States)

Marker, Simone; Carradec, Quentin; Tanty, Véronique; Arnaiz, Olivier; Meyer, Eric

2014-01-01

In most eukaryotes, small RNA-mediated gene silencing pathways form complex interacting networks. In the ciliate Paramecium tetraurelia, at least two RNA interference (RNAi) mechanisms coexist, involving distinct but overlapping sets of protein factors and producing different types of short interfering RNAs (siRNAs). One is specifically triggered by high-copy transgenes, and the other by feeding cells with double-stranded RNA (dsRNA)-producing bacteria. In this study, we designed a forward genetic screen for mutants deficient in dsRNA-induced silencing, and a powerful method to identify the relevant mutations by whole-genome sequencing. We present a set of 47 mutant alleles for five genes, revealing two previously unknown RNAi factors: a novel Paramecium-specific protein (Pds1) and a Cid1-like nucleotidyl transferase. Analyses of allelic diversity distinguish non-essential and essential genes and suggest that the screen is saturated for non-essential, single-copy genes. We show that non-essential genes are specifically involved in dsRNA-induced RNAi while essential ones are also involved in transgene-induced RNAi. One of the latter, the RNA-dependent RNA polymerase RDR2, is further shown to be required for all known types of siRNAs, as well as for sexual reproduction. These results open the way for the dissection of the genetic complexity, interconnection, mechanisms and natural functions of RNAi pathways in P. tetraurelia. PMID:24860163

Enhanced hexose fermentation by Saccharomyces cerevisiae through integration of stoichiometric modeling and genetic screening.

Science.gov (United States)

Quarterman, Josh; Kim, Soo Rin; Kim, Pan-Jun; Jin, Yong-Su

2015-01-20

In order to determine beneficial gene deletions for ethanol production by the yeast Saccharomyces cerevisiae, we performed an in silico gene deletion experiment based on a genome-scale metabolic model. Genes coding for two oxidative phosphorylation reactions (cytochrome c oxidase and ubiquinol cytochrome c reductase) were identified by the model-based simulation as potential deletion targets for enhancing ethanol production and maintaining acceptable overall growth rate in oxygen-limited conditions. Since the two target enzymes are composed of multiple subunits, we conducted a genetic screening study to evaluate the in silico results and compare the effect of deleting various portions of the respiratory enzyme complexes. Over two-thirds of the knockout mutants identified by the in silico study did exhibit experimental behavior in qualitative agreement with model predictions, but the exceptions illustrate the limitation of using a purely stoichiometric model-based approach. Furthermore, there was a substantial quantitative variation in phenotype among the various respiration-deficient mutants that were screened in this study, and three genes encoding respiratory enzyme subunits were identified as the best knockout targets for improving hexose fermentation in microaerobic conditions. Specifically, deletion of either COX9 or QCR9 resulted in higher ethanol production rates than the parental strain by 37% and 27%, respectively, with slight growth disadvantages. Also, deletion of QCR6 led to improved ethanol production rate by 24% with no growth disadvantage. The beneficial effects of these gene deletions were consistently demonstrated in different strain backgrounds and with four common hexoses. The combination of stoichiometric modeling and genetic screening using a systematic knockout collection was useful for narrowing a large set of gene targets and identifying targets of interest. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetic basis of hearing loss in Spanish, Hispanic and Latino populations.

Science.gov (United States)

Mittal, Rahul; Patel, Amit P; Nguyen, Desiree; Pan, Debbie R; Jhaveri, Vasanti M; Rudman, Jason R; Dharmaraja, Arjuna; Yan, Denise; Feng, Yong; Chapagain, Prem; Lee, David J; Blanton, Susan H; Liu, Xue Zhong

2018-03-20

Hearing loss (HL) is the most common neurosensory disorder affecting humans. The screening, prevention and treatment of HL require a better understanding of the underlying molecular mechanisms. Genetic predisposition is one of the most common factors that leads to HL. Most HL studies include few Spanish, Hispanic and Latino participants, leaving a critical gap in our understanding about the prevalence, impact, unmet health care needs, and genetic factors associated with hearing impairment among Spanish, Hispanic and Latino populations. The few studies which have been performed show that the gene variants commonly associated with HL in non-Spanish and non-Hispanic populations are infrequently responsible for hearing impairment in Spanish as well as Hispanic and Latino populations (hereafter referred to as Hispanic). To design effective screening tools to detect HL in Spanish and Hispanic populations, studies must be conducted to determine the gene variants that are most commonly associated with hearing impairment in this racial/ethnic group. In this review article, we summarize gene variants and loci associated with HL in Spanish and Hispanic populations. Identifying new genetic variants associated with HL in Spanish and Hispanic populations will pave the way to develop effective screening tools and therapeutic strategies for HL. Copyright © 2018 Elsevier B.V. All rights reserved.

AMMOS: Automated Molecular Mechanics Optimization tool for in silico Screening

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Pajeva Ilza

2008-10-01

Full Text Available Abstract Background Virtual or in silico ligand screening combined with other computational methods is one of the most promising methods to search for new lead compounds, thereby greatly assisting the drug discovery process. Despite considerable progresses made in virtual screening methodologies, available computer programs do not easily address problems such as: structural optimization of compounds in a screening library, receptor flexibility/induced-fit, and accurate prediction of protein-ligand interactions. It has been shown that structural optimization of chemical compounds and that post-docking optimization in multi-step structure-based virtual screening approaches help to further improve the overall efficiency of the methods. To address some of these points, we developed the program AMMOS for refining both, the 3D structures of the small molecules present in chemical libraries and the predicted receptor-ligand complexes through allowing partial to full atom flexibility through molecular mechanics optimization. Results The program AMMOS carries out an automatic procedure that allows for the structural refinement of compound collections and energy minimization of protein-ligand complexes using the open source program AMMP. The performance of our package was evaluated by comparing the structures of small chemical entities minimized by AMMOS with those minimized with the Tripos and MMFF94s force fields. Next, AMMOS was used for full flexible minimization of protein-ligands complexes obtained from a mutli-step virtual screening. Enrichment studies of the selected pre-docked complexes containing 60% of the initially added inhibitors were carried out with or without final AMMOS minimization on two protein targets having different binding pocket properties. AMMOS was able to improve the enrichment after the pre-docking stage with 40 to 60% of the initially added active compounds found in the top 3% to 5% of the entire compound collection

Identification and characterization of tebuconazole transformation products in soil by combining suspect screening and molecular typology

International Nuclear Information System (INIS)

Storck, Veronika; Lucini, Luigi; Mamy, Laure; Ferrari, Federico; Papadopoulou, Evangelia S.; Nikolaki, Sofia; Karas, Panagiotis A.; Servien, Remi; Karpouzas, Dimitrios G.; Trevisan, Marco; Benoit, Pierre; Martin-Laurent, Fabrice

