Scalable human ES culture for therapeutic use: propagation, differentiation, genetic modification and regulatory issues.

PubMed

Rao, M

2008-01-01

Embryonic stem cells unlike most adult stem cell populations can replicate indefinitely while preserving genetic, epigenetic, mitochondrial and functional profiles. ESCs are therefore an excellent candidate cell type for providing a bank of cells for allogenic therapy and for introducing targeted genetic modifications for therapeutic intervention. This ability of prolonged self-renewal of stem cells and the unique advantages that this offers for gene therapy, discovery efforts, cell replacement, personalized medicine and other more direct applications requires the resolution of several important manufacturing, gene targeting and regulatory issues. In this review, we assess some of the advance made in developing scalable culture systems, improvement in vector design and gene insertion technology and the changing regulatory landscape.

Williams syndrome-specific neuroanatomical profile and its associations with behavioral features.

PubMed

Fan, Chun Chieh; Brown, Timothy T; Bartsch, Hauke; Kuperman, Joshua M; Hagler, Donald J; Schork, Andrew; Searcy, Yvonne; Bellugi, Ursula; Halgren, Eric; Dale, Anders M

2017-01-01

Williams Syndrome (WS) is a rare genetic disorder with unique behavioral features. Yet the rareness of WS has limited the number and type of studies that can be conducted in which inferences are made about how neuroanatomical abnormalities mediate behaviors. In this study, we extracted a WS-specific neuroanatomical profile from structural magnetic resonance imaging (MRI) measurements and tested its association with behavioral features of WS. Using a WS adult cohort (22 WS, 16 healthy controls), we modeled a sparse representation of a WS-specific neuroanatomical profile. The predictive performances are robust within the training cohort (10-fold cross-validation, AUC = 1.0) and accurately identify all WS individuals in an independent child WS cohort (seven WS, 59 children with diverse developmental status, AUC = 1.0). The WS-specific neuroanatomical profile includes measurements in the orbitofrontal cortex, superior parietal cortex, Sylvian fissures, and basal ganglia, and variability within these areas related to the underlying size of hemizygous deletion in patients with partial deletions. The profile intensity mediated the overall cognitive impairment as well as personality features related to hypersociability. Our results imply that the unique behaviors in WS were mediated through the constellation of abnormalities in cortical-subcortical circuitry consistent in child WS and adult WS. The robustness of the derived WS-specific neuroanatomical profile also demonstrates the potential utility of our approach in both clinical and research applications.

Trends in Tramadol: Pharmacology, Metabolism, and Misuse.

PubMed

Miotto, Karen; Cho, Arthur K; Khalil, Mohamed A; Blanco, Kirsten; Sasaki, Jun D; Rawson, Richard

2017-01-01

Tramadol is a unique analgesic medication, available in variety of formulations, with both monoaminergic reuptake inhibitory and opioid receptor agonist activity increasingly prescribed worldwide as an alternative for high-affinity opioid medication in the treatment of acute and chronic pain. It is a prodrug that is metabolized by cytochrome P450 (CYP) enzymes CYP2D6 and CYP3A4 to its more potent opioid analgesic metabolites, particularly the O-demethylation product M1. The opioid analgesic potency of a given dose of tramadol is influenced by an individual's CYP genetics, with poor metabolizers experiencing little conversion to the active M1 opioid metabolite and individuals with a high metabolic profile, or ultra-metabolizers, experiencing the greatest opioid analgesic effects. The importance of the CYP metabolism has led to the adoption of computer clinical decision support with pharmacogenomics tools guiding tramadol treatment in major medical centers. Tramadol's simultaneous opioid agonist action and serotonin (5-HT) and norepinephrine reuptake inhibitory effects result in a unique side effect profile and important drug interactions that must be considered. Abrupt cessation of tramadol increases the risk for both opioid and serotonin-norepinephrine reuptake inhibitor withdrawal syndromes. This review provides updated important information on the pharmacology, pharmacokinetics, CYP genetic polymorphisms, drug interactions, toxicity, withdrawal, and illicit use of tramadol.

Impact of human population history on distributions of individual-level genetic distance

PubMed Central

2005-01-01

Summaries of human genomic variation shed light on human evolution and provide a framework for biomedical research. Variation is often summarised in terms of one or a few statistics (eg FST and gene diversity). Now that multilocus genotypes for hundreds of autosomal loci are available for thousands of individuals, new approaches are applicable. Recently, trees of individuals and other clustering approaches have demonstrated the power of an individual-focused analysis. We propose analysing the distributions of genetic distances between individuals. Each distribution, or common ancestry profile (CAP), is unique to an individual, and does not require a priori assignment of individuals to populations. Here, we consider a range of models of population history and, using coalescent simulation, reveal the potential insights gained from a set of CAPs. Information lies in the shapes of individual profiles -- sometimes captured by variance of individual CAPs -- and the variation across profiles. Analysis of short tandem repeat genotype data for over 1,000 individuals from 52 populations is consistent with dramatic differences in population histories across human groups. PMID:15814064

A preliminary assessment of genetic relationships among agronomically important cultivars of black pepper

PubMed Central

Joy, Nisha; Abraham, Z; Soniya, EV

2007-01-01

Background The impact of diseases such as Phytophthora foot rot and the replacement of unproductive cultivars by high yielding ones has brought about the disappearance of varieties in Piper species, like any other crop. Black pepper (King of spices), is a major spice crop consumed throughout the world. It is widely cultivated across various parts of the world apart from India. The different cultivars may be genetically related and could be a source of valuable genes for disease resistance and an increase in quantity and quality. Even though Western Ghats in India is believed to be the site of origin of this crop, numerous accessions from the NBPGR have not yet been evaluated. Our study aims to investigate the genetic relatedness in major cultivars of black pepper using Amplified Fragment Length Polymorphism. Results Amplified Fragment Length Polymorphic (AFLP) DNA analysis was performed in thirty popular cultivars of black pepper from National Bureau of Plant Genetic Resources (NBPGR), India. Fingerprint profiles were generated initially with, five different primer combinations, from which three primer pair combinations (EAGC/MCAA, EAGG/MCTA and EAGC/MCTG) gave consistent and scorable banding patterns. From 173 scorable markers, 158(> 90%) were polymorphic which shows there is considerable variation in the available germplasm. The dendrogram derived by unweighted pair group method analysis (UPGMA) grouped the accessions into three major clusters and four diverse cultivars with only 30% similarity. Karimunda, a widely grown and popular cultivar was unique in the fingerprint profiles obtained. Conclusion There are currently few fingerprinting studies using the valuable spice crop black pepper. We found considerable genetic variability among cultivars of black pepper. Fingerprinting analysis with AFLP proved to be an ideal tool for cultivar identification and phylogenetic studies. It shows the high level of polymorphism and the unique characterization of the major cultivars. An extensive range of similarity value between the cultivars was noted (6.01 to 98.13). Further screening of more cultivars will provide valuable information for current breeding programmes. PMID:17603884

The uses of AFLP for detecting DNA polymorphism, genotype identification and genetic diversity between yeasts isolated from Mexican agave-distilled beverages and from grape musts.

