Science.gov

Sample records for molecular genetic study

  1. Molecular genetic study of human arginase deficiency

    PubMed Central

    Grody, Wayne W.; Klein, Deborah; Dodson, Amy E.; Kern, Rita M.; Wissmann, Paul B.; Goodman, Barbara K.; Bassand, Patrick; Marescau, Bert; Kang, Soo-Sang; Leonard, James V.; Cederbaum, Stephen D.

    1992-01-01

    We have explored the molecular pathology in 28 individuals homozygous or heterozygous for liver arginase deficiency (hyperargininemia) by a combination of Southern analysis, western blotting, DNA sequencing, and PCR. This cohort represents the majority of arginase-deficient individuals worldwide. Only 2 of 15 homozygous patients on whom red blood cells were available had antigenically cross-reacting material as ascertained by western blot analysis using anti–liver arginase antibody. Southern blots of patient genomic DNAs, cut with a variety of restriction enzymes and probed with a near-full-length (1,450-bp) human liver arginase cDNA clone, detected no gross gene deletions. Loss of a TaqI cleavage site was identified in three individuals: in a homozygous state in a Saudi Arabian patient at one site, at a different site in homozygosity in a German patient, and in heterozygosity in a patient from Australia. The changes in the latter two were localized to exon 8, through amplification of this region by PCR and electrophoretic analysis of the amplified fragment after treatment with TaqI; the precise base changes (Arg291X and Thr290Ser) were confirmed by sequencing. It it interesting that the latter nucleotide variant (Thr290Ser) was found to lie adjacent to the TaqI site rather than within it, though whether such a conservative amino acid substitution represents a true pathologic mutation remains to be determined. We conclude that arginase deficiency, though rare, is a heterogeneous disorder at the genotypic level, generally encompassing a variety of point mutations rather than substantial structural gene deletions. ImagesFigure 1Figure 3Figure 4Figure 5 PMID:1598908

  2. Molecular Genetic Strategies in the Study of Corticohippocampal Circuits.

    PubMed

    Angelakos, Christopher C; Abel, Ted

    2015-07-01

    The first reproductively viable genetically modified mice were created in 1982 by Richard Palmiter and Ralph Brinster (Palmiter RD, Brinster RL, Hammer RE, Trumbauer ME, Rosenfeld MG, Birnberg NC, Evans RM. 1982. Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature 300: 611-615). In the subsequent 30 plus years, numerous ground-breaking technical advancements in genetic manipulation have paved the way for improved spatially and temporally targeted research. Molecular genetic studies have been especially useful for probing the molecules and circuits underlying how organisms learn and remember—one of the most interesting and intensively investigated questions in neuroscience research. Here, we discuss selected genetic tools, focusing on corticohippocampal circuits and their implications for understanding learning and memory. PMID:26134320

  3. Genetic breeding and diversity of the genus Passiflora: progress and perspectives in molecular and genetic studies.

    PubMed

    Cerqueira-Silva, Carlos Bernard M; Jesus, Onildo N; Santos, Elisa S L; Corrêa, Ronan X; Souza, Anete P

    2014-01-01

    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. PMID:25196515

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

    PubMed Central

    Cerqueira-Silva, Carlos Bernard M.; Jesus, Onildo N.; Santos, Elisa S. L.; Corrêa, Ronan X.; Souza, Anete P.

    2014-01-01

    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. PMID:25196515

  5. Applications of Molecular Genetics to the Study of Asthma.

    PubMed

    Sanz-Lozano, Catalina S; García-Solaesa, Virginia; Davila, Ignacio; Isidoro-García, María

    2016-01-01

    Asthma is a multifactorial disease. This fact, associated to the diversity of asthma phenotypes, has made difficult to obtain a clear pattern of inheritance. With the huge development of molecular genetics technologies, candidate gene studies are giving way to different types of studies from the genomic point of view.These approaches are allowing the identification of several genes associated with asthma. However, in these studies, there are some conflicting results between different populations and there is still a lack of knowledge about the actual influence of the gene variants. Some confounding factors are, among others, the inappropriate sample size, population stratification, differences in the classification of the phenotypes, or inadequate coverage of the genes.To confirm the real effect of the reported associations, it is necessary to consider both the genetic and environmental factors and perform functional studies that explain the molecular mechanisms mediating between the emergence of gene variants and the development of the disease.The development of experimental techniques opens a new horizon that allows the identification of major genetic factors of susceptibility to asthma. The resulting classification of the population groups based on their genetic characteristics, will allow the application of specific and highly efficient treatments. PMID:27300527

  6. Soybean Molecular Genetic Diversity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A history of the various DNA marker types used in the assessment of molecular genetic diversity in soybean [Glycine max (L.) Merr.] is followed by a description of a number of studies on the assessment of genetic diversity. These studies include a review of reports on 1) the quantification and comp...

  7. Hamartomatous polyps - a clinical and molecular genetic study.

    PubMed

    Jelsig, Anne Marie

    2016-08-01

    Hamartomatous polyps (HPs) in the gastrointestinal (GI) tract are rare compared to other types of GI polyps, yet they are the most common type of polyp in children. The symptoms are usually rectal bleeding, abdominal pain, obstipation, anaemia, and/or small bowel obstruction. The polyps are typically removed concurrently with endoscopy when located in the colon, rectum, or stomach, whereas polyps in the small bowel are removed during push-enteroscopy, device-assisted enteroscopy, or by surgery. HPs can be classified as juvenile polyps or Peutz-Jeghers polyps based on their histopathological 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 syndromes (HPS). Patients with HPS have an increased risk of cancer, recurrences of polyps, and extraintestinal complications. The syndromes are important to diagnose, as patients should be offered surveillance from childhood or early adolescence. The syndromes include juvenile polyposis syndrome, Peutz-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 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 in the colon and rectum in Denmark in 1995-2014. Based on the Danish Pathology Data Bank we found that 1772 patients had 2108 JPs examined in the period, and we

  8. Choosing the right molecular genetic markers for studying biodiversity: from molecular evolution to practical aspects.

    PubMed

    Chenuil, Anne; Anne, Chenuil

    2006-05-01

    The use of molecular genetic markers (MGMs) has become widespread among evolutionary biologists, and the methods of analysis of genetic data improve rapidly, yet an organized framework in which scientists can work is lacking. Elements of molecular evolution are summarized to explain the origin of variation at the DNA level, its measures, and the relationships linking genetic variability to the biological parameters of the studied organisms. MGM are defined by two components: the DNA region(s) screened, and the technique used to reveal its variation. Criteria of choice belong to three categories: (1) the level of variability, (2) the nature of the information (e.g. dominance vs. codominance, ploidy, ... ) which must be determined according to the biological question and (3) some practical criteria which mainly depend on the equipment of the laboratory and experience of the scientist. A three-step procedure is proposed for drawing up MGMs suitable to answer given biological questions, and compiled data are organized to guide the choice at each step: (1) choice, determined by the biological question, of the level of variability and of the criteria of the nature of information, (2) choice of the DNA region and (3) choice of the technique. PMID:16850217

  9. A molecular-genetic approach to studying source-sink interactions in Arabidopsis thalian. Final report

    SciTech Connect

    Gibson, S. I.

    2000-06-01

    This is a final report describing the results of the research funded by the DOE Energy Biosciences Program grant entitled ''A Molecular-Genetic Approach to Studying Source-Sink Interactions in Arabidiopsis thaliana''.

  10. Introductory molecular genetics

    SciTech Connect

    Edwards-Moulds, J.

    1986-01-01

    This book begins with an overview of the current principles of genetics and molecular genetics. Over this foundation, it adds detailed and specialized information: a description of the translation, transcription, expression and regulation of DNA and RNA; a description of the manipulation of genetic material via promoters, enhancers, and gene splicing; and a description of cloning techniques, especially those for blood group genes. The last chapter looks to the impact of molecular genetics on transfusion medicine.

  11. Biochemical and Molecular Genetic Studies on Biosilica Morphogenesis in Diatoms

    NASA Astrophysics Data System (ADS)

    Kroger, N.; Poulsen, N.

    2006-12-01

    Diatoms are a large group of unicellular microalgae encased by silica cell walls that exhibit species-specific micro-and nanopatterns. Previously, we have characterized from diatoms unique phosphoproteins (termed silaffins) and unusually long polyamine chains (termed LCPA), which have both been implicated in biosilica formation. While the chemical structures of LCPA are largely conserved among different diatom species, the silaffins exhibit extensive structural variations. In vitro studies on the silica formation activities of silaffins and LCPA from the diatom Thalassiosira pseudonana indicate that silica morphogenesis is primarily determined by silaffins rather than LCPA. Recently, the complete genome sequence of T. pseudonana has become available, which for the first time opens the door to employ functional genomic approaches for studying the mechanism of silica biomineralization. To this end we have established the first genetic transformation system for T. pseudonana, which will be instrumental for analyzing the functions of silaffins in vivo, and for identifying new components of the diatom silica forming machinery. Here we describe the current knowledge on the structures and properties of silaffins and LCPA, the methods for genetic manipulation of T. pseudonana, and the first experimental steps towards functional genomics in diatoms.

  12. Clusters of Concepts in Molecular Genetics: A Study of Swedish Upper Secondary Science Students' Understanding

    ERIC Educational Resources Information Center

    Gericke, Niklas; Wahlberg, Sara

    2013-01-01

    To understand genetics, students need to be able to explain and draw connections between a large number of concepts. The purpose of the study reported herein was to explore the way upper secondary science students reason about concepts in molecular genetics in order to understand protein synthesis. Data were collected by group interviews. Concept…

  13. Molecular genetics of ependymoma

    PubMed Central

    Yao, Yuan; Mack, Stephen C.; Taylor, Michael D.

    2011-01-01

    Brain tumors are the leading cause of cancer death in children, with ependymoma being the third most common and posing a significant clinical burden. Its mechanism of pathogenesis, reliable prognostic indicators, and effective treatments other than surgical resection have all remained elusive. Until recently, ependymoma research was hindered by the small number of tumors available for study, low resolution of cytogenetic techniques, and lack of cell lines and animal models. Ependymoma heterogeneity, which manifests as variations in tumor location, patient age, histological grade, and clinical behavior, together with the observation of a balanced genomic profile in up to 50% of cases, presents additional challenges in understanding the development and progression of this disease. Despite these difficulties, we have made significant headway in the past decade in identifying the genetic alterations and pathways involved in ependymoma tumorigenesis through collaborative efforts and the application of microarray-based genetic (copy number) and transcriptome profiling platforms. Genetic characterization of ependymoma unraveled distinct mRNA-defined subclasses and led to the identification of radial glial cells as its cell type of origin. This review summarizes our current knowledge in the molecular genetics of ependymoma and proposes future research directions necessary to further advance this field. PMID:21959044

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

    ERIC Educational Resources Information Center

    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…

  15. Primer on molecular genetics

    SciTech Connect

    Not Available

    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.

  16. Twin Studies and Their Implications for Molecular Genetic Studies: Endophenotypes Integrate Quantitative and Molecular Genetics in ADHD Research

    ERIC Educational Resources Information Center

    Wood, Alexis C.; Neale, Michael C.

    2010-01-01

    Objective: To describe the utility of twin studies for attention-deficit/hyperactivity disorder (ADHD) research and demonstrate their potential for the identification of alternative phenotypes suitable for genomewide association, developmental risk assessment, treatment response, and intervention targets. Method: Brief descriptions of the classic…

  17. Molecular Genetic Studies of Gene Identification for Osteoporosis: A 2004 Update

    PubMed Central

    Liu, Yong-Jun; Shen, Hui; Xiao, Peng; Xiong, Dong-Hai; Li, Li-Hua; Recker, Robert R; Deng, Hong-Wen

    2007-01-01

    This review summarizes comprehensively the most important and representative molecular genetics studies of gene identification for osteoporosis published up to the end of December 2004. It is intended to constitute a sequential update of our previously published review covering the available data up to the end of 2002. Evidence from candidate gene association studies and genome-wide linkage studies in humans, as well as quantitative trait locus mapping animal models are reviewed separately. Studies of transgenic and knockout mice models relevant to osteoporosis are summarized. An important extension of this update is incorporation of functional genomic studies (including DNA microarrays and proteomics) on osteogenesis and osteoporosis, in light of the rapid advances and the promising prospects of the field. Comments are made on the most notable findings and representative studies for their potential influence and implications on our present understanding of genetics of osteoporosis. The format adopted by this review should be ideal for accommodating future new advances and studies. PMID:16995806

  18. Molecular genetic study of introgression between Saccharomyces bayanus and S. cerevisiae.

    PubMed

    Naumova, Elena S; Naumov, Gennadi I; Masneuf-Pomarède, Isabelle; Aigle, Michel; Dubourdieu, Denis

    2005-10-30

    The genomic constitution of different S. bayanus strains and natural interspecific Saccharomyces hybrids has been studied by genetic and molecular methods. Unlike S. bayanus var. uvarum, some S. bayanus var. bayanus strains (the type culture CBS 380, CBS 378, CBS 425, CBS 1548) harbour a number of S. cerevisiae subtelomeric sequences: Y', pEL50, SUC, RTM and MAL. The two varieties, having 86-100% nDNA-nDNA reassociation, are partly genetically isolated from one another but completely isolated from S. cerevisiae. Genetic and molecular data support the maintaining of var. bayanus and var. uvarum strains in the species S. bayanus. Using Southern hybridization with species-specific molecular markers, RFLP of the MET2 gene and flow cytometry analysis, we showed that the non-S. cerevisiae parents are different in lager brewing yeasts and in wine hybrid strains. Our results suggest that S. pastorianus is a hybrid between S. cerevisiae and S. bayanus var. bayanus, while S. bayanus var. uvarum contributed to the formation of the wine hybrids S6U and CID1. According to the partial sequence of ACT1 gene and flow cytometry analysis, strain CID1 is a triple hybrid between S. cerevisiae, S. kudriavzevii and S. bayanus var. uvarum. PMID:16240458

  19. Molecular genetic and molecular evolutionary studies on the bacteriochlorophyll synthesis genes of Rhodobacter capsulatus

    SciTech Connect

    Burke-Agueero, D.H.

    1992-08-01

    Rhodobacter capsulatus, purple bacterium capable of either aerobic or photosynthetic growth, has proven to be very useful in genetic studies of photosynthesis. Forty-four genes clustered together within a 46 kilobase region are required to establish photosynthetic ability in R. capsulatus. Approximately twenty of these genes are involved in bacteriochlorophyll synthesis of which eight ``bch`` genes are the subject of this thesis. Six of these genes were found to code for the two ring reductases. The first converts protochlorophyllide (PChlide) into a chlorin, the immediate precursor to chlorophyll a, and then into a bacteriochlorin. Each reductase is shown to be made up of three subunits. PChlide reductase is coded by the genes bchN, bchB, and bchL. Proteins with amino acid sequences markedly similar to those of bchN and bchL have been shown in other organisms to be required for chlorophyll synthesis; hence, their designation as chlN and chlB. A third chloroplast-encoded gene of heretofore unknown function shares amino acid identities with bchB and is probably the third subunit of the plant PChlide reductase. The bchA locus, which encodes the chlorin reductase, is found to be made up of three separate, translationally coupled genes, referred to as bchX, bchY, and bchZ. Amino acid similarities between bchX, bchL, and the nitrogenase reductase protein nifH suggest that all three classes of proteins share certain three-dimensional structural features, including elements that are central to the enzymatic mechanism of nifH. PChlide reductase and chlorin reductase are clearly derived from a common ancestor. Several lines of analysis suggests the ancestor of both enzyme systems reduced PChlide twice to produce bacteriochlorophyll supporting the concept bacteriochlorophyll as the ancestral reaction center pigment.

  20. Molecular genetic and molecular evolutionary studies on the bacteriochlorophyll synthesis genes of Rhodobacter capsulatus

    SciTech Connect

    Burke-Agueero, D.H.

    1992-08-01

    Rhodobacter capsulatus, purple bacterium capable of either aerobic or photosynthetic growth, has proven to be very useful in genetic studies of photosynthesis. Forty-four genes clustered together within a 46 kilobase region are required to establish photosynthetic ability in R. capsulatus. Approximately twenty of these genes are involved in bacteriochlorophyll synthesis of which eight bch'' genes are the subject of this thesis. Six of these genes were found to code for the two ring reductases. The first converts protochlorophyllide (PChlide) into a chlorin, the immediate precursor to chlorophyll a, and then into a bacteriochlorin. Each reductase is shown to be made up of three subunits. PChlide reductase is coded by the genes bchN, bchB, and bchL. Proteins with amino acid sequences markedly similar to those of bchN and bchL have been shown in other organisms to be required for chlorophyll synthesis; hence, their designation as chlN and chlB. A third chloroplast-encoded gene of heretofore unknown function shares amino acid identities with bchB and is probably the third subunit of the plant PChlide reductase. The bchA locus, which encodes the chlorin reductase, is found to be made up of three separate, translationally coupled genes, referred to as bchX, bchY, and bchZ. Amino acid similarities between bchX, bchL, and the nitrogenase reductase protein nifH suggest that all three classes of proteins share certain three-dimensional structural features, including elements that are central to the enzymatic mechanism of nifH. PChlide reductase and chlorin reductase are clearly derived from a common ancestor. Several lines of analysis suggests the ancestor of both enzyme systems reduced PChlide twice to produce bacteriochlorophyll supporting the concept bacteriochlorophyll as the ancestral reaction center pigment.

  1. Substantial genetic link between IQ and working memory: implications for molecular genetic studies on schizophrenia. the European twin study of schizophrenia (EUTwinsS).

    PubMed

    Goldberg, Ximena; Alemany, Silvia; Rosa, Araceli; Picchioni, Marco; Nenadic, Igor; Owens, Sheena F; Rijsdijk, Fruhling; Rebollo, Irene; Sauer, Heinrich; Murray, Robin M; Fañanás, Lourdes; Toulopoulou, Timothea

    2013-06-01

    While evidence is accumulating to support specific neurocognitive deficits as putative endophenotypes for schizophrenia, the heritability of these deficits in healthy subjects and whether they share common genetic influences, is not well established. In the present study, 529 healthy adult twins from two centers within the European Twin Study Network on Schizophrenia (EUTwinsS) were assessed on two domains that are consistently found to be particularly compromised in schizophrenia. Specifically, Intellectual Quotient Score (IQ) and the Letter-Number Sequencing Test (LNS), a measure of working memory, were measured in all twins. Latent variable components were explored through structural equation modeling, and common genetic underpinnings were examined using bivariate analyses. Results showed that the phenotypic correlation between IQ and working memory was almost entirely attributed to shared genetic variance (95.5%). We discuss the potential use of a combined measure of IQ and working memory to improve the power of molecular studies in detecting the genetic mechanisms underlying schizophrenia. PMID:23650229

  2. Molecular Genetic Studies of Gene Identification for Osteoporosis: The 2009 Update

    PubMed Central

    Xu, Xiang-Hong; Dong, Shan-Shan; Guo, Yan; Yang, Tie-Lin; Lei, Shu-Feng; Papasian, Christopher J.; Zhao, Ming; Deng, Hong-Wen

    2010-01-01

    Osteoporosis is a complex human disease that results in increased susceptibility to fragility fractures. It can be phenotypically characterized using several traits, including bone mineral density, bone size, bone strength, and bone turnover markers. The identification of gene variants that contribute to osteoporosis phenotypes, or responses to therapy, can eventually help individualize the prognosis, treatment, and prevention of fractures and their adverse outcomes. Our previously published reviews have comprehensively summarized the progress of molecular genetic studies of gene identification for osteoporosis and have covered the data available to the end of September 2007. This review represents our continuing efforts to summarize the important and representative findings published between October 2007 and November 2009. The topics covered include genetic association and linkage studies in humans, transgenic and knockout mouse models, as well as gene-expression microarray and proteomics studies. Major results are tabulated for comparison and ease of reference. Comments are made on the notable findings and representative studies for their potential influence and implications on our present understanding of the genetics of osteoporosis. PMID:20357209

  3. Studying human disease genes in Caenorhabditis elegans: a molecular genetics laboratory project.

    PubMed

    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 associated with human disease. In a large-enrollment, sophomore-level laboratory course, groups of three to four students were assigned a gene associated with either breast cancer (brc-1), Wilson disease (cua-1), ovarian dysgenesis (fshr-1), or colon cancer (mlh-1). Students compared observable phenotypes of wild-type C. elegans and C. elegans with a homozygous deletion in the assigned gene. They confirmed the genetic deletion with nested polymerase chain reaction and performed a bioinformatics analysis to predict how the deletion would affect the encoded mRNA and protein. Students also performed RNA interference (RNAi) against their assigned gene and evaluated whether RNAi caused a phenotype similar to that of the genetic deletion. As a capstone activity, students prepared scientific posters in which they presented their data, evaluated whether C. elegans was a useful model system for studying their assigned genes, and proposed future directions. Assessment showed gains in understanding genotype versus phenotype, RNAi, common bioinformatics tools, and the utility of model organisms. PMID:22665589

  4. Molecular genetics of alopecias.

    PubMed

    Ramot, Yuval; Zlotogorski, Abraham

    2015-01-01

    Recent developments in research methods and techniques, such as whole-exome and -genome sequencing, have substantially improved our understanding of genetic conditions. Special progress has been made in the field of genotrichoses, or hereditary hair diseases, a field that has been obscure for many years. The underlying genes for many of the monogenic hair diseases are now known. Additionally, complex analyses of large cohorts of patients have given us the first clues to the genes associated with polygenic hair disorders, such as androgenetic alopecia and alopecia areata. Thanks to these major findings, the sophisticated regulation of the morphogenesis, development and growth of hair follicles has begun to be revealed, and new players in this delicate molecular interplay have been exposed. PMID:26370647

  5. Molecular genetics of retinitis pigmentosa.

    PubMed Central

    Farber, D. B.; Heckenlively, J. R.; Sparkes, R. S.; Bateman, J. B.

    1991-01-01

    Retinitis pigmentosa is a model for the study of genetic diseases. Its genetic heterogeneity is reflected in the different forms of inheritance (autosomal dominant, autosomal recessive, or X-linked) and, in a few families, in the presence of mutations in the visual pigment rhodopsin. Clinical and molecular genetic studies of these disorders are discussed. Animal models of retinal degeneration have been investigated for many years with the hope of gaining insight into the cause of photoreceptor cell death. Recently, the genes responsible for two of these animal disorders, the rds and rd mouse genes, have been isolated and characterized. The retinal degeneration of the rd mouse is presented in detail. The possible involvement of human analogues of these mouse genes in human retinal diseases is being investigated. Images PMID:1771877

  6. [Advances in the studies on the molecular and genetic aspects of epilepsy].

    PubMed

    Wang, Xu; Wang, Tao; Yuan, Ming-xiong; Liu, Mu-gen; Wang, Qing

    2005-06-01

    Epilepsy is one of the most common and debilitating neurological diseases that affects more than 40 million people worldwide. Genetic factors contribute to the pathogenesis of epilepsy. Molecular genetic studies have identified 15 disease-causing genes for epilepsy. The majority of the genes encode ion channels, including voltage-gated potassium channels KCNQ2 and KCNQ3, sodium channels SCN1A, SCN2A, and SCN1B, chloride channels CLCN2, and ligand-gated ion channels CHRNA4, CHRNB2, GABRG2, and GABRA1. Interestingly, non-ion channel genes have also been identified as epilepsy genes, and these genes include G-protein-coupled receptor MASS1/VLGR1, GM3 synthase, and proteins with unknown functions such as LGI1, NHLRC1, and EFHC1. These studies make genetic testing possible in some patients, and further characterization of the identified epilepsy genes may lead to the development of new drugs and new treatments for patients with epilepsy. PMID:16038283

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

    PubMed

    de Oliveira Francisco, Flávio; Santiago, Leandro Rodrigues; Arias, Maria Cristina

    2013-03-01

    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. PMID:23569417

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

    PubMed Central

    de Oliveira Francisco, Flávio; Santiago, Leandro Rodrigues; Arias, Maria Cristina

    2013-01-01

    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. PMID:23569417

  9. Evolving Molecular Genetics of Glioblastoma

    PubMed Central

    Li, Qiu-Ju; Cai, Jin-Quan; Liu, Cheng-Yin

    2016-01-01

    Objective: To summary the recent advances in molecular research of glioblastoma (GBM) and current trends in personalized therapy of this disease. Data Sources: Data cited in this review were obtained mainly from PubMed in English up to 2015, with keywords “molecular”, “genetics”, “GBM”, “isocitrate dehydrogenase”, “telomerase reverse transcriptase”, “epidermal growth factor receptor”, “PTPRZ1-MET”, and “clinical treatment”. Study Selection: Articles regarding the morphological pathology of GBM, the epidemiology of GBM, genetic alteration of GBM, and the development of treatment for GBM patients were identified, retrieved, and reviewed. Results: There is a large amount of data supporting the view that these recurrent genetic aberrations occur in a specific context of cellular origin, co-oncogenic hits and are present in distinct patient populations. Primary and secondary GBMs are distinct disease entities that affect different age groups of patients and develop through distinct genetic aberrations. These differences are important, especially because they may affect sensitivity to radio- and chemo-therapy and should thus be considered in the identification of targets for novel therapeutic approaches. Conclusion: This review highlights the molecular and genetic alterations of GBM, indicating that they are of potential value in the diagnosis and treatment for patients with GBM. PMID:26879021

  10. Molecular genetics of Thiobacillus ferrooxidans.

    PubMed Central

    Rawlings, D E; Kusano, T

    1994-01-01

    Thiobacillus ferrooxidans is a gram-negative, highly acidophilic (pH 1.5 to 2.0), autotrophic bacterium that obtains its energy through the oxidation of ferrous iron or reduced inorganic sulfur compounds. It is usually dominant in the mixed bacterial populations that are used industrially for the extraction of metals such as copper and uranium from their ores. More recently, these bacterial consortia have been used for the biooxidation of refractory gold-bearing arsenopyrite ores prior to the recovery of gold by cyanidation. The commercial use of T. ferrooxidans has led to an increasing interest in the genetics and molecular biology of the bacterium. Initial investigations were aimed at determining whether the unique physiology and specialized habitat of T. ferrooxidans had been accompanied by a high degree of genetic drift from other gram-negative bacteria. Early genetic studies were comparative in nature and concerned the isolation of genes such as nifHDK, glnA, and recA, which are widespread among bacteria. From a molecular biology viewpoint, T. ferrooxidans appears to be a typical member of the proteobacteria. In most instances, cloned gene promoters and protein products have been functional in Escherichia coli. Although T. ferrooxidans has proved difficult to transform with DNA, research on indigenous plasmids and the isolation of the T. ferrooxidans merA gene have resulted in the development of a low-efficiency electroporation system for one strain of T. ferrooxidans. The most recent studies have focused on the molecular genetics of the pathways associated with nitrogen metabolism, carbon dioxide fixation, and components of the energy-producing mechanisms. PMID:8177170

  11. Applying Genetics and Molecular Biology to the Study of the Human Pathogen Cryptococcus neoformans

    PubMed Central

    Chun, Cheryl D.; Madhani, Hiten D.

    2013-01-01

    The basidiomycete yeast Crytococcus neoformans is a prominent human pathogen. It primarily infects immunocompromised individuals producing a meningoencephalitis that is lethal if untreated. Recent advances in its genetics and molecular biology have made it a model system for understanding both the Basidiomycota phylum and mechanisms of fungal pathogenesis. The relative ease of experimental manipulation coupled with the development of murine models for human disease allow for powerful studies in the mechanisms of virulence and host responses. This chapter introduces the organism and its life cycle and then provides detailed step-by-step protocols for culture, manipulation of the genome, analysis of nucleic acids and proteins, and assessment of virulence and expression of virulence factors. PMID:20946836

  12. Heritability and Molecular-Genetic Basis of Resting EEG Activity: A Genome-Wide Association Study

    PubMed Central

    Malone, Stephen M.; Burwell, Scott J.; Vaidyanathan, Uma; Miller, Michael B.; McGue, Matt; Iacono, William G.

    2014-01-01

    Several EEG parameters are potential endophenotypes for different psychiatric disorders. The present study consists of a comprehensive behavioral- and molecular-genetic analysis of such parameters in a large community sample (N = 4,026) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric heritability estimates ranged from .49 to .85, with a median of .78. The additive effect of all SNPs (SNP heritability) varied across electrodes. Although individual SNPs were not significantly associated with EEG parameters, several genes were associated with delta power. We also obtained an association between the GABRA2 gene and beta power (p < .014), consistent with findings reported by others, although this did not survive Bonferroni correction. If EEG parameters conform to a largely polygenic model of inheritance, larger sample sizes will be required to detect individual variants reliably. PMID:25387704

  13. Genetic approaches for studying myiasis-causing flies: molecular markers and mitochondrial genomics.

    PubMed

    de Azeredo-Espin, Ana Maria Lima; Lessinger, Ana Cláudia

    2006-01-01

    "Myiasis-causing flies" is a generic term that includes species from numerous dipteran families, mainly Calliphoridae and Oestridae, of which blowflies, screwworm flies and botflies are among the most important. This group of flies is characterized by the ability of their larvae to develop in animal flesh. When the host is a live vertebrate, such parasitism by dipterous larvae is known as primary myiasis. Myiasis-causing flies can be classified as saprophagous (free-living species), facultative or obligate parasites. Many of these flies are of great medical and veterinary importance in Brazil because of their role as key livestock insect-pests and vectors of pathogens, in addition to being considered important legal evidence in forensic entomology. The characterization of myiasis-causing flies using molecular markers to study mtDNA (by RFLP) and nuclear DNA (by RAPD and microsatellite) has been used to identify the evolutionary mechanisms responsible for specific patterns of genetic variability. These approaches have been successfully used to analyze the population structures of the New World screwworm fly Cochliomyia hominivorax and the botfly Dermatobia hominis. In this review, various aspects of the organization, evolution and potential applications of the mitochondrial genome of myiasis-causing flies in Brazil, and the analysis of nuclear markers in genetic studies of populations, are discussed. PMID:16502089

  14. Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction

    PubMed Central

    Engleman, Eric A.; Katner, Simon N.; Neal-Beliveau, Bethany S.

    2016-01-01

    Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH’s effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system–dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine

  15. Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction.

    PubMed

    Engleman, Eric A; Katner, Simon N; Neal-Beliveau, Bethany S

    2016-01-01

    Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH's effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system-dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine neurotransmission

  16. Understanding the molecular basis of celiac disease: what genetic studies reveal.

    PubMed

    Monsuur, Alienke J; Wijmenga, Cisca

    2006-01-01

    Celiac disease (CD) is characterized by a chronic immune reaction in the small intestine to the gluten proteins that are present in a (Western) daily diet. Besides the well known involvement of the HLA class II histocompatibility antigen (HLA)-DQ2.5 and -DQ8 heterodimers (encoded by particular combinations of the HLA-DQA1 and -DQB1 gene) in CD and the minor contribution of the CTLA-4 gene, recently the myosin IXB (MYO9B) gene has also been found to be genetically associated. This review covers the general aspects of CD as well as current insight into important molecular aspects. We evaluate the role of susceptibility genes in CD by following gluten along its path from ingestion to uptake in the body, which leads us through the three aspects of CD's pathology. The first is the presence of gluten in the lumen of the intestine, where it is broken down by several enzymes. The second is the intestinal barrier through which gluten peptides pass. The third is the reaction of the immune system in response to gluten peptides, in which both the innate and the adaptive immune systems play a role. Our main conclusion, based on the current genetic and functional studies, is that we should look for causal genes in the barrier function as well as in the immune systems. PMID:17438672

  17. Molecular Genetics of Mycobacteriophages

    PubMed Central

    HATFULL, GRAHAM F.

    2014-01-01

    Mycobacteriophages have provided numerous essential tools for mycobacterial genetics, including delivery systems for transposons, reporter genes, and allelic exchange substrates, and components for plasmid vectors and mutagenesis. Their genetically diverse genomes also reveal insights into the broader nature of the phage population and the evolutionary mechanisms that give rise to it. The substantial advances in our understanding of the biology of mycobacteriophages including a large collection of completely sequenced genomes indicates a rich potential for further contributions in tuberculosis genetics and beyond. PMID:25328854

  18. [Molecular genetics study of hereditary spastic paraplegia accompanied by distal amyotrophy-an update].

    PubMed

    Wang, Zhen-zhen; Cen, Zhi-dong; Luo, Wei

    2013-08-01

    Hereditary spastic paraplegia(HSP or SPG) is a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive spasticity, weakness of lower limbs, and pathologically by retrograde axonal degeneration of corticospinal tracts and posterior spinal tracts. Presence of additional features allows differentiation between simple and complex forms of the disease. Genetically, 16 loci for HSP accompanied by distal amyotrophy have been mapped, for which 13 genes have been identified. With the identification of causative genes, the molecular mechanism of this disease is gradually elucidated. PMID:23926010

  19. Are Endophenotypes Based on Measures of Executive Functions Useful for Molecular Genetic Studies of ADHD?

    ERIC Educational Resources Information Center

    Doyle, Alysa E.; Faraone, Stephen V.; Seidman, Larry J.; Willcutt, Erik G.; Nigg, Joel T.; Waldman, Irwin D.; Pennington, Bruce F.; Peart, Joanne; Biederman, Joseph

    2005-01-01

    Background: Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or…

  20. X-linked ichthyosis without STS deficiency: Clinical, genetical, and molecular studies

    SciTech Connect

    Robledo, R.; Melis, P.; Schillinger, E.; Siniscalco, M.

    1995-11-06

    We report on a Sardinian pedigree with congenital ichthyosis associated with normal levels of steroid sulfatase and a normal molecular pattern, as detectable with a cDNA probe for the steroid sulfatase (STS) gene. Though the pattern of transmission of the disease is consistent with X-linked recessive inheritance, this form of ichthyosis was found to segregate independently of genetic polymorphisms detected by probes of the region Xp22.3, where the STS locus has been mapped. The search for close genetic linkages with other polymorphic markers scattered along the entire X chromosome has so far been fruitless. For the time being, the main conclusion derived from these data is that STS deficiency is not a sine qua non for X-linked ichthyosis which may also result from a mutational event at an X-chromosomal site genetically unlinked to the STS locus. 16 refs., 4 figs.

  1. Molecular evaluation of genetic diversity and association studies in rice (Oryza sativa L.).

    PubMed

    Vanniarajan, C; Vinod, K K; Pereira, Andy

    2012-01-01

    In the present study, we tested rice genotypes that included un(der)exploited landraces of Tamil Nadu along with indica and japonica test cultivars to ascertain their genetic diversity structure. Highly polymorphic microsatellite markers were used for generating marker segregation data. A novel measure, allele discrimination index, was used to determine subpopulation differentiation power of each marker. Phenotypic data were collected for yield and component traits. Pattern of molecular differentiation separated indica and japonica genotypes; indica genotypes had two subpopulations within. Landraces were found to have indica genome, but formed a separate subgroup with low linkage disequilibrium. The landraces further separated into distinct group in both hierarchical clustering analysis using neighbour-joining method as well as in the model based population structure analysis. Japonica and the remaining indica cultivars formed two other distinct groups. Linkage disequilibrium observed in the whole population was considerably reduced in subpopulations. Low linkage disequilibrium of landforms suggests their narrow adaptation in local geographical niche. Many population specific alleles could be identified particularly for japonica cultivars and landraces. Association analysis revealed nine marker-trait associations with three agronomic traits, of which 67% were previously reported. Although the testing landraces together with known cultivars had permitted genomewide association mapping, the experiment offers scope to study more landraces collected from the entire geographical region for drawing more reliable information. PMID:22546822

  2. Molecular Genetics in Glaucoma

    PubMed Central

    Liu, Yutao

    2015-01-01

    Glaucoma is a family of diseases whose pathology is defined by the progressive loss of retinal ganglion cells. Clinically, glaucoma presents as a distinctive optic neuropathy with associated visual field loss. Primary open-angle glaucoma (POAG), chronic angle closure glaucoma (ACG), and exfoliation glaucoma (XFG) are the most prevalent forms of glaucoma globally and are the most common causes of glaucoma-related blindness worldwide. A host of genetic and environmental factors contribute to glaucoma phenotypes. This review examines the current status of genetic investigations of POAG, ACG, XFG, including the less common forms of glaucoma primary congenital glaucoma (PCG), the developmental glaucomas, and pigment dispersion glaucoma. PMID:21871452

  3. Molecular genetic and quantitative trait divergence associated with recent homoploid hybrid speciation: a study of Senecio squalidus (Asteraceae).

    PubMed

    Brennan, A C; Barker, D; Hiscock, S J; Abbott, R J

    2012-02-01

    Hybridization is increasingly seen as a trigger for rapid evolution and speciation. To quantify and qualify divergence associated with recent homoploid hybrid speciation, we compared quantitative trait (QT) and molecular genetic variation between the homoploid hybrid species Senecio squalidus and its parental species, S. aethnensis and S. chrysanthemifolius, and also their naturally occurring Sicilian hybrids. S. squalidus originated and became invasive in the United Kingdom following the introduction of hybrid plants from Mount Etna, Sicily, about 300 years ago. We recorded considerable molecular genetic differentiation between S. squalidus and its parents and their Sicilian hybrids in terms of both reduced genetic diversity and altered allele frequencies, potentially due to the genetic bottleneck associated with introduction to the United Kingdom. S. squalidus is also distinct from its parents and Sicilian hybrids for QTs, but less so than for molecular genetic markers. We suggest that this is due to resilience of polygenic QTs to changes in allele frequency or lack of selection for hybrid niche divergence in geographic isolation. While S. squalidus is intermediate or parental-like for most QTs, some trangressively distinct traits were observed, which might indicate emerging local adaptation in its invasive range. This study emphasizes the important contribution of founder events and geographic isolation to successful homoploid hybrid speciation. PMID:21829224

  4. Molecular genetic and quantitative trait divergence associated with recent homoploid hybrid speciation: a study of Senecio squalidus (Asteraceae)

    PubMed Central

    Brennan, A C; Barker, D; Hiscock, S J; Abbott, R J

    2012-01-01

    Hybridization is increasingly seen as a trigger for rapid evolution and speciation. To quantify and qualify divergence associated with recent homoploid hybrid speciation, we compared quantitative trait (QT) and molecular genetic variation between the homoploid hybrid species Senecio squalidus and its parental species, S. aethnensis and S. chrysanthemifolius, and also their naturally occurring Sicilian hybrids. S. squalidus originated and became invasive in the United Kingdom following the introduction of hybrid plants from Mount Etna, Sicily, about 300 years ago. We recorded considerable molecular genetic differentiation between S. squalidus and its parents and their Sicilian hybrids in terms of both reduced genetic diversity and altered allele frequencies, potentially due to the genetic bottleneck associated with introduction to the United Kingdom. S. squalidus is also distinct from its parents and Sicilian hybrids for QTs, but less so than for molecular genetic markers. We suggest that this is due to resilience of polygenic QTs to changes in allele frequency or lack of selection for hybrid niche divergence in geographic isolation. While S. squalidus is intermediate or parental-like for most QTs, some trangressively distinct traits were observed, which might indicate emerging local adaptation in its invasive range. This study emphasizes the important contribution of founder events and geographic isolation to successful homoploid hybrid speciation. PMID:21829224

  5. [Molecular genetics of Parkinson's disease].

    PubMed

    Toda, Tatsushi

    2007-08-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder in the world. The occurrence of PD is largely sporadic, while several families with Mendelian segregation of PD have been reported. PD is thought to be caused by mitochondrial dysfunction, oxidative stress and inflammation based on multiple genetic and environmental factors, resulting in the apoptosis of dopaminergic cells. Six causal genes for Mendelian inherited PD have been identified to date, which indicate the importance of the ubiquitin-proteasome pathway in the molecular pathogenesis of dopaminergic cell death. Recent studies have also indicated the involvement of genetic factors in the pathogenesis of sporadic PD. Many association studies on candidate genes have examined the relationship between PD and polymorphisms; We identified a-synuclein as a definite susceptibility gene for sporadic PD. Since 2001, significant linkage to several loci have been reported in samples of affected sibling pairs. With the recent advances in human genome analyses, genome-wide association studies by SNP chip are being performed to identify susceptibility genes and to establish tailor-made medicine for PD. PMID:17713117

  6. Molecular Imaging in Genetic Medicine

    PubMed Central

    Jacob, Ayden; Van Gestel, Frederick; Yaghoubi, Shahriar

    2016-01-01

    The field of biomedical imaging has made significant advances in recent times. This includes extremely high-resolution anatomic imaging and functional imaging of physiologic and pathologic processes as well as novel modalities in optical imaging to evaluate molecular features within the cellular environment. The latter has made it possible to image phenotypic markers of various genotypes that are implicated in human development, behavior, and disease. This article discusses the role of molecular imaging in genetic and precision medicine.  PMID:27186447

  7. Molecular genetics of colorectal cancer.

    PubMed

    Bogaert, Julie; Prenen, Hans

    2014-01-01

    Approximately 90% of colorectal cancer cases are sporadic without family history or genetic predisposition, while in less than 10% a causative genetic event has been identified. Historically, colorectal cancer classification was only based on clinical and pathological features. Many efforts have been made to discover the genetic and molecular features of colorectal cancer, and there is more and more evidence that these features determine the prognosis and response to (targeted) treatment. Colorectal cancer is a heterogeneous disease, with three known major molecular groups. The most common is the chromosomal instable group, characterized by an accumulation of mutations in specific oncogenes and tumor suppressor genes. The second is the microsatellite instable group, caused by dysfunction of DNA mismatch repair genes leading to genetic hypermutability. The CpG Island Methylation phenotype is the third group, distinguished by hypermethylation. Colorectal cancer subtyping has also been addressed using genome-wide gene expression profiling in large patient cohorts and recently several molecular classification systems have been proposed. In this review we would like to provide an up-to-date overview of the genetic aspects of colorectal cancer. PMID:24714764

  8. Molecular genetic medicine. Vol. 2

    SciTech Connect

    Friedmann, T.

    1992-01-01

    Theodore Friedmann has put together an interesting spectrum of articles for volume 2 of Molecular Genetic Medicine. Perhaps related to his own interest in the X chromosome, three articles deal with X-chromosomal topics, while two deal with autosomal disorders and two treat viral disorders. The fragile-X syndrome is thoroughly covered by Brown and Jenkins with an article that is heavily weighted to clinical aspects and now out-of-date RFLP approaches. The timeliness of the volume is insured by the coverage (albeit brief) that they give to the cloning of FMR-1. Gartler et al. present a balanced review of X inactivation - the oft-surveyed subject was comprehensively covered in a manner that provided new perspectives. Lambert et al. provide an exhaustive review of natural and induced mutation of hypoxanthine phosphoribosyltransferase. For autosomal disorders, an excellent review of the molecular genetics of hemoglobin syntheses and their alterations in disease is provided by Berg and Schecter. The level of detail presented seemed just right to this reviewer. A concise review of recent advances in the study of Down syndrome and its animal model, trisomy 16 mice, is provided by Holtzman and Epstein. With regard to viral topics, Chisari thoughtfully reviews hepatitis B virus structure and function and the possible pathogenic mechanisms involved in its induction of hepatocellular carcinoma. Wong-Staal and Haseltine's up-to-date review of the increasingly complex regulatory genes of HIV is marred by a mix-up in figure legends - an exception to an otherwise well-proofread book. In summary, this is a good volume of its type and is recommended for those who might benefit from reading such review articles.

  9. Advances in molecular genetic studies of attention deficit hyperactivity disorder in China

    PubMed Central

    GAO, Qian; LIU, Lu; QIAN, Qiujin; WANG, Yufeng

    2014-01-01

    Summary Attention deficit hyperactivity disorder (ADHD) is a common psychiatric condition in children worldwide that typically includes a combination of symptoms of inattention and hyperactivity/impulsivity. Genetic factors are believed to be important in the development and course of ADHD so many candidate genes studies and genome-wide association studies (GWAS) have been conducted in search of the genetic mechanisms that cause or influence the condition. This review provides an overview of gene association and pharmacogenetic studies of ADHD from mainland China and elsewhere that use Han Chinese samples. To date, studies from China and elsewhere remain inconclusive so future studies need to consider alternative analytic techniques and test new biological hypotheses about the relationship of neurotransmission and neurodevelopment to the onset and course of this disabling condition. PMID:25317006

  10. Heritability and molecular genetic basis of electrodermal activity: A genome-wide ssociation study

    PubMed Central

    Vaidyanathan, Uma; Isen, Joshua D.; Malone, Stephen M.; Miller, Michael B.; McGue, Matthew; Iacono, William G.

    2014-01-01

    The molecular genetic basis of electrodermal activity (EDA) was analyzed using 527,829 single nucleotide polymorphisms (SNPs) in a large population-representative sample of twins and parents (N = 4,424) in relation to various EDA indices. Biometric analyses suggested that approximately 50% or more of variance in all EDA indices was heritable. The combined effect of all SNPs together accounted for a significant amount of variance in each index, affirming their polygenic basis and heritability. However, none of the SNPs were genome-wide significant for any EDA index. Previously reported SNP associations with disorders such as substance dependence or schizophrenia, which have been linked to EDA abnormalities, were not significant; nor were associations between EDA and genes in specific neurotransmitter systems. These results suggest that EDA is influenced by multiple genes rather than by polymorphisms with large effects. PMID:25387706

  11. Genetic and Molecular Ecotoxicology: A Research Framework

    PubMed Central

    Anderson, Susan; Sadinski, Walter; Shugart, Lee; Brussard, Peter; Depledge, Michael; Ford, Tim; Hose, JoEllen; Stegeman, John; Suk, William; Wirgin, Isaac; Wogan, Gerald

    1994-01-01

    Participants at the Napa Conference on Genetic and Molecular Ecotoxicology assessed the status of this field in light of heightened concerns about the genetic effects of exposure to hazardous substances and recent advancements in our capabilities to measure those effects. We present here a synthesis of the ideas discussed throughout the conference, including definitions of important concepts in the field and critical research needs and opportunities. While there were many opinions expressed on these topics, there was general agreement that there are substantive new opportunities to improve the impact of genetic and molecular ecotoxicology on prediction of sublethal effects of exposure to hazardous substances. Future studies should emphasize integration of genetic ecotoxicology, ecological genetics, and molecular biology and should be directed toward improving our understanding of the ecological implications of genotoxic responses. Ecological implications may be assessed at either the population or ecosystem level; however, a population-level focus may be most pragmatic. Recent technical advancements in measuring genetic and molecular responses to toxicant exposure will spur rapid progress. These new techniques have considerable promise for increasing our understanding of both mechanisms of toxicity on genes or gene products and the relevance of detrimental effects to individual fitness. — Environ Health Perspect 102(Suppl 12):3–8 (1994) PMID:7713030

  12. Study Of Genetic Diversity Between Grasspea Landraces Using Morphological And Molecular Marker

    NASA Astrophysics Data System (ADS)

    Sedehi, Abbasali Vahabi; Lotfi, Asefeh; Solooki, Mahmood

    2008-01-01

    Grass pea is a beneficial crop to Iran since it has some major advantageous such as high grain and forage quality, high drought tolerance and medium level of salinity tolerance and a good native germplasm variation which accessible for breeding programs. This study was carried out to evaluate morphological traits of the grass pea landraces using a randomized complete block design with 3 replications at Research Farm of Isfahan University of Technology. To evaluate genetic diversity of 14 grass pea landraces from various locations in Iran were investigated using 32 RAPD & ISJ primers at Biocenter of University of Zabol. Analysis of variance indicated a highly significant differences among 14 grass pea landrace for the morphological traits. Average of polymorphism percentage of RAPD primer was 73.9%. Among used primer, 12 random primers showed polymorphism and a total of 56 different bands were observed in the genotypes. Jafar-abad and Sar-chahan genotypes with similarity coefficient of 66% and Khoram-abad 2 and Khoram-abad 7 genotypes with similarity coefficient of 3% were the most related and the most distinct genotypes, respectively. Fourteen primers out of 17 semi random primers produced 70 polymorphic bands which included 56% of the total 126 produced bands. Genetic relatedness among population was investigated using Jacard coefficient and unweighted pair group mean analysis (UPGMA) algorithm. The result of this research verified possibility of use of RAPD & ISJ markers for estimation of genetic diversity, management of genetic resources and determination of repetitive accessions in grass pea.

  13. (-)-Menthol biosynthesis and molecular genetics.

    PubMed

    Croteau, Rodney B; Davis, Edward M; Ringer, Kerry L; Wildung, Mark R

    2005-12-01

    (-)-Menthol is the most familiar of the monoterpenes as both a pure natural product and as the principal and characteristic constituent of the essential oil of peppermint (Mentha x piperita). In this paper, we review the biosynthesis and molecular genetics of (-)-menthol production in peppermint. In Mentha species, essential oil biosynthesis and storage is restricted to the peltate glandular trichomes (oil glands) on the aerial surfaces of the plant. A mechanical method for the isolation of metabolically functional oil glands, has provided a system for precursor feeding studies to elucidate pathway steps, as well as a highly enriched source of the relevant biosynthetic enzymes and of their corresponding transcripts with which cDNA libraries have been constructed to permit cloning and characterization of key structural genes. The biosynthesis of (-)-menthol from primary metabolism requires eight enzymatic steps, and involves the formation and subsequent cyclization of the universal monoterpene precursor geranyl diphosphate to the parent olefin (-)-(4S)-limonene as the first committed reaction of the sequence. Following hydroxylation at C3, a series of four redox transformations and an isomerization occur in a general "allylic oxidation-conjugate reduction" scheme that installs three chiral centers on the substituted cyclohexanoid ring to yield (-)-(1R, 3R, 4S)-menthol. The properties of each enzyme and gene of menthol biosynthesis are described, as are their probable evolutionary origins in primary metabolism. The organization of menthol biosynthesis is complex in involving four subcellular compartments, and regulation of the pathway appears to reside largely at the level of gene expression. Genetic engineering to up-regulate a flux-limiting step and down-regulate a side route reaction has led to improvement in the composition and yield of peppermint oil. PMID:16292524

  14. (-)-Menthol biosynthesis and molecular genetics

    NASA Astrophysics Data System (ADS)

    Croteau, Rodney B.; Davis, Edward M.; Ringer, Kerry L.; Wildung, Mark R.

    2005-12-01

    (-)-Menthol is the most familiar of the monoterpenes as both a pure natural product and as the principal and characteristic constituent of the essential oil of peppermint ( Mentha x piperita). In this paper, we review the biosynthesis and molecular genetics of (-)-menthol production in peppermint. In Mentha species, essential oil biosynthesis and storage is restricted to the peltate glandular trichomes (oil glands) on the aerial surfaces of the plant. A mechanical method for the isolation of metabolically functional oil glands, has provided a system for precursor feeding studies to elucidate pathway steps, as well as a highly enriched source of the relevant biosynthetic enzymes and of their corresponding transcripts with which cDNA libraries have been constructed to permit cloning and characterization of key structural genes. The biosynthesis of (-)-menthol from primary metabolism requires eight enzymatic steps, and involves the formation and subsequent cyclization of the universal monoterpene precursor geranyl diphosphate to the parent olefin (-)-(4 S)-limonene as the first committed reaction of the sequence. Following hydroxylation at C3, a series of four redox transformations and an isomerization occur in a general “allylic oxidation-conjugate reduction” scheme that installs three chiral centers on the substituted cyclohexanoid ring to yield (-)-(1 R, 3 R, 4 S)-menthol. The properties of each enzyme and gene of menthol biosynthesis are described, as are their probable evolutionary origins in primary metabolism. The organization of menthol biosynthesis is complex in involving four subcellular compartments, and regulation of the pathway appears to reside largely at the level of gene expression. Genetic engineering to up-regulate a flux-limiting step and down-regulate a side route reaction has led to improvement in the composition and yield of peppermint oil.

  15. Simulating a base population in honey bee for molecular genetic studies

    PubMed Central

    2012-01-01

    Background Over the past years, reports have indicated that honey bee populations are declining and that infestation by an ecto-parasitic mite (Varroa destructor) is one of the main causes. Selective breeding of resistant bees can help to prevent losses due to the parasite, but it requires that a robust breeding program and genetic evaluation are implemented. Genomic selection has emerged as an important tool in animal breeding programs and simulation studies have shown that it yields more accurate breeding value estimates, higher genetic gain and low rates of inbreeding. Since genomic selection relies on marker data, simulations conducted on a genomic dataset are a pre-requisite before selection can be implemented. Although genomic datasets have been simulated in other species undergoing genetic evaluation, simulation of a genomic dataset specific to the honey bee is required since this species has a distinct genetic and reproductive biology. Our software program was aimed at constructing a base population by simulating a random mating honey bee population. A forward-time population simulation approach was applied since it allows modeling of genetic characteristics and reproductive behavior specific to the honey bee. Results Our software program yielded a genomic dataset for a base population in linkage disequilibrium. In addition, information was obtained on (1) the position of markers on each chromosome, (2) allele frequency, (3) χ2 statistics for Hardy-Weinberg equilibrium, (4) a sorted list of markers with a minor allele frequency less than or equal to the input value, (5) average r2 values of linkage disequilibrium between all simulated marker loci pair for all generations and (6) average r2 value of linkage disequilibrium in the last generation for selected markers with the highest minor allele frequency. Conclusion We developed a software program that takes into account the genetic and reproductive biology specific to the honey bee and that can be used to

  16. Studies on the molecular pathogenesis of extraskeletal myxoid chondrosarcoma-cytogenetic, molecular genetic, and cDNA microarray analyses.

    PubMed

    Sjögren, Helene; Meis-Kindblom, Jeanne M; Orndal, Charlotte; Bergh, Peter; Ptaszynski, Konrad; Aman, Pierre; Kindblom, Lars-Gunnar; Stenman, Göran

    2003-03-01

    Extraskeletal myxoid chondrosarcomas (EMCs) are characterized by recurrent chromosome translocations resulting in fusions of the nuclear receptor TEC to various NH(2)-terminal partners. Here we describe the phenotypic, cytogenetic, and molecular genetic characteristics of a series of 10 EMCs. Using spectral karyotyping and fluorescence in situ hybridization, clonal chromosome abnormalities were detected in all but one tumor. A t(9;22)(q22;q12) translocation was found in three cases; a del(22)(q12-13)in one case; and variant translocations, including t(9;17)(q22;q11-12), t(7;9;17)(q32;q22;q11), and t(9;15)(q22;q21), were detected in one case each. Recurrent, secondary abnormalities, including trisomy 1q, 7, 8, 12, and 19, were found in seven tumors. All tumors contained translocation-generated or cryptic gene fusions, including EWS-TEC (five cases, of which one was a novel fusion), TAF2N-TEC (four cases), and TCF12-TEC (one case). cDNA microarray analysis of the gene expression patterns of two EMCs and a myxoid liposarcoma reference tumor revealed a remarkably distinct and uniform expression profile in both EMCs despite the fact that they had different histologies and expressed different fusion transcripts. The most differentially expressed gene in both tumors was CHI3L1, which encodes a secreted glycoprotein (YKL-40) previously implicated in various pathological conditions of extracellular matrix degradation as well as in cancer. Our findings suggests that EMC exhibits a tumor-specific gene expression profile, including overexpression of several cancer-related genes as well as genes implicated in chondrogenesis and neural-neuroendocrine differentiation, thus distinguishing it from other soft tissue sarcomas. PMID:12598313

  17. A molecular genetic study of autism and related phenotypes in extended pedigrees

    PubMed Central

    2013-01-01

    Background Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. Methods We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. Results Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas 'repetitive behavior’, showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. Conclusions These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears

  18. Molecular advances in genetic skin diseases.

    PubMed

    Siegel, Dawn H; Howard, Renee

    2002-08-01

    The genes for several genetic skin diseases have been identified in recent years. This development improves diagnostic capabilities and genetic counseling, and investigators can now turn to the molecular mechanisms involved in the pathogenesis of these diseases. The identification of the causative genes has led to the generation of mouse models for some genetic skin diseases. A study of the keratin 10 deficient mouse, a model for epidermolytic hyperkeratosis, and a mouse model for Bloom syndrome are reviewed in this article. Several studies also evaluate the relation between genotype and phenotype. In this article, the clinical findings and molecular advances in tuberous sclerosis complex, neurofibromatosis type 1, Bloom syndrome, epidermolytic hyperkeratosis, X-linked ichthyosis, Netherton syndrome, and Hermansky-Pudlak syndrome are reviewed. PMID:12130905

  19. A twin and molecular genetics study of sleep paralysis and associated factors.

    PubMed

    Denis, Dan; French, Christopher C; Rowe, Richard; Zavos, Helena M S; Nolan, Patrick M; Parsons, Michael J; Gregory, Alice M

    2015-08-01

    Sleep paralysis is a relatively common but under-researched phenomenon. In this paper we examine prevalence in a UK sample and associations with candidate risk factors. This is the first study to investigate the heritability of sleep paralysis in a twin sample and to explore genetic associations between sleep paralysis and a number of circadian expressed single nucleotide polymorphisms. Analyses are based on data from the Genesis1219 twin/sibling study, a community sample of twins/siblings from England and Wales. In total, data from 862 participants aged 22-32 years (34% male) were used in the study. This sample consisted of monozygotic and dizygotic twins and siblings. It was found that self-reports of general sleep quality, anxiety symptoms and exposure to threatening events were all associated independently with sleep paralysis. There was moderate genetic influence on sleep paralysis (53%). Polymorphisms in the PER2 gene were associated with sleep paralysis in additive and dominant models of inheritance-although significance was not reached once a Bonferroni correction was applied. It is concluded that factors associated with disrupted sleep cycles appear to be associated with sleep paralysis. In this sample of young adults, sleep paralysis was moderately heritable. Future work should examine specific polymorphisms associated with differences in circadian rhythms and sleep homeostasis further in association with sleep paralysis. PMID:25659590

  20. Autosomal dominant retinitis pigmentosa with apparent incomplete penetrance: a clinical, electrophysiological, psychophysical, and molecular genetic study.

    PubMed Central

    Moore, A T; Fitzke, F; Jay, M; Arden, G B; Inglehearn, C F; Keen, T J; Bhattacharya, S S; Bird, A C

    1993-01-01

    Twenty five symptomatic individuals and six asymptomatic obligate gene carriers from four families with autosomal dominant retinitis pigmentosa (adRP) showing apparent incomplete penetrance have been studied. Symptomatic individuals from three families showed early onset of night blindness, non-recordable rod electroretinograms, and marked elevation of both rod and cone thresholds in all subjects tested. In the fourth family, there was more variation in the age of onset of night blindness and some symptomatic individuals showed well preserved rod and cone function in some retinal areas. All asymptomatic individuals tested had evidence of mild abnormalities of rod and cone function, indicating that these families show marked variation in expressivity rather than true non-penetrance of the adRP gene. No mutations of the rhodopsin or RDS genes were found in these families and the precise genetic mutation(s) remain to be identified. PMID:8025041

  1. Phylogenetic and Molecular Variability Studies Reveal a New Genetic Clade of Citrus leprosis virus C

    PubMed Central

    Ramos-González, Pedro Luis; Chabi-Jesus, Camila; Guerra-Peraza, Orlene; Breton, Michèle Claire; Arena, Gabriella Dias; Nunes, Maria Andreia; Kitajima, Elliot Watanabe; Machado, Marcos Antonio; Freitas-Astúa, Juliana

    2016-01-01

    Citrus leprosis virus C (CiLV-C) causes a severe disease affecting citrus orchards in the Western hemisphere. This study reveals the molecular variability of the virus by analyzing four genomic regions (p29, p15, MP and RNA2-intergenic region) distributed over its two RNAs. Nucleotide diversity (π) values were relatively low but statistically different over the analyzed genes and subpopulations, indicating their distinct evolutionary history. Values of πp29 and πMP were higher than those of πp15 and πRNA2–IR, whereas πMP was increased due to novel discovered isolates phylogenetically clustered in a divergent clade that we called SJP. Isolate BR_SP_SJP_01 RNA1 and RNA2 sequences, clade SJP, showed an identity of 85.6% and 88.4%, respectively, with those corresponding to CiLV-C, the type member of the genus Cilevirus, and its RNA2 5′-proximal region was revealed as a minor donor in a putative inter-clade recombination event. In addition to citrus, BR_SP_SJP_01 naturally infects the weed Commelina benghalensis and is efficiently transmitted by Brevipalpus yothersi mites. Our data demonstrated that negative selection was the major force operating in the evaluated viral coding regions and defined amino acids putatively relevant for the biological function of cilevirus proteins. This work provides molecular tools and sets up a framework for further epidemiological studies. PMID:27275832

  2. Phylogenetic and Molecular Variability Studies Reveal a New Genetic Clade of Citrus leprosis virus C.

    PubMed

    Ramos-González, Pedro Luis; Chabi-Jesus, Camila; Guerra-Peraza, Orlene; Breton, Michèle Claire; Arena, Gabriella Dias; Nunes, Maria Andreia; Kitajima, Elliot Watanabe; Machado, Marcos Antonio; Freitas-Astúa, Juliana

    2016-01-01

    Citrus leprosis virus C (CiLV-C) causes a severe disease affecting citrus orchards in the Western hemisphere. This study reveals the molecular variability of the virus by analyzing four genomic regions (p29, p15, MP and RNA2-intergenic region) distributed over its two RNAs. Nucleotide diversity (π) values were relatively low but statistically different over the analyzed genes and subpopulations, indicating their distinct evolutionary history. Values of πp29 and πMP were higher than those of πp15 and πRNA2-IR, whereas πMP was increased due to novel discovered isolates phylogenetically clustered in a divergent clade that we called SJP. Isolate BR_SP_SJP_01 RNA1 and RNA2 sequences, clade SJP, showed an identity of 85.6% and 88.4%, respectively, with those corresponding to CiLV-C, the type member of the genus Cilevirus, and its RNA2 5'-proximal region was revealed as a minor donor in a putative inter-clade recombination event. In addition to citrus, BR_SP_SJP_01 naturally infects the weed Commelina benghalensis and is efficiently transmitted by Brevipalpus yothersi mites. Our data demonstrated that negative selection was the major force operating in the evaluated viral coding regions and defined amino acids putatively relevant for the biological function of cilevirus proteins. This work provides molecular tools and sets up a framework for further epidemiological studies. PMID:27275832

  3. Molecular genetics of myocardial infarction

    PubMed Central

    Ichihara, Sahoko; Nishida, Tamotsu

    2008-01-01

    Abstract Myocardial infarction (MI) is an important clinical problem because of its large contribution to mortality. The main causal and treatable risk factors for MI include hypertension, hypercholesterolemia or dyslipidemia, diabetes mellitus, and smoking. In addition to these risk factors, recent studies have shown the importance of genetic factors and interactions between multiple genes and environmental factors. Disease prevention is an important strategy for reducing the overall burden of MI, with the identification of markers for disease risk being key both for risk prediction and for potential intervention to lower the chance of future events. Although genetic linkage analyses of families and sib-pairs as well as candidate gene and genome-wide association studies have implicated several loci and candidate genes in predisposition to coronary heart disease (CHD) or MI, the genes that contribute to genetic susceptibility to these conditions remain to be identified definitively. In this review, we summarize both candidate loci for CHD or MI identified by linkage analyses and candidate genes examined by association studies. We also review in more detail studies that have revealed the association with MI or CHD of polymorphisms in MTHFR, LPL, and APOE by the candidate gene approach and those in LTA and at chromosomal region 9p21.3 by genome-wide scans. Such studies may provide insight into the function of implicated genes as well as into the role of genetic factors in the development of CHD and MI. PMID:18704761

  4. Genetics of asthma: a molecular biologist perspective

    PubMed Central

    Kumar, Amrendra; Ghosh, Balaram

    2009-01-01

    Asthma belongs to the category of classical allergic diseases which generally arise due to IgE mediated hypersensitivity to environmental triggers. Since its prevalence is very high in developed or urbanized societies it is also referred to as "disease of civilizations". Due to its increased prevalence among related individuals, it was understood quite long back that it is a genetic disorder. Well designed epidemiological studies reinforced these views. The advent of modern biological technology saw further refinements in our understanding of genetics of asthma and led to the realization that asthma is not a disorder with simple Mendelian mode of inheritance but a multifactorial disorder of the airways brought about by complex interaction between genetic and environmental factors. Current asthma research has witnessed evidences that are compelling researchers to redefine asthma altogether. Although no consensus exists among workers regarding its definition, it seems obvious that several pathologies, all affecting the airways, have been clubbed into one common category called asthma. Needless to say, genetic studies have led from the front in bringing about these transformations. Genomics, molecular biology, immunology and other interrelated disciplines have unearthed data that has changed the way we think about asthma now. In this review, we center our discussions on genetic basis of asthma; the molecular mechanisms involved in its pathogenesis. Taking cue from the existing data we would briefly ponder over the future directions that should improve our understanding of asthma pathogenesis. PMID:19419542

  5. Genetics of asthma: a molecular biologist perspective.

    PubMed

    Kumar, Amrendra; Ghosh, Balaram

    2009-01-01

    Asthma belongs to the category of classical allergic diseases which generally arise due to IgE mediated hypersensitivity to environmental triggers. Since its prevalence is very high in developed or urbanized societies it is also referred to as "disease of civilizations". Due to its increased prevalence among related individuals, it was understood quite long back that it is a genetic disorder. Well designed epidemiological studies reinforced these views. The advent of modern biological technology saw further refinements in our understanding of genetics of asthma and led to the realization that asthma is not a disorder with simple Mendelian mode of inheritance but a multifactorial disorder of the airways brought about by complex interaction between genetic and environmental factors. Current asthma research has witnessed evidences that are compelling researchers to redefine asthma altogether. Although no consensus exists among workers regarding its definition, it seems obvious that several pathologies, all affecting the airways, have been clubbed into one common category called asthma. Needless to say, genetic studies have led from the front in bringing about these transformations. Genomics, molecular biology, immunology and other interrelated disciplines have unearthed data that has changed the way we think about asthma now. In this review, we center our discussions on genetic basis of asthma; the molecular mechanisms involved in its pathogenesis. Taking cue from the existing data we would briefly ponder over the future directions that should improve our understanding of asthma pathogenesis. PMID:19419542

  6. Molecular-Genetic Imaging of Cancer

    PubMed Central

    Minn, Il; Menezes, Mitchell E.; Sarkar, Siddik; Yarlagadda, Keerthi; Das, Swadesh K.; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B.; Pomper, Martin G.