2016-01-01

Pesticides generate transformation products (TPs) when they are released into the environment. These TPs may be of ecotoxicological importance. Past studies have demonstrated how difficult it is to predict the occurrence of pesticide TPs and their environmental risk. The monitoring approaches mostly used in current regulatory frameworks target only known ecotoxicologically relevant TPs. Here, we present a novel combined approach which identifies and categorizes known and unknown pesticide TPs in soil by combining suspect screening time-of-flight mass spectrometry with in silico molecular typology. We used an empirical and theoretical pesticide TP library for compound identification by both non-target and target time-of-flight (tandem) mass spectrometry, followed by structural proposition through a molecular structure correlation program. In silico molecular typology was then used to group TPs according to common molecular descriptors and to indirectly elucidate their environmental parameters by analogy to known pesticide compounds with similar molecular descriptors. This approach was evaluated via the identification of TPs of the triazole fungicide tebuconazole occurring in soil during a field dissipation study. Overall, 22 empirical and 12 yet unknown TPs were detected, and categorized into three groups with defined environmental properties. This approach combining suspect screening time-of-flight mass spectrometry with molecular typology could be extended to other organic pollutants and used to rationalize the choice of TPs to be investigated towards a more comprehensive environmental risk assessment scheme. - Highlights: • Combined method to detect and categorize pesticide transformation products in soil. • Detection by QTOF-MS of new tebuconazole transformation products without standards. • Estimation by in silico molecular typology of their environmental parameters. • Method to rationally choose relevant transformation products to be studied. • The

Identification of single-copy orthologous genes between Physalis and Solanum lycopersicum and analysis of genetic diversity in Physalis using molecular markers.

Science.gov (United States)

Wei, Jingli; Hu, Xiaorong; Yang, Jingjing; Yang, Wencai

2012-01-01

The genus Physalis includes a number of commercially important edible and ornamental species. Its high nutritional value and potential medicinal properties leads to the increased commercial interest in the products of this genus worldwide. However, lack of molecular markers prevents the detailed study of genetics and phylogeny in Physalis, which limits the progress of breeding. In the present study, we compared the DNA sequences between Physalis and tomato, and attempted to analyze genetic diversity in Physalis using tomato markers. Blasting 23180 DNA sequences derived from Physalis against the International Tomato Annotation Group (ITAG) Release2.3 Predicted CDS (SL2.40) discovered 3356 single-copy orthologous genes between them. A total of 38 accessions from at least six species of Physalis were subjected to genetic diversity analysis using 97 tomato markers and 25 SSR markers derived from P. peruviana. Majority (73.2%) of tomato markers could amplify DNA fragments from at least one accession of Physalis. Diversity in Physalis at molecular level was also detected. The average Nei's genetic distance between accessions was 0.3806 with a range of 0.2865 to 0.7091. These results indicated Physalis and tomato had similarity at both molecular marker and DNA sequence levels. Therefore, the molecular markers developed in tomato can be used in genetic study in Physalis.

Introductory guide to the statistics of molecular genetics.

Science.gov (United States)

Eley, Thalia C; Rijsdijk, Frühling

2005-10-01

This introductory guide presents the main two analytical approaches used by molecular geneticists: linkage and association. Traditional linkage and association methods are described, along with more recent advances in methodologies such as those using a variance components approach. New methods are being developed all the time but the core principles of linkage and association remain the same. The basis of linkage is the transmission of a marker along with a disease within families, whereas association is based on the comparison of marker frequencies in case and control groups. It is becoming increasingly clear that effect sizes of individual markers on diseases and traits are likely to be very small. As such, much greater power is needed, and correspondingly greater sample sizes. Although non-replication is still a problem, molecular genetic studies in some areas such as attention deficit/hyperactivity disorder (ADHD) are starting to show greater convergence. Epidemiologists and other researchers with large well-characterized samples will be well placed to use these methods. Inter-disciplinary studies can then ask far more interesting questions such as those relating to developmental, multivariate and gene-environment interaction hypotheses.

Molecular genetics of pancreatic neoplasms and their morphologic correlates: an update on recent advances and potential diagnostic applications.

Science.gov (United States)

Reid, Michelle D; Saka, Burcu; Balci, Serdar; Goldblum, Andrew S; Adsay, N Volkan

2014-02-01

To summarize the most clinically and biologically relevant advances in molecular/genetic characteristics of various pancreatic neoplasms, with morphologic correlation. Whole-exome sequencing of numerous benign and malignant pancreatic tumors, along with the plethora of highly sensitive molecular studies now available for analyzing these tumors, provide mounting evidence to support the long-held belief that cancer is essentially a genetic disease. These genetic discoveries have not only helped to confirm the age-old, morphology-based classifications of pancreatic neoplasia but have shed new light on their mechanisms. Many of these molecular discoveries are currently being used in preoperative diagnosis. Mutations in KRAS, P16/CDKN2A, TP53, and SMAD4/DPC4 are commonly seen in ductal neoplasia but not in nonductal tumors; ductal adenocarcinomas with SMAD4/DPC4 loss are associated with widespread metastasis and poor prognosis. GNAS and RNF43 mutations have been discovered in most intraductal pancreatic mucinous neoplasms, providing critical molecular fingerprints for their diagnosis. Mutation in DAXX/ATRX is only seen in pancreatic neuroendocrine tumors, making it a useful potential marker in distinguishing these tumors from mimics. When combined with morphologic observations, molecular studies will increase our understanding of the pathogenesis and morphomolecular signatures associated with specific neoplasms and provide new horizons for precision medicine and targeted therapies.

[The significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis].

Science.gov (United States)

Zhang, J; Wang, Y N; Wang, J S; Wu, L; Wei, N; Fu, L; Gao, Z; Chen, J H; Pei, R J; Wang, Z

2016-07-01

To investigate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis (HLH). Four cases of primary HLH patients with PRF1, UNC13D and SH2D1A gene mutations were conducted pedigree investigation, including family genetic screening and detections of immunological parameters (NK cell activity, CD107a degranulation and expression of HLH related defective protein), to evaluate the significance of these different indicators in the diagnosis of primary HLH and explore their correlations. The DNA mutations of the four families included missense mutation c.T172C (p.S58P) and non- frameshift deletions c.1083_1094del (p.361_365del), missense mutation c.C1349T (p.T450M) and frameshift mutation c.1090_1091delCT (p.T364fsX93) in PRF1 gene, missense mutation c.G2588A (p.G863D) in UNC13D gene and hemizygous mutation c.32T>G (p.I11S) in SH2D1A gene. The patients and their family members presented decreased NK cell activities. Individuals who carried mutations of PRF1 gene and SH2D1A gene showed low expression of perforin (PRF1) and signaling lymphocytic activation molecule associated protein (SAP). And the patient with UNC13D gene mutation and his family member with identical mutation showed significant reducing cytotoxic degranulation function (expression of CD107a). Pedigree genetic screening and rapid detection of immunological parameters might play an important role in the diagnosis of primary HLH, and both of them had good consistency. As an efficient detection means, the rapid immunological detection indicators would provide reliable basis for the early diagnosis of the primary HLH.

Molecular epidemiology and evolutionary genetics of Mycobacterium tuberculosis in Taipei

OpenAIRE

Su Ih-Jen; Lee Shi-Yi; Tsai Wen-Shing; Sun Jun-Ren; Chang Jia-Ru; Lin Chih-Wei; Tseng Fan-Chen; Dou Horng-Yunn; Lu Jang-Jih

2008-01-01

Abstract Background The control of tuberculosis in densely populated cities is complicated by close human-to-human contacts and potential transmission of pathogens from multiple sources. We conducted a molecular epidemiologic analysis of 356 Mycobacterium tuberculosis (MTB) isolates from patients presenting pulmonary tuberculosis in metropolitan Taipei. Classical antibiogram studies and genetic characterization, using mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (M...