PubMed

Flores Berrios, E P; Alba González, J F; Arrizon Gaviño, J P; Romano, P; Capece, A; Gschaedler Mathis, A

2005-01-01

The objectives were to determine the variability and to compare the genetic diversity obtained using amplified fragment length polymorphism (AFLP) markers in analyses of wine, tequila, mezcal, sotol and raicilla yeasts. A molecular characterization of yeasts isolated from Mexican agave musts, has been performed by AFLP marker analysis, using reference wine strains from Italian and South African regions. A direct co-relation between genetic profile, origin and fermentation process of strains was found especially in strains isolated from agave must. In addition, unique molecular markers were obtained for all the strains using six combination primers, confirming the discriminatory power of AFLP markers. This is the first report of molecular characterization between yeasts isolated from different Mexican traditional agave-distilled beverages, which shows high genetic differences with respect to wine strains.

Assessment of genetic diversity in lettuce (Lactuca sativa L.) germplasm using RAPD markers.

PubMed

Sharma, Shubhangi; Kumar, Pankaj; Gambhir, Geetika; Kumar, Ramesh; Srivastava, D K

2018-01-01

The importance of germplasm characterization is an important link between the conservation and utilization of plant genetic resources in various breeding programmes. In the present study, genetic variability and relationships among 25 Lactuca sativa L. genotypes were tested using random amplified polymorphic DNA (RAPD) molecular markers. A total of 45 random decamer oligonucleotide primers were examined to generate RAPD profiles, out of these reproducible patterns were obtained with 22 primers. A total of 87 amplicon were obtained, out of which all were polymorphic and 7 were unique bands. The level of polymorphism across genotypes was 100% as revealed by RAPD. Genetic similarity matrix, based on Jaccard's coefficients ranged from 13.7 to 84.10% indicating a wide genetic base. Dendrogram was constructed by unweighted pair group method with arithmetic averages method. RAPD technology could be useful for identification of different accessions as well as assessing the genetic similarity among different genotypes of lettuce. The study reveals the limited genetic base and the needs to diversify using new sources from the germplasm.

Unique Features of Ethnic Mongolian Gut Microbiome revealed by metagenomic analysis.

PubMed

Liu, Wenjun; Zhang, Jiachao; Wu, Chunyan; Cai, Shunfeng; Huang, Weiqiang; Chen, Jing; Xi, Xiaoxia; Liang, Zebin; Hou, Qiangchuan; Zhou, Bing; Qin, Nan; Zhang, Heping

2016-10-06

The human gut microbiota varies considerably among world populations due to a variety of factors including genetic background, diet, cultural habits and socioeconomic status. Here we characterized 110 healthy Mongolian adults gut microbiota by shotgun metagenomic sequencing and compared the intestinal microbiome among Mongolians, the Hans and European cohorts. The results showed that the taxonomic profile of intestinal microbiome among cohorts revealed the Actinobaceria and Bifidobacterium were the key microbes contributing to the differences among Mongolians, the Hans and Europeans at the phylum level and genus level, respectively. Metagenomic species analysis indicated that Faecalibacterium prausnitzii and Coprococcus comeswere enrich in Mongolian people which might contribute to gut health through anti-inflammatory properties and butyrate production, respectively. On the other hand, the enriched genus Collinsella, biomarker in symptomatic atherosclerosis patients, might be associated with the high morbidity of cardiovascular and cerebrovascular diseases in Mongolian adults. At the functional level, a unique microbial metabolic pathway profile was present in Mongolian's gut which mainly distributed in amino acid metabolism, carbohydrate metabolism, energy metabolism, lipid metabolism, glycan biosynthesis and metabolism. We can attribute the specific signatures of Mongolian gut microbiome to their unique genotype, dietary habits and living environment.

The potential of tumor-derived exosomes for noninvasive cancer monitoring

PubMed Central

Whiteside, Theresa L.

2016-01-01

Tumor-derived exosomes (TEXs) are emerging as a new type of cancer biomarker. TEXs are membrane-bound, virus-size vesicles of endocytic origin present in all body fluids of cancer patients. Based on the expanding albeit incomplete knowledge of their biogenesis, secretion by tumor cells and cancer cell-specific molecular and genetic contents, TEXs are viewed as promising, clinically-relevant surrogates of cancer progression and response to therapy. Preliminary proteomic, genetic and functional profiling of tumor cell-derived or cancer plasma-derived exosomes confirms their unique characteristics. Alterations in protein or nucleic acid profiles of exosomes in plasma of cancer patients responding to therapies appear to correlate with clinical endpoints. However, methods for TEX isolation and separation from the bulk of human plasma-derived exosomes are not yet established and their role as biomarkers remains to be confirmed. Further development and validation of TEXs as noninvasive, liquid equivalents of tumor biopsies are necessary to move this effort forward. PMID:26289602

The potential of tumor-derived exosomes for noninvasive cancer monitoring.

PubMed

Whiteside, Theresa L

2015-01-01

Tumor-derived exosomes (TEX) are emerging as a new type of cancer biomarker. TEX are membrane-bound, virus-size vesicles of endocytic origin present in all body fluids of cancer patients. Based on the expanding albeit incomplete knowledge of their biogenesis, secretion by tumor cells and cancer cell-specific molecular and genetic contents, TEX are viewed as promising, clinically-relevant surrogates of cancer progression and response to therapy. Preliminary proteomic, genetic and functional profiling of tumor cell-derived or cancer plasma-derived exosomes confirms their unique characteristics. Alterations in protein or nucleic acid profiles of exosomes in plasma of cancer patients responding to therapies appear to correlate with clinical endpoints. However, methods for TEX isolation and separation from the bulk of human plasma-derived exosomes are not yet established and their role as biomarkers remains to be confirmed. Further development and validation of TEX as noninvasive, liquid equivalents of tumor biopsies are necessary to move this effort forward.

Genetic differences in the serum proteome of horses, donkeys and mules are detectable by protein profiling.

PubMed

Henze, Andrea; Aumer, Franziska; Grabner, Arthur; Raila, Jens; Schweigert, Florian J

2011-10-01

Although horses and donkeys belong to the same genus, their genetic characteristics probably result in specific proteomes and post-translational modifications (PTM) of proteins. Since PTM can alter protein properties, specific PTM may contribute to species-specific characteristics. Therefore, the aim of the present study was to analyse differences in serum protein profiles of horses and donkeys as well as mules, which combine the genetic backgrounds of both species. Additionally, changes in PTM of the protein transthyretin (TTR) were analysed. Serum protein profiles of each species (five animals per species) were determined using strong anion exchanger ProteinChips® (Bio-Rad, Munich, Germany) in combination with surface-enhanced laser desorption ionisation-time of flight MS. The PTM of TTR were analysed subsequently by immunoprecipitation in combination with matrix-assisted laser desorption ionisation-time of flight MS. Protein profiling revealed species-specific differences in the proteome, with some protein peaks present in all three species as well as protein peaks that were unique for donkeys and mules, horses and mules or for horses alone. The molecular weight of TTR of horses and donkeys differed by 30 Da, and both species revealed several modified forms of TTR besides the native form. The mass spectra of mules represented a merging of TTR spectra of horses and donkeys. In summary, the present study indicated that there are substantial differences in the proteome of horses and donkeys. Additionally, the results probably indicate that the proteome of mules reveal a higher similarity to donkeys than to horses.