    2015-01-01

    Molecular-genetic imaging of cancer using nonviral delivery systems has great potential for clinical application as a safe, efficient, noninvasive tool for visualization of various cellular processes including detection of cancer, and its attendant metastases. In recent years, significant effort has been expended in overcoming technical hurdles to enable clinical adoption of molecular-genetic imaging. This chapter will provide an introduction to the components of molecular-genetic imaging and recent advances on each component leading to safe, efficient clinical applications for detecting cancer. Combination with therapy, namely, generating molecular-genetic theranostic constructs, will provide further impetus for clinical translation of this promising technology. PMID:25287688

  7. Lethal carnitine palmitoyltransferase (CPT) II deficiency in newborns: A molecular-genetic study

    SciTech Connect

    Taroni, F.; Gellera, C.; Cavadini, P.

    1994-09-01

    Classically, CPT II deficiency presents in young adults with recurrent episodes of paroxysmal myoglobinuria triggered by prolonged exercise, cold, or fever. More severe forms of CPT II deficiency have recently been observed in children and newborns. Here, were present biochemical and molecular studies of lethal neonatal CPT II deficiency in a premature Haitian infant of nonconsanguineous parents. He presented at birth with severe respiratory distress, cardiac arrhythmia and heart failure. His condition worsened and he died on the 4th day of life. Postmortem examination showed hypertrophied, dilated heart, and lipid storage in liver, heart and kidney. An older sibling had died unexpectantly at 4 days of age with postmortem evidence of fatty infiltration of liver, kidney, heart and muscle. Biochemical study of cultured fibroblasts demonstrated dramatic reduction of palmitate oxidation (to < 3%) and very low residual CPT II activity ({le}15%). No CPT II protein was detected by Western blot analysis of fibroblasts. However, immunoprecitation of cells pulse-labeled with L-[{sup 35}S] methionine demonstrated normal amounts of newly synthesized CPT II, thus suggesting altered stability of the enzyme. To identify the molecular defect in his patient, individual CPT II exons were amplified by genomic PCR and directly sequenced. A missense mutation was found in exon 4, resulting in the nonconservative amino acid substitution at codon 227 (Pro227Leu). SSCP analysis of a genomic PCR fragment encompassing the mutation demonstrated that the patient was homozygous and the parents were heterozygous for this mutation. The mutation was detected neither in a large number of controls nor in other CPT II deficient patients. Finally, CPT II activity in COS-1 cells transfected with mutated CPT II cDNA was <8% than that in cells transfected with wild-type cDNA, thus demonstrating the pathogenic role of this mutation.

  8. Genetic neurological channelopathies: molecular genetics and clinical phenotypes

    PubMed Central

    Spillane, J; Kullmann, D M; Hanna, M G

    2016-01-01

    Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies. PMID:26558925

  9. Genetic neurological channelopathies: molecular genetics and clinical phenotypes.

    PubMed

    Spillane, J; Kullmann, D M; Hanna, M G

    2016-01-01

    Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies. PMID:26558925

  10. {open_quotes}Unspecific{close_quotes} X-linked mental retardation: Clinical, genetic and molecular studies

    SciTech Connect

    Ropers, H.H.; Maacel, S. van der; Knoers, N.

    1994-09-01

    Previous linkage studies have assigned a gene for non-syndromic X-linked mental retardation (XMR) to at least 8 different regions on the X-chromosome. The fragile X-syndrome (FRAXA) does not account for more than 40% of all cases; in most XMR families early diagnosis and prevention is not possible. As part of a systematic study into {open_quotes}unspecific{close_quotes} XMR involving more than 30 non-FRAXA families, linkage studies have enabled us to map the respective genes in 4 families to the Xp11.4-q12 interval with peak lod scores around the ALAS2 locus. In three other families, the gene defect could be assigned to the KAL-DMD, DXS424-FRAXAC2 and DSX52-Xqter intervals, respectively. In one of these families, small stature due to growth hormone deficiency was observed as a distinctive clinical feature. Molecular cloning of the breakpoint in a mentally retarded girl with a balanced t(Xq13;13q) translocation has enabled us to isolate an X-chromosomal gene which is disrupted in this patient and is highly expressed in brain. YAC cloning strategies are being employed to clone another XMR gene, which has been identified previously in the vicinity of the CHM locus and genes involved in mentally retarded patients with two different inversions, inv(X)(q21p11) and inv(X)(p21q24), respectively.

  11. Microbial Biofilms: from Ecology to Molecular Genetics

    PubMed Central

    Davey, Mary Ellen; O'toole, George A.

    2000-01-01

    Biofilms are complex communities of microorganisms attached to surfaces or associated with interfaces. Despite the focus of modern microbiology research on pure culture, planktonic (free-swimming) bacteria, it is now widely recognized that most bacteria found in natural, clinical, and industrial settings persist in association with surfaces. Furthermore, these microbial communities are often composed of multiple species that interact with each other and their environment. The determination of biofilm architecture, particularly the spatial arrangement of microcolonies (clusters of cells) relative to one another, has profound implications for the function of these complex communities. Numerous new experimental approaches and methodologies have been developed in order to explore metabolic interactions, phylogenetic groupings, and competition among members of the biofilm. To complement this broad view of biofilm ecology, individual organisms have been studied using molecular genetics in order to identify the genes required for biofilm development and to dissect the regulatory pathways that control the plankton-to-biofilm transition. These molecular genetic studies have led to the emergence of the concept of biofilm formation as a novel system for the study of bacterial development. The recent explosion in the field of biofilm research has led to exciting progress in the development of new technologies for studying these communities, advanced our understanding of the ecological significance of surface-attached bacteria, and provided new insights into the molecular genetic basis of biofilm development. PMID:11104821

  12. Heritability and molecular genetic basis of antisaccade eye tracking error rate: a genome-wide association study.

    PubMed

    Vaidyanathan, Uma; Malone, Stephen M; Donnelly, Jennifer M; Hammer, Micah A; Miller, Michael B; McGue, Matt; Iacono, William G

    2014-12-01

    Antisaccade deficits reflect abnormalities in executive function linked to various disorders including schizophrenia, externalizing psychopathology, and neurological conditions. We examined the genetic bases of antisaccade error in a sample of community-based twins and parents (N = 4,469). Biometric models showed that about half of the variance in the antisaccade response was due to genetic factors and half due to nonshared environmental factors. Molecular genetic analyses supported these results, showing that the heritability accounted for by common molecular genetic variants approximated biometric estimates. Genome-wide analyses revealed several SNPs as well as two genes-B3GNT7 and NCL-on Chromosome 2 associated with antisaccade error. SNPs and genes hypothesized to be associated with antisaccade error based on prior work, although generating some suggestive findings for MIR137, GRM8, and CACNG2, could not be confirmed. PMID:25387707

  13. The molecular genetics of holoprosencephaly.

    PubMed

    Roessler, Erich; Muenke, Maximilian

    2010-02-15

    Holoprosencephaly (HPE) has captivated the imagination of Man for millennia because its most extreme manifestation, the single-eyed cyclopic newborn infant, brings to mind the fantastical creature Cyclops from Greek mythology. Attempting to understand this common malformation of the forebrain in modern medical terms requires a systematic synthesis of genetic, cytogenetic, and environmental information typical for studies of a complex disorder. However, even with the advances in our understanding of HPE in recent years, there are significant obstacles remaining to fully understand its heterogeneity and extensive variability in phenotype. General lessons learned from HPE will likely be applicable to other malformation syndromes. Here we outline the common, and rare, genetic and environmental influences on this conserved developmental program of forebrain development and illustrate the similarities and differences between these malformations in humans and those of animal models. PMID:20104595

  14. Single-copy gene based 50 K SNP chip for genetic studies and molecular breeding in rice

    PubMed Central

    Singh, Nisha; Jayaswal, Pawan Kumar; Panda, Kabita; Mandal, Paritra; Kumar, Vinod; Singh, Balwant; Mishra, Shefali; Singh, Yashi; Singh, Renu; Rai, Vandna; Gupta, Anita; Raj Sharma, Tilak; Singh, Nagendra Kumar

    2015-01-01

    Single nucleotide polymorphism (SNP) is the most abundant DNA sequence variation present in plant genomes. Here, we report the design and validation of a unique genic-SNP genotyping chip for genetic and evolutionary studies as well as molecular breeding applications in rice. The chip incorporates 50,051 SNPs from 18,980 different genes spanning 12 rice chromosomes, including 3,710 single-copy (SC) genes conserved between wheat and rice, 14,959 SC genes unique to rice, 194 agronomically important cloned rice genes and 117 multi-copy rice genes. Assays with this chip showed high success rate and reproducibility because of the SC gene based array with no sequence redundancy and cross-hybridisation problems. The usefulness of the chip in genetic diversity and phylogenetic studies of cultivated and wild rice germplasm was demonstrated. Furthermore, its efficacy was validated for analysing background recovery in improved mega rice varieties with submergence tolerance developed through marker-assisted backcross breeding. PMID:26111882

  15. Hypescheme: an operational criteria checklist and minimum data set for molecular genetic studies of attention deficit and hyperactivity disorders.

    PubMed

    Curran, S; Newman, S; Taylor, E; Asherson, P

    2000-06-12

    Investigators engaged in mapping the genetic basis of attention deficit hyperactivity disorder (ADHD) currently use a number of measures for the collection of clinical information. This gives rise to difficulties in comparing datasets and research communications between independent groups. This paper describes the development of Hypescheme, which is an operational criteria checklist for ADHD, oppositional defiant disorder (ODD), and conduct disorder (CD), and is proposed as a minimum dataset for those engaged in molecular genetic studies of ADHD. Hypescheme consists of a computerised data checklist system that includes all the operational criteria required for both DSM-IV and ICD-10 diagnostic criteria and a systematic record of information about comorbid psychiatric, developmental, and neurological disorders. Using this data, an algorithm applies both DSM-IV and ICD-10 criteria to generate operational diagnostics under both these systems. Hypescheme is not designed to replace current assessment protocols but to be a final common checklist that can be completed by experienced researchers using all available data. PMID:10898893

  16. Strategies for molecular genetic studies of preserved deep-sea macrofauna

    NASA Astrophysics Data System (ADS)

    Boyle, Elizabeth E.; Zardus, John D.; Chase, Michael R.; Etter, Ron J.; Rex, Michael A.

    2004-10-01

    With the development of new methods to sequence DNA from preserved organisms, existing archival collections can be used to document the population genetic structure of deep-sea species. This has made possible the first direct inferences about patterns of evolutionary diversification in the soft-sediment macrofauna. Here we report protocols and success rates for amplifying and sequencing regions of the mitochondrial 16S rDNA, Cytochrome oxidase I (COI), and Cytochrome b (cytb) genes from formalin-fixed protobranch bivalves and gastropods, major components of the deep-sea benthos. DNA was extracted from 1532 individuals of 12 common bathyal and abyssal species that had been fixed in formalin and preserved in alcohol for up to 36 years. DNA was also extracted from 53 individuals that were dried upon collection, some of which were collected more than 100 years ago. The overall success rate for amplification by PCR was 44%, but this varied considerably among species, stations, and cruises. When DNA amplified, sequencing success was generally high, averaging 85% and ranging from 19% to 100%. The reliability of amplification and sequencing depend strongly on how samples are treated during collection and storage. Amplification success was similar among samples collected from the same station and samples collected on the same cruise. We provide recommendations on strategies for primer design, PCR, and sample selection to improve success rates for genetic analysis of preserved deep-sea organisms. The success rates from different collections, sampling stations, and cruises provide important guidance for selecting material for future genetic work on deep-sea collections examined here.

  17. Molecular Genetic of Atopic dermatitis: An Update

    PubMed Central

    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

  18. Molecular Genetics of Tooth Development

    PubMed Central

    Bei, Marianna

    2009-01-01

    Organogenesis depends upon a well-ordered series of inductive events involving coordination of molecular pathways that regulate the generation and patterning of specific cell types. Key questions in organogenesis involve the identification of the molecular mechanisms by which proteins interact to organize distinct pattern formation and cell fate determination. Tooth development is an excellent context for investigating this complex problem because of the wealth of information emerging from studies of model organisms and human mutations. Since there are no obvious sources of stem cells in adult human teeth, any attempt to create teeth de novo will likely require the re-programming of other cell types. Thus, the fundamental understanding of the control mechanisms responsible for normal tooth patterning in the embryo will help us understand cell fate specificity and may provide valuable information towards tooth organ regeneration. PMID:19875280

  19. Studies of Resurgent Bed Bugs: Population Genetic Structure, Impact of Aggregation on Development and Molecular Screening for Bartonella

    NASA Astrophysics Data System (ADS)

    Saenz, Virna Lisa

    The recent resurgence of bed bugs (Cimex lectularius L.) has created an unprecedented demand for research on its biology. The main objectives of this dissertation research were to investigate several aspects of bed bug biology: infestation and dispersal dynamics at a large and small geographical scale using molecular markers, to determine the impact of aggregation on bed bug development and to screen bed bug populations for a re-emergent pathogen. First, we studied the infestation and dispersal dynamics of bed bugs at large geographical scale (e.g., across cities, states). Although bed bug infestations are on the rise, there is a poor understanding of their dispersal patterns and sources of infestation. We conducted a genetic study of 21 bed bug infestations from the eastern United States. We genotyped samples comprised of 8 - 10 individuals per infestation at nine polymorphic microsatellite loci. Despite high genetic diversity across all infestations, with 5 -- 17 alleles per locus (mean = 10.3), we found low genetic diversity (1 -- 4 alleles per locus) within all but one of the infestations. These results suggest that nearly all the studied infestations were started by a small propagule possibly consisting of a singly mated female and/or her progeny. All infestations were strongly genetically differentiated from each other (mean pairwise FST between populations = 0.68) and we did not find strong evidence of a geographic pattern of structuring. The high level of genetic diversity across infestations from the eastern United States together with the lack of geographically organized structure is consistent with multiple introductions into the United States from foreign sources. This work is described in Chapter 2 and was published in the Journal of Medical Entomology in 2012. Second, we investigated dispersal and infestation dynamics of bed bugs at a fine geographical scale within three multistory apartment buildings: one from Raleigh, NC and two from Jersey City, NJ

  20. Molecular genetics of febrile seizures.

    PubMed

    Nakayama, Junko; Arinami, Tadao

    2006-08-01

    Febrile seizures (FSs) represent the most common form of childhood seizures, occurring in 2-5% of infants in Europe and North America and in 6-9% in Japan. It has been recognized that there is a significant genetic component for susceptibility to this type of seizure. Six susceptibility FS loci have been identified on chromosomes 8q13-q21 (FEB1), 19p (FEB2), 2q23-q24 (FEB3), 5q14-q15 (FEB4), 6q22-q24 (FEB5), and 18p11 (FEB6). Furthermore, mutations in the voltage-gated sodium channel alpha-1, alpha-2 and beta-1 subunit genes (SCN1A, SCN2A and SCN1B) and the GABA(A) receptor gamma-2 subunit gene (GABRG2) have been identified in families with a clinical subset of seizures termed "generalized epilepsy with febrile seizure plus (GEFS+)". However, the causative genes have not been identified in most patients with FSs or GEFS+. Common forms of FSs are genetically complex disorders believed to be influenced by variations in several susceptibility genes. Recently, several association studies in FSs have been reported, but the results vary among different groups and no consistent or convincing FS susceptibility genes have emerged. To find a true association, larger sample size and newer methodologic refinements are recommended. PMID:16887333

  1. Molecular Genetic Analysis of Phototropism in Arabidopsis

    PubMed Central

    Sakai, Tatsuya; Haga, Ken

    2012-01-01

    Plant life is strongly dependent on the environment, and plants regulate their growth and development in response to many different environmental stimuli. One of the regulatory mechanisms involved in these responses is phototropism, which allows plants to change their growth direction in response to the location of the light source. Since the study of phototropism by Darwin, many physiological studies of this phenomenon have been published. Recently, molecular genetic analyses of Arabidopsis have begun to shed light on the molecular mechanisms underlying this response system, including phototropin blue light photoreceptors, phototropin signaling components, auxin transporters, auxin action mechanisms and others. This review highlights some of the recent progress that has been made in further elucidating the phototropic response, with particular emphasis on mutant phenotypes. PMID:22864452

  2. Genetics and molecular biology of breast cancer

    SciTech Connect

    King, M.C.; Lippman, M.

    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.

  3. Sporadic Early-Onset Colorectal Cancer Is a Specific Sub-Type of Cancer: A Morphological, Molecular and Genetics Study

    PubMed Central

    Kirzin, Sylvain; Marisa, Laetitia; Guimbaud, Rosine; De Reynies, Aurélien; Legrain, Michèle; Laurent-Puig, Pierre; Cordelier, Pierre; Pradère, Bernard; Bonnet, Delphine; Meggetto, Fabienne; Portier, Guillaume; Brousset, Pierre; Selves, Janick

    2014-01-01

    Sporadic early onset colorectal carcinoma (EOCRC) which has by definition no identified hereditary predisposition is a growing problem that remains poorly understood. Molecular analysis could improve identification of distinct sub-types of colorectal cancers (CRC) with therapeutic implications and thus can help establish that sporadic EOCRC is a distinct entity. From 954 patients resected for CRC at our institution, 98 patients were selected. Patients aged 45–60 years were excluded to help define “young” and “old” groups. Thirty-nine cases of sporadic EOCRC (patients≤45 years with microsatellite stable tumors) were compared to both microsatellite stable tumors from older patients (36 cases, patients>60 years) and to groups of patients with microsatellite instability. Each group was tested for TP53, KRAS, BRAF, PIK3CA mutations and the presence of a methylator phenotype. Gene expression profiles were also used for pathway analysis. Compared to microsatellite stable CRC from old patients, sporadic EOCRC were characterized by distal location, frequent synchronous metastases and infrequent synchronous adenomas but did not have specific morphological characteristics. A familial history of CRC was more common in sporadic EOCRC patients despite a lack of identified hereditary conditions (p = 0.013). Genetic studies also showed the absence of BRAF mutations (p = 0.022) and the methylator phenotype (p = 0.005) in sporadic EOCRC compared to older patients. Gene expression analysis implicated key pathways such as Wnt/beta catenin, MAP Kinase, growth factor signaling (EGFR, HGF, PDGF) and the TNFR1 pathway in sporadic EOCRC. Wnt/beta catenin signaling activation was confirmed by aberrant nuclear beta catenin immunostaining (p = 0.01). This study strongly suggests that sporadic EOCRC is a distinct clinico-molecular entity presenting as a distal and aggressive disease associated with chromosome instability. Furthermore, several signaling pathways

  4. Molecular genetics in affective illness

    SciTech Connect

    Mendlewicz, J.; Sevy, S.; Mendelbaum, K. )

    1993-01-01

    Genetic transmission in manic depressive illness (MDI) has been explored in twins, adoption, association, and linkage studies. The X-linked transmission hypothesis has been tested by using several markers on chromosome X: Xg blood group, color blindness, glucose-6-phosphate dehydrogenase (G6PD), factor IX (hemophilia B), and DNA probes such as DXS15, DXS52, F8C, ST14. The hypothesis of autosomal transmission has been tested by association studies with the O blood group located on chromosome 9, as well as linkage studies on chromosome 6 with the Human Leucocyte Antigens (HLA) haplotypes and on Chromosome 11 with DNA markers for the following genes: D2 dopamine receptor, tyrosinase, C-Harvey-Ras-A (HRAS) oncogene, insuline (ins), and tyrosine hydroxylase (TH). Although linkage studies support the hypothesis of a major locus for the transmission of MDI in the Xq27-28 region, several factors are limiting the results, and are discussed in the present review. 105 refs., 1 fig., 2 tabs.

  5. Molecular Genetic and Genomic Approaches to Study Flowering and Early Fruit Development in Cucumis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have utilized a transgenic approach to study sex expression in melon as regulated by ethylene production and perception. These studies have indicated dual roles for ethylene in sex determination and maturation of the carpel bearing flower, as well as involvement of ethylene in fruit set and resou...

  6. The molecular basis of genetic dominance.

    PubMed Central

    Wilkie, A O

    1994-01-01

    Studies of mutagenesis in many organisms indicate that the majority (over 90%) of mutations are recessive to wild type. If recessiveness represents the 'default' state, what are the distinguishing features that make a minority of mutations give rise to dominant or semidominant characters? This review draws on the rapid expansion in knowledge of molecular and cellular biology to classify the molecular mechanisms of dominant mutation. The categories discussed include (1) reduced gene dosage, expression, or protein activity (haploinsufficiency); (2) increased gene dosage; (3) ectopic or temporally altered mRNA expression; (4) increased or constitutive protein activity; (5) dominant negative effects; (6) altered structural proteins; (7) toxic protein alterations; and (8) new protein functions. This provides a framework for understanding the basis of dominant genetic phenomena in humans and other organisms. Images PMID:8182727

  7. [Mutational Analysis of Hemophilia B in Russia: Molecular-Genetic Study].

    PubMed

    Surin, V L; Demidova, E Yu; Selivanova, D S; Luchinina, Yu A; Salomashkina, V V; Pshenichnikova, O S; Likhacheva, E A

    2016-04-01

    Hemophilia B is a hereditary X-linked coagulation disorder. This pathology is caused by various defects in the factor IX gene, which is, being about 34 kb long and consisting of eight exons, localized in the Xq27 locus of the. X-chromosome long arm. Mutations were revealed in 56 unrelated patients with hemophilia B in this study by using direct sequencing of factor IX gene functionally important fragments. Forty-six mutations were found with prevailing missense mutations (n = 30). The rest of the mutations were nonsense (n = 4) and splicing (n = 4) mutations, large deletions (n = 3), microdeletions (n = 2), microinsertions (n = 2), and promoter mutations (n = 1). Eleven of 46 mutations were previously unknown for human populations. PMID:27529981

  8. Molecular genetics of Alzheimer's disease and aging.

    PubMed

    Cacabelos, Ramon; Fernandez-Novoa, Lucia; Lombardi, Valter; Kubota, Yasuhiko; Takeda, Masatoshi

    2005-07-01

    , accumulation of aberrant or misfolded proteins, protofibril formation, ubiquitin-proteasome system dysfunction, excitotoxic reactions, oxidative and nitrosative stress, mitochondrial injury, synaptic failure, altered metal homeostasis, dysfunction of axonal and dendritic transport, and chaperone misoperation may converge in pathogenic pathways leading to premature death and neurodegeneration. Some of these mechanisms are common to several neurodegenerative disorders, which differ depending upon the gene(s) affected and the involvement of specific genetic networks, together with epigenetic factors and environmental events. Many genes potentially associated with Alzheimer's disease in some studies cannot be confirmed as candidate genes in replication studies, indicating that methodological problems and genomic complexity are leading to erroneous conclusions. A different approach to Alzheimer's disease functional genomics is to integrate individual genetic information in polygenic genotypes (haplotype-like model) and to investigate genotype-phenotype correlations and genotype-related pharmacogenomic behaviors. The application of functional genomics to Alzheimer's disease can be a suitable strategy for molecular diagnosis and for understanding pathophysiological mechanisms associated with Alzheimer's disease-related neurodegeneration. Furthermore, the pharmacogenomics of Alzheimer's disease may contribute in the future to optimize drug development and therapeutics, increasing efficacy and safety, and reducing side-effects and unnecessary costs. PMID:16470248

  9. Heritability and molecular genetic basis of acoustic startle eye blink and affectively modulated startle response: A genome-wide association study

    PubMed Central

    VAIDYANATHAN, UMA; MALONE, STEPHEN M.; MILLER, MICHAEL B.; McGUE, MATT; IACONO, WILLIAM G.

    2014-01-01

    Acoustic startle responses have been studied extensively in relation to individual differences and psychopathology. We examined three indices of the blink response in a picture-viewing paradigm—overall startle magnitude across all picture types, and aversive and pleasant modulation scores—in 3,323 twins and parents. Biometric models and molecular genetic analyses showed that half the variance in overall startle was due to additive genetic effects. No single nucleotide polymorphism was genome-wide significant, but GRIK3 did produce a significant effect when examined as part of a candidate gene set. In contrast, emotion modulation scores showed little evidence of heritability in either biometric or molecular genetic analyses. However, in a genome-wide scan, PARP14 did produce a significant effect for aversive modulation. We conclude that, although overall startle retains potential as an endophenotype, emotion-modulated startle does not. PMID:25387708

  10. Analysis of Molecular Genetics Content in Spanish Secondary School Textbooks

    ERIC Educational Resources Information Center

    Martinez-Gracia, M. V.; Gil-Quilez, M. J.; Osada, J.

    2006-01-01

    The treatment of molecular biology in thirty-four Spanish high school biology textbooks has been analysed using a check-list made up of twenty-three items. The study showed a tendency to confuse the genetic code with genetic information. The treatment of DNA transcription, regulation of gene expression and translation were presented as masses of…

  11. Molecular Genetics of Mitochondrial Disorders

    ERIC Educational Resources Information Center

    Wong, Lee-Jun C.

    2010-01-01

    Mitochondrial respiratory chain (RC) disorders (RCDs) are a group of genetically and clinically heterogeneous diseases because of the fact that protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis, structure, and function of mitochondria, including DNA…

  12. Studies of Resurgent Bed Bugs: Population Genetic Structure, Impact of Aggregation on Development and Molecular Screening for Bartonella

    NASA Astrophysics Data System (ADS)

    Saenz, Virna Lisa

    The recent resurgence of bed bugs (Cimex lectularius L.) has created an unprecedented demand for research on its biology. The main objectives of this dissertation research were to investigate several aspects of bed bug biology: infestation and dispersal dynamics at a large and small geographical scale using molecular markers, to determine the impact of aggregation on bed bug development and to screen bed bug populations for a re-emergent pathogen. First, we studied the infestation and dispersal dynamics of bed bugs at large geographical scale (e.g., across cities, states). Although bed bug infestations are on the rise, there is a poor understanding of their dispersal patterns and sources of infestation. We conducted a genetic study of 21 bed bug infestations from the eastern United States. We genotyped samples comprised of 8 - 10 individuals per infestation at nine polymorphic microsatellite loci. Despite high genetic diversity across all infestations, with 5 -- 17 alleles per locus (mean = 10.3), we found low genetic diversity (1 -- 4 alleles per locus) within all but one of the infestations. These results suggest that nearly all the studied infestations were started by a small propagule possibly consisting of a singly mated female and/or her progeny. All infestations were strongly genetically differentiated from each other (mean pairwise FST between populations = 0.68) and we did not find strong evidence of a geographic pattern of structuring. The high level of genetic diversity across infestations from the eastern United States together with the lack of geographically organized structure is consistent with multiple introductions into the United States from foreign sources. This work is described in Chapter 2 and was published in the Journal of Medical Entomology in 2012. Second, we investigated dispersal and infestation dynamics of bed bugs at a fine geographical scale within three multistory apartment buildings: one from Raleigh, NC and two from Jersey City, NJ

  13. Molecular Genetic Analysis of Chlamydia Species.

    PubMed

    Sixt, Barbara S; Valdivia, Raphael H

    2016-09-01

    Species of Chlamydia are the etiologic agent of endemic blinding trachoma, the leading cause of bacterial sexually transmitted diseases, significant respiratory pathogens, and a zoonotic threat. Their dependence on an intracellular growth niche and their peculiar developmental cycle are major challenges to elucidating their biology and virulence traits. The last decade has seen tremendous advances in our ability to perform a molecular genetic analysis of Chlamydia species. Major achievements include the generation of large collections of mutant strains, now available for forward- and reverse-genetic applications, and the introduction of a system for plasmid-based transformation enabling complementation of mutations; expression of foreign, modified, or reporter genes; and even targeted gene disruptions. This review summarizes the current status of the molecular genetic toolbox for Chlamydia species and highlights new insights into their biology and new challenges in the nascent field of Chlamydia genetics. PMID:27607551

  14. [The research-study of pneumococci transformation in the laboratory, and the rise of bacterial genetics and molecular biology].

    PubMed

    Carrada-Bravo, Teodoro

    2016-02-01

    The virulence of pneumococci for mice depends on the production of a polysaccharide-capsule, which encloses the bacteria and protects it against phagocytosis. Capsulated pneumococci yield smooth, brilliant colonies designated S, but mutant strains arise frequently which have lost the capacity to sinthetise the capsule, are avirulent and rough designated R. F. Griffith discovery of bacterial "transformation" in 1928, is a landmark in the history of genetics, because hereditary determinants could be transferred from one bacteria to another, and laid the foundation for the subsequent recognition of deoxyribonucleic acid (DNA) as the hereditary material. A systematic analysis of the chemical nature of the "transforming principle", by O. T. Avery and his colleagues during next 10 years, culminated in a formidable weight of evidence that it possessed all properties of DNA. In 1953, J. D. Watson and F. H. C Crick by a brilliant synthesis, fitted the chemical X-ray diffraction data together into a symmetrical double-helix structure, which possessed the inherent properties of genetic material, and carries the information necessary to direct all biochemical-cellular activities and self-replications. This paper describes de early rise and development of bacterial genetics and molecular biology. PMID:26965880

  15. Molecular genetics of testicular germ cell tumors

    PubMed Central

    Sheikine, Yuri; Genega, Elizabeth; Melamed, Jonathan; Lee, Peng; Reuter, Victor E.; Ye, Huihui

    2012-01-01

    Testicular germ cell tumors (TGCT) are the most common malignancy in young men. While most TGCT are potentially curable, approximately 5% of patients with TGCT may develop chemoresistance and die from the disease. This review article summarizes current knowledge in genetics underlying the development, progression and chemoresistance of TGCT. Most post-pubertal TGCT originate from intratubular germ cell neoplasia unclassified (IGCNU), which are transformed fetal gonocytes. Development of IGCNU may involve aberrantly activated KITLG/KIT pathway and overexpression of embryonic transcription factors such as NANOG and POU5F1, which leads to suppression of apoptosis, increased proliferation, and accumulation of mutations in gonocytes. Invasive TGCT consistently show gain of chromosome 12p, typically isochromosome 12p. Single gene mutations are uncommon in TGCT. KIT, TP53, KRAS/NRAS, and BRAF are genes most commonly mutated in TGCT and implicated in their pathogenesis. Different histologic subtypes of TGCT possess different gene expression profiles that reflect different directions of differentiation. Their distinct gene expression profiles are likely caused by epigenetic regulation, in particular DNA methylation, but not by gene copy number alterations. Resistance of TGCT to chemotherapy has been linked to karyotypic aberrations, single-gene mutations, and epigenetic regulation of gene expression in small-scale studies. The study of TGCT genetics could ultimately translate into development of new molecular diagnostic and therapeutic modalities for these tumors and improve the care of patients with these malignancies. PMID:22432056

  16. Quantitative Genetics in the Era of Molecular Genetics: Learning Abilities and Disabilities as an Example

    ERIC Educational Resources Information Center

    Haworth, Claire M. A.; Plomin, Robert

    2010-01-01

    Objective: To consider recent findings from quantitative genetic research in the context of molecular genetic research, especially genome-wide association studies. We focus on findings that go beyond merely estimating heritability. We use learning abilities and disabilities as examples. Method: Recent twin research in the area of learning…

  17. Analyses of genetic ancestry enable key insights for molecular ecology.

    PubMed

    Gompert, Zachariah; Buerkle, C Alex

    2013-11-01

    Gene flow and recombination in admixed populations produce genomes that are mosaic combinations of chromosome segments inherited from different source populations, that is, chromosome segments with different genetic ancestries. The statistical problem of estimating genetic ancestry from DNA sequence data has been widely studied, and analyses of genetic ancestry have facilitated research in molecular ecology and ecological genetics. In this review, we describe and compare different model-based statistical methods used to infer genetic ancestry. We describe the conceptual and mathematical structure of these models and highlight some of their key differences and shared features. We then discuss recent empirical studies that use estimates of genetic ancestry to analyse population histories, the nature and genetic basis of species boundaries, and the genetic architecture of traits. These diverse studies demonstrate the breadth of applications that rely on genetic ancestry estimates and typify the genomics-enabled research that is becoming increasingly common in molecular ecology. We conclude by identifying key research areas where future studies might further advance this field. PMID:24103088

  18. Molecular Genetics of Supernumerary Tooth Formation

    PubMed Central

    Wang, Xiu-Ping; Fan, Jiabing

    2011-01-01

    Summary Despite advances in the knowledge of tooth morphogenesis and differentiation, relatively little is known about the aetiology and molecular mechanisms underlying supernumerary tooth formation. A small number of supernumerary teeth may be a common developmental dental anomaly, while multiple supernumerary teeth usually have a genetic component and they are sometimes thought to represent a partial third dentition in humans. Mice, which are commonly used for studying tooth development, only exhibit one dentition, with very few mouse models exhibiting supernumerary teeth similar to those in humans. Inactivation of Apc or forced activation of Wnt/β(catenin signalling results in multiple supernumerary tooth formation in both humans and in mice, but the key genes in these pathways are not very clear. Analysis of other model systems with continuous tooth replacement or secondary tooth formation, such as fish, snake, lizard, and ferret, is providing insights into the molecular and cellular mechanisms underlying succesional tooth development, and will assist in the studies on supernumerary tooth formation in humans. This information, together with the advances in stem cell biology and tissue engineering, will pave ways for the tooth regeneration and tooth bioengineering. PMID:21309064

  19. Molecular and comparative genetics of mental retardation.

    PubMed Central

    Inlow, Jennifer K; Restifo, Linda L

    2004-01-01

    Affecting 1-3% of the population, mental retardation (MR) poses significant challenges for clinicians and scientists. Understanding the biology of MR is complicated by the extraordinary heterogeneity of genetic MR disorders. Detailed analyses of >1000 Online Mendelian Inheritance in Man (OMIM) database entries and literature searches through September 2003 revealed 282 molecularly identified MR genes. We estimate that hundreds more MR genes remain to be identified. A novel test, in which we distributed unmapped MR disorders proportionately across the autosomes, failed to eliminate the well-known X-chromosome overrepresentation of MR genes and candidate genes. This evidence argues against ascertainment bias as the main cause of the skewed distribution. On the basis of a synthesis of clinical and laboratory data, we developed a biological functions classification scheme for MR genes. Metabolic pathways, signaling pathways, and transcription are the most common functions, but numerous other aspects of neuronal and glial biology are controlled by MR genes as well. Using protein sequence and domain-organization comparisons, we found a striking conservation of MR genes and genetic pathways across the approximately 700 million years that separate Homo sapiens and Drosophila melanogaster. Eighty-seven percent have one or more fruit fly homologs and 76% have at least one candidate functional ortholog. We propose that D. melanogaster can be used in a systematic manner to study MR and possibly to develop bioassays for therapeutic drug discovery. We selected 42 Drosophila orthologs as most likely to reveal molecular and cellular mechanisms of nervous system development or plasticity relevant to MR. PMID:15020472

  20. Molecular genetics of febrile seizures.

    PubMed

    Iwasaki, Nobuaki; Nakayama, Junko; Hamano, Kenzo; Matsui, Akira; Arinami, Tadao

    2002-01-01

    Febrile seizures are the most common form of convulsion, occurring in 2-5% of infants in Europe and North America and in 6-9% in Japan. In large families, the febrile seizure (FS) susceptibility trait is inherited by the autosomal dominant pattern with reduced penetrance. Two putative FS loci, FEB1 (chromosome 8q13-q21) and FEB2 (chromosome 19p13.3) have been mapped. A clinical subset of FS, termed generalized epilepsy with febrile seizures plus (GEFS+), was reported. In GEFS+ families, a mutation in the voltage-gated sodium channel beta1 subunit gene (SCN1B) at chromosome 19q13.1 and two mutations of the same alpha1 subunit gene (SCN1A) at chromosome 2q24 were identified. These loci are linked to febrile convulsions in large families. We conducted a genome-wide linkage search for FS in one large family with subsequent linkage confirmation in 39 nuclear families using nonparametric allele-sharing methods, and found a new FS susceptibility locus, FEB4 (chromosome 5q14-q15). In contrast to the FEB1, FEB2, and GEFS+ genetic loci, linkage to FEB4 was suggested in nuclear FS families, indicating that FEB4 may be the most common linkage locus in FS families. PMID:12383277

  1. Juvenile myoclonic epilepsy with generalised and focal electroencephalographic abnormalities: a case report with a molecular genetic study.

    PubMed

    Bartocci, A; Elia, M; Calì, F; Tiacci, C; Cantisani, A T; Perticoni, G

    2007-10-01

    This is the case of a 16-year-old girl with juvenile myoclonic epilepsy (JME) and maternal family history positive for epilepsy and febrile seizures, presenting ictal and interictal generalised, as well as focal paroxysmal abnormalities over the right central-temporal regions activated during sleep. The brain magnetic resonance image was normal and the seizures responded to therapy with valproate and lamotrigine. A molecular genetic analysis led to the identification of a polymorphism (A-->G) in position 10 in the intron 3 (rs949626) of the EFHC1 gene; and a polymorphism (T-->C) of the exon of the GABRA1 gene, without aminoacidic exchange. In the literature this is the first case of JME with electroencephalograph focal epileptiform abnormalities, but without EFHC1 and GABRA1 gene mutations. PMID:17972043

  2. Genetic variants in Alzheimer disease - molecular and brain network approaches.

    PubMed

    Gaiteri, Chris; Mostafavi, Sara; Honey, Christopher J; De Jager, Philip L; Bennett, David A

    2016-07-01

    Genetic studies in late-onset Alzheimer disease (LOAD) are aimed at identifying core disease mechanisms and providing potential biomarkers and drug candidates to improve clinical care of AD. However, owing to the complexity of LOAD, including pathological heterogeneity and disease polygenicity, extraction of actionable guidance from LOAD genetics has been challenging. Past attempts to summarize the effects of LOAD-associated genetic variants have used pathway analysis and collections of small-scale experiments to hypothesize functional convergence across several variants. In this Review, we discuss how the study of molecular, cellular and brain networks provides additional information on the effects of LOAD-associated genetic variants. We then discuss emerging combinations of these omic data sets into multiscale models, which provide a more comprehensive representation of the effects of LOAD-associated genetic variants at multiple biophysical scales. Furthermore, we highlight the clinical potential of mechanistically coupling genetic variants and disease phenotypes with multiscale brain models. PMID:27282653

  3. Genetic and molecular alterations across medulloblastoma subgroups.

    PubMed

    Skowron, Patryk; Ramaswamy, Vijay; Taylor, Michael D

    2015-10-01

    Medulloblastoma is the most common malignant brain tumour diagnosed in children. Over the last few decades, advances in radiation and chemotherapy have significantly improved the odds of survival. Nevertheless, one third of all patients still succumb to their disease, and many long-term survivors are afflicted with neurocognitive sequelae. Large-scale multi-institutional efforts have provided insight into the transcriptional and genetic landscape of medulloblastoma. Four distinct subgroups of medulloblastoma have been identified, defined by distinct transcriptomes, genetics, demographics and outcomes. Integrated genomic profiling of each of these subgroups has revealed distinct genetic alterations, driving pathways and in some instances cells of origin. In this review, we highlight, in a subgroup-specific manner, our current knowledge of the genetic and molecular alterations in medulloblastoma and underscore the possible avenues for future therapeutic intervention. PMID:26350064

  4. Molecular Genetic Investigations of Autism.

    ERIC Educational Resources Information Center

    Maestrini, Elena; Marlow, Angela J.; Weeks, Daniel E.; Monaco, Anthony P.

    1998-01-01

    Describes a current research study which is attempting to identify autism susceptibility loci by a systematic screening of the whole human genome by using multiplex families. It reviews the resources and methods used in the study including extensive collection of family data, semiautomated genotyping technology, and specialized statistical…

  5. ISSR, an effective molecular approach for studying genetic variability among Schistosoma japonicum isolates from different provinces in mainland China.

    PubMed

    Zhao, Guang-Hui; Li, Juan; Zou, Feng-Cai; Mo, Xi-Hao; Yuan, Zi-Guo; Lin, Rui-Qing; Weng, Ya-Biao; Zhu, Xing-Quan

    2009-09-01

    In the present study, inter-simple sequence repeats (ISSRs) markers were used to examine the genetic variability of Schistosoma japonicum isolates from different provinces in mainland China, using S. japonicum from Japan and S. mansoni from Puerto Rico for comparison. Of the 30 primers screened, 4 produced highly reproducible ISSR fragments. Using these primers, 107 discernible DNA fragments were generated with 105 (98.13%) being polymorphic, indicating considerable genetic variation among the examined S. japonicum isolates. The percentage of polymorphic bands among S. japonicum isolates from mainland China and Japan was 82.24%, 43.93% among mountainous type isolates and 64.49% among lake/marshland type isolates from mainland China. UPGMA analysis revealed that all of the S. japonicum samples were grouped into two clades, the first contained isolates from mainland China, and the other one contained samples from Japan. Within the cluster of S. japonicum isolates from mainland China, isolates from mountainous Sichuan and Yunnan provinces grouped together, whereas isolates from lake/marshland regions (Anhui, Jiangsu and Hubei provinces) clustered together. The results of present study demonstrated that the ISSR markers are useful for studying genetic diversity and population structure of S. japonicum isolates from mainland China. PMID:19539784

  6. Molecular Genetic Manipulation of Vector Mosquitoes

    PubMed Central

    Terenius, Olle; Marinotti, Osvaldo; Sieglaff, Douglas; James, Anthony A.

    2008-01-01

    Genetic strategies for reducing populations of vector mosquitoes or replacing them with those that are not able to transmit pathogens benefit greatly from molecular tools that allow gene manipulation and transgenesis. Mosquito genome sequences and associated EST (Expressed Sequence Tags) databases enable large-scale investigations to provide new insights into evolutionary, biochemical, genetic, metabolic and physiological pathways. Additionally, comparative genomics reveals the bases for evolutionary mechanisms with particular focus on specific interactions between vectors and pathogens. We discuss how this information may be exploited for the optimization of transgenes that interfere with the propagation and development of pathogens in their mosquito hosts. PMID:18996342

  7. Application of Molecular Genetics and Transformation to Barley Improvement

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter of the new barley monograph summarizes current applications of molecular genetics and transformation to barley improvement. The chapter describes recent applications of molecular markers including association genetics, QTL mapping and marker assisted selection in barley programs, and in...

  8. Genetic and molecular changes in ovarian cancer

    PubMed Central

    Hollis, Robert L; Gourley, Charlie

    2016-01-01

    Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications. However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research. PMID:27458531

  9. A Preliminary Study of Genetic Variation in Populations of Monstera adansonii var. klotzschiana (Araceae) from North-East Brazil, Estimated with AFLP Molecular Markers

    PubMed Central

    Andrade, I. M.; Mayo, S. J.; van den Berg, C.; Fay, M. F.; Chester, M.; Lexer, C.; Kirkup, D.

    2007-01-01

    Background and Aims This study sought genetic evidence of long-term isolation in populations of Monstera adansonii var. klotzschiana (Araceae), a herbaceous, probably outbreeding, humid forest hemi-epiphyte, in the brejo forests of Ceará (north-east Brazil), and clarification of their relationships with populations in Amazonia and the Atlantic forest of Brazil. Methods Within-population genetic diversity and between-population dissimilarity were estimated using AFLP molecular markers in 75 individuals from eight populations located in Ceará, the Brazilian Atlantic Forest and Amazonia. Key Results The populations showed a clinal pattern of weak genetic differentiation over a large geographical region (FST = 0·1896). A strong correlation between genetic and geographical distance (Mantel test: r = 0·6903, P = 0·002) suggests a historical pattern of isolation by distance. Genetic structure analysis revealed at least two distinct gene pools in the data. The two isolated Ceará populations are significantly different from each other (pairwise ΦPT = 0·137, P = 0·003) and as diverse (Nei's gene diversity, average He = 0·1832, 0·1706) as those in the Atlantic and Amazon forest regions. The population in southern Brazil is less diverse (Nei's gene diversity, average He = 0·127) than the rest. The Ceará populations are related to those of the Atlantic forest rather than those from Amazonia (AMOVA, among-groups variation = 11·95 %, P = 0·037). Conclusions The gene pools detected within an overall pattern of clinal variation suggest distinct episodes of gene flow, possibly correlated with past humid forest expansions. The Ceará populations show no evidence of erosion of genetic diversity, although this was expected because of their isolation. Their genetic differentiation and relatively high diversity reinforce the importance of conserving the endangered brejo forests. PMID:17823112

  10. Overview of molecular, cellular, and genetic neurotoxicology.

    PubMed

    Wallace, David R

    2005-05-01

    It has become increasingly evident that the field of neurotoxicology is not only rapidly growing but also rapidly evolving, especially over the last 20 years. As the number of drugs and environmental and bacterial/viral agents with potential neurotoxic properties has grown, the need for additional testing has increased. Only recently has the technology advanced to a level that neurotoxicologic studies can be performed without operating in a "black box." Examination of the effects of agents that are suspected of being toxic can occur on the molecular (protein-protein), cellular (biomarkers, neuronal function), and genetic (polymorphisms) level. Together, these areas help to elucidate the potential toxic profiles of unknown (and in some cases, known) agents. The area of proteomics is one of the fastest growing areas in science and particularly applicable to neurotoxicology. Lubec et al, provide a review of the potential and limitations of proteomics. Proteomics focuses on a more comprehensive view of cellular proteins and provides considerably more information about the effects of toxins on the CNS. Proteomics can be classified into three different focuses: post-translational modification, protein-expression profiling, and protein-network mapping. Together, these methods represent a more complete and powerful image of protein modifications following potential toxin exposure. Cellular neurotoxicology involves many cellular processes including alterations in cellular energy homeostasis, ion homeostasis, intracellular signaling function, and neurotransmitter release, uptake, and storage. The greatest hurdle in cellular neurotoxicology has been the discovery of appropriate biomarkers that are reliable, reproducible, and easy to obtain. There are biomarkers of exposure effect, and susceptibility. Finding the appropriate biomarker for a particular toxin is a daunting task. The appropriate biomarker for a particular toxin is a daunting task. The advantage to biomarker

  11. An update on the molecular genetics toolbox for staphylococci

    PubMed Central

    Prax, Marcel; Lee, Chia Y.

    2013-01-01

    Staphylococci are Gram-positive spherical bacteria of enormous clinical and biotechnological relevance. Staphylococcus aureus has been extensively studied as a model pathogen. A plethora of methods and molecular tools has been developed for genetic modification of at least ten different staphylococcal species to date. Here we review recent developments of various genetic tools and molecular methods for staphylococcal research, which include reporter systems and vectors for controllable gene expression, gene inactivation, gene essentiality testing, chromosomal integration and transposon delivery. It is furthermore illustrated how mutant strain construction by homologous or site-specific recombination benefits from sophisticated counterselection methods. The underlying genetic components have been shown to operate in wild-type staphylococci or modified chassis strains. Finally, possible future developments in the field of applied Staphylococcus genetics are highlighted. PMID:23378573

  12. Heritability and molecular-genetic basis of the P3 event-related brain potential: A genome-wide association study

    PubMed Central

    MALONE, STEPHEN M.; VAIDYANATHAN, UMA; BASU, SAONLI; MILLER, MICHAEL B.; MCGUE, MATT; IACONO, WILLIAM G.

    2014-01-01

    P3 amplitude is a candidate endophenotype for disinhibitory psychopathology, psychosis, and other disorders. The present study is a comprehensive analysis of the behavioral- and molecular-genetic basis of P3 amplitude and a P3 genetic factor score in a large community sample (N = 4,211) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric models indicated that as much as 65% of the variance in each measure was due to additive genes. All SNPs in aggregate accounted for approximately 40% to 50% of the heritable variance. However, analyses of individual SNPs did not yield any significant associations. Analyses of individual genes did not confirm previous associations between P3 amplitude and candidate genes but did yield a novel association with myelin expression factor 2 (MYEF2). Main effects of individual variants may be too small to be detected by GWAS without larger samples. PMID:25387705

  13. Genetic variation and dopamine D2 receptor availability: a systematic review and meta-analysis of human in vivo molecular imaging studies

    PubMed Central

    Gluskin, B S; Mickey, B J

    2016-01-01

    The D2 dopamine receptor mediates neuropsychiatric symptoms and is a target of pharmacotherapy. Inter-individual variation of D2 receptor density is thought to influence disease risk and pharmacological response. Numerous molecular imaging studies have tested whether common genetic variants influence D2 receptor binding potential (BP) in humans, but demonstration of robust effects has been limited by small sample sizes. We performed a systematic search of published human in vivo molecular imaging studies to estimate effect sizes of common genetic variants on striatal D2 receptor BP. We identified 21 studies examining 19 variants in 11 genes. The most commonly studied variant was a single-nucleotide polymorphism in ANKK1 (rs1800497, Glu713Lys, also called ‘Taq1A'). Fixed- and random-effects meta-analyses of this variant (5 studies, 194 subjects total) revealed that striatal BP was significantly and robustly lower among carriers of the minor allele (Lys713) relative to major allele homozygotes. The weighted standardized mean difference was −0.57 under the fixed-effect model (95% confidence interval=(−0.87, −0.27), P=0.0002). The normal relationship between rs1800497 and BP was not apparent among subjects with neuropsychiatric diseases. Significant associations with baseline striatal D2 receptor BP have been reported for four DRD2 variants (rs1079597, rs1076560, rs6277 and rs1799732) and a PER2 repeat polymorphism, but none have yet been tested in more than two independent samples. Our findings resolve apparent discrepancies in the literature and establish that rs1800497 robustly influences striatal D2 receptor availability. This genetic variant is likely to contribute to important individual differences in human striatal function, neuropsychiatric disease risk and pharmacological response. PMID:26926883

  14. Molecular genetic approaches to understanding disease.

    PubMed Central

    Savill, J.

    1997-01-01

    Molecular genetics has greatly increased the understanding of diseases in which there is a single gene defect such as cystic fibrosis. Discovering the gene responsible and its function not only helps determine the pathogenesis of the disease but also offers a possible treatment-gene therapy. Polygenic disorders such as diabetes may soon yield their secrets to the same approach. Animal models of genetic diseases are proving useful research tools, and transgenesis has made xenografting possible. Furthermore, antisense technology allows specific inhibition of undesirably overexpressed genes such as those driving unwanted vascular cell proliferation and restenosis after angioplasty. The completion of the human genome project should make the search for "disease" gene much quicker and will increase still further the importance of these gene based approaches toward diseases. PMID:9006475

  15. Molecular and genetic inflammation networks in major human diseases.

    PubMed

    Zhao, Yongzhong; Forst, Christian V; Sayegh, Camil E; Wang, I-Ming; Yang, Xia; Zhang, Bin

    2016-07-19

    It has been well-recognized that inflammation alongside tissue repair and damage maintaining tissue homeostasis determines the initiation and progression of complex diseases. Albeit with the accomplishment of having captured the most critical inflammation-involved molecules, genetic susceptibilities, epigenetic factors, and environmental factors, our schemata on the role of inflammation in complex diseases remain largely patchy, in part due to the success of reductionism in terms of research methodology per se. Omics data alongside the advances in data integration technologies have enabled reconstruction of molecular and genetic inflammation networks which shed light on the underlying pathophysiology of complex diseases or clinical conditions. Given the proven beneficial role of anti-inflammation in coronary heart disease as well as other complex diseases and immunotherapy as a revolutionary transition in oncology, it becomes timely to review our current understanding of the molecular and genetic inflammation networks underlying major human diseases. In this review, we first briefly discuss the complexity of infectious diseases and then highlight recently uncovered molecular and genetic inflammation networks in other major human diseases including obesity, type II diabetes, coronary heart disease, late onset Alzheimer's disease, Parkinson's disease, and sporadic cancer. The commonality and specificity of these molecular networks are addressed in the context of genetics based on genome-wide association study (GWAS). The double-sword role of inflammation, such as how the aberrant type 1 and/or type 2 immunity leads to chronic and severe clinical conditions, remains open in terms of the inflammasome and the core inflammatome network features. Increasingly available large Omics and clinical data in tandem with systems biology approaches have offered an exciting yet challenging opportunity toward reconstruction of more comprehensive and dynamic molecular and genetic

  16. Genetics and molecular biology of hypotension

    NASA Technical Reports Server (NTRS)

    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.

  17. Psychobiology and molecular genetics of resilience.

    PubMed

    Feder, Adriana; Nestler, Eric J; Charney, Dennis S

    2009-06-01

    Every individual experiences stressful life events. In some cases acute or chronic stress leads to depression and other psychiatric disorders, but most people are resilient to such effects. Recent research has begun to identify the environmental, genetic, epigenetic and neural mechanisms that underlie resilience, and has shown that resilience is mediated by adaptive changes in several neural circuits involving numerous neurotransmitter and molecular pathways. These changes shape the functioning of the neural circuits that regulate reward, fear, emotion reactivity and social behaviour, which together are thought to mediate successful coping with stress. PMID:19455174

  18. Psychobiology and molecular genetics of resilience

    PubMed Central

    Feder, Adriana; Nestler, Eric J.; Charney, Dennis S.

    2010-01-01

    Every individual experiences stressful life events. In some cases acute or chronic stress leads to depression and other psychiatric disorders, but most people are resilient to such effects. Recent research has begun to identify the environmental, genetic, epigenetic and neural mechanisms that underlie resilience, and has shown that resilience is mediated by adaptive changes in several neural circuits involving numerous neurotransmitter and molecular pathways. These changes shape the functioning of the neural circuits that regulate reward, fear, emotion reactivity and social behaviour, which together are thought to mediate successful coping with stress. PMID:19455174

  19. Of mice and men: molecular genetics of congenital heart disease.

    PubMed

    Andersen, Troels Askhøj; Troelsen, Karin de Linde Lind; Larsen, Lars Allan

    2014-04-01

    Congenital heart disease (CHD) affects nearly 1 % of the population. It is a complex disease, which may be caused by multiple genetic and environmental factors. Studies in human genetics have led to the identification of more than 50 human genes, involved in isolated CHD or genetic syndromes, where CHD is part of the phenotype. Furthermore, mapping of genomic copy number variants and exome sequencing of CHD patients have led to the identification of a large number of candidate disease genes. Experiments in animal models, particularly in mice, have been used to verify human disease genes and to gain further insight into the molecular pathology behind CHD. The picture emerging from these studies suggest that genetic lesions associated with CHD affect a broad range of cellular signaling components, from ligands and receptors, across down-stream effector molecules to transcription factors and co-factors, including chromatin modifiers. PMID:23934094

  20. The molecular genetics of cultivated mushrooms.

    PubMed

    Whiteford, J R; Thurston, C F

    2000-01-01

    The types, economic significance and methods of production of the principal cultivated mushrooms are described in outline. These organisms are all less than ideal for conventional genetic analysis and breeding, so molecular methods afford a particular opportunity to advance our understanding of their biology and potentially give the prospect of improvement by gene manipulation. The sequences described are limited to those found in GenBank by August 1999. The gene sequences isolated from the white button mushroom Agaricus bisporus, the shiitake Lentinula edodes, the oyster mushrooms Pleurotus spp., the paddy straw mushroom Volvariella volvacea and the enotake Flammulina velutipes are described. The largest group are genes from A. bisporus, which includes 29 for intracellular proteins and 12 for secreted proteins. In comparison, only a total of 26 sequences can be reported for the other cultivated species. A. bisporus is also the only cultivated species for which molecular karyotyping is already supported by reliable markers for all 13 of its chromosomes. PMID:10907549

  1. Molecular population genetic analysis of emerged bacterial pathogens: selected insights.

    PubMed Central

    Musser, J. M.

    1996-01-01

    Research in bacterial population genetics has increased in the last 10 years. Population genetic theory and tools and related strategies have been used to investigate bacterial pathogens that have contributed to recent episodes of temporal variation in disease frequency and severity. A common theme demonstrated by these analyses is that distinct bacterial clones are responsible for disease outbreaks and increases in infection frequency. Many of these clones are characterized by unique combinations of virulence genes or alleles of virulence genes. Because substantial interclonal variance exists in relative virulence, molecular population genetic studies have led to the concept that the unit of bacterial pathogenicity is the clone or cell line. Continued new insights into host parasite interactions at the molecular level will be achieved by combining clonal analysis of bacterial pathogens with large-scale comparative sequencing of virulence genes. PMID:8903193

  2. Molecular Genetics of Pediatric Soft Tissue Tumors

    PubMed Central

    Chang, Chung-Che; Shidham, Vinod B.

    2003-01-01

    The application of molecular genetics to pediatric soft tissue tumors has grown tremendously over the last decade. It has resulted in the identification of novel genes that have provided us with an increased understanding of oncogenesis. Furthermore, these findings have identified diagnostic and potentially prognostic factors for patient management. Molecular diagnostic techniques, such as reverse transcription PCR (RT-PCR) and fluorescence in situ hybridization (FISH), have become important tools for evaluating pediatric soft tissue tumors. By detecting characteristic fusion genes, these techniques have greatly increased the diagnostic accuracy of histopathological classification. One of the exciting promises of the development of these molecular techniques is their ability to detect micrometastasis and minimal residual disease. Monitoring of minimal residual disease in pediatric soft tissue tumors by quantitative RT-PCR may provide important prognostic information. Furthermore, the potential development of targeted therapy based on the understanding of the molecular pathology of a specific soft tissue tumor may complement existing treatments and improve disease outcome. PMID:12876204

  3. Generation and analysis of ESTs from strawberry (Fragaria xananassa) fruits and evaluation of their utility in genetic and molecular studies

    PubMed Central

    2010-01-01

    Background Cultivated strawberry is a hybrid octoploid species (Fragaria xananassa Duchesne ex. Rozier) whose fruit is highly appreciated due to its organoleptic properties and health benefits. Despite recent studies on the control of its growth and ripening processes, information about the role played by different hormones on these processes remains elusive. Further advancement of this knowledge is hampered by the limited sequence information on genes from this species, despite the abundant information available on genes from the wild diploid relative Fragaria vesca. However, the diploid species, or one ancestor, only partially contributes to the genome of the cultivated octoploid. We have produced a collection of expressed sequence tags (ESTs) from different cDNA libraries prepared from different fruit parts and developmental stages. The collection has been analysed and the sequence information used to explore the involvement of different hormones in fruit developmental processes, and for the comparison of transcripts in the receptacle of ripe fruits of diploid and octoploid species. The study is particularly important since the commercial fruit is indeed an enlarged flower receptacle with the true fruits, the achenes, on the surface and connected through a network of vascular vessels to the central pith. Results We have sequenced over 4,500 ESTs from Fragaria xananassa, thus doubling the number of ESTs available in the GenBank of this species. We then assembled this information together with that available from F. xananassa resulting a total of 7,096 unigenes. The identification of SSRs and SNPs in many of the ESTs allowed their conversion into functional molecular markers. The availability of libraries prepared from green growing fruits has allowed the cloning of cDNAs encoding for genes of auxin, ethylene and brassinosteroid signalling processes, followed by expression studies in selected fruit parts and developmental stages. In addition, the sequence

  4. Promoting Middle School Students' Understandings of Molecular Genetics

    NASA Astrophysics Data System (ADS)

    Duncan, Ravit Golan; Freidenreich, Hava Bresler; Chinn, Clark A.; Bausch, Andrew

    2011-03-01

    Genetics is the cornerstone of modern biology and understanding genetics is a critical aspect of scientific literacy. Research has shown, however, that many high school graduates lack fundamental understandings in genetics necessary to make informed decisions or to participate in public debates over emerging technologies in molecular genetics. Currently, much of genetics instruction occurs at the high school level. However, recent policy reports suggest that we may need to begin introducing aspects of core concepts in earlier grades and to successively develop students' understandings of these concepts in subsequent grades. Given the paucity of research about genetics learning at the middle school level, we know very little about what students in earlier grades are capable of reasoning about in this domain. In this paper, we discuss a research study aimed at fostering deeper understandings of molecular genetics at the middle school level. As part of the research we designed a two-week model-based inquiry unit implemented in two 7th grade classrooms ( N = 135). We describe our instructional design and report results based on analysis of pre/post assessments and written artifacts of the unit. Our findings suggest that middle school students can develop: (a) a view of genes as productive instructions for proteins, (b) an understanding of the role of proteins in mediating genetic effects, and (c) can use this knowledge to reason about a novel genetic phenomena. However, there were significant differences in the learning gains in both classrooms and we provide speculative explanations of what may have caused these differences.

  5. Molecular and genetic ecotoxicologic approaches to aquatic environmental bioreporting.

    PubMed Central

    Beaty, B J; Black, W C; Carlson, J O; Clements, W H; DuTeau, N; Harrahy, E; Nuckols, J; Kenneth, E; Olson, K E; Rayms-Keller, A

    1998-01-01

    Molecular and population genetic ecotoxicologic approaches are being developed for the utilization of arthropods as bioreporters of heavy metal mixtures in the environment. The explosion of knowledge in molecular biology, molecular genetics, and biotechnology provides an unparalleled opportunity to use arthropods as bioreporter organisms. Interspecific differences in aquatic arthropod populations have been previously demonstrated in response to heavy metal insult in the Arkansas River (AR) California Gulch Superfund site (CGSS). Population genetic analyses were conducted on the mayfly Baetis tricaudatus. Genetic polymorphisms were detected in polymerase chain reaction amplified 16S mitochondrial rDNA (a selectively neutral gene) of B tricaudatus using single-strand conformation polymorphism analysis. Genetic differences may have resulted from impediments to gene flow in the population caused by mortality arising from exposure to heavy metal mixture pollution. In laboratory studies a candidate metal-responsive mucinlike gene, which is metal and dose specific, has been identified in Chironomus tentans and other potential AR-CGSS bioreporter species. Population genetic analyses using the mucinlike gene may provide insight into the role of this selectable gene in determining the breeding structure of B. tricaudatus in the AR-CGSS and may provide mechanistic insight into determinants of aquatic arthropod response to heavy metal insult. Metal-responsive (MR) genes and regulatory sequences are being isolated, characterized, and assayed for differential gene expression in response to heavy metal mixture pollution in the AR-CGSS. Identified promoter sequences can then be engineered into previously developed MR constructs to provide sensitive in vitro assays for environmental bioreporting of heavy metal mixtures. The results of the population genetic studies are being entered into an AR geographic information system that contains substantial biological, chemical, and

  6. Functional genomics bridges the gap between quantitative genetics and molecular biology

    PubMed Central

    Lappalainen, Tuuli

    2015-01-01

    Deep characterization of molecular function of genetic variants in the human genome is becoming increasingly important for understanding genetic associations to disease and for learning to read the regulatory code of the genome. In this paper, I discuss how recent advances in both quantitative genetics and molecular biology have contributed to understanding functional effects of genetic variants, lessons learned from eQTL studies, and future challenges in this field. PMID:26430152

  7. [Progress in the molecular genetic mechanism of gonadoblastoma].

    PubMed

    Lili, Yu; Wanru, Dong; Minghui, Chen; Xiangyang, Kong

    2015-11-01

    Gonadoblastoma (GB), a rare in situ germ cell tumor derived from sex cord and germ cells, is closely associated with gonadal dysgenesis. About 80% of GB individuals exhibit 46, XY female phenotype while the others are 45, XY and 46, XX with disorders of sex development. Moreover, 35% of GB can eventually develop into malignant tumors, such as seminoma and dysgerminoma tumors. The molecular genetic mechanism of GB remains to be fully uncovered due to phenotypic and genetic heterogeneity. Increasing studies show that the formation of GB is closely related to genes regulating sexual differentiation and determination (e.g., SRY, WT1, SOX9, Foxl2, TSPY, etc), and is affected by the interaction of genetic and epigenetic regulation. Here we describe the clinical and pathological features, diagnosis and treatment of GB, and also summarize the molecular genetic and epigenetic mechanisms underlying the gonadal abnormalities that lead to GB. We analyze and construct the common gene regulatory networks related to the development of GB, and describe some obstacles and deficiencies in current studies to provide innovative perspectives on further studying the pathological and molecular mechanisms of GB. PMID:26582524

  8. Molecular genetic analysis of Down syndrome.

    PubMed

    Patterson, David

    2009-07-01

    Down syndrome (DS) is caused by trisomy of all or part of human chromosome 21 (HSA21) and is the most common genetic cause of significant intellectual disability. In addition to intellectual disability, many other health problems, such as congenital heart disease, Alzheimer's disease, leukemia, hypotonia, motor disorders, and various physical anomalies occur at an elevated frequency in people with DS. On the other hand, people with DS seem to be at a decreased risk of certain cancers and perhaps of atherosclerosis. There is wide variability in the phenotypes associated with DS. Although ultimately the phenotypes of DS must be due to trisomy of HSA21, the genetic mechanisms by which the phenotypes arise are not understood. The recent recognition that there are many genetically active elements that do not encode proteins makes the situation more complex. Additional complexity may exist due to possible epigenetic changes that may act differently in DS. Numerous mouse models with features reminiscent of those seen in individuals with DS have been produced and studied in some depth, and these have added considerable insight into possible genetic mechanisms behind some of the phenotypes. These mouse models allow experimental approaches, including attempts at therapy, that are not possible in humans. Progress in understanding the genetic mechanisms by which trisomy of HSA21 leads to DS is the subject of this review. PMID:19526251

  9. Use of molecular markers to study the effects of environmental impacts on genetic diversity in brown bullhead (Ameirus nebulosus) populations.