Screening of genetic parameters for soluble protein expression in Escherichia coli

DEFF Research Database (Denmark)

Vernet, Erik; Kotzsch, Alexander; Voldborg, Bjørn

2011-01-01

Soluble expression of proteins in a relevant form for functional and structural investigations still often remains a challenge. Although many biochemical factors are known to affect solubility, a thorough investigation of yield-limiting factors is normally not feasible in high-throughput efforts....... Here we present a screening strategy for expression of biomedically relevant proteins in Escherichia coli using a panel of six different genetic variations. These include engineered strains for rare codon supplementation, increased disulfide bond formation in the cytoplasm and novel vectors...... for secretion to the periplasm or culture medium. Combining these variants with expression construct truncations design, we report on parallel cloning and expression of more than 300 constructs representing 24 selected proteins; including full-length variants of human growth factors, interleukins and growth...

Avoiding pitfalls in molecular genetic testing: case studies of high-resolution array comparative genomic hybridization testing in the definitive diagnosis of Mowat-Wilson syndrome.

Science.gov (United States)

Kluk, Michael Joseph; An, Yu; James, Philip; Coulter, David; Harris, David; Wu, Bai-Lin; Shen, Yiping

2011-05-01

The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both cases was negative, but the application of high-resolution array comparative genomic hybridization technology lead to definitive diagnosis in both cases. We summarize the clinical findings and molecular testing in each case, discuss the differential diagnoses, and review the clinical and pathological findings of Mowat-Wilson syndrome. This report highlights the importance for those involved in molecular testing to know the nature of the underlying genetic abnormalities associated with the suspected diagnosis, to recognize the limitations of each testing platform, and to persistently pursue repeat testing using high-resolution technologies when indicated. This concept is applicable to both germline and somatic molecular genetic testing. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

[Noonan syndrome can be diagnosed clinically and through molecular genetic analyses].

Science.gov (United States)

Henningsen, Marie Krab; Jelsig, Anne Marie; Andersen, Helle; Brusgaard, Klaus; Ousager, Lilian Bomme; Hertz, Jens Michael

2015-08-03

Noonan syndrome is part of the group of RASopathies caused by germ line mutations in genes involved in the RAS/MAPK pathway. There is substantial phenotypic overlap among the RASopathies. Diagnosis of Noonan syndrome is often based on clinical features including dysmorphic facial features, short stature and congenital heart disease. Rapid advances in sequencing technology have made molecular genetic analyses a helpful tool in diagnosing and distinguishing Noonan syndrome from other RASopathies.

Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics

Science.gov (United States)

Lau, Wan F.; Withka, Jane M.; Hepworth, David; Magee, Thomas V.; Du, Yuhua J.; Bakken, Gregory A.; Miller, Michael D.; Hendsch, Zachary S.; Thanabal, Venkataraman; Kolodziej, Steve A.; Xing, Li; Hu, Qiyue; Narasimhan, Lakshmi S.; Love, Robert; Charlton, Maura E.; Hughes, Samantha; van Hoorn, Willem P.; Mills, James E.

2011-07-01

Fragment Based Drug Discovery (FBDD) continues to advance as an efficient and alternative screening paradigm for the identification and optimization of novel chemical matter. To enable FBDD across a wide range of pharmaceutical targets, a fragment screening library is required to be chemically diverse and synthetically expandable to enable critical decision making for chemical follow-up and assessing new target druggability. In this manuscript, the Pfizer fragment library design strategy which utilized multiple and orthogonal metrics to incorporate structure, pharmacophore and pharmacological space diversity is described. Appropriate measures of molecular complexity were also employed to maximize the probability of detection of fragment hits using a variety of biophysical and biochemical screening methods. In addition, structural integrity, purity, solubility, fragment and analog availability as well as cost were important considerations in the selection process. Preliminary analysis of primary screening results for 13 targets using NMR Saturation Transfer Difference (STD) indicates the identification of uM-mM hits and the uniqueness of hits at weak binding affinities for these targets.

Molecular genetic diversity of Punica granatum L. (pomegranate) as revealed by microsatellite DNA markers

Science.gov (United States)

Pomegranate (Punica granatum L.) is one of the oldest known edible fruits and more and more it arouse interest of scientific community given its numerous biological activities. However, information about its genetic resources and characterization using reliable molecular markers are still scarce. In...

Risks of Colorectal Cancer Screening

Science.gov (United States)

... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

Study of inter species diversity and population structure by molecular genetic method in Iranian Artemia

OpenAIRE

Hajirostamloo, Mahbobeh

2005-01-01

Artemia is a small crustacean that adapted to live in brine water and has been seen in different brine water sources in Iran. Considering the importance of genetic studies manifest inter population differences in species, to estimate genetic structure, detect difference at molecular level and separate different Artemia populations of Iran, also study of phylogenic relationships among them, samples of Artemia were collected from nine region: Urmia lake in West Azerbaijan, Sh...

A genetic screen reveals Arabidopsis stomatal and/or apoplastic defenses against Pseudomonas syringae pv. tomato DC3000.

Directory of Open Access Journals (Sweden)

Weiqing Zeng

2011-10-01

Full Text Available Bacterial infection of plants often begins with colonization of the plant surface, followed by entry into the plant through wounds and natural openings (such as stomata, multiplication in the intercellular space (apoplast of the infected tissues, and dissemination of bacteria to other plants. Historically, most studies assess bacterial infection based on final outcomes of disease and/or pathogen growth using whole infected tissues; few studies have genetically distinguished the contribution of different host cell types in response to an infection. The phytotoxin coronatine (COR is produced by several pathovars of Pseudomonas syringae. COR-deficient mutants of P. s. tomato (Pst DC3000 are severely compromised in virulence, especially when inoculated onto the plant surface. We report here a genetic screen to identify Arabidopsis mutants that could rescue the virulence of COR-deficient mutant bacteria. Among the susceptible to coronatine-deficient Pst DC3000 (scord mutants were two that were defective in stomatal closure response, two that were defective in apoplast defense, and four that were defective in both stomatal and apoplast defense. Isolation of these three classes of mutants suggests that stomatal and apoplastic defenses are integrated in plants, but are genetically separable, and that COR is important for Pst DC3000 to overcome both stomatal guard cell- and apoplastic mesophyll cell-based defenses. Of the six mutants defective in bacterium-triggered stomatal closure, three are defective in salicylic acid (SA-induced stomatal closure, but exhibit normal stomatal closure in response to abscisic acid (ABA, and scord7 is compromised in both SA- and ABA-induced stomatal closure. We have cloned SCORD3, which is required for salicylic acid (SA biosynthesis, and SCORD5, which encodes an ATP-binding cassette (ABC protein, AtGCN20/AtABCF3, predicted to be involved in stress-associated protein translation control. Identification of SCORD5 begins to

Infrastructure and Educational Needs of Newborn Screening Short-Term Follow-Up Programs within the Southeast Regional Newborn Screening & Genetics Collaborative: A Pilot Survey