Sleep and rhythm consequences of a genetically induced loss of serotonin.

PubMed

Leu-Semenescu, Smaranda; Arnulf, Isabelle; Decaix, Caroline; Moussa, Fathi; Clot, Fabienne; Boniol, Camille; Touitou, Yvan; Levy, Richard; Vidailhet, Marie; Roze, Emmanuel

2010-03-01

A genetic deficiency in sepiapterin reductase leads to a combined deficit of serotonin and dopamine. The motor phenotype is characterized by a dopa-responsive fluctuating generalized dystonia-parkinsonism. The non-motor symptoms are poorly recognized. In particular, the effects of brain serotonin deficiency on sleep have not been thoroughly studied. We examine the sleep, sleep-wake rhythms, CSF neurotransmitters, and melatonin profile in a patient with sepiapterin reductase deficiency. The patient was a 28-year-old man with fluctuating generalized dystonia-parkinsonism caused by sepiapterin reductase deficiency. A sleep interview, wrist actigraphy, sleep log over 14 days, 48-h continuous sleep and core temperature monitoring, and measurement of CSF neurotransmitters and circadian serum melatonin and cortisol levels before and after treatment with 5-hydroxytryptophan (the precursor of serotonin) and levodopa were performed. Before treatment, the patient had mild hypersomnia with long sleep time (704 min), ultradian sleep-wake rhythm (sleep occurred every 11.8 +/- 5.3 h), organic hyperphagia, attentionlexecutive dysfunction, and no depression. The serotonin metabolism in the CSF was reduced, and the serum melatonin profile was flat, while cortisol and core temperature profiles were normal. Supplementation with 5-hydroxytryptophan, but not with levodopa, normalized serotonin metabolism in the CSF, reduced sleep time to 540 min, normalized the eating disorder and the melatonin profile, restored a circadian sleep-wake rhythm (sleep occurred every 24 +/- 1.7 h, P < 0.0001), and improved cognition. In this unique genetic paradigm, the melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep-wake rhythm.

Identification of Chemical-Genetic Interactions via Parallel Analysis of Barcoded Yeast Strains.

PubMed

Suresh, Sundari; Schlecht, Ulrich; Xu, Weihong; Miranda, Molly; Davis, Ronald W; Nislow, Corey; Giaever, Guri; St Onge, Robert P

2016-09-01

The Yeast Knockout Collection is a complete set of gene deletion strains for the budding yeast, Saccharomyces cerevisiae In each strain, one of approximately 6000 open-reading frames is replaced with a dominant selectable marker flanked by two DNA barcodes. These barcodes, which are unique to each gene, allow the growth of thousands of strains to be individually measured from a single pooled culture. The collection, and other resources that followed, has ushered in a new era in chemical biology, enabling unbiased and systematic identification of chemical-genetic interactions (CGIs) with remarkable ease. CGIs link bioactive compounds to biological processes, and hence can reveal the mechanism of action of growth-inhibitory compounds in vivo, including those of antifungal, antibiotic, and anticancer drugs. The chemogenomic profiling method described here measures the sensitivity induced in yeast heterozygous and homozygous deletion strains in the presence of a chemical inhibitor of growth (termed haploinsufficiency profiling and homozygous profiling, respectively, or HIPHOP). The protocol is both scalable and amenable to automation. After competitive growth of yeast knockout collection cultures, with and without chemical inhibitors, CGIs can be identified and quantified using either array- or sequencing-based approaches as described here. © 2016 Cold Spring Harbor Laboratory Press.

European securitization and biometric identification: the uses of genetic profiling.

PubMed

Johnson, Paul; Williams, Robin

2007-01-01

The recent loss of confidence in textual and verbal methods for validating the identity claims of individual subjects has resulted in growing interest in the use of biometric technologies to establish corporeal uniqueness. Once established, this foundational certainty allows changing biographies and shifting category memberships to be anchored to unchanging bodily surfaces, forms or features. One significant source for this growth has been the "securitization" agendas of nation states that attempt the greater control and monitoring of population movement across geographical borders. Among the wide variety of available biometric schemes, DNA profiling is regarded as a key method for discerning and recording embodied individuality. This paper discusses the current limitations on the use of DNA profiling in civil identification practices and speculates on future uses of the technology with regard to its interoperability with other biometric databasing systems.

Characterization of Colistin-Resistant Escherichia coli Isolated from Diseased Pigs in France

PubMed Central

Delannoy, Sabine; Le Devendec, Laetitia; Jouy, Eric; Fach, Patrick; Drider, Djamel; Kempf, Isabelle

2017-01-01

We studied a collection of 79 colistin-resistant Escherichia coli isolates isolated from diseased pigs in France between 2009 and 2013. We determined a number of phenotypic and genetic characters using broth microdilution to characterize their antimicrobial susceptibility. We performed pulse field gel electrophoresis (PFGE) to assess their genetic diversity and assign them to phylogroups. High-throughput real-time PCR micro-array was used to screen for a selection of genetic markers of virulence, and PCR and sequencing of the main recognized resistance genes allowed us to investigate the mechanisms of colistin resistance. Results showed that isolates belonged to several phylogroups and most had a unique PFGE profile. More than 50% of the isolates were also resistant to sulfonamides, trimethoprim, tetracycline, ampicillin or chloramphenicol. The mcr-1 gene was detected in 70 out of 79 isolates and was transferred by conjugation in 33 of them, sometimes together with resistance to sulfonamides, trimethoprim, tetracycline, ampicillin, chloramphenicol, cefotaxime, or gentamicin. Mutations in the amino-acid sequences of proteins MgrB, PhoP, PhoQ, PmrB, but not PmrA, were detected in isolates with or without the mcr-1 gene. More than one-third of the isolates harbored the F18, F4, astA, hlyA, estI, estII, elt, stx2e, iha, orfA, orfB, paa, terE, ecs1763, or ureD virulence markers. In conclusion, although most isolates had a unique PFGE profile, a few particular combinations of phylogenetic groups, virulence genes and mutations in the sequenced genes involved in colistin resistance were identified on a number of occasions, suggesting the persistence of certain isolates over several years. PMID:29209292

Autism-associated gene expression in peripheral leucocytes commonly observed between subjects with autism and healthy women having autistic children.