    PubMed

    Silbiger, R N; Leonard, A C; Dimsoski, P; Foré, S; Guttman, S I; Roth, A C; Gordon, D A; Wessendarp, T; Toth, G P; Smith, M K

    2001-11-01

    Conservation biology needs sound biological information in order to maintain biological diversity in the face of the current rate of loss. An important component of the information needed is the level of genetic diversity within and between populations, especially for those species faced with exposure to environmental stressors. We applied multilocus DNA profile analysis (highly variable number tandem repeats [HVNTR] and randomly amplified polymorphic DNA [RAPD] techniques) and allozyme analysis to test whether individuals from historically degraded sites display levels of genetic diversity different from individuals taken from reference sites. Four Lake Erie tributaries, two impacted and two reference sites, were the sources of brown bullhead (Ameiurus nebulosus) samples. Pairwise comparison of the sampled populations demonstrated an association of decreased genetic diversity with exposure of brown bullhead to stressors using both RAPD and HVNTR analysis. PMID:11699785

  10. Bottlenecks in molecular testing for rare genetic diseases.

    PubMed

    Willems, Patrick J

    2008-06-01

    Despite the impressive progress in our understanding of the genetic causes of genetic diseases over the past decade, molecular diagnosis for rare genetic disorders is still in its infancy, being slow, expensive, unreliable, insufficient, and ill-organized in many countries. This leaves the gap between the hype of the current genomic research and the hope for a simple genetic diagnosis too large for patients and families affected with genetic disease. The bottlenecks in the molecular testing for rare genetic disorders are discussed below. PMID:18412107

  11. SITVITWEB--a publicly available international multimarker database for studying Mycobacterium tuberculosis genetic diversity and molecular epidemiology.

    PubMed

    Demay, Christophe; Liens, Benjamin; Burguière, Thomas; Hill, Véronique; Couvin, David; Millet, Julie; Mokrousov, Igor; Sola, Christophe; Zozio, Thierry; Rastogi, Nalin

    2012-06-01

    Among various genotyping methods to study Mycobacterium tuberculosis complex (MTC) genotypic polymorphism, spoligotyping and mycobacterial interspersed repetitive units-variable number of DNA tandem repeats (MIRU-VNTRs) have recently gained international approval as robust, fast, and reproducible typing methods generating data in a portable format. Spoligotyping constituted the backbone of a publicly available database SpolDB4 released in 2006; nonetheless this method possesses a low discriminatory power when used alone and should be ideally used in conjunction with a second typing method such as MIRU-VNTRs for high-resolution epidemiological studies. We hereby describe a publicly available international database named SITVITWEB which incorporates such multimarker data allowing to have a global vision of MTC genetic diversity worldwide based on 62,582 clinical isolates corresponding to 153 countries of patient origin (105 countries of isolation). We report a total of 7105 spoligotype patterns (corresponding to 58,180 clinical isolates) - grouped into 2740 shared-types or spoligotype international types (SIT) containing 53,816 clinical isolates and 4364 orphan patterns. Interestingly, only 7% of the MTC isolates worldwide were orphans whereas more than half of SITed isolates (n=27,059) were restricted to only 24 most prevalent SITs. The database also contains a total of 2379 MIRU patterns (from 8161 clinical isolates) from 87 countries of patient origin (35 countries of isolation); these were grouped in 847 shared-types or MIRU international types (MIT) containing 6626 isolates and 1533 orphan patterns. Lastly, data on 5-locus exact tandem repeats (ETRs) were available on 4626 isolates from 59 countries of patient origin (22 countries of isolation); a total of 458 different VNTR patterns were observed - split into 245 shared-types or VNTR International Types (VIT) containing 4413 isolates) and 213 orphan patterns. Datamining of SITVITWEB further allowed to update

  12. An inbred line of the diploid strawberry Fragaria vesca f. semperflorens for genomic and molecular genetic studies in the Rosaceae

    PubMed Central

    2009-01-01

    a small genome, a seed to seed cycle of 3.0 - 3.5 months, and produce fruit in 7.5 cm pots in a growth chamber. YW5AF7 is runnerless and therefore easy to maintain in the greenhouse, forms abundant branch crowns for vegetative propagation, and produces highly aromatic yellow fruit throughout the year in the greenhouse. F. vesca can be transformed with Agrobacterium tumefaciens, making these plants suitable for insertional mutagenesis, RNAi and overexpression studies that can be compared against a stable baseline of phenotypic descriptors and can be readily genetically substantiated. PMID:19878589

  13. Molecular Genetic Tools and Techniques for Marchantia polymorpha Research.

    PubMed

    Ishizaki, Kimitsune; Nishihama, Ryuichi; Yamato, Katsuyuki T; Kohchi, Takayuki

    2016-02-01

    Liverworts occupy a basal position in the evolution of land plants, and are a key group to address a wide variety of questions in plant biology. Marchantia polymorpha is a common, easily cultivated, dioecious liverwort species, and is emerging as an experimental model organism. The haploid gametophytic generation dominates the diploid sporophytic generation in its life cycle. Genetically homogeneous lines in the gametophyte generation can be established easily and propagated through asexual reproduction, which aids genetic and biochemical experiments. Owing to its dioecy, male and female sexual organs are formed in separate individuals, which enables crossing in a fully controlled manner. Reproductive growth can be induced at the desired times under laboratory conditions, which helps genetic analysis. The developmental process from a single-celled spore to a multicellular body can be observed directly in detail. As a model organism, molecular techniques for M. polymorpha are well developed; for example, simple and efficient protocols of Agrobacterium-mediated transformation have been established. Based on them, various strategies for molecular genetics, such as introduction of reporter constructs, overexpression, gene silencing and targeted gene modification, are available. Herein, we describe the technologies and resources for reverse and forward genetics in M. polymorpha, which offer an excellent experimental platform to study the evolution and diversity of regulatory systems in land plants. PMID:26116421

  14. [Glucotransporters: clinical, molecular and genetic aspects].

    PubMed

    Sandoval-Muñiz, Roberto de Jesús; Vargas-Guerrero, Belinda; Flores-Alvarado, Luis Javier; Gurrola-Díaz, Carmen Magdalena

    2016-01-01

    Oxidation of glucose is the major source of obtaining cell energy, this process requires glucose transport into the cell. However, cell membranes are not permeable to polar molecules such as glucose; therefore its internalization is accomplished by transporter proteins coupled to the cell membrane. In eukaryotic cells, there are two types of carriers coupled to the membrane: 1) cotransporter Na+-glucose (SGLT) where Na+ ion provides motive power for the glucose´s internalization, and 2) the glucotransporters (GLUT) act by facilitated diffusion. This review will focus on the 14 GLUT so far described. Despite the structural homology of GLUT, different genetic alterations of each GLUT cause specific clinical entities. Therefore, the aim of this review is to gather the molecular and biochemical available information of each GLUT as well as the particular syndromes and pathologies related with GLUT´s alterations and their clinical approaches. PMID:27595260

  15. Familial renal cancer: molecular genetics and surgical management.

    PubMed

    Barrisford, Glen W; Singer, Eric A; Rosner, Inger L; Linehan, W Marston; Bratslavsky, Gennady

    2011-01-01

    Familial renal cancer (FRC) is a heterogeneous disorder comprised of a variety of subtypes. Each subtype is known to have unique histologic features, genetic alterations, and response to therapy. Through the study of families affected by hereditary forms of kidney cancer, insights into the genetic basis of this disease have been identified. This has resulted in the elucidation of a number of kidney cancer gene pathways. Study of these pathways has led to the development of novel targeted molecular treatments for patients affected by systemic disease. As a result, the treatments for families affected by von Hippel-Lindau (VHL), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis renal cell carcinoma (HLRCC), and Birt-Hogg-Dubé (BHD) are rapidly changing. We review the genetics and contemporary surgical management of familial forms of kidney cancer. PMID:22312516

  16. Genetic and molecular alterations in meningiomas.

    PubMed

    Alexiou, George A; Markoula, Sofia; Gogou, Pinelopi; Kyritsis, Athanasios P

    2011-05-01

    Meningiomas are the most common benign intracranial tumors in adults arising from the dura matter. The etiology of meningiomas is mostly unknown, although several risk factors have been described, such as ionizing radiation, head injury, hormones and genetic factors. According to WHO they are classified into 3 grades, grade I, grade II and grade III. Meningiomas express various hormonal and growth factor receptors, such as progesterone, estrogen, somatostatin, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) receptors, which may be related to their biological behavior and response to treatment. Chromosomal abnormalities linked to meningiomas involve chromosomes 22, 1p, 9p, 10p, 11, 14q, 15, 17, and 18q. In addition, genes that may be involved in the formation of meningiomas include NF2, DAL-1, p14 (ARF), p53, MDM2, Rb, p16 and c-myc. It is likely that detailed molecular information will aid in establishing a molecular grading of these tumors and predict response to treatment and survival. PMID:21227570

  17. Biosynthesis and Molecular Genetics of Polyketides in Marine Dinoflagellates

    PubMed Central

    Kellmann, Ralf; Stüken, Anke; Orr, Russell J. S.; Svendsen, Helene M.; Jakobsen, Kjetill S.

    2010-01-01

    Marine dinoflagellates are the single most important group of algae that produce toxins, which have a global impact on human activities. The toxins are chemically diverse, and include macrolides, cyclic polyethers, spirolides and purine alkaloids. Whereas there is a multitude of studies describing the pharmacology of these toxins, there is limited or no knowledge regarding the biochemistry and molecular genetics involved in their biosynthesis. Recently, however, exciting advances have been made. Expressed sequence tag sequencing studies have revealed important insights into the transcriptomes of dinoflagellates, whereas other studies have implicated polyketide synthase genes in the biosynthesis of cyclic polyether toxins, and the molecular genetic basis for the biosynthesis of paralytic shellfish toxins has been elucidated in cyanobacteria. This review summarises the recent progress that has been made regarding the unusual genomes of dinoflagellates, the biosynthesis and molecular genetics of dinoflagellate toxins. In addition, the evolution of these metabolic pathways will be discussed, and an outlook for future research and possible applications is provided. PMID:20479965

  18. Genetic diversity of popcorn genotypes using molecular analysis.

    PubMed

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

    2015-01-01

    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. PMID:26345916

  19. Myeloproliferative neoplasms: Current molecular biology and genetics.

    PubMed

    Saeidi, Kolsoum

    2016-02-01

    Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by increased production of mature blood cells. Philadelphia chromosome-negative MPNs (Ph-MPNs) consist of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). A number of stem cell derived mutations have been identified in the past 10 years. These findings showed that JAK2V617F, as a diagnostic marker involving JAK2 exon 14 with a high frequency, is the best molecular characterization of Ph-MPNs. Somatic mutations in an endoplasmic reticulum chaperone, named calreticulin (CALR), is the second most common mutation in patients with ET and PMF after JAK2 V617F mutation. Discovery of CALR mutations led to the increased molecular diagnostic of ET and PMF up to 90%. It has been shown that JAK2V617F is not the unique event in disease pathogenesis. Some other genes' location such as TET oncogene family member 2 (TET2), additional sex combs-like 1 (ASXL1), casitas B-lineage lymphoma proto-oncogene (CBL), isocitrate dehydrogenase 1/2 (IDH1/IDH2), IKAROS family zinc finger 1 (IKZF1), DNA methyltransferase 3A (DNMT3A), suppressor of cytokine signaling (SOCS), enhancer of zeste homolog 2 (EZH2), tumor protein p53 (TP53), runt-related transcription factor 1 (RUNX1) and high mobility group AT-hook 2 (HMGA2) have also identified to be involved in MPNs phenotypes. Here, current molecular biology and genetic mechanisms involved in MNPs with a focus on the aforementioned factors is presented. PMID:26697989

  20. Molecular Genetics of Beauveria bassiana Infection of Insects.

    PubMed

    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. PMID:27131326

  1. Reasoning across Ontologically Distinct Levels: Students' Understandings of Molecular Genetics

    ERIC Educational Resources Information Center

    Duncan, Ravit Golan; Reiser, Brian J.

    2007-01-01

    In this article we apply a novel analytical framework to explore students' difficulties in understanding molecular genetics--a domain that is particularly challenging to learn. Our analytical framework posits that reasoning in molecular genetics entails mapping across ontologically distinct levels--an information level containing the genetic…

  2. Child Development and Molecular Genetics: 14 Years Later

    ERIC Educational Resources Information Center

    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…

  3. Improved Student Linkage of Mendelian and Molecular Genetic Concepts through a Yeast-Based Laboratory Module

    ERIC Educational Resources Information Center

    Wolyniak, Michael J.

    2013-01-01

    A study of modern genetics requires students to successfully unite the principles of Mendelian genetics with the functions of DNA. Traditional means of teaching genetics are often successful in teaching Mendelian and molecular ideas but not in allowing students to see how the two subjects relate. The laboratory module presented here attempts to…

  4. Molecular genetics at the Fort Collins Science Center

    USGS Publications Warehouse

    Oyler-McCance, S.J.; Stevens, P.D.

    2011-01-01

    The Fort Collins Science Center operates a molecular genetic and systematics research facility (FORT Molecular Ecology Laboratory) that uses molecular genetic tools to provide genetic information needed to inform natural resource management decisions. For many wildlife species, the data generated have become increasingly important in the development of their long-term management strategies, leading to a better understanding of species diversity, population dynamics and ecology, and future conservation and management needs. The Molecular Ecology Lab serves Federal research and resource management agencies by developing scientifically rigorous research programs using nuclear, mitochondrial and chloroplast DNA to help address many of today's conservation biology and natural resource management issues.

  5. Pathology and Molecular Genetics of Meningioma: Recent Advances

    PubMed Central

    SHIBUYA, Makoto

    2015-01-01

    Meningiomas are the most common intracranial primary neoplasm in adults. Although the spectrum of clinical and molecular genetic issues regarding meningiomas remains undefined, novel genetic alterations that are associated with tumor morphology, malignancy, or location have recently been discovered. This review focuses on recent advances in understanding of the heterogenous pathology of meningiomas, particularly on associations between the clinical, histological, etiological, epidemiological, and molecular genetical aspects of the neoplasm. PMID:25744347

  6. [Advance in molecular genetic research on primary congenital glaucoma].

    PubMed

    Li, Xiulan; Liu, Haotian; Zhang, Dingding

    2016-04-01

    Primary congenital glaucoma (PCG) is one of the major diseases causing blindness in children, but its pathogenesis has remained unclear. Genetic factors play an important role in the pathogenesis of PCG. Molecular genetics of candidate genes such as CYP1B1, MYOC, LTBP2 and FOXC1 has so far been explored, but no disease-causing gene has been identified. Molecular genetic research on PCG including candidate gene screening and research strategies are reviewed here. PMID:27060330

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

    PubMed

    Tropf, Felix C; Stulp, Gert; Barban, Nicola; Visscher, Peter M; Yang, Jian; Snieder, Harold; Mills, Melinda C

    2015-01-01

    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. PMID:26039877

  8. Human Fertility, Molecular Genetics, and Natural Selection in Modern Societies

    PubMed Central

    Tropf, Felix C.; Stulp, Gert; Barban, Nicola; Visscher, Peter M.; Yang, Jian; Snieder, Harold; Mills, Melinda C.

    2015-01-01

    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. PMID:26039877

  9. Molecular and genetic control of plant thermomorphogenesis.

    PubMed

    Quint, Marcel; Delker, Carolin; Franklin, Keara A; Wigge, Philip A; Halliday, Karen J; van Zanten, Martijn

    2016-01-01

    Temperature is a major factor governing the distribution and seasonal behaviour of plants. Being sessile, plants are highly responsive to small differences in temperature and adjust their growth and development accordingly. The suite of morphological and architectural changes induced by high ambient temperatures, below the heat-stress range, is collectively called thermomorphogenesis. Understanding the molecular genetic circuitries underlying thermomorphogenesis is particularly relevant in the context of climate change, as this knowledge will be key to rational breeding for thermo-tolerant crop varieties. Until recently, the fundamental mechanisms of temperature perception and signalling remained unknown. Our understanding of temperature signalling is now progressing, mainly by exploiting the model plant Arabidopsis thaliana. The transcription factor PHYTOCHROME INTERACTING FACTOR 4 (PIF4) has emerged as a critical player in regulating phytohormone levels and their activity. To control thermomorphogenesis, multiple regulatory circuits are in place to modulate PIF4 levels, activity and downstream mechanisms. Thermomorphogenesis is integrally governed by various light signalling pathways, the circadian clock, epigenetic mechanisms and chromatin-level regulation. In this Review, we summarize recent progress in the field and discuss how the emerging knowledge in Arabidopsis may be transferred to relevant crop systems. PMID:27250752

  10. The Molecular Genetic Architecture of Self-Employment

    PubMed Central

    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 (σg2/σP2 = 25%, h2 = 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 p<10−5 were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship 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

  11. The molecular genetic architecture of self-employment.

    PubMed

    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 p<10(-5) were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship 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

  12. Pathology, Molecular Genetics, and Epigenetics of Diffuse Intrinsic Pontine Glioma

    PubMed Central

    Buczkowicz, Pawel; Hawkins, Cynthia

    2015-01-01

    Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain cancer with no effective therapy. Histological similarity of DIPG to supratentorial high-grade astrocytomas of adults has led to assumptions that these entities possess similar underlying molecular properties and therefore similar therapeutic responses to standard therapies. The failure of all clinical trials in the last 30 years to improve DIPG patient outcome has suggested otherwise. Recent studies employing next-generation sequencing and microarray technologies have provided a breadth of evidence highlighting the unique molecular genetics and epigenetics of this cancer, distinguishing it from both adult and pediatric cerebral high-grade astrocytomas. This review describes the most common molecular genetic and epigenetic signatures of DIPG in the context of molecular subgroups and histopathological diagnosis, including this tumor entity’s unique mutational landscape, copy number alterations, and structural variants, as well as epigenetic changes on the global DNA and histone levels. The increased knowledge of DIPG biology and histopathology has opened doors to new diagnostic and therapeutic avenues. PMID:26175967

  13. Pathology, Molecular Genetics, and Epigenetics of Diffuse Intrinsic Pontine Glioma.

    PubMed

    Buczkowicz, Pawel; Hawkins, Cynthia

    2015-01-01

    Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain cancer with no effective therapy. Histological similarity of DIPG to supratentorial high-grade astrocytomas of adults has led to assumptions that these entities possess similar underlying molecular properties and therefore similar therapeutic responses to standard therapies. The failure of all clinical trials in the last 30 years to improve DIPG patient outcome has suggested otherwise. Recent studies employing next-generation sequencing and microarray technologies have provided a breadth of evidence highlighting the unique molecular genetics and epigenetics of this cancer, distinguishing it from both adult and pediatric cerebral high-grade astrocytomas. This review describes the most common molecular genetic and epigenetic signatures of DIPG in the context of molecular subgroups and histopathological diagnosis, including this tumor entity's unique mutational landscape, copy number alterations, and structural variants, as well as epigenetic changes on the global DNA and histone levels. The increased knowledge of DIPG biology and histopathology has opened doors to new diagnostic and therapeutic avenues. PMID:26175967

  14. [Molecular genetics of lissencephaly and microcephaly].

    PubMed

    Mochida, Ganeshwaran Hitoshi

    2008-04-01

    Genetic malformations of the cerebral cortex are an important cause of neurological disability in children. The genes implicated in these disorders are essential for normal cerebral cortical development. Therefore, identifying these genes and studying their functions will help us further the understanding of the normal biological mechanisms of brain development. Lissencephaly and microcephaly are two groups of disorders that have been intensely studied and several causative genes within each group have been identified. Type I (classical) lissencephaly is characterized by a smooth-appearing brain with a lack or severe reduction of normal gyri. Three of its identified causative genes (LIS1, DCX and TUBA1A) are related to microtubules, which are essential for neuronal migration in the developing cerebral cortex. Microcephaly vera is a form of microcephaly with four responsible genes reported to date. Three of them (ASPM, CENPJ and CDK5RAP2) localize to the mitotic centrosome, and one (MCPH1) is implicated in cell cycle checkpoint regulation and DNA damage response. This suggests that abnormalities of neural progenitor cell division are fundamental to the pathogenesis of microcephaly vera. These genes for microcephaly vera are also suggested to have played a role in evolutionary volume expansion of the human cerebral cortex. These examples show that genetic studies of lissencephaly and microcephaly have been very fruitful in providing novel insights into various aspects of human cerebral cortical development. PMID:18421985

  15. Molecular basis and genetic predisposition to intracranial aneurysm

    PubMed Central

    Weinsheimer, Shantel; Ronkainen, Antti; Kuivaniemi, Helena

    2014-01-01

    Intracranial aneurysms, also called cerebral aneurysms, are dilatations in the arteries that supply blood to the brain. Rupture of an intracranial aneurysm leads to a subarachnoid hemorrhage, which is fatal in about 50% of the cases. Intracranial aneurysms can be repaired surgically or endovascularly, or by combining these two treatment modalities. They are relatively common with an estimated prevalence of unruptured aneurysms of 2%–6% in the adult population, and are considered a complex disease with both genetic and environmental risk factors. Known risk factors include smoking, hypertension, increasing age, and positive family history for intracranial aneurysms. Identifying the molecular mechanisms underlying the pathogenesis of intracranial aneurysms is complex. Genome-wide approaches such as DNA linkage and genetic association studies, as well as microarray-based mRNA expression studies, provide unbiased approaches to identify genetic risk factors and dissecting the molecular pathobiology of intracranial aneurysms. The ultimate goal of these studies is to use the information in clinical practice to predict an individual's risk for developing an aneurysm or monitor its growth or rupture risk. Another important goal is to design new therapies based on the information on mechanisms of disease processes to prevent the development or halt the progression of intracranial aneurysms. PMID:25117779

  16. Recent progress in molecular genetic studies on the carotenoid transport system using cocoon-color mutants of the silkworm.

    PubMed

    Tsuchida, Kozo; Sakudoh, Takashi

    2015-04-15

    The existence of tissue-specific delivery for certain carotenoids is supported by genetic evidence from the silkworm Bombyx mori and the identification of cocoon color mutant genes, such as Yellow blood (Y), Yellow cocoon (C), and Flesh cocoon (F). Mutants with white cocoons are defective in one of the steps involved in transporting carotenoids from the midgut lumen to the middle silk gland via the hemolymph lipoprotein, lipophorin, and the different colored cocoons are caused by the accumulation of specific carotenoids into the middle silk gland. The Y gene encodes carotenoid-binding protein (CBP), which is expected to function as the cytosolic transporter of carotenoids across the enterocyte and epithelium of the middle silk gland. The C and F genes encode the C locus-associated membrane protein, which is homologous to a mammalian high-density lipoprotein receptor-2 (Cameo2) and scavenger receptor class B member 15 (SCRB15), respectively; these membrane proteins are expected to function as non-internalizing lipophorin receptors in the middle silk gland. Cameo2 and SCRB15 belong to the cluster determinant 36 (CD36) family, with Cameo2 exhibiting specificity not only for lutein, but also for zeaxanthin and astaxanthin, while SCRB15 seems to have specificity toward carotene substrates such as α-carotene and β-carotene. These findings suggest that Cameo2 and SCRB15 can discriminate the chemical structure of lutein and β-carotene from circulating lipophorin during uptake. These data provide the first evidence that CD36 family proteins can discriminate individual carotenoid molecules in lipophorin. PMID:25579881

  17. Molecular Population Genetic Structure in the Piping Plover

    USGS Publications Warehouse

    Miller, Mark P.; Haig, Susan M.; Gratto-Trevor, Cheri L.; Mullins, Thomas D.

    2009-01-01

    The Piping Plover (Charadrius melodus) is a migratory shorebird currently listed as Endangered in Canada and the U.S. Great Lakes, and threatened throughout the remainder of its U.S. breeding and winter range. In this study, we undertook the first comprehensive molecular genetic-based investigation of Piping Plovers. Our primary goals were to (1) address higher level subspecific taxonomic issues, (2) characterize population genetic structure, and (3) make inferences regarding past bottlenecks or population expansions that have occurred within this species. Our analyses included samples of individuals from 23 U.S. States and Canadian Provinces, and were based on mitochondrial DNA sequences (580 bp, n = 245 individuals) and eight nuclear microsatellite loci (n = 229 individuals). Our findings illustrate strong support for separate Atlantic and Interior Piping Plover subspecies (C. m. melodus and C. m. circumcinctus, respectively). Birds from the Great Lakes region were allied with the Interior subspecies group and should be taxonomically referred to as C. m. circumcinctus. Population genetic analyses suggested that genetic structure was stronger among Atlantic birds relative to the Interior group. This pattern indicates that natal and breeding site fidelity may be reduced among Interior birds. Furthermore, analyses suggested that Interior birds have previously experienced genetic bottlenecks, whereas no evidence for such patterns existed among the Atlantic subspecies. Likewise, genetic analyses indicated that the Great Lakes region has experienced a population expansion. This finding may be interpreted as population growth following a previous bottleneck event. No genetic evidence for population expansions was found for Atlantic, Prairie Canada, or U.S. Northern Great Plains individuals. We interpret our population history insights in light of 25 years of Piping Plover census data. Overall, differences observed between Interior and Atlantic birds may reflect

  18. Molecular and genetic basis of depression.

    PubMed

    Roy, Madhumita; Tapadia, Madhu G; Joshi, Shobhna; Koch, Biplob

    2014-12-01

    Joyousness or sadness is normal reaction to state of life. If any of these lead to certain semi-permanent changes in daily life, then it is termed as mental disorder. Depression is one of the mental disorders with a state of low mood and aversion to activities that exerts a negative effect on a person's thoughts and behaviour. Adolescent group is probably the world's largest active group of people, who are getting prone to this state of mind leading to their diminished mental and physical abilities. Depression is closely linked to stress and thus a chronic stressful life can increase the risk of depression. Depression is a complex disease having both genetic and environmental components as contributing factors. In this study an attempt has been made to put forward the understanding of the known genes and their functional relationships with depression and stress with special reference to BDNF and 5-HTTLPR. Analysis of common genetic variants associated with depression, especially in the members of a family who had a previous history, might help in identifying the individuals at risk prior to the onset of depression. PMID:25572252

  19. Molecular genetics of human myopia: an update.

    PubMed

    Young, Terri L

    2009-01-01

    Myopia, or nearsightedness, is the most common human eye disorder in the world, and is a significant global public health concern. Along with cataract, macular degeneration, infectious disease, and vitamin A deficiency, myopia is one of the most important causes of visual impairment worldwide. Severe or high-grade myopia is a leading cause of blindness because of its associated ocular morbidities of retinal detachment, macular choroidal degeneration, premature cataract, and glaucoma. Ample evidence documents the heritability of the non-syndromic forms of this condition, especially for high-grade myopia, commonly referred to as myopic spherical refractive power of 5 to 6 diopters or higher. Multiple high-grade myopia genetic loci have been identified, and confirmatory studies identifying high-grade and moderate myopia loci have also occurred. In general, myopia susceptibility genes are unknown with few association studies performed, and without confirmation in other research laboratories or testing of separate patient cohorts. PMID:19104467

  20. Apocalypse...now? Molecular epidemiology, predictive genetic tests, and social communication of genetic contents.

    PubMed

    Castiel, L D

    1999-01-01

    The author analyzes the underlying theoretical aspects in the construction of the molecular watershed of epidemiology and the concept of genetic risk, focusing on issues raised by contemporary reality: new technologies, globalization, proliferation of communications strategies, and the dilution of identity matrices. He discusses problems pertaining to the establishment of such new interdisciplinary fields as molecular epidemiology and molecular genetics. Finally, he analyzes the repercussions of the social communication of genetic content, especially as related to predictive genetic tests and cloning of animals, based on triumphal, deterministic metaphors sustaining beliefs relating to the existence and supremacy of concepts such as 'purity', 'essence', and 'unification' of rational, integrated 'I's/egos'. PMID:10089550

  1. Genetic and molecular characterization of the human osteosarcoma 3AB-OS cancer stem cell line: a possible model for studying osteosarcoma origin and stemness.

    PubMed

    Di Fiore, Riccardo; Fanale, Daniele; Drago-Ferrante, Rosa; Chiaradonna, Ferdinando; Giuliano, Michela; De Blasio, Anna; Amodeo, Valeria; Corsini, Lidia R; Bazan, Viviana; Tesoriere, Giovanni; Vento, Renza; Russo, Antonio

    2013-06-01

    Finding new treatments targeting cancer stem cells (CSCs) within a tumor seems to be critical to halt cancer and improve patient survival. Osteosarcoma is an aggressive tumor affecting adolescents, for which there is no second-line chemotherapy. Uncovering new molecular mechanisms underlying the development of osteosarcoma and origin of CSCs is crucial to identify new possible therapeutic strategies. Here, we aimed to characterize genetically and molecularly the human osteosarcoma 3AB-OS CSC line, previously selected from MG63 cells and which proved to have both in vitro and in vivo features of CSCs. Classic cytogenetic studies demonstrated that 3AB-OS cells have hypertriploid karyotype with 71-82 chromosomes. By comparing 3AB-OS CSCs to the parental cells, array CGH, Affymetrix microarray, and TaqMan® Human MicroRNA array analyses identified 49 copy number variations (CNV), 3,512 dysregulated genes and 189 differentially expressed miRNAs. Some of the chromosomal abnormalities and mRNA/miRNA expression profiles appeared to be congruent with those reported in human osteosarcomas. Bioinformatic analyses selected 196 genes and 46 anticorrelated miRNAs involved in carcinogenesis and stemness. For the first time, a predictive network is also described for two miRNA family (let-7/98 and miR-29a,b,c) and their anticorrelated mRNAs (MSTN, CCND2, Lin28B, MEST, HMGA2, and GHR), which may represent new biomarkers for osteosarcoma and may pave the way for the identification of new potential therapeutic targets. PMID:23129384

  2. Predation on larval suckers in the Williamson River Delta revealed by molecular genetic assays—A pilot study

    USGS Publications Warehouse

    Hereford, Danielle M.; Ostberg, Carl O.; Burdick, Summer M.

    2016-01-01

    Predation of endangered Lost River suckers (Deltistes luxatus) and shortnose suckers (Chasmistes brevirostris) during larval egress to Upper Klamath Lake from the Williamson River is poorly understood but may be an important factor limiting recruitment into adult spawning populations. Native and non-native piscivores are abundant in nursery wetland habitat, but larval predation has not been directly studied for all species. Larvae lack hard body structures and digest rapidly in predator digestive systems. Therefore, traditional visual methods for diet analysis may fail to identify the extent of predation on larvae. The goals of this study were to (1) use quantitative polymerase chain reaction (qPCR) and single nucleotide polymorphism (SNP) assays developed for Lost River and shortnose suckers to assay predator stomach contents for sucker DNA, and (2) to assess our ability to use this technique to study predation. Predators were captured opportunistically during larval sucker egress. Concurrent feeding trials indicate that most predators—yellow perch (Perca flaverscens), fathead minnow (Pimephales promelas), blue chub (Gila coerulea), Klamath tui chub (Siphatales bicolor bicolor), Klamath Lake sculpin (Cottus princeps), slender sculpin (Cottus tenuis)—preyed on sucker larvae in the laboratory. However, sucker DNA was not detected in fathead minnow stomachs. Of the stomachs screened from fish captured in the Williamson River Delta, 15.6 percent of yellow perch contained sucker DNA. This study has demonstrated that the application of qPCR and SNP assays is effective for studying predation on larval suckers. We suggest that techniques associated with dissection or detection of sucker DNA from fathead minnow stomachs need improvement.

  3. Workshop on molecular methods for genetic diagnosis. Final technical report

    SciTech Connect

    Rinchik, E.M.

    1997-07-01

    The Sarah Lawrence College Human Genetics Program received Department of Energy funding to offer a continuing medical education workshop for genetic counselors in the New York metropolitan area. According to statistics from the National Society of Genetic Counselors, there are approximately 160 genetic counselors working in the tri-state area (New York, New Jersey, and Connecticut), and many of them had been working in the field for more than 10 years. Thus, there was a real need to offer these counselors an in-depth opportunity to learn the specifics of the major advances in molecular genetics, and, in particular, the new approaches to diagnostic testing for genetic disease. As a result of the DOE Award DE-FG02-95ER62048 ($20,583), in July 1995 we offered the {open_quotes}Workshop on Molecular Methods for Genetic Diagnosis{close_quotes} for 24 genetic counselors in the New York metropolitan area. The workshop included an initial review session on the basics of molecular biology, lectures and discussions on past and current topics in molecular genetics and diagnostic procedures, and, importantly, daily laboratory exercises. Each counselor gained not only background, but also firsthand experience, in the major techniques of biochemical and molecular methods for diagnosing genetic diseases as well as in mathematical and computational techniques involved in human genetics analyses. Our goal in offering this workshop was not to make genetic counselors experts in these laboratory diagnostic techniques, but to acquaint them, by hands-on experience, about some of the techniques currently in use. We also wanted to provide them a technical foundation upon which they can understand and appreciate new technical developments arising in the near future.

  4. [Progress in molecular genetics of epilepsy].

    PubMed

    Tang, Beisha; Zhang, Yuhu

    2002-12-01

    Epilepsy is a group of disorders characterized by recurrent seizures. The etiologies of idiopathic epilepsy commonly have a genetic basis. Gene mutations causing several of the inherited epilepsies have been mapped. In this review, the authors summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, emphasizing how genetic defects may correlate with the pathophysiological mechanisms of brain hyperexcitability and gene defects can lead to epilepsy by altering multiple and diverse aspects of neuronal function. PMID:12476426

  5. Molecular genetic analysis of six Dutch families with atrial fibrillation

    PubMed Central

    Entius, M.M.; Groenewegen, A.; Pronk, A.; van der Smagt, J.J; Loh, P.; Hauer, R.N.; Derksen, R.; van Gelder, I.C.; Lok, D.J.A.; Doevendans, P.A.

    2005-01-01

    Background Atrial fibrillation (AF), the most common cardiac arrhythmia, is characterised by rapid and irregular contraction of the atrium. The risk of AF increases with age and AF increases the risk of various heart disorders, stroke and mortality. AF can occur in a sporadic or familial form. The underlying mechanism leading to AF is not well known but genetic analysis can increase our insight into the molecular pathways in AF. Detailed information on the molecular mechanisms of a disorder increase options for diagnosis and treatment. Recently, a gain-of-function mutation in exon of the KCNQ1 gene located on chromosome 11 was identified in a large Chinese AF family. KCNQ1 associates with KCNE1 or KCNE2 (both located on chromosome 21) to form cardiac potassium channels. Subsequent analysis of Chinese families showed a KCNE2 mutation in two families. Other genetic studies show linkage to chromosome 6 and 10, indicating genetic heterogeneity. A number of studies have shown that altered expression of the atrial connexin40 protein is a risk factor for AF. Connexin genes encode gap-junction proteins that are important in cardiac conduction and for normal wave propagation. Objectives/methods In this study we analysed the role of KCNQ1, KCNE1 coding region and Cx40 promoter region in six Dutch AF families by sequence analysis. Conclusion No mutations were found in these genes. The absence of mutations indicates genetic heterogeneity in familial AF; however, further research is needed. Candidate genes are being sequenced, linkage analysis in a large family will be performed and additional AF families will be collected. ImagesFigure 1 PMID:25696507

  6. Sudden unexpected death in epilepsy genetics: Molecular diagnostics and prevention.

    PubMed

    Goldman, Alica M; Behr, Elijah R; Semsarian, Christopher; Bagnall, Richard D; Sisodiya, Sanjay; Cooper, Paul N

    2016-01-01

    Epidemiologic studies clearly document the public health burden of sudden unexpected death in epilepsy (SUDEP). Clinical and experimental studies have uncovered dynamic cardiorespiratory dysfunction, both interictally and at the time of sudden death due to epilepsy. Genetic analyses in humans and in model systems have facilitated our current molecular understanding of SUDEP. Many discoveries have been informed by progress in the field of sudden cardiac death and sudden infant death syndrome. It is becoming apparent that SUDEP genomic complexity parallels that of sudden cardiac death, and that there is a pauci1ty of analytically useful postmortem material. Because many challenges remain, future progress in SUDEP research, molecular diagnostics, and prevention rests in international, collaborative, and transdisciplinary dialogue in human and experimental translational research of sudden death. PMID:26749013

  7. VIP and PACAP. Recent insights into their functions/roles in physiology and disease from molecular and genetic studies

    PubMed Central

    Moody, Terry W.; Ito, Tetsuhide; Osefo, Nuramy; Jensen, Robert T.

    2010-01-01

    Purpose of review VIP and PACAP as well as the three classes of G-protein-coupled receptors mediating their effects, are widely distributed in the CNS and peripheral tissues. These peptides are reported to have many effects in different tissues, which are physiological or pharmacological, and which receptor mediates which effect, has been difficult to determine, primarily due to lack of potent, stable, selective agonists/antagonists. Recently the use of animals with targeted knockout (KO) of the peptide or a specific receptor has provided important insights into the role of their role in normal physiology and disease states. Recent findings During the review period, considerable progress and insights has occurred in the understanding of the role of VIP/PACAP as well as their receptors in a number of different disorders/areas. Particularly, insights into their roles in energy metabolism, glucose regulation, various gastrointestinal processes including GI inflammatory conditions and motility and their role in the CNS as well as CNS diseases has greatly expanded. Summary PACAP/VIP as well as there three classes of receptors are important in many physiological/pathophysiological processes, some of which are identified in these studies using knockout animals. These studies may lead to new novel treatment approaches. Particularly important are their roles in glucose metabolism and on islets leading to possible novel approaches in diabetes; their novel anti-inflammatory, cytoprotective effects, their CNS neuroprotective effects, and their possible roles in diseases such as schizophrenia and chronic depression. PMID:21157320

  8. Impairment of Colour Vision in Diabetes with No Retinopathy: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SNDREAMS- II, Report 3)

    PubMed Central

    Gella, Laxmi; Raman, Rajiv; Kulothungan, Vaitheeswaran; Pal, Swakshyar Saumya; Ganesan, Suganeswari; Sharma, Tarun

    2015-01-01

    Purpose To assess impairment of colour vision in type 2 diabetics with no diabetic retinopathy and elucidate associated risk factors in a population-based cross-sectional study. Methods This is part of Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular-genetics Study (SN-DREAMS II) which was conducted between 2007–2010. FM 100 hue-test was performed in 253 subjects with no clinical evidence of diabetic retinopathy. All subjects underwent detailed ophthalmic evaluation including cataract grading using LOCS III and 45° 4-field stereoscopic fundus photography. Various ocular and systemic risk factors for impairment of colour vision (ICV) were assessed in subjects with diabetes but no retinopathy. P value of < 0.05 was considered statistically significant. Results The mean age of the study sample was 57.08 ± 9.21 (range: 44–86 years). Gender adjusted prevalence of ICV among subjects with diabetes with no retinopathy was 39.5% (CI: 33.5–45.5). The mean total error score in the study sample was 197.77 ± 100 (range: 19–583). The risk factors for ICV in the study were women OR: 1.79 (1.00–3.18), increased resting heart rate OR: 1.04 (1.01–1.07) and increased intraocular pressure OR: 1.12 (1.00–1.24). Significant protective factor was serum high-density lipoprotein OR: 0.96 (0.93–0.99). Conclusions Acquired ICV is an early indicator of neurodegenerative changes in the retina. ICV found in diabetic subjects without retinopathy may be of non-vascular etiology. PMID:26053017

  9. Molecular genetics and targeted therapeutics in biliary tract carcinoma

    PubMed Central

    Marks, Eric I; Yee, Nelson S

    2016-01-01

    The primary malignancies of the biliary tract, cholangiocarcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma (BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract. PMID:26819503

  10. Molecular recognition at the active site of subtilisin BPN': crystallographic studies using genetically engineered proteinaceous inhibitor SSI (Streptomyces subtilisin inhibitor).

    PubMed

    Takeuchi, Y; Noguchi, S; Satow, Y; Kojima, S; Kumagai, I; Miura, K; Nakamura, K T; Mitsui, Y

    1991-06-01

    Unlike trypsin-like serine proteases having only one conspicuous binding pocket in the active site, subtilisin BPN' has two such pockets, the S1 and S4 pockets, which accommodate the P1 and P4 residues of ligands (after Schechter and Berger notation) respectively. Using computer graphics, the geometrical nature of the two pockets was carefully examined and strategies for site-directed mutagenesis studies were set up against a protein SSI (Streptomyces subtilisin inhibitor), which is a strong proteinaceous inhibitor (or a substrate analogue) of subtilisin BPN'. It was decided to convert the P1 residue, methionine 73, into lysine (M73K) with or without additional conversion of the P4 residue, methionine 70, into glycine (M70G). The crystal structures of the two complexes of subtilisin BPN', one with the single mutant SSI (M73K) and the other with the double mutant SSI (M73K, M70G) were solved showing that (i) small 'electrostatic induced-fit movement' occurs in the S1 pocket upon introducing the terminal plus charge of the lysine side chain, and (ii) large 'mechanical induced-fit movement' occurs in the S4 pocket upon reducing the size of the P4 side chain from methionine to glycine. In both (i) and (ii), the induced-fit movement occurred in a concerted fashion involving both the enzyme and 'substrate' amino acid residues. The term 'substrate-assisted stabilization' was coined to stress the cooperative nature of the induced-fit movements. PMID:1891457

  11. Molecular genetics of chromosome 21 and Down Syndrome

    SciTech Connect

    Epstein, C.; Patterson, D.

    1990-01-01

    This book explores the fundamental nature of Down Syndrome pathology as related to the structure and expression of the genes that are known to be critical in its development. It offers a comprehensive account of the most up-to-date research and an overview of the advances in molecular analysis techniques that are revolutionizing the entire field of chromosome mapping. The book discusses how individual genes in this chromosome have been isolated and studied in both cellular and in vivo models, and chapters cover a variety of specific topics including patterns of recombination according to age and sex seen in genetic linkage mapping of chromosome 21; the possible role of centromere and chromosome structure in nondisjunction; molecular mapping of the down syndrome phenotype; the interferon receptor and inducer genes; and more.

  12. Genetic variation in polyploid forage grass: Assessing the molecular genetic variability in the Paspalum genus

    PubMed Central

    2013-01-01

    Background Paspalum (Poaceae) is an important genus of the tribe Paniceae, which includes several species of economic importance for foraging, turf and ornamental purposes, and has a complex taxonomical classification. Because of the widespread interest in several species of this genus, many accessions have been conserved in germplasm banks and distributed throughout various countries around the world, mainly for the purposes of cultivar development and cytogenetic studies. Correct identification of germplasms and quantification of their variability are necessary for the proper development of conservation and breeding programs. Evaluation of microsatellite markers in different species of Paspalum conserved in a germplasm bank allowed assessment of the genetic differences among them and assisted in their proper botanical classification. Results Seventeen new polymorphic microsatellites were developed for Paspalum atratum Swallen and Paspalum notatum Flüggé, twelve of which were transferred to 35 Paspalum species and used to evaluate their variability. Variable degrees of polymorphism were observed within the species. Based on distance-based methods and a Bayesian clustering approach, the accessions were divided into three main species groups, two of which corresponded to the previously described Plicatula and Notata Paspalum groups. In more accurate analyses of P. notatum accessions, the genetic variation that was evaluated used thirty simple sequence repeat (SSR) loci and revealed seven distinct genetic groups and a correspondence of these groups to the three botanical varieties of the species (P. notatum var. notatum, P. notatum var. saurae and P. notatum var. latiflorum). Conclusions The molecular genetic approach employed in this study was able to distinguish many of the different taxa examined, except for species that belong to the Plicatula group, which has historically been recognized as a highly complex group. Our molecular genetic approach represents a

  13. Molecular genetics and pathogenesis of cardiomyopathy.

    PubMed

    Kimura, Akinori

    2016-01-01

    Cardiomyopathy is defined as a disease of functional impairment in the cardiac muscle and its etiology includes both extrinsic and intrinsic factors. Cardiomyopathy caused by the intrinsic factors is called as primary cardiomyopathy of which two major clinical phenotypes are hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Genetic approaches have revealed the disease genes for hereditary primary cardiomyopathy and functional studies have demonstrated that characteristic functional alterations induced by the disease-associated mutations are closely related to the clinical types, such that increased and decreased Ca(2+) sensitivities of muscle contraction are associated with HCM and DCM, respectively. In addition, recent studies have suggested that mutations in the Z-disc components found in HCM and DCM may result in increased and decreased stiffness of sarcomere, respectively. Moreover, functional analysis of mutations in the other components of cardiac muscle have suggested that the altered response to metabolic stresses is associated with cardiomyopathy, further indicating the heterogeneity in the etiology and pathogenesis of cardiomyopathy. PMID:26178429

  14. Clinical and molecular genetics of Carney complex.

    PubMed

    Rothenbuhler, Anya; Stratakis, Constantine A

    2010-06-01

    Carney complex (CNC) is a rare multiple familial neoplasia syndrome that is characterized by multiple types of skin tumors and pigmented lesions, endocrine neoplasms, myxomas and schwannomas and is inherited in an autosomal dominant manner. Clinical and pathologic diagnostic criteria are well established. Over 100 pathogenic variants in the regulatory subunit type 1A (RI-A) of the cAMP-dependent protein kinase (PRKAR1A) have been detected in approximately 60% of CNC patients, most leading to R1A haploinsufficiency. Other CNC-causing genes remain to be identified. Recent studies provided some genotype-phenotype correlations in CNC patients carrying PRKAR1A-inactivating mutations, which provide useful information for genetic counseling and/or prognosis; however, CNC remains a disease with significant clinical heterogeneity. Recent mouse and in vitro studies have shed light into how R1A haploinsufficiency causes tumors. PRKAR1A defects appear to be weak tumorigenic signals for most tissues; Wnt signaling activation and cell cycle dysregulation appear to be important mediators of the tumorigenic effect of a defective R1A. PMID:20833331

  15. Genetic, molecular, and morphological analysis of compound leaf development.

    PubMed

    Goliber, T; Kessler, S; Chen, J J; Bharathan, G; Sinha, N

    1999-01-01

    Leaves, the plant organs responsible for capturing and converting most of the 170 billion metric tons of carbon fixed globally each year, can be broadly grouped into two morphological categories: simple and compound. Although simple-leaved species such as corn and Arabidopsis have traditionally been favored model systems for studying leaf development, recent years have seen an increase in genetic and molecular studies of compound leaf development. Two compound-leaved species in particular have emerged as model systems: tomato and pea. A variety of mutations which alter leaf morphology in these species have been described, and analyses of these mutations have allowed the construction of testable models of leaf development. Also, the knotted-like homeobox (KNOX) genes, which were originally discovered as regulators of meristem function, now appear to have a role in compound leaf development. In addition to the recent genetic and molecular analyses of tomato and pea, insight into the nature of compound leaf development may be gained through the study of (a) heteroblasty and heterophylly, phenomena in which a range of leaf forms can be produced by a single shoot, and (b) the evolutionary origins of compound leaves. PMID:9891889

  16. The centenary progress of molecular genetics. A 100th anniversary of T. H. Morgan's discoveries.

    PubMed

    Keros, Tomislav; Borovecki, Fran; Jemersić, Lorena; Konjević, Dean; Roić, Besi; Balatinec, Jelena

    2010-09-01

    A century ago, Thomas Hunt Morgan, the American scientist, studied the cytogenetic changes of drosophila and came to cytogenetic explanation of Mendel's basic laws of genetic heredity. These studies resulted in today's Mendel-Morgan chromosomal theory of heredity. On the occasion of the hundredth anniversary of this important discovery the authors have decided to give a review of the most significant achievements in the field of molecular genetics until the completion of the Human Genome Project. The most important points concerning the technology of DNA recombination and genetic engineering are also presented. The final section discusses the significance of previous achievements of molecular genetics in biomedicine and other related fields. There is also a tabular presentation of the sequence of the most important findings in the field of molecular genetics through time. PMID:20977123

  17. Genetic and molecular distinctions in spinal ependymomas: A review.

    PubMed

    Connolly, Ian D; Ali, Rohaid; Li, Yingmei; Gephart, Melanie Hayden

    2015-12-01

    While gross total resection of spinal ependymomas prevents recurrence, this surgical result is not always possible. Increasing evidence suggests that ependymomas occurring in the spine are genetically distinct from those originating in the brain. Herein we review the most recent developments detailing the molecular and genetic characteristics of spinal ependymomas, which may inform more effective and personalized adjuvant therapies for spinal ependymomas that are ineligible for gross total resection. We performed a key-word search for articles published on the molecular, genetic, chromosomal, and epigenetic transformations inherent in spinal ependymomas. We reviewed appropriate articles and their relevant citations. While resection can often achieve favorable outcomes in the treatment of spinal ependymoma, more research on the unique molecular, genetic, chromosomal and epigenetic traits must be conducted in order to tailor treatment and intervention for those patients for whom total resection is not possible. PMID:26519890

  18. A genetic dichotomy between pure sclerosing epithelioid fibrosarcoma (SEF) and hybrid SEF/low-grade fibromyxoid sarcoma: a pathologic and molecular study of 18 cases.

    PubMed

    Prieto-Granada, Carlos; Zhang, Lei; Chen, Hsiao-Wei; Sung, Yun-Shao; Agaram, Narasimhan P; Jungbluth, Achim A; Antonescu, Cristina R

    2015-01-01

    Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue tumor exhibiting considerable morphologic overlap with low-grade fibromyxoid sarcoma (LGFMS). Moreover, both SEF and LGFMS show MUC4 expression by immunohistochemistry. While the majority of LGFMS cases are characterized by a FUS-CREB3L1 fusion, both FUS-CREB3L2 and EWSR1-CREB3L1 fusions were recently demonstrated in a small number of LGFMS and SEF/LGFMS hybrid tumors. In contrast, recent studies pointed out that SEF harbor frequent EWSR1 rearrangements, with only a minority of cases showing FUS-CREB3L2 fusions. In an effort to further characterize the molecular characteristics of pure SEF and hybrid SEF/LGFMS lesions, we undertook a clinicopathologic, immunohistochemical and genetic analysis of a series of 10 SEF and 8 hybrid SEF/LGFMS tumors. The mortality rate was similar between the two groups, 44% within the pure SEF group and 37% in the hybrid SEF/LGFMS with a mean overall follow-up of 66 months. All but one pure SEF and all hybrid SEF/LGFMS-tested cases showed MUC4 immunoreactivity. The majority (90%) of pure SEF cases showed EWSR1 gene rearrangements by fluorescence in situ hybridization with only one case exhibiting FUS rearrangement. Of the nine EWSR1 positive cases, six cases harbored CREB3L1 break-apart, two had CREB3L2 rearrangement (a previously unreported finding) and one lacked evidence of CREB3L1/2 abnormalities. In contrast, all hybrid SEF/LGFMS tumors exhibited FUS and CREB3L2 rearrangements. These results further demarcate a relative cytogenetic dichotomy between pure SEF, often characterized by EWSR1 rearrangements, and hybrid SEF/LGFMS, harboring FUS-CREB3L2 fusion; the latter group recapitulating the genotype of LGFMS. PMID:25231134

  19. Study of genetic variation of eggplant cultivars by using RAPD-PCR molecular markers and the relationship with Phomopsis blight disease reaction.

    PubMed

    Asad, H A; Meah, M B; Begum, S N; Khalil, M I; Rafii, M Y; Latif, M A

    2015-01-01

    Disease susceptibility and genetic variability in 10 eggplant genotypes were studied after inoculating Phomopsis vexans under confined field conditions. Random amplified polymorphic DNA (RAPD) markers were used to assess genetic variation and relationships among eggplant genotypes. The disease index of leaves ranged 0.208-13.79%, while fruit infection ranged 2.15-42.76%. Two varieties, Dohazari G and Laffa S, were found to be susceptible, 6 were moderately resistant, 1 was moderately susceptible, and BAU Begun-1 was resistant to P. vexans. Amplification of genomic DNA by using 3 RAPD primers produced 20 bands: 14 (70%) were polymorphic and 6 (30%) were monomorphic. The highest intra-variety similarity indices values were found in ISD 006, Ishurdi L, Jessore L, and BAU Begun-1 (100%), while the lowest was in Dohazari G (90%). The lowest genetic distance (0.0513) and the highest genetic identity (0.9500) were observed between the ISD 006 and Ishurdi L combinations. A comparatively higher genetic distance (0.3724) and the lowest genetic identity (0.6891) were observed between the ISD 006 and Dohazari G combinations. A dendogram was constructed based on Nei's genetic distance, which produced 2 main clusters of the genotypes - Cluster I: ISD 006, Ishurdi L, Marich begun L, BAU Begun-1, Marich begun S, and Chega and Cluster 2: Laffa S, Dohazari G, Jessore L, and Singhnath. Genetic variation and its relationship with disease susceptibility were assessed using RAPD markers, to develop disease-resistant varieties and improve eggplant crops. PMID:26681048

  20. Effect of Bead and Illustrations Models on High School Students' Achievement in Molecular Genetics

    ERIC Educational Resources Information Center

    Rotbain, Yosi; Marbach-Ad, Gili; Stavy, Ruth

    2006-01-01

    Our main goal in this study was to explore whether the use of models in molecular genetics instruction in high school can contribute to students' understanding of concepts and processes in genetics. Three comparable groups of 11th and 12th graders participated: The control group (116 students) was taught in the traditional lecture format, while…

  1. Genetics and molecular biology of brain calcification.

    PubMed

    Deng, Hao; Zheng, Wen; Jankovic, Joseph

    2015-07-01

    Brain calcification is a common neuroimaging finding in patients with neurological, metabolic, or developmental disorders, mitochondrial diseases, infectious diseases, traumatic or toxic history, as well as in otherwise normal older people. Patients with brain calcification may exhibit movement disorders, seizures, cognitive impairment, and a variety of other neurologic and psychiatric symptoms. Brain calcification may also present as a single, isolated neuroimaging finding. When no specific cause is evident, a genetic etiology should be considered. The aim of the review is to highlight clinical disorders associated with brain calcification and provide summary of current knowledge of diagnosis, genetics, and pathogenesis of brain calcification. PMID:25906927

  2. DNA marker applications to molecular genetics and genomics in tomato

    PubMed Central

    Shirasawa, Kenta; Hirakawa, Hideki

    2013-01-01

    Tomato is an important crop and regarded as an experimental model of the Solanaceae family and of fruiting plants in general. To enhance breeding efficiency and advance the field of genetics, tomato has been subjected to DNA marker studies as one of the earliest targets in plants. The developed DNA markers have been applied to the construction of genetic linkage maps and the resultant maps have contributed to quantitative trait locus (QTL) and gene mappings for agronomically important traits, as well as to comparative genomics of Solanaceae. The recently released whole genome sequences of tomato enable us to develop large numbers of DNA markers comparatively easily, and even promote new genotyping methods without DNA markers. In addition, databases for genomes, DNA markers, genetic linkage maps and other omics data, e.g., transcriptome, proteome, metabolome and phenome information, will provide useful information for molecular breeding in tomatoes. The use of DNA marker technologies in conjunction with new breeding techniques will promise to advance tomato breeding. PMID:23641178

  3. Molecular phylogeny and genetic diversity of Lygus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inter- and intraspecific genetic diversity in North American Lygus was using nuclear and mitochondrial DNA. DNA sequences have been obtained from the mitochondrial cox1 and cox2 genes, the nuclear ITS1 spacer, and regions flanking microsatellites (MSFR). The Fargo lab sequenced a region overlapp...

  4. Corn Storage Protein - A Molecular Genetic Model

    SciTech Connect

    Messing, Joachim

    2013-05-31

    Corn is the highest yielding crop on earth and probably the most valuable agricultural product of the United States. Because it converts sun energy through photosynthesis into starch and proteins, we addressed energy savings by focusing on protein quality. People and animals require essential amino acids derived from the digestion of proteins. If proteins are relatively low in certain essential amino acids, the crop becomes nutritionally defective and has to be supplemented. Such deficiency affects meat and fish production and countries where corn is a staple. Because corn seed proteins have relatively low levels of lysine and methionine, a diet has to be supplemented with soybeans for the missing lysine and with chemically synthesized methionine. We therefore have studied genes expressed during maize seed development and their chromosomal organization. A critical technical requirement for the understanding of the molecular structure of genes and their positional information was DNA sequencing. Because of the length of sequences, DNA sequencing methods themselves were insufficient for this type of analysis. We therefore developed the so-called “DNA shotgun sequencing” strategy, where overlapping DNA fragments were sequenced in parallel and used to reconstruct large DNA molecules via overlaps. Our publications became the most frequently cited ones during the decade of 1981-1990 and former Associate Director of Science for the Office of Basic Energy Sciences Patricia M. Dehmer presented our work as one of the great successes of this program. A major component of the sequencing strategy was the development of bacterial strains and vectors, which were also used to develop the first biotechnology crops. These crops possessed new traits thanks to the expression of foreign genes in plants. To enable such expression, chimeric genes had to be constructed using our materials and methods by the industry. Because we made our materials and methods freely available to

  5. Molecular genetics of facioscapulohumeral muscular dystrophy (FSHD).

    PubMed

    Fisher, J; Upadhyaya, M

    1997-01-01

    Facioscapulohumeral muscular dystrophy (FSHD; MIM 158900), is an autosomal dominant neuromuscular disorder. The disease is characterized by the weakness of the muscles of the face, upper-arm and shoulder girdle. The gene for FSHD has been mapped to 4q35 (FSHD1A) and is closely linked to D4F1O4S1, which detects two highly polymorphic loci (located at 4q35 and 10q26), with restriction enzyme EcoRI. The polymorphic EcoRI fragment detected with D4F1O4S1 is composed almost entirely of D4Z4 (3.3 kb) tandem repeats. In FSHD patients a deletion of the integral number of D4Z4 repeats generates a fragment which is usually smaller than 35 kb, whereas in normal controls, the size usually ranges from 50 to 300 kb. These 'small' EcoRI fragments segregate with FSHD in families but appear as de novo deletions in the majority of sporadic cases. Each 3.3 kb repeat contains two homeobox domains neither of which has yet been proven to encode a protein. D4Z4 is located adjacent to the 4q telomere and cross hybridizes to several different regions of the genome. Although D4Z4 probably does not encode a protein with any direct association to FSHD, a clear correlation has been shown between the deletion size at this locus and the age at onset of the disease in FSHD patients. In approximately 5-10% of FSHD families the disease locus is unlinked to 4q35 (locus designated FSHD1B), however, none of the non 4q35 loci for FSHD have yet been chromosomally located. Thus so far, only one gene, FRG1 (FSHD region gene 1) has been identified from the FSHD candidate region on 4q35. The apparent low level of expressed sequences from within this region, the integral deletions of D4Z4 repeats observed in FSHD patients and the close proximity of these repeats to the 4q telomere, all suggest that the disease may be the result of position effect variegation. To date, the molecular diagnosis of FSHD with D4F104S1 has been most secure in those families which are linked to other 4q35 markers. Recent studies

  6. Recent insights into the molecular genetics of dementia

    PubMed Central

    Rademakers, Rosa; Rovelet-Lecrux, Anne

    2010-01-01

    Our understanding of the molecular genetic basis of two common neurodegenerative dementias, Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) has greatly advanced in recent years. Progranulin mutations were identified as a major cause of FTLD and a potential susceptibility factor for other forms of dementia. In addition, through copy-number analyses of previously identified disease genes and the study of microRNA regulation in dementia, new evidence emerged to support the view that subtle variability in the expression of known disease proteins may increase the risk for sporadic forms of dementia. Finally, in late-onset AD populations, the first genome-wide association studies were performed and novel potential AD susceptibility genes reported. These exciting findings provide novel insights into the disease mechanisms underlying dementia and hold promise for the development of potential treatments. PMID:19640594

  7. [Research progress on molecular genetics of forest musk deer].

    PubMed

    Jie, Hang; Zheng, Cheng-li; Wang, Jian-ming; Feng, Xiao-lan; Zeng, De-jun; Zhao, Gui-jun

    2015-11-01

    Forest musk deer is one of the large-scale farming musk deer animals with the largest population at the same time. The male musk deer can secrete valuable medicines, which has high medicinal and economic value. Due to the loss of habitat and indiscriminate hunting, the numbers of wild population specie and the distribution have been drastically reduced. Therefore, in-depth understanding of the molecular genetics progress of forest musk deer will pave a way for musk deer protection and breeding. In this review, the progress associated with the molecular marker, genetic classification, artificial breeding, musk secretion and disease in past decades were reviewed, in order to provide a theoretical basis for subsequent molecular genetic researches in forest musk deer. PMID:27097400

  8. Primer on Molecular Genetics; DOE Human Genome Program

    DOE R&D Accomplishments Database

    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.

  9. Primer on molecular genetics. DOE Human Genome Program

    SciTech Connect

    Not Available

    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.

  10. Molecular genetics of sarcomas: applications to diagnoses and therapy.

    PubMed

    Toguchida, Junya; Nakayama, Tomitaka

    2009-09-01

    Sarcomas are mesenchymal cancers consisting of tumors with various clinical and pathological features. Some of them compel affected individuals to lose important musculoskeletal functions, and some of them are highly malignant and life-threatening. A great amount of genetic information for sarcomas has accumulated during the past two decades, contributing diagnoses and treatments. From the standpoint of molecular genetics, sarcomas are classified into two groups: those with defined genetic alterations and those with various genetic alterations. The genetic alterations in the first group include reciprocal translocations resulting in fusion oncoproteins and oncogenic mutations of defined genes such as those of the c-kit gene in gastrointestinal stromal tumors. The function of fusion proteins includes transcription regulator, signal transducer, chromatic remodeling factor, and growth factor, some of which are suitable targets for the molecular therapy. In tumors belonging to the second group, the number of which is far larger than those of the first group, considerable genetic heterogeneity was found even among tumors with same pathological diagnosis. The disruption of the RB and p53 pathways was frequently found, resulting in the dysregulation of cell cycle and the genomic instability. The application of molecular target therapy for tumors in this group requires novel strategies to overcome cross talk between different signal pathways. Recent evidence from in vitro and in vivo experiments has indicated that the cells of origin of sarcomas are tissue stem cells such as mesenchymal stem cells, and the application of stem cell biology holds the promise of novel treatment options. PMID:19555393

  11. INTRANODAL PALISADED MYOFIBROBLASTOMA: ANOTHER MESENCHYMAL NEOPLASM WITH CTNNB1 (BETA-CATENIN GENE) MUTATIONS. CLINICOPATHOLOGIC, IMMUNOHISTOCHEMICAL, AND MOLECULAR GENETIC STUDY OF 18 CASES

    PubMed Central

    Laskin, William B.; Lasota, Jerzy; Fetsch, John F.; Felisiak-Golabek, Anna; Wang, Zeng-Feng; Miettinen, Markku

    2014-01-01

    Intranodal palisaded myofibroblastoma is a benign, lymph node-based myofibroblastic tumor of unknown pathogenesis. We report the clinicopathological, immunohistochemical, and genetic molecular features of this rare entity. The study cohort consisted of 14 males and 4 females ranging in age from 31 to 65 (mean, 47; median 49) years with tumors arising in inguinal lymph nodes (n=15), a neck lymph node (n=1), and undesignated lymph nodes (n=2). Most individuals presented with a painless mass or lump. Possible trauma/injury to the inguinal region was documented in four cases. Tumors ranged in size from 1.0 to 4.2 (mean, 3.1; median; 3.0) cm. Microscopically, the process presented as a well-circumscribed, often times pseudoencapsulated nodule (n=17) or nodules (n=1). Tumors consisted of a cellular proliferation of cytologically bland, spindled cells arranged in short fascicles and whorls within a finely collagenous(n=11) or myxocollagenous(n=7) matrix. In 12 tumors, scattered fibromatosis-like fascicles of spindled cells were noted. Histological features characteristic of the process included nuclear palisades (n=16 cases), collagenous bodies (n=15), and perinuclear intracytoplasmic hyaline globules (n=10). Mitotic activity ranged from 0 to 8 (mean,2; median, 1) mitotic figures/50 high-powered fields with no atypical division figures identified. Immunohistochemically, all tumors tested expressed (vimentin (n=3), smooth-muscle actin and/or muscle-specific actin (n=5, each), and nuclear beta-catenin and cyclin D1 (n=8, each). The latter two results prompted a screening for mutations in the beta-catenin gene glycogen synthase kinase-3 beta phosphorylation mutational “hotspot” region in exon 3 using PCR amplification and Sanger sequencing. Single nucleotide substitutions leading to missense mutations at the protein level were identified in 7 of 8 (88%) analyzed tumors and are responsible for the abnormal expression of beta-catenin and cyclin D1. These results

  12. Molecular, metabolic, and genetic control: An introduction.

    PubMed

    Tyson, John J.; Mackey, Michael C.