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Cecelia A. Bellcross

2015-10-01

Full Text Available Newborn screening (NBS follow-up protocols vary significantly by state, and there is a need to better understand the infrastructure and communication flow of NBS programs. In addition, assessment of the educational needs of families and providers with regard to the implications of NBS results is required to inform the development of appropriate informational resources and training opportunities. To begin to address these issues, we administered a web-based survey to state NBS coordinators within the Southeast Regional Newborn Screening & Genetics Collaborative (SERC. Fourteen coordinators responded to the survey, including at least one from each of the 10 SERC states/territories. Over one-third of respondents had never received formal training regarding the metabolic conditions identified on NBS. Most communicated results via telephone or fax, though two centers indicated use of a web-based platform. Only two programs were involved in directly reporting results to the family. Four programs reported a long-term follow-up protocol. Deficits were noted for primary care provider (PCP knowledge of metabolic disorders identified on NBS, and how to inform parents of abnormal results. Close to half indicated that the adequacy of the number of genetic counselors, dietitians, and medical/biochemical geneticists was minimal to insufficient. Respondents uniformly recognized the importance of providing additional educational and informational resources in multiple categories to NBS staff, PCPs, and families.

Haploid genetic screens identify an essential role for PLP2 in the downregulation of novel plasma membrane targets by viral E3 ubiquitin ligases.

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Richard T Timms

Full Text Available The Kaposi's sarcoma-associated herpesvirus gene products K3 and K5 are viral ubiquitin E3 ligases which downregulate MHC-I and additional cell surface immunoreceptors. To identify novel cellular genes required for K5 function we performed a forward genetic screen in near-haploid human KBM7 cells. The screen identified proteolipid protein 2 (PLP2, a MARVEL domain protein of unknown function, as essential for K5 activity. Genetic loss of PLP2 traps the viral ligase in the endoplasmic reticulum, where it is unable to ubiquitinate and degrade its substrates. Subsequent analysis of the plasma membrane proteome of K5-expressing KBM7 cells in the presence and absence of PLP2 revealed a wide range of novel K5 targets, all of which required PLP2 for their K5-mediated downregulation. This work ascribes a critical function to PLP2 for viral ligase activity and underlines the power of non-lethal haploid genetic screens in human cells to identify the genes involved in pathogen manipulation of the host immune system.

Implication of Gastric Cancer Molecular Genetic Markers in Surgical Practice.

Science.gov (United States)

Nemtsova, Marina V; Strelnikov, Vladimir V; Tanas, Alexander S; Bykov, Igor I; Zaletaev, Dmitry V; Rudenko, Viktoria V; Glukhov, Alexander I; Kchorobrich, Tatiana V; Li, Yi; Tarasov, Vadim V; Barreto, George E; Aliev, Gjumrakch

2017-10-01

We have investigated aberrant methylation of genes CDH1, RASSF1A, MLH1, N33, DAPK, expression of genes hTERT, MMP7, MMP9, BIRC5 (survivin), PTGS2, and activity of telomerase of 106 gastric tumor samples obtained intra-operatively and 53 gastric tumor samples from the same group of patients obtained endoscopically before surgery. Biopsy specimens obtained from 50 patients with chronic calculous cholecystitis were used as a control group. Together with tissue samples obtained from different sites remote to tumors, a total of 727 samples have been studied. The selected parameters comprise a system of molecular markers that can be used in both diagnostics of gastric cancer and in dynamic monitoring of patients after surgery. Special attention was paid to the use of molecular markers for the diagnostics of malignant process in the material obtained endoscopically since the efficacy of morphological diagnostics in biopsies is compromised by intratumoral heterogeneity, which may prevent reliable identification of tumor cells in the sampling. Our data indicated that certain molecular genetic events provided more sensitive yet specific markers of the tumor. We demonstrated that molecular profiles detected in preoperative biopsies were confirmed by the material obtained intra-operatively. The use of endoscopic material facilitates gastric tumors pre-operative diagnostics, improving early detection of gastric cancer and potential effective treatment strategies.

Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background.

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Saskia Decuypere

Full Text Available The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L. donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread

Diagnostic yield of molecular autopsy in patients with sudden arrhythmic death syndrome using targeted exome sequencing

DEFF Research Database (Denmark)

Nunn, Laurence M; Lopes, Luis R; Syrris, Petros

2016-01-01

AIMS: The targeted genetic screening of Sudden Arrhythmic Death Syndrome (SADS) probands in a molecular autopsy has a diagnostic yield of up to 35%. Exome sequencing has the potential to improve this yield. The primary aim of this study is to examine the feasibility and diagnostic utility...... of targeted exome screening in SADS victims, utilizing familial clinical screening whenever possible. METHODS AND RESULTS: To determine the feasibility and diagnostic yield of targeted exome sequencing deoxyribonucleic acid (DNA) was isolated from 59 SADS victims (mean age 25 years, range 1-51 years...... previously published rare (0.02-0.5%) candidate mutations-a total yield of 29%. Co-segregation fully confirmed two private SCN5A Na channel mutations. Variants of unknown significance were detected in a further 34% of probands. CONCLUSION: Molecular autopsy using targeted exome sequencing has a relatively...

Identification of single-copy orthologous genes between Physalis and Solanum lycopersicum and analysis of genetic diversity in Physalis using molecular markers.

Directory of Open Access Journals (Sweden)

Jingli Wei

Full Text Available The genus Physalis includes a number of commercially important edible and ornamental species. Its high nutritional value and potential medicinal properties leads to the increased commercial interest in the products of this genus worldwide. However, lack of molecular markers prevents the detailed study of genetics and phylogeny in Physalis, which limits the progress of breeding. In the present study, we compared the DNA sequences between Physalis and tomato, and attempted to analyze genetic diversity in Physalis using tomato markers. Blasting 23180 DNA sequences derived from Physalis against the International Tomato Annotation Group (ITAG Release2.3 Predicted CDS (SL2.40 discovered 3356 single-copy orthologous genes between them. A total of 38 accessions from at least six species of Physalis were subjected to genetic diversity analysis using 97 tomato markers and 25 SSR markers derived from P. peruviana. Majority (73.2% of tomato markers could amplify DNA fragments from at least one accession of Physalis. Diversity in Physalis at molecular level was also detected. The average Nei's genetic distance between accessions was 0.3806 with a range of 0.2865 to 0.7091. These results indicated Physalis and tomato had similarity at both molecular marker and DNA sequence levels. Therefore, the molecular markers developed in tomato can be used in genetic study in Physalis.

Biochemical and molecular genetic studies on some cyanobacterial isolates

International Nuclear Information System (INIS)

Kamal, E.A.R.; Ebrahim, S.A.A.