PubMed

Kuwano, Yuki; Kamio, Yoko; Kawai, Tomoko; Katsuura, Sakurako; Inada, Naoko; Takaki, Akiko; Rokutan, Kazuhito

2011-01-01

Autism spectrum disorder (ASD) is a severe neuropsychiatric disorder which has complex pathobiology with profound influences of genetic factors in its development. Although the numerous autism susceptible genes were identified, the etiology of autism is not fully explained. Using DNA microarray, we examined gene expression profiling in peripheral blood from 21 individuals in each of the four groups; young adults with ASD, age- and gender-matched healthy subjects (ASD control), healthy mothers having children with ASD (asdMO), and asdMO control. There was no blood relationship between ASD and asdMO. Comparing the ASD group with control, 19 genes were found to be significantly changed. These genes were mainly involved in cell morphology, cellular assembly and organization, and nerve system development and function. In addition, the asdMO group possessed a unique gene expression signature shown as significant alterations of protein synthesis despite of their nonautistic diagnostic status. Moreover, an ASD-associated gene expression signature was commonly observed in both individuals with ASD and asdMO. This unique gene expression profiling detected in peripheral leukocytes from affected subjects with ASD and unaffected mothers having ASD children suggest that a genetic predisposition to ASD may be detectable even in peripheral cells. Altered expression of several autism candidate genes such as FMR-1 and MECP2, could be detected in leukocytes. Taken together, these findings suggest that the ASD-associated genes identified in leukocytes are informative to explore the genetic, epigenetic, and environmental background of ASD and might become potential tools to assess the crucial factors related to the clinical onset of the disorder.

Single-Cell RNA-Seq of Mouse Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic Parkinson Disease.

PubMed

Hook, Paul W; McClymont, Sarah A; Cannon, Gabrielle H; Law, William D; Morton, A Jennifer; Goff, Loyal A; McCallion, Andrew S

2018-03-01

Genetic variation modulating risk of sporadic Parkinson disease (PD) has been primarily explored through genome-wide association studies (GWASs). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal time points. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a postnatal neuroblast population and substantia nigra (SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including genes with known PD associations and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised in Cplx1-null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research. Copyright © 2018 American Society of Human Genetics. All rights reserved.

Genetic variation in Mycobacterium tuberculosis isolates from a London outbreak associated with isoniazid resistance.

PubMed

Satta, Giovanni; Witney, Adam A; Shorten, Robert J; Karlikowska, Magdalena; Lipman, Marc; McHugh, Timothy D

2016-08-16

The largest outbreak of isoniazid-resistant (INH-R) Mycobacterium tuberculosis in Western Europe is centred in North London, with over 400 cases diagnosed since 1995. In the current study, we evaluated the genetic variation in a subset of clinical samples from the outbreak with the hypothesis that these isolates have unique biological characteristics that have served to prolong the outbreak. Fitness assays, mutation rate estimation, and whole-genome sequencing were performed to test for selective advantage and compensatory mutations. This detailed analysis of the genetic variation of these INH-R samples suggests that this outbreak consists of successful, closely related, circulating strains with heterogeneous resistance profiles and little or no associated fitness cost or impact on their mutation rate. Specific deletions and SNPs could be a peculiar feature of these INH-R M. tuberculosis isolates, and could potentially explain their persistence over the years.

Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota.

PubMed

Serino, Matteo; Luche, Elodie; Gres, Sandra; Baylac, Audrey; Bergé, Mathieu; Cenac, Claire; Waget, Aurelie; Klopp, Pascale; Iacovoni, Jason; Klopp, Christophe; Mariette, Jerome; Bouchez, Olivier; Lluch, Jerome; Ouarné, Francoise; Monsan, Pierre; Valet, Philippe; Roques, Christine; Amar, Jacques; Bouloumié, Anne; Théodorou, Vassilia; Burcelin, Remy

2012-04-01

The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an additional group of mice was given a gluco-oligosaccharide (GOS)-supplemented HFD (HFD+GOS). Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibres. The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.

Hereditary Nonpolyposis Colorectal Cancer and Cancer Syndromes: Recent Basic and Clinical Discoveries

PubMed Central

Chen, Erbao; Xu, Xiaojing

2018-01-01

Approximately one-third of individuals diagnosed with colorectal cancer have a family history of cancer, suggesting that CRCs may result from a heritable component. Despite the availability of current gene-identification techniques, only 5% of all CRCs emerge from well-identifiable inherited causes for predisposition, including polyposis and nonpolyposis syndromes. Hereditary nonpolyposis colorectal cancer represents a large proportion of cases, and robustly affected patients are at increased risk for early onset, synchronous, and metachronous colorectal malignancies and extracolonic malignancies. HNPCC encompasses several cancer syndromes, such as Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X, which have remarkable clinical presentations and overlapping genetic profiles that make clinical diagnosis a challenging task. Therefore, distinguishing between the HNPCC disorders is crucial for physicians as an approach to tailor different recommendations for patients and their at-risk family members according to the risks for colonic and extracolonic cancer associated with each syndrome. Identification of these potential patients through epidemiological characteristics and new genetic testing can estimate the individual risk, which informs appropriate cancer screening, surveillance, and/or treatment strategies. In the past three years, many appealing and important advances have been made in our understanding of the relationship between HNPCC and CRC-associated syndromes. The knowledge from the genetic profile of cancer syndromes and unique genotype-phenotype profiles in the different syndromes has changed our cognition. Therefore, this review presents and discusses HNPCC and several common nonpolyposis syndromes with respect to molecular phenotype, histopathologic features, and clinical presentation. PMID:29849630

Genetic Basis of Positive and Negative Symptom Domains in Schizophrenia.

PubMed

Xavier, Rose Mary; Vorderstrasse, Allison

2017-10-01

Schizophrenia is a highly heritable disorder, the genetic etiology of which has been well established. Yet despite significant advances in genetics research, the pathophysiological mechanisms of this disorder largely remain unknown. This gap has been attributed to the complexity of the polygenic disorder, which has a heterogeneous clinical profile. Examining the genetic basis of schizophrenia subphenotypes, such as those based on particular symptoms, is thus a useful strategy for decoding the underlying mechanisms. This review of literature examines the recent advances (from 2011) in genetic exploration of positive and negative symptoms in schizophrenia. We searched electronic databases PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature using key words schizophrenia, symptoms, positive symptoms, negative symptoms, cognition, genetics, genes, genetic predisposition, and genotype in various combinations. We identified 115 articles, which are included in the review. Evidence from these studies, most of which are genetic association studies, identifies shared and unique gene associations for the symptom domains. Genes associated with neurotransmitter systems and neuronal development/maintenance primarily constitute the shared associations. Needed are studies that examine the genetic basis of specific symptoms within the broader domains in addition to functional mechanisms. Such investigations are critical to developing precision treatment and care for individuals afflicted with schizophrenia.

Active BRAF-V600E is the key player in generation of a sessile serrated polyp-specific DNA methylation profile

PubMed Central

Dehghanizadeh, Somaye; Khoddami, Vahid; Mosbruger, Timothy L.; Hammoud, Sue S.; Edes, Kornelia; Berry, Therese S.; Done, Michelle; Samowitz, Wade S.; DiSario, James A.; Luba, Daniel G.; Burt, Randall W.