    2001-03-01

    The living cell is a miniature, self-reproducing, biochemical machine. Like all machines, it has a power supply, a set of working components that carry out its necessary tasks, and control systems that ensure the proper coordination of these tasks. In this Special Issue, we focus on the molecular regulatory systems that control cell metabolism, gene expression, environmental responses, development, and reproduction. As for the control systems in human-engineered machines, these regulatory networks can be described by nonlinear dynamical equations, for example, ordinary differential equations, reaction-diffusion equations, stochastic differential equations, or cellular automata. The articles collected here illustrate (i) a range of theoretical problems presented by modern concepts of cellular regulation, (ii) some strategies for converting molecular mechanisms into dynamical systems, (iii) some useful mathematical tools for analyzing and simulating these systems, and (iv) the sort of results that derive from serious interplay between theory and experiment. (c) 2001 American Institute of Physics. PMID:12779443

  13. Molecular genetics and epigenetics of CACTA elements.

    PubMed

    Fedoroff, Nina V

    2013-01-01

    The CACTA transposons, so named for a highly conserved motif at element ends, comprise one of the most abundant superfamilies of Class 2 (cut-and-paste) plant transposons. CACTA transposons characteristically include subterminal sequences of several hundred nucleotides containing closely spaced direct and inverted repeats of a short, conserved sequence of 14-15 bp. The Supressor-mutator (Spm) transposon, identified and subjected to detailed genetic analysis by Barbara McClintock, remains the paradigmatic element of the CACTA family. The Spm transposon encodes two proteins required for transposition, the transposase (TnpD) and a regulatory protein (TnpA) that binds to the subterminal repeats. Spm expression is subject to both genetic and epigenetic regulation. The Spm-encoded TnpA serves as an activator of the epigenetically inactivated, methylated Spm, stimulating both transient and heritable activation of the transposon. TnpA also serves as a negative regulator of the demethylated active element promoter and is required, in addition to the TnpD, for transposition. PMID:23918429

  14. Molecular genetics and antisocial behavior: where do we stand?

    PubMed

    Iofrida, Caterina; Palumbo, Sara; Pellegrini, Silvia

    2014-11-01

    Over the last two decades, it has become increasingly evident that control of aggressive behavior is modulated by the individual genetic profile as well. Several candidate genes have been proposed to play a role in the risk to develop antisocial behavior, and distinct brain imaging studies have shown that specific cortical areas may be functionally and/or structurally impaired in impulsive violent subjects on the basis of their genotypes. In this paper, we review the findings regarding four polymorphisms-MAOA (Monoamine oxidase A) uVNTR, SLC6A4 (solute carrier family 6 (neurotransmitter transporter), member 4) 5HTTLPR, COMT (Catechol-O-methyltransferase) Val158Met and DRD4 (dopamine D4 receptor) VNTR 1-11-that all have been found to be associated with an increased vulnerability for antisocial and impulsive behavior in response to aversive environmental conditions. These results, however, have not been replicated by other studies, likely because of crucial methodological discrepancies, including variability in the criteria used to define antisocial behavior and assessment of environmental factors. Finally, it has been recently proposed that these genetic variants may actually increase the individual susceptibility not merely to the negative environmental factors, but to the positive ones as well. In this view, such alleles would play a wider modulatory role, by acting as "plasticity" rather than "vulnerability" genes. Overall, these findings have potential important implications that span well outside of neuroscience and psychiatry, to embrace ethics, philosophy, and the law itself, as they pose new challenges to the very notion of Free Will. Novel properly controlled studies that examine multi-allelic genetic profiles, rather than focusing on distinct single variants, will make it possible to achieve a clearer understanding of the molecular underpinnings of the nature by nurture interaction. PMID:24764243

  15. A role for molecular genetics in biological conservation.

    PubMed Central

    O'Brien, S J

    1994-01-01

    The recognition of recent accelerated depletion of species as a consequence of human industrial development has spawned a wide interest in identifying threats to endangered species. In addition to ecological and demographic perils, it has become clear that small populations that narrowly survive demographic contraction may undergo close inbreeding, genetic drift, and loss of overall genomic variation due to allelic loss or reduction to homozygosity. I review here the consequences of such genetic depletion revealed by applying molecular population genetic analysis to four endangered mammals: African cheetah, lion, Florida panther, and humpback whale. The accumulated genetic results, combined with physiological, ecological, and ethological data, provide a multifaceted perspective of the process of species diminution. An emerging role of population genetics, phylogenetics, and phylogeography as indicators of a population's natural history and its future prognosis provides valuable data of use in the development of conservation management plans for endangered species. PMID:7912434

  16. Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics

    PubMed Central

    Kreek, Mary Jeanne; Levran, Orna; Reed, Brian; Schlussman, Stefan D.; Zhou, Yan; Butelman, Eduardo R.

    2012-01-01

    Addictive diseases, including addiction to heroin, prescription opioids, or cocaine, pose massive personal and public health costs. Addictions are chronic relapsing diseases of the brain caused by drug-induced direct effects and persisting neuroadaptations at the epigenetic, mRNA, neuropeptide, neurotransmitter, or protein levels. These neuroadaptations, which can be specific to drug type, and their resultant behaviors are modified by various internal and external environmental factors, including stress responsivity, addict mindset, and social setting. Specific gene variants, including variants encoding pharmacological target proteins or genes mediating neuroadaptations, also modify vulnerability at particular stages of addiction. Greater understanding of these interacting factors through laboratory-based and translational studies have the potential to optimize early interventions for the therapy of chronic addictive diseases and to reduce the burden of relapse. Here, we review the molecular neurobiology and genetics of opiate addiction, including heroin and prescription opioids, and cocaine addiction. PMID:23023708

  17. Molecular Genetics of Disease Resistance in Cereals

    PubMed Central

    AYLIFFE, MICHAEL A.; LAGUDAH, EVANS S.

    2004-01-01

    • Aims This Botanical Briefing attempts to summarize what is currently known about the molecular bases of disease resistance in cereal species and suggests future research directions. • Scope An increasing number of resistance (R) genes have been isolated from rice, maize, wheat and barley that encode both structurally related and unique proteins. This R protein diversity may be attributable to the different modus operandi employed by pathogen species in some cases, but it is also a consequence of multiple defence strategies being employed against phytopathogens. Mutational analysis of barley has identified additional genes required for activation of an R gene-mediated defence response upon pathogen infection. In some instances very closely related barley R proteins require different proteins for defence activation, demonstrating that, within a single plant species, multiple resistance signalling pathways and different resistance strategies have evolved to confer protection against a single pathogen species. Despite the apparent diversity of cereal resistance mechanisms, some of the additional molecules required for R protein function are conserved amongst cereal and dicotyledonous species and even other eukaryotic species. Thus the derivation of functional homologues and interacting partner proteins from other species is contributing to the understanding of resistance signalling in cereals. The potential and limit of utilizing the rice genome sequence for further R gene isolation from cereal species is also considered, as are the new biotechnological possibilities for disease control arising from R gene isolation. • Conclusions Molecular analyses in cereals have further highlighted the complexity of plant–pathogen co-evolution and have shown that numerous active and passive defence strategies are employed by plants against phytopathogens. Many advances in understanding the molecular basis of disease resistance in cereals have focused on monogenic

  18. Molecular genetics of ligninase expression. Progress report

    SciTech Connect

    Cullen, D.

    1995-07-01

    The objectives of this research for the past three years have been to (1) elucidate the structure and genomic organization of genes involved in lignin degradation; and (2) investigate the expression of these genes in Phanerochaete chrysosporium and in heterologous hosts. Major accomplishments include the following: (1) the P. chrysosporium gene encoding glyoxal oxidase has been cloned, sequenced, and efficiently expressed in Aspergillus; (2) mapping methods were developed allowing the integration of genetic and physical maps of P. chrysosporium; (3) highly specific and sensitive PCR techniques were developed for discriminating closely related mRNAs. Application of this technique will help to identify specific genes involved in degradation of lignin and organopollutants; (4) investigations have revealed a novel insertional mutation in lignin peroxidase gene lipI.

  19. Genomics, molecular genetics and the food industry.

    PubMed

    Pridmore, R D; Crouzillat, D; Walker, C; Foley, S; Zink, R; Zwahlen, M C; Brüssow, H; Pétiard, V; Mollet, B

    2000-03-31

    The production of foods for an increasingly informed and selective consumer requires the coordinated activities of the various branches of the food chain in order to provide convenient, wholesome, tasty, safe and affordable foods. Also, the size and complexity of the food sector ensures that no single player can control a single process from seed production, through farming and processing to a final product marketed in a retail outlet. Furthermore, the scientific advances in genome research and their exploitation via biotechnology is leading to a technology driven revolution that will have advantages for the consumer and food industry alike. The segment of food processing aids, namely industrial enzymes which have been enhanced by the use of biotechnology, has proven invaluable in the production of enzymes with greater purity and flexibility while ensuring a sustainable and cheap supply. Such enzymes produced in safe GRAS microorganisms are available today and are being used in the production of foods. A second rapidly evolving segment that is already having an impact on our foods may be found in the new genetically modified crops. While the most notorious examples today were developed by the seed companies for the agro-industry directed at the farming sector for cost saving production of the main agronomical products like soya and maize, its benefits are also being seen in the reduced use of herbicides and pesticides which will have long term benefits for the environment. Technology-driven advances for the food processing industry and the consumer are being developed and may be divided into two separate sectors that will be presented in greater detail: 1. The application of genome research and biotechnology to the breeding and development of improved plants. This may be as an aid for the cataloging of industrially important plant varieties, the rapid identification of key quality traits for enhanced classical breeding programs, or the genetic modification of

  20. Editorial: The Advent of a Molecular Genetics of General Intelligence.

    ERIC Educational Resources Information Center

    Weiss, Volkmar

    1995-01-01

    Raw IQ scores do not demonstrate the bell curve created by normalized scores, even the bell-shaped distribution does not require large numbers of underlying genes. Family data support a major gene locus of IQ. The correlation between glutathione peroxidase and IQ should be investigated through molecular genetics. (SLD)

  1. Molecular genetics of infantile nervous system channelopathies.

    PubMed

    Gardiner, Mark

    2006-12-01

    Inherited or de novo mutations in at least a dozen genes encoding ion channels may present as paroxysmal disorders during the neonatal period or first year of life. These channelopathies include genes encoding voltage-gated channels specific for sodium (SCN1A, SCN2A, SCN1B, SCN9A) and potassium (KCNQ2, KCNQ3) which account for a variety of epilepsy phenotypes ranging from mild, such as Benign familial neonatal seizures (BFNS) to severe, such as Dravet syndrome (severe myoclonic epilepsy of infancy, SMEI) and the rare and unusual syndrome paroxysmal extreme pain disorder (PEPD). Ligand-gated channels involved include the GABA(A) receptor in a variety of epilepsy phenotypes and the human glycine receptor. Mutations in five genes encoding subunits of this receptor and accessory molecules underlie hyperekplexia or stiff-baby syndrome. All these conditions are rare but correct diagnosis is of value not only for genetic counselling but to allow the specific treatment which is available. PMID:17049761

  2. Intelligent DNA-based molecular diagnostics using linked genetic markers

    SciTech Connect

    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.

  3. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  4. Comparative studies on limb morphogenesis in mice and bats: a functional genetic approach towards a molecular understanding of diversity in organ formation.

    PubMed

    Cretekos, C J; Rasweiler, J J; Behringer, R R

    2001-01-01

    The basis of species-specific morphogenesis has been a topic of fascination and speculation for centuries. In 1828, Karl Ernst von Baer noted that at the pharyngula stage of development all vertebrate embryos are morphologically very similar. Most subsequent hypotheses have proposed that the vertebrate body plan develops by a conserved mechanism, and that divergent forms develop by differential elaboration on this basic plan. Gene cloning and expression studies have largely confirmed that the genetic pathways of embryonic patterning are highly conserved. The finding that the proteins encoded by paralogous and orthologous genes within and between species can functionally replace each another is no longer novel; in most cases this is the expected result. How, then, does divergent morphology arise between species? One hypothesis that fits well with comparative data is that divergent morphogenesis arises from genetic differences in the timing, level and pattern of orthologous gene expression during development. This idea is being tested using a functional genetic approach comparing limb morphogenesis between the mouse and bat. PMID:11999322

  5. Genetic diversity analysis of common beans based on molecular markers.

    PubMed

    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. PMID:22215964

  6. Genetic diversity analysis of common beans based on molecular markers

    PubMed Central

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

    2011-01-01

    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. PMID:22215964

  7. Molecular Genetics of Root Thigmoresponsiveness in Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Masson, Patrick H.

    2002-01-01

    The molecular mechanisms that allow plant roots to use gravity and touch as growth guides are investigated. We are using a molecular genetic strategy in Arabidopsis thaliana to study these processes. When Arabidopsis thaliana seedlings grow on tilted hard-agar surfaces, their roots develop a wavy pattern of growth which appears to derive from a succession of left-handed and right-handed circumnutation-like processes triggered by gravity and touch stimulation (Okada and Shimura, 1990; Rutherford et al., 1998; Rutherford and Masson, 1996). Interestingly, mutations that affect root waving on tilted hard-agar surfaces can be identified and characterized. Some of these mutations affect root gravitropism, while others appear to be responsible for the production of abnormal waves (no waves, compressed or square waves, coils) without affecting gravitropism. The specific objectives of this project were to functionally characterize two genes (WVD2 and WVD6) which are required for root waving on tilted agar surfaces, but not for root gravitropism. Specific objectives included a physiological and cytological analysis of the mutants, and molecular cloning and characterization of the corresponding genes. As summarized in this paper, we have reached these objectives. We have also identified and partially characterized other mutations that affect root skewing on hard-agar surfaces (sku5-1 and ago1), and have completed our work on the root-wave phenotype associated with mutations in genes of the tryptophan biosynthesis pathway (Lynn et al., 1999; Rutherford et al., 1998; Sedbrook et al., 2000, 2002). We briefly describe our progress on the cloning and characterization of WVD6, WVD2 and SKU5, and provide a list of papers (published, or in preparation) that derived from this grant. We also discuss the biological implications of our findings, with special emphasis on the analysis of WVD2.

  8. Molecular analysis of genetic diseases: an overview for clinicians.

    PubMed

    Javed, A A; Huang, Y; Bombard, A T

    1995-01-01

    The identification of fetal genetic disease has, for the most part, relied on examination of an end product, such as analysis of factor VIII levels obtained from cord blood in fetuses at risk for hemophilia. Advances in molecular genetics have shifted our focus in prenatal diagnosis away from protein product analysis toward etiology, making new discoveries gleaned from the Human Genome Project relevant to clinicians. This review discusses the basic principles involved in gene-based diagnosis, highlighting the complexities of current approaches to molecular diagnosis of fetal genetic disease. Given an understanding of both the theory and practice of genetic analysis, the review covers the fundamental principles of molecular biology (structure, function, packaging, and regulation) and discusses recombinant DNA techniques presently used for the analysis of mutations. Clinical examples are presented to introduce the techniques most commonly employed in service laboratories: direct detection assays, where the specific mutation is recognized, and indirect detection assays, useful for the deduction of an inheritance pattern where the actual mutation or its gene is not known but may be closely linked to known DNA polymorphisms. PMID:7858372

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

    PubMed Central

    Küpper Cardoso Perseguini, Juliana Morini; Chioratto, Alisson Fernando; Zucchi, Maria Imaculada; Colombo, Carlos Augusto; Carbonell, Sérgio Augusto Moraes; Costa Mondego, Jorge Mauricio; Gazaffi, Rodrigo; Franco Garcia, Antonio Augusto; de Campos, Tatiana; de Souza, Anete Pereira; Rubiano, Luciana Benchimol

    2011-01-01

    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. PMID:21637550

  10. Objectives, criteria and methods for using molecular genetic data in priority setting for conservation of animal genetic resources.

    PubMed

    Boettcher, P J; Tixier-Boichard, M; Toro, M A; Simianer, H; Eding, H; Gandini, G; Joost, S; Garcia, D; Colli, L; Ajmone-Marsan, P

    2010-05-01

    The genetic diversity of the world's livestock populations is decreasing, both within and across breeds. A wide variety of factors has contributed to the loss, replacement or genetic dilution of many local breeds. Genetic variability within the more common commercial breeds has been greatly decreased by selectively intense breeding programmes. Conservation of livestock genetic variability is thus important, especially when considering possible future changes in production environments. The world has more than 7500 livestock breeds and conservation of all of them is not feasible. Therefore, prioritization is needed. The objective of this article is to review the state of the art in approaches for prioritization of breeds for conservation, particularly those approaches that consider molecular genetic information, and to identify any shortcomings that may restrict their application. The Weitzman method was among the first and most well-known approaches for utilization of molecular genetic information in conservation prioritization. This approach balances diversity and extinction probability to yield an objective measure of conservation potential. However, this approach was designed for decision making across species and measures diversity as distinctiveness. For livestock, prioritization will most commonly be performed among breeds within species, so alternatives that measure diversity as co-ancestry (i.e. also within-breed variability) have been proposed. Although these methods are technically sound, their application has generally been limited to research studies; most existing conservation programmes have effectively primarily based decisions on extinction risk. The development of user-friendly software incorporating these approaches may increase their rate of utilization. PMID:20500756

  11. Genetic studies in alcohol research

    SciTech Connect

    Karp, R.W.

    1994-12-15

    The National Institute on Alcohol Abuse and Alcoholism (NIAAA) supports research to elucidate the specific genetic factors, now largely unknown, which underlie susceptibility to alcoholism and its medical complications (including fetal alcohol syndrome). Because of the genetic complexity and heterogeneity of alcoholism, identification of the multiple underlying factors will require the development of new study designs and methods of analysis of data from human families. While techniques of genetic analysis of animal behavioral traits (e.g., targeted gene disruption, quantitative trait locus (QTL) mapping) are more powerful that those applicable to humans (e.g., linkage and allelic association studies), the validation of animal behaviors as models of aspects of human alcoholism has been problematic. Newly developed methods for mapping QTL influencing animal behavioral traits can not only permit analyses of human family data to be directly informed by the results of animal studies, but can also serve as a novel means of validating animal models of aspects of alcoholism. 55 refs.

  12. The Ischemic Stroke Genetics Study (ISGS) Protocol

    PubMed Central

    Meschia, James F; Brott, Thomas G; Brown, Robert D; Crook, Richard JP; Frankel, Michael; Hardy, John; Merino, José G; Rich, Stephen S; Silliman, Scott; Worrall, Bradford Burke

    2003-01-01

    Background The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype. Methods/Design The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes β-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future. Discussion The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes. PMID:12848902

  13. Molecular genetic analysis of plant gravitropism

    NASA Technical Reports Server (NTRS)

    Lomax, T. L.

    1997-01-01

    The analysis of mutants is a powerful approach for elucidating the components of complex biological processes. A growing number of mutants have been isolated which affect plant gravitropism and the classes of mutants found thus far provide important information about the gravity response mechanism. The wide variety of mutants isolated, especially in Arabidopsis, indicates that gravitropism is a complex, multi-step process. The existence of mutants altered in either root gravitropism alone, shoot gravitropism alone, or both indicates that the root and shoot gravitropic mechanisms have both separate and common steps. Reduced starch mutants have confirmed the role of amyloplasts in sensing the gravity signal. The hormone auxin is thought to act as the transducing signal between the sites of gravity perception (the starch parenchyma cells surrounding the vascular tissue in shoots and the columella cells of root caps) and asymmetric growth (the epidermal cells of the elongation zone(s) of each organ). To date, all mutants that are resistant to high concentrations of auxin have also been found to exhibit a reduced gravitropic response, thus supporting the role of auxin. Not all gravitropic mutants are auxin-resistant, however, indicating that there are additional steps which do not involve auxin. Studies with mutants of tomato which exhibit either reduced or reversed gravitropic responses further support the role of auxin redistribution in gravitropism and suggest that both red light and cytokinin interact with gravitropism through controlling lateral auxin transport. Plant responses to gravity thus likely involve changes in both auxin transport and sensitivity.

  14. Molecular barriers to processes of genetic reprogramming and cell transformation.

    PubMed

    Chestkov, I V; Khomyakova, E A; Vasilieva, E A; Lagarkova, M A; Kiselev, S L

    2014-12-01

    Genetic reprogramming by ectopic expression of transcription factor genes induces the pluripotent state in somatic cells. This technology provides an opportunity to establish pluripotent stem cells for each person, as well as to get better understanding of epigenetic mechanisms controlling cell state. Interestingly, some of the molecular processes that accompany somatic cell reprogramming in vitro are also characteristic for tumor manifestation. Thus, similar "molecular barriers" that control the stability of epigenetic state exist for both processes of pluripotency induction and malignant transformation. The reprogramming of tumor cells is interesting in two aspects: first, it will determine the contribution of epigenetic changes in carcinogenesis; second, it gives an approach to evaluate tumor stem cells that are supposed to form the entire cell mass of the tumor. This review discusses the key stages of genetic reprogramming, the similarity and difference between the reprogramming process and malignant transformation. PMID:25716723

  15. Molecular genetic testing and the future of clinical genomics

    PubMed Central

    Katsanis, Sara Huston; Katsanis, Nicholas

    2015-01-01

    Genomic technologies are reaching the point of being able to detect genetic variation in patients at high accuracy and reduced cost, offering the promise of fundamentally altering medicine. Still, although scientists and policy advisers grapple with how to interpret and how to handle the onslaught and ambiguity of genome-wide data, established and well-validated molecular technologies continue to have an important role, especially in regions of the world that have more limited access to next-generation sequencing capabilities. Here we review the range of methods currently available in a clinical setting as well as emerging approaches in clinical molecular diagnostics. In parallel, we outline implementation challenges that will be necessary to address to ensure the future of genetic medicine. PMID:23681062

  16. Antigenic variation: Molecular and genetic mechanisms of relapsing disease

    SciTech Connect

    Cruse, J.M.; Lewis, R.E.

    1987-01-01

    This book contains 10 chapters. They are: Contemporary Concepts of Antigenic Variation; Antigenic Variation in the Influenza Viruses; Mechanisms of Escape of Visna Lentiviruses from Immunological Control; A Review of Antigenic Variation by the Equine Infectious Anemia Virus; Biologic and Molecular Variations in AIDS Retrovirus Isolates; Rabies Virus Infection: Genetic Mutations and the Impact on Viral Pathogenicity and Immunity; Immunobiology of Relapsing Fever; Antigenic Variation in African Trypanosomes; Antigenic Variation and Antigenic Diversity in Malaria; and Mechanisms of Immune Evasion in Schistosomiasis.

  17. Molecular genetic contributions to socioeconomic status and intelligence.

    PubMed

    Marioni, Riccardo E; Davies, Gail; Hayward, Caroline; Liewald, Dave; Kerr, Shona M; Campbell, Archie; Luciano, Michelle; Smith, Blair H; Padmanabhan, Sandosh; Hocking, Lynne J; Hastie, Nicholas D; Wright, Alan F; Porteous, David J; Visscher, Peter M; Deary, Ian J

    2014-05-01

    Education, socioeconomic status, and intelligence are commonly used as predictors of health outcomes, social environment, and mortality. Education and socioeconomic status are typically viewed as environmental variables although both correlate with intelligence, which has a substantial genetic basis. Using data from 6815 unrelated subjects from the Generation Scotland study, we examined the genetic contributions to these variables and their genetic correlations. Subjects underwent genome-wide testing for common single nucleotide polymorphisms (SNPs). DNA-derived heritability estimates and genetic correlations were calculated using the 'Genome-wide Complex Trait Analyses' (GCTA) procedures. 21% of the variation in education, 18% of the variation in socioeconomic status, and 29% of the variation in general cognitive ability was explained by variation in common SNPs (SEs ~ 5%). The SNP-based genetic correlations of education and socioeconomic status with general intelligence were 0.95 (SE 0.13) and 0.26 (0.16), respectively. There are genetic contributions to intelligence and education with near-complete overlap between common additive SNP effects on these traits (genetic correlation ~ 1). Genetic influences on socioeconomic status are also associated with the genetic foundations of intelligence. The results are also compatible with substantial environmental contributions to socioeconomic status. PMID:24944428

  18. Genetic and Molecular Mapping of Chromosome Region 85a in Drosophila Melanogaster

    PubMed Central

    Jones, W. K.; Rawls-Jr., J. M.

    1988-01-01

    Chromosome region 85A contains at least 12 genetic complementation groups, including the genes dhod, pink and hunchback. In order to better understand the organization of this chromosomal segment and to permit molecular studies of these genes, we have carried out a genetic analysis coupled with a chromosome walk to isolate the DNA containing these genes. Complementation tests with chromosomal deficiencies permitted unambiguous ordering of most of the complementation groups identified within the 85A region. Recombinant bacteriophage clones were isolated that collectively span over 120 kb of 85A DNA and these were used to produce a molecular map of the region. The breakpoint sites of a number of 85A chromosome rearrangements were localized on the molecular map, thereby delimiting regions of the DNA that contain the various genetic complementation groups. PMID:2852138

  19. Utilization of a novel deuterostome model for the study of regeneration genetics: molecular cloning of genes that are differentially expressed during early stages of larval sea star regeneration.

    PubMed

    Vickery, M C; Vickery, M S; McClintock, J B; Amsler, C D

    2001-01-10

    Sea stars share many characteristics with vertebrates, including deuterostome type development. We previously reported that sea star larvae are capable of complete regeneration (with organogenesis) of missing body parts. Here we report the first application of whole-body cDNA subtractive hybridization for the identification of regeneration-specific gene expression in a deuterostome. We identified nine novel cDNAs from genes differentially expressed during early larval sea star regeneration, including a serine protease which may have a function similar to that of trypsin/plasmin-like proteases during vertebrate wound repair and regeneration. This study demonstrates that sea star larvae can provide a valuable new deuterostome model for the study of regeneration genetics, with potential applications in vertebrate regeneration. PMID:11179669

  20. Pseudomonas viridiflava, a Multi Host Plant Pathogen with Significant Genetic Variation at the Molecular Level

    PubMed Central

    Mpalantinaki, Evaggelia; Ververidis, Filippos; Goumas, Dimitrios E.

    2012-01-01

    The pectinolytic species Pseudomonas viridiflava has a wide host range among plants, causing foliar and stem necrotic lesions and basal stem and root rots. However, little is known about the molecular evolution of this species. In this study we investigated the intraspecies genetic variation of P. viridiflava amongst local (Cretan), as well as international isolates of the pathogen. The genetic and phenotypic variability were investigated by molecular fingerprinting (rep-PCR) and partial sequencing of three housekeeping genes (gyrB, rpoD and rpoB), and by biochemical and pathogenicity profiling. The biochemical tests and pathogenicity profiling did not reveal any variability among the isolates studied. However, the molecular fingerprinting patterns and housekeeping gene sequences clearly differentiated them. In a broader phylogenetic comparison of housekeeping gene sequences deposited in GenBank, significant genetic variability at the molecular level was found between isolates of P. viridiflava originated from different host species as well as among isolates from the same host. Our results provide a basis for more comprehensive understanding of the biology, sources and shifts in genetic diversity and evolution of P. viridiflava populations and should support the development of molecular identification tools and epidemiological studies in diseases caused by this species. PMID:22558343

  1. Human molecular genetics research at the International Centre for Genetic Engineering and Biotechnology.

    PubMed

    Falaschi, P A

    1997-01-01

    The ICGEB started its activity in 1987 as a special project of UNIDO (United Nations Industrial Development Organization) and operates now as a fully autonomous International Organization, of which 40 countries are members at present. The mandate of ICGEB is to become a Centre of excellence for research and training in modern biology addressed to the needs of the developing world. The ICGEB consists of two main laboratories, one in Trieste (where the direction of the Centre is also located) and one in New Delhi, plus a network of 30 Affiliated Centres. The Centre operates through: 1) specific research programs of hish scientific content at the Trieste and New Delhi laboratories; 2) long term training through post-doctoral and pre-doctoral fellowships; 3) short term training; 4) collaborative research program, through which the Centre finances research projects of major impact to the need of the Member States; 5) scientific services, namely consultation for scientific programs, distribution of reagents and a bioinformatics network particularly geared to the human genome research. The research on human molecular genetics in particularly active in the Trieste Component and concerns the study at the molecular level of several genes important for human health: control of DNA replication, response to infectious diseases, cardiocirculatory diseases, cystic fibrosis and cancer. The methodologies for developing new diagnostic methods and for developing gene therapy protocols are actively pursued. Through these programs, the member countries have access to state-of-the-art technologies anf know-how essential for the development of the molecular approaches to medicine brought forward by the study of the human genome. PMID:9561632

  2. Molecular Genetic Tools and Techniques in Fission Yeast.

    PubMed

    Murray, Johanne M; Watson, Adam T; Carr, Antony M

    2016-01-01

    The molecular genetic tools used in fission yeast have generally been adapted from methods and approaches developed for use in the budding yeast, Saccharomyces cerevisiae Initially, the molecular genetics of Schizosaccharomyces pombe was developed to aid gene identification, but it is now applied extensively to the analysis of gene function and the manipulation of noncoding sequences that affect chromosome dynamics. Much current research using fission yeast thus relies on the basic processes of introducing DNA into the organism and the extraction of DNA for subsequent analysis. Targeted integration into specific genomic loci is often used to create site-specific mutants or changes to noncoding regulatory elements for subsequent phenotypic analysis. It is also regularly used to introduce additional sequences that generate tagged proteins or to create strains in which the levels of wild-type protein can be manipulated through transcriptional regulation and/or protein degradation. Here, we draw together a collection of core molecular genetic techniques that underpin much of modern research using S. pombe We summarize the most useful methods that are routinely used and provide guidance, learned from experience, for the successful application of these methods. PMID:27140925

  3. [Genetic study of allergic diseases].

    PubMed

    Zhang, Yuan; Zhang, Luo

    2012-09-01

    Allergic diseases mentioned in this review is regarding to I type allergic inflammation induced by an IgE-mediated reaction, including asthma, allergic rhinitis, atopic dermatitis and food allergy. It is convinced that allergic diseases belong to multiple genes diseases and are controlled by both genetic and environmental factors. Meanwhile there exists gene-gene as well as gene-environment interactions during the development of the disease. The aim of this review is to summarize the toolkit, advance, inherent difficulties and future clinical application prospect in genetic studies of allergic disease. PMID:23214325

  4. Genetics of Tinnitus: An Emerging Area for Molecular Diagnosis and Drug Development.

    PubMed

    Lopez-Escamez, Jose A; Bibas, Thanos; Cima, Rilana F F; Van de Heyning, Paul; Knipper, Marlies; Mazurek, Birgit; Szczepek, Agnieszka J; Cederroth, Christopher R

    2016-01-01

    Subjective tinnitus is the perception of sound in the absence of external or bodily-generated sounds. Chronic tinnitus is a highly prevalent condition affecting over 70 million people in Europe. A wide variety of comorbidities, including hearing loss, psychiatric disorders, neurodegenerative disorders, and temporomandibular joint (TMJ) dysfunction, have been suggested to contribute to the onset or progression of tinnitus; however, the precise molecular mechanisms of tinnitus are not well understood and the contribution of genetic and epigenetic factors remains unknown. Human genetic studies could enable the identification of novel molecular therapeutic targets, possibly leading to the development of novel pharmaceutical therapeutics. In this article, we briefly discuss the available evidence for a role of genetics in tinnitus and consider potential hurdles in designing genetic studies for tinnitus. Since multiple diseases have tinnitus as a symptom and the supporting genetic evidence is sparse, we propose various strategies to investigate the genetic underpinnings of tinnitus, first by showing evidence of heritability using concordance studies in twins, and second by improving patient selection according to phenotype and/or etiology in order to control potential biases and optimize genetic data output. The increased knowledge resulting from this endeavor could ultimately improve the drug development process and lead to the preventive or curative treatment of tinnitus. PMID:27594824

  5. Genetics of Tinnitus: An Emerging Area for Molecular Diagnosis and Drug Development

    PubMed Central

    Lopez-Escamez, Jose A.; Bibas, Thanos; Cima, Rilana F. F.; Van de Heyning, Paul; Knipper, Marlies; Mazurek, Birgit; Szczepek, Agnieszka J.; Cederroth, Christopher R.

    2016-01-01

    Subjective tinnitus is the perception of sound in the absence of external or bodily-generated sounds. Chronic tinnitus is a highly prevalent condition affecting over 70 million people in Europe. A wide variety of comorbidities, including hearing loss, psychiatric disorders, neurodegenerative disorders, and temporomandibular joint (TMJ) dysfunction, have been suggested to contribute to the onset or progression of tinnitus; however, the precise molecular mechanisms of tinnitus are not well understood and the contribution of genetic and epigenetic factors remains unknown. Human genetic studies could enable the identification of novel molecular therapeutic targets, possibly leading to the development of novel pharmaceutical therapeutics. In this article, we briefly discuss the available evidence for a role of genetics in tinnitus and consider potential hurdles in designing genetic studies for tinnitus. Since multiple diseases have tinnitus as a symptom and the supporting genetic evidence is sparse, we propose various strategies to investigate the genetic underpinnings of tinnitus, first by showing evidence of heritability using concordance studies in twins, and second by improving patient selection according to phenotype and/or etiology in order to control potential biases and optimize genetic data output. The increased knowledge resulting from this endeavor could ultimately improve the drug development process and lead to the preventive or curative treatment of tinnitus. PMID:27594824

  6. Classical and Molecular Genetic Research on General Cognitive Ability.

    PubMed

    McGue, Matt; Gottesman, Irving I

    2015-01-01

    Arguably, no psychological variable has received more attention from behavioral geneticists than what has been called "general cognitive ability" (as well as "general intelligence" or "g"), and for good reason. GCA has a rich correlational network, implying that it may play an important role in multiple domains of functioning. GCA is highly correlated with various indicators of educational attainment, yet its predictive utility is not limited to academic achievement. It is also correlated with work performance, navigating the complexities of everyday life, the absence of various social pathologies (such as criminal convictions), and even health and mortality. Although the causal basis for these associations is not always known, it is nonetheless the case that research on GCA has the potential to provide insights into the origins of a wide range of important social outcomes. In this essay, our discussion of why GCA is considered a fundamentally important dimension of behavior on which humans differ is followed by a look at behavioral genetics research on CGA. We summarize behavioral genetics research that has sought to identify and quantify the total contributions of genetic and environmental factors to individual differences in GCA as well as molecular genetic research that has sought to identify genetic variants that underlie inherited effects. PMID:26413945

  7. Molecular Genetic Testing in Pain and Addiction: Facts, Fiction and Clinical Utility

    PubMed Central

    Blum, Kenneth; Hauser, Mary; Fratantonio, James; Badgaiyan, Rajendra D.

    2015-01-01

    The Brain Reward Cascade (BRC) is an interaction of neurotransmitters and their respective genes to control the amount of dopamine released within the brain. Any variations within this pathway, whether genetic or environmental (epigenetic), may result in addictive behaviors as well as altered pain tolerance. While there are many studies claiming a genetic association with addiction and other behavioral infractions, defined as Reward Deficiency Syndrome (RDS), not all are scientifically accurate and in some case just wrong. Albeit our bias, we discuss herein the facts and fictions behind molecular genetic testing in RDS (including pain and addiction) and the significance behind the development of the Genetic Addiction Risk Score (GARSPREDX™), the first test to accurately predict one's genetic risk for RDS. PMID:26807291

  8. [Molecular epidemiology of imported malaria in Italy: the use of genetic markers and in vitro sensitivity test in a study of chloroquine resistance in Plasmodium falciparum].

    PubMed

    Menegon, Michela; Sannella, Anna Rosa; Severini, Carlo; Paglia, Maria Grazia; Matteelli, Alberto; Caramello, Pietro; Severini, Francesco; Taramelli, Donatella; Majori, Giancarlo

    2006-01-01

    The emergence of Plasmodium falciparum drug-resistance, especially chloroquine resistance, represents one of the main obstacles to the control of malaria. Several studies have shown that in P. falciparum the mechanism of chloroquine resistance is linked to specific point mutations in the pfcrt gene of the parasite. In the present study we have analyzed 120 Italian imported malaria cases to evaluate the prevalence of 76T and 220S mutantions in the pfcrt gene. Moreover, the correlation between the presence of pfcrt point mutations and in vitro chloroquine resistance has been evaluated on 25 plasmodial isolates. The results showed a high prevalence of the pfcrt point mutations in isolates analyzed and a significant association between point mutations and in vitro chloroquine resistance. Molecular screening on imported malaria cases can be a useful tool to be employed in surveillance activity and also in monitoring the development and spread of drug resistance in endemic areas. PMID:17033142

  9. Molecular identification of genetically distinct accessions in the USDA chickpea core collection.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Knowledge of the molecular genetic variation of the accessions of core collections will be important for their efficient use in breeding programs, and for conservation purposes. The present study was undertaken for genotyping the part of the USDA chickpea core collection (Hannan et al 1994) with 20 ...

  10. High volume molecular genetic identification of single nucleotide polymorphisms using Genetic Bit Analysis Application to human genetic diagnosis

    SciTech Connect

    Boyce-Jacino, M.T.; Reynolds, J.; Nikiforov, T.

    1994-09-01

    The most common type of genetic disease-associated mutation is the single nucleotide polymorphism (SNP). Because most genetic diseases can be caused by multiple SNPs in the same gene, effective routine diagnosis of complex genetic diseases is dependent on a simple and reliable method of interrogating SNP sites. Molecular Tool`s solid phase assay capable of direct genotyping (single base sequencing) of SNP sites, Genetic Bit Analysis (GBA), involves hybridization-capture of a single-stranded PCR product to a sequence-specific, microtiter plate-bound oligonucleotide primer. The captured PCR product then acts as template for single-base extension of the capture primer across the polymorphic site, enabling direct determination of the base composition of the polymorphism through a simple colormetric assay. Genotyping in a high volume, semi-automated, processing system with a current capacity of 100 SNP interrogations per technician per day enables the screening of candidate mutations rapidly and cost-effectively, critically important to comprehensive genetic diagnosis. Using this gel-free technology, we have developed prototype diagnostic tests for CFTR and ApoE polymorphisms which enable direct sequencing of the polymorphic base at each site of interest. Routine clinical diagnosis of genetically complex diseases such as cystic fibrosis is dependent on this combination of robust biochemistry and simple format. Additionally, the ability to transfer the format and biochemistry to any disease gene of interest enables the broad application of this technology to clinical diagnostics, especially for genetically complex diseases.

  11. Molecular Approaches to Genetically Improve the Accumulation of Health-Promoting Secondary Metabolites in Staple Crops—A Case Study: The Lipoxygenase-B1 Genes and Regulation of the Carotenoid Content in Pasta Products

    PubMed Central

    Borrelli, Grazia M.; Trono, Daniela

    2016-01-01

    Secondary metabolites, also known as phytochemicals, represent a large subset of plant molecules that include compounds with health-promoting effects. Indeed, a number of epidemiological studies have shown that, when taken regularly and in adequate amounts, these molecules can have long-term beneficial effects on human health, through reduction of the incidence of degenerative diseases, such as cardiovascular diseases, obesity, diabetes, and cancer. As the dietary intake of these phytochemicals is often inadequate, various strategies are in use to improve their content in staple crops, and the end-products thereof. One of the most effective strategies is crop improvement through genetic approaches, as this is the only way to generate new cultivars in which the high accumulation of a given phytochemical is stably fixed. Efforts to genetically improve quality traits are rapidly evolving, from classical breeding to molecular-assisted approaches; these require sound understanding of the molecular bases underlying the traits, to identify the genes/alleles that control them. This can be achieved through global analysis of the metabolic pathway responsible for phytochemical accumulation, to identify the link between phytochemical content and the activities of key enzymes that regulate the metabolic pathway, and between the key enzymes and their encoding genes/alleles. Once these have been identified, they can be used as markers for selection of new improved genotypes through biotechnological approaches. This review provides an overview of the major health-promoting properties shown to be associated with the dietary intake of phytochemicals, and describes how molecular approaches provide means for improving the health quality of edible crops. Finally, a case study is illustrated, of the identification in durum wheat of the Lipoxygenase-B1 genes that control the final carotenoid content in semolina-based foods, such as pasta products. PMID:27455242

  12. Molecular Approaches to Genetically Improve the Accumulation of Health-Promoting Secondary Metabolites in Staple Crops-A Case Study: The Lipoxygenase-B1 Genes and Regulation of the Carotenoid Content in Pasta Products.

    PubMed

    Borrelli, Grazia M; Trono, Daniela

    2016-01-01

    Secondary metabolites, also known as phytochemicals, represent a large subset of plant molecules that include compounds with health-promoting effects. Indeed, a number of epidemiological studies have shown that, when taken regularly and in adequate amounts, these molecules can have long-term beneficial effects on human health, through reduction of the incidence of degenerative diseases, such as cardiovascular diseases, obesity, diabetes, and cancer. As the dietary intake of these phytochemicals is often inadequate, various strategies are in use to improve their content in staple crops, and the end-products thereof. One of the most effective strategies is crop improvement through genetic approaches, as this is the only way to generate new cultivars in which the high accumulation of a given phytochemical is stably fixed. Efforts to genetically improve quality traits are rapidly evolving, from classical breeding to molecular-assisted approaches; these require sound understanding of the molecular bases underlying the traits, to identify the genes/alleles that control them. This can be achieved through global analysis of the metabolic pathway responsible for phytochemical accumulation, to identify the link between phytochemical content and the activities of key enzymes that regulate the metabolic pathway, and between the key enzymes and their encoding genes/alleles. Once these have been identified, they can be used as markers for selection of new improved genotypes through biotechnological approaches. This review provides an overview of the major health-promoting properties shown to be associated with the dietary intake of phytochemicals, and describes how molecular approaches provide means for improving the health quality of edible crops. Finally, a case study is illustrated, of the identification in durum wheat of the Lipoxygenase-B1 genes that control the final carotenoid content in semolina-based foods, such as pasta products. PMID:27455242

  13. Advances in the Molecular Genetics of Non-syndromic Syndactyly

    PubMed Central

    Deng, Hao; Tan, Ting

    2015-01-01

    Syndactyly, webbing of adjacent digits with or without bony fusion, is one of the most common hereditary limb malformations. It occurs either as an isolated abnormality or as a component of more than 300 syndromic anomalies. There are currently nine types of phenotypically diverse nonsyndromic syndactyly. Non-syndromic syndactyly is usually inherited as an autosomal dominant trait, although the more severe presenting types and subtypes may show autosomal recessive or X-linked pattern of inheritance. The phenotype appears to be not only caused by a main gene, but also dependant on genetic background and subsequent signaling pathways involved in limb formation. So far, the principal genes identified to be involved in congenital syndactyly are mainly involved in the zone of polarizing activity and sonic hedgehog pathway. This review summarizes the recent progress made in the molecular genetics, including known genes and loci responsible for non-syndromic syndactyly, and the signaling pathways those genetic factors involved in, as well as clinical features and animal models. We hope our review will contribute to the understanding of underlying pathogenesis of this complicated disorder and have implication on genetic counseling. PMID:26069458

  14. Genetic, epigenetic, and molecular landscapes of multifocal and multicentric glioblastoma.

    PubMed

    Liu, Qun; Liu, Yuexin; Li, Wenliang; Wang, Xiaoguang; Sawaya, Raymond; Lang, Frederick F; Yung, W K Alfred; Chen, Kexin; Fuller, Gregory N; Zhang, Wei

    2015-10-01

    Ten to twenty percent of newly diagnosed glioblastoma (GBM) patients initially present with multiple lesions, termed multifocal or multicentric GBM (M-GBM). The prognosis of these patients is poorer than that of solitary GBM (S-GBM) patients. However, it is unknown whether multifocality has a genetic, epigenetic, or molecular basis. Here, we identified the genetic and epigenetic characteristics of M-GBM by performing a comprehensive analysis of multidimensional data, including imaging, genetic, epigenetic, and gene expression profiles, from 30 M-GBM cases in The Cancer Genome Atlas database and comparing the results with those of 173 S-GBM cases. We found that M-GBMs had no IDH1, ATRX, or PDGFRA mutations and were significantly associated with the mesenchymal subtype. We also identified the CYB5R2 gene to be hypo-methylated and overexpressed in M-GBMs. The expression level of CYB5R2 was significantly associated with patient survival in two major independent GBM cohorts, totaling 758 cases. The IDH1 mutation was markedly associated with CYB5R2 promoter methylation, but the survival influence of CYB5R2 was independent of IDH1 mutation status. CYB5R2 expression was significantly associated with collagen maturation and the catabolic process and immunoregulation pathways. These results reveal that M-GBMs have some underlying genetic and epigenetic characteristics that are associated with poor prognosis and that CYB5R2 is a new epigenetic marker for GBM prognosis. PMID:26323991

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

    PubMed

    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. PMID:27016693

  16. The molecular genetics of intrahepatic cholestasis of pregnancy

    PubMed Central

    Dixon, P H; Williamson, C

    2008-01-01

    Intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis, causes maternal pruritus and liver impairment, and may be complicated by spontaneous preterm labour, fetal asphyxial events and intrauterine death. Our understanding of the aetiology of this disease has expanded significantly in the last decade due to a better understanding of the role played by genetic factors. In particular, advances in our knowledge of bile homeostasis has led to the identification of genes that play a considerable role in susceptibility to ICP. In this review we consider these advances and discuss the disease in the context of bile synthesis and metabolism, focusing on the genetic discoveries that have shed light on the molecular aetiology and pathophysiology of the condition.

  17. Molecular prevalence of multiple genetic disorders in Border collies in Japan and recommendations for genetic counselling.

    PubMed

    Mizukami, K; Yabuki, A; Kohyama, M; Kushida, K; Rahman, M M; Uddin, M M; Sawa, M; Yamato, O

    2016-08-01

    Reproductive management is necessary to prevent deleterious genetic disorders in purebred dogs, but comprehensive studies aimed at prevention of multiple underlying genetic disorders in a single breed have not been performed. The aims of this study were to examine mutant allele frequencies associated with multiple genetic disorders, using Border collies as a representative breed, and to make recommendations for prevention of the disorders. Genotyping of known mutations associated with seven recessive genetic disorders was performed using PCR assays. More than half (56%) of the Border collies had no mutant alleles associated with any of the seven disorders, suggesting that these disorders can be removed from the population over several generations. Since frequencies of each mutant allele differed among disorders, reproductive management should be performed after the establishment of prevention schemes that are appropriate for each disorder, the type and specificity of genetic test available, and the effective population size in each breeding colony. PMID:27387721

  18. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0.

    PubMed

    Tamura, Koichiro; Stecher, Glen; Peterson, Daniel; Filipski, Alan; Kumar, Sudhir

    2013-12-01

    We announce the release of an advanced version of the Molecular Evolutionary Genetics Analysis (MEGA) software, which currently contains facilities for building sequence alignments, inferring phylogenetic histories, and conducting molecular evolutionary analysis. In version 6.0, MEGA now enables the inference of timetrees, as it implements the RelTime method for estimating divergence times for all branching points in a phylogeny. A new Timetree Wizard in MEGA6 facilitates this timetree inference by providing a graphical user interface (GUI) to specify the phylogeny and calibration constraints step-by-step. This version also contains enhanced algorithms to search for the optimal trees under evolutionary criteria and implements a more advanced memory management that can double the size of sequence data sets to which MEGA can be applied. Both GUI and command-line versions of MEGA6 can be downloaded from www.megasoftware.net free of charge. PMID:24132122

  19. Molecular and genetic aspects of odontogenic tumors: a review.

    PubMed

    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. PMID:26221475

  20. Molecular and genetic aspects of odontogenic tumors: a review

    PubMed Central

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

    2015-01-01

    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. PMID:26221475

  1. The importance of molecular analyses for understanding the genetic diversity of Histoplasma capsulatum: an overview.

    PubMed

    Vite-Garín, Tania; Estrada-Bárcenas, Daniel Alfonso; Cifuentes, Joaquín; Taylor, Maria Lucia

    2014-01-01

    Advances in the classification of the human pathogen Histoplasma capsulatum (H. capsulatum) (ascomycete) are sustained by the results of several genetic analyses that support the high diversity of this dimorphic fungus. The present mini-review highlights the great genetic plasticity of H. capsulatum. Important records with different molecular tools, mainly single- or multi-locus sequence analyses developed with this fungus, are discussed. Recent phylogenetic data with a multi-locus sequence analysis using 5 polymorphic loci support a new clade and/or phylogenetic species of H. capsulatum for the Americas, which was associated with fungal isolates obtained from the migratory bat Tadarida brasiliensis. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). PMID:24252830

  2. Microchip-based Devices for Molecular Diagnosis of Genetic Diseases.

    PubMed

    Cheng; Fortina; Surrey; Kricka; Wilding

    1996-09-01

    Microchips, constructed with a variety of microfabrication technologies (photolithography, micropatterning, microjet printing, light-directed chemical synthesis, laser stereochemical etching, and microcontact printing) are being applied to molecular biology. The new microchip-based analytical devices promise to solve the analytical problems faced by many molecular biologists (eg, contamination, low throughput, and high cost). They may revolutionize molecular biology and its application in clinical medicine, forensic science, and environmental monitoring. A typical biochemical analysis involves three main steps: (1) sample preparation, (2) biochemical reaction, and (3) detection (either separation or hybridization may be involved) accompanied by data acquisition and interpretation. The construction of a miniturized analyzer will therefore necessarily entail the miniaturization and integration of all three of these processes. The literature related to the miniaturization of these three processes indicates that the greatest emphasis so far is on the investigation and development of methods for the detection of nucleic acid, followed by the optimization of a biochemical reaction, such as the polymerase chain reaction. The first step involving sample preparation has received little attention. In this review the state of the art of, microchip-based, miniaturized analytical processes (eg, sample preparation, biochemical reaction, and detection of products) are outlined and the applications of microchip-based devices in the molecular diagnosis of genetic diseases are discussed. PMID:10462559

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

    PubMed Central

    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. PMID:26697053

  4. Monogenec Arrhythmic Syndromes: From Molecular and Genetic Aspects to Bedside

    PubMed Central

    E.Z., Golukhova; O.I., Gromova; R.A., Shomahov; N.I., Bulaeva; L.A., Bockeria

    2016-01-01

    The abrupt cessation of effective cardiac function that is generally due to heart rhythm disorders can cause sudden and unexpected death at any age and is referred to as a syndrome called “sudden cardiac death” (SCD). Annually, about 400,000 cases of SCD occur in the United States alone. Less than 5% of the resuscitation techniques are effective. The prevalence of SCD in a population rises with age according to the prevalence of coronary artery disease, which is the most common cause of sudden cardiac arrest. However, there is a peak in SCD incidence for the age below 5 years, which is equal to 17 cases per 100,000 of the population. This peak is due to congenital monogenic arrhythmic canalopathies. Despite their relative rarity, these cases are obviously the most tragic. The immediate causes, or mechanisms, of SCD are comprehensive. Generally, it is arrhythmic death due to ventricular tachyarrythmias – sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Bradyarrhythmias and pulseless electrical activity account for no more than 40% of all registered cardiac arrests, and they are more often the outcome of the abovementioned arrhythmias. Our current understanding of the mechanisms responsible for SCD has emerged from decades of basic science investigation into the normal electrophysiology of the heart, the molecular physiology of cardiac ion channels, the fundamental cellular and tissue events associated with cardiac arrhythmias, and the molecular genetics of monogenic disorders of the heart rhythm (for example, the long QT syndrome). This review presents an overview of the molecular and genetic basis of SCD in the long QT syndrome, Brugada syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and idiopathic ventricular fibrillation, and arrhythmogenic right ventricular dysplasia, and sudden cardiac death prevention strategies by modern techniques (including implantable cardioverter-defibrillator) PMID:27437140

  5. Monogenec Arrhythmic Syndromes: From Molecular and Genetic Aspects to Bedside.

    PubMed

    E Z, Golukhova; O I, Gromova; R A, Shomahov; N I, Bulaeva; L A, Bockeria

    2016-01-01

    The abrupt cessation of effective cardiac function that is generally due to heart rhythm disorders can cause sudden and unexpected death at any age and is referred to as a syndrome called "sudden cardiac death" (SCD). Annually, about 400,000 cases of SCD occur in the United States alone. Less than 5% of the resuscitation techniques are effective. The prevalence of SCD in a population rises with age according to the prevalence of coronary artery disease, which is the most common cause of sudden cardiac arrest. However, there is a peak in SCD incidence for the age below 5 years, which is equal to 17 cases per 100,000 of the population. This peak is due to congenital monogenic arrhythmic canalopathies. Despite their relative rarity, these cases are obviously the most tragic. The immediate causes, or mechanisms, of SCD are comprehensive. Generally, it is arrhythmic death due to ventricular tachyarrythmias - sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Bradyarrhythmias and pulseless electrical activity account for no more than 40% of all registered cardiac arrests, and they are more often the outcome of the abovementioned arrhythmias. Our current understanding of the mechanisms responsible for SCD has emerged from decades of basic science investigation into the normal electrophysiology of the heart, the molecular physiology of cardiac ion channels, the fundamental cellular and tissue events associated with cardiac arrhythmias, and the molecular genetics of monogenic disorders of the heart rhythm (for example, the long QT syndrome). This review presents an overview of the molecular and genetic basis of SCD in the long QT syndrome, Brugada syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia and idiopathic ventricular fibrillation, and arrhythmogenic right ventricular dysplasia, and sudden cardiac death prevention strategies by modern techniques (including implantable cardioverter-defibrillator). PMID:27437140

  6. Studies in genetic discrimination. Final progress report

    SciTech Connect

    Not Available

    1994-06-01

    We have screened 1006 respondents in a study of genetic discrimination. Analysis of these responses has produced evidence of the range of institutions engaged in genetic discrimination and demonstrates the impact of this discrimination on the respondents to the study. We have found that both ignorance and policy underlie genetic discrimination and that anti-discrimination laws are being violated.

  7. Fingerprinting and Genetic Stability of Rubus Using Molecular Markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DNA markers were used to identify raspberries and blackberries and to evaluate genetic stability of four cryopreserved Rubus accessions following 12 years of storage in liquid nitrogen. In the first study, 12 genomic Simple Sequence Repeat (SSR) markers and one Expressed Sequence Tag- (EST)-SSR wer...

  8. Molecular genetics of childhood papillary thyroid carcinomas after irradiation: high prevalence of RET rearrangement.

    PubMed

    Rabes, H M; Klugbauer, S

    1998-01-01

    Epidemiological studies have revealed a connection between thyroid carcinogenesis and a history of radiation. The molecular mechanisms involved are not well understood. It has been claimed that RAS, p53 or GSP mutations and RET or TRK rearrangements might play a role in adult thyroid tumors. In childhood, the thyroid gland is particularly sensitive to ionizing radiation. The reactor accident in Chernobyl provided a unique chance to study molecular genetic aberrations in a cohort of children who developed papillary thyroid carcinomas after a short latency time after exposure to high doses of radioactive iodine isotopes. According to the concepts of molecular genetic epidemiology, exposure to a specific type of irradiation might result in a typical molecular lesion. Childhood papillary thyroid tumors after Chernobyl exhibit a high prevalence of RET rearrangement as almost the only molecular alteration. The majority showed RET/PTC3 (i.e., ELE/RET rearrangements), including several subtypes. Less frequently, RET/PTC1 (i.e., H4/RET rearrangements), and a novel type (RET/PTC5, i.e., RFG5/RET) were observed. Proof of reciprocal transcripts suggests that a balanced intrachromosomal inversion leads to this rearrangement. Breakpoint analyses revealed short homologous nucleotide stretches at the fusion points. In all types of rearrangement, the RET tyrosine kinase domain becomes controlled by 5' fused regulatory sequences of ubiquitously expressed genes that display coiled-coil regions with dimerization potential. Oncogenic activation of RET is apparently due to ligand-independent constitutive ectopic RET tyrosine kinase activity. The analysis of this cohort of children with radiation-induced thyroid tumors after Chernobyl provides insights into typical molecular aberrations in relation to a specific mode of environmental exposure and may serve as a paradigm for molecular genetic epidemiology. PMID:10027005

  9. Exploring human brain lateralization with molecular genetics and genomics.

    PubMed

    Francks, Clyde

    2015-11-01

    Lateralizations of brain structure and motor behavior have been observed in humans as early as the first trimester of gestation, and are likely to arise from asymmetrical genetic-developmental programs, as in other animals. Studies of gene expression levels in postmortem tissue samples, comparing the left and right sides of the human cerebral cortex, have generally not revealed striking transcriptional differences between the hemispheres. This is likely due to lateralization of gene expression being subtle and quantitative. However, a recent re-analysis and meta-analysis of gene expression data from the adult superior temporal and auditory cortex found lateralization of transcription of genes involved in synaptic transmission and neuronal electrophysiology. Meanwhile, human subcortical mid- and hindbrain structures have not been well studied in relation to lateralization of gene activity, despite being potentially important developmental origins of asymmetry. Genetic polymorphisms with small effects on adult brain and behavioral asymmetries are beginning to be identified through studies of large datasets, but the core genetic mechanisms of lateralized human brain development remain unknown. Identifying subtly lateralized genetic networks in the brain will lead to a new understanding of how neuronal circuits on the left and right are differently fine-tuned to preferentially support particular cognitive and behavioral functions. PMID:25950729

  10. The use of genetic markers in the molecular epidemiology of histoplasmosis: a systematic review.

    PubMed

    Damasceno, L S; Leitão, T M J S; Taylor, M L; Muniz, M M; Zancopé-Oliveira, R M

    2016-01-01

    Histoplasmosis is a systemic mycosis caused by Histoplasma capsulatum, a dimorphic fungal pathogen that can infect both humans and animals. This disease has worldwide distribution and affects mainly immunocompromised individuals. In the environment, H. capsulatum grows as mold but undergoes a morphologic transition to the yeast morphotype under special conditions. Molecular techniques are important tools to conduct epidemiologic investigations for fungal detection, identification of infection sources, and determination of different fungal genotypes associated to a particular disease symptom. In this study, we performed a systematic review in the PubMed database to improve the understanding about the molecular epidemiology of histoplasmosis. This search was restricted to English and Spanish articles. We included a combination of specific keywords: molecular typing [OR] genetic diversity [OR] polymorphism [AND] H. capsulatum; molecular epidemiology [AND] histoplasmosis; and molecular epidemiology [AND] Histoplasma. In addition, we used the specific terms: histoplasmosis [AND] outbreaks. Non-English or non-Spanish articles, dead links, and duplicate results were excluded from the review. The results reached show that the main methods used for molecular typing of H. capsulatum were: restriction fragment length polymorphism, random amplified polymorphic DNA, microsatellites polymorphism, sequencing of internal transcribed spacers region, and multilocus sequence typing. Different genetic profiles were identified among H. capsulatum isolates, which can be grouped according to their source, geographical origin, and clinical manifestations. PMID:26589702

  11. Wrinkled Peas and White-Eyed Fruit Flies: The Molecular Basis of Two Classical Genetic Traits.

    ERIC Educational Resources Information Center

    Guilfoile, Patrick

    1997-01-01

    Focuses on bridging the gap between classical and molecular genetics for two traits: wrinkled seeds in garden peas and white eye color in fruit flies. Discusses the molecular details of the underlying basis of these traits. Contains 15 references. (JRH)

  12. Molecular and genetic basis of X-linked immunodeficiency disorders

    SciTech Connect

    Puck, J.M. )

    1994-03-01

    Within a short time interval the specific gene defects causing three X-linked human immunodeficiencies, agammaglobulinemia (XLA), hyper-IgM syndrome (HIGM), and severe combined immunodeficiency (XSCID), have been identified. These represent the first human disease phenotypes associated with each of three gene families already recognized to be important in lymphocyte development and signaling: XLA is caused by mutations of a B cell-specific intracellular tyrosine kinase; HIGM, by mutations in the TNF-related CD40 ligand, through which T cells deliver helper signals by direct contact with B cell CD40; and XSCID, by mutations in the [gamma] chain of the lymphocyte receptor for IL-2. Each patient mutation analyzed to date has been unique, representing both a challenge for genetic diagnosis and management and an important resource for dissecting molecular domains and understanding the physiologic function of the gene products.

  13. Molecular genetic basis of pod corn (Tunicate maize)

    PubMed Central

    Wingen, Luzie U.; Münster, Thomas; Faigl, Wolfram; Deleu, Wim; Sommer, Hans; Saedler, Heinz; Theißen, Günter

    2012-01-01

    Pod corn is a classic morphological mutant of maize in which the mature kernels of the cob are covered by glumes, in contrast to generally grown maize varieties in which kernels are naked. Pod corn, known since pre-Columbian times, is the result of a dominant gain-of-function mutation at the Tunicate (Tu) locus. Some classic articles of 20th century maize genetics reported that the mutant Tu locus is complex, but molecular details remained elusive. Here, we show that pod corn is caused by a cis-regulatory mutation and duplication of the ZMM19 MADS-box gene. Although the WT locus contains a single-copy gene that is expressed in vegetative organs only, mutation and duplication of ZMM19 in Tu lead to ectopic expression of the gene in the inflorescences, thus conferring vegetative traits to reproductive organs. PMID:22517751

  14. Molecular biology and genetics of embryonic eyelid development.

    PubMed

    Rubinstein, Tal J; Weber, Adam C; Traboulsi, Elias I

    2016-09-01

    The embryology of the eyelid is a complex process that includes interactions between the surface ectoderm and mesenchymal tissues. In the mouse and human, the eyelids form and fuse before birth; they open prenatally in the human and postnatally in the mouse. In the mouse, cell migration is stimulated by different growth factors such as FGF10, TGF-α, Activin B, and HB-EGF. These growth factors modulate downstream BMP4 signaling, the ERK cascade, and JNK/c-JUN. Several mechanisms, such as the Wnt/β-catenin signaling pathway, may inhibit and regulate eyelid fusion. Eyelid opening, on the other hand, is driven by the BMP/Smad signaling system. Several human genetic disorders result from dysregulation of the above molecular pathways. PMID:26863902

  15. [Research progress on molecular genetics of male homosexuality].

    PubMed

    Tu, Dan; Xu, Ruiwei; Zhao, Guanglu; Wang, Binbin; Feng, Tiejian

    2016-08-01

    Sexual orientation is influenced by both environmental factors and biological factors. Family and twin studies have shown that genetic factors play an important role in the formation of male homosexuality. Genome-wide scan also revealed candidate chromosomal regions which may be associated with male homosexuality, but so far no clearly related genes have been found. This article reviews the progress of relevant studies and candidate genes which are related to male homosexuality. PMID:27455023

  16. Environmental and Climatic Determinants of Molecular Diversity and Genetic Population Structure in a Coenagrionid Damselfly

    PubMed Central

    Wellenreuther, Maren; Sánchez-Guillén, Rosa A.; Cordero-Rivera, Adolfo; Svensson, Erik I.; Hansson, Bengt

    2011-01-01

    Identifying environmental factors that structure intraspecific genetic diversity is of interest for both habitat preservation and biodiversity conservation. Recent advances in statistical and geographical genetics make it possible to investigate how environmental factors affect geographic organisation and population structure of molecular genetic diversity within species. Here we present a study on a common and wide ranging insect, the blue tailed damselfly Ischnuraelegans, which has been the target of many ecological and evolutionary studies. We addressed the following questions: (i) Is the population structure affected by longitudinal or latitudinal gradients?; (ii) Do geographic boundaries limit gene flow?; (iii) Does geographic distance affect connectivity and is there a signature of past bottlenecks?; (iv) Is there evidence of a recent range expansion and (vi) what is the effect of geography and climatic factors on population structure? We found low to moderate genetic sub-structuring between populations (mean FST = 0.06, Dest = 0.12), and an effect of longitude, but not latitude, on genetic diversity. No significant effects of geographic boundaries (e.g. water bodies) were found. FST-and Dest-values increased with geographic distance; however, there was no evidence for recent bottlenecks. Finally, we did not detect any molecular signatures of range expansions or an effect of geographic suitability, although local precipitation had a strong effect on genetic differentiation. The population structure of this small insect has probably been shaped by ecological factors that are correlated with longitudinal gradients, geographic distances, and local precipitation. The relatively weak global population structure and high degree of genetic variation within populations suggest that I. elegans has high dispersal ability, which is consistent with this species being an effective and early coloniser of new habitats. PMID:21655216

  17. [Screening for hereditary neuromuscular disorders with molecular genetic methods in the Roma population of Hungary].