2011-01-01

In the present study, the isolation and purification of a set of Cyanobacteria strains belonging to genus Oscillatoria was undertaken, followed by the analyses of phylogenetic relationships using different biochemical and molecular genetic techniques (SOS-PAGE and RAPO-PCR). A total of 45 protein bands were observed within the studied Osci/latoria isolates by SOS-PAGE (only three unique bands, eight monomorphic bands and 37 polymorphic bands). On the other hand, extracted ONA from isolates was used to identify the molecular fingerprints. A sum of 94 polymorphic bands was generated by these primers in the Ocsi/laloria genotypes under study. A total of 20 unique bands were identified out of the polymorphic ones. These unique bands were used to discriminate among the studied Ocsi/latoria isolates. Most isolates of Ocsi/latoria genotypes were discriminated by one or more unique bands. Numerical taxonomic using 45 protein attributes of 19 isolates and RAPO markers on five isolates. Two methods -Clustering (UPGMA) and Principal Component Analysis (PCA) were used for these analyses. The similarities and clusters produced between the studied isolates were discussed.

Biochemical and molecular genetic studies on some cyanobacterial isolates

Energy Technology Data Exchange (ETDEWEB)

Kamal, E A.R. [Umm Al-Qura University, Makkah (Saudi Arabia). Dept. of Biology; Ebrahim, S A.A. [Ain Sham University, Cairo (Egypt). Dept. of Cytogenetic

2011-11-15

In the present study, the isolation and purification of a set of Cyanobacteria strains belonging to genus Oscillatoria was undertaken, followed by the analyses of phylogenetic relationships using different biochemical and molecular genetic techniques (SOS-PAGE and RAPO-PCR). A total of 45 protein bands were observed within the studied Osci/latoria isolates by SOS-PAGE (only three unique bands, eight monomorphic bands and 37 polymorphic bands). On the other hand, extracted ONA from isolates was used to identify the molecular fingerprints. A sum of 94 polymorphic bands was generated by these primers in the Ocsi/laloria genotypes under study. A total of 20 unique bands were identified out of the polymorphic ones. These unique bands were used to discriminate among the studied Ocsi/latoria isolates. Most isolates of Ocsi/latoria genotypes were discriminated by one or more unique bands. Numerical taxonomic using 45 protein attributes of 19 isolates and RAPO markers on five isolates. Two methods -Clustering (UPGMA) and Principal Component Analysis (PCA) were used for these analyses. The similarities and clusters produced between the studied isolates were discussed.

Searching for non-genetic molecular and imaging PTSD risk and resilience markers: Systematic review of literature and design of the German Armed Forces PTSD biomarker study.

Science.gov (United States)

Schmidt, Ulrike; Willmund, Gerd-Dieter; Holsboer, Florian; Wotjak, Carsten T; Gallinat, Jürgen; Kowalski, Jens T; Zimmermann, Peter

2015-01-01

Biomarkers allowing the identification of individuals with an above average vulnerability or resilience for posttraumatic stress disorder (PTSD) would especially serve populations at high risk for trauma exposure like firefighters, police officers and combat soldiers. Aiming to identify the most promising putative PTSD vulnerability markers, we conducted the first systematic review on potential imaging and non-genetic molecular markers for PTSD risk and resilience. Following the PRISMA guidelines, we systematically screened the PubMed database for prospective longitudinal clinical studies and twin studies reporting on pre-trauma and post-trauma PTSD risk and resilience biomarkers. Using 25 different combinations of search terms, we retrieved 8151 articles of which we finally included and evaluated 9 imaging and 27 molecular studies. In addition, we briefly illustrate the design of the ongoing prospective German Armed Forces (Bundeswehr) PTSD biomarker study (Bw-BioPTSD) which not only aims to validate these previous findings but also to identify novel and clinically applicable molecular, psychological and imaging risk, resilience and disease markers for deployment-related psychopathology in a cohort of German soldiers who served in Afghanistan. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular-Simulation-Driven Fragment Screening for the Discovery of New CXCL12 Inhibitors.

Science.gov (United States)

Martinez-Rosell, Gerard; Harvey, Matt J; De Fabritiis, Gianni

2018-03-26

Fragment-based drug discovery (FBDD) has become a mainstream approach in drug design because it allows the reduction of the chemical space and screening libraries while identifying fragments with high protein-ligand efficiency interactions that can later be grown into drug-like leads. In this work, we leverage high-throughput molecular dynamics (MD) simulations to screen a library of 129 fragments for a total of 5.85 ms against the CXCL12 monomer, a chemokine involved in inflammation and diseases such as cancer. Our in silico binding assay was able to recover binding poses, affinities, and kinetics for the selected library and was able to predict 8 mM-affinity fragments with ligand efficiencies higher than 0.3. All of the fragment hits present a similar chemical structure, with a hydrophobic core and a positively charged group, and bind to either sY7 or H1S68 pockets, where they share pharmacophoric properties with experimentally resolved natural binders. This work presents a large-scale screening assay using an exclusive combination of thousands of short MD adaptive simulations analyzed with a Markov state model (MSM) framework.

Development of a forward genetic screen to isolate oil mutants in the green microalga Chlamydomonas reinhardtii.

Science.gov (United States)

Cagnon, Caroline; Mirabella, Boris; Nguyen, Hoa Mai; Beyly-Adriano, Audrey; Bouvet, Séverine; Cuiné, Stéphan; Beisson, Fred; Peltier, Gilles; Li-Beisson, Yonghua

2013-12-02

Oils produced by microalgae are precursors to biodiesel. To achieve a profitable production of biodiesel from microalgae, identification of factors governing oil synthesis and turnover is desirable. The green microalga Chlamydomonas reinhardtii is amenable to genetic analyses and has recently emerged as a model to study oil metabolism. However, a detailed method to isolate various types of oil mutants that is adapted to Chlamydomonas has not been reported. We describe here a forward genetic approach to isolate mutants altered in oil synthesis and turnover from C. reinhardtii. It consists of a three-step screening procedure: a primary screen by flow cytometry of Nile red stained transformants grown in 96-deep-well plates under three sequential conditions (presence of nitrogen, then absence of nitrogen, followed by oil remobilization); a confirmation step using Nile red stained biological triplicates; and a validation step consisting of the quantification by thin layer chromatography of oil content of selected strains. Thirty-one mutants were isolated by screening 1,800 transformants generated by random insertional mutagenesis (1.7%). Five showed increased oil accumulation under the nitrogen-replete condition and 13 had altered oil content under nitrogen-depletion. All mutants were affected in oil remobilization. This study demonstrates that various types of oil mutants can be isolated in Chlamydomonas based on the method set-up here, including mutants accumulating oil under optimal biomass growth. The strategy conceived and the protocol set-up should be applicable to other microalgal species such as Nannochloropsis and Chlorella, thus serving as a useful tool in Chlamydomonas oil research and algal biotechnology.

Carrier screening for thalassemia and hemoglobinopathies in Canada.