2018-01-01

Background Sessile serrated polyps (SSPs) have emerged as important precursors for a large number of sporadic colorectal cancers. They are difficult to detect during colonoscopy due to their flat shape and the excessive amounts of secreted mucin that cover the polyps. The underlying genetic and epigenetic basis for the emergence of SSPs is largely unknown with existing genetic studies confined to a limited number of oncogenes and tumor suppressors. A full characterization of the genetic and epigenetic landscape of SSPs would provide insight into their origin and potentially offer new biomarkers useful for detection of SSPs in stool samples. Methods We used a combination of genome-wide mutation detection, exome sequencing and DNA methylation profiling (via methyl-array and whole-genome bisulfite sequencing) to analyze multiple samples of sessile serrated polyps and compared these to familial adenomatous polyps. Results Our analysis revealed BRAF-V600E as the sole recurring somatic mutation in SSPs with no additional major genetic mutations detected. The occurrence of BRAF-V600E was coincident with a unique DNA methylation pattern revealing a set of DNA methylation markers showing significant (~3 to 30 fold) increase in their methylation levels, exclusively in SSP samples. These methylation patterns effectively distinguished sessile serrated polys from adenomatous polyps and did so more effectively than parallel gene expression profiles. Conclusions This study provides an important example of a single oncogenic mutation leading to reproducible global DNA methylation changes. These methylated markers are specific to SSPs and could be of important clinical relevance for the early diagnosis of SSPs using non-invasive approaches such as fecal DNA testing. PMID:29590112

Identification and Characterization of Memecylon Species Using Isozyme Profiling

PubMed Central

Bharathi, T. R.; Sekhar, Shailasree; Geetha, N.; Niranjana, S. R.; Prakash, H. S.

2017-01-01

Background: The protein/isozyme fingerprint is useful in differentiating the species and acts as a biochemical marker for identification and systematic studies of medicinal plant species. Objective: In the present study, protein and isozyme profiles for peroxidase, esterase, acid phosphatase, polyphenol oxidase, alcohol dehydrogenase, and alkaline phosphatase of five species of Memecylon (Melastomataceae), Memecylon umbellatum, Memecylon edule, Memecylon talbotianum, Memecylon malabaricum, and Memecylon wightii were investigated. Materials and Methods: Fresh leaves were used to prepare crude enzyme extract for analyzing the five enzymes isozyme variations. Separation of isozymes was carried out using polyacrylamide gel electrophoresis (PAGE) and the banding patterns of protein were scored. Pair-wise comparisons of genotypes, based on the presence or absence of unique and shared polymorphic products, were used to regenerate similarity coefficients. The similarity coefficients were then used to construct dendrograms, using the unweighted pair group method with arithmetic averages. Results: A total of 50 bands with various Rf values and molecular weight were obtained through PAGE analysis. Among the five Memecylon species, more number of bands was produced in M. wightii and less number of bands was observed in M. edule. The results of similarity indices grouped M. malabaricum and M. wightii in one cluster with 98% similarity and M. umbellatum, M. edule, and M. talbotianum are grouped in another cluster with 79% similarity showing close genetic similarities which is in accordance with the morphological identification of Memecylon species. Conclusion: The protein/isozyme fingerprint is useful in differentiating the species and acts as a biochemical marker for identification of Memecylon species. SUMMARY Biochemical characterization of Memecylon species was evaluated by SDS-PAGE of extracted protein and isozyme profiling on native PAGE.After electrophoresis, each gel was stained with specific stains. Genetic distance relationships were evaluated based on the banding patterns of protein on isozymes.Unique banding pattern of esterase, peroxidase, acid phosphatase, alcohol dehydrogenase and polyphenol oxidase are observed in all the five species of Memecylon, which represent the fingerprint of Memecylon species.SDS-PAGE and isozyme profiling of five Memecylon species revealed that M. malabaricum and M. wightii grouped in one cluster and M. umbellatum, M. edule and M. talbotianum grouped in another cluster showing close genetic similarities which is in accordance with the morphological identification of Memecylon species.This is the first report on the comparison of protein and isozyme profile of five different Memecylon species. Abbreviations Used: SDS-PAGE: Sodium docecyl sulfate polyacrylamide gel electrophoresis; NTSYS PC2: Numerical taxonomy system, version 2.2 for Windows XP, Vista, Win7, Win 8 and Win10 including 64 bit PMID:29263637

Fuel spill identification using solid-phase extraction and solid-phase microextraction. 1. Aviation turbine fuels.

PubMed

Lavine, B K; Brzozowski, D M; Ritter, J; Moores, A J; Mayfield, H T

2001-12-01

The water-soluble fraction of aviation jet fuels is examined using solid-phase extraction and solid-phase microextraction. Gas chromatographic profiles of solid-phase extracts and solid-phase microextracts of the water-soluble fraction of kerosene- and nonkerosene-based jet fuels reveal that each jet fuel possesses a unique profile. Pattern recognition analysis reveals fingerprint patterns within the data characteristic of fuel type. By using a novel genetic algorithm (GA) that emulates human pattern recognition through machine learning, it is possible to identify features characteristic of the chromatographic profile of each fuel class. The pattern recognition GA identifies a set of features that optimize the separation of the fuel classes in a plot of the two largest principal components of the data. Because principal components maximize variance, the bulk of the information encoded by the selected features is primarily about the differences between the fuel classes.

Network Modeling of MDM2 Inhibitor-Oxaliplatin Combination Reveals Biological Synergy in wt-p53 solid tumors

PubMed Central

Azmi, Asfar S.; Banerjee, Sanjeev; Ali, Shadan; Wang, Zhiwei; Bao, Bin; Beck, Frances W.J.; Maitah, Main; Choi, Minsig; Shields, Tony F.; Philip, Philip A.; Sarkar, Fazlul H.; Mohammad, Ramzi M.

2011-01-01

Earlier we had shown that the MDM2 inhibitor (MI-219) belonging to the spiro-oxindole family can synergistically enhance the efficacy of platinum chemotherapeutics leading to 50% tumor free survival in a genetically complex pancreatic ductal adenocarcinoma (PDAC) xenograft model. In this report, we have taken a systems and network modeling approach in order to understand central mechanisms behind MI219-oxaliplatin synergy with validation in PDAC, colon and breast cancer cell lines. Microarray profiling of drug treatments (MI-219, oxaliplatin or their combination) in capan-2 cells reveal a similar unique set of gene alterations that is duplicated in other solid tumor cells. As single agent, MI-219 or oxaliplatin induced alterations in 48 and 761 genes respectively. The combination treatment resulted in 767 gene alterations with emergence of 286 synergy unique genes. Ingenuity network modeling of combination and synergy unique genes showed the crucial role of five key local networks CREB, CARF, EGR1, NF-kB and E Cadherin. The network signatures were validated at the protein level in all three cell lines. Individually silencing central nodes in these five hubs resulted in abrogation of MI-219-oxaliplatin activity confirming their critical role in aiding p53 mediated apoptotic response. We anticipate that our MI219-oxaliplatin network blueprints can be clinically translated in the rationale design and application of this unique therapeutic combination in a genetically pre-defined subset of patients. PMID:21623005

Carotenoid composition of the flowers of Mimulus lewisii and related species: Implications regarding the prevalence and origin of two unique, allenic pigments.