    PubMed

    Herczegfalvi, Agnes; Pikó, Henriett; Karcagi, Veronika

    2008-11-30

    Recent medical genetic research has identified a number of novel, or previously known, but rare conditions, caused by private founder mutations. The Finnish and Ashkenazi Jew populations provide the best examples for identifying genes in unique genetic disorders. In these populations, research efforts and high-level medical services resulted in intense improvements of medical care and in organization of population-based screening programs. Hereditary disorders of the Roma populations are known for a long time. The genetic background of these diseases has been established by extensive molecular genetic studies. The Romas represent 6% of the Hungarian population and live under extremely bad health conditions. Therefore, our aim was to map the incidence of the hereditary neuromuscular disorders among the Hungarian Roma population. Moreover, we intended to provide proper information, genetic counseling and possible prevention strategies for the families at risk, which should represent a primer task in public health. Because of our experience in neuromuscular disorders, we choose six, frequent, autosomal recessive disorders for these clinical and genetic studies: hereditary motor and sensory neuropathy type Lom (HMSNL), hereditary motor and sensory neuropathy type Russe (HMSNR), congenital cataracts facial dysmorphism syndrome (CCFDN), limb-girdle muscular dystrophy 2C (LGMD2C), congenital myasthenic syndrome (CMS) and spinal muscular atrophy (SMA). Following identification of the founder mutations, the possibility of prenatal diagnosis and carrier screening for family members will contribute to the decrease of the recurrence risk for these severe, mostly untreatable disorders. PMID:19070320

  18. Molecular genetic defect underlying {alpha}-L-iduronidase pseudodeficiency

    SciTech Connect

    Aronovich, E.L.; Pan, D.; Whitley, C.B.

    1996-01-01

    Mucopolysaccharidosis type I (i.e., Hurler, Hurler-Scheie, and Scheie syndromes) and type II (i.e., Hunter syndrome) are lysosomal storage disorders resulting from {alpha}-L-iduronidase (IDUA) deficiency and iduronate-2-sulfatase (IDS) deficiency, respectively. The a priori probability that both disorders would occur in a single individual is {approximately}1 in 5 billion. Nevertheless, such a proband was referred for whom clinical findings (i.e., a male with characteristic facies, dysostosis multiplex, and mental retardation) and biochemical tests indicated these concomitant diagnoses. Multiple techniques, including automated sequencing of the entire IDS and IDUA coding regions, were employed to unravel the molecular genetic basis of these intriguing observations. The common IDS mutation R468W was identified in the proband, his mother, and his sister, thus explaining their biochemical phenotypes. Additionally, the proband, his sister, and his father were found to be heterozygous for a common IDUA mutation, W402X. Notably, a new IDUA mutation A300T was also identified in the proband, his sister, and his mother, accounting for reduced IDUA activity in these individuals; the asymptomatic sister, whose cells demonstrated normal glycosaminoglycan metabolism, is thus a compound heterozygote for W402X and the new allele. This A300T mutation is the first IDUA pseudodeficiency gene to be elucidated at the molecular level. 37 refs., 7 figs., 3 tabs.

  19. Molecular photoionization studies

    SciTech Connect

    Dehmer, P.M.

    1983-01-01

    This program is concerned with the study of the electronic structure of small molecules and clusters of molecules. Of particular interest is the interaction of discrete electronic states with one another and with the various ionization and dissociation continua. Since the Second Annual Meeting of the DOE-OHER Program on The Physics and Chemistry of Energy-Related Atmospheric Pollutants in April 1981, significant progress has been made in the following areas: (1) the study of the electronic structure of dimers and small clusters of rare gas atoms using photoionization techniques; (2) similar studies on clusters of CO/sub 2/ molecules; (3) the study of electronic structure of rare gas dimers and trimers using photoelectron and photoelectron-photoion coincidence techniques; (4) the investigation of the relationship between Rydberg states in atoms, van der Waals molecules, and chemically-bonded molecules; (5) the extension of the study of photoabsorption, photoionization, and predissociation processes in H/sub 2/ to the unsymmetric isotope HD; (6) the study of photoelectron spectra of H/sub 2/ and C/sub 2/H/sub 2/; (7) a review of some of the aspects of dissociation processes in small molecules; and (8) the creation of a new program to study the spectra and dynamics of the photoionization processes in small molecules using the technique of multiphoton ionization followed by mass and electron energy analysis of the product ions and electrons. Some of the highlights of this work are reviewed.

  20. Genetic and molecular dosimetry of HZE radiation (7-IML-1)

    NASA Technical Reports Server (NTRS)

    Nelson, Gregory A.

    1992-01-01

    The objectives of the study are to determine the kinetics of production and to characterize the unique aspects of genetic and developmental lesion induced in animal cells by radiation present in the space environment. Special attention is given to heavy charged particles. The organism Caenorhabditis elegans, a simple nematode, is used as a model system for a coordinated set of ground-based and flight experiments.

  1. Genetic, molecular and physiological basis of variation in Drosophila gut immunocompetence

    PubMed Central

    Bou Sleiman, Maroun S.; Osman, Dani; Massouras, Andreas; Hoffmann, Ary A.; Lemaitre, Bruno; Deplancke, Bart

    2015-01-01

    Gut immunocompetence involves immune, stress and regenerative processes. To investigate the determinants underlying inter-individual variation in gut immunocompetence, we perform enteric infection of 140 Drosophila lines with the entomopathogenic bacterium Pseudomonas entomophila and observe extensive variation in survival. Using genome-wide association analysis, we identify several novel immune modulators. Transcriptional profiling further shows that the intestinal molecular state differs between resistant and susceptible lines, already before infection, with one transcriptional module involving genes linked to reactive oxygen species (ROS) metabolism contributing to this difference. This genetic and molecular variation is physiologically manifested in lower ROS activity, lower susceptibility to ROS-inducing agent, faster pathogen clearance and higher stem cell activity in resistant versus susceptible lines. This study provides novel insights into the determinants underlying population-level variability in gut immunocompetence, revealing how relatively minor, but systematic genetic and transcriptional variation can mediate overt physiological differences that determine enteric infection susceptibility. PMID:26213329

  2. Genetic profiling of the Plasmodium falciparum population using antigenic molecular markers.

    PubMed

    Gupta, Purva; Singh, Ruchi; Khan, Haris; Raza, Adil; Yadavendu, Veena; Bhatt, R M; Singh, Vineeta

    2014-01-01

    About 50% of malaria infections in India are attributed to Plasmodium falciparum but relatively little is known about the genetic structure of the parasite populations. The molecular genotyping of the parasite populations by merozoite surface protein (msp1 and msp2) and glutamate-rich protein (glurp) genes identifies the existing parasite population in the regions which help in understanding the molecular mechanisms involved in the parasite's drive for survival. This study reveals the genetic profile of the parasite population in selected regions across the country with varying degree of endemicity among them. We also report the prevalence of Pfcrt mutations in this parasite population to evaluate the pattern of drug resistance development in them. PMID:25405214

  3. A molecular-genetic approach to studying source-sink interactions in Arabidopsis thaliana. Final report, April 1, 1995--March 31, 1998

    SciTech Connect

    Gibson, S.I.

    1998-11-01

    The ultimate goal of this research is to elucidate the molecular mechanisms by which the complex interactions between sources and sinks of fixed carbon are controlled in plants. As soluble sugar levels have been shown to play a vital role in a variety of source-sink interactions, a key aspect of the authors research is to determine the role of sugar-regulated gene expression in mediating source-sink interactions. In addition, as a critical aspect of source-sink interactions is the channeling of fixed carbon into different storage forms, they have pursued the findings that fumaric acid represents a significant form of storage carbon in Arabidopsis thaliana and other plant species. In the future, a better understanding of the mechanisms by which interactions between sources and sinks of fixed carbon are coordinated will be a pre-requisite to developing more rationale approaches to improving harvest indices in crop species.

  4. Molecular Genetic Testing in Reward Deficiency Syndrome (RDS): Facts and Fiction

    PubMed Central

    Blum, Kenneth; Badgaiyan, Rajendra D.; Agan, Gozde; Fratantonio, James; Simpatico, Thomas; Febo, Marcelo; Haberstick, Brett C.; Smolen, Andrew; Gold, Mark S.

    2015-01-01

    Background The Brain Reward Cascade (BRC) is an interaction of neurotransmitters and their respective genes to control the amount of dopamine released within the brain. Any variations within this pathway, whether genetic or environmental (epigenetic), may result in addictive behaviors or RDS, which was coined to define addictive behaviors and their genetic components. Methods To carry out this review we searched a number of important databases including: Filtered: Cochrane Systematic reviews; DARE; Pubmed Central Clinical Quaries; National Guideline Clearinghouse and unfiltered resources: PsychINFO; ACP PIER; PsychSage; Pubmed/Medline. The major search terms included: dopamine agonist therapy for Addiction; dopamine agonist therapy for Reward dependence; dopamine antagonistic therapy for addiction; dopamine antagonistic therapy for reward dependence and neurogenetics of RDS. Results While there are many studies claiming a genetic association with RDS behavior, not all are scientifically accurate. Conclusion Albeit our bias, this Clinical Pearl discusses the facts and fictions behind molecular genetic testing in RDS and the significance behind the development of the Genetic Addiction Risk Score (GARSPREDX™), the first test to accurately predict one’s genetic risk for RDS. PMID:26052557

  5. Plasmid Vectors and Molecular Building Blocks for the Development of Genetic Manipulation Tools for Trypanosoma cruzi

    PubMed Central

    Bouvier, León A.; Cámara, María de los Milagros; Canepa, Gaspar E.; Miranda, Mariana R.; Pereira, Claudio A.

    2013-01-01

    The post genomic era revealed the need for developing better performing, easier to use and more sophisticated genetic manipulation tools for the study of Trypanosoma cruzi, the etiological agent of Chagas disease. In this work a series of plasmids that allow genetic manipulation of this protozoan parasite were developed. First of all we focused on useful tools to establish selection strategies for different strains and which can be employed as expression vectors. On the other hand molecular building blocks in the form of diverse selectable markers, modifiable fluorescent protein and epitope-tag coding sequences were produced. Both types of modules were harboured in backbone molecules conceived to offer multiple construction and sub-cloning strategies. These can be used to confer new properties to already available genetic manipulation tools or as starting points for whole novel designs. The performance of each plasmid and building block was determined independently. For illustration purposes, some simple direct practical applications were conducted. PMID:24205392

  6. Plasmid vectors and molecular building blocks for the development of genetic manipulation tools for Trypanosoma cruzi.

    PubMed

    Bouvier, León A; Cámara, María de los Milagros; Canepa, Gaspar E; Miranda, Mariana R; Pereira, Claudio A

    2013-01-01

    The post genomic era revealed the need for developing better performing, easier to use and more sophisticated genetic manipulation tools for the study of Trypanosoma cruzi, the etiological agent of Chagas disease. In this work a series of plasmids that allow genetic manipulation of this protozoan parasite were developed. First of all we focused on useful tools to establish selection strategies for different strains and which can be employed as expression vectors. On the other hand molecular building blocks in the form of diverse selectable markers, modifiable fluorescent protein and epitope-tag coding sequences were produced. Both types of modules were harboured in backbone molecules conceived to offer multiple construction and sub-cloning strategies. These can be used to confer new properties to already available genetic manipulation tools or as starting points for whole novel designs. The performance of each plasmid and building block was determined independently. For illustration purposes, some simple direct practical applications were conducted. PMID:24205392

  7. Population genetic structure of rare and endangered plants using molecular markers

    USGS Publications Warehouse

    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

  8. Teaching Applied Genetics and Molecular Biology to Agriculture Engineers. Application of the European Credit Transfer System

    ERIC Educational Resources Information Center

    Weiss, J.; Egea-Cortines, M.

    2008-01-01

    We have been teaching applied molecular genetics to engineers and adapted the teaching methodology to the European Credit Transfer System. We teach core principles of genetics that are universal and form the conceptual basis of most molecular technologies. The course then teaches widely used techniques and finally shows how different techniques…

  9. Reverse Genetics System for Studying Human Rhinovirus Infections

    PubMed Central

    Lee, Wai-Ming; Wang, Wensheng; Bochkov, Yury A; Lee, Iris

    2015-01-01

    SUMMARY Human rhinovirus (HRV) contains a 7.2 Kb messenger-sense RNA genome which is the template for reproducing progeny viruses after it enters the cytoplasm of a host cell. Reverse genetics refers to the regeneration of progeny viruses from an artificial cDNA copy of the RNA genome of an RNA virus. It has been a powerful molecular genetic tool for studying HRV and other RNA viruses because the artificial DNA stage makes it practical to introduce specific mutations into the viral RNA genome. This chapter uses HRV-16 as the model virus to illustrate the strategy and the methods for constructing and cloning the artificial cDNA copy of a full-length HRV genome, identifying the infectious cDNA clone isolates, and selecting the most vigorous cDNA clone isolate to serve as the standard parental clone for future molecular genetic study of the virus. PMID:25261313

  10. Study in molecular lasers

    NASA Astrophysics Data System (ADS)

    Burns, G.; Kutz, H. D.; Cohen, L. K.; Billard, T. C.

    1984-10-01

    A sensitive LIF system was constructed, using a Nd:YAG plus dye laser. The signal was accumulated and analyzed by employing a Tektronix R7912 transient Digitizer and a PDP-11 minicomputer. Reactivity of HF (v=5) was studied. Using the same equipment, a time-delayed photoemission from a trialkali photosensitive semiconductor was observed and results are now being examined. Using 3-D trajectory calculations a new computational observable, the relative nonequilibrium distribution (RNED) function at the steady state was determined for the Br + Ar reaction at 3500K. It is characterized by one adjustable parameter equal to 12, while the transition state theory prescribes that it should be infinitely large. RNED will be used to test and refine modern theories of reaction kinetics.

  11. NACE: A web-based tool for prediction of intercompartmental efficiency of human molecular genetic networks.

    PubMed

    Popik, Olga V; Ivanisenko, Timofey V; Saik, Olga V; Petrovskiy, Evgeny D; Lavrik, Inna N; Ivanisenko, Vladimir A

    2016-06-15

    Molecular genetic processes generally involve proteins from distinct intracellular localisations. Reactions that follow the same process are distributed among various compartments within the cell. In this regard, the reaction rate and the efficiency of biological processes can depend on the subcellular localisation of proteins. Previously, the authors proposed a method of evaluating the efficiency of biological processes based on the analysis of the distribution of protein subcellular localisation (Popik et al., 2014). Here, NACE is presented, which is an open access web-oriented program that implements this method and allows the user to evaluate the intercompartmental efficiency of human molecular genetic networks. The method has been extended by a new feature that provides the evaluation of the tissue-specific efficiency of networks for more than 2800 anatomical structures. Such assessments are important in cases when molecular genetic pathways in different tissues proceed with the participation of various proteins with a number of intracellular localisations. For example, an analysis of KEGG pathways, conducted using the developed program, showed that the efficiencies of many KEGG pathways are tissue-specific. Analysis of efficiencies of regulatory pathways in the liver, linking proteins of the hepatitis C virus with human proteins involved in the KEGG apoptosis pathway, showed that intercompartmental efficiency might play an important role in host-pathogen interactions. Thus, the developed tool can be useful in the study of the effectiveness of functioning of various molecular genetic networks, including metabolic, regulatory, host-pathogen interactions and others taking into account tissue-specific gene expression. The tool is available via the following link: http://www-bionet.sscc.ru/nace/. PMID:27109913

  12. Psychometric precision in phenotype definition is a useful step in molecular genetic investigation of psychiatric disorders.

    PubMed

    Xu, M K; Gaysina, D; Barnett, J H; Scoriels, L; van de Lagemaat, L N; Wong, A; Richards, M; Croudace, T J; Jones, P B

    2015-01-01

    Affective disorders are highly heritable, but few genetic risk variants have been consistently replicated in molecular genetic association studies. The common method of defining psychiatric phenotypes in molecular genetic research is either a summation of symptom scores or binary threshold score representing the risk of diagnosis. Psychometric latent variable methods can improve the precision of psychiatric phenotypes, especially when the data structure is not straightforward. Using data from the British 1946 birth cohort, we compared summary scores with psychometric modeling based on the General Health Questionnaire (GHQ-28) scale for affective symptoms in an association analysis of 27 candidate genes (249 single-nucleotide polymorphisms (SNPs)). The psychometric method utilized a bi-factor model that partitioned the phenotype variances into five orthogonal latent variable factors, in accordance with the multidimensional data structure of the GHQ-28 involving somatic, social, anxiety and depression domains. Results showed that, compared with the summation approach, the affective symptoms defined by the bi-factor psychometric model had a higher number of associated SNPs of larger effect sizes. These results suggest that psychometrically defined mental health phenotypes can reflect the dimensions of complex phenotypes better than summation scores, and therefore offer a useful approach in genetic association investigations. PMID:26125156

  13. Effect of bead and illustrations models on high school students' achievement in molecular genetics

    NASA Astrophysics Data System (ADS)

    Rotbain, Yosi; Marbach-Ad, Gili; Stavy, Ruth

    2006-05-01

    Our main goal in this study was to explore whether the use of models in molecular genetics instruction in high school can contribute to students' understanding of concepts and processes in genetics. Three comparable groups of 11th and 12th graders participated: The control group (116 students) was taught in the traditional lecture format, while the others received instructions which integrated a bead model (71 students), or an illustration model (71 students). Similar instructions and the same guiding questions accompanied the two models. We used three instruments: a multiple-choice and an open-ended written questionnaire, as well as personal interviews. Five of the multiple-choice questions were also given to students before receiving their genetics instruction (pretest). We found that students who used one of the two types of models improved their knowledge in molecular genetics compared to the control group. However, the open-ended questions revealed that bead model activity was significantly more effective than illustration activity. On the basis of these findings we conclude that, though it is advisable to use a three-dimensional model, such as the bead model, engaging students in activities with illustrations can still improve their achievement in comparison to traditional instruction.

  14. Quantitative genetic studies of antisocial behaviour.

    PubMed

    Viding, Essi; Larsson, Henrik; Jones, Alice P

    2008-08-12

    This paper will broadly review the currently available twin and adoption data on antisocial behaviour (AB). It is argued that quantitative genetic research can make a significant contribution to further the understanding of how AB develops. Genetically informative study designs are particularly useful for investigating several important questions such as whether: the heritability estimates vary as a function of assessment method or gender; the relative importance of genetic and environmental influences varies for different types of AB; the environmental risk factors are truly environmental; and genetic vulnerability influences susceptibility to environmental risk. While the current data are not yet directly translatable for prevention and treatment programmes, quantitative genetic research has concrete translational potential. Quantitative genetic research can supplement neuroscience research in informing about different subtypes of AB, such as AB coupled with callous-unemotional traits. Quantitative genetic research is also important in advancing the understanding of the mechanisms by which environmental risk operates. PMID:18434281

  15. Molecular stripping in the NFκB / IκB / DNA genetic regulatory network

    NASA Astrophysics Data System (ADS)

    Potoyan, Davit; Wolynes, Peter

    Genetic switches based on the NFκB / IκB / DNA system are master regulators of an array of cellular responses. Recent kinetic experiments have shown that IκB can actively remove NF κB bound to its genetic sites via a process called ''molecular stripping''. This allows the NFκB / IκB / DNA switch to function under kinetic control rather than the thermodynamic control contemplated in the traditional models of gene switches. Using molecular dynamics simulations of coarse grained predictive energy landscape models for the constituent proteins by themselves and interacting with the DNA we explore the functional motions of the transcription factor NFκB and its various binary and ternary complexes with DNA and the inhibitor I κB. These studies show that the function of the NFκB / IκB / DNA genetic switch is realized via an allosteric mechanism. Molecular stripping occurs through the activation of a domain twist mode by the binding of IκB which occurs through conformational selection. Free energy calculations for DNA binding show that the binding of IκB not only results in a significant decrease of the affinity of the transcription factor for the DNA but also kinetically speeds DNA release. Projections of the

  16. Molecular stripping in the NF-κB/IκB/DNA genetic regulatory network

    PubMed Central

    Potoyan, Davit A.; Zheng, Weihua; Komives, Elizabeth A.; Wolynes, Peter G.

    2016-01-01

    Genetic switches based on the NF-κB/IκB/DNA system are master regulators of an array of cellular responses. Recent kinetic experiments have shown that IκB can actively remove NF-κB bound to its genetic sites via a process called “molecular stripping.” This allows the NF-κB/IκB/DNA switch to function under kinetic control rather than the thermodynamic control contemplated in the traditional models of gene switches. Using molecular dynamics simulations of coarse-grained predictive energy landscape models for the constituent proteins by themselves and interacting with the DNA we explore the functional motions of the transcription factor NF-κB and its various binary and ternary complexes with DNA and the inhibitor IκB. These studies show that the function of the NF-κB/IκB/DNA genetic switch is realized via an allosteric mechanism. Molecular stripping occurs through the activation of a domain twist mode by the binding of IκB that occurs through conformational selection. Free energy calculations for DNA binding show that the binding of IκB not only results in a significant decrease of the affinity of the transcription factor for the DNA but also kinetically speeds DNA release. Projections of the free energy onto various reaction coordinates reveal the structural details of the stripping pathways. PMID:26699500

  17. Molecular genetics of attention-deficit/hyperactivity disorder: an overview

    PubMed Central

    Becker, Katja; Scherag, Susann; Franke, Barbara; Coghill, David

    2010-01-01

    As heritability is high in attention-deficit/hyperactivity disorder (ADHD), genetic factors must play a significant role in the development and course of this disorder. In recent years a large number of studies on different candidate genes for ADHD have been published, most have focused on genes involved in the dopaminergic neurotransmission system, such as DRD4, DRD5, DAT1/SLC6A3, DBH, DDC. Genes associated with the noradrenergic (such as NET1/SLC6A2, ADRA2A, ADRA2C) and serotonergic systems (such as 5-HTT/SLC6A4, HTR1B, HTR2A, TPH2) have also received considerable interest. Additional candidate genes related to neurotransmission and neuronal plasticity that have been studied less intensively include SNAP25, CHRNA4, NMDA, BDNF, NGF, NTF3, NTF4/5, GDNF. This review article provides an overview of these candidate gene studies, and summarizes findings from recently published genome-wide association studies (GWAS). GWAS is a relatively new tool that enables the identification of new ADHD genes in a hypothesis-free manner. Although these latter studies could be improved and need to be replicated they are starting to implicate processes like neuronal migration and cell adhesion and cell division as potentially important in the aetiology of ADHD and have suggested several new directions for future ADHD genetics studies. PMID:20145962

  18. [Recent advances in molecular genetics of GM2 gangliosidosis].

    PubMed

    Wakamatsu, N

    1995-12-01

    Recent advances in molecular genetics of GM2 gangliosidosis are reviewed. GM2 gangliosidosis is an autosomal recessive, neurodegenerative disease caused by a deficiency of beta-hexosaminidase (Hex, EC 3.2.1.52) A activity, resulting in accumulation of GM2 ganglioside in the lysosomes of neuronal cells. There are two catalytically active forms of this enzyme: Hex A, composed of one alpha and one beta subunits. Three forms of this disease, Tay-Sachs disease, Sandhoff disease, and GM2 activator deficiency, have been recognized according to whether the defect involves the alpha subunit, beta subunit, or GM2 activator protein, respectively. A number of gene abnormalities responsible for the disease have been identified and mutations specific for phenotypes and racial backgrounds are summarized. Recently, the murine models of human Tay-Sachs disease and Sandhoff disease have been produced. With the finding of dramatically clinical phenotypes in these mice, these models could be useful for research on the pathogenesis or therapy of these diseases. PMID:8577047

  19. Genetics and molecular pathogenesis of mitochondrial respiratory chain diseases.

    PubMed

    Hanna, M G; Nelson, I P

    1999-05-01

    Dysfunction of the mitochondrial respiratory chain has been recognised as a cause of human disease for over 30 years. Advances in the past 10 years have led to a better understanding of the genetics and molecular pathogenesis of many of these disorders. Over 100 primary defects in mitochondrial DNA (mtDNA) are now implicated in the pathogenesis of a group of disorders which are collectively known as the mitochondrial encephalomyopathies, and which most frequently involve skeletal muscle and/or the central nervous system. Although impaired oxidative phosphorylation is likely to be the final common pathway leading to the cellular dysfunction associated with such mtDNA mutations, the complex relationship between genotype and phenotype remains largely unexplained. Most of the genes which encode the respiratory chain reside in the nucleus, yet only five nuclear genes have been implicated in human respiratory chain diseases. There is evidence that respiratory chain dysfunction is present in common neurological diseases such as Parkinson's disease and Huntington's disease. The precise cause of this respiratory chain dysfunction and its relationship to the disease process are unclear. This review focuses upon respiratory chain disorders associated with primary defects in mtDNA. PMID:10379358

  20. Molecular genetics of human primary microcephaly: an overview

    PubMed Central

    2015-01-01

    Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental retardation. Microcephaly is the outcome of a smaller but architecturally normal brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a neurogenic mitotic disorder, though affected patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1-MCPH12) have been mapped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. Additional findings have further elucidated the microcephaly aetiology and pathophysiology, which has informed the clinical management of families suffering from MCPH. The provision of molecular diagnosis and genetic counselling may help to decrease the frequency of this disorder. PMID:25951892

  1. Molecular genetics of human primary microcephaly: an overview.

    PubMed

    Faheem, Muhammad; Naseer, Muhammad Imran; Rasool, Mahmood; Chaudhary, Adeel G; Kumosani, Taha A; Ilyas, Asad Muhammad; Pushparaj, Peter; Ahmed, Farid; Algahtani, Hussain A; Al-Qahtani, Mohammad H; Saleh Jamal, Hasan

    2015-01-01

    Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental retardation. Microcephaly is the outcome of a smaller but architecturally normal brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a neurogenic mitotic disorder, though affected patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1-MCPH12) have been mapped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. Additional findings have further elucidated the microcephaly aetiology and pathophysiology, which has informed the clinical management of families suffering from MCPH. The provision of molecular diagnosis and genetic counselling may help to decrease the frequency of this disorder. PMID:25951892

  2. [Molecular, genetic and physiological analysis of photoinhibition and photosynthetic

    SciTech Connect

    Not Available

    1992-01-01

    A major goal of this project is to use a combined molecular genetic, biochemical and physiological approach to understand the relationship between photosynthetic performance and the structure of the multifunctional D1 reaction center protein of Photosystem II encoded by the chloroplast psbA gene. Relative to other chloroplast proteins, turover of D1 is rapid and highly light dependent and de novo synthesis of D1 is required for a plant's recovery from short term exposure to irradiances which induce photoinhibitory damage. These observations have led to models for a damage/repair cycle of PSII involving the targeted degradation and replacement of photodamaged D1. To investigate the effects of perturbing the D1 cycle on photosynthesis and autotrophic growth under high and low irradiance, we have examined the consequences of site-specific mutations of the psbA and 16S rRNA genes affecting synthesis, maturation and function/stability of the D1 protein introduced into the chloroplast genome of wildtype strain of the green alga Chlamydomonas reinhardtii using biolistic transformation.

  3. [MELAS syndrome. Clinical aspects, MRI, biochemistry and molecular genetics].

    PubMed

    Damian, M S; Reichmann, H; Seibel, P; Bachmann, G; Schachenmayr, W; Dorndorf, W

    1994-04-01

    MELAS is a mitochondrial cytopathy characterized by encephalopathy with stroke-like episodes and lactic acidosis. Most patients exhibit an A-G transition mutation at np 3243 of mitochondrial DNA (tRNA(Leu)(UUR)). We present a family of four in which the mutation was discovered in blood and in muscle mt DNA. Two patients had the classic MELAS syndrome with multiple stroke-like episodes. Some episodes were precipitated by metabolic stress. The remaining two patients had an oligosymptomatic disease with mild chronic encephalopathy, small stature and hearing loss. MRI was followed over a period of 4-8 years, during which the MELAS patients showed progression from nonspecific multifocal signal change to typical extensive cortico-subcortical parieto-occipital lesions and progressive cerebral atrophy. MRI in the oligosymptomatic cases was normal, or showed non-progressive cerebellar atrophy. Biochemical findings were non-specific, indicating increased mitochondrial volume in all cases, and a relatively complex IV defect in one case. All patients were treated with coenzyme Q with varying clinical response. The percentage of mutant mt DNA in blood and muscle did not correlate with clinical severity. Pathogenetic theories based on molecular genetics, and the therapeutic regimen in terms of the underlying biochemical concepts are discussed. PMID:8015633

  4. Molecular marker development and genetic diversity exploration by RNA-seq in Platycodon grandiflorum.

    PubMed

    Kim, Hyun Jung; Jung, Jungsu; Kim, Myung-Shin; Lee, Je Min; Choi, Doil; Yeam, Inhwa

    2015-10-01

    Platycodon grandiflorum, generally known as the bellflower or balloon flower, is the only species in the genus Platycodon of the family Campanulaceae. Platycodon plants have been traditionally used as a medicinal crop in East Asia for their antiphlogistic, antitussive, and expectorant properties. Despite these practical uses, marker-assisted selection and molecular breeding in platycodons have lagged due to the lack of genetic information on this genus. In this study, we performed RNA-seq analysis of three platycodon accessions to develop molecular markers and explore genetic diversity. First, genic simple sequence repeats (SSRs) were retrieved and compared; dinucleotide motifs were the most abundant repeats (39%-40%) followed by trinucleotide (25%-31%), tetranucleotide (1.5%-1.9%), and pentanucleotide (0.3%-1.0%) repeats. The result of in silico SSR analysis, three SSR markers were detected and showed possibility to distinguish three platycodon accessions. After several filtering procedures, 180 single nucleotide polymorphisms (SNPs) were used to design 40 cleaved amplified polymorphic sequence (CAPS) markers. Twelve of these PCR-based markers were validated as highly polymorphic and utilized to investigate genetic diversity in 21 platycodon accessions collected from various regions of South Korea. Collectively, the 12 markers yielded 35 alleles, with an average of 3 alleles per locus. Polymorphism information content (PIC) values ranged from 0.087 to 0.693, averaging 0.373 per locus. Since platycodon genetics have not been actively studied, the sequence information and the DNA markers generated from our research have the potential to contribute to further genetic improvements, genomic studies, and gene discovery in this genus. PMID:26501479

  5. Molecular biodiversity. Case study: Porifera (sponges).

    PubMed

    Müller, Werner E G; Brümmer, Franz; Batel, Renato; Müller, Isabel M; Schröder, Heinz C

    2003-03-01

    Biological diversity--or biodiversity--is the term given to the variety of life on Earth and the natural patterns it forms. The biodiversity we see today is the fruit of billions of years of evolution, shaped by natural processes and, increasingly, by the influence of humans. It forms the web of life of which we are an integral part and upon which we so fully depend. The research on molecular biodiversity tries to lay the scientific foundation of a rational conservation policy that has its roots in various disciplines including systematics/taxonomy (species richness), present day ecology (diversity of ecological systems), and functional genetics (genetic diversity). The results of ongoing genome analyses (genome projects and expressed sequence tag projects) and the achievements of molecular evolution may allow us not only to quantitate the diversity of the present biota but also to extrapolate to their diversification in the future. A link between biodiversity and genomics/molecular evolution will create a platform which we hope may facilitate a sustainable management of organismic life and ensure its exploitation for human benefit. In the present review we outline possible strategies, using the Porifera (sponges) as a prominent example. On the basis of solid taxonomy and ecological data, the high value of this phylum for human application becomes obvious, especially with regard to the field of chemical ecology and the desire to find novel potential drugs for clinical use. In addition, the benefit of trying to make sense of molecular biodiversity using sponges as an example can be seen in the fact that the study of these animals, which are "living fossils", gives us a good insight into the history of our planet, especially with respect to the evolution of Metazoa. PMID:12649752

  6. [The problem of molecular-genetic identification of sweat and grease deposits in the human fingerprints].

    PubMed

    Faleeva, T G; Ivanov, I N; Mishin, E S; Vnukova, N V; Kornienko, I V

    2016-01-01

    The objective of the present experimental molecular-genetic study of DNA contained in of human fingerprints was to establish the relationship between the reference genetic profiles and the genotypes of the individuals leaving their fingerprints on a smooth metal object. The biological material for the purpose of the investigation was sampled at different time intervals. The were taken using a scotch tape and used to obtain the complete genetic profile immediately after the fingerprints had been left as well as within the next 24 hours and one week. It proved impossible to identify the complete genetic profile one month after the fingerprints had been left. The alleles not typical for reference samples were identified within one week after swabbing the material from the metal surface. The results of the sudy can be explained by the decrease of the concentration of the initial DNA-matrix in the samples due to its degradation in the course of time. It is concluded that the parallel genetic analysis is needed if reliable evidence of identity of the profiles of interest or its absence is to be obtained. PMID:27070033

  7. Molecular Genetics of Alcohol Dependence and Related Endophenotypes

    PubMed Central

    Le Strat, Yann; Ramoz, Nicolas; Schumann, Gunter; Gorwood, Philip

    2008-01-01

    Alcohol dependence is a worldwide public health problem, and involves both environmental and genetic vulnerability factors. The heritability of alcohol dependence is rather high, ranging between 50% and 60%, although alcohol dependence is a polygenic, complex disorder. Genome-wide scans on large cohorts of multiplex families, including the collaborative study on genetics of alcoholism (COGA), emphasized the role of many chromosome regions and some candidate genes. The genes encoding the alcohol-metabolizing enzymes, or those involved in brain reward pathways, have been involved. Since dopamine is the main neurotransmitter in the reward circuit, genes involved in the dopaminergic pathway represent candidates of interest. Furthermore, gamma-amino-butyric acid (GABA) neurotransmitter mediates the acute actions of alcohol and is involved in withdrawal symptomatology. Numerous studies showed an association between variants within GABA receptors genes and the risk of alcohol dependence. In accordance with the complexity of the “alcohol dependence” phenotype, another field of research, related to the concept of endophenotypes, received more recent attention. The role of vulnerability genes in alcohol dependence is therefore re-assessed focusing on different phenotypes and endophenotypes. The latter include brain oscillations, EEG alpha and beta variants and alpha power, and amplitude of P300 amplitude elicited from a visual oddball task. Recent enhancement on global characterizations of the genome by high-throughput approach for genotyping of polymorphisms and studies of transcriptomics and proteomics in alcohol dependence is also reviewed. PMID:19506733

  8. Molecular Mechanisms of Drug Resistance in Natural Leishmania Populations Vary with Genetic Background

    PubMed Central

    Decuypere, Saskia; Vanaerschot, Manu; Brunker, Kirstyn; Imamura, Hideo; Müller, Sylke; Khanal, Basudha; Rijal, Suman; Dujardin, Jean-Claude; Coombs, Graham H.

    2012-01-01

    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 applicability. PMID:22389733

  9. Molecular approaches for a better understanding of the epidemiology and population genetics of Leishmania.

    PubMed

    Schönian, G; Kuhls, K; Mauricio, I L

    2011-04-01

    Molecular approaches are being used increasingly for epidemiological studies of visceral and cutaneous leishmaniases. Several molecular markers resolving genetic differences between Leishmania parasites at species and strain levels have been developed to address key epidemiological and population genetic questions. The current gold standard, multilocus enzyme typing (MLEE), needs cultured parasites and lacks discriminatory power. PCR assays identifying species directly with clinical samples have proven useful in numerous field studies. Multilocus sequence typing (MLST) is potentially the most powerful phylogenetic approach and will, most probably, replace MLEE in the future. Multilocus microsatellite typing (MLMT) is able to discriminate below the zymodeme level and seems to be the best candidate for becoming the gold standard for distinction of strains. Population genetic studies by MLMT revealed geographical and hierarchic population structure in L. tropica, L. major and the L. donovani complex. The existence of hybrids and gene flow between Leishmania populations suggests that sexual recombination is more frequent than previously thought. However, typing and analytical tools need to be further improved. Accessible databases should be created and sustained for integrating data obtained by different researchers. This would allow for global analyses and help to avoid biases in analyses due to small sample sizes. PMID:21078222

  10. MOLECULAR GENETIC APPROACHES TO PEST AND NONTARGET POPULATION MONITORING

    EPA Science Inventory

    The U.S. Environmental Protection Agency has interest in a number of applications of genetic monitoring methodologies. Genetic monitoring in agroecosystems can provide valuable environmental information regarding both traditional and novel pesticides. One group of pesticides of...

  11. Molecular genetic analysis of patients with sporadic and X-linked infantile nystagmus

    PubMed Central

    Zhao, Hui; Huang, Xiu-Feng; Zheng, Zhi-Li; Deng, Wen-Li; Lei, Xin-Lan; Xing, Dong-Jun; Ye, Liang; Xu, Su-Zhong; Chen, Jie; Zhang, Fang; Yu, Xin-Ping; Jin, Zi-Bing

    2016-01-01

    Objectives Infantile nystagmus (IN) is a genetically heterogeneous condition characterised by involuntary rhythmic oscillations of the eyes accompanied by different degrees of vision impairment. Two genes have been identified as mainly causing IN: FRMD7 and GPR143. The aim of our study was to identify the genetic basis of both sporadic IN and X-linked IN. Design Prospective analysis. Patients Twenty Chinese patients, including 15 sporadic IN cases and 5 from X-linked IN families, were recruited and underwent molecular genetic analysis. We first performed PCR-based DNA sequencing of the entire coding region and the splice junctions of the FRMD7 and GPR143 genes in participants. Mutational analysis and co-segregation confirmation were then performed. Setting All clinical examinations and genetic experiments were performed in the Eye Hospital of Wenzhou Medical University. Results Two mutations in the FRMD7 gene, including one novel nonsense mutation (c.1090C>T, p.Q364X) and one reported missense mutation (c.781C>G, p.R261G), were identified in two of the five (40%) X-linked IN families. However, none of putative mutations were identified in FRMD7 or GPR143 in any of the sporadic cases. Conclusions The results suggest that mutations in FRMD7 appeared to be the major genetic cause of X-linked IN, but not of sporadic IN. Our findings provide further insights into FRMD7 mutations, which could be helpful for future genetic diagnosis and genetic counselling of Chinese patients with nystagmus. PMID:27036142

  12. Molecular biology and genetics of the acetate-utilizing methanogenic bacteria

    SciTech Connect

    Gunsalus, R.P.

    1991-01-01

    Acetate conversion to methane and C0{sub 2} by the methanogenic archaebacteria is a primary rate limiting step in anaerobic biodegradative processes in nature. However, the genetic study of these organisms has not been experimentally tractable due to the inability to grow and plate the organisms as single cells, and to extract high molecular weight DNA and RNA without shearing. The acetate-utilizing species, Methanosarcina thermolphila TM-1, is being used for the proposed genetic and molecular studies because, unlike previously described acetotrophic methanosarcina that have a thick heteropolysaccharide cell wall, this species can be cultured in a unicellular form that has a protein cell wall lacking the heteropolysaccharide layer. These cells can be gently disrupted to obtain protoplasts or lysed to yield intact genomic DNA and RNA. Experiments are in progress to develop a gene transfer system in this bacterial species. Methods are being developed and refined for the efficient plating of M. thermophila on defined media, for chemical mutagenesis, and for the isolation of mutants defective in acetate utilization. Chromosomal DNA libraries have been constructed from M. thermophila and are being used to clone genes involved in the acetate utilization pathway (e.g. carbon monoxide dehydrogenase). Once cloned, analysis of the molecular mechanisms responsible for their regulatory control will be performed. These studies should aid our understanding of the pathway for acetate utilization in M. thermophila and serve as a model for elucidating regulatory mechanisms in the acetotrophic methanogens.

  13. Molecular study of patients with auditory neuropathy.

    PubMed

    Carvalho, Guilherme Machado De; Ramos, Priscila Zonzini; Castilho, Arthur Menino; Guimarães, Alexandre Caixeta; Sartorato, Edi Lúcia

    2016-07-01

    Auditory neuropathy is a type of hearing loss that constitutes a change in the conduct of the auditory stimulus by the involvement of inner hair cells or auditory nerve synapses. It is characterized by the absence or alteration of waves in the examination of brainstem auditory evoked potentials, with otoacoustic and/or cochlear microphonic issues. At present, four loci associated with non‑syndromic auditory neuropathy have been mapped: Autosomal recessive deafness‑9 [DFNB9; the otoferlin (OTOF) gene] and autosomal recessive deafness‑59 [DFNB59; the pejvakin (PJVK) gene], associated with autosomal recessive inheritance; the autosomal dominant auditory neuropathy gene [AUNA1; the diaphanous‑3 (DIAPH3) gene]; and AUNX1, linked to chromosome X. Furthermore, mutations of connexin 26 [the gap junction β2 (GJB2) gene] have also been associated with the disease. OTOF gene mutations exert a significant role in auditory neuropathy. In excess of 80 pathogenic mutations have been identified in individuals with non‑syndromic deafness in populations of different origins, with an emphasis on the p.Q829X mutation, which was found in ~3% of cases of deafness in the Spanish population. The identification of genetic alterations responsible for auditory neuropathy is one of the challenges contributing to understand the molecular bases of the different phenotypes of hearing loss. Thus, the present study aimed to investigate molecular changes in the OTOF gene in patients with auditory neuropathy, and to develop a DNA chip for the molecular diagnosis of auditory neuropathy using mass spectrometry for genotyping. Genetic alterations were investigated in 47 patients with hearing loss and clinical diagnosis of auditory neuropathy, and the c.35delG mutation in the GJB2 gene was identified in three homozygous patients, and the heterozygous parents of one of these cases. Additionally, OTOF gene mutations were tracked by complete sequencing of 48 exons, although these results

  14. Genetic diversity and molecular evolution of arabis mosaic virus based on the CP gene sequence.

    PubMed

    Gao, Fangluan; Lin, Wuzhen; Shen, Jianguo; Liao, Furong

    2016-04-01

    Arabis mosaic virus (ArMV) is a virus with a wide host range. In this study, the genetic diversity of ArMV and the molecular mechanisms underlying its evolution were investigated using the coat protein (CP) sequence. Of the 33 ArMV isolates studied, three were found to be recombinants. The other 30 recombination-free ArMV isolates could be separated into two major lineages with a significant F ST value (0.384) and tended to cluster according to their geographical origin. Different evolutionary constraints were detected for the two linages, pointing to a role of natural selection in the differentiation of ArMV. PMID:26758729

  15. Molecular genetics of myosin motors in Arabidopsis. Final report, July 1, 1992--June 30, 1996

    SciTech Connect

    Schiefelbein, J.

    1997-02-01

    The normal growth and development of plant cells depends on the precise organization and distribution of the cellular contents. The basic goal of this investigation was to define a group of the molecules that are involved in organizing and transporting plant cell components. Based largely on studies of animal and fungal cells, one of the molecules thought to be involved in intracellular trafficking in plants is the actin-based motor protein myosin. Therefore, the major aim of this study was to isolate and analyze plant genes encoding myosin proteins. The plant of choice for these experiments was Arabidopsis thaliana, which offers numerous advantages for molecular genetics research.

  16. Genetic subdivisions within Trypanosoma cruzi (Discrete Typing Units) and their relevance for molecular epidemiology and experimental evolution

    PubMed Central

    Tibayrenc, Michel

    2003-01-01

    Background This paper summarizes the main results obtained on Trypanosoma cruzi genetic diversity and population structure since this parasite became the theme of many genetic and molecular studies in the early seventies. Results T. cruzi exibits a paradigmatic pattern of long-term, clonal evolution, which has structured its natural populations into several discrete genetic subdivisions or "Discrete Typing Units" (DTU). Rare hybridization events are nevertheless detectable in natural populations and have been recently obtained in the laboratory. Conclusions The DTUs and natural clones of T. cruzi constitute relevant units for molecular epidemiology and experimental evolution. Experimental mating opens the way to an in-depth knowledge of this parasite's formal genetics. PMID:14613498

  17. Molecular toolbox for the identification of unknown genetically modified organisms.

    PubMed

    Ruttink, Tom; Demeyer, Rolinde; Van Gulck, Elke; Van Droogenbroeck, Bart; Querci, Maddalena; Taverniers, Isabel; De Loose, Marc

    2010-03-01

    Competent laboratories monitor genetically modified organisms (GMOs) and products derived thereof in the food and feed chain in the framework of labeling and traceability legislation. In addition, screening is performed to detect the unauthorized presence of GMOs including asynchronously authorized GMOs or GMOs that are not officially registered for commercialization (unknown GMOs). Currently, unauthorized or unknown events are detected by screening blind samples for commonly used transgenic elements, such as p35S or t-nos. If (1) positive detection of such screening elements shows the presence of transgenic material and (2) all known GMOs are tested by event-specific methods but are not detected, then the presence of an unknown GMO is inferred. However, such evidence is indirect because it is based on negative observations and inconclusive because the procedure does not identify the causative event per se. In addition, detection of unknown events is hampered in products that also contain known authorized events. Here, we outline alternative approaches for analytical detection and GMO identification and develop new methods to complement the existing routine screening procedure. We developed a fluorescent anchor-polymerase chain reaction (PCR) method for the identification of the sequences flanking the p35S and t-nos screening elements. Thus, anchor-PCR fingerprinting allows the detection of unique discriminative signals per event. In addition, we established a collection of in silico calculated fingerprints of known events to support interpretation of experimentally generated anchor-PCR GM fingerprints of blind samples. Here, we first describe the molecular characterization of a novel GMO, which expresses recombinant human intrinsic factor in Arabidopsis thaliana. Next, we purposefully treated the novel GMO as a blind sample to simulate how the new methods lead to the molecular identification of a novel unknown event without prior knowledge of its transgene

  18. [Molecular genetics of functional articulation disorder in children].

    PubMed

    Zhao, Yun-Jing; Ma, Hong-Wei

    2012-04-01

    Genetic factors are an important cause of functional articulation disorder in children. This article reviews some genes and chromosome regions associated with a genetic susceptibility to functional articulation disorders. The forkhead box P2 (FOXP2) gene on chromosome 7 is introduced in details including its structure, expression and function. The relationship between the FOXP2 gene and developmental apraxia of speech is discussed. As a transcription factor, FOXP2 gene regulates the expression of many genes. CNTNAP2 as an important target gene of FOXP2 is a key gene influencing language development. Functional articulation disorder may be developed to dyslexia, therefore some candidate regions and genes related to dyslexia, such as 3p12-13, 15q11-21, 6p22 and 1p34-36, are also introduced. ROBO1 gene in 3p12.3, ZNF280D gene, TCF12 gene, EKN1 gene in 15q21, and KIAA0319 gene in 6p22 have been candidate genes for the study of functional articulation disorder. PMID:22537967

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

    NASA Technical Reports Server (NTRS)

    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.

  20. Genetic Diversity and Molecular Evolution of Chinese Waxy Maize Germplasm

    PubMed Central

    Zheng, Hongjian; Wang, Hui; Yang, Hua; Wu, Jinhong; Shi, Biao; Cai, Run; Xu, Yunbi; Wu, Aizhong; Luo, Lijun

    2013-01-01

    Waxy maize (Zea mays L. var. certaina Kulesh), with many excellent characters in terms of starch composition and economic value, has grown in China for a long history and its production has increased dramatically in recent decades. However, the evolution and origin of waxy maize still remains unclear. We studied the genetic diversity of Chinese waxy maize including typical landraces and inbred lines by SSR analysis and the results showed a wide genetic diversity in the Chinese waxy maize germplasm. We analyzed the origin and evolution of waxy maize by sequencing 108 samples, and downloading 52 sequences from GenBank for the waxy locus in a number of accessions from genus Zea. A sharp reduction of nucleotide diversity and significant neutrality tests (Tajima’s D and Fu and Li’s F*) were observed at the waxy locus in Chinese waxy maize but not in nonglutinous maize. Phylogenetic analysis indicated that Chinese waxy maize originated from the cultivated flint maize and most of the modern waxy maize inbred lines showed a distinct independent origin and evolution process compared with the germplasm from Southwest China. The results indicated that an agronomic trait can be quickly improved to meet production demand by selection. PMID:23818949

  1. Characterizing the ADHD Phenotype for Genetic Studies

    ERIC Educational Resources Information Center

    Stevenson, Jim; Asherson, Phil; Hay, David; Levy, Florence; Swanson, Jim; Thapar, Anita; Willcutt, Erik

    2005-01-01

    The genetic study of ADHD has made considerable progress. Further developments in the field will be reliant in part on identifying the most appropriate phenotypes for genetic analysis. The use of both categorical and dimensional measures of symptoms related to ADHD has been productive. The use of multiple reporters is a valuable feature of the…

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

    PubMed

    Sercundes, Michelle Klein; Valadas, Samantha Yuri Oshiro Branco; Keid, Lara Borges; Oliveira, Tricia Maria Ferreira Souza; Ferreira, Helena Lage; Vitor, Ricardo Wagner de Almeida; Gregori, Fábio; Soares, Rodrigo Martins

    2016-01-01

    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 genus Hammondia 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. PMID:27007245

  3. Novel Genetic and Molecular Tools for the Investigation and Control of Dengue Virus Transmission by Mosquitoes.

    PubMed

    Franz, Alexander W E; Clem, Rollie J; Passarelli, A Lorena

    2014-03-01

    Aedes aegypti is the principal vector of dengue virus (DENV) throughout the tropical world. This anthropophilic mosquito species needs to be persistently infected with DENV before it can transmit the virus through its saliva to a new vertebrate host. In the mosquito, DENV is confronted with several innate immune pathways, among which RNA interference is considered the most important. The Ae. aegypti genome project opened the doors for advanced molecular studies on pathogen-vector interactions including genetic manipulation of the vector for basic research and vector control purposes. Thus, Ae. aegypti has become the primary model for studying vector competence for arboviruses at the molecular level. Here, we present recent findings regarding DENV-mosquito interactions, emphasizing how innate immune responses modulate DENV infections in Ae. aegypti. We also describe the latest advancements in genetic manipulation of Ae. aegypti and discuss how this technology can be used to investigate vector transmission of DENV at the molecular level and to control transmission of the virus in the field. PMID:24693489

  4. Molecular tools for studying plant genetic diversity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ubiquitous nature of DNA is a central theme for all biology. The nucleus of each cell that makes up an organism contains genomic DNA, which is the blueprint for life. The differential expression of genes within each cell gives rise to different tissues, organs and, ultimately, different organi...

  5. Molecular and Genetic Studies of Congenital Myopathies

    ClinicalTrials.gov

    2015-10-26

    Central Core Disease; Centronuclear Myopathy; Congenital Fiber Type Disproportion; Multiminicore Disease; Myotubular Myopathy; Nemaline Myopathy; Rigid Spine Muscular Dystrophy; Undefined Congenital Myopathy

  6. Molecular genetic studies of complete hydatidiform moles

    PubMed Central

    Nash, Benjamin M.; Wright, Dale C.

    2015-01-01

    Complete hydatidiform moles (CHM) are abnormal pregnancies with no fetal development resulting from having two paternal genomes with no maternal contribution. It is important to distinguish CHM from partial hydatidiform moles, and non-molar abortuses, due to the increased risk of gestational trophoblastic neoplasia. We evaluated a series of products of conception (POC) (n=643) investigated by genome-wide microarray comparative genomic hybridisation (CGH) with the aim of refining our strategy for the identification of complete moles. Among 32 suspected molar pregnancies investigated by STR genotyping to supplement microarray CGH testing, we found 31.3% (10/32) CHM; all identified among 3.6% (10/272) early first trimester POC. We suggest that when using microarray CGH that genotyping using targeted STR analysis should be performed for all POC referrals to aid in the identification of CHM. PMID:26835372

  7. Molecular genetic studies of complete hydatidiform moles.

    PubMed

    Carey, Louise; Nash, Benjamin M; Wright, Dale C

    2015-04-01

    Complete hydatidiform moles (CHM) are abnormal pregnancies with no fetal development resulting from having two paternal genomes with no maternal contribution. It is important to distinguish CHM from partial hydatidiform moles, and non-molar abortuses, due to the increased risk of gestational trophoblastic neoplasia. We evaluated a series of products of conception (POC) (n=643) investigated by genome-wide microarray comparative genomic hybridisation (CGH) with the aim of refining our strategy for the identification of complete moles. Among 32 suspected molar pregnancies investigated by STR genotyping to supplement microarray CGH testing, we found 31.3% (10/32) CHM; all identified among 3.6% (10/272) early first trimester POC. We suggest that when using microarray CGH that genotyping using targeted STR analysis should be performed for all POC referrals to aid in the identification of CHM. PMID:26835372

  8. Diagnostic gold standard for soft tissue tumours: morphology or molecular genetics?

    PubMed

    Pfeifer, J D; Hill, D A; O'Sullivan, M J; Dehner, L P

    2000-12-01

    The recognition of recurrent genetic alterations in specific tumour types has provided the basis for the reclassification of certain soft tissue neoplasms, and molecular analysis of patient material has the potential to provide both diagnostic and prognostic information. In this review, we evaluate the role of molecular genetic testing as the prospective 'gold standard' for sarcoma diagnosis. Molecular genetic testing, as with every new method, promises to improve accuracy and to be more sensitive and less subjective, claims that have been made previously by histochemistry, electron microscopy and immunohistochemistry. Technical limitations in molecular assays, as well as more general specificity issues, decrease the clinical usefulness of molecular pathological testing significantly and suggest that, at present, molecular evaluation is best considered an ancillary technique that neither supersedes other ancillary techniques nor eclipses traditional pathological examination. PMID:11122430

  9. Individual differences in cognition, affect, and performance: Behavioral, neuroimaging, and molecular genetic approaches

    PubMed Central

    Parasuraman, Raja; Jiang, Yang

    2012-01-01

    We describe the use of behavioral, neuroimaging, and genetic methods to examine individual differences in cognition and affect, guided by three criteria: (1) relevance to human performance in work and everyday settings; (2) interactions between working memory, decision-making, and affective processing; and (3) examination of individual differences. The results of behavioral, functional MRI (fMRI), event-related potential (ERP), and molecular genetic studies show that analyses at the group level often mask important findings associated with sub-groups of individuals. Dopaminergic/noradrenergic genes influencing prefrontal cortex activity contribute to inter-individual variation in working memory and decision behavior, including performance in complex simulations of military decision-making. The interactive influences of individual differences in anxiety, sensation seeking, and boredom susceptibility on evaluative decision-making can be systematically described using ERP and fMRI methods. We conclude that a multi-modal neuroergonomic approach to examining brain function (using both neuroimaging and molecular genetics) can be usefully applied to understanding individual differences in cognition and affect and has implications for human performance at work. PMID:21569853

  10. The Molecular Genetics of Bacteriophage: The Work of Norton Zinder

    PubMed Central

    Kresge, Nicole; Simoni, Robert D.; Hill, Robert L.

    2011-01-01

    In 1966, Norton Zinder and Joshua Lederberg discovered that Salmonella could exchange genes via bacteriophages. They named this phenomenon “genetic transduction.” This discovery set Zinder on a lifelong journey researching bacteriophage. In the two Journal of Biological Chemistry (JBC) Classic papers reprinted here, Zinder and Nina Fedoroff present their findings on the phage f2 replicase. Properties of the Phage f2 Replicase. I. Optimal Conditions for Replicase Activity and Analysis of the Polynucleotide Product Synthesized in Vitro (Fedoroff, N. V., and Zinder, N. D. (1972) J. Biol. Chem. 247, 4577–4585) Properties of the Phage f2 Replicase. II. Comparative Studies on the Ribonucleic Acid-dependent and Poly(C)-dependent Activities of the Replicase (Fedoroff, N. V., and Zinder, N. D. (1972) J. Biol. Chem. 247, 4586–4592) PMID:21830328

  11. Molecular Approaches to Studying Denitrification

    NASA Astrophysics Data System (ADS)

    Voytek, M. A.

    2001-05-01

    Denitrification is carried out by a diverse array of microbes, mainly as an alternative mode of respiration that allows the organisms to respire using oxidized N compounds instead of oxygen. A common approach in biogeochemistry to the study of the regulation of denitrification is to assess activity by mass balance of substrates and products or direct rate measurements and has intrinsically assumed resource regulation of denitrification. Reported rates can vary significantly even among ecosystems characterized by similar environmental conditions, thus indicating that direct control by abiotic factors often is not sufficient to predict denitrification rates accurately in natural environments. Alternatively, a microbiological approach would proceed with the identification of the organisms responsible and an evaluation of the effect of environmental factors on the biochemical pathways involved. Traditional studies have relied on culturing techniques, such as most probable number enrichments, and have failed to assess the role of the predominately uncultivable members of the microbial community. A combination of biogeochemical measurements and the assessment of the microbial community is necessary and becoming increasingly possible with the development and application of molecular techniques. In order to understand how the composition and physiological behavior of the microbial community affects denitrification rates, we use a suite of molecular techniques developed for phylogenetic and metabolic characterization of denitrifying communities. Molecular tools available for quantifying denitrifying bacteria and assessing their diversity and activity are summarized. Their application is illustrated with examples from marine and freshwater environments. Emerging techniques and their application to ground water studies will be discussed.

  12. Genetic and molecular analysis of tomato Cf genes for resistance to Cladosporium fulvum.

    PubMed Central

    Thomas, C M; Dixon, M S; Parniske, M; Golstein, C; Jones, J D

    1998-01-01

    In many plant-pathogen interactions resistance to disease is controlled by the interaction of plant-encoded resistance (R) genes and pathogen-encoded avirulence (Avr) genes. The interaction between tomato and the leaf mould pathogen Cladosporium fulvum is an ideal system to study the molecular basis of pathogen perception by plants. A total of four tomato genes for resistance to C. fulvum (Cf-2, Cf-4, Cf-5 and Cf-9) have been isolated from two genetically complex chromosomal loci. Their gene products recognize specific C. fulvum-encoded avirulence gene products (Avr2, Avr4, Avr5 and Avr9) by an unknown molecular mechanism. Cf genes encode extracellular membrane-anchored glycoproteins comprised predominantly of 24 amino acid leucine-rich repeats (LRRs). Cf genes from the same locus encode proteins which are more than 90% identical. Most of the amino-acid sequence differences correspond to the solvent-exposed residues within a beta-strand/beta-turn structural motif which is highly conserved in LRR proteins. Sequence variability within this motif is predicted to affect the specificity of ligand binding. Our analysis of Cf gene loci at the molecular level has shown they comprise tandemly duplicated homologous genes, and suggests a molecular mechanism for the generation of sequence diversity at these loci. Our analysis provides further insight into the molecular basis of pathogen perception by plants and the organization and evolution of R gene loci. PMID:9800204

  13. Molecular Mechanisms in Genetically Defined Autoinflammatory Diseases: Disorders of Amplified Danger Signaling*

    PubMed Central

    de Jesus, Adriana Almeida; Canna, Scott W.; Liu, Yin; Goldbach-Mansky, Raphaela

    2015-01-01

    Patients with autoinflammatory diseases present with noninfectious fever flares and systemic and/or disease-specific organ inflammation. Their excessive proinflammatory cytokine and chemokine responses can be life threatening and lead to organ damage over time. Studying such patients has revealed genetic defects that have helped unravel key innate immune pathways, including excessive IL-1 signaling, constitutive NF-κB activation, and, more recently, chronic type I IFN signaling. Discoveries of monogenic defects that lead to activation of proinflammatory cytokines have inspired the use of anticytokine-directed treatment approaches that have been life changing for many patients and have led to the approval of IL-1-blocking agents for a number of autoinflammatory conditions. In this review, we describe the genetically characterized autoinflammatory diseases, we summarize our understanding of the molecular pathways that drive clinical phenotypes and that continue to inspire the search for novel treatment targets, and we provide a conceptual framework for classification. PMID:25706096

  14. Molecular genetics and genomics of the Rosoideae: state of the art and future perspectives.

    PubMed

    Longhi, Sara; Giongo, Lara; Buti, Matteo; Surbanovski, Nada; Viola, Roberto; Velasco, Riccardo; Ward, Judson A; Sargent, Daniel J

    2014-01-01

    The Rosoideae is a subfamily of the Rosaceae that contains a number of species of economic importance, including the soft fruit species strawberry (Fragaria ×ananassa), red (Rubus idaeus) and black (Rubus occidentalis) raspberries, blackberries (Rubus spp.) and one of the most economically important cut flower genera, the roses (Rosa spp.). Molecular genetics and genomics resources for the Rosoideae have developed rapidly over the past two decades, beginning with the development and application of a number of molecular marker types including restriction fragment length polymorphisms, amplified fragment length polymorphisms and microsatellites, and culminating in the recent publication of the genome sequence of the woodland strawberry, Fragaria vesca, and the development of high throughput single nucleotide polymorphism (SNP)-genotyping resources for Fragaria, Rosa and Rubus. These tools have been used to identify genes and other functional elements that control traits of economic importance, to study the evolution of plant genome structure within the subfamily, and are beginning to facilitate genomic-assisted breeding through the development and deployment of markers linked to traits such as aspects of fruit quality, disease resistance and the timing of flowering. In this review, we report on the developments that have been made over the last 20 years in the field of molecular genetics and structural genomics within the Rosoideae, comment on how the knowledge gained will improve the efficiency of cultivar development and discuss how these advances will enhance our understanding of the biological processes determining agronomically important traits in all Rosoideae species. PMID:26504527

  15. Molecular genetics and genomics of the Rosoideae: state of the art and future perspectives

    PubMed Central

    Longhi, Sara; Giongo, Lara; Buti, Matteo; Surbanovski, Nada; Viola, Roberto; Velasco, Riccardo; Ward, Judson A; Sargent, Daniel J

    2014-01-01

    The Rosoideae is a subfamily of the Rosaceae that contains a number of species of economic importance, including the soft fruit species strawberry (Fragaria ×ananassa), red (Rubus idaeus) and black (Rubus occidentalis) raspberries, blackberries (Rubus spp.) and one of the most economically important cut flower genera, the roses (Rosa spp.). Molecular genetics and genomics resources for the Rosoideae have developed rapidly over the past two decades, beginning with the development and application of a number of molecular marker types including restriction fragment length polymorphisms, amplified fragment length polymorphisms and microsatellites, and culminating in the recent publication of the genome sequence of the woodland strawberry, Fragaria vesca, and the development of high throughput single nucleotide polymorphism (SNP)-genotyping resources for Fragaria, Rosa and Rubus. These tools have been used to identify genes and other functional elements that control traits of economic importance, to study the evolution of plant genome structure within the subfamily, and are beginning to facilitate genomic-assisted breeding through the development and deployment of markers linked to traits such as aspects of fruit quality, disease resistance and the timing of flowering. In this review, we report on the developments that have been made over the last 20 years in the field of molecular genetics and structural genomics within the Rosoideae, comment on how the knowledge gained will improve the efficiency of cultivar development and discuss how these advances will enhance our understanding of the biological processes determining agronomically important traits in all Rosoideae species. PMID:26504527

  16. Sequencing cDNAs: An Introduction to DNA Sequence Analysis in the Undergraduate Molecular Genetics Course.

    ERIC Educational Resources Information Center

    Galewsky, Samuel

    2000-01-01

    Introduces a series of molecular genetics laboratories where students pick a single colony from a Drosophila melanogester embryo cDNA library and purify the plasmid, then analyze the insert through restriction digests and gel electrophoresis. (Author/YDS)

  17. Domestication of Plants in the Americas: Insights from Mendelian and Molecular Genetics

    PubMed Central

    Pickersgill, Barbara

    2007-01-01

    Background Plant domestication occurred independently in four different regions of the Americas. In general, different species were domesticated in each area, though a few species were domesticated independently in more than one area. The changes resulting from human selection conform to the familiar domestication syndrome, though different traits making up this syndrome, for example loss of dispersal, are achieved by different routes in crops belonging to different families. Genetic and Molecular Analyses of Domestication Understanding of the genetic control of elements of the domestication syndrome is improving as a result of the development of saturated linkage maps for major crops, identification and mapping of quantitative trait loci, cloning and sequencing of genes or parts of genes, and discoveries of widespread orthologies in genes and linkage groups within and between families. As the modes of action of the genes involved in domestication and the metabolic pathways leading to particular phenotypes become better understood, it should be possible to determine whether similar phenotypes have similar underlying genetic controls, or whether human selection in genetically related but independently domesticated taxa has fixed different mutants with similar phenotypic effects. Conclusions Such studies will permit more critical analysis of possible examples of multiple domestications and of the origin(s) and spread of distinctive variants within crops. They also offer the possibility of improving existing crops, not only major food staples but also minor crops that are potential export crops for developing countries or alternative crops for marginal areas. PMID:17766847

  18. WONOEP appraisal: new genetic approaches to study epilepsy

    PubMed Central

    Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A.; Grisar, Thierry; Gilby, Krista L.; Vinet, Jonathan; Kadam, Shilpa D.; Becker, Albert J.