Science.gov (United States)

Langlois, Sylvie; Ford, Jason C; Chitayat, David

2008-10-01

To provide recommendations to physicians, midwives, genetic counsellors, and clinical laboratory scientists involved in pre-conceptional or prenatal care regarding carrier screening for thalassemia and hemoglobinopathies (e.g., sickle cell anemia and other qualitative hemoglobin disorders). To determine the populations to be screened and the appropriate tests to offer to minimize practice variations across Canada. The Medline database was searched for relevant articles published between 1986 and 2007 on carrier screening for thalassemia and hemoglobinopathies. Key textbooks were also reviewed. Recommendations were quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on Preventive Health Care. The evidence collected from the Medline search was reviewed by the Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists (CCMG) and the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC). Screening of individuals at increased risk of being carriers for thalassemia and hemoglobinopathies can identify couples with a 25% risk of having a pregnancy with a significant genetic disorder for which prenatal diagnosis is possible. Ideally, screening should be done pre-conceptionally. However, for a significant proportion of patients, the screening will occur during the pregnancy, and the time constraint for obtaining screening results may result in psychological distress. This guideline does not include a cost analysis. 1. Carrier screening for thalassemia and hemoglobinopathies should be offered to a woman if she and/or her partner are identified as belonging to an ethnic population whose members are at higher risk of being carriers. Ideally, this screening should be done pre-conceptionally or as early as possible in the pregnancy. (II-2A) 2. Screening should consist of a complete blood count, as well as hemoglobin electrophoresis or hemoglobin high performance liquid chromatography. This

Genetic Aspects of Nephrotic Syndrome

DEFF Research Database (Denmark)

Joshi, Shivani

Nephrotic syndrome (NS) is characterized by severe proteinuria, hypoalbuminemia, and edema. Depending on response to steroid treatment, patients either have steroid sensitive NS (SSNS) or steroid resistant NS (SRNS). Patients with SRNS often have a poor renal prognosis, focal segmental glomerulos......Nephrotic syndrome (NS) is characterized by severe proteinuria, hypoalbuminemia, and edema. Depending on response to steroid treatment, patients either have steroid sensitive NS (SSNS) or steroid resistant NS (SRNS). Patients with SRNS often have a poor renal prognosis, focal segmental...... steroid dependence or become frequent relapsers. Repeated courses of corticosteroid treatment often cause significant associated morbidity. Familial occurrence of SSNS is rare and suggests a potential genetic origin. However, very little data on molecular genetics of familial SSNS is available...... SSNS. Study I is the first study to describe the genetic findings in 39 patients with sporadic FSGS and/or SRNS, in a highly selected Danish population. We developed a screening tool (high resolution melting analysis) to search for variants in NPHS1, NPHS2, and INF2 genes. This method was shown...

Scarlet Fever Upsurge in England and Molecular-Genetic Analysis in North-West London, 2014

Centers for Disease Control (CDC) Podcasts

2016-08-16

Sarah Gregory reads an abridged version of the article, Scarlet Fever Upsurge in England and Molecular-Genetic Analysis in North-West London, 2014.  Created: 8/16/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/16/2016.

[Neonatal screening of hemoglobinopathies and G6PD deficiency in Catalonia (Spain). Molecular study of sickle cell disease associated with alpha thalassemia and G6PD deficiency].

Science.gov (United States)

Mañú Pereira, María Del Mar; Cabot, Anna; Martínez González, Ana; Sitjà Navarro, Eulalia; Cararach, Vicent; Sabrià, Josep; Boixaderas, Jordi; Teixidor, Roser; Bosch, Albert; López Vílchez, M Angeles; Martín Ibáñez, Itziar; Carrión, Teresa; Plaja, Pere; Sánchez, Mario; Vives Corrons, José Luis

2007-06-30

The prevalence of hemoglobinopathies and glucose-6-phosphate dehidrogenase (G6PD) deficiency in the Catalan neonatal population is increasing due to immigration. Coinheritance of more than a single RBC genetic defect is becoming more frequent and diagnostic pitfalls are also increasing. We intended to demonstrate the need to perform an early diagnosis of sickle cell disease (SCD) by means of neonatal screening, to establish the prevalence of SCD associated with alpha thalassemia and G6PD deficiency and to identify genotypes associated with sickle cell disease and G6PD deficiency. 4,020 blood samples from newborns were screened. For the screening of hemoglobinopathies the high performance liquid chromatography method was used and for G6PD deficiency the fluorescent spot test was employed. We studied the association between betaS gene and alpha thalassaemia del-3.7 Kb. SCD and G6PD deficiency genotypes were established. Prevalence of SCD in population at risk was 1/475 newborns. Prevalence of G6PD deficiency in population at risk was 1/43, and in autochthonous population was 1/527 newborns. In all the cases, sickle hemoglobin was confirmed by ARMS (amplification refractory mutation system). Association between betaS gene and alpha thalassaemia del-3.7 Kb was found in 32.2% of the samples, and an association between betaS gene and G6PD deficiency was observed in 7% of the samples. This study confirms the high prevalence of SCD and G6PD deficiency in population at risk as well as their genetic and clinical heterogeneity. The study of genotype/phenotype relationships allows a better knowledge of molecular mechanism and is useful to establish suitable criteria of diagnosis.

Quality assurance practices in Europe: a survey of molecular genetic testing laboratories

Science.gov (United States)

Berwouts, Sarah; Fanning, Katrina; Morris, Michael A; Barton, David E; Dequeker, Elisabeth

2012-01-01

In the 2000s, a number of initiatives were taken internationally to improve quality in genetic testing services. To contribute to and update the limited literature available related to this topic, we surveyed 910 human molecular genetic testing laboratories, of which 291 (32%) from 29 European countries responded. The majority of laboratories were in the public sector (81%), affiliated with a university hospital (60%). Only a minority of laboratories was accredited (23%), and 26% was certified. A total of 22% of laboratories did not participate in external quality assessment (EQA) and 28% did not use reference materials (RMs). The main motivations given for accreditation were to improve laboratory profile (85%) and national recognition (84%). Nearly all respondents (95%) would prefer working in an accredited laboratory. In accredited laboratories, participation in EQA (Pquality assurance (Pquality implementation score (QIS), we showed that accredited laboratories (average score 92) comply better than certified laboratories (average score 69, Pquality indicators. We conclude that quality practices vary widely in European genetic testing laboratories. This leads to a potentially dangerous situation in which the quality of genetic testing is not consistently assured. PMID:22739339

Synthetic biology and molecular genetics in non-conventional yeasts: Current tools and future advances.

Science.gov (United States)

Wagner, James M; Alper, Hal S

2016-04-01

Coupling the tools of synthetic biology with traditional molecular genetic techniques can enable the rapid prototyping and optimization of yeast strains. While the era of yeast synthetic biology began in the well-characterized model organism Saccharomyces cerevisiae, it is swiftly expanding to include non-conventional yeast production systems such as Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. These yeasts already have roles in the manufacture of vaccines, therapeutic proteins, food additives, and biorenewable chemicals, but recent synthetic biology advances have the potential to greatly expand and diversify their impact on biotechnology. In this review, we summarize the development of synthetic biological tools (including promoters and terminators) and enabling molecular genetics approaches that have been applied in these four promising alternative biomanufacturing platforms. An emphasis is placed on synthetic parts and genome editing tools. Finally, we discuss examples of synthetic tools developed in other organisms that can be adapted or optimized for these hosts in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

New multiplex PCR methods for rapid screening of genetically modified organisms in foods.

Science.gov (United States)

Datukishvili, Nelly; Kutateladze, Tamara; Gabriadze, Inga; Bitskinashvili, Kakha; Vishnepolsky, Boris

2015-01-01

We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs). New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV) 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS) terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps) gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab) gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS) and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products.

New multiplex PCR methods for rapid screening of genetically modified organisms in foods

Directory of Open Access Journals (Sweden)

Nelly eDatukishvili

2015-07-01

Full Text Available We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs. New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products.

Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico.

Science.gov (United States)

Jhong, Chien-Hung; Riyaphan, Jirawat; Lin, Shih-Hung; Chia, Yi-Chen; Weng, Ching-Feng

2015-01-01

The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants. © 2015 International Union of Biochemistry and Molecular Biology.

Variabilidade genética de acessos de maracujá-suspiro com base em marcadores moleculares Genetic variability of wild passion fruit determined by molecular markers

Directory of Open Access Journals (Sweden)

Keize Pereira Junqueira

2007-01-01

Full Text Available Passiflora nitida é uma espécie silvestre amplamente distribuída pelo território brasileiro, constituindo-se em fonte de resistência a doenças foliares e de raízes. O objetivo deste trabalho foi avaliar a variabilidade genética entre acessos de P. nitida procedentes de diferentes tipos fitofisionômicos de Cerrado e estados brasileiros (Goiás, Distrito Federal, Tocantins, Mato Grosso e Amazonas, usando marcadores moleculares RAPD. O DNA genômico de cada acesso foi extraído, e doze iniciadores decâmeros foram utilizados para a obtenção de marcadores moleculares RAPD, que foram convertidos em matriz de dados binários, a partir da qual foram estimadas as distâncias genéticas entre os acessos e realizadas análises de agrupamento e de dispersão gráfica. Foram obtidos 196 marcadores para P. nitida, dos quais 63,81% foram polimórficos. As distâncias genéticas entre os acessos de maracujá variaram de 0,031 a 0,614 e, considerando apenas P. nitida, de 0,031 a 0,417. Os marcadores moleculares demonstraram alta variabilidade genética dos acessos de P. nitida. Menores distâncias genéticas foram verificadas entre os acessos originados do mesmo estado. Considerando-se os acessos de um mesmo estado, menores distâncias genéticas foram verificadas entre os acessos provenientes de tipos fitofisionômicos próximos. O acesso "Manaus 2" apresentou o maior distanciamento genético em relação aos demais acessos.Passiflora nitida is a wild species widely distributed in Brazilian territory. It is a source of resistance to foliar and soil borne diseases. The objective of this work was to evaluate the genetic variability among accessions of P. nitida proceeding from different types of Cerrado (Brazilian savannah vegetation and brazilian states (Goiás, Distrito Federal, Tocantins, Mato Grosso and Amazonas using RAPD molecular markers. The genomic DNA of each origin was extracted and amplified using 12 decamer primers to obtain RAPD

Raman spectroscopy-based screening of hepatitis C and associated molecular changes

Science.gov (United States)

Bilal, Maria; Bilal, M.; Saleem, M.; Khan, Saranjam; Ullah, Rahat; Fatima, Kiran; Ahmed, M.; Hayat, Abbas; Shahzada, Shaista; Ullah Khan, Ehsan

2017-09-01

This study presents the optical screening of hepatitis C and its associated molecular changes in human blood sera using a partial least-squares regression model based on their Raman spectra. In total, 152 samples were tested through enzyme-linked immunosorbent assay for confirmation. This model utilizes minor spectral variations in the Raman spectra of the positive and control groups. Regression coefficients of this model were analyzed with reference to the variations in concentration of associated molecules in these two groups. It was found that trehalose, chitin, ammonia, and cytokines are positively correlated while lipids, beta structures of proteins, and carbohydrate-binding proteins are negatively correlated with hepatitis C. The regression vector yielded by this model is utilized to predict hepatitis C in unknown samples. This model has been evaluated by a cross-validation method, which yielded a correlation coefficient of 0.91. Moreover, 30 unknown samples were screened for hepatitis C infection using this model to test its performance. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve from these predictions were found to be 93.3%, 100%, 96.7%, and 1, respectively.

Cell-Based Reporter System for High-Throughput Screening of MicroRNA Pathway Inhibitors and Its Limitations

Czech Academy of Sciences Publication Activity Database

Bruštíková, Kateřina; Sedlák, David; Kubíková, Jana; Škuta, Ctibor; Šolcová, Kateřina; Malík, Radek; Bartůněk, Petr; Svoboda, Petr

2018-01-01

Roč. 9 (2018), č. článku 45. ISSN 1664-8021 R&D Projects: GA ČR GA13-29531S; GA MŠk LO1220; GA MŠk LM2015063; GA MŠk LM2011022 Institutional support: RVO:68378050 Keywords : miRNA * high-throughput screening * miR-30 * let-7 * Argonaute Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.789, year: 2016

Molecular Testing for Gastrointestinal Cancer

Directory of Open Access Journals (Sweden)

Hye Seung Lee

2017-03-01

Full Text Available With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC and colorectal cancer (CRC. Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4. A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2 and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

Congruence between morphological and molecular markers inferred from the analysis of the intra-morphotype genetic diversity and the spatial structure of Oxalis tuberosa Mol.

Science.gov (United States)

Pissard, Audrey; Arbizu, Carlos; Ghislain, Marc; Faux, Anne-Michèle; Paulet, Sébastien; Bertin, Pierre

2008-01-01

Oxalis tuberosa is an important crop cultivated in the highest Andean zones. A germplasm collection is maintained ex situ by CIP, which has developed a morphological markers system to classify the accessions into morphotypes, i.e. groups of morphologically identical accessions. However, their genetic uniformity is currently unknown. The ISSR technique was used in two experiments to determine the relationships between both morphological and molecular markers systems. The intra-morphotype genetic diversity, the spatial structures of the diversity and the congruence between both markers systems were determined. In the first experience, 44 accessions representing five morphotypes, clearly distinct from each other, were analyzed. At the molecular level, the accessions exactly clustered according to their morphotypes. However, a genetic variability was observed inside each morphotype. In the second experiment, 34 accessions gradually differing from each other on morphological base were analyzed. The morphological clustering showed no geographical structure. On the opposite, the molecular analysis showed that the genetic structure was slightly related to the collection site. The correlation between both markers systems was weak but significant. The lack of perfect congruence between morphological and molecular data suggests that the morphological system may be useful for the morphotypes management but is not appropriate to study the genetic structure of the oca. The spatial structure of the genetic diversity can be related to the evolution of the species and the discordance between the morphological and molecular structures may result from similar selection pressures at different places leading to similar forms with a different genetic background.

Molecular Genetic Insights on Cheetah (Acinonyx jubatus) Ecology and Conservation in Namibia

OpenAIRE

Marker, Laurie L.; Wilkerson, Alison J. Pearks; Sarno, Ronald J.; Martenson, Janice; Breitenmoser-Würsten, Christian; O'Brien, Stephen J.; Johnson, Warren E.

2017-01-01

The extent and geographic patterns of molecular genetic diversity of the largest remaining free-ranging cheetah population were described in a survey of 313 individuals from throughout Namibia. Levels of relatedness, including paternity/maternity (parentage), were assessed across all individuals using 19 polymorphic microsatellite loci, and unrelated cheetahs (n = 89) from 7 regions were genotyped at 38 loci to document broad geographical patterns. There was limited differentiation among regi...

[Molecular diagnostics of ALK-positive lung cancer].