PubMed

LaFountain, Amy M; Frank, Harry A; Yuan, Yao-Wu

2015-05-01

The genus Mimulus has been used as a model system in a wide range of ecological and evolutionary studies and contains many species with carotenoid pigmented flowers. However, the detailed carotenoid composition of these flowers has never been reported. In this paper the floral carotenoid composition of 11 Mimulus species are characterized using high-performance liquid chromatography, mass spectrometry and chemical methods with a particular focus on the genetic model species, Mimulus lewisii. M. lewisii flowers have five major carotenoids: antheraxanthin, violaxanthin, neoxanthin, and the unique allenic carotenoids, deepoxyneoxanthin and mimulaxanthin. This carotenoid profile is consistent with the expression levels of putative carotenoid biosynthetic genes in the M. lewisii flower. The other 10 species possess the same five carotenoids or a subset of these. Comparison of the carotenoid profiles among species in a phylogenetic context provides new insights into the biosynthesis and evolution of deepoxyneoxanthin and mimulaxanthin. This work also lays the foundation for future studies regarding transcriptional control of the carotenoid biosynthesis pathway in Mimulus flowers. Copyright © 2015 Elsevier Inc. All rights reserved.

Diversity Arrays Technology (DArT) for whole-genome profiling of barley

PubMed Central

Wenzl, Peter; Carling, Jason; Kudrna, David; Jaccoud, Damian; Huttner, Eric; Kleinhofs, Andris; Kilian, Andrzej

2004-01-01

Diversity Arrays Technology (DArT) can detect and type DNA variation at several hundred genomic loci in parallel without relying on sequence information. Here we show that it can be effectively applied to genetic mapping and diversity analyses of barley, a species with a 5,000-Mbp genome. We tested several complexity reduction methods and selected two that generated the most polymorphic genomic representations. Arrays containing individual fragments from these representations generated DArT fingerprints with a genotype call rate of 98.0% and a scoring reproducibility of at least 99.8%. The fingerprints grouped barley lines according to known genetic relationships. To validate the Mendelian behavior of DArT markers, we constructed a genetic map for a cross between cultivars Steptoe and Morex. Nearly all polymorphic array features could be incorporated into one of seven linkage groups (98.8%). The resulting map comprised ≈385 unique DArT markers and spanned 1,137 centimorgans. A comparison with the restriction fragment length polymorphism-based framework map indicated that the quality of the DArT map was equivalent, if not superior, to that of the framework map. These results highlight the potential of DArT as a generic technique for genome profiling in the context of molecular breeding and genomics. PMID:15192146

Population and genetic outcomes 20 years after reintroducing bobcats (Lynx rufus) to Cumberland Island, Georgia USA

USGS Publications Warehouse

Diefenbach, Duane R.; Hansen, Leslie A.; Bohling, Justin H.; Miller-Butterworth, Cassandra

2015-01-01

In 1988–1989, 32 bobcats Lynx rufus were reintroduced to Cumberland Island (CUIS), Georgia, USA, from which they had previously been extirpated. They were monitored intensively for 3 years immediately post-reintroduction, but no estimation of the size or genetic diversity of the population had been conducted in over 20 years since reintroduction. We returned to CUIS in 2012 to estimate abundance and effective population size of the present-day population, as well as to quantify genetic diversity and inbreeding. We amplified 12 nuclear microsatellite loci from DNA isolated from scats to establish genetic profiles to identify individuals. We used spatially explicit capture–recapture population estimation to estimate abundance. From nine unique genetic profiles, we estimate a population size of 14.4 (SE = 3.052) bobcats, with an effective population size (Ne) of 5–8 breeding individuals. This is consistent with predictions of a population viability analysis conducted at the time of reintroduction, which estimated the population would average 12–13 bobcats after 10 years. We identified several pairs of related bobcats (parent-offspring and full siblings), but ~75% of the pairwise comparisons were typical of unrelated individuals, and only one individual appeared inbred. Despite the small population size and other indications that it has likely experienced a genetic bottleneck, levels of genetic diversity in the CUIS bobcat population remain high compared to other mammalian carnivores. The reintroduction of bobcats to CUIS provides an opportunity to study changes in genetic diversity in an insular population without risk to this common species. Opportunities for natural immigration to the island are limited; therefore, continued monitoring and supplemental bobcat reintroductions could be used to evaluate the effect of different management strategies to maintain genetic diversity and population viability. The successful reintroduction and maintenance of a bobcat population on CUIS illustrates the suitability of translocation as a management tool for re-establishing felid populations.

Functional Genomics Using the Saccharomyces cerevisiae Yeast Deletion Collections.

PubMed

Nislow, Corey; Wong, Lai Hong; Lee, Amy Huei-Yi; Giaever, Guri

2016-09-01

Constructed by a consortium of 16 laboratories, the Saccharomyces genome-wide deletion collections have, for the past decade, provided a powerful, rapid, and inexpensive approach for functional profiling of the yeast genome. Loss-of-function deletion mutants were systematically created using a polymerase chain reaction (PCR)-based gene deletion strategy to generate a start-to-stop codon replacement of each open reading frame by homologous recombination. Each strain carries two molecular barcodes that serve as unique strain identifiers, enabling their growth to be analyzed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays or through the use of next-generation sequencing technologies. Functional profiling of the deletion collections, using either strain-by-strain or parallel assays, provides an unbiased approach to systematically survey the yeast genome. The Saccharomyces yeast deletion collections have proved immensely powerful in contributing to the understanding of gene function, including functional relationships between genes and genetic pathways in response to diverse genetic and environmental perturbations. © 2016 Cold Spring Harbor Laboratory Press.

Large-scale gene discovery in the pea aphid Acyrthosiphon pisum (Hemiptera)

PubMed Central

Sabater-Muñoz, Beatriz; Legeai, Fabrice; Rispe, Claude; Bonhomme, Joël; Dearden, Peter; Dossat, Carole; Duclert, Aymeric; Gauthier, Jean-Pierre; Ducray, Danièle Giblot; Hunter, Wayne; Dang, Phat; Kambhampati, Srini; Martinez-Torres, David; Cortes, Teresa; Moya, Andrès; Nakabachi, Atsushi; Philippe, Cathy; Prunier-Leterme, Nathalie; Rahbé, Yvan; Simon, Jean-Christophe; Stern, David L; Wincker, Patrick; Tagu, Denis

2006-01-01

Aphids are the leading pests in agricultural crops. A large-scale sequencing of 40,904 ESTs from the pea aphid Acyrthosiphon pisum was carried out to define a catalog of 12,082 unique transcripts. A strong AT bias was found, indicating a compositional shift between Drosophila melanogaster and A. pisum. An in silico profiling analysis characterized 135 transcripts specific to pea-aphid tissues (relating to bacteriocytes and parthenogenetic embryos). This project is the first to address the genetics of the Hemiptera and of a hemimetabolous insect. PMID:16542494

Cellar-Associated Saccharomyces cerevisiae Population Structure Revealed High-Level Diversity and Perennial Persistence at Sauternes Wine Estates