    2014-01-01

    Objective New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming and optogenetic manipulations within epileptic networks are progressively unravelling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiological impacts of mutations in epilepsy-associated genes on a multilayer level, from cells to circuits. Methods This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy in Quebec, Canada. Results Next-generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and have revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell-types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knockdown approaches, are enabling functional validation with exquisite cell-type and temporal specificity. In addition, optogenetics, using cell-type specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. Genetically-encoded cell-type labeling is also providing new means to assess the role of the non-neuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next-generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and non

  19. WONOEP appraisal: new genetic approaches to study epilepsy.

    PubMed

    Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A; Grisar, Thierry; Gilby, Krista L; Vinet, Jonathan; Kadam, Shilpa D; Becker, Albert J

    2014-08-01

    New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming, and optogenetic manipulations within epileptic networks are progressively unraveling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiologic effects of mutations in epilepsy-associated genes on a multilayer level, from cells to circuits. This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy (WONOEP 2013) in Quebec, Canada. Next-generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and has revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knock-down approaches, are enabling functional validation with exquisite cell-type and temporal specificity. In addition, optogenetics, using cell-type-specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. In addition, genetically encoded cell-type labeling is providing new means to assess the role of the nonneuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next-generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and noncoding

  20. Learning Molecular Genetics in Teacher-Led Outreach Laboratories

    ERIC Educational Resources Information Center

    Ben-Nun, Michal Stolarsky; Yarden, Anat

    2009-01-01

    Learning modern genetics is challenging and students have difficulty acquiring a coherent cognitive mental model of abstract concepts such as DNA, bacteria and enzymes. Here we investigated students' mental models of genetics through analysis and interpretation of the discourse that took place while high-school students practised hands-on…

  1. Use of Computer Simulations in Microbial and Molecular Genetics.

    ERIC Educational Resources Information Center

    Wood, Peter

    1984-01-01

    Describes five computer programs: four simulations of genetic and physical mapping experiments and one interactive learning program on the genetic coding mechanism. The programs were originally written in BASIC for the VAX-11/750 V.3. mainframe computer and have been translated into Applesoft BASIC for Apple IIe microcomputers. (JN)

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

    PubMed

    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

  3. Molecular-genetic mapping of zebrafish mutants with variable phenotypic penetrance.

    PubMed

    Jain, Roshan A; Wolman, Marc A; Schmidt, Lauren A; Burgess, Harold A; Granato, Michael

    2011-01-01

    Forward genetic screens in vertebrates are powerful tools to generate models relevant to human diseases, including neuropsychiatric disorders. Variability in phenotypic penetrance and expressivity is common in these disorders and behavioral mutant models, making their molecular-genetic mapping a formidable task. Using a 'phenotyping by segregation' strategy, we molecularly map the hypersensitive zebrafish houdini mutant despite its variable phenotypic penetrance, providing a generally applicable strategy to map zebrafish mutants with subtle phenotypes. PMID:22039502

  4. Molecular-Genetic Mapping of Zebrafish Mutants with Variable Phenotypic Penetrance

    PubMed Central

    Schmidt, Lauren A.; Burgess, Harold A.; Granato, Michael

    2011-01-01

    Forward genetic screens in vertebrates are powerful tools to generate models relevant to human diseases, including neuropsychiatric disorders. Variability in phenotypic penetrance and expressivity is common in these disorders and behavioral mutant models, making their molecular-genetic mapping a formidable task. Using a ‘phenotyping by segregation’ strategy, we molecularly map the hypersensitive zebrafish houdini mutant despite its variable phenotypic penetrance, providing a generally applicable strategy to map zebrafish mutants with subtle phenotypes. PMID:22039502

  5. Molecular Genetics of Metal Detoxification: Prospects for Phytoremediation

    SciTech Connect

    Ow, David W. ow@pgec.ams.usda.gov

    2000-09-01

    Unlike compounds that can be broken down, the remediation of most heavy metals and radionuclides requires physical extraction from contaminated sources. Plants can extract inorganics, but effective phytoextraction requires plants that produce high biomass, grow rapidly and possess high capacity-uptake for the inorganic substance. Either hyperaccumulator plants must be bred for increased growth and biomass or hyperaccumulation traits must be engineered into fast growing, high biomass plants. This latter approach requires fundamental knowledge of the molecular mechanisms in the uptake and storage of inorganics. Much has been learned in recent years on how plants and certain fungi chelate and transport selected heavy metals. This progress has been facilitated by the use of Schizosaccharomyces pombe as a model system. The use of a model organism for study permits rapid characterization of the molecular process. As target genes are identified in a model organism, their sequences can be modified for expression in a heterologous host or aid in the search of homologous genes in more complex organisms. Moreover, as plant nutrient uptake is intrinsically linked to the association with rhizospheric fungi, elucidating metal sequestration in this fungus permits additional opportunities for engineering rhizospheric microbes to assist in phytoextraction.

  6. Molecular genetic and genetic correlations in sodium channelopathies: Lack of founder effect and evidence for a second gene

    SciTech Connect

    Wang, J.; Zhou, J.; Feero, W.G.; Conwit, R.; Galloway, G.; Hoffman, E.P. ); Wessel, H.B. Univ. of Pittsburgh, PA ); Todorovic, S.M. ); Barany, F. ); Hausmanowa-Petrusewicz, I.; Fidzianska, A. ); Arahata, K. ); Sillen, A. ); Marks, H.G. ); Hartlage, P. ); Ricker, K. ); Lehmann-Horn, F. ); Hayakawa, H. )

    1993-06-01

    The authors present a correlation of molecular genetic data (mutations) and genetic data (dinucleotide-repeat polymorphisms) for a cohort of seven hyperkalemic periodic paralysis (HyperPP) and two paramyotonia congenita (PC) families from diverse ethnic backgrounds. They found that each of three previously identified point mutations of the adult skeletal muscle sodium-channel gene occurred on two different dinucleotide-repeat haplotypes. These results indicate that dinucleotide-repeat haplotypes are not predictive of allelic heterogeneity in sodium channelopathies, contrary to previous suggestions. In addition, they identified a HyperPP pedigree in which the dominant disorder was not linked to the sodium-channel gene. Thus, a second locus can give rise to a similar clinical phenotype. Some individuals in this pedigree exhibited a base change causing the nonconservative substitution of an evolutionarily conserved amino acid. Because this change was not present in 240 normal chromosomes and was near another HyperPP mutation, it fulfilled the most commonly used criteria for being a mutation rather than a polymorphism. However, linkage studies using single-strand conformation polymorphism-derived and sequence-derived haplotypes excluded this base change as a causative mutation: these data serve as a cautionary example of potential pitfalls in the delineation of change-of-function point mutations. 35 refs., 5 figs., 1 tab.

  7. Molecular genetic variation in cultivated peanuts germplasm of Henan and detection of their elite allelic variations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Groundnut or peanut (Arachis hypogaea L.) is an economically important crop worldwide as a source of protein and cooking oil, particularly in developing countries. Because of its narrow genetic background and shortage of polymorphic genetic markers, molecular characterization of cultivated peanuts i...

  8. Assessment of Genetic and Molecular Approaches for the Prediction of Wheat Quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Assessment of genetic and molecular approaches for the prediction of wheat quality. R.A. Graybosch, USDA-ARS, Lincoln, NE, U.S.A. Over the past four decades, the field of plant breeding and genetics has been revolutionized by technological advances in the areas of DNA manipulation and evaluation. Fo...

  9. Molecular genetic variation in cultivated peanut cultivars and breeding lines revealed by highly informative SSR markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Groundnut or peanut (Arachis hypogaea L.) is an economically important crop worldwide as a source of protein and cooking oil, particularly in developing countries. Because of its narrow genetic background and shortage of polymorphic genetic markers, molecular characterization of cultivated peanuts e...

  10. [Molecular genetics of familial tumour syndromes of the central nervous system].

    PubMed

    Murnyák, Balázs; Szepesi, Rita; Hortobágyi, Tibor

    2015-02-01

    Although most of the central nervous system tumours are sporadic, rarely they are associated with familial tumour syndromes. These disorders usually present with an autosomal dominant inheritance and neoplasia develops at younger age than in sporadic cases. Most of these tumours are bilateral, multiplex or multifocal. The causative mutations occur in genes involved in cell cycle regulation, cell growth, differentiation and DNA repair. Studying these hereditary cancer predisposition syndromes associated with nervous system tumours can facilitate the deeper understanding of the molecular background of sporadic tumours and the development of novel therapeutic agents. This review is an update on hereditary tumour syndromes with nervous system involvement with emphasis on molecular genetic characteristics and their clinical implications. PMID:25618858

  11. Assessment of genetic diversity among faba bean genotypes using agro-morphological and molecular markers.

    PubMed

    Ammar, Megahed H; Alghamdi, Salem S; Migdadi, Hussein M; Khan, Muhammad A; El-Harty, Ehab H; Al-Faifi, Sulieman A

    2015-05-01

    Forty faba bean (Vicia faba L.) genotypes were evaluated for their agro-morphological performance and molecular diversity under Central Region of Saudi Arabia conditions during 2010-11 and 2011-12 seasons. Field performance results showed that faba genotypes exhibited a significant amount of variation for their agro-morphological studied parameters. Giza40 recorded the tallest genotype (139.5 cm), highest number of seeds per plants (100.8), and the highest seed yield per plant (70.8 g). The best performing genotypes were Giza40, FLIP03-014FB, Gazira1 and Goff1. Genetic variability among genotypes was determined using Sequence Related Amplified Polymorphism (SRAP) and Amplified Fragment Length Polymorphism (AFLP) markers. A total of 183 amplified fragments (alleles) and 1758 polymorphic fragments (bands) in SRAP and 202 alleles and 716 bands in AFLP were obtained using six SRAP and four AFLP primer combinations respectively. Polymorphism information content (PIC) values for AFLP and SRAP markers were higher than 0.8, indicating the existence of a considerable amount of genetic diversity among faba tested genotypes. The UPGMA based clustering of faba genotypes was largely based on origin and/or genetic background. Result of cluster analysis based on SRAP showed weak and not significant correlation while, it was highly significant based on AFLP analysis with agro-morphological characters (r = 0.01, p > 0.54 and r = 0.26, p < 0.004 respectively). Combined SRAP and AFLP markers proved to be significantly useful for genetic diversity assessment at molecular level. They exhibited high discrimination power, and were able to distinguish the faba bean genotypes with high efficiency and accuracy levels. PMID:25972757

  12. Assessment of genetic diversity among faba bean genotypes using agro-morphological and molecular markers

    PubMed Central

    Ammar, Megahed H.; Alghamdi, Salem S.; Migdadi, Hussein M.; Khan, Muhammad A.; El-Harty, Ehab H.; Al-Faifi, Sulieman A.

    2015-01-01

    Forty faba bean (Vicia faba L.) genotypes were evaluated for their agro-morphological performance and molecular diversity under Central Region of Saudi Arabia conditions during 2010–11 and 2011–12 seasons. Field performance results showed that faba genotypes exhibited a significant amount of variation for their agro-morphological studied parameters. Giza40 recorded the tallest genotype (139.5 cm), highest number of seeds per plants (100.8), and the highest seed yield per plant (70.8 g). The best performing genotypes were Giza40, FLIP03-014FB, Gazira1 and Goff1. Genetic variability among genotypes was determined using Sequence Related Amplified Polymorphism (SRAP) and Amplified Fragment Length Polymorphism (AFLP) markers. A total of 183 amplified fragments (alleles) and 1758 polymorphic fragments (bands) in SRAP and 202 alleles and 716 bands in AFLP were obtained using six SRAP and four AFLP primer combinations respectively. Polymorphism information content (PIC) values for AFLP and SRAP markers were higher than 0.8, indicating the existence of a considerable amount of genetic diversity among faba tested genotypes. The UPGMA based clustering of faba genotypes was largely based on origin and/or genetic background. Result of cluster analysis based on SRAP showed weak and not significant correlation while, it was highly significant based on AFLP analysis with agro-morphological characters (r = 0.01, p > 0.54 and r = 0.26, p < 0.004 respectively). Combined SRAP and AFLP markers proved to be significantly useful for genetic diversity assessment at molecular level. They exhibited high discrimination power, and were able to distinguish the faba bean genotypes with high efficiency and accuracy levels. PMID:25972757

  13. Molecular genetic techniques for gene manipulation in Candida albicans

    PubMed Central

    Xu, Qiu-Rong; Yan, Lan; Lv, Quan-Zhen; Zhou, Mi; Sui, Xue; Cao, Yong-Bing; Jiang, Yuan-Ying

    2014-01-01

    Candida albicans is one of the most common fungal pathogen in humans due to its high frequency as an opportunistic and pathogenic fungus causing superficial as well as invasive infections in immunocompromised patients. An understanding of gene function in C. albicans is necessary to study the molecular basis of its pathogenesis, virulence and drug resistance. Several manipulation techniques have been used for investigation of gene function in C. albicans, including gene disruption, controlled gene expression, protein tagging, gene reintegration, and overexpression. In this review, the main cassettes containing selectable markers used for gene manipulation in C. albicans are summarized; the advantages and limitations of these cassettes are discussed concerning the influences on the target gene expression and the virulence of the mutant strains. PMID:24759671

  14. [Molecular biology in genetic counseling of Duchenne and Becker myopathy].

    PubMed

    Philip, N; Voelckel, M A; Girardot, L; Lambert, J C; Moncla, A; Mattei, J F; Giraud, F

    1992-01-01

    From 1985-1991, molecular biology studies were carried out in 115 families affected with X-linked muscular dystrophy (DMD/BMD), including 59 prenatal diagnoses. The approach has changed over the last 6 years when new intragenic markers and cDNA probes became available. The polymerase chain reaction technique allows a rapid detection of dystrophin deletions, but classical Southern blot technique remains useful for restriction length polymorphism analysis. Fifty percent (42/85) of patients with DMD/BMD exhibited deletions of the dystrophin gene. In affected families with a detectable deletion, carrier detection is possible by gene dosage analysis and prenatal diagnosis is reliable. When no deletion is found, carrier detection and prenatal diagnosis depends on linkage analysis using polymorphic probes. Due to the high recombination rate, several markers need to be used. The information provided by linkage analysis must be interpreted given the proper family structure. PMID:1338927

  15. Molecular prevalence and genetic characterization of piroplasms in dogs from Tunisia.

    PubMed

    Rjeibi, Mohamed R; Amairia, Safa; Rouatbi, Mariem; Ben Salem, Fatma; Mabrouk, Moez; Gharbi, Mohamed

    2016-10-01

    In this study, the prevalence of piroplasms in dogs was assessed using polymerase chain reaction (PCR) to identify Babesia and Theileria species in 200 dogs from Northern and Central Tunisia between spring and autumn 2014. The overall molecular prevalence for piroplasms was 14·5% ± 0·05 (29/200); PCR detected 2 species, namely Babesia vogeli and Theileria annulata with an overall prevalence of 12·5 ± 0·04 and 2% ± 0·02, respectively. No differences in the molecular prevalences of B. vogeli were revealed for age and sex (P > 0·05). The molecular prevalence of B. vogeli was significantly higher in central Tunisia (26·5% ± 0·01) compared with the North (9·6% ± 0·04) (P 0·05). Comparison of the partial sequences of 18S rRNA and Tams 1 genes confirmed the presence of 2 novel B. vogeli and T. annulata genotypes. This is the first molecular detection of T. annulata and genetic characterization of dogs' piroplasms in Tunisia. Further studies are needed to better assess the epidemiological feature of piroplasms infection in North Africa. PMID:27417681

  16. Cystic fibrosis genetics: from molecular understanding to clinical application

    PubMed Central

    Cutting, Garry R.

    2015-01-01

    The availability of the human genome sequence and tools for interrogating individual genomes provide an unprecedented opportunity to apply genetics to medicine. Mendelian conditions, which are caused by dysfunction of a single gene, offer powerful examples that illustrate how genetics can provide insights into disease. Cystic fibrosis, one of the more common lethalautosomal recessive Mendelian disorders, is presented here as an example. Recent progress in elucidating disease mechanism and causes of phenotypic variation, as well as in the development of treatments, demonstrates that genetics continues to play an important part in cystic fibrosis research 25 years after the d iscove1y of the disease-causing gene. PMID:25404111

  17. Cystic fibrosis genetics: from molecular understanding to clinical application.

    PubMed

    Cutting, Garry R

    2015-01-01

    The availability of the human genome sequence and tools for interrogating individual genomes provide an unprecedented opportunity to apply genetics to medicine. Mendelian conditions, which are caused by dysfunction of a single gene, offer powerful examples that illustrate how genetics can provide insights into disease. Cystic fibrosis, one of the more common lethal autosomal recessive Mendelian disorders, is presented here as an example. Recent progress in elucidating disease mechanism and causes of phenotypic variation, as well as in the development of treatments, demonstrates that genetics continues to play an important part in cystic fibrosis research 25 years after the discovery of the disease-causing gene. PMID:25404111

  18. Molecular detection and genetic diversity of Babesia gibsoni in dogs in India.

    PubMed

    Singh, M N; Raina, O K; Sankar, M; Rialch, Ajayta; Tigga, M N; Kumar, G Ravi; Banerjee, P S

    2016-07-01

    Babesia gibsoni is a tick borne intraerythrocytic protozoan parasite causing piroplasmosis in dogs and has been predominantly reported in Asian countries, including Japan, Korea, Taiwan, Malaysia, Bangladesh and India. The present communication is the first evidence on the genetic diversity of B. gibsoni of dogs in India. Blood samples were collected from 164 dogs in north and northeast states of India and 13 dogs (7.9%) were found positive for B. gibsoni infection by microscopic examination of blood smears. Molecular confirmation of these microscopic positive cases for B. gibsoni was carried out by 18S rRNA nested-PCR, followed by sequencing. Nested-PCR for the 18S rRNA gene was also carried out on microscopically B. gibsoni negative samples that detected a higher percentage of dogs (28.6%) infected with B. gibsoni. Genetic diversity in B. gibsoni in India was determined by studying B. gibsoni thrombospondin-related adhesive protein (BgTRAP) gene fragments (855bp) in 19 isolates from four north and northeast states of India. Phylogenetic analysis of the BgTRAP gene revealed that B. gibsoni parasite in India and Bangladesh formed a distinct cluster away from other Asian B. gibsoni isolates available from Japan, Taiwan and Korea. In addition, tandem repeat analysis of the BgTRAP gene clearly showed considerable genetic variation among Indian isolates that was shared by B. gibsoni isolates of Bangladesh. These results suggested that B. gibsoni parasites in a different genetic clade are endemic in dogs in India and Bangladesh. Further studies are required for better understanding of the genetic diversity of B. gibsoni prevalent in India and in its neighbouring countries. PMID:27020545

  19. Theoretical studies of molecular processes

    NASA Astrophysics Data System (ADS)

    Cui, Qiang

    1997-09-01

    The current thesis concerns with theoretical studies of molecular processes and consists of two parts. The first part includes theoretical studies of dynamics of unimolecular and bimolecular reactions, in particular those involving non-adiabatic processes. In chapter 2 and 3, we have presented our studies of detailed mechanisms for the photodissociation of C2H2 and C2H, and the ion-molecule reactions of C2H2+ + CH4 or NH3, respectively. In chapter 4, we have presented our study that extends TST to non-adiabatic reactions, and an application of the theory of the spin-forbidden reaction of CH(2/Pi)+N2. In chapter 5, we have included our analyses on the photodissociation of triplet ketene, where an extensive seam has been found all along the reaction coordinate. Finally, in Chapter 6, we have presented our study on the photodissociation of O3/sp-, which includes qualitative electronic structure calculations and construction of global potential energy functions for coupled electronic states. The second part of the thesis deals with theoretical studies of organometallic reactions, metal clusters, and gas-surface interactions. With theoretical calculations, one can study the reactivities of transition metal compounds systematically, which allows one to understand the key parameters that control the reactivities of those compounds. In chapter 2, we have presented our implementation of analytical hessian for effective core potential, which makes normal mode analysis possible for large organometallic systems and has proven to be very useful in the study of systems containing transition metals. In chapter 3-5, we have included our studies on the detailed mechanisms of several interesting reactions including platinum/palladium(0) catalyzed diboration and thioboration reactions of acetylene and olefin, and H- H/C-H bond activation on small metal clusters Pt/Pdn(n = 1[-]3). For truly large systems such as surfaces or proteins, full quantum mechanical treatments are

  20. The Human as an Experimental System in Molecular Genetics.

    ERIC Educational Resources Information Center

    White, Ray; Caskey, C. Thomas

    1988-01-01

    Discusses insights discovered from research into human biology that are raising possibilities for therapy, prevention of disease, and challenges to society in the form of ethical decisions about the appropriate application of genetic information. (Author/RT)

  1. [Genetic Diagnosis and Molecular Therapies for Duchenne Muscular Dystrophy].

    PubMed

    Takeshima, Yasuhiro

    2015-10-01

    Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease and is characterized by progressive muscle wasting, ultimately resulting in the death of patients in their twenties or thirties. DMD is characterized by a deficiency of the muscle dystrophin as a result of mutations in the dystrophin gene. Currently, no effective treatment for DMD is available. Promising molecular therapies which are mutation-specific have been developed. Transformation of an out-of-frame mRNA into an in-frame dystrophin message by inducing exon skipping is considered one of the approaches most likely to lead to success. We demonstrated that the intravenous administration of the antisense oligonucleotide against the splicing enhancer sequence results in exon skipping and production of the dystrophin protein in DMD case for the first time. After extensive studies, anti-sense oligonucleotides comprising different monomers have undergone clinical trials and provided favorable results, enabling improvements in ambulation of DMD patients. Induction of the read-through of nonsense mutations is expected to produce dystrophin in DMD patients with nonsense mutations, which are detected in 19% of DMD cases. The clinical effectiveness of gentamicin and PTC124 has been reported. We have demonstrated that arbekacin-mediated read-through can markedly ameliorate muscular dystrophy in vitro. We have already begun a clinical trial of nonsense mutation read-through therapy using arbekacin. Some of these drug candidates are planned to undergo submission for approval to regulatory agencies in the US and EU. We hope that these molecular therapies will contribute towards DMD treatment. PMID:26897856

  2. Molecular Evaluation of Genetic Diversity in Wild-Type Mastic Tree (Pistacia lentiscus L.).

    PubMed

    Abuduli, Alimu; Aydin, Yıldız; Sakiroglu, Muhammet; Onay, Ahmet; Ercisli, Sezai; Uncuoglu, Ahu Altinkut

    2016-10-01

    In this study, the patterns of genetic variation and phylogenetic relationships of mastic tree (Pistacia lentiscus L.) genotypes including 12 males and 12 females were evaluated using SSR, RAPD, ISSR, and ITS markers yielding 40, 703, 929 alleles, and 260-292 base pairs for ITS1 region, respectively. The average number of alleles produced from SSR, RAPD, and ISSR primers were 5.7, 14, and 18, respectively. The grouping pattern obtained from Bayesian clustering method based on each marker dataset was produced. Principal component analyses (PCA) of molecular data was investigated and neighbor joining dendrograms were subsequently created. Overall, the results indicated that ISSR and RAPD markers were the most powerful to differentiate the genotypes in comparison with other types of molecular markers used in this study. The ISSR results indicated that male and female genotypes were distinctly separated from each other. In this frame, M9 (Alaçatı) and M10 (Mesta Sakız Adası-Chios) were the closest genotypes and while F11 (Seferihisar) and F12 (Bornova/Gökdere) genotypes fall into same cluster and showing closer genetic relation. The RAPD pattern indicated that M8 (Urla) and M10 (Mesta Sakız Adası-Chios), and F10 (Mesta Sakız Adası-Chios) and F11 (Seferihisar) genotypes were the closest male and female genotypes, respectively. PMID:27246402

  3. Genetic Analysis and Molecular Identification of Virulence in Xanthomonas oryzae pv. oryzae Isolates

    PubMed Central

    Onasanya, Amos; Onasanya, R. O.; Ojo, Abiodun A.; Adewale, B. O.

    2013-01-01

    Bacterial leaf blight (BLB) of rice is a very destructive disease worldwide and is caused by Xanthomonas oryzae pv. oryzae (Xoo). The aim of the present study was to examine if the Xoo virulence pathotypes obtained using phenotypic pathotyping could be confirmed using molecular approach. After screening of 60 Operon primers with genomic DNA of two Xoo isolates (virulent pathotype, Vr, and mildly virulent pathotype, MVr), 12 Operon primers that gave reproducible and useful genetic information were selected and used to analyze 50 Xoo isolates from 7 West African countries. Genetic analysis revealed two major Xoo virulence genotypes (Mta and Mtb) with Mta having two subgroups (Mta1 and Mta2). Mta1 (Vr1) subgroup genotype has occurrence in six countries and Mta2 (Vr2) in three countries while Mtb genotype characterized mildly virulence (MVr) Xoo isolates present in five countries. The study revealed possible linkage and correlation between phenotypic pathotyping and molecular typing of Xoo virulence. Xoo virulence genotypes were known to exist within country and there was evidence of Xoo pathogen migration between countries. Durable resistance rice cultivars would need to overcome both Mta and Mtb Xoo virulence genotypes in order to survive after their deployment into different rice ecologies in West Africa. PMID:27335673

  4. Molecular Genetics Techniques to Develop New Treatments for Brain Cancers

    SciTech Connect

    Fox, Jacob; Fathallan-Shaykh, Hassan

    2006-09-22

    The objectives of this report are: (1) to devise novel molecular gene therapies for malignant brain tumors, (2) advance our understanding of the immune system in the central nervous system; and (3) apply genomics to find molecular probes to diagnose brain tumors, predict prognosis, biological behavior and their response to treatment.

  5. Ecology has contrasting effects on genetic variation within species versus rates of molecular evolution across species in water beetles.

    PubMed

    Fujisawa, Tomochika; Vogler, Alfried P; Barraclough, Timothy G

    2015-01-22

    Comparative analysis is a potentially powerful approach to study the effects of ecological traits on genetic variation and rate of evolution across species. However, the lack of suitable datasets means that comparative studies of correlates of genetic traits across an entire clade have been rare. Here, we use a large DNA-barcode dataset (5062 sequences) of water beetles to test the effects of species ecology and geographical distribution on genetic variation within species and rates of molecular evolution across species. We investigated species traits predicted to influence their genetic characteristics, such as surrogate measures of species population size, latitudinal distribution and habitat types, taking phylogeny into account. Genetic variation of cytochrome oxidase I in water beetles was positively correlated with occupancy (numbers of sites of species presence) and negatively with latitude, whereas substitution rates across species depended mainly on habitat types, and running water specialists had the highest rate. These results are consistent with theoretical predictions from nearly-neutral theories of evolution, and suggest that the comparative analysis using large databases can give insights into correlates of genetic variation and molecular evolution. PMID:25621335

  6. Ecology has contrasting effects on genetic variation within species versus rates of molecular evolution across species in water beetles

    PubMed Central

    Fujisawa, Tomochika; Vogler, Alfried P.; Barraclough, Timothy G.

    2015-01-01

    Comparative analysis is a potentially powerful approach to study the effects of ecological traits on genetic variation and rate of evolution across species. However, the lack of suitable datasets means that comparative studies of correlates of genetic traits across an entire clade have been rare. Here, we use a large DNA-barcode dataset (5062 sequences) of water beetles to test the effects of species ecology and geographical distribution on genetic variation within species and rates of molecular evolution across species. We investigated species traits predicted to influence their genetic characteristics, such as surrogate measures of species population size, latitudinal distribution and habitat types, taking phylogeny into account. Genetic variation of cytochrome oxidase I in water beetles was positively correlated with occupancy (numbers of sites of species presence) and negatively with latitude, whereas substitution rates across species depended mainly on habitat types, and running water specialists had the highest rate. These results are consistent with theoretical predictions from nearly-neutral theories of evolution, and suggest that the comparative analysis using large databases can give insights into correlates of genetic variation and molecular evolution. PMID:25621335

  7. Generalized Glucocorticoid Resistance: Clinical Aspects, Molecular Mechanisms, and Implications of a Rare Genetic Disorder

    PubMed Central

    Charmandari, Evangelia; Kino, Tomoshige; Ichijo, Takamasa; Chrousos, George P.

    2008-01-01

    Context: Primary generalized glucocorticoid resistance is a rare genetic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. We review the clinical aspects, molecular mechanisms, and implications of this disorder. Evidence Acquisition: We conducted a systematic review of the published, peer-reviewed medical literature using MEDLINE (1975 through February 2008) to identify original articles and reviews on this topic. Evidence Synthesis: We have relied on the experience of a number of experts in the field, including our extensive personal experience. Conclusions: The clinical spectrum of primary generalized glucocorticoid resistance is broad, ranging from asymptomatic to severe cases of hyperandrogenism, fatigue, and/or mineralocorticoid excess. The molecular basis of the condition has been ascribed to mutations in the human glucocorticoid receptor (hGR) gene, which impair glucocorticoid signal transduction and reduce tissue sensitivity to glucocorticoids. A consequent increase in the activity of the hypothalamic-pituitary-adrenal axis compensates for the reduced sensitivity of peripheral tissues to glucocorticoids at the expense of ACTH hypersecretion-related pathology. The study of functional defects of natural hGR mutants enhances our understanding of the molecular mechanisms of hGR action and highlights the importance of integrated cellular and molecular signaling mechanisms for maintaining homeostasis and preserving normal physiology. PMID:18319312

  8. Clinical, genetic, and molecular aspects of split-hand/foot malformation: an update.

    PubMed

    Gurrieri, Fiorella; Everman, David B

    2013-11-01

    We here provide an update on the clinical, genetic, and molecular aspects of split-hand/foot malformation (SHFM). This rare condition, affecting 1 in 8,500-25,000 newborns, is extremely complex because of its variability in clinical presentation, irregularities in its inheritance pattern, and the heterogeneity of molecular genetic alterations that can be found in affected individuals. Both syndromal and nonsyndromal forms are reviewed and the major molecular genetic alterations thus far reported in association with SHFM are discussed. This updated overview should be helpful for clinicians in their efforts to make an appropriate clinical and genetic diagnosis, provide an accurate recurrence risk assessment, and formulate a management plan. PMID:24115638

  9. 59. Cold Spring Harbor symposium on quantitative biology: Molecular genetics of cancer

    SciTech Connect

    1994-12-31

    Investigation of the mechanistic aspects of cancer has its roots in the studies on tumor viruses and their effects on cell proliferation, function, and growth. This outstanding progress was well documented in previous Cold Spring Harbor Symposia on Quantitative Biology. In the early to mid 1980s, progress on the development of chromosome mapping strategies and the accumulation of DNA probes that identified polymorphisms, encouraged by the international Human Genome Project, enabled the identification of other genes that contributed to familial inheritance of high susceptibility to specific cancers. This approach was very successful and led to a degree of optimism that one aspect of cancer, the multistep genetic process from early neoplasia to metastatic tumors, was beginning to be understood. It therefore seemed appropriate that the 59th Symposium on Quantitative Biology focus attention on the Molecular Genetics of Cancer. The concept was to combine the exciting progress on the identification of new genetic alterations in human tumor cells with studies on the function of the cancer gene products and how they go awry in tumor cells.

  10. The history of Old World camelids in the light of molecular genetics.

    PubMed

    Burger, Pamela Anna

    2016-06-01

    Old World camels have come into the focus as sustainable livestock species, unique in their morphological and physiological characteristics and capable of providing vital products even under extreme environmental conditions. The evolutionary history of dromedary and Bactrian camels traces back to the middle Eocene (around 40 million years ago, mya), when the ancestors of Camelus emerged on the North American continent. While the genetic status of the two domestic species has long been established, the wild two-humped camel has only recently been recognized as a separate species, Camelus ferus, based on molecular genetic data. The demographic history established from genome drafts of Old World camels shows the independent development of the three species over the last 100,000 years with severe bottlenecks occurring during the last glacial period and in the recent past. Ongoing studies involve the immune system, relevant production traits, and the global population structure and domestication of Old World camels. Based on the now available whole genome drafts, specific metabolic pathways have been described shedding new light on the camels' ability to adapt to desert environments. These new data will also be at the origin for genome-wide association studies to link economically relevant phenotypes to genotypes and to conserve the diverse genetic resources in Old World camelids. PMID:27048619

  11. Molecular newborn screening of four genetic diseases in Guizhou Province of South China.

    PubMed

    Huang, Shengwen; Xu, Yin; Liu, Xingmei; Zhou, Man; Wu, Xian; Jia, Yankai

    2016-10-10

    Genetic disorders have been a major concern for public health in China, especially in the rural regions. However, there is little information available about prevalence of many common single-gene disorders in Guizhou Province in the south western part of China. In the present study, we performed a molecular newborn screening for four genetic disorders, including beta-thalassemia (β-thal), glucose-6-phosphate dehydrogenase (G6PD) deficiency, phenylketonuria (PKU), and non-syndromic hearing loss and deafness (NSHL) in this region. A total of 515 newborns were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) developed for screening the mutations causing these four disorders, and then confirmed by Sanger sequencing. The results showed that 48 out of 515 newborns were carriers of mutations related to these four diseases, with a frequency of 1 in 11 (9.32%). The carrier frequencies for each disease are: β-thal 2.72%; G6PD deficiency 1.94%; PKU 0.78% and NSHL 4.47%. The genotyping results by MALDI-TOF MS were concordant with Sanger sequencing results within 30 randomly selected samples. This is the first study that reveals carrier frequencies of these four diseases in Guizhou Province. These data provide valuable information for the genetic counseling and disease prevention in Guizhou and southwest China. PMID:27395428

  12. Genetic diversity and molecular phylogeography of Chinese domestic goats by large-scale mitochondrial DNA analysis.

    PubMed

    Zhao, Yongju; Zhao, Runze; Zhao, Zhongquan; Xu, Huizhong; Zhao, Erhu; Zhang, Jiahua

    2014-06-01

    Mitochondrial DNA (mtDNA) D-loop sequences of 666 individuals (including 109 new individuals, 557 individuals retrieved from GenBank) from 33 Chinese domestic goat breeds throughout China were used to investigate their mtDNA variability and molecular phylogeography. The results showed that all goat breeds in this study proved to be extremely diverse, and the average haplotype diversity and nucleotide diversity were 0.990 ± 0.001 and 0.032 ± 0.001, respectively. The 666 sequences gave 326 different haplotypes. Phylogenetic analyses revealed that there were 4 mtDNA haplogroups identified in Chinese domestic goats, in which haplogroup A was predominant and widely distributed. Our finding was consistent with archaeological data and other genetic diversity studies. Amova analysis showed there was significant geographical structuring. Almost 84.31% of genetic variation was included in the within-breed variance component and only 4.69% was observed among the geographic distributions. This genetic diversity results further supported the previous view of multiple maternal origins of Chinese domestic goats, and the results on the phylogenetic relationship contributed to a better understanding of the history of goat domestication and modern production of domestic goats. PMID:24532161

  13. Genetic Divergence in Mandible Form in Relation to Molecular Divergence in Inbred Mouse Strains

    PubMed Central

    Atchley, W. R.; Newman, S.; Cowley, D. E.

    1988-01-01

    Genetic divergence in the form of the mandible is examined in ten inbred strains of mice. Several univariate and multivariate genetic distance estimates are given for the morphological data and these estimates are compared to measures of genealogical and molecular divergence. Highly significant divergence occurs among the ten strains in all 11 mandible traits considered individually and simultaneously. Genealogical relationship among strains is highly correlated with genetic divergence in single locus molecular traits. However, the concordance between genealogical relationship and multivariate genetic divergence in morphology is much more complex. Whether there is a significant correlation between morphological divergence and genealogy depends upon the method of analysis and the particular genetic distance statistic being employed. PMID:3220250

  14. [Genetic differentiation of Caucasian wood mice: comparison of isozymic, chromosomal and molecular divergence].

    PubMed

    Chelomina, G N; Pavlenko, M V; Kartavtseva, I V; Boeskorov, G G; Liapunova, E A; Vorontsov, N N

    1998-02-01

    Data on the complex genetic analysis of three sympatric species of Caucasian wood mice, Apodemus ponticus, A. fulvipectus, and A. uralensis are presented. A high degree of genetic differentiation at the isozymic, karyological and molecular (nuclear DNA) levels was revealed. The genetic distances between each pair of species varied significantly within a wide range depending on the analyzed level of the organization of genetic material. Mean values of genetic divergence from one species to another were also variable. These findings indicated that evolution of chromosomes was slower than that of isozymes, and the degree of species divergence was similar on cytogenetic and molecular levels. They also suggested that the rates of species evolution could vary in different phyletic lineages and on different levels of organization. Some phyletic lineages of Apodemus could be distinguished by different directions of evolution. PMID:9589852

  15. Clinician Perspectives about Molecular Genetic Testing for Heritable Conditions and Development of a Clinician-Friendly Laboratory Report

    PubMed Central

    Lubin, Ira M.; McGovern, Margaret M.; Gibson, Zoe; Gross, Susan J.; Lyon, Elaine; Pagon, Roberta A.; Pratt, Victoria M.; Rashid, Jamila; Shaw, Colleen; Stoddard, Lander; Trotter, Tracy L.; Williams, Marc S.; Amos Wilson, Jean; Pass, Kenneth

    2009-01-01

    The use of molecular genetic tests for heritable conditions is expected to increase in medical settings, where genetic knowledge is often limited. As part of a project to improve the clarity of genetic test result reports to minimize misunderstandings that could compromise patient care, we sought input about format and content from practicing primary care clinicians. In facilitated workgroup discussions, clinicians from pediatric, obstetrics-gynecology, and family practice provided their perspectives about molecular genetic testing with a focus on the laboratory reporting of test results. Common principles for enhancing the readability and comprehension of test result reports were derived from these discussions. These principles address the presentation of patient- and test-specific information, the test result interpretation, and guidance for future steps. Model test result reports for DNA-based cystic fibrosis testing are presented that were developed based on workgroup discussions, previous studies, and professional guidelines. The format of these model test reports, which are applicable to a variety of molecular genetic tests, should be useful for communicating essential information from the laboratory to health care professionals. PMID:19197001

  16. Molecular mechanisms of genetic adaptation to xenobiotic compounds.

    PubMed Central

    van der Meer, J R; de Vos, W M; Harayama, S; Zehnder, A J

    1992-01-01

    Microorganisms in the environment can often adapt to use xenobiotic chemicals as novel growth and energy substrates. Specialized enzyme systems and metabolic pathways for the degradation of man-made compounds such as chlorobiphenyls and chlorobenzenes have been found in microorganisms isolated from geographically separated areas of the world. The genetic characterization of an increasing number of aerobic pathways for degradation of (substituted) aromatic compounds in different bacteria has made it possible to compare the similarities in genetic organization and in sequence which exist between genes and proteins of these specialized catabolic routes and more common pathways. These data suggest that discrete modules containing clusters of genes have been combined in different ways in the various catabolic pathways. Sequence information further suggests divergence of catabolic genes coding for specialized enzymes in the degradation of xenobiotic chemicals. An important question will be to find whether these specialized enzymes evolved from more common isozymes only after the introduction of xenobiotic chemicals into the environment. Evidence is presented that a range of genetic mechanisms, such as gene transfer, mutational drift, and genetic recombination and transposition, can accelerate the evolution of catabolic pathways in bacteria. However, there is virtually no information concerning the rates at which these mechanisms are operating in bacteria living in nature and the response of such rates to the presence of potential (xenobiotic) substrates. Quantitative data on the genetic processes in the natural environment and on the effect of environmental parameters on the rate of evolution are needed. PMID:1480115

  17. Novel molecular markers of Chlamydia pecorum genetic diversity in the koala (Phascolarctos cinereus)

    PubMed Central

    2011-01-01

    Background Chlamydia pecorum is an obligate intracellular bacterium and the causative agent of reproductive and ocular disease in several animal hosts including koalas, sheep, cattle and goats. C. pecorum strains detected in koalas are genetically diverse, raising interesting questions about the origin and transmission of this species within koala hosts. While the ompA gene remains the most widely-used target in C. pecorum typing studies, it is generally recognised that surface protein encoding genes are not suited for phylogenetic analysis and it is becoming increasingly apparent that the ompA gene locus is not congruent with the phylogeny of the C. pecorum genome. Using the recently sequenced C. pecorum genome sequence (E58), we analysed 10 genes, including ompA, to evaluate the use of ompA as a molecular marker in the study of koala C. pecorum genetic diversity. Results Three genes (incA, ORF663, tarP) were found to contain sufficient nucleotide diversity and discriminatory power for detailed analysis and were used, with ompA, to genotype 24 C. pecorum PCR-positive koala samples from four populations. The most robust representation of the phylogeny of these samples was achieved through concatenation of all four gene sequences, enabling the recreation of a "true" phylogenetic signal. OmpA and incA were of limited value as fine-detailed genetic markers as they were unable to confer accurate phylogenetic distinctions between samples. On the other hand, the tarP and ORF663 genes were identified as useful "neutral" and "contingency" markers respectively, to represent the broad evolutionary history and intra-species genetic diversity of koala C. pecorum. Furthermore, the concatenation of ompA, incA and ORF663 sequences highlighted the monophyletic nature of koala C. pecorum infections by demonstrating a single evolutionary trajectory for koala hosts that is distinct from that seen in non-koala hosts. Conclusions While the continued use of ompA as a fine

  18. Theoretical studies of molecular collisions

    NASA Technical Reports Server (NTRS)

    Kouri, Donald J.

    1991-01-01

    The following subject areas are covered: (1) total integral reactive cross sections and vibrationally resolved reaction probabilities for F + H2 = HF + H; (2) a theoretical study of inelastic O + N2 collisions; (3) body frame close coupling wave packet approach to gas phase atom-rigit rotor inelastic collisions; (4) wave packet study of gas phase atom-rigit motor scattering; (5) the application of optical potentials for reactive scattering; (6) time dependent, three dimensional body frame quantal wave packet treatment of the H + H2 exchange reaction; (7) a time dependent wave packet approach to atom-diatom reactive collision probabilities; (8) time dependent wave packet for the complete determination of s-matrix elements for reactive molecular collisions in three dimensions; (9) a comparison of three time dependent wave packet methods for calculating electron-atom elastic scattering cross sections; and (10) a numerically exact full wave packet approach to molecule-surface scattering.

  19. Abundant Genetic Overlap between Blood Lipids and Immune-Mediated Diseases Indicates Shared Molecular Genetic Mechanisms

    PubMed Central

    Andreassen, Ole A.; Desikan, Rahul S.; Wang, Yunpeng; Thompson, Wesley K.; Schork, Andrew J.; Zuber, Verena; Doncheva, Nadezhda T.; Ellinghaus, Eva; Albrecht, Mario; Mattingsdal, Morten; Franke, Andre; Lie, Benedicte A.; Mills, Ian; Aukrust, Pål; McEvoy, Linda K.; Djurovic, Srdjan; Karlsen, Tom H.; Dale, Anders M.

    2015-01-01

    Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS) to investigate shared single nucleotide polymorphisms (SNPs) between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals), applying new False Discovery Rate (FDR) methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG), low density lipoproteins (LDL), high density lipoproteins (HDL)] and a selection of archetypal immune-mediated diseases (Crohn’s disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis). We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88), LDL (n = 87) and HDL (n = 52). Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2) and intestinal host-microbe interactions (e.g. ATG16L1). We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents. PMID:25853426

  20. The genetic and molecular bases of monogenic disorders affecting proteolytic systems

    PubMed Central

    Richard, I

    2005-01-01

    Complete and limited proteolysis represents key events that regulate many biological processes. At least 5% of the human genome codes for components of proteolytic processes if proteases, inhibitors, and cofactors are taken into account. Accordingly, disruption of proteolysis is involved in numerous pathological conditions. In particular, molecular genetic studies have identified a growing number of monogenic disorders caused by mutations in protease coding genes, highlighting the importance of this class of enzymes in development, organogenesis, immunity, and brain function. This review provides insights into the current knowledge about the molecular genetic causes of these disorders. It should be noted that most are due to loss of function mutations, indicating absolute requirement of proteolytic activities for normal cellular functions. Recent progress in understanding the function of the implicated proteins and the disease pathogenesis is detailed. In addition to providing important clues to the diagnosis, treatment, and pathophysiology of disease, functional characterisation of mutations in proteolytic systems emphasises the pleiotropic functions of proteases in the body homeostasis. PMID:15994873

  1. Research in China on the molecular genetics of schizophrenia

    PubMed Central

    Cui, Donghong; Jiang, Kaida

    2012-01-01

    Summary Schizophrenia is a complex disease caused by genetic and environmental factors with a global heritability of more than 80%. By the end of the 1970s, Chinese scientists reported a heritability of schizophrenia of 82.9% in the Chinese Han population. Continuous improvements in research techniques and the recruitment of larger samples have made it possible for Chinese scientists to identify a number of candidate susceptibility genes for schizophrenia. This article reviews the results in genetic research of schizophrenia by Chinese scientists over the last five decades PMID:25324626

  2. Molecular biology and genetic diversity of Rift Valley fever virus

    PubMed Central

    Ikegami, Tetsuro

    2013-01-01

    Rift Valley fever virus (RVFV), a member of the family Bunyaviridae, genus Phlebovirus, is the causative agent of Rift Valley fever (RVF), a mosquito-borne disease of ruminant animals and humans. The generation of a large sequence database has facilitated studies of the evolution and spread of the virus. Bayesian analyses indicate that currently circulating strains of RVFV are descended from an ancestral species that emerged from a natural reservoir in Africa when large-scale cattle and sheep farming were introduced during the 19th century. Viruses descended from multiple lineages persist in that region, through infection of reservoir animals and vertical transmission in mosquitoes, emerging in years of heavy rainfall to cause epizootics and epidemics. On a number of occasions, viruses from these lineages have been transported outside the enzootic region through the movement of infected animals or mosquitoes, triggering outbreaks in countries such as Egypt, Saudi Arabia, Mauritania and Madagascar, where RVF had not previously been seen. Such viruses could potentially become established in their new environments through infection of wild and domestic ruminants and other animals and vertical transmission in local mosquito species. Despite their extensive geographic dispersion, all strains of RVFV remain closely related at the nucleotide and amino acid level. The high degree of conservation of genes encoding the virion surface glycoproteins suggests that a single vaccine should protect against all currently circulating RVFV strains. Similarly, preservation of the sequence of the RNA-dependent RNA polymerase across viral lineages implies that antiviral drugs targeting the enzyme should be effective against all strains. Researchers should be encouraged to collect additional RVFV isolates and perform whole-genome sequencing and phylogenetic analysis, so as to enhance our understanding of the continuing evolution of this important virus. This review forms part of a series

  3. [RET/PTC Gene Rearrangements in the Sporadic and Radiogenic Thyroid Tumors: Molecular Genetics, Radiobiology and Molecular Epidemiology].

    PubMed

    Ushenkova, L N; Koterov, A N; Biryukov, A P

    2015-01-01

    A review of molecular genetic, radiobiological and molecular epidemiological studies of gene (chromosome) rearrangements RET/PTC in the cells of the thyroid gland as well as the laws in relation to radiation exposure in vitro, in vivo and human populations identified with them are submitted. The data on the c-RET gene and its chimeric constructs with the gene-donors (RET/PTC rearrangements) are considered. The information about the history of the RET/PTC discovery, their types, carcinogenic potential and specificity both to tumor and non-tumor thyroid disease especially for papillary thyroid carcinoma are provided. The data (seven studies) on the induction of RET/PTC after irradiation of tumor and normal thyroid cells in vitro and mice are reviewed. The mechanisms of RET/PTC induction may be associated with DNA double strand breaks and oxidative stress. Some information (three publications) about the possibility of RET/PTC induction by low doses of radiation with low LET (to 0.1 Gy) is given and it is concluded that their potential evidentiary is generally weak. The achievements in the molecular epidemiology of RET/PTC frequency for exposed and unexposed cohorts are stated. At the same time it is noted that, despite the vast array. of data accumulated from 30 countries of the world and more than 20 years of research, the formed provisions are weakly confirmed statistically and have no base corresponding to the canons of evidence-based medicine. The possibility of use of the RET/PTC presence or their frequencies as markers of the papillary thyroid carcinomas and, specifically, their radiogenic forms, is considered. In the first case the answer may be positive, while in the second, the situation is characterized by uncertainty. Based to the above mentioned we came to a conclusion about the need of a pooled or meta-analysis of the totality of the published data. PMID:26310016

  4. Pituitary Tumors in Childhood: an update in their diagnosis, treatment and molecular genetics

    PubMed Central

    Keil, Margaret F.; Stratakis, Constantine A.

    2009-01-01

    Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to 1 per million children. Only 2 - 6% of surgically treated pituitary tumors occur in children. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Tumors within the pituitary fossa are of two types mainly, craniopharyngiomas and adenomas; craniopharyngiomas cause symptoms by compressing normal pituitary, causing hormonal deficiencies and producing mass effects on surrounding tissues and the brain; adenomas produce a variety of hormonal conditions such as hyperprolactinemia, Cushing disease and acromegaly or gigantism. Little is known about the genetic causes of sporadic lesions, which comprise the majority of pituitary tumors, but in children, more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as multiple endocrine neoplasia type 1 (MEN 1), Carney complex, familial isolated pituitary adenoma (FIPA), and McCune-Albright syndrome. The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments. PMID:18416659

  5. Genetic diversity analysis of Croton antisyphiliticus Mart. using AFLP molecular markers.

    PubMed

    Oliveira, T G; Pereira, A M S; Coppede, J S; França, S C; Ming, L C; Bertoni, B W

    2016-01-01

    Croton antisyphiliticus Mart. is a medicinal plant native to Cerrado vegetation in Brazil, and it is popularly used to treat urogenital tract infections. The objective of the present study was to assess the genetic variability of natural C. antisyphiliticus populations using AFLP molecular markers. Accessions were collected in the states of Minas Gerais, São Paulo, and Goiás. The genotyping of individuals was performed using a LI-COR® DNA Analyzer 4300. The variability within populations was found to be greater than the variability between them. The F(ST) value was 0.3830, which indicated that the populations were highly structured. A higher percentage of polymorphic loci (92.16%) and greater genetic diversity were found in the population accessions from Pratinha-MG. Gene flow was considered restricted (N(m) = 1.18), and there was no correlation between genetic and geographic distances. The populations of C. antisyphiliticus exhibited an island-model structure, which demonstrates the vulnerability of the species. PMID:26909989

  6. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity

    PubMed Central

    Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I.; Taylor, Kent D.; Azziz, Ricardo; Goodarzi, Mark O.

    2015-01-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS. PMID:26305227

  7. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    PubMed

    Jones, Michelle R; Brower, Meredith A; Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I; Taylor, Kent D; Azziz, Ricardo; Goodarzi, Mark O

    2015-08-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS. PMID:26305227

  8. Molecular and genetic regulation of tree branch orientation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ability to genetically manipulate tree form can significantly benefit orchard and tree plantation management by enabling higher density plantings, mechanized harvesting, and reduce both chemical use and costly manual labor. Using both Prunus persica and Arabidopsis thaliana, we identified an an...

  9. Tripsacum genetics: from observations along a river to molecular genomics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A combination review of Tripsacum genetics research and update on current efforts in the field are provided in commemoration of the significant contributions of Dr. Walton C. Galinat to our understanding of this intriguing genus. Tripsacum research has involved many researchers over the years, many...

  10. Recent advances in molecular genetic linkage maps of cultivated peanut

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The competitiveness of peanuts in domestic and global markets has been threatened by losses in productivity and quality that are attributed to diseases, pests, environmental stresses and allergy or food safety issues. Narrow genetic diversity and deficiency of polymorphic DNA markers had severely hi...

  11. Linguini Models of Molecular Genetic Mapping and Fingerprinting.

    ERIC Educational Resources Information Center

    Thompson, James N., Jr.; Gray, Stanton B.; Hellack, Jenna J.

    1997-01-01

    Presents an exercise using linguini noodles to demonstrate an aspect of DNA fingerprinting. DNA maps that show genetic differences can be produced by digesting a certain piece of DNA with two or more restriction enzymes both individually and in combination. By rearranging and matching linguini fragments, students can recreate the original pattern…

  12. MolabIS - An integrated information system for storing and managing molecular genetics data

    PubMed Central

    2011-01-01

    Background Long-term sample storage, tracing of data flow and data export for subsequent analyses are of great importance in genetics studies. Therefore, molecular labs do need a proper information system to handle an increasing amount of data from different projects. Results We have developed a molecular labs information management system (MolabIS). It was implemented as a web-based system allowing the users to capture original data at each step of their workflow. MolabIS provides essential functionality for managing information on individuals, tracking samples and storage locations, capturing raw files, importing final data from external files, searching results, accessing and modifying data. Further important features are options to generate ready-to-print reports and convert sequence and microsatellite data into various data formats, which can be used as input files in subsequent analyses. Moreover, MolabIS also provides a tool for data migration. Conclusions MolabIS is designed for small-to-medium sized labs conducting Sanger sequencing and microsatellite genotyping to store and efficiently handle a relative large amount of data. MolabIS not only helps to avoid time consuming tasks but also ensures the availability of data for further analyses. The software is packaged as a virtual appliance which can run on different platforms (e.g. Linux, Windows). MolabIS can be distributed to a wide range of molecular genetics labs since it was developed according to a general data model. Released under GPL, MolabIS is freely available at http://www.molabis.org. PMID:22040322

  13. Gastrointestinal stromal tumors: molecular markers and genetic subtypes.

    PubMed

    Barnett, Christine M; Corless, Christopher L; Heinrich, Michael C

    2013-10-01

    Mutation-activated signaling from the KIT and PDGFRA kinases has been successfully targeted in gastrointestinal stromal tumors (GISTs), with subtle differences between the mutations serving to refine prognosis and more precisely tailor therapy. There is a growing understanding of the molecular drivers of GISTs lacking mutations in KIT or PDGFRA, so called wild-type GISTs, further aiding in management decisions. This article provides an overview of all the known molecular subtypes of GIST and provides information about clinical correlates, treatment, and prognosis depending on the subtype. PMID:24093165

  14. Indel Group in Genomes (IGG) Molecular Genetic Markers.

    PubMed

    Toal, Ted W; Burkart-Waco, Diana; Howell, Tyson; Ron, Mily; Kuppu, Sundaram; Britt, Anne; Chetelat, Roger; Brady, Siobhan M

    2016-09-01

    Genetic markers are essential when developing or working with genetically variable populations. Indel Group in Genomes (IGG) markers are primer pairs that amplify single-locus sequences that differ in size for two or more alleles. They are attractive for their ease of use for rapid genotyping and their codominant nature. Here, we describe a heuristic algorithm that uses a k-mer-based approach to search two or more genome sequences to locate polymorphic regions suitable for designing candidate IGG marker primers. As input to the IGG pipeline software, the user provides genome sequences and the desired amplicon sizes and size differences. Primer sequences flanking polymorphic insertions/deletions are produced as output. IGG marker files for three sets of genomes, Solanum lycopersicum/Solanum pennellii, Arabidopsis (Arabidopsis thaliana) Columbia-0/Landsberg erecta-0 accessions, and S. lycopersicum/S. pennellii/Solanum tuberosum (three-way polymorphic) are included. PMID:27436831

  15. New technologies in molecular genetics: the impact on epilepsy research.

    PubMed

    Helbig, Ingo

    2014-01-01

    Technical advances in the last decade have finally enabled researchers to identify epilepsy-associated genetic variants by querying virtually the entire genome. In the first decade of the twenty-first century, this technical revolution began with the advent of array comparative genomic hybridization and single nucleotide polymorphism arrays. These technologies made it possible for the first time to screen for common genetic variants and rare small deletions and duplications, referred to as microdeletions and microduplications. More recently, the repertoire of technologies has expanded to exome-wide and genome-wide sequencing approaches. These technologies led to a virtual explosion of gene identifications both in familial cases and in rare severe epilepsies, referred to as epileptic encephalopathies. This chapter aims to provide an overview of the achievements of these new technologies and the challenges that the field is currently facing. PMID:25194493

  16. The molecular genetic makeup of acute lymphoblastic leukemia.

    PubMed

    Mullighan, Charles G

    2012-01-01

    Genomic profiling has transformed our understanding of the genetic basis of acute lymphoblastic leukemia (ALL). Recent years have seen a shift from microarray analysis and candidate gene sequencing to next-generation sequencing. Together, these approaches have shown that many ALL subtypes are characterized by constellations of structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations, several of which have clear implications for risk stratification and targeted therapeutic intervention. Mutations in genes regulating lymphoid development are a hallmark of ALL, and alterations of the lymphoid transcription factor gene IKZF1 (IKAROS) are associated with a high risk of treatment failure in B-ALL. Approximately 20% of B-ALL cases harbor genetic alterations that activate kinase signaling that may be amenable to treatment with tyrosine kinase inhibitors, including rearrangements of the cytokine receptor gene CRLF2; rearrangements of ABL1, JAK2, and PDGFRB; and mutations of JAK1 and JAK2. Whole-genome sequencing has also identified novel targets of mutation in aggressive T-lineage ALL, including hematopoietic regulators (ETV6 and RUNX1), tyrosine kinases, and epigenetic regulators. Challenges for the future are to comprehensively identify and experimentally validate all genetic alterations driving leukemogenesis and treatment failure in childhood and adult ALL and to implement genomic profiling into the clinical setting to guide risk stratification and targeted therapy. PMID:23233609

  17. Genetic introgression and species boundary of two geographically overlapping pine species revealed by molecular markers.

    PubMed

    Zhang, Defang; Xia, Tao; Yan, Maomao; Dai, Xiaogang; Xu, Jin; Li, Shuxian; Yin, Tongming

    2014-01-01

    Gene introgression and hybrid barriers have long been a major focus of studies of geographically overlapping species. Two pine species, Pinus massoniana and P. hwangshanensis, are frequently observed growing adjacent to each other, where they overlap in a narrow hybrid zone. As a consequence, these species constitute an ideal system for studying genetic introgression and reproductive barriers between naturally hybridizing, adjacently distributed species. In this study, we sampled 270 pine trees along an elevation gradient in Anhui Province, China and analyzed these samples using EST-SSR markers. The molecular data revealed that direct gene flow between the two species was fairly low, and that the majority of gene introgression was intermediated by backcrossing. On the basis of empirical observation, the on-site distribution of pines was divided into a P. massoniana zone, a hybrid zone, and a P. hwangshanensis zone. STRUCTURE analysis revealed the existence of a distinct species boundary between the two pine species. The genetic boundary of the hybrid zone, on the other hand, was indistinct owing to intensive backcrossing with parental species. Compared with P. massoniana, P. hwangshanensis was found to backcross with the hybrids more intensively, consistent with the observation that morphological and anatomical characteristics of trees in the contact zone were biased towards P. hwangshanensis. The introgression ability of amplified alleles varied across species, with some being completely blocked from interspecific introgression. Our study has provided a living example to help explain the persistence of adjacently distributed species coexisting with their interfertile hybrids. PMID:24977711

  18. Australian endemic pest tephritids: genetic, molecular and microbial tools for improved Sterile Insect Technique.

    PubMed

    Raphael, Kathryn A; Shearman, Deborah C A; Gilchrist, A Stuart; Sved, John A; Morrow, Jennifer L; Sherwin, William B; Riegler, Markus; Frommer, Marianne

    2014-01-01

    Among Australian endemic tephritid fruit flies, the sibling species Bactrocera tryoni and Bactrocera neohumeralis have been serious horticultural pests since the introduction of horticulture in the nineteenth century. More recently, Bactrocera jarvisi has also been declared a pest in northern Australia. After several decades of genetic research there is now a range of classical and molecular genetic tools that can be used to develop improved Sterile Insect Technique (SIT) strains for control of these pests. Four-way crossing strategies have the potential to overcome the problem of inbreeding in mass-reared strains of B. tryoni. The ability to produce hybrids between B. tryoni and the other two species in the laboratory has proved useful for the development of genetically marked strains. The identification of Y-chromosome markers in B. jarvisi means that male and female embryos can be distinguished in any strain that carries a B. jarvisi Y chromosome. This has enabled the study of homologues of the sex-determination genes during development of B jarvisi and B. tryoni, which is necessary for the generation of genetic-sexing strains. Germ-line transformation has been established and a draft genome sequence for B. tryoni released. Transcriptomes from various species, tissues and developmental stages, to aid in identification of manipulation targets for improving SIT, have been assembled and are in the pipeline. Broad analyses of the microbiome have revealed a metagenome that is highly variable within and across species and defined by the environment. More specific analyses detected Wolbachia at low prevalence in the tropics but absent in temperate regions, suggesting a possible role for this endosymbiont in future control strategies. PMID:25470996

  19. Australian endemic pest tephritids: genetic, molecular and microbial tools for improved Sterile Insect Technique

    PubMed Central

    2014-01-01

    Among Australian endemic tephritid fruit flies, the sibling species Bactrocera tryoni and Bactrocera neohumeralis have been serious horticultural pests since the introduction of horticulture in the nineteenth century. More recently, Bactrocera jarvisi has also been declared a pest in northern Australia. After several decades of genetic research there is now a range of classical and molecular genetic tools that can be used to develop improved Sterile Insect Technique (SIT) strains for control of these pests. Four-way crossing strategies have the potential to overcome the problem of inbreeding in mass-reared strains of B. tryoni. The ability to produce hybrids between B. tryoni and the other two species in the laboratory has proved useful for the development of genetically marked strains. The identification of Y-chromosome markers in B. jarvisi means that male and female embryos can be distinguished in any strain that carries a B. jarvisi Y chromosome. This has enabled the study of homologues of the sex-determination genes during development of B jarvisi and B. tryoni, which is necessary for the generation of genetic-sexing strains. Germ-line transformation has been established and a draft genome sequence for B. tryoni released. Transcriptomes from various species, tissues and developmental stages, to aid in identification of manipulation targets for improving SIT, have been assembled and are in the pipeline. Broad analyses of the microbiome have revealed a metagenome that is highly variable within and across species and defined by the environment. More specific analyses detected Wolbachia at low prevalence in the tropics but absent in temperate regions, suggesting a possible role for this endosymbiont in future control strategies. PMID:25470996

  20. Aggression in non-human vertebrates: Genetic mechanisms and molecular pathways.

    PubMed

    Freudenberg, Florian; Carreño Gutierrez, Hector; Post, Antonia M; Reif, Andreas; Norton, William H J

    2016-07-01

    Aggression is an adaptive behavioral trait that is important for the establishment of social hierarchies and competition for mating partners, food, and territories. While a certain level of aggression can be beneficial for the survival of an individual or species, abnormal aggression levels can be detrimental. Abnormal aggression is commonly found in human patients with psychiatric disorders. The predisposition to aggression is influenced by a combination of environmental and genetic factors and a large number of genes have been associated with aggression in both human and animal studies. In this review, we compare and contrast aggression studies in zebrafish and mouse. We present gene ontology and pathway analyses of genes linked to aggression and discuss the molecular pathways that underpin agonistic behavior in these species. © 2015 Wiley Periodicals, Inc. PMID:26284957

  1. Molecular genetics of Müllerian duct formation, regression and differentiation

    PubMed Central

    Mullen, Rachel D.; Behringer, Richard R.

    2015-01-01

    The Müllerian duct forms the female reproductive tract consisting of the oviducts, uterus, cervix and upper vagina. Female reproductive tract function is vital to fertility, providing the site of fertilization, embryo implantation and fetal development. Developmental defects in the formation, and diseases of the female reproductive tract, including cancer and endometriosis, are prevalent in humans and can result in infertility and death. Further, because the Müllerian ducts are initially formed regardless of genotypic sex, mesenchymal-to-epithelial signaling is required in males to mediate Müllerian duct regression and prevents the development of Müllerian-derived organs. In males, defects in Müllerian duct regression result in the retention of female reproductive tract organs and have been described in several human syndromes. Although to date not reported in humans, ectopic activation of Müllerian duct regression signaling components in females can result in aplasia of the female reproduction tract. Clearly, Müllerian duct development is important to human health, however the molecular mechanisms remain largely undetermined. Molecular genetics studies of human disease and mouse models have provided new insights into molecular signaling during Müllerian duct development, regression and differentiation. This review will provide an overview of Müllerian duct development and important genes and signaling mechanisms involved. PMID:25033758

  2. Introductory Guide to the Statistics of Molecular Genetics

    ERIC Educational Resources Information Center

    Eley, Thalia C.; Rijsdijk, Fruhling

    2005-01-01

    Background: This introductory guide presents the main two analytical approaches used by molecular geneticists: linkage and association. Methods: Traditional linkage and association methods are described, along with more recent advances in methodologies such as those using a variance components approach. Results: New methods are being developed all…

  3. The Fragile X Syndrome: From Molecular Genetics to Neurobiology

    ERIC Educational Resources Information Center

    Willemsen, Rob; Oostra, Ben A.; Bassell, Gary J.; Dictenberg, Jason

    2004-01-01

    Since the identification of the FMR1 gene basic research has been focused on the molecular characterization of the FMR1 gene product, the fragile X mental retardation protein (FMRP). Recent developments in fragile X research have provided new insights and knowledge about the physiological function of FMRP in the cell and the nerve cell in…

  4. DNA in soil: adsorption, genetic transformation, molecular evolution and genetic microchip.

    PubMed

    Trevors, J T

    1996-07-01

    This review examines interactions between DNA and soil with an emphasis on the persistence and stability of DNA in soil. The role of DNA in genetic transformation in soil microorganisms will also be discussed. In addition, a postulated mechanism for stabilization and elongation/assembly of primitive genetic material and the role of soil particles, salt concentrations, temperature cycling and crystal formation is examined. PMID:8836436

  5. Genetic diversity in Tunisian populations of faba bean (Vicia faba L.) based on morphological traits and molecular markers.