Science.gov (United States)

Tímár, József; Lotz, Gábor; Rásó, Erzsébet; Moldvay, Judit

2017-09-20

ALK translocation is the 3rd most frequent genetic aberration in lung adenocarcinoma, and several inhibitors are now clinically available in first and second line settings. Accordingly, molecular diagnostics of ALK-positive lung cancer is very important and can be done with the rational combination of several methods. All international recommendations suggest that, except for cytological samples, screening technology for ALK-positive tumors is immunohistochemistry using a validated test. It is highly recommended that in case of ALK protein positive samples gene translocation must be confirmed by fluorescent in situ hybridization (FISH). In case of cytological samples FISH technique must be used as ALK diagnostics. In equivocal cases the genetic alteration of ALK can be confirmed by alternative molecular techniques such as next generation sequencing or RNAbased PCR methods. Upon administration of ALK inhibitors, acquired resistance is frequent which is mostly due to ALK amplification and/or mutation. It is evident that the diagnostics of these secondary ALK gene alterations must be done from recurrent tumors or circulating nucleic acids.

Testing for direct genetic effects using a screening step in family-based association studies

Directory of Open Access Journals (Sweden)

Sharon M Lutz

2013-11-01

Full Text Available In genome wide association studies (GWAS, families based studies tend to have less power to detect genetic associations than population based studies, such as case-control studies. This can be an issue when testing if genes in a family based GWAS have a direct effect on the phenotype of interest or if the genes act indirectly through a secondary phenotype. When multiple SNPs are tested for a direct effect in the family based study, a screening step can be used to minimize the burden of multiple comparisons in the causal analysis. We propose a 2-stage screening step that can be incorporated into the family based association test (FBAT approach similar to the conditional mean model approach in the VanSteen-algorithm [1]. Simulations demonstrate that the type 1 error is preserved and this method is advantageous when multiple markers are tested. This method is illustrated by an application to the Framingham Heart Study.

Evaluation of schistosome promoter expression for transgenesis and genetic analysis.

Directory of Open Access Journals (Sweden)

Shuang Liang

Full Text Available Schistosome worms of the genus Schistosoma are the causative agents of schistosomiasis, a devastating parasitic disease affecting more than 240 million people worldwide. Schistosomes have complex life cycles, and have been challenging to manipulate genetically due to the dearth of molecular tools. Although the use of gene overexpression, gene knockouts or knockdowns are straight-forward genetic tools applied in many model systems, gene misexpression and genetic manipulation of schistosome genes in vivo has been exceptionally challenging, and plasmid based transfection inducing gene expression is limited. We recently reported the use of polyethyleneimine (PEI as a simple and effective method for schistosome transfection and gene expression. Here, we use PEI-mediated schistosome plasmid transgenesis to define and compare gene expression profiles from endogenous and nonendogenous promoters in the schistosomula stage of schistosomes that are potentially useful to misexpress (underexpress or overexpress gene product levels. In addition, we overexpress schistosome genes in vivo using a strong promoter and show plasmid-based misregulation of genes in schistosomes, producing a clear and distinct phenotype--death. These data focus on the schistosomula stage, but they foreshadow strong potential for genetic characterization of schistosome molecular pathways, and potential for use in overexpression screens and drug resistance studies in schistosomes using plasmid-based gene expression.

Avoiding Pitfalls in Molecular Genetic Testing: Case Studies of High-Resolution Array Comparative Genomic Hybridization Testing in the Definitive Diagnosis of Mowat-Wilson Syndrome

OpenAIRE

Kluk, Michael Joseph; An, Yu; James, Philip; Coulter, David; Harris, David; Wu, Bai-Lin; Shen, Yiping

2011-01-01

The molecular testing options available for the diagnosis of genetic disorders are numerous and include a variety of different assay platforms. The consultative input of molecular pathologists and cytogeneticists, working closely with the ordering clinicians, is often important for definitive diagnosis. Herein, we describe two patients who had long histories of unexplained signs and symptoms with a high clinical suspicion of an underlying genetic etiology. Initial molecular testing in both ca...

Molecular Markers and Cotton Genetic Improvement: Current Status and Future Prospects

Directory of Open Access Journals (Sweden)

Waqas Malik

2014-01-01

Full Text Available Narrow genetic base and complex allotetraploid genome of cotton (Gossypium hirsutum L. is stimulating efforts to avail required polymorphism for marker based breeding. The availability of draft genome sequence of G. raimondii and G. arboreum and next generation sequencing (NGS technologies facilitated the development of high-throughput marker technologies in cotton. The concepts of genetic diversity, QTL mapping, and marker assisted selection (MAS are evolving into more efficient concepts of linkage disequilibrium, association mapping, and genomic selection, respectively. The objective of the current review is to analyze the pace of evolution in the molecular marker technologies in cotton during the last ten years into the following four areas: (i comparative analysis of low- and high-throughput marker technologies available in cotton, (ii genetic diversity in the available wild and improved gene pools of cotton, (iii identification of the genomic regions within cotton genome underlying economic traits, and (iv marker based selection methodologies. Moreover, the applications of marker technologies to enhance the breeding efficiency in cotton are also summarized. Aforementioned genomic technologies and the integration of several other omics resources are expected to enhance the cotton productivity and meet the global fiber quantity and quality demands.

Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire: development and testing of a screening questionnaire for use in clinical cancer genetics

NARCIS (Netherlands)

Eijzenga, W.; Bleiker, E.M.A.; Hahn, D.E.E.; Kluijt, I.; Sidharta, G.N.; Gundy, C.; Aaronson, N.K.

2014-01-01

Background: Up to three-quarters of individuals who undergo cancer genetic counseling and testing report psychosocial problems specifically related to that setting. The objectives of this study were to develop and evaluate the screening properties of a questionnaire designed to assess specific

Vegetable Genetic Resources in China

Directory of Open Access Journals (Sweden)

Haiping WANG

2018-03-01

Full Text Available China is recognized as an important region for plant biodiversity based on its vast and historical collection of vegetable germplasm. The aim of this review is to describe the exploration status of vegetable genetic resources in China, including their collection, preservation, evaluation, and utilization. China has established a number of national-level vegetable genetic resources preservation units, including the National Mid-term Genebank for Vegetable Germplasm Resources, the National Germplasm Repository for Vegetatively-Propagated Vegetables, and the National Germplasm Repository for Aquatic Vegetables. In 2015, at least 36 000 accessions were collected and preserved in these units. In the past decade, 44 descriptors and data standards for different species have been published, and most accessions have been evaluated for screening the germplasms for specific important traits such as morphological characteristics, disease resistance, pest resistance, and stress tolerance. Moreover, the genetic diversity and evolution of some vegetable germplasms have been evaluated at the molecular level. Recently, more than 1 000 accessions were distributed to researchers and breeders each year by various means for vegetable research and production. However, additional wild-relative and abroad germplasms from other regions need to be collected and preserved in the units to expand genetic diversity. Furthermore, there is a need to utilize advanced techniques to better understand the background and genetic diversity of a wide range of vegetable genetic resources. This review will provide agricultural scientists’ insights into the genetic diversity in China and provide information on the distribution and potential utilization of these valuable genetic resources. Keywords: vegetable, genetic resource, preservation, evaluation, utilization