PubMed Central

Börlin, Marine; Venet, Pauline; Claisse, Olivier; Salin, Franck

2016-01-01

ABSTRACT Three wine estates (designated A, B, and C) were sampled in Sauternes, a typical appellation of the Bordeaux wine area producing sweet white wine. From those wine estates, 551 yeast strains were collected between 2012 and 2014, added to 102 older strains from 1992 to 2011 from wine estate C. All the strains were analyzed through 15 microsatellite markers, resulting in 503 unique Saccharomyces cerevisiae genotypes, revealing high genetic diversity and a low presence of commercial yeast starters. Population analysis performed using Fst genetic distance or ancestry profiles revealed that the two closest wine estates, B and C, which have juxtaposed vineyard plots and common seasonal staff, share more related isolates with each other than with wine estate A, indicating exchange between estates. The characterization of isolates collected 23 years ago at wine estate C in relation to recent isolates obtained at wine estate B revealed the long-term persistence of isolates. Last, during the 2014 harvest period, a temporal succession of ancestral subpopulations related to the different batches associated with the selective picking of noble rotted grapes was highlighted. IMPORTANCE High genetic diversity of S. cerevisiae isolates from spontaneous fermentation on wine estates in the Sauternes appellation of Bordeaux was revealed. Only 7% of all Sauternes strains were considered genetically related to specific commercial strains. The long-term persistence (over 20 years) of S. cerevisiae profiles on a given wine estate is highlighted. PMID:26969698

Cellar-Associated Saccharomyces cerevisiae Population Structure Revealed High-Level Diversity and Perennial Persistence at Sauternes Wine Estates.

PubMed

Börlin, Marine; Venet, Pauline; Claisse, Olivier; Salin, Franck; Legras, Jean-Luc; Masneuf-Pomarede, Isabelle

2016-05-15

Three wine estates (designated A, B, and C) were sampled in Sauternes, a typical appellation of the Bordeaux wine area producing sweet white wine. From those wine estates, 551 yeast strains were collected between 2012 and 2014, added to 102 older strains from 1992 to 2011 from wine estate C. All the strains were analyzed through 15 microsatellite markers, resulting in 503 unique Saccharomyces cerevisiae genotypes, revealing high genetic diversity and a low presence of commercial yeast starters. Population analysis performed using Fst genetic distance or ancestry profiles revealed that the two closest wine estates, B and C, which have juxtaposed vineyard plots and common seasonal staff, share more related isolates with each other than with wine estate A, indicating exchange between estates. The characterization of isolates collected 23 years ago at wine estate C in relation to recent isolates obtained at wine estate B revealed the long-term persistence of isolates. Last, during the 2014 harvest period, a temporal succession of ancestral subpopulations related to the different batches associated with the selective picking of noble rotted grapes was highlighted. High genetic diversity of S. cerevisiae isolates from spontaneous fermentation on wine estates in the Sauternes appellation of Bordeaux was revealed. Only 7% of all Sauternes strains were considered genetically related to specific commercial strains. The long-term persistence (over 20 years) of S. cerevisiae profiles on a given wine estate is highlighted. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Characterization of the genetic variation present in CYP3A4 in three South African populations.

PubMed

Drögemöller, Britt; Plummer, Marieth; Korkie, Lundi; Agenbag, Gloudi; Dunaiski, Anke; Niehaus, Dana; Koen, Liezl; Gebhardt, Stefan; Schneider, Nicol; Olckers, Antonel; Wright, Galen; Warnich, Louise

2013-01-01

The CYP3A4 enzyme is the most abundant human cytochrome P450 (CYP) and is regarded as the most important enzyme involved in drug metabolism. Inter-individual and inter-population variability in gene expression and enzyme activity are thought to be influenced, in part, by genetic variation. Although Southern African individuals have been shown to exhibit the highest levels of genetic diversity, they have been under-represented in pharmacogenetic research to date. Therefore, the aim of this study was to identify genetic variation within CYP3A4 in three South African population groups comprising of 29 Khoisan, 65 Xhosa and 65 Mixed Ancestry (MA) individuals. To identify known and novel CYP3A4 variants, 15 individuals were randomly selected from each of the population groups for bi-directional Sanger sequencing of ~600 bp of the 5'-upstream region and all thirteen exons including flanking intronic regions. Genetic variants detected were genotyped in the rest of the cohort. In total, 24 SNPs were detected, including CYP3A4(*)12, CYP3A4(*)15, and the reportedly functional CYP3A4(*)1B promoter polymorphism, as well as two novel non-synonymous variants. These putatively functional variants, p.R162W and p.Q200H, were present in two of the three populations and all three populations, respectively, and in silico analysis predicted that the former would damage the protein product. Furthermore, the three populations were shown to exhibit distinct genetic profiles. These results confirm that South African populations show unique patterns of variation in the genes encoding xenobiotic metabolizing enzymes. This research suggests that population-specific genetic profiles for CYP3A4 and other drug metabolizing genes would be essential to make full use of pharmacogenetics in Southern Africa. Further investigation is needed to determine if the identified genetic variants influence CYP3A4 metabolism phenotype in these populations.

Pelvic incidence variation among individuals: functional influence versus genetic determinism.

PubMed

Chen, Hong-Fang; Zhao, Chang-Qing

2018-03-20

Pelvic incidence has become one of the most important sagittal parameters in spinal surgery. Despite its great importance, pelvic incidence can vary from 33° to 85° in the normal population. The reasons for this great variability in pelvic incidence remain unexplored. The objective of this article is to present some possible interpretations for the great variability in pelvic incidence under both normal and pathological conditions and to further understand the determinants of pelvic incidence from the perspective of the functional requirements for bipedalism and genetic backgrounds via a literature review. We postulate that both pelvic incidence and pelvic morphology may be genetically predetermined, and a great variability in pelvic incidence may already exist even before birth. This great variability may also serve as a further reminder that the sagittal profile, bipedal locomotion mode, and genetic background of every individual are unique and specific, and clinicians should avoid making universally applying broad generalizations of pelvic incidence. Although PI is an important parameter and there are many theories behind its variability, we still do not have clear mechanistic answers.