    PubMed

    Backouchi, I Z; Aouida, M; Khemiri, N; Jebara, M

    2015-01-01

    Genetic diversity within Vicia faba L. is key to the genetic improvement of this important species. In this study, morphological traits and RAPD molecular markers were used to assess the levels of polymorphism across 12 Tunisian populations, three major and nine minor from different locations. Analysis of morphological traits indicated that the three major populations showed significant differences and the nine minor populations exhibited considerable variation for most traits. The grain yield of the Alia population could be increased by inoculation. Of the seven primers tested, it was clear that the Cs12 primer would be recommend for genetic diversity analysis of V. faba.Within population genetic diversity exhibited 94% of total diversity. Intra-population genetic diversity (HS) was 0.16, which was clearly higher than between population genetic diversity (DST = 0.06) UPG-MA showed a high level of genetic variation between major and minor populations of V. faba L. Particularly the minor populations showed a high level of diversity and was divided into two subclusters. Ltaifia was separated from the other populations. In addition to a high grain yield, these populations showed the lowest Nei and Shannon indices (H = 0.08 and I = 0.13) justifying their homogeneity. For these reasons, these cultivars can be considered a selected population. However, the Takelsa population showed the highest Nei and Shannon indices (H = 0.13 and I = 0.21), indicating that this population was the most heterogeneous, which is interesting for breeding programs. PMID:26214437

  6. Antenatal genetic studies in twin pregnancies.

    PubMed

    Redwine, F O; Cruikshank, D P; Brown, J

    1984-01-01

    The diagnosis of multiple gestation at the time of genetic amniocentesis is a routine occurrence. In a combined series of 2765 patients referred for antenatal genetic studies from the Medical College of Virginia and the University of Iowa, 34 twin pregnancies were encountered (1.2%). Twenty-six of the patients with twins were referred for advanced maternal age. The other indications were previous neural tube defects (1), previous trisomy 21 (2), known carriers of Tay Sachs disease (2), previous Turner's syndrome (1), family history of trisomy 21 (1), and one pregnancy was referred because of an abnormal ultrasound. Amniocentesis procedures, outcome of the twin pregnancies, and genetic counseling issues, are discussed. PMID:6741416

  7. MILLIMETER-SCALE GENETIC GRADIENTS AND COMMUNITY-LEVEL MOLECULAR CONVERGENCE IN A HYPERSALINE MICROBIAL MAT

    SciTech Connect

    Fenner, Marsha W; Kunin, Victor; Raes, Jeroen; Harris, J. Kirk; Spear, John R.; Walker, Jeffrey J.; Ivanova, Natalia; Mering, Christian von; Bebout, Brad M.; Pace, Norman R.; Bork, Peer; Hugenholtz, Philip

    2008-04-30

    To investigate the extent of genetic stratification in structured microbial communities, we compared the metagenomes of 10 successive layers of a phylogenetically complex hypersaline mat from Guerrero Negro, Mexico. We found pronounced millimeter-scale genetic gradients that are consistent with the physicochemical profile of the mat. Despite these gradients, all layers displayed near identical and acid-shifted isoelectric point profiles due to a molecular convergence of amino acid usage indicating that hypersalinity enforces an overriding selective pressure on the mat community.

  8. Genetic studies in the Amish community.

    PubMed

    Patton, Michael A

    2005-01-01

    The Amish community was established in Pennsylvania, Ohio and Indiana. They form a distinct and biologically isolated community by virtue of their strong cultural and religious beliefs. This paper outlines aspects of the Amish culture and reviews some of the recent genetic studies that have been undertaken in this community. PMID:16096212

  9. Genetic and Molecular Basis of Kingella kingae Encapsulation.

    PubMed

    Starr, Kimberly F; Porsch, Eric A; Seed, Patrick C; St Geme, Joseph W

    2016-06-01

    Kingella kingae is a common cause of invasive disease in young children and was recently found to produce a polysaccharide capsule containing N-acetylgalactosamine (GalNAc) and β-3-deoxy-d-manno-octulosonic acid (βKdo). Given the role of capsules as important virulence factors and effective vaccine antigens, we set out to determine the genetic determinants of K. kingae encapsulation. Using a transposon library and a screen for nonencapsulated mutants, we identified the previously identified ctrABCD (ABC transporter) operon, a lipA (kpsC)-like gene, a lipB (kpsS)-like gene, and a putative glycosyltransferase gene designated csaA (capsule synthesis type a gene A). These genes were found to be present at unlinked locations scattered throughout the genome, an atypical genetic arrangement for Gram-negative bacteria that elaborate a capsule dependent on an ABC-type transporter for surface localization. The csaA gene product contains a predicted glycosyltransferase domain with structural homology to GalNAc transferases and a predicted capsule synthesis domain with structural homology to Kdo transferases, raising the possibility that this enzyme is responsible for alternately linking GalNAc to βKdo and βKdo to GalNAc. Consistent with this conclusion, mutation of the DXD motif in the GalNAc transferase domain and of the HP motif in the Kdo transferase domain resulted in a loss of encapsulation. Examination of intracellular and surface-associated capsule in deletion mutants and complemented strains further implicated the lipA (kpsC)-like gene, the lipB (kpsS)-like gene, and the csaA gene in K. kingae capsule production. These data define the genetic requirements for encapsulation in K. kingae and demonstrate an atypical organization of capsule synthesis, assembly, and export genes. PMID:27045037

  10. Regulating Intracellular Calcium in Plants: From Molecular Genetics to Physiology

    SciTech Connect

    Heven Sze

    2008-06-22

    To grow, develop, adapt, and reproduce, plants have evolved mechanisms to regulate the uptake, translocation and sorting of calcium ions into different cells and subcellular compartments. Yet how plants accomplish this remarkable feat is still poorly understood. The spatial and temporal changes in intracellular [Ca2+] during growth and during responses to hormonal and environmental stimuli indicate that Ca2+ influx and efflux transporters are diverse and tightly regulated in plants. The specific goals were to determine the biological roles of multiple Ca pumps (ECAs) in the model plant Arabidopsis thaliana. We had pioneered the use of K616 yeast strain to functionally express plant Ca pumps, and demonstrated two distinct types of Ca pumps in plants (Sze et al., 2000. Annu Rev Plant Biol. 51,433). ACA2 represented one type that was auto-inhibited by the N-terminal region and stimulated by calmodulin. ECA1 represented another type that was not sensitive to calmodulin and phylogenetically distinct from ACAs. The goal to determine the biological roles of multiple ECA-type Ca pumps in Arabidopsis has been accomplished. Although we demonstrated ECA1 was a Ca pump by functional expression in yeast, the in vivo roles of ECAs was unclear. A few highlights are described. ECA1 and/or ECA4 are Ca/Mn pumps localized to the ER and are highly expressed in all cell types. Using homozygous T-DNA insertional mutants of eca1, we demonstrated that the ER-bound ECA1 supports growth and confers tolerance of plants growing on medium low in Ca or containing toxic levels of Mn. This is the first genetic study to determine the in vivo function of a Ca pump in plants. A phylogenetically distinct ECA3 is also a Ca/Mn pump that is localized to endosome, such as post-Golgi compartments. Although it is expressed at lower levels than ECA1, eca3 mutants are impaired in Ca-dependent root growth and in pollen tube elongation. Increased secretion of wall proteins in mutants suggests that Ca and Mn

  11. Genetic characterisation and molecular epidemiology of Ascaris spp. from humans and pigs in Brazil.

    PubMed

    Iñiguez, Alena M; Leles, Daniela; Jaeger, Lauren H; Carvalho-Costa, Filipe A; Araújo, Adauto

    2012-10-01

    The molecular epidemiology of Ascaris spp. of human and pig origin has been studied as a means to assess the potential of pigs as reservoirs for human ascariasis. In this study, human (H) and pig (P) Ascaris spp. haplotypes from two Brazilian regions were characterised based on two mitochondrial genes, nad1 and cox1. The results show six haplotypes of the cox1 gene, with two haplotypes (H9P9 and P3) corresponding to haplotypes previously characterised in China. Because P3 was found in humans in this study, it was designated as H14P3. Furthermore, five new Ascaris spp. nad1 haplotypes from humans (H12-H16) and five from pigs (P16-P20) were observed, with one being highly frequent and present in both hosts, here designated as H12P17. Phylogenetic and network analysis demonstrated that the molecular epidemiology of Ascaris spp. in Brazil is driven by the globally distributed haplotypes cox1 H14P3 and nad1 H12P17. In conclusion, in this study genetic characterisation of Ascaris spp. showed that humans and pigs share common haplotypes that are also present in two widely separated geographical regions of Brazil. PMID:22944771

  12. Molecular profiling for genetic variability in Capsicum species based on ISSR and RAPD markers.

    PubMed

    Thul, Sanjog T; Darokar, Mahendra P; Shasany, Ajit K; Khanuja, Suman P S

    2012-06-01

    The taxonomic identity of Capsicum species is found to be difficult as it displays variations at morpho-chemical characters. Twenty-two accessions of six Capsicum species, namely, C. annuum, C. baccatum, C. chinense, C. eximium, C. frutescens, and C. luteum were investigated for phenotypic diversity based on flower color and for genetic differences by molecular makers. The genetic cluster analyses of 27 RAPD and eight ISSR primers, respectively, revealed genetic similarities in the ranges of 23-88% and 11-96%. Principal component analysis of the pooled RAPD and ISSR data further supports the genetic similarity and groupings. Different species showed variations in relation to corolla shade of flower. C. annuum accessions formed a single cluster in the molecular analysis as maintaining their flower characteristic. C. chinense accession shared flower features with the accessions of C. frutescens and were found to be closer at genotypic level. C. luteum was found to be rather closer to C. baccatum complex, both phenotypically and genetically. The only accession of C. eximium presenting purple flowers falls apart from the groupings. The floral characteristics and the molecular markers are found to be useful toward the delineation of the species specificity in Capsicum collection and identification of genetic stock. PMID:21861246

  13. [Molecular genetic and bacteriological methods for the diagnosis of multidrug resistant M. tuberculosis].

    PubMed

    Agaev, F F; Aliev, K A; Salimova, N A; Abuzarov, R M; Gasymov, I A; Griadunov, D A

    2009-01-01

    For the early diagnosis of multidrug resistant tuberculosis, 67 sputum samples obtained from primary patients with different clinical forms of pulmonary tuberculosis were examined by the molecular genetic test using the TB-Biochip test system. Having a high sensitivity and specificity, the molecular genetic test for determining the drug sensitivity of Mycobacterium tuberculosis substantially accelerates its diagnosis (2-3 days) before the real-time mode of a patient's admission to the clinic. The method allows identification of mutations in the rpoB (resistance to R), katG, inhG, and ahpC (resistance to H) genes, which permits timely correction of performed specific treatment. PMID:19886013

  14. The molecular genetics of Marfan syndrome and related disorders

    PubMed Central

    Robinson, P N; Arteaga‐Solis, E; Baldock, C; Collod‐Béroud, G; Booms, P; De Paepe, A; Dietz, H C; Guo, G; Handford, P A; Judge, D P; Kielty, C M; Loeys, B; Milewicz, D M; Ney, A; Ramirez, F; Reinhardt, D P; Tiedemann, K; Whiteman, P; Godfrey, M

    2006-01-01

    Marfan syndrome (MFS), a relatively common autosomal dominant hereditary disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular systems, is caused by mutations in the gene for fibrillin‐1 (FBN1). The leading cause of premature death in untreated individuals with MFS is acute aortic dissection, which often follows a period of progressive dilatation of the ascending aorta. Recent research on the molecular physiology of fibrillin and the pathophysiology of MFS and related disorders has changed our understanding of this disorder by demonstrating changes in growth factor signalling and in matrix‐cell interactions. The purpose of this review is to provide a comprehensive overview of recent advances in the molecular biology of fibrillin and fibrillin‐rich microfibrils. Mutations in FBN1 and other genes found in MFS and related disorders will be discussed, and novel concepts concerning the complex and multiple mechanisms of the pathogenesis of MFS will be explained. PMID:16571647

  15. Presymptomatic studies in genetic frontotemporal dementia.

    PubMed

    Rohrer, J D; Warren, J D; Fox, N C; Rossor, M N

    2013-10-01

    Approximately 20% of patients with the neurodegenerative disorder frontotemporal dementia (FTD) have an autosomal dominant pattern of inheritance. Genetic FTD is caused by mutations in three genes in most cases (progranulin, microtubule-associated protein tau and chromosome 9 open reading frame 72) although a number of other genes are rare causes. Studies of other neurodegenerative diseases have shown imaging and biomarker evidence of disease onset many years prior to the development of symptoms. Similar studies in genetic FTD are now revealing evidence of a series of presymptomatic changes, initially in plasma biomarkers followed by MR imaging abnormalities of functional and structural connectivity and then grey matter atrophy. Lastly, neuropsychometric tests become abnormal in proximity to the onset of symptoms. Such studies have been relatively small until now but research centres with an expertise in genetic FTD are now forming consortia such as the Genetic Frontotemporal Dementia Initiative (GenFI) to create larger cohorts that can form the basis of future clinical trials. PMID:24012408

  16. Provisional hypotheses for the molecular genetics of cognitive development: Imaging genetic pathways in the anterior cingulate cortex

    PubMed Central

    Fossella, John; Fan, Jin; Liu, Xun; Guise, Kevin; Brocki, Karin; Hof, Patrick R.; Kittappa, Raja; McKay, Ronald; Posner, Michael

    2008-01-01

    Brain imaging genetic research involves a multitude of methods and spans many traditional levels of analysis. Given the vast permutations among several million common genetic variants with thousands of brain tissue voxels and a wide array of cognitive tasks that activate specific brain systems, we are prompted to develop specific hypotheses that synthesize converging evidence and state clear predictions about the anatomical sources, magnitude and direction (increases vs. decreases) of allele- and task-specific brain activity associations. To begin to develop a framework for shaping our imaging genetic hypotheses, we focus on previous results and the wider imaging genetic literature. Particular emphasis is placed on converging evidence that links system-level and biochemical studies with models of synaptic function. In shaping our own imaging genetic hypotheses on the development of Attention Networks, we review relevant literature on core models of synaptic physiology and development in the anterior cingulate cortex. PMID:18261834

  17. Pathways and barriers to genetic testing and screening: Molecular genetics meets the high-risk family. Final report

    SciTech Connect

    Duster, T.

    1998-11-01

    The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.

  18. An update on molecular genetics of gastrointestinal stromal tumours

    PubMed Central

    Tornillo, L; Terracciano, L M

    2006-01-01

    Gastrointestinal stromal tumours (GISTs) are the most common primary mesenchymal tumours of the gastrointestinal tract. Most of them show activating mutations of the genes coding for KIT or platelet‐derived growth factor receptor α (PDGFRα), two receptor tyrosine kinases (RTKs). The RTK inhibitor Imatinib (Gleevec®, Novartis, Switzerland), induces regression of the tumour. The level of response to treatment, together with other clinicopathological parameters is related to the type and site of the activating mutation, thus suggesting that these tumours should be classified according to the molecular context. This is confirmed also by the phenomenon of the resistance to treatment, which arises because of different mechanisms (second mutation, amplification, activation of other RTKs) and can be fought only by specific RTK inhibitors, that are at present under development. RTK activation involves an homogeneous transduction pathway whose components (MAPK, AKT, PI3K, mTOR and RAS) are possible targets of new molecular treatment. A new paradigm of classification integrating the classic pathological criteria with the molecular changes will permit personalised prognosis and treatment. PMID:16731599

  19. The evolving molecular genetics of low-grade glioma

    PubMed Central

    Venneti, Sriram; Huse, Jason T.

    2015-01-01

    Low-grade gliomas (LGG) constitute grade I and grade II tumors of astrocytic and grade II tumors of oligodendroglial lineage. Although these tumors are typically slow growing, they may be associated with significant morbidity and mortality due to recurrence and malignant progression, even in the setting of optimal resection. LGG in pediatric and adult age groups are currently classified by morphologic criteria. Recent years have heralded a molecular revolution in understanding brain tumors, including LGG. Next generation sequencing has definitively demonstrated that pediatric and adult LGG fundamentally differ in their underlying molecular characteristics, despite being histologically similar. Pediatric LGG show alterations in FGFR1 and BRAF in pilocytic astrocytomas and FGFR1 alterations in diffuse astrocytomas, each converging on the MAP kinase-signaling pathway. Adult LGG are characterized by IDH1/2 mutations and ATRX mutations in astrocytic tumors and IDH1/2 mutations and 1p/19q codeletions in oligodendroglial tumors. TERT promoter mutations are also noted in LGG and are mainly associated with oligodendrogliomas. These findings have considerably refined approaches to classifying these tumors. Moreover, many of the molecular alterations identified in LGG directly impact on prognosis, tumor biology, and the development of novel therapies. PMID:25664944

  20. Study design in genetic epidemiology: theoretical and practical considerations.

    PubMed

    Whittemore, A S; Nelson, L M

    1999-01-01

    Recent advances in molecular genetics have created new opportunities and challenges for genetic epidemiologists. Here we review some of the issues that arise when designing a study involving the genetic epidemiology of chronic diseases of late onset, such as cancer. We discuss two considerations that influence the choice of design. The first consideration is the study's goals. We describe the goals of identifying new susceptibility genes for a disease, of estimating important characteristics of known genes, and of learning how to prevent the disease in the genetically susceptible. We indicate how these goals affect the choice of design and present some guidelines for choosing designs that effectively address them. The second consideration is the set of practical constraints to successfully conducting the research. These contraints include problems of potential selection bias, reduced response rates, problems particular to family registries, problems particular to the cultures of various ethnic groups, and ethical issues. We indicate how these constraints affect the choice of design and discuss ways to deal with them. PMID:10854488

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

    PubMed Central

    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

  2. [Certification system for technological professionals towards standardization of molecular-genetic testing].

    PubMed

    Miyachi, Hayato

    2012-06-01

    The College of Laboratory Medicine of Japan, in collaboration with the Japanese Society of Laboratory Medicine, has developed a certification examination for technological professionals for the purpose of nurturing professionals possessing a high level of competency in the field of molecular analysis or molecular-genetic testing, and thus providing the quality health care services. Certification levels are separated into two levels: molecular analysis technologist and specialist. The former measures basic knowledge and skills. The latter measures the competencies defined in the statement, which includes compliance with the standards or guidelines for quality assurance of molecular-genetic testing. The former began in 2007, and 398 professionals have been certified in 5 years. The latter is beginning in 2012. Personnel qualification linked with the standards is expected to be an efficient and effective approach to providing the quality service. PMID:22880236

  3. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis

    PubMed Central

    Rothenberg, Marc E.

    2015-01-01

    Eosinophilic esophagitis (EoE) was historically distinguished from gastroesophageal reflux disease on the basis of histology and lack of responsiveness to acid suppressive therapy, but it is now appreciated that esophageal eosinophilia can respond to proton pump inhibitors. Genetic and environmental factors contribute to risk for EoE—particularly early-life events. Disease pathogenesis involves activation of epithelial inflammatory pathways (production of eotaxin-3 [encoded by CCL26]), impaired barrier function (mediated by loss of desmoglein-1), increased production and/or activity of transforming growth factor-β, and induction of allergic inflammation by eosinophils and mast cells. Susceptibility has been associated with variants at 5q22 (TSLP) and 2p23 (CAPN14), indicating roles for allergic sensitization and esophageal specific protease pathways. We propose that EoE is a unique disease characterized by food hypersensitivity, strong hereditability influenced by early-life exposures and esophageal specific genetic risk variants, and allergic inflammation and that the disease is remitted by disrupting inflammatory and T-helper type 2 cytokine–mediated responses and through dietary elimination therapy. PMID:25666870

  4. Molecular Genetic Evidence for Shared Etiology of Autism and Prodigy.

    PubMed

    Ruthsatz, Joanne; Petrill, Stephen A; Li, Ning; Wolock, Samuel L; Bartlett, Christopher W

    2015-01-01

    Child prodigies are rare individuals with an exceptional working memory and unique attentional skills that may facilitate the attainment of professional skill levels at an age well before what is observed in the general population. Some characteristics of prodigy have been observed to be quantitatively similar to those observed in autism spectrum disorder (ASD), suggesting possible shared etiology, though objectively validated prodigies are so rare that evidence has been sparse. We performed a family-based genome-wide linkage analysis on 5 nuclear and extended families to search for genetic loci that influence the presence of both prodigy and ASD, assuming that the two traits have the same genetic etiology in the analysis model in order to find shared loci. A shared locus on chromosome 1p31-q21 reached genome-wide significance with two extended family-based linkage methods consisting of the Bayesian PPL method and the LOD score maximized over the trait parameters (i.e., MOD), yielding a simulation-based empirical significance of p = 0.000742 and p = 0.000133, respectively. Within linkage regions, we performed association analysis and assessed if copy number variants could account for the linkage signal. No evidence of specificity for either the prodigy or the ASD trait was observed. This finding suggests that a locus on chromosome 1 increases the likelihood of both prodigy and autism in these families. PMID:25791271

  5. Non-invasive genetic sampling for molecular sexing and microsatellite genotyping of hyacinth macaw (Anodorhynchus hyacinthinus)

    PubMed Central

    Presti, Flavia T.; Meyer, Janaína; Antas, Paulo T.Z.; Guedes, Neiva M.R.; Miyaki, Cristina Y.

    2013-01-01

    Molted feather sampling is a useful tool for genetic analyses of endangered species, but it is often very laborious due to the low quality and quantity of the DNA obtained. In the present study we show the parts of feathers that resulted in better yield of DNA. In descending order these were: blood clot outside the umbilicus, umbilicus (without blood clot), tip, inner membrane, and small calamus. Compared to DNA extracted from blood samples, DNA extracted from feathers produced microsatellite alleles of poorer quality and had to be processed immediately after extraction. As expected due to the level of DNA degradation, molecular sexing protocols that result in shorter PCR products were more efficient. PMID:23569419

  6. The genetic stability of potato spindle tuber viroid (PSTVd) molecular variants.

    PubMed Central

    Góra-Sochacka, A; Kierzek, A; Candresse, T; Zagórski, W

    1997-01-01

    RNA viruses propagate as a population of genetically related entities composing a quasi-species. Specific representatives are the result of both a high mutation rate during replication and competition between the continuously arising sequence variants. Similar to other RNA pathogens, potato spindle tuber viroid (PSTVd) propagates as a population of similar but nonidentical sequences. The sequence of progeny molecules derived from cloned molecular variants of PSTVd were studied after one and six consecutive plant passages. Although the severe parental sequence S23 was found to be genetically stable, all five other parental sequences analyzed, irrespective of their pathogenicity, led to the appearance of complex populations. Divergence of the progeny was observed at the sequence level, but also, more surprisingly, at the level of the pathogenicity of individual progeny molecules. In two cases, the parental sequence was retained in the progeny population. In the other cases, it was completely out-competed and eliminated, sometimes in as little as one plant passage. Although it has been observed previously that artificially mutated PSTVd molecules may revert rapidly to the wild-type sequence, this study presents direct evidence for the rapid evolution of naturally occurring PSTVd sequence variants. PMID:8990400

  7. "Mucin"-secreting papillary renal cell carcinoma: clinicopathological, immunohistochemical, and molecular genetic analysis of seven cases.

    PubMed

    Pivovarcikova, Kristyna; Peckova, Kvetoslava; Martinek, Petr; Montiel, Delia Perez; Kalusova, Kristyna; Pitra, Tomas; Hora, Milan; Skenderi, Faruk; Ulamec, Monika; Daum, Ondrej; Rotterova, Pavla; Ondic, Ondrej; Dubova, Magdalena; Curik, Romuald; Dunatov, Ana; Svoboda, Tomas; Michal, Michal; Hes, Ondrej

    2016-07-01

    Mucin and mucin-like material are features of mucinous tubular and spindle renal cell carcinoma (MTS RCC) but are rarely seen in papillary renal cell carcinoma (PRCC). We reviewed 1311 PRCC and identified 7 tumors containing extracellular and/or intracellular mucinous/mucin-like material (labeled as PRCCM). We analyzed these using morphological, histochemical, immunohistochemical, and molecular genetic methods (arrayCGH, FISH). Clinical data were available for six of the seven patients (five males and one female, age range 61-78 years). Follow-up was available for four patients (2-4 years); one patient died of widespread metastases. Tumor size ranged from 3 to 5 cm (mean 3.8). Of all cases, histological architecture showed a predominantly papillary pattern. Mucin or mucin-like was extracellular in one, intracellular in three, and both intra/extracellular in three cases. All tumors were positive for AMACR, vimentin, and OSCAR, while CK7 was positive in four. Mucicarmine stain was positive in all cases, PAS in six and Alcian blue in three cases. Five tumors were positive for MUC 1, but none were positive for MUC 2, MUC 4, or MUC 6. In only four cases, genetic analysis could be performed. Gain of chromosomes 7 and 17 was found in two cases; gain of 17 only was found in one case. Loss of heterozygosity of 3p was found in one case together with polysomy of chromosomes 7 and 17. No abnormalities of VHL, fumarate dehydrogenase, and TFE3 genes were detected. We conclude that PRCCM is a rare but challenging subtype of RCC that deserves to be further studied. In all the tumors, the mucin-like material was found in those stained with mucicarmin, but other conventional and immunohistochemical stains did not reveal consistent features of a single mucin. The molecular-genetic profile of these tumors was most consistent with that of typical papillary RCC, although one case had mixed genetic features of papillary and clear RCC. PRCCM has metastatic potential, as evidenced by

  8. Genetically encoded Ca2+ indicators: using genetics and molecular design to understand complex physiology

    PubMed Central

    Kotlikoff, Michael I

    2007-01-01

    This article reviews genetically encoded Ca2+ indicators (GECIs), with a focus on the use of these novel molecules in the context of understanding complex cell signalling in mammals, in vivo. The review focuses on the advantages and limitations of specific GECI design strategies and the results of experiments in which these molecules have been expressed in transgenic mice, concentrating particularly on recent experiments from our laboratory in which physiological signalling could be monitored in vivo. Finally, newer strategies for effective genetic specification of GECIs are briefly reviewed. PMID:17038427

  9. Molecular Genetic Analysis of Activation-tagged Transcription Factors Thought to be Involved in Photomorphogenesis

    SciTech Connect

    Neff, Michael

    2011-06-23

    Plants utilize light as a source of information via families of photoreceptors such as the red/far-red absorbing phytochromes (PHY) and the blue/UVA absorbing cryptochromes (CRY). The main goal of the Neff lab is to use molecular-genetic mutant screens to elucidate signaling components downstream of these photoreceptors. Activation-tagging mutagenesis led to the identification of two putative transcription factors that may be involved in both photomorphogenesis and hormone signaling pathways. sob1-D (suppressor of phyB-dominant) mutant phenotypes are caused by the over-expression of a Dof transcription factor previously named OBP3. Our previous studies indicate that OBP3 is a negative regulator of light-mediated cotyledon expansion and may be involved in modulating responsiveness to the growth-regulating hormone auxin. The sob2-D mutant uncovers a role for LEP, a putative AP2/EREBP-like transcription factor, in seed germination, hypocotyl elongation and responsiveness to the hormone abscisic acid. Based on photobiological and genetic analysis of OBP3-knockdown and LEP-null mutations, we hypothesize that these transcription factors are involved in both light-mediated seedling development and hormone signaling. To examine the role that these genes play in photomorphogenesis we will: 1) Further explore the genetic role of OBP3 in cotyledon/leaf expansion and other photomorphogenic processes as well as examine potential physical interactions between OBP3 and CRY1 or other signaling components that genetically interact with this transcription factor 2) Test the hypothesis that OBP3 is genetically involved in auxin signaling and root development as well as examine the affects of this hormone and light on OBP3 protein accumulation. 3) Test the hypothesis that LEP is involved in seed germination, seedling photomorphogenesis and hormone signaling. Together these experiments will lead to a greater understanding of the complexity of interactions between photoreceptors and DNA

  10. Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and pleura: therapeutic targets.

    PubMed

    Motadi, L R; Misso, N L; Dlamini, Z; Bhoola, K D

    2007-12-20

    Cancers of the lung and pleura remain a major cause of cancer deaths, both in men and women, with strong causal relationships between cigarette smoking and asbestos fibres, and deaths from lung cancer and mesothelioma, respectively. The poor survival rates for small cell lung cancer and mesotheliomas argue powerfully for greater understanding of mechanisms of carcinogenesis, genetic abnormalities and the role of tumour suppressor genes and proteins in carcinomas of the lung and pleura. Despite progress in the development of newer cytotoxic drugs, lung cancer remains a lethal disease. Chemotherapy and radiotherapy produce only a modest improvement in survival of patients with advanced disease. Increased knowledge of molecular mechanisms of lung cancer and apoptosis are providing opportunities for treating lung cancer with new classes of molecularly targeted drugs. These novel therapies should target the abnormalities in lung cancer by maximizing the effects of anti-tumour molecules, with minimal side effects on normal tissues. Of the several molecular targets, those receiving attention are p53 gene replacement, Bcl-2 downregulation, apoptosis by induced by TNF, the FAS/CD95 receptor system and TRAIL, and inhibition of NF-kappaB. Although several studies have shown benefits, there is a need for well planned clinical trials of drugs that target the apoptotic cascade. Stem cell therapy and gene replacement offer the prospect of novel approaches that are likely in the near future to play a definitive role in the treatment of advanced lung cancer. Furthermore, with their apparent minimal toxicity to normal tissues, the newer molecular targets represent attractive investigational directions for innovative cancer therapies. PMID:18039530

  11. Radiation mutagenesis from molecular and genetic points of view

    SciTech Connect

    Chen, D.J.C.; Park, M.S.; Okinaka, R.T.; Jaberaboansari, A.

    1993-02-01

    An important biological effect of ionizing radiation on living organisms is mutation induction. Mutation is also a primary event in the etiology of cancer. The chain events, from induction of DNA damage by ionizing radiation to processing of these damages by the cellular repair/replication machinery, that lead to mutation are not well understood. The development of quantitative methods for measuring mutation-induction, such as the HPRT system, in cultured mammalian cells has provided an estimate of the mutagenic effects of x- and {gamma}-rays as wen as of high LET radiation in both rodent and human cells. A major conclusion from these mutagenesis data is that high LET radiation induces mutations more efficiently than g-rays. Molecular analysis of mutations induced by sparsely ionizing radiation have detected major structural alterations at the gene level. Our molecular results based on analysis of human HPRT deficient mutants induced by {gamma}-rays, {alpha}-particles and high energy charged particles indicate that higher LET radiation induce more total and large deletion mutations than {gamma}-rays. Utilizing molecular techniques including polymerase chain reaction (PCR), Single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE) and Direct DNA sequencing, mutational spectra induced by ionizing radiation have been compared in different cell systems. Attempts have also been made to determine the mutagenic potential and the nature of mutation induced by low dose rate {gamma}-rays. Defective repair, in the form of either a diminished capability for repair or inaccurate repair, can lead to increased risk of heritable mutations from radiation exposure. Therefore, the effects of DNA repair deficiency on the mutation induction in mammalian cells is reviewed.

  12. Radiation mutagenesis from molecular and genetic points of view

    SciTech Connect

    Chen, D.J.C.; Park, M.S.; Okinaka, R.T.; Jaberaboansari, A.

    1993-01-01

    An important biological effect of ionizing radiation on living organisms is mutation induction. Mutation is also a primary event in the etiology of cancer. The chain events, from induction of DNA damage by ionizing radiation to processing of these damages by the cellular repair/replication machinery, that lead to mutation are not well understood. The development of quantitative methods for measuring mutation-induction, such as the HPRT system, in cultured mammalian cells has provided an estimate of the mutagenic effects of x- and [gamma]-rays as wen as of high LET radiation in both rodent and human cells. A major conclusion from these mutagenesis data is that high LET radiation induces mutations more efficiently than g-rays. Molecular analysis of mutations induced by sparsely ionizing radiation have detected major structural alterations at the gene level. Our molecular results based on analysis of human HPRT deficient mutants induced by [gamma]-rays, [alpha]-particles and high energy charged particles indicate that higher LET radiation induce more total and large deletion mutations than [gamma]-rays. Utilizing molecular techniques including polymerase chain reaction (PCR), Single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE) and Direct DNA sequencing, mutational spectra induced by ionizing radiation have been compared in different cell systems. Attempts have also been made to determine the mutagenic potential and the nature of mutation induced by low dose rate [gamma]-rays. Defective repair, in the form of either a diminished capability for repair or inaccurate repair, can lead to increased risk of heritable mutations from radiation exposure. Therefore, the effects of DNA repair deficiency on the mutation induction in mammalian cells is reviewed.

  13. The Molecular Genetics of Fluoroquinolone Resistance in Mycobacterium tuberculosis.

    PubMed

    Mayer, Claudine; Takiff, Howard

    2014-08-01

    The fluoroquinolones (FQs) are synthetic antibiotics effectively used for curing patients with multidrug-resistant tuberculosis (TB). When a multidrug-resistant strain develops resistance to the FQs, as in extensively drug-resistant strains, obtaining a cure is much more difficult, and molecular methods can help by rapidly identifying resistance-causing mutations. The only mutations proven to confer FQ resistance in M. tuberculosis occur in the FQ target, the DNA gyrase, at critical amino acids from both the gyrase A and B subunits that form the FQ binding pocket. GyrA substitutions are much more common and generally confer higher levels of resistance than those in GyrB. Molecular techniques to detect resistance mutations have suboptimal sensitivity because gyrase mutations are not detected in a variable percentage of phenotypically resistant strains. The inability to find gyrase mutations may be explained by heteroresistance: bacilli with a resistance-conferring mutation are present only in a minority of the bacterial population (>1%) and are therefore detected by the proportion method, but not in a sufficient percentage to be reliably detected by molecular techniques. Alternative FQ resistance mechanisms in other bacteria--efflux pumps, pentapeptide proteins, or enzymes that inactivate the FQs--have not yet been demonstrated in FQ-resistant M. tuberculosis but may contribute to intrinsic levels of resistance to the FQs or induced tolerance leading to more frequent gyrase mutations. Moxifloxacin is currently the best anti-TB FQ and is being tested for use with other new drugs in shorter first-line regimens to cure drug-susceptible TB. PMID:26104201

  14. Physiological, Molecular and Genetic Mechanisms of Long-Term Habituation

    SciTech Connect

    Calin-Jageman, Robert J

    2009-09-12

    Work funded on this grant has explored the mechanisms of long-term habituation, a ubiquitous form of learning that plays a key role in basic cognitive functioning. Specifically, behavioral, physiological, and molecular mechanisms of habituation have been explored using a simple model system, the tail-elicited siphon-withdrawal reflex (T-SWR) in the marine mollusk Aplysia californica. Substantial progress has been made on the first and third aims, providing some fundamental insights into the mechanisms by which memories are stored. We have characterized the physiological correlates of short- and long-term habituation. We found that short-term habituation is accompanied by a robust sensory adaptation, whereas long-term habituation is accompanied by alterations in sensory and interneuron synaptic efficacy. Thus, our data indicates memories can be shifted between different sites in a neural network as they are consolidated from short to long term. At the molecular level, we have accomplished microarray analysis comparing gene expression in both habituated and control ganglia. We have identified a network of putatively regulated transcripts that seems particularly targeted towards synaptic changes (e.g. SNAP25, calmodulin) . We are now beginning additional work to confirm regulation of these transcripts and build a more detailed understanding of the cascade of molecular events leading to the permanent storage of long-term memories. On the third aim, we have fostered a nascent neuroscience program via a variety of successful initiatives. We have funded over 11 undergraduate neuroscience scholars, several of whom have been recognized at national and regional levels for their research. We have also conducted a pioneering summer research program for community college students which is helping enhance access of underrepresented groups to life science careers. Despite minimal progress on the second aim, this project has provided a) novel insight into the network mechanisms by

  15. Molecular genetics and the evolution of ultraviolet vision in vertebrates

    PubMed Central

    Shi, Yongsheng; Radlwimmer, F. Bernhard; Yokoyama, Shozo

    2001-01-01

    Despite the biological importance of UV vision, its molecular bases are not well understood. Here, we present evidence that UV vision in vertebrates is determined by eight specific amino acids in the UV pigments. Amino acid sequence analyses show that contemporary UV pigments inherited their UV sensitivities from the vertebrate ancestor by retaining most of these eight amino acids. In the avian lineage, the ancestral pigment lost UV sensitivity, but some descendants regained it by one amino acid change. Our results also strongly support the hypothesis that UV pigments have an unprotonated Schiff base-linked chromophore. PMID:11573008

  16. The Relevance of HLA Sequencing in Population Genetics Studies

    PubMed Central

    Sanchez-Mazas, Alicia

    2014-01-01

    Next generation sequencing (NGS) is currently being adapted by different biotechnological platforms to the standard typing method for HLA polymorphism, the huge diversity of which makes this initiative particularly challenging. Boosting the molecular characterization of the HLA genes through efficient, rapid, and low-cost technologies is expected to amplify the success of tissue transplantation by enabling us to find donor-recipient matching for rare phenotypes. But the application of NGS technologies to the molecular mapping of the MHC region also anticipates essential changes in population genetic studies. Huge amounts of HLA sequence data will be available in the next years for different populations, with the potential to change our understanding of HLA variation in humans. In this review, we first explain how HLA sequencing allows a better assessment of the HLA diversity in human populations, taking also into account the methodological difficulties it introduces at the statistical level; secondly, we show how analyzing HLA sequence variation may improve our comprehension of population genetic relationships by facilitating the identification of demographic events that marked human evolution; finally, we discuss the interest of both HLA and genome-wide sequencing and genotyping in detecting functionally significant SNPs in the MHC region, the latter having also contributed to the makeup of the HLA molecular diversity observed today. PMID:25126587

  17. [Characteristics of molecular genetics and research progress on mitochondrial diseases].

    PubMed

    Zhang, Meng; Si, Yanmei; Zhao, Juan

    2016-10-01

    Mitochondrial diseases is a group of metabolic disorders caused by abnormal structure and dysfunction of mitochondrial DNA (mtDNA). Abnormalities of mtDNA include point mutations, deletions, and rearrangements and depletion of mtDNA. These may affect the ability of mitochondria to generate energy in cells of various tissues and organs. As many factors are involved in the regulation of mtDNA mutations, most mitochondrial diseases may manifest great genetic heterogeneity and a wide spectrum of clinical manifestations. On the other hand, for the low prevalence of single disease, these disorders may be easily missed or with delayed diagnosis. This review focuses on the pathological mutations and benign variations of mtDNA, and research progress on such disorders. PMID:27577231

  18. Clinical and molecular genetic aspects of hereditary multiple cutaneous leiomyomatosis.

    PubMed

    Badeloe, Sadhanna; Frank, Jorge

    2009-01-01

    Multiple cutaneous and uterine leiomyomatosis syndrome (MCUL; OMIM 150800) is an autosomal dominantly inherited tumor predisposition disorder, characterized by leiomyomas of the skin and uterus. When associated with kidney cancer, this syndrome is known as hereditary leiomyomatosis and renal cell cancer (HLRCC; OMIM 605839). All disease variants result from heterozygous mutations in the fumarate hydratase (FH) gene. Cutaneous leiomyoma can easily be recognized and confirmed by histological examination. Recognition of these benign skin tumors can lead to the diagnosis of MCUL or HLRCC. Timely diagnosis is crucial for offering affected individuals and families potentially life-saving regular prophylactic screening examinations for renal tumors. Here we provide an overview of clinical and genetic features of this complex tumor syndrome and discuss patient management and current therapeutic strategies. PMID:19939761

  19. Molecular epidemiology and genetic diversity of hepatitis B virus in Ethiopia.

    PubMed

    Hundie, Gadissa Bedada; Raj, V Stalin; Michael, Daniel Gebre; Pas, Suzan D; Osterhaus, Albert D M E; Koopmans, Marion P; Smits, Saskia L; Haagmans, Bart L

    2016-06-01

    Although hepatitis B virus (HBV) infection is hyperendemic in Ethiopia and constitutes a major public health problem, little is known about its genetic diversity, genotypes, and circulation. The aim of this study was to determine the molecular epidemiology and genetic diversity of HBV in Ethiopia, using 391 serum samples collected from HBsAg-positive blood donors living in five different geographic regions. The HBV S/pol gene was amplified, sequenced, and HBV genotypes, subgenotypes, serotypes, and major hydrophilic region (MHR) variants were determined. Phylogenetic analysis of 371 samples (95%) revealed the distribution of genotypes A (78%) and D (22%) in Ethiopia. Further phylogenetic analysis identified one subgenotype (A1) within genotype A, and 4 subgenotypes within genotype D (D1; 1.3%, D2; 55%, D4; 2.5%, and D6; 8.8%). Importantly, 24 isolates (30%) of genotype D formed a novel phylogenetic cluster, distinct from any known D subgenotypes, and two A/D recombinants. Analysis of predicted amino-acid sequences within the HBsAg revealed four serotypes: adw2 (79%), ayw1 (3.1%), ayw2 (7.8%), and ayw3 (11.6%). Subsequent examination of sequences showed that 51 HBV isolates (14%) had mutations in the MHR and 8 isolates (2.2%) in the reverse transcriptase known to confer antiviral resistance. This study provides the first description of HBV genetic diversity in Ethiopia with a predominance of subgenotypes A1 and D2, and also identified HBV isolates that could represent a novel subgenotype. Furthermore, a significant prevalence of HBsAg variants in Ethiopian population is revealed. J. Med. Virol. 88:1035-1043, 2016. © 2015 Wiley Periodicals, Inc. PMID:26629781

  20. A Global Population Genetic Study of Pantala flavescens

    PubMed Central

    Troast, Daniel; Suhling, Frank; Jinguji, Hiroshi; Sahlén, Göran; Ware, Jessica

    2016-01-01

    Among terrestrial arthropods, the dragonfly species Pantala flavescens is remarkable due to their nearly global distribution and extensive migratory ranges; the largest of any known insect. Capable of migrating across oceans, the potential for high rates of gene flow among geographically distant populations is significant. It has been hypothesized that P. flavescens may be a global panmictic population but no sufficient genetic evidence has been collected thus far. Through a population genetic analysis of P. flavescens samples from North America, South America, and Asia, the current study aimed to examine the extent at which gene flow is occurring on a global scale and discusses the implications of the genetic patterns we uncovered on population structure and genetic diversity of the species. This was accomplished using PCR-amplified cytochrome oxidase one (CO1) mitochondrial DNA data to reconstruct phylogenetic trees, a haplotype network, and perform molecular variance analyses. Our results suggested high rates of gene flow are occurring among all included geographic regions; providing the first significant evidence that Pantala flavescens should be considered a global panmictic population. PMID:26934181

  1. A Global Population Genetic Study of Pantala flavescens.

    PubMed

    Troast, Daniel; Suhling, Frank; Jinguji, Hiroshi; Sahlén, Göran; Ware, Jessica

    2016-01-01

    Among terrestrial arthropods, the dragonfly species Pantala flavescens is remarkable due to their nearly global distribution and extensive migratory ranges; the largest of any known insect. Capable of migrating across oceans, the potential for high rates of gene flow among geographically distant populations is significant. It has been hypothesized that P. flavescens may be a global panmictic population but no sufficient genetic evidence has been collected thus far. Through a population genetic analysis of P. flavescens samples from North America, South America, and Asia, the current study aimed to examine the extent at which gene flow is occurring on a global scale and discusses the implications of the genetic patterns we uncovered on population structure and genetic diversity of the species. This was accomplished using PCR-amplified cytochrome oxidase one (CO1) mitochondrial DNA data to reconstruct phylogenetic trees, a haplotype network, and perform molecular variance analyses. Our results suggested high rates of gene flow are occurring among all included geographic regions; providing the first significant evidence that Pantala flavescens should be considered a global panmictic population. PMID:26934181

  2. Molecular and genetic aspects of controlling the soilborne necrotrophic pathogens Rhizoctonia and Pythium.

    PubMed

    Okubara, Patricia A; Dickman, Martin B; Blechl, Ann E

    2014-11-01

    The soilborne necrotrophic pathogens Rhizoctonia and Pythium infect a wide range of crops in the US and worldwide. These pathogens pose challenges to growers because the diseases they cause are not adequately controlled by fungicides, rotation or, for many hosts, natural genetic resistance. Although a combination of management practices are likely to be required for control of Rhizoctonia and Pythium, genetic resistance remains a key missing component. This review discusses the recent deployment of introduced genes and genome-based information for control of Rhizoctonia, with emphasis on three pathosystems: Rhizoctonia solani AG8 and wheat, R. solani AG1-IA and rice, and R. solani AG3 or AG4 and potato. Molecular mechanisms underlying disease suppression will be addressed, if appropriate. Although less is known about genes and factors suppressive to Pythium, pathogen genomics and biological control studies are providing useful leads to effectors and antifungal factors. Prospects for resistance to Rhizoctonia and Pythium spp. will continue to improve with growing knowledge of pathogenicity strategies, host defense gene action relative to the pathogen infection process, and the role of environmental factors on pathogen-host interactions. PMID:25438786

  3. Muscle histopathology in today's era of molecular genetics: Role and limitations

    PubMed Central

    Pant, Ishita; Chaturvedi, Sujata; Bala, Kiran; Kushwaha, Suman

    2015-01-01

    Introduction: Past few decades have seen an increasing application of techniques like electron microscopy, western blotting, and molecular genetics in the evaluation of muscle diseases. However, due to their limited availability, histopathological interpretation of muscle biopsies still remains an important component of diagnostic approach to muscle diseases. A systematic methodology is required in the evaluation and interpretation of muscle biopsies. This study was undertaken to analyze the histopathological spectrum of 164 muscle biopsies and to assess the diagnostic yield of basic histopathological procedures in the work up of muscle biopsy. Materials and Methods: Retrospective analysis was done for 164 cases of muscle biopsies. Step-wise approach was adopted to assess the efficacy of routine stains, enzyme histochemistry, and immunohistochemistry. Based on hematoxylin and rosin (H and E) appearance, biopsies were broadly categorized into destructive, nondestructive but myopathic, and inflammatory morphology. Role of special stains, enzyme, and immunohistochemical stains in each category was then evaluated. Results: On the basis of histopathological features, 164 muscle biopsies were broadly categorized into biopsies with abnormal histopathological features (115) and biopsies with normal histopathology (49). Abnormal muscle biopsies were further categorized into destructive morphology (56.5%), nondestructive but myopathic morphology (30.5%), and inflammatory pathology (13%). A near definitive diagnosis could be made in 115 cases out of 164 muscle biopsies on the basis of routine histopathology, enzyme histochemistry, and immunohistochemistry. Conclusion: Though advanced techniques like electron microscopy, western blotting, and molecular genetics are essential for confirmatory diagnosis, a substantive diagnostic yield can be offered with the basic armamentarium of routine (frozen) stains, enzyme histochemistry, and immunohistochemistry. PMID:26713009

  4. Mutation analysis and molecular genetics of epidermolysis bullosa.

    PubMed

    Pulkkinen, L; Uitto, J

    1999-02-01

    Cutaneous basement membrane zone (BMZ) consists of a number of attachment structures that are critical for stable association of the epidermis to the underlying dermis. These include hemidesmosomes, anchoring filaments and anchoring fibrils which form an interconnecting network extending from the intracellular milieu of basal keratinocytes across the dermal-epidermal basement membrane to the underlying dermis. Aberrations in this network structure, e.g. due to genetic lesions in the corresponding genes, can result in fragility of the skin at the level of the cutaneous BMZ. The prototype of such diseases is epidermolysis bullosa (EB), a heterogeneous group of genodermatoses characterized by fragility and blistering of the skin, often associated with extracutaneous manifestations, and inherited either in an autosomal dominant or autosomal recessive manner. Based on constellations of the phenotypic manifestations, severity of the disease, and the level of tissue separation within the cutaneous BMZ, EB has been divided into clinically distinct subcategories, including the simplex, hemidesmosomal, junctional and dystrophic variants. Elucidation of BMZ gene/protein systems and development of mutation detection strategies have allowed identification of mutations in 10 different BMZ genes which can explain the clinical heterogeneity of EB. These include mutations in the type VII collagen gene (COL7A1) in the dystrophic (severely scarring) forms of EB; mutations in the laminin 5 genes (LAMA3, LAMB3 and LAMC2) in a lethal (Herlitz) variant of junctional EB; aberrations in the type XVII collagen gene (COL17A1) in non-lethal forms of junctional EB; mutations in the alpha6 and beta4 integrin genes in a distinct hemidesmosomal variant of EB with congenital pyloric atresia; and mutations in the plectin gene (PLEC1) in a form of EB associated with late-onset muscular dystrophy. Identification of mutations in these gene/protein systems attests to their critical importance in the

  5. Pitfalls in the molecular genetic diagnosis of Leber hereditary optic neuropathy (LHON).

    PubMed Central

    Johns, D R; Neufeld, M J

    1993-01-01

    Pathogenetic mutations in mtDNA are found in the majority of patients with Leber hereditary optic neuropathy (LHON), and molecular genetic techniques to detect them are important for the diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease. We found a number of mtDNA polymorphisms that occur adjacent to known LHON-associated mutations and that confound their molecular genetic detection. These transition mutations occur at mtDNA nt 11779 (SfaNI site loss, 11778 mutation), nt 3459 (BsaHI site loss, 3460 mutation), nt 15258 (AccI site loss, 15257 mutation), nt 14485 (mismatch primer Sau3AI site loss, 14484 mutation), and nt 13707 (BstNI site loss, 13708 mutation). Molecular genetic detection of the most common pathogenetic mtDNA mutations in LHON, using a single restriction enzyme, may be confounded by adjacent polymorphisms that occur with a false-positive rate of 2%-7%. PMID:8213820

  6. The latest progress in sugarcane molecular genetics research at the USDA-ARS, Sugarcane Research Laboratory

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2005, two sugar molecular genetics tools were developed in the USDA-ARS, Southeast Area, Sugarcane Research Laboratory at Houma, LA. One is the high throughput fluorescence- and capillary electrophoregrams (CE)-based SSR genotyping tool and the other is single pollen collection and SSR genotyping...

  7. Genetics and Faith: Religious Enchantment through Creative Engagement with Molecular Biology

    ERIC Educational Resources Information Center

    Jenkins, Kathleen E.

    2007-01-01

    In this article I develop heuristic types for understanding how the U.S. evangelical Christian subculture engages the newer science of molecular biology as it works to legitimate and enchant religious worldview: 1.) "symbolic engagement," employing genes and DNA as sacred icon; 2.) "disputatious engagement," debating genetic essentialism and…

  8. Molecular genetics of the Wolbachia endosymbionts that infect the parasitoids of tephritid fruit flies.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Limited information exists on the molecular genetics of the Wolbachia endosymbionts that infect the parasitoids of tephritid fruit flies. A better understanding of the bacteria could allow sex ratio manipulations that would improve the mass-rearing of natural enemies. Scientists at the Center for Me...

  9. Genetic Correlations Between Carcass Traits And Molecular Breeding Values In Angus Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This research elucidated genetic relationships between carcass traits, ultrasound indicator traits, and their respective molecular breeding values (MBV). Animals whose MBV data were used to estimate (co)variance components were not previously used in development of the MBV. Results are presented fo...

  10. Merging molecular data for evaluating cross country genetic diversity of pigs.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Integration of molecular data generated by microsatellite panels recommended by FAO around the world should be initiated in order to accomplish objectives stated in the Global Plan of Action for Animal Genetic Resources. To that end microsatellite datasets from U.S. (n=179, including imported Chines...

  11. Pitfalls in the molecular genetic diagnosis of Leber hereditary optic neuropathy (LHON)

    SciTech Connect

    Johns, D.R. ); Neufeld, M.J. )

    1993-10-01

    Pathogenetic mutations in mtDNA are found in the majority of patients with Leber hereditary optic neuropathy (LHON), and molecular genetic techniques to detect them are important for diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease. The authors found a number of mtDNA polymorphisms that occur adjacent to known LHON-associated mutations and that confound their molecular genetic detection. These transition mutations occur at mtDNA nt 11779 (SfaNI site loss, 11778 mutation), nt 3459 (BsaHI site loss, 3460 mutation), nt 15258 (AccI site loss, 15257 mutation), nt 14485 (mismatch primer Sau3AI site loss, 14484 mutation), and nt 13707 (BstNI site loss, 13708 mutation). Molecular genetic detection of the most common pathogenetic mtDNA mutations in LHON, using a single restriction enzyme, may be confounded by adjacent polymorphisms that occur with a false-positive rate of 2%-7%. 19 refs.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  13. The GenTechnique Project: Developing an Open Environment for Learning Molecular Genetics.

    ERIC Educational Resources Information Center

    Calza, R. E.; Meade, J. T.

    1998-01-01

    The GenTechnique project at Washington State University uses a networked learning environment for molecular genetics learning. The project is developing courseware featuring animation, hyper-link controls, and interactive self-assessment exercises focusing on fundamental concepts. The first pilot course featured a Web-based module on DNA…

  14. 76 FR 18227 - Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-01

    ... in the Federal Register of February 7, 2011 (76 FR 6623). In the notice, FDA requested public comment.... Background In the Federal Register of February 7, 2011 (76 FR 6623), FDA published a notice announcing a... HUMAN SERVICES Food and Drug Administration Molecular and Clinical Genetics Panel of the Medical...

  15. Effects of Freshwater Pollution on the Genetics of Zebra Mussels (Dreissena polymorpha) at the Molecular and Population Level

    PubMed Central

    Thomas, Emilia G.; Šrut, Maja; Štambuk, Anamaria; Klobučar, Göran I. V.; Seitz, Alfred; Griebeler, Eva Maria

    2014-01-01

    Revealing long-term effects of contaminants on the genetic structure of organisms inhabiting polluted environments should encompass analyses at the population, molecular, and cellular level. Following this concept, we studied the genetic constitution of zebra mussel populations from a polluted (Dp) and reference sites (Cl) at the river Drava, Croatia, and applied microsatellite and DNA damage analyses (Comet assay, micronucleus test (MNT)). Additionally, mussels from both populations were exposed to polluted wastewater in the laboratory for three days, and DNA damage was analyzed to evaluate acclimatization and genetic adaptation of the investigated populations to the polluted environment. The two populations differed in their genetic constitution. Microsatellite analysis suggested that Dp had undergone a genetic bottleneck. Comet assay did not indicate any difference in DNA damage between the two populations, but MNT revealed that Dp had an increased percentage of micronuclei in hemocytes in comparison to Cl. The laboratory experiment revealed that Dp had a lower percentage of tail DNA and a higher percentage of micronuclei than Cl. These differences between populations were possibly caused by an overall decreased fitness of Dp due to genetic drift and by an enhanced DNA repair mechanism due to acclimatization to pollution in the source habitat. PMID:24883328

  16. Effects of freshwater pollution on the genetics of zebra mussels (Dreissena polymorpha) at the molecular and population level.

    PubMed

    Thomas, Emilia G; Srut, Maja; Stambuk, Anamaria; Klobučar, Göran I V; Seitz, Alfred; Griebeler, Eva Maria

    2014-01-01

    Revealing long-term effects of contaminants on the genetic structure of organisms inhabiting polluted environments should encompass analyses at the population, molecular, and cellular level. Following this concept, we studied the genetic constitution of zebra mussel populations from a polluted (Dp) and reference sites (Cl) at the river Drava, Croatia, and applied microsatellite and DNA damage analyses (Comet assay, micronucleus test (MNT)). Additionally, mussels from both populations were exposed to polluted wastewater in the laboratory for three days, and DNA damage was analyzed to evaluate acclimatization and genetic adaptation of the investigated populations to the polluted environment. The two populations differed in their genetic constitution. Microsatellite analysis suggested that Dp had undergone a genetic bottleneck. Comet assay did not indicate any difference in DNA damage between the two populations, but MNT revealed that Dp had an increased percentage of micronuclei in hemocytes in comparison to Cl. The laboratory experiment revealed that Dp had a lower percentage of tail DNA and a higher percentage of micronuclei than Cl. These differences between populations were possibly caused by an overall decreased fitness of Dp due to genetic drift and by an enhanced DNA repair mechanism due to acclimatization to pollution in the source habitat. PMID:24883328

  17. Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding

    PubMed Central

    Chen, Liang; Mathema, Barun; Chavda, Kalyan D.; DeLeo, Frank R.; Bonomo, Robert A.; Kreiswirth, Barry N.

    2015-01-01

    Klebsiella pneumoniae carbapenemases (KPCs) were first identified in 1996 in the USA. Since then, regional outbreaks of KPC-producing K. pneumoniae have occurred in the USA, and have spread internationally. Dissemination of blaKPC involves both horizontal transfer of blaKPC genes and plasmids, and clonal spread. Of epidemiological significance, the international spread of KPC-producing K. pneumoniae is primarily associated with a single multilocus sequence type (ST), ST258, and its related variants. However, the molecular factors contributing to the success of ST258 largely remain unclear. Here, we review the recent progresses in understanding KPC-producing K. pneumoniae that is contributing to our knowledge of plasmid and genome composition and structure among the KPC epidemic clone, and identify possible factors that influence its epidemiological success. PMID:25304194

  18. [Molecular genetics and determination of time since death - short communication].

    PubMed

    Šaňková, Markéta; Račanská, Michaela

    2016-01-01

    Estimation of time since death, i.e. the post-mortem interval (PMI), is one of the most problematic issues in forensic practice. Accurate determination of the PMI still remains very complicated task even for an experienced forensic pathologist.Physical changes including algor, livor and rigor mortis can be observed already during the first hours after death of an individual. Unfortunately, the estimation of PMI on the basis of these changes is often burdened with a certain degree of inaccuracy, which is caused by the temperature of surrounding environment, constitution of the body, cause of the death, location of the body, drug abuse etc.Accurate PMI estimation requires assessment of such parameters, which change constantly from the moment of death, but independently on ambient factors. According to current research in the field of molecular biology, it appears that a post-mortem degradation of nucleic acids (both DNA and RNA) will correspond to this definition. PMID:27526264

  19. Cullin Family Proteins and Tumorigenesis: Genetic Association and Molecular Mechanisms

    PubMed Central

    Chen, Zhi; Sui, Jie; Zhang, Fan; Zhang, Caiguo

    2015-01-01

    Cullin family proteins function as scaffolds to form numerous E3 ubiquitin ligases with RING proteins, adaptor proteins and substrate recognition receptors. These E3 ligases further recognize numerous substrates to participate in a variety of cellular processes, such as DNA damage and repair, cell death and cell cycle progression. Clinically, cullin-associated E3 ligases have been identified to involve numerous human diseases, especially with regard to multiple cancer types. Over the past few years, our understanding of cullin proteins and their functions in genome stability and tumorigenesis has expanded enormously. Herein, this review briefly provides current perspectives on cullin protein functions, and mainly summarizes and discusses molecular mechanisms of cullin proteins in tumorigenesis. PMID:25663940

  20. The molecular genetics of the telomere biology disorders.

    PubMed

    Bertuch, Alison A

    2016-08-01

    The importance of telomere function for human health is exemplified by a collection of Mendelian disorders referred to as the telomere biology disorders (TBDs), telomeropathies, or syndromes of telomere shortening. Collectively, the TBDs cover a spectrum of conditions from multisystem disease presenting in infancy to isolated disease presentations in adulthood, most notably idiopathic pulmonary fibrosis. Eleven genes have been found mutated in the TBDs to date, each of which is linked to some aspect of telomere maintenance. This review summarizes the molecular defects that result from mutations in these genes, highlighting recent advances, including the addition of PARN to the TBD gene family and the discovery of heterozygous mutations in RTEL1 as a cause of familial pulmonary fibrosis. PMID:26400640

  1. Clinical and molecular genetic features of ARC syndrome.

    PubMed

    Gissen, Paul; Tee, Louise; Johnson, Colin A; Genin, Emmanuelle; Caliebe, Almuth; Chitayat, David; Clericuzio, Carol; Denecke, Jonas; Di Rocco, Maja; Fischler, Björn; FitzPatrick, David; García-Cazorla, Angeles; Guyot, Delphine; Jacquemont, Sebastien; Koletzko, Sibylle; Leheup, Bruno; Mandel, Hanna; Sanseverino, Maria Teresa Vieira; Houwen, Roderick H J; McKiernan, Patrick J; Kelly, Deirdre A; Maher, Eamonn R

    2006-10-01

    Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome (MIM 208085) is an autosomal recessive multisystem disorder that may be associated with germline VPS33B mutations. VPS33B is involved in regulation of vesicular membrane fusion by interacting with SNARE proteins, and evidence of abnormal polarised membrane protein trafficking has been reported in ARC patients. We characterised clinical and molecular features of ARC syndrome in order to identify potential genotype-phenotype correlations. The clinical phenotype of 62 ARC syndrome patients was analysed. In addition to classical features described previously, all patients had severe failure to thrive, which was not adequately explained by the degree of liver disease and 10% had structural cardiac defects. Almost half of the patients who underwent diagnostic organ biopsy (7/16) developed life-threatening haemorrhage. We found that most patients (9/11) who suffered severe haemorrhage (7 post biopsy and 4 spontaneous) had normal platelet count and morphology. Germline VPS33B mutations were detected in 28/35 families (48/62 individuals) with ARC syndrome. Several mutations were restricted to specific ethnic groups. Thus p.Arg438X mutation was common in the UK Pakistani families and haplotyping was consistent with a founder mutation with the most recent common ancestor 900-1,000 years ago. Heterozygosity was found in the VPS33B locus in some cases of ARC providing the first evidence of a possible second ARC syndrome gene. In conclusion we state that molecular diagnosis is possible for most children in whom ARC syndrome is suspected and VPS33B mutation analysis should replace organ biopsy as a first line diagnostic test for ARC syndrome. PMID:16896922

  2. Theoretical Studies of Molecular Spectra

    NASA Technical Reports Server (NTRS)

    McKay, Christopher (Technical Monitor); Freedman, Richard S.

    2002-01-01

    This summary describes the research activities of the principal investigator during the reporting period. The research includes spectroscopy, management of molecular databases, and generation of spectral line profiles and opacity data. The spectroscopy research includes oxygen broadening of nitric oxide (NO), analysis of CO2 spectra, analysis of HNO3 spectra, and analysis of CO spectra.

  3. Molecular and Chemical Genetic Approaches to Developmental Origins of Aging and Disease in Zebrafish

    PubMed Central

    Sasaki, Tomoyuki; Kishi, Shuji

    2013-01-01

    The incidence of diseases increases rapidly with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but mostly inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states in response to different environmental or genetic perturbations. On the one hand, we hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds of adaptive plasticity by chemical genetic approaches, we have been investigating whether any relationship exists between the regulatory mechanisms that function in early development and in senescence using the zebrafish (Danio rerio), a small freshwater fish and a useful model animal for genetic studies. We have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during embryogenesis (“embryonic senescence”), subsequently showing shortened lifespan in adulthoods. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other hand, unexpected senescence-related genes might also be involved in the early developmental process and regulation. The ease of manipulation using the zebrafish system allows us to conduct an exhaustive exploration of novel genes and small molecular compounds that can be linked to the senescence phenotype, and thereby facilitates searching for the evolutionary and developmental origins

  4. Saul R. Korey Lecture. Molecular genetics of Tay-Sachs and related disorders: a personal account.

    PubMed

    Suzuki, K

    1994-07-01

    The history of human genetic lysosomal disorders began in 1881 with the description of what is now known as Tay-Sachs disease. In the early 1960s, when I entered the field while I was a neurology resident, the first phase of studies of lysosomal disorders was being replaced with the second analytical biochemistry phase. Saul Korey, the first Chairman of the Department of Neurology, Albert Einstein College of Medicine, initiated the first integrated approach with a team consisting of clinical neurologists, neuropathologists, electron microscopists, cell biologists, organic chemists, and enzymologists. Despite his tragic death in 1963 in his mid-forties, the field flourished along the line of his vision through the third enzymology phase to the fourth and current molecular biology phase. The concept of Tay-Sachs disease as the only ganglioside storage disease has expanded to two forms of gangliosidoses, GM1- and GM2-gangliosidoses, and the latter into three distinct genetic disorders. Tay-Sachs disease, Sandhoff disease and the GM2 activator protein deficiency. More recently, all three genes coding for the three proteins each responsible for distinct genetic forms of GM2-gangliosidosis--beta-hexosaminidase alpha and beta subunits and the GM2 activator protein--have been cloned and many disease-causing mutations have been identified. We have reached the halfway point in our quest for eventual understanding of the pathogenesis and effective treatment of these disorders, starting from the clinical phenotype through biochemistry to the gene. With this new knowledge on the gene level, we should be tracing the route back to enzymology, biology and pathogenetic mechanism of these disorders in the years to come.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8021707

  5. Molecular Genetics of the RNA Polymerase II General Transcriptional Machinery

    PubMed Central

    Hampsey, Michael

    1998-01-01

    Transcription initiation by RNA polymerase II (RNA pol II) requires interaction between cis-acting promoter elements and trans-acting factors. The eukaryotic promoter consists of core elements, which include the TATA box and other DNA sequences that define transcription start sites, and regulatory elements, which either enhance or repress transcription in a gene-specific manner. The core promoter is the site for assembly of the transcription preinitiation complex, which includes RNA pol II and the general transcription fctors TBP, TFIIB, TFIIE, TFIIF, and TFIIH. Regulatory elements bind gene-specific factors, which affect the rate of transcription by interacting, either directly or indirectly, with components of the general transcriptional machinery. A third class of transcription factors, termed coactivators, is not required for basal transcription in vitro but often mediates activation by a broad spectrum of activators. Accordingly, coactivators are neither gene-specific nor general transcription factors, although gene-specific coactivators have been described in metazoan systems. Transcriptional repressors include both gene-specific and general factors. Similar to coactivators, general transcriptional repressors affect the expression of a broad spectrum of genes yet do not repress all genes. General repressors either act through the core transcriptional machinery or are histone related and presumably affect chromatin function. This review focuses on the global effectors of RNA polymerase II transcription in yeast, including the general transcription factors, the coactivators, and the general repressors. Emphasis is placed on the role that yeast genetics has played in identifying these factors and their associated functions. PMID:9618449

  6. Clinical and Molecular Genetics of the Phosphodiesterases (PDEs)

    PubMed Central

    Azevedo, Monalisa F.; Faucz, Fabio R.; Bimpaki, Eirini; Horvath, Anelia; Levy, Isaac; de Alexandre, Rodrigo B.; Ahmad, Faiyaz; Manganiello, Vincent

    2014-01-01

    Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that have the unique function of terminating cyclic nucleotide signaling by catalyzing the hydrolysis of cAMP and GMP. They are critical regulators of the intracellular concentrations of cAMP and cGMP as well as of their signaling pathways and downstream biological effects. PDEs have been exploited pharmacologically for more than half a century, and some of the most successful drugs worldwide today affect PDE function. Recently, mutations in PDE genes have been identified as causative of certain human genetic diseases; even more recently, functional variants of PDE genes have been suggested to play a potential role in predisposition to tumors and/or cancer, especially in cAMP-sensitive tissues. Mouse models have been developed that point to wide developmental effects of PDEs from heart function to reproduction, to tumors, and beyond. This review brings together knowledge from a variety of disciplines (biochemistry and pharmacology, oncology, endocrinology, and reproductive sciences) with emphasis on recent research on PDEs, how PDEs affect cAMP and cGMP signaling in health and disease, and what pharmacological exploitations of PDEs may be useful in modulating cyclic nucleotide signaling in a way that prevents or treats certain human diseases. PMID:24311737

  7. Primary familial brain calcification: update on molecular genetics.

    PubMed

    Taglia, Ilaria; Bonifati, Vincenzo; Mignarri, Andrea; Dotti, Maria Teresa; Federico, Antonio

    2015-05-01

    Primary familial brain calcification is a neuropsychiatric disorder with calcium deposits in the brain, especially in basal ganglia, cerebellum and subcortical white matter. The disease is characterized by a clinical heterogeneity, with a various combination of symptoms that include movement disorders and psychiatric disturbances; asymptomatic patients have been also reported. To date, three causative genes have been found: SLC20A2, PDGFRB and PDGFB. SLC20A2 gene codes for the 'sodium-dependent phosphate transporter 2' (PiT-2), a cell membrane transporters of inorganic phosphate, involved in Pi uptake by cells and maintenance of Pi body levels. Over 40 pathogenic variants of SLC20A2 have been reported, affecting the regulation of Pi homeostasis. It was hypothesized that SLC20A2 mutations cause brain calcification most likely through haploinsufficiency. PDGFRB encodes for the platelet-derived growth factor receptor-β (PDGFRβ), a cell-surface tyrosine-kinase (RTK) receptor that regulates cell proliferation, migration, survival and differentiation. PDGFB encodes for the 'platelet-derived growth factor beta' (PDGFβ), the ligand of PDGFRβ. The loss of function of PDGFRβ and PDGFβ could lead to the impairment of the pericytes function and blood brain barrier integrity, causing vascular and perivascular calcium accumulation. SLC20A2 accounts for about 40 % of familial form and 14 % of sporadic cases, while PDGFRB and PDGFB mutations are likely rare. However, approximately 50 % of patients are not genetically defined and there should be at least another causative gene. PMID:25686613

  8. [Progress in molecular genetics of generalized epilepsy with febrile seizures plus].

    PubMed

    Sun, Hui Hui; Zhang, Yue Hua

    2008-04-01

    Generalized epilepsy with febrile seizures plus (GEFS+) is a familial inherited epileptic syndrome characterized by phenotypic heterogeneity from the milder febrile seizures to the severest epileptic encephalopathy such as severe myoclonic epilepsy in infancy (SMEI). GEFS+ is a disorder with a genetic heterogeneity. Molecular genetics have revealed that four genes are associated with the pathogenesis of GEFS+. These include mutations in genes encoding subunits of neuronal voltage-gated sodium channels (SCN1A, SCN1B, SCN2A) and gamma(2) subunit of the gamma amino-butyric acid (GABA)(A) receptor (GABRG2). These genes have been confirmed as having a role in autosomal dominant GEFS+ families. In addition, the phenotypes of the affected members may depend on the types and locations of these gene mutations. This review states the molecular genetic progress of GEFS+ in brief. PMID:18458705

  9. Genetic diversity in Treponema pallidum: implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws

    PubMed Central

    Šmajs, David; Norris, Steven J.; Weinstock, George M.

    2013-01-01

    Pathogenic uncultivable treponemes, similar to syphilis-causing Treponema pallidum subspecies pallidum, include T. pallidum ssp. pertenue, T. pallidum ssp. endemicum and Treponema carateum, which cause yaws, bejel and pinta, respectively. Genetic analyses of these pathogens revealed striking similarity among these bacteria and also a high degree of similarity to the rabbit pathogen, T. paraluiscuniculi, a treponeme not infectious to humans. Genome comparisons between pallidum and non-pallidum treponemes revealed genes with potential involvement in human infectivity, whereas comparisons between pallidum and pertenue treponemes identified genes possibly involved in the high invasivity of syphilis treponemes. Genetic variability within syphilis strains is considered as the basis of syphilis molecular epidemiology with potential to detect more virulent strains, whereas genetic variability within a single strain is related to its ability to elude the immune system of the host. Genome analyses also shed light on treponemal evolution and on chromosomal targets for molecular diagnostics of treponemal infections. PMID:22198325

  10. Genetic diversity in Treponema pallidum: implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws.

    PubMed

    Smajs, David; Norris, Steven J; Weinstock, George M

    2012-03-01

    Pathogenic uncultivable treponemes, similar to syphilis-causing Treponema pallidum subspecies pallidum, include T. pallidum ssp. pertenue, T. pallidum ssp. endemicum and Treponema carateum, which cause yaws, bejel and pinta, respectively. Genetic analyses of these pathogens revealed striking similarity among these bacteria and also a high degree of similarity to the rabbit pathogen, Treponema paraluiscuniculi, a treponeme not infectious to humans. Genome comparisons between pallidum and non-pallidum treponemes revealed genes with potential involvement in human infectivity, whereas comparisons between pallidum and pertenue treponemes identified genes possibly involved in the high invasivity of syphilis treponemes. Genetic variability within syphilis strains is considered as the basis of syphilis molecular epidemiology with potential to detect more virulent strains, whereas genetic variability within a single strain is related to its ability to elude the immune system of the host. Genome analyses also shed light on treponemal evolution and on chromosomal targets for molecular diagnostics of treponemal infections. PMID:22198325

  11. 76 FR 6623 - Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Molecular and Clinical Genetics Panel of the Medical Devices... (FDA). The meeting will be open to the public. Name of Committee: Molecular and Clinical Genetics...

  12. Genetically encoded sensors of protein hydrodynamics and molecular proximity

    PubMed Central

    Hoepker, Alexander C.; Wang, Ariel; Le Marois, Alix; Suhling, Klaus; Yan, Yuling; Marriott, Gerard

    2015-01-01

    The specialized light organ of the ponyfish supports the growth of the bioluminescent symbiont Photobacterium leiognathi. The bioluminescence of P. leiognathi is generated within a heteromeric protein complex composed of the bacterial luciferase and a 20-kDa lumazine binding protein (LUMP), which serves as a Förster resonance energy transfer (FRET) acceptor protein, emitting a cyan-colored fluorescence with an unusually long excited state lifetime of 13.6 ns. The long fluorescence lifetime and small mass of LUMP are exploited for the design of highly optimized encoded sensors for quantitative fluorescence anisotropy (FA) measurements of protein hydrodynamics. In particular, large differences in the FA values of the free and target-bound states of LUMP fusions appended with capture sequences of up to 20 kDa are used in quantitative FA imaging and analysis of target proteins. For example, a fusion protein composed of LUMP and a 5-kDa G protein binding domain is used as an FA sensor to quantify the binding of the GTP-bound cell division control protein 42 homolog (Cdc42) (21 kDa) in solution and within Escherichia coli. Additionally, the long fluorescence lifetime and the surface-bound fluorescent cofactor 6,7-dimethyl-8- (1′-dimethyl-ribityl) lumazine in LUMP are utilized in the design of highly optimized FRET probes that use Venus as an acceptor probe. The efficiency of FRET in a zero-length LUMP-Venus fusion is 62% compared to ∼31% in a related CFP-Venus fusion. The improved FRET efficiency obtained by using LUMP as a donor probe is used in the design of a FRET-optimized genetically encoded LUMP-Venus substrate for thrombin. PMID:25931526

  13. Molecular epidemiology, population genetics, and pathogenic role of Helicobacter pylori

    PubMed Central

    Suzuki, Rumiko; Shiota, Seiji; Yamaoka, Yoshio

    2012-01-01

    Helicobacter pylori infection is linked to various gastroduodenal diseases; however, only approximately 20% of infected individuals develop severe diseases. Despite the high prevalence of H. pylori infection in Africa and South Asia, the incidence of gastric cancer in these areas is much lower than in other countries. Furthermore, the incidence of gastric cancer tends to decrease from north to south in East Asia. Such geographic differences in the pathology can be explained, at least in part, by the presence of different types of H. pylori virulence factors, especially cagA, vacA, and the right end of the cag pathogenicity island. The genotype of the virulence genes is also useful as a tool to track human migration utilizing the high genetic diversity and frequent recombination between different H. pylori strains. Multilocus sequence typing (MLST) analysis using 7 housekeeping genes can also help predict the history of human migrations. Population structure analysis based on MLST has revealed 7 modern population types of H. pylori, which derived from 6 ancestral populations. Interestingly, the incidence of gastric cancer is closely related to the distribution of H. pylori populations. The different incidence of gastric cancer can be partly attributed to the different genotypes of H. pylori circulating in different geographic areas. Although approaches by MLST and virulence factors are effective, these methods focus on a small number of genes and may miss information conveyed by the rest of the genome. Genome-wide analyses using DNA microarray or whole-genome sequencing technology give a broad view on the genome of H. pylori. In particular, next-generation sequencers, which can read DNA sequences in less time and at lower costs than Sanger sequencing, enabled us to efficiently investigate not only the evolution of H. pylori, but also novel virulence factors and genomic changes related to drug resistance. PMID:22197766

  14. Knowledge Gaining by Human Genetic Studies on Tuberculosis Susceptibility

    PubMed Central

    Qu, Hui-Qi; Fisher-Hoch, Susan P; McCormick, Joseph B

    2011-01-01

    Tuberculosis (TB) is a serious health issue in the developing world. Lack of knowledge on the etiological mechanisms of TB hinders the development of effective strategies for the treatment or prevention of TB disease. Human genetic study is an indispensable approach to understand the molecular basis of common diseases. Numerous efforts were made to screen the human genome for TB susceptibility by linkage mapping. A large number of candidate-based association studies of TB were performed to examine the association of predicted functional DNA variations in candidate genes. Recently, the first genome-wide association study (GWAS) on TB was reported. The GWAS is a proof-of-principle evidence which justifies the genetic approach to understand TB. Further hypothesis-free efforts on TB research may renovate the traditional idea of TB genetic susceptibility as none of the candidate genes with important roles in containing Mycobacterium tuberculosis (MTB) infection was identified of association with active TB, while the TB-associated loci in the GWAS harbors no gene with function in MTB infection. PMID:21179108

  15. Molecular genetics of the human MHC complement gene cluster.

    PubMed

    Yu, C Y

    1998-01-01

    The human major histocompatibility complex (MHC) complement gene cluster (MCGC) is a highly variable region that is characterized by polymorphisms, variations in gene size and gene number, and associations with diseases. Deficiencies in complement C2 are either due to abolition of C2 protein synthesis by mini-deletions that caused frameshift mutations, or blocked secretion of the C2 protein by single amino acid substitutions. One, two or three C4 genes may be present in a human MCGC haplotype and these genes may code for C4A, C4B, or both. Deficiencies of C4A or C4B proteins are attributed to the expression of identical C4 isotypes or allotypes from the C4 loci, the absence or deletion of a C4 gene, 2-bp insertion at exon 29 or 1-bp deletion at exon 20 that caused frameshift mutations. The C4 genes are either 21 or 14.6 kb in size due to the presence of endogenous retrovirus HERV-K(C4) in the intron 9 of long C4 genes. A deletion or duplication of a C4 gene is always accompanied by its neighboring genes, RP at the 5' region, and CYP21 and TNX at the 3' region. These four genes form a genetic unit termed the RCCX module. In an RCCX bimodular structure, the pseudogene CYP21A, and partially duplicated gene segments TNXA and RP2 are present between the two C4 loci. The RCCX modular variations in gene number and gene size contributed to unequal crossovers and exchanges of polymorphic sequences/mutations, resulting in the homogenization of C4 polymorphisms and acquisitions of deleterious mutations in RP1, C4A, C4B, CYP21B and TNXB genes. RD, SKI2W, DOM3Z and RP1 are the four novel genes found between Bf and C4. RD and Ski2w proteins may be related to RNA splicing, RNA turnover and regulation of translation. The functions of Dom3z and RP1 are being investigated. The complete genomic DNA sequence between C2 and TNX is now available. This should facilitate a complete documentation of polymorphisms, mutations and disease associations for the MCGC. PMID:10072631

  16. Fundamental studies of molecular multiphoton ionization

    SciTech Connect

    Miller, J.C.; Compton, R.N.

    1984-04-01

    For several years the authors have performed fundamental studies of molecular multiphoton ionization (MPI). We will present a potpourri of techniques and results chosen to illustrate the interesting complexities of molecular MPI. Techniques used include time-of-flight mass spectroscopy, photoelectron spectroscopy, supersonic expansion cooling of molecular beams, harmonic generation, two-color laser MPI, and polarization spectroscopy. Whenever possible the relevance of these results to resonance ionization spectroscopy schemes will be delineated. 23 references, 10 figures.

  17. Molecular genetics of root gravitropism and waving in Arabidopsis thaliana

    NASA Technical Reports Server (NTRS)

    Sedbrook, J.; Boonsirichai, K.; Chen, R.; Hilson, P.; Pearlman, R.; Rosen, E.; Rutherford, R.; Batiza, A.; Carroll, K.; Schulz, T.; Masson, P. H.

    1998-01-01

    When Arabidopsis thaliana seedlings grow embedded in an agar-based medium, their roots grow vertically downward. This reflects their ability to sense the gravity vector and to position their tip parallel to it (gravitropism). We have isolated a number of mutations affecting root gravitropism in Arabidopsis thaliana. One of these mutations, named arg1, affects root and hypocotyl gravitropism without promoting defects in starch content or in the ability of seedlings' organs to respond to plant hormones. The ARG1 gene was cloned and shown to code for a protein with a J domain at its amino terminus and a second sequence motif found in several cytoskeleton binding proteins. Mutations in the AGR1 locus promote a strong defect in root gravitropism. Some alleles also confer an increased root resistance to exogenous ethylene and an increased sensitivity to auxin. AGR1 was cloned and found to encode a putative transmembrane protein which might be involved in polar auxin transport, or in regulating the differential growth response to gravistimulation. When Arabidopsis seedlings grow on the surface of agar-based media tilted backward, their roots wave. That wavy pattern of root growth derives from a combined response to gravity, touch and other surface-derived stimuli. It is accompanied by a reversible rotation of the root tip about its axis. A number of mutations affect the presence or the shape of root waves on tilted agar-based surfaces. One of them, wvc1, promotes the formation of compressed root waves under these conditions. The physiological and molecular analyses of this mutant suggest that a tryptophan-derived molecule other than IAA might be an important regulator of the curvature responsible for root waving.

  18. Friedreich’s ataxia: Pathology, pathogenesis, and molecular genetics

    PubMed Central

    Koeppen, Arnulf H.

    2011-01-01

    The pathogenic mutation in Friedreich’s ataxia (FRDA) is a homozygous guanine-adenine-adenine (GAA) trinucleotide repeat expansion on chromosome 9q13 that causes a transcriptional defect of the frataxin gene. Deficiency of frataxin, a small mitochondrial protein, is responsible for all clinical and morphological manifestations of FRDA. This autosomal recessive disease affects central and peripheral nervous systems, heart, skeleton, and endocrine pancreas. Long expansions lead to early onset, severe clinical illness, and death in young adult life. Patients with short expansions have a later onset and a more benign course. Some are not diagnosed during life. The neurological phenotype reflects lesions in dorsal root ganglia (DRG), sensory peripheral nerves, corticospinal tracts, and dentate nuclei (DN). Most patients succumb to cardiomyopathy, and many become diabetic during the course of their disease. This review seeks to reconcile the diverse clinical features with pathological and molecular data. In the pathogenesis of the lesion in DRG, dorsal spinal roots, and sensory peripheral nerves, developmental defects and atrophy occur in combination. The progressive lesion of the DN lacks a known developmental component. Destruction of the DN, optic atrophy, and degeneration of the corticospinal tracts are intrinsic central nervous system lesions. Fiber loss in dorsal columns and spinocerebellar tracts, and atrophy of the neurons in the dorsal nuclei of Clarke are secondary to the lesion in DRG. The role of frataxin deficiency in the pathogenesis of FRDA is still unclear because the protein has multiple functions in the normal state, including biogenesis of iron–sulfur clusters; iron chaperoning; iron storage; and control of iron-mediated oxidative tissue damage. PMID:21315377

  19. Molecular Genetics of Hypophosphatasia and Phenotype-Genotype Correlations.

    PubMed

    Mornet, Etienne

    2015-01-01

    Hypophosphatasia (HPP) is due to deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNAP). This enzyme cleaves extracellular substrates inorganic pyrophosphates (PPi), pyridoxal-5'-phosphate (PLP), phosphoethanolamine (PEA) and nucleotides, and probably other substrates not yet identified. During the last 15 years the role of TNAP in mineralization, and to a less degree in brain, has been investigated, providing hypotheses and explanations for both bone and neuronal HPP phenotypes. ALPL, the gene encoding TNAP, is subject to many mutations, mostly missense mutations. A few number of mutations are recurrently found and may be quite frequent in particular populations. This reflects founder effects. The great variety of mutations results in a great number of compound heterozygous genotypes and in highly variable clinical expressivity. A good correlation was observed between the severity of the disease and in vitro enzymatic activity of the mutant protein measured after site-directed mutagenesis. Many missense mutations found in severe hypophosphatasia produced a mutant protein that failed to reach the cell membrane , was accumulated in the cis-Golgi and was subsequently degraded in the proteasome. Missense mutations located in the catalytic site or in the homodimer interface were often shown by site-directed mutagenesis to have a dominant negative effect. Currently molecular diagnosis of HPP is based on the sequencing of the coding sequence of ALPL that allows detection of approximately 95 % of mutations in severe cases. In addition, other genes, especially genes encoding proteins involved in the regulation of extracellular PPi concentration, could modify the phenotype (modifier genes). PMID:26219705

  20. Principles of genetic variations and molecular diseases: applications in hemophilia A.

    PubMed

    Lannoy, N; Hermans, C

    2016-08-01

    DNA structure alterations are the ultimate source of genetic variations. Without them, evolution would be impossible. While they are essential for DNA diversity, defects in DNA synthesis can lead to numerous genetic diseases. Due to increasingly innovative technologies, our knowledge of the human genome and genetic diseases has grown considerably over the last few years, allowing us to detect another class of variants affecting the chromosomal structure. DNA sequence can be altered in multiple ways: DNA sequence changes by substitution, deletion, or duplication of some nucleotides; chromosomal structure alterations by deletion, duplication, translocation, and inversion, ranging in size from kilobases to mega bases; changes in the cell's genome size. If the alteration is located within a gene and sufficiently deleterious, it can cause genetic disorders. Due to the F8 gene's high rate of new small mutations and its location at the tip of X chromosome, containing high repetitive sequences, a wide variety of genetic variants has been described as the cause of hemophilia A (HA). In addition to the F8 intron 22 repeat inversion, HA can also result from point mutations, other inversions, complex rearrangements, such as duplications or deletions, and transposon insertions causing phenotypes of variable severity characterized by complete or partial deficiency of circulating FVIII. This review aims to present the origins, mechanisms, and consequences of F8 alterations. A sound understanding of the multiple genetic mechanisms responsible for HA is essential to determine the appropriate strategy for molecular diagnosis and detected each type of genetic variant. PMID:27296059

  1. Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update.

    PubMed

    Ramaswamy, S; Musser, J M

    1998-01-01

    Knowledge of the molecular genetic basis of resistance to antituberculous agents has advanced rapidly since we reviewed this topic 3 years ago. Virtually all isolates resistant to rifampin and related rifamycins have a mutation that alters the sequence of a 27-amino-acid region of the beta subunit of ribonucleic acid (RNA) polymerase. Resistance to isoniazid (INH) is more complex. Many resistant organisms have mutations in the katG gene encoding catalase-peroxidase that result in altered enzyme structure. These structural changes apparently result in decreased conversion of INH to a biologically active form. Some INH-resistant organisms also have mutations in the inhA locus or a recently characterized gene (kasA) encoding a beta-ketoacyl-acyl carrier protein synthase. Streptomycin resistance is due mainly to mutations in the 16S rRNA gene or the rpsL gene encoding ribosomal protein S12. Resistance to pyrazinamide in the great majority of organisms is caused by mutations in the gene (pncA) encoding pyrazinamidase that result in diminished enzyme activity. Ethambutol resistance in approximately 60% of organisms is due to amino acid replacements at position 306 of an arabinosyltransferase encoded by the embB gene. Amino acid changes in the A subunit of deoxyribonucleic acid gyrase cause fluoroquinolone resistance in most organisms. Kanamycin resistance is due to nucleotide substitutions in the rrs gene encoding 16S rRNA. Multidrug resistant strains arise by sequential accumulation of resistance mutations for individual drugs. Limited evidence exists indicating that some drug resistant strains with mutations that severely alter catalase-peroxidase activity are less virulent in animal models. A diverse array of strategies is available to assist in rapid detection of drug resistance-associated gene mutations. Although remarkable advances have been made, much remains to be learned about the molecular genetic basis of drug resistance in Mycobacterium tuberculosis. It is

  2. Molecular detection and genetic characterization of kobuviruses and astroviruses in asymptomatic local pigs in East Africa

    PubMed Central

    Okoth, Edward; Junga, Joseph O.; Ogara, William O.; Njahira, Moses N.; Wang, Qiuhong; Vlasova, Anastasia N.; Djikeng, Appolinaire

    2014-01-01

    In this study, swine fecal specimens (n = 251) collected from nursing and weaned piglets raised under smallholder production systems were screened for the presence of kobuviruses by RT-PCR. Porcine kobuviruses were detected in 13.1 % (33/251) of the samples. We demonstrated that porcine kobuvirus infections exist in indigenous pigs in Kenya and Uganda and that the prevalence was higher in young piglets than older pigs: nursing piglets (15 %), post-weaning (3-month-old) pigs (17 %), 4-month-old pigs (10 %). Genetic analysis of the partial RNA-dependent RNA polymerase (RdRp) region (690 nt) revealed that kobuviruses circulating in East Africa are diverse, sharing nucleotide sequence identities ranging from 89.7 to 99.1 % and 88 to 92.3 % among them and with known porcine kobuviruses, respectively. The nucleotide sequence identities between our kobuvirus strains and those of human, bovine and canine kobuviruses were 69.4-70.7 %, 73.1-74.4 % and 67-70.7 %, respectively. Additionally, upon sequencing selected samples that showed consistent 720-bp RT-PCR bands while using the same primer set, we detected porcine astroviruses in our samples belonging to type 2 and type 3 mamastroviruses. To our knowledge, this study reports the first detection and molecular analysis of both porcine kobuviruses and astroviruses in an African region. Further studies are required to determine the role of these viruses in gastrointestinal infections of pigs in this region and to determine the genetic diversity of the circulating strains to develop accurate diagnostic tools and implement appropriate control strategies. PMID:24327095

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

    PubMed

    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. PMID:26161476

  4. Molecular electronics studies by synchrotron radiation

    SciTech Connect

    Wee, Andrew T. S.; Chen Wei; Chi Dongchen; Chen Shi; Wang Li; Gao Xingyu

    2009-01-29

    In molecular electronics research, the molecule-metal interfacial properties crucially control the electronic properties of the devices fabricated. We use synchrotron radiation techniques of PES and NEXAFS, complemented by STM, to study the molecular orientation and interfacial charge transfer processes of model molecule-metal systems.

  5. [Genetic predisposition and Pediatric Acute Respiratory Distress Syndrome: New tools for genetic study].

    PubMed

    Erranz, M Benjamín; Wilhelm, B Jan; Riquelme, V Raquel; Cruces, R Pablo

    2015-01-01

    Acute respiratory distress syndrome (ARDS) is the most severe form of respiratory failure. Theoretically, any acute lung condition can lead to ARDS, but only a small percentage of individuals actually develop the disease. On this basis, genetic factors have been implicated in the risk of developing ARDS. Based on the pathophysiology of this disease, many candidate genes have been evaluated as potential modifiers in patient, as well as in animal models, of ARDS. Recent experimental data and clinical studies suggest that variations of genes involved in key processes of tissue, cellular and molecular lung damage may influence susceptibility and prognosis of ARDS. However, the pathogenesis of pediatric ARDS is complex, and therefore, it can be expected that many genes might contribute. Genetic variations such as single nucleotide polymorphisms and copy-number variations are likely associated with susceptibility to ARDS in children with primary lung injury. Genome-wide association (GWA) studies can objectively examine these variations, and help identify important new genes and pathogenetic pathways for future analysis. This approach might also have diagnostic and therapeutic implications, such as predicting patient risk or developing a personalized therapeutic approach to this serious syndrome. PMID:26235685

  6. Understanding Molecular Genetics through a Drawing-Based Activity

    ERIC Educational Resources Information Center

    Rotbain, Yosi; Marbach-Ad, Gili; Stavy, Ruth

    2005-01-01

    The activity uses drawings typically found in textbooks, engaging students in physical and mental activities such as drawing, painting and figure completion--as well as finding missing words and answering guiding questions. The activity deals with three topics: the structure of DNA, DNA replication and protein synthesis. In this study we…

  7. An Exercise in Molecular Epidemiology: Human Rhinovirus Prevalence and Genetics

    ERIC Educational Resources Information Center

    Albright, Catherine J.; Hall, David J.

    2011-01-01

    Human rhinovirus (HRV) is one of the most common human respiratory pathogens and is responsible for the majority of upper respiratory illnesses. Recently, a phylogeny was constructed from all known American Type Culture Collection (ATCC) HRV sequences. From this study, three HRV classifications (HRVA, HRVB, and HRVC) were determined and techniques…

  8. Genetic analysis of Tunisian families with Usher syndrome type 1: toward improving early molecular diagnosis

    PubMed Central

    Ben-Rebeh, Imen; Bonnet, Crystel; Bouassida, Walid; Hadjamor, Imen; Ayadi, Hammadi; Ghorbel, Abdelmonem; Petit, Christine; Masmoudi, Saber

    2016-01-01

    Purpose Usher syndrome accounts for about 50% of all hereditary deaf-blindness cases. The most severe form of this syndrome, Usher syndrome type I (USH1), is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. Six USH1 genes have been identified, MYO7A, CDH23, PCDH15, USH1C, SANS, and CIB2, encoding myosin VIIA, cadherin-23, protocadherin-15, harmonin, scaffold protein containing ankyrin repeats and a sterile alpha motif (SAM) domain, and calcium- and integrin-binding member 2, respectively. Methods In the present study, we recruited four Tunisian families with a diagnosis of USH1, together with healthy unrelated controls. Affected members underwent detailed audiologic and ocular examinations. We used the North African Deafness (NADf) chip to search for known North African mutations associated with USH. Then, we selected microsatellite markers covering USH1 known loci to genotype the DNA samples. Finally, we performed DNA sequencing of three known USH1 genes: MYO7A, PCDH15, and USH1C. Results Four biallelic mutations, all single base changes, were found in the MYO7A, USH1C, and PCDH15 genes. These mutations consist of a previously reported splicing defect c.470+1G>A in MYO7A, three novel variants, including two nonsense (p.Arg3X and p.Arg134X) in USH1C and PCDH15, respectively, and one frameshift (p.Lys615Asnfs*6) in MYO7A. Conclusions We found a remarkable genetic heterogeneity in the studied families with USH1 with a variety of mutations, among which three were novel. These novel mutations will be included in the NADf mutation screening chip that will allow a higher diagnosis efficiency of this extremely genetically heterogeneous disease. Ultimately, efficient molecular diagnosis of USH in a patient’s early childhood is of utmost importance, allowing better educational and therapeutic management. PMID:27440999

  9. New Insights into the Molecular Epidemiology and Population Genetics of Schistosoma mansoni in Ugandan Pre-school Children and Mothers

    PubMed Central

    Betson, Martha; Sousa-Figueiredo, Jose C.; Kabatereine, Narcis B.; Stothard, J. Russell

    2013-01-01

    Significant numbers of pre-school children are infected with Schistosoma mansoni in sub-Saharan Africa and are likely to play a role in parasite transmission. However, they are currently excluded from control programmes. Molecular phylogenetic studies have provided insights into the evolutionary origins and transmission dynamics of S. mansoni, but there has been no research into schistosome molecular epidemiology in pre-school children. Here, we investigated the genetic diversity and population structure of S. mansoni in pre-school children and mothers living in lakeshore communities in Uganda and monitored for changes over time after praziquantel treatment. Parasites were sampled from children (<6 years) and mothers enrolled in the longitudinal Schistosomiasis Mothers and Infants Study at baseline and at 6-, 12- and 18-month follow-up surveys. 1347 parasites from 35 mothers and 45 children were genotyped by direct sequencing of the cytochrome c oxidase (cox1) gene. The cox1 region was highly diverse with over 230 unique sequences identified. Parasite populations were genetically differentiated between lakes and non-synonymous mutations were more diverse at Lake Victoria than Lake Albert. Surprisingly, parasite populations sampled from children showed a similar genetic diversity to those sampled from mothers, pointing towards a non-linear relationship between duration of exposure and accumulation of parasite diversity. The genetic diversity six months after praziquantel treatment was similar to pre-treatment diversity. Our results confirm the substantial genetic diversity of S. mansoni in East Africa and provide significant insights into transmission dynamics within young children and mothers, important information for schistosomiasis control programmes. PMID:24349589

  10. Applications of Multiple Nuclear Genes to the Molecular Phylogeny, Population Genetics and Hybrid Identification in the Mangrove Genus Rhizophora

    PubMed Central

    Chen, Yongmei; Hou, Yansong; Guo, Zixiao; Wang, Wenqing; Zhong, Cairong; Zhou, Renchao; Shi, Suhua

    2015-01-01

    The genus Rhizophora is one of the most important components of mangrove forests. It is an ideal system for studying biogeography, molecular evolution, population genetics, hybridization and conservation genetics of mangroves. However, there are no sufficient molecular markers to address these topics. Here, we developed 77 pairs of nuclear gene primers, which showed successful PCR amplifications across all five Rhizophora species and sequencing in R. apiculata. Here, we present three tentative applications using a subset of the developed nuclear genes to (I) reconstruct the phylogeny, (II) examine the genetic structure and (III) identify natural hybridization in Rhizophora. Phylogenetic analyses support the hypothesis that Rhizophora had disappeared in the Atlantic-East Pacific (AEP) region and was re-colonized from the IWP region approximately 12.7 Mya. Population genetics analyses in four natural populations of R. apiculata in Hainan, China, revealed extremely low genetic diversity, strong population differentiation and extensive admixture, suggesting that the Pleistocene glaciations, particularly the last glacial maximum, greatly influenced the population dynamics of R. apiculata in Hainan. We also verified the hybrid status of a morphologically intermediate individual between R. apiculata and R. stylosa in Hainan. Based on the sequences of five nuclear genes and one chloroplast intergenic spacer, this individual is likely to be an F1 hybrid, with R. stylosa as its maternal parent. The nuclear gene markers developed in this study should be of great value for characterizing the hybridization and introgression patterns in other cases of this genus and testing the role of natural selection using population genomics approaches. PMID:26674070

  11. Applications of Multiple Nuclear Genes to the Molecular Phylogeny, Population Genetics and Hybrid Identification in the Mangrove Genus Rhizophora.

    PubMed

    Chen, Yongmei; Hou, Yansong; Guo, Zixiao; Wang, Wenqing; Zhong, Cairong; Zhou, Renchao; Shi, Suhua

    2015-01-01

    The genus Rhizophora is one of the most important components of mangrove forests. It is an ideal system for studying biogeography, molecular evolution, population genetics, hybridization and conservation genetics of mangroves. However, there are no sufficient molecular markers to address these topics. Here, we developed 77 pairs of nuclear gene primers, which showed successful PCR amplifications across all five Rhizophora species and sequencing in R. apiculata. Here, we present three tentative applications using a subset of the developed nuclear genes to (I) reconstruct the phylogeny, (II) examine the genetic structure and (III) identify natural hybridization in Rhizophora. Phylogenetic analyses support the hypothesis that Rhizophora had disappeared in the Atlantic-East Pacific (AEP) region and was re-colonized from the IWP region approximately 12.7 Mya. Population genetics analyses in four natural populations of R. apiculata in Hainan, China, revealed extremely low genetic diversity, strong population differentiation and extensive admixture, suggesting that the Pleistocene glaciations, particularly the last glacial maximum, greatly influenced the population dynamics of R. apiculata in Hainan. We also verified the hybrid status of a morphologically intermediate individual between R. apiculata and R. stylosa in Hainan. Based on the sequences of five nuclear genes and one chloroplast intergenic spacer, this individual is likely to be an F1 hybrid, with R. stylosa as its maternal parent. The nuclear gene markers developed in this study should be of great value for characterizing the hybridization and introgression patterns in other cases of this genus and testing the role of natural selection using population genomics approaches. PMID:26674070

  12. Association between Maternal Fish Consumption and Gestational Weight Gain: Influence of Molecular Genetic Predisposition to Obesity

    PubMed Central

    Larsen, Sofus C.; Ängquist, Lars; Laurin, Charles; Morgen, Camilla S.; Jakobsen, Marianne U.; Paternoster, Lavinia; Smith, George Davey; Olsen, Sjurdur F.; Sørensen, Thorkild I. A.; Nohr, Ellen A.

    2016-01-01

    Background Studies suggest that fish consumption can restrict weight gain. However, little is known about how fish consumption affects gestational weight gain (GWG), and whether this relationship depends on genetic makeup. Objective To examine the association between fish consumption and GWG, and whether this relationship is dependent on molecular genetic predisposition to obesity. Design A nested case-cohort study based on the Danish National Birth Cohort (DNBC) sampling the most obese women (n = 990) and a random sample of the remaining participants (n = 1,128). Replication of statistically significant findings was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 4,841). We included 32 body mass index (BMI) associated single nucleotide polymorphisms (SNPs) and 5 SNPs found associated with GWG. BMI associated SNPs were combined in a genetic risk score (GRS). Associations between consumption of fish, GRS or individual variants and GWG were analysed, and interactions between fish and the GRS or individual variants were examined. Results In the DNBC, each portion/week (150 g) of fatty fish was associated with a higher GWG of 0.58 kg (95% CI: 0.16, 0.99, P<0.01). For total fish and lean fish, similar patterns were observed, but these associations were not statistically significant. We found no association between GRS and GWG, and no interactions between GRS and dietary fish on GWG. However, we found an interaction between the PPARG Pro12Ala variant and dietary fish. Each additional Pro12Ala G-allele was associated with a GWG of -0.83 kg (95% CI: -1.29, -0.37, P<0.01) per portion/week of dietary fish, with the same pattern for both lean and fatty fish. In ALSPAC, we were unable to replicate these findings. Conclusion We found no consistent evidence of association between fish consumption and GWG, and our results indicate that the association between dietary fish and GWG has little or no dependency on GRS or individual SNPs. PMID:26930408

  13. Cytogenetic and Molecular Genetic Characterization of Children with Short Stature

    PubMed Central

    HOVNIK, Tinka; ŠMIGOC SCHWEIGER, Darja; KOTNIK, Primož; KOVAČ, Jernej; BATTELINO, Tadej; TREBUŠAK PODKRAJŠEK, Katarina

    2015-01-01

    Background The deficiency of SHOX gene (short stature homeobox-containing gene) has been recognized as the most frequent monogenetic cause of short stature. SHOX gene has been associated with short stature in Turner syndrome and Leri Weill dyschondrosteosis as well with non-syndromic idiopathic short stature. The aim of this study was to determine the frequency of SHOX deletions and mutations in a cohort of Slovenian children with short stature, and to delineate indications for routine SHOX gene mutation screening. Methods and results 40 selected subjects with idiopathic short stature were screened for entire SHOX gene deletion and for mutations in the SHOX gene coding region (exon 2 to 6), together with sequences flanking the exon-intron boundaries. FISH analysis on metaphase and interphase spreads revealed no entire gene deletion. Additionally, no pathogenic point mutations or smaller deletion/duplications were identified in this study group. Conclusions SHOX gene deletions and point mutations are not a common cause of idiopathic short stature in a cohort of Slovenian children with short stature. Therefore, the frequency of SHOX mutations must be much lower as expected based on the reported data.

  14. Genetic diversity of Capsicum chinensis (Solanaceae) accessions based on molecular markers and morphological and agronomic traits.

    PubMed

    Finger, F L; Lannes, S D; Schuelter, A R; Doege, J; Comerlato, A P; Gonçalves, L S A; Ferreira, F R A; Clovis, L R; Scapim, C A

    2010-01-01

    We estimated the genetic diversity of 49 accessions of the hot pepper species Capsicum chinensis through analyses of 12 physicochemical traits of the fruit, eight multi-categorical variables, and with 32 RAPD primers. Data from the physicochemical traits were submitted to analysis of variance to estimate the genetic parameters, and their means were clustered by the Scott-Knott test. The matrices from the individual and combined distance were estimated by multivariate analyses before applying Tocher's optimization method. All physicochemical traits were examined for genetic variability by analysis of variance. The responses of these traits showed more contribution from genetic than from environmental factors, except the percentage of dry biomass, content of soluble solids and vitamin C level. Total capsaicin had the greatest genetic divergence. Nine clusters were formed from the quantitative data based on the generalized distance of Mahalanobis, using Tocher's method; four were formed from the multi-categorical data using the Cole-Rodgers coefficient, and eight were formed from the molecular data using the Nei and Li coefficient. The accessions were distributed into 14 groups using Tocher's method, and no significant correlation between pungency and origin was detected. Uni- and multivariate analyses permitted the identification of marked genetic diversity and fruit attributes capable of being improved through breeding programs. PMID:20882481

  15. Mining the human genome after Association for Molecular Pathology v. Myriad Genetics

    PubMed Central

    Evans, Barbara J

    2014-01-01

    The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved—but still imperfect—framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics. Genet Med 16 7, 504–509. PMID:24357850

  16. The role of clinical pharmacology in molecular genetics

    NASA Technical Reports Server (NTRS)

    Robertson, D.

    1997-01-01

    PROBLEM: Discovering the causes of unusual phenotypes in human subjects is an important aspect of patient-oriented research. MATERIAL: The tools of clinical pharmacology are uniquely useful in addressing these problems. PATIENTS, SUBJECTS, OR CASE HISTORIES: We evaluated a 42-year-old patient with lifelong orthostatic hypotension and ptosis of the eyelids. He underwent a series of biochemical, physiological, and pharmacological tests outlined in this article. RESULTS: These studies indicated that sympathetic innervation was intact but that the sympathetic neurotransmitter was dopamine rather than norepinephrine. These results demonstrated that dopamine-beta-hydroxylase deficiency underlies the clinical abnormalities of this patient. CONCLUSION: In selected individuals with unusual phenotypes, the techniques of clinical chemistry and clinical pharmacology can define the nature of the defect at almost the resolution of the human genome.

  17. Drosophila melanogaster as a genetic model system to study neurotransmitter transporters

    PubMed Central

    Martin, Ciara A.; Krantz, David E.

    2014-01-01

    The model genetic organism Drosophila melanogaster, commonly known as the fruit fly, uses many of the same neurotransmitters as mammals and very similar mechanisms of neurotransmitter storage, release and recycling. This system offers a variety of powerful molecular-genetic methods for the study of transporters, many of which would be difficult in mammalian models. We review here progress made using Drosophila to understand the function and regulation of neurotransmitter transporters and discuss future directions for its use. PMID:24704795

  18. Molecular biology and genetics of the acetate-utilizing methanogenic bacteria. Progress report, [July 1, 1988--June 30, 1991

    SciTech Connect

    Gunsalus, R.P.

    1991-12-31

    Acetate conversion to methane and C0{sub 2} by the methanogenic archaebacteria is a primary rate limiting step in anaerobic biodegradative processes in nature. However, the genetic study of these organisms has not been experimentally tractable due to the inability to grow and plate the organisms as single cells, and to extract high molecular weight DNA and RNA without shearing. The acetate-utilizing species, Methanosarcina thermolphila TM-1, is being used for the proposed genetic and molecular studies because, unlike previously described acetotrophic methanosarcina that have a thick heteropolysaccharide cell wall, this species can be cultured in a unicellular form that has a protein cell wall lacking the heteropolysaccharide layer. These cells can be gently disrupted to obtain protoplasts or lysed to yield intact genomic DNA and RNA. Experiments are in progress to develop a gene transfer system in this bacterial species. Methods are being developed and refined for the efficient plating of M. thermophila on defined media, for chemical mutagenesis, and for the isolation of mutants defective in acetate utilization. Chromosomal DNA libraries have been constructed from M. thermophila and are being used to clone genes involved in the acetate utilization pathway (e.g. carbon monoxide dehydrogenase). Once cloned, analysis of the molecular mechanisms responsible for their regulatory control will be performed. These studies should aid our understanding of the pathway for acetate utilization in M. thermophila and serve as a model for elucidating regulatory mechanisms in the acetotrophic methanogens.

  19. Identification of Single-Copy Orthologous Genes between Physalis and Solanum lycopersicum and Analysis of Genetic Diversity in Physalis Using Molecular Markers

    PubMed Central

    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. PMID:23166835

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

    PubMed

    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. PMID:23166835

  1. Genetic studies of freshwater turtle and tortoises: a review of the past 70 years

    USGS Publications Warehouse

    FitzSimmons, Nancy N.; Hart, Kristen M.

    2007-01-01

    Powerful molecular techniques have been developed over many decades for resolving genetic relationships, population genetic structure, patterns of gene flow, mating systems, and the amount of genetic diversity in animals. Genetic studies of turtles were among the earliest and the rapid application of new genetic tools and analytical techniques is still apparent in the literature on turtles. At present, of the 198 freshwater turtles and tortoises that are listed as not extinct by the IUCN Red List, 69 species worldwide are listed as endangered or critically endangered, and an additional 56 species are listed as vulnerable. Of the ca. 300 species of the freshwater turtles and tortoises in the world, ca. 42% are considered to be facing a high risk extinction, and there is a need to focus intense conservation attention on these species. This includes a need to (i) assess our current state of knowledge regarding the application of genetics to studies of freshwater turtles and tortoises and (ii) determine future research directions. Here, we review all available published studies for the past 70 years that were written in English and used genetic markers (e.g. karyotypes, allozymes, DNA loci) to better understand the biology of freshwater turtles and tortoises. We review the types of studies conducted in relation to the species studied and quantify the countries where the studies were performed. We rack the changing use of different genetic markers through time and report on studies focused on aspects of molecular evolution within turtle genomes. We address the usefulness of particular genetic markers to answer phylogenetic questions and present data comparing population genetic structure and mating systems across species. We draw specific attention to whether authors have considered issues to turtle conservation in their research or provided new insights that have been translated into recommendations for conservation management.

  2. Synthetic biology and molecular genetics in non-conventional yeasts: Current tools and future advances.

    PubMed

    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. PMID:26701310

  3. ASM conference report: genetics and molecular biology of industrial microorganisms 1984

    SciTech Connect

    Not Available

    1985-01-01

    The ASM Conference on Genetics and Molecular Biology of Industrial Microorganisms was held Sept. 30 to Oct. 3, 1984 in Bloomington, Indiana. The meetings reflected the progress in applying molecular techniques to the genetic analysis of industrial microorganisms. Topics of discussion included; gene expression in yeasts; the cloning of an Aspergillus sp. gene for glucomylase into S. cerevisiae; the construction of a yeast acentric ring plasmid (YARpl); the cloning of hygromycin resistant genes into Cephalosporium; optimization of gene expression in E. coli; a model for the initiation of translation in E. coli based on experiments with T4rIIb mutants; the role of proteases in protein turnover; evidence indicating which segments on RNAs are needed for the initiation of DNA synthesis; the application of various gene expression systems for the production of vaccines; the sporulation genes of Bacillus; the inducible chloramphenicol resistance found in Bacillus; gene expression in Streptomyces; enzyme activities in Streptomyces; and cloning of genes involved in antibiotic biosynthesis.

  4. Molecular, genetic and stem cell-mediated therapeutic strategies for spinal muscular atrophy (SMA)

    PubMed Central

    Zanetta, Chiara; Riboldi, Giulietta; Nizzardo, Monica; Simone, Chiara; Faravelli, Irene; Bresolin, Nereo; Comi, Giacomo P; Corti, Stefania

    2014-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease. It is the first genetic cause of infant mortality. It is caused by mutations in the survival motor neuron 1 (SMN1) gene, leading to the reduction of SMN protein. The most striking component is the loss of alpha motor neurons in the ventral horn of the spinal cord, resulting in progressive paralysis and eventually premature death. There is no current treatment other than supportive care, although the past decade has seen a striking advancement in understanding of both SMA genetics and molecular mechanisms. A variety of disease modifying interventions are rapidly bridging the translational gap from the laboratory to clinical trials. In this review, we would like to outline the most interesting therapeutic strategies that are currently developing, which are represented by molecular, gene and stem cell-mediated approaches for the treatment of SMA. PMID:24400925

  5. Population Structure, Genetic Diversity and Molecular Marker-Trait Association Analysis for High Temperature Stress Tolerance in Rice

    PubMed Central

    Barik, Saumya Ranjan; Sahoo, Ambika; Mohapatra, Sudipti; Nayak, Deepak Kumar; Mahender, Anumalla; Meher, Jitandriya; Anandan, Annamalai

    2016-01-01

    Rice exhibits enormous genetic diversity, population structure and molecular marker-traits associated with abiotic stress tolerance to high temperature stress. A set of breeding lines and landraces representing 240 germplasm lines were studied. Based on spikelet fertility percent under high temperature, tolerant genotypes were broadly classified into four classes. Genetic diversity indicated a moderate level of genetic base of the population for the trait studied. Wright’s F statistic estimates showed a deviation of Hardy-Weinberg expectation in the population. The analysis of molecular variance revealed 25 percent variation between population, 61 percent among individuals and 14 percent within individuals in the set. The STRUCTURE analysis categorized the entire population into three sub-populations and suggested that most of the landraces in each sub-population had a common primary ancestor with few admix individuals. The composition of materials in the panel showed the presence of many QTLs representing the entire genome for the expression of tolerance. The strongly associated marker RM547 tagged with spikelet fertility under stress and the markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling the high temperature stress tolerance were detected through both mixed linear model and general linear model TASSEL analysis. These markers can be deployed as a resource for marker-assisted breeding program of high temperature stress tolerance. PMID:27494320

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

    PubMed

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

    2015-08-01

    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. PMID:26321587

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

    SciTech Connect

    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.

  8. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes.

    PubMed Central

    Shaw, K J; Rather, P N; Hare, R S; Miller, G H

    1993-01-01

    The three classes of enzymes which inactivate aminoglycosides and lead to bacterial resistance are reviewed. DNA hybridization studies have shown that different genes can encode aminoglycoside-modifying enzymes with identical resistance profiles. Comparisons of the amino acid sequences of 49 aminoglycoside-modifying enzymes have revealed new insights into the evolution and relatedness of these proteins. A preliminary assessment of the amino acids which may be important in binding aminoglycosides was obtained from these data and from the results of mutational analysis of several of the genes encoding aminoglycoside-modifying enzymes. Recent studies have demonstrated that aminoglycoside resistance can emerge as a result of alterations in the regulation of normally quiescent cellular genes or as a result of acquiring genes which may have originated from aminoglycoside-producing organisms or from other resistant organisms. Dissemination of these genes is aided by a variety of genetic elements including integrons, transposons, and broad-host-range plasmids. As knowledge of the molecular structure of these enzymes increases, progress can be made in our understanding of how resistance to new aminoglycosides emerges. Images PMID:8385262

  9. An assessment of molecular pathways of obesity susceptible to nutrient, toxicant and genetically induced epigenetic perturbation.

    PubMed

    Xue, Jing; Ideraabdullah, Folami Y

    2016-04-01

    In recent years, the etiology of human disease has greatly improved with the inclusion of epigenetic mechanisms, in particular as a common link between environment and disease. However, for most diseases we lack a detailed interpretation of the epigenetic regulatory pathways perturbed by environment and causal mechanisms. Here, we focus on recent findings elucidating nutrient-related epigenetic changes linked to obesity. We highlight studies demonstrating that obesity is a complex disease linked to disruption of epigenetically regulated metabolic pathways in the brain, adipose tissue and liver. These pathways regulate (1) homeostatic and hedonic eating behaviors, (2) adipocyte differentiation and fat accumulation, and (3) energy expenditure. By compiling these data, we illustrate that obesity-related phenotypes are repeatedly linked to disruption of critical epigenetic mechanisms that regulate key metabolic genes. These data are supported by genetic mutation of key epigenetic regulators, and many of the diet-induced epigenetic mechanisms of obesity are also perturbed by exposure to environmental toxicants. Identifying similarly perturbed epigenetic mechanisms in multiple experimental models of obesity strengthens the translational applications of these findings. We also discuss many of the ongoing challenges to understanding the role of environmentally induced epigenetic pathways in obesity and suggest future studies to elucidate these roles. This assessment illustrates our current understanding of molecular pathways of obesity that are susceptible to environmental perturbation via epigenetic mechanisms. Thus, it lays the groundwork for dissecting the complex interactions between diet, genes and toxicants that contribute to obesity and obesity-related phenotypes. PMID:27012616

  10. Acrocomia emensis (Arecaceae) genetic structure and diversity using SSR molecular markers.

    PubMed

    Neiva, D S; Melo Júnior, A F; Oliveira, D A; Royo, V A; Brandão, M M; Menezes, E V

    2016-01-01

    Acrocomia emensis, popularly known as the creeping tucum, belongs to the family Arecaceae, and is an oilseed specie of the Brazilian Savannah. The expansion of agricultural activity has rapidly destroyed its natural habitat, leading to a decrease in its population size. Genetic studies can be used to investigate the genetic variability, and may assist with the charting future conservation strategies. In this study the genetic diversity and structure of 150 individuals sampled in three locations in Minas Gerais were analysed, based on the transferability of six microsatellite markers, previously developed for A. aculeata. The results indicate that the populations studied have low levels of genetic variability (Ho = 0.148) and high, positive and significant inbreeding coefficient, indicating an excess of homozygotes. The average heterozygosity within the population (Hs = 0.700) accounted for 95.03% of the total genetic diversity, indicating that there is greater variability within population than between them, consistent with low genetic differentiation between population (GST = 0.046). Bayesian analysis identified three distinct groups; however, populations shared large numbers of alleles, which can be explained by the reduced distance between populations. These results reveal the need to implement genetic conservation programs for the maintenance of this species and to prioritize population from Bonito and Brasília, which showed the lowest values of genetic diversity. PMID:27050985

  11. Analysis of genetic diversity of Persea bombycina "Som" using RAPD-based molecular markers.

    PubMed

    Bhau, Brijmohan Singh; Medhi, Kalyani; Das, Ambrish P; Saikia, Siddhartha P; Neog, Kartik; Choudhury, S N

    2009-08-01

    The utility of RAPD markers in assessing genetic diversity and phenetic relationships in Persea bombycina, a major tree species for golden silk (muga) production, was investigated using 48 genotypes from northeast India. Thirteen RAPD primer combinations generated 93 bands. On average, seven RAPD fragments were amplified per reaction. In a UPGMA phenetic dendrogram based on Jaccard's coefficient, the P. bombycina accessions showed a high level of genetic variation, as indicated by genetic similarity. The grouping in the phenogram was highly consistent, as indicated by high values of cophenetic correlation and high bootstrap values at the key nodes. The accessions were scattered on a plot derived from principal correspondence analysis. The study concluded that the high level of genetic diversity in the P. bombycina accessions may be attributed to the species' outcrossing nature. This study may be useful in identifying diverse genetic stocks of P. bombycina, which may then be conserved on a priority basis. PMID:19424786

  12. Genetically-defined novel oral squamous cell carcinoma cell lines for the development of molecular therapies.

    PubMed

    Fadlullah, Muhammad Zaki Hidayatullah; Chiang, Ivy Kim-Ni; Dionne, Kalen R; Yee, Pei San; Gan, Chai Phei; Sam, Kin Kit; Tiong, Kai Hung; Wen Ng, Adrian Kwok; Martin, Daniel; Lim, Kue Peng; Kallarakkal, Thomas George; Wan Mustafa, Wan Mahadzir; Lau, Shin Hin; Abraham, Mannil Thomas; Zain, Rosnah Binti; Abdul Rahman, Zainal Ariff; Molinolo, Alfredo; Patel, Vyomesh; Gutkind, J Silvio; Tan, Aik Choon; Cheong, Sok Ching

    2016-04-01

    Emerging biological and translational insights from large sequencing efforts underscore the need for genetically-relevant cell lines to study the relationships between genomic alterations of tumors, and therapeutic dependencies. Here, we report a detailed characterization of a novel panel of clinically annotated oral squamous cell carcinoma (OSCC) cell lines, derived from patients with diverse ethnicity and risk habits. Molecular analysis by RNAseq and copy number alterations (CNA) identified that the cell lines harbour CNA that have been previously reported in OSCC, for example focal amplications in 3q, 7p, 8q, 11q, 20q and deletions in 3p, 5q, 8p, 18q. Similarly, our analysis identified the same cohort of frequently mutated genes previously reported in OSCC including TP53, CDKN2A, EPHA2, FAT1, NOTCH1, CASP8 and PIK3CA. Notably, we identified mutations (MLL4, USP9X, ARID2) in cell lines derived from betel quid users that may be associated with this specific risk factor. Gene expression profiles of the ORL lines also aligned with those reported for OSCC. By focusing on those gene expression signatures that are predictive of chemotherapeutic response, we observed that the ORL lines broadly clustered into three groups (cell cycle, xenobiotic metabolism, others). The ORL lines noted to be enriched in cell cycle genes responded preferentially to the CDK1 inhibitor RO3306, by MTT cell viability assay. Overall, our in-depth characterization of clinically annotated ORL lines provides new insight into the molecular alterations synonymous with OSCC, which can facilitate in the identification of biomarkers that can be used to guide diagnosis, prognosis, and treatment of OSCC. PMID:27050151

  13. Molecular characterization and genetic diversity of insecticidal crystal protein genes in native Bacillus thuringiensis isolates.

    PubMed

    Mahadeva Swamy, H M; Asokan, R; Mahmood, Riaz; Nagesha, S N

    2013-04-01

    The Western Ghats of Karnataka natural ecosystem are among the most diverse and is one of the eight hottest hotspots of biological diversity in the world, that runs along the western part of India through four states including Karnataka. Bacillus thuringiensis (Bt) strains were isolated from soils of Western Ghats of Karnataka and characterized by molecular and analytical methods as a result of which 28 new Bt-like isolates were identified. Bt strains were isolated from soil samples using sodium acetate selection method. The morphology of crystals was studied using light and phase contrast microscopy. Isolates were further characterized for insecticidal cry gene by PCR, composition of toxins in bacterial crystals by SDS-PAGE cloning, sequencing and evaluation of toxicity was done. As a result 28 new Bt-like isolates were identified. Majority of the isolates showed the presence of a 55 kDa protein bands on SDS-PAGE while the rest showed 130, 73, 34, and 25 kDa bands. PCR analysis revealed predominance of Coleopteran-active cry genes in these isolates. The variations in the nucleotide sequences, crystal morphology, and mass of crystal protein(s) purified from the Bt isolates revealed genetic and molecular diversity. Three strains containing Coleopteran-active cry genes showed higher activity against larvae Myllocerus undecimpustulatus undatus Marshall (Coleoptera: Curculionidae) than B. thuringiensis subsp. Morrisoni. Results indicated that Bt isolates could be utilized for bioinsecticide production, aiming to reduce the use of chemical insecticide which could be useful to use in integrated pest management to control agriculturally important pests for sustainable crop production. PMID:23207696

  14. Genetics and Molecular Biology of the Electron Flow for Sulfate Respiration in Desulfovibrio

    PubMed Central

    Keller, Kimberly L.; Wall, Judy D.

    2011-01-01

    Progress in the genetic manipulation of the Desulfovibrio strains has provided an opportunity to explore electron flow pathways during sulfate respiration. Most bacteria in this genus couple the oxidation of organic acids or ethanol with the reduction of sulfate, sulfite, or thiosulfate. Both fermentation of pyruvate in the absence of an alternative terminal electron acceptor, disproportionation of fumarate and growth on H2 with CO2 during sulfate reduction are exhibited by some strains. The ability to produce or consume H2 provides Desulfovibrio strains the capacity to participate as either partner in interspecies H2 transfer. Interestingly the mechanisms of energy conversion, pathways of electron flow and the parameters determining the pathways used remain to be elucidated. Recent application of molecular genetic tools for the exploration of the metabolism of Desulfovibrio vulgaris Hildenborough has provided several new datasets that might provide insights and constraints to the electron flow pathways. These datasets include (1) gene expression changes measured in microarrays for cells cultured with different electron donors and acceptors, (2) relative mRNA abundances for cells growing exponentially in defined medium with lactate as carbon source and electron donor plus sulfate as terminal electron acceptor, and (3) a random transposon mutant library selected on medium containing lactate plus sulfate supplemented with yeast extract. Studies of directed mutations eliminating apparent key components, the quinone-interacting membrane-bound oxidoreductase (Qmo) complex, the Type 1 tetraheme cytochrome c3 (Tp1-c3), or the Type 1 cytochrome c3:menaquinone oxidoreductase (Qrc) complex, suggest a greater flexibility in electron flow than previously considered. The new datasets revealed the absence of random transposons in the genes encoding an enzyme with homology to Coo membrane-bound hydrogenase. From this result, we infer that Coo hydrogenase plays an important role

  15. Molecular regulators of nerve conduction - Lessons from inherited neuropathies and rodent genetic models.

    PubMed

    Li, Jun

    2015-05-01

    Myelinated nerve fibers are highly compartmentalized. Helically wrapped lipoprotein membranes of myelin are integrated with subsets of proteins specifically in each compartment to shape the physiological behavior of these nerve fibers. With the advance of molecular biology and genetics, many functions of these proteins have been revealed over the past decade. In this review, we will first discuss how action potential propagation has been understood by classical electrophysiological studies. In particular, the discussion will be concentrated on how the geometric dimensions of myelinated nerve fibers (such as internodal length and myelin thickness) may affect nerve conduction velocity. This discussion will then extend into how specific myelin proteins may shape these geometric parameters, thereby regulating action potential propagation. For instance, periaxin may specifically affect the internodal length, but not other parameters. In contrast, neuregulin-1 may affect myelin thickness, but not axon diameter or internodal length. Finally, we will discuss how these basic neurobiological observations can be applied to inherited peripheral nerve diseases. PMID:25792482

  16. Spinal muscular atrophy type III: Molecular genetic characterization of Turkish patients.

    PubMed

    Bora-Tatar, Gamze; Yesbek-Kaymaz, Ayse; Bekircan-Kurt, Can Ebru; Erdem-Özdamar, Sevim; Erdem-Yurter, Hayat

    2015-12-01

    Spinal Muscular Atrophy (SMA) is a neurodegenerative disease with autosomal recessive inheritance. Homozygous loss of exon 7 of the Survival of motor neuron 1 (SMN1) gene is the main cause of SMA. Although progressive muscle weakness and atrophy are common symptoms, disease severity varies from severe to mild. Type III is one of the milder and less frequent forms of SMA. In this study, we report molecular genetic characteristics of 24 Turkish type III SMA patients. Homozygous loss of SMN1 exon 7 and 8 was analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex ligation dependent probe amplification (MLPA). SMN2, homologue of SMN1, and Neuronal apoptosis inhibitory protein (NAIP) genes were also evaluated considering their influence on disease severity. We determined that male patients who were born in consanguineous families were predominant in our cohort and these patients mostly carry the homozygous loss of SMN1 exon 7 and 8 and four copies of SMN2 gene without NAIP deletions. PMID:26548498

  17. Molecular Regulators of Nerve Conduction - Lessons from Inherited Neuropathies and Rodent Genetic Models

    PubMed Central

    Li, Jun

    2015-01-01

    Myelinated nerve fibers are highly compartmentalized. Helically wrapped lipoprotein membranes of myelin are integrated with subsets of proteins specifically in each compartment to shape the physiological behavior of these nerve fibers. With the advance of molecular biology and genetics, many functions of these proteins have been revealed over the past decade. In this review, we will first discuss how action potential propagation has been understood by classical electrophysiological studies. In particular, the discussion will be concentrated on how the geometric dimensions of myelinated nerve fibers (such as internodal length and myelin thickness) may affect nerve conduction velocity. This discussion will then extend into how specific myelin proteins may shape these geometric parameters, thereby regulating action potential propagation. For instance, periaxin may specifically affect the internodal length, but not other parameters. In contrast, neuregulin-1 may affect myelin thickness, but not axon diameter or internodal length. Finally, we will discuss how these basic neurobiological observations can be applied to inherited peripheral nerve diseases. PMID:25792482

  18. The Genetic and Molecular Basis of O-Antigenic Diversity in Burkholderia pseudomallei Lipopolysaccharide

    PubMed Central

    Tuanyok, Apichai; Stone, Joshua K.; Mayo, Mark; Kaestli, Mirjam; Gruendike, Jeffrey; Georgia, Shalamar; Warrington, Stephanie; Mullins, Travis; Allender, Christopher J.; Wagner, David M.; Chantratita, Narisara; Peacock, Sharon J.; Currie, Bart J.; Keim, Paul

    2012-01-01

    Lipopolysaccharide (LPS) is one of the most important virulence and antigenic components of Burkholderia pseudomallei, the causative agent of melioidosis. LPS diversity in B. pseudomallei has been described as typical, atypical or rough, based upon banding patterns on SDS-PAGE. Here, we studied the genetic and molecular basis of these phenotypic differences. Bioinformatics was used to determine the diversity of genes known or predicted to be involved in biosynthesis of the O-antigenic moiety of LPS in B. pseudomallei and its near-relative species. Multiplex-PCR assays were developed to target diversity of the O-antigen biosynthesis gene patterns or LPS genotypes in B. pseudomallei populations. We found that the typical LPS genotype (LPS genotype A) was highly prevalent in strains from Thailand and other countries in Southeast Asia, whereas the atypical LPS genotype (LPS genotype B) was most often detected in Australian strains (∼13.8%). In addition, we report a novel LPS ladder pattern, a derivative of the atypical LPS phenotype, associated with an uncommon O-antigen biosynthesis gene cluster that is found in only a small B. pseudomallei sub-population. This new LPS group was designated as genotype B2. We also report natural mutations in the O-antigen biosynthesis genes that potentially cause the rough LPS phenotype. We postulate that the diversity of LPS may correlate with differential immunopathogenicity and virulence among B. pseudomallei strains. PMID:22235357

  19. Molecular toolbox for genetic manipulation of the stalked budding bacterium Hyphomonas neptunium.

    PubMed

    Jung, Alexandra; Eisheuer, Sabrina; Cserti, Emöke; Leicht, Oliver; Strobel, Wolfgang; Möll, Andrea; Schlimpert, Susan; Kühn, Juliane; Thanbichler, Martin

    2015-01-01

    The alphaproteobacterium Hyphomonas neptunium proliferates by a unique budding mechanism in which daughter cells emerge from the end of a stalk-like extension emanating from the mother cell body. Studies of this species so far have been hampered by the lack of a genetic system and of molecular tools allowing the regulated expression of target genes. Based on microarray analyses, this work identifies two H. neptunium promoters that are activated specifically by copper and zinc. Functional analyses show that they have low basal activity and a high dynamic range, meeting the requirements for use as a multipurpose expression system. To facilitate their application, the two promoters were incorporated into a set of integrative plasmids, featuring a choice of two different selection markers and various fluorescent protein genes. These constructs enable the straightforward generation and heavy metal-inducible synthesis of fluorescent protein fusions in H. neptunium, thereby opening the door to an in-depth analysis of polar growth and development in this species. PMID:25398860

  20. Molecular Toolbox for Genetic Manipulation of the Stalked Budding Bacterium Hyphomonas neptunium

    PubMed Central

    Jung, Alexandra; Eisheuer, Sabrina; Cserti, Emöke; Leicht, Oliver; Strobel, Wolfgang; Möll, Andrea; Schlimpert, Susan; Kühn, Juliane

    2014-01-01

    The alphaproteobacterium Hyphomonas neptunium proliferates by a unique budding mechanism in which daughter cells emerge from the end of a stalk-like extension emanating from the mother cell body. Studies of this species so far have been hampered by the lack of a genetic system and of molecular tools allowing the regulated expression of target genes. Based on microarray analyses, this work identifies two H. neptunium promoters that are activated specifically by copper and zinc. Functional analyses show that they have low basal activity and a high dynamic range, meeting the requirements for use as a multipurpose expression system. To facilitate their application, the two promoters were incorporated into a set of integrative plasmids, featuring a choice of two different selection markers and various fluorescent protein genes. These constructs enable the straightforward generation and heavy metal-inducible synthesis of fluorescent protein fusions in H. neptunium, thereby opening the door to an in-depth analysis of polar growth and development in this species. PMID:25398860