Bifidobacterium animalis subsp. lactis ATCC 27673 Is a Genomically Unique Strain within Its Conserved Subspecies

PubMed Central

Loquasto, Joseph R.; Barrangou, Rodolphe; Dudley, Edward G.; Stahl, Buffy; Chen, Chun

2013-01-01

Many strains of Bifidobacterium animalis subsp. lactis are considered health-promoting probiotic microorganisms and are commonly formulated into fermented dairy foods. Analyses of previously sequenced genomes of B. animalis subsp. lactis have revealed little genetic diversity, suggesting that it is a monomorphic subspecies. However, during a multilocus sequence typing survey of Bifidobacterium, it was revealed that B. animalis subsp. lactis ATCC 27673 gave a profile distinct from that of the other strains of the subspecies. As part of an ongoing study designed to understand the genetic diversity of this subspecies, the genome of this strain was sequenced and compared to other sequenced genomes of B. animalis subsp. lactis and B. animalis subsp. animalis. The complete genome of ATCC 27673 was 1,963,012 bp, contained 1,616 genes and 4 rRNA operons, and had a G+C content of 61.55%. Comparative analyses revealed that the genome of ATCC 27673 contained six distinct genomic islands encoding 83 open reading frames not found in other strains of the same subspecies. In four islands, either phage or mobile genetic elements were identified. In island 6, a novel clustered regularly interspaced short palindromic repeat (CRISPR) locus which contained 81 unique spacers was identified. This type I-E CRISPR-cas system differs from the type I-C systems previously identified in this subspecies, representing the first identification of a different system in B. animalis subsp. lactis. This study revealed that ATCC 27673 is a strain of B. animalis subsp. lactis with novel genetic content and suggests that the lack of genetic variability observed is likely due to the repeated sequencing of a limited number of widely distributed commercial strains. PMID:23995933

Genetic and Environmental Influences on Individual Differences in Attitudes Toward Homosexuality: An Australian Twin Study

PubMed Central

Shekar, Sri N.; Zietsch, Brendan P.; Eaves, Lindon J.; Bailey, J. Michael; Boomsma, Dorret I.; Martin, Nicholas G.

2008-01-01

Previous research has shown that many heterosexuals hold negative attitudes toward homosexuals and homosexuality (homophobia). Although a great deal of research has focused on the profile of homophobic individuals, this research provides little theoretical insight into the aetiology of homophobia. To examine genetic and environmental influences on variation in attitudes toward homophobia, we analysed data from 4,688 twins who completed a questionnaire concerning sexual behaviour and attitudes, including attitudes toward homosexuality. Results show that, in accordance with literature, males have significantly more negative attitudes toward homosexuality than females and non-heterosexuals are less homophobic than heterosexuals. In contrast with some earlier findings, age had no significant effect on the homophobia scores in this study. Genetic modelling showed that variation in homophobia scores could be explained by additive genetic (36%), shared environmental (18%) and unique environmental factors (46%). However, corrections based on previous findings show that the shared environmental estimate may be almost entirely accounted for as extra additive genetic variance arising from assortative mating for homophobic attitudes. The results suggest that variation in attitudes toward homosexuality is substantially inherited, and that social environmental influences are relatively minor. PMID:18347968

Development and application of SINE multilocus and quantitative genetic markers to study oilseed rape (Brassica napus L.) crops.

PubMed

Allnutt, T R; Roper, K; Henry, C

2008-01-23

A genetic marker system based on the S1 Short Interspersed Elements (SINEs) in the important commercial crop, oilseed rape ( Brassica napus L.) has been developed. SINEs provided a successful multilocus, dominant marker system that was capable of clearly delineating winter- and spring-type crop varieties. Sixteen of 20 varieties tested showed unique profiles from the 17 polymorphic SINE markers generated. The 3' or 5' flank region of nine SINE markers were cloned, and DNA was sequenced. In addition, one putative pre-transposition SINE allele was cloned and sequenced. Two SINE flanking sequences were used to design real-time PCR assays. These quantitative SINE assays were applied to study the genetic structure of eight fields of oilseed rape crops. Studied fields were more genetically diverse than expected for the chosen loci (mean H T = 0.23). The spatial distribution of SINE marker frequencies was highly structured in some fields, suggesting locations of volunteer impurities within the crop. In one case, the assay identified a mislabeling of the crop variety. SINE markers were a useful tool for crop genetics, phylogenetics, variety identification, and purity analysis. The use and further application of quantitative, real-time PCR markers are discussed.

Enclaves of genetic diversity resisted Inca impacts on population history.

PubMed

Barbieri, Chiara; Sandoval, José R; Valqui, Jairo; Shimelman, Aviva; Ziemendorff, Stefan; Schröder, Roland; Geppert, Maria; Roewer, Lutz; Gray, Russell; Stoneking, Mark; Fujita, Ricardo; Heggarty, Paul

2017-12-12

The Inca Empire is claimed to have driven massive population movements in western South America, and to have spread Quechua, the most widely-spoken language family of the indigenous Americas. A test-case is the Chachapoyas region of northern Peru, reported as a focal point of Inca population displacements. Chachapoyas also spans the environmental, cultural and demographic divides between Amazonia and the Andes, and stands along the lowest-altitude corridor from the rainforest to the Pacific coast. Following a sampling strategy informed by linguistic data, we collected 119 samples, analysed for full mtDNA genomes and Y-chromosome STRs. We report a high indigenous component, which stands apart from the network of intense genetic exchange in the core central zone of Andean civilization, and is also distinct from neighbouring populations. This unique genetic profile challenges the routine assumption of large-scale population relocations by the Incas. Furthermore, speakers of Chachapoyas Quechua are found to share no particular genetic similarity or gene-flow with Quechua speakers elsewhere, suggesting that here the language spread primarily by cultural diffusion, not migration. Our results demonstrate how population genetics, when fully guided by the archaeological, historical and linguistic records, can inform multiple disciplines within anthropology.

Examining the etiological associations among higher-order temperament dimensions

PubMed Central

Allan, Nicholas P.; Mikolajewski, Amy J.; Lonigan, Christopher J.; Hart, Sara A.; Taylor, Jeanette

2014-01-01

A multivariate independent pathway model was used to examine the shared and unique genetic and environmental influences of Positive Affect (PA), Negative Affect (NA), and effortful control (EC) in a sample of 686 twin pairs (M age = 10.07, SD = 1.74). There were common genetic influences and nonshared environmental influences shared across all three temperament dimensions and shared environmental influences in common to NA and EC. There were also significant independent genetic influences unique to PA and NA and significant independent shared environmental influences unique to PA. This study demonstrates that there are genetic and environmental influences that affect the covariance among temperament dimensions as well as unique genetic and environmental influences that influence the dimensions independently. PMID:24729641

Personalized medicine could transform healthcare

PubMed Central

Mathur, Sunil; Sutton, Joseph

2017-01-01

Personalized medicine (PM) is about tailoring a treatment as individualized as the disease. The approach relies on identifying genetic, epigenomic, and clinical information that allows the breakthroughs in our understanding of how a person's unique genomic portfolio makes them vulnerable to certain diseases. PM approach is a complete extension of traditional approach (One-Size-Fits-All) to increasing our ability to predict which medical treatments will be safe and effective for individual patient, and which ones will not be, based on the patient's unique genetic profile. Implementation of PM has the potential to reduce financial and time expenditure, and increase quality of life and life extension of patients. Knowledge of PM facilitates earlier disease detection via enhanced use of existing biomarkers and detection of early genomic and epigenomic events in disease development, particularly carcinogenesis. The PM approach predominantly focuses on preventative medicine and favours taking pro-active actions rather than just reactive. This approach delays or prevents the need to apply more severe treatments which are usually less tolerated and with increased quality of life and financial considerations. Increasing healthcare costs have placed additional pressure on government funded healthcare systems globally, especially regarding end of life care. PM may increase the effectiveness of existing treatments and negate the inherent problems associated with non-PM approaches. PM is a young but rapidly expanding field of healthcare where a physician can select a treatment based on a patient's genetic profile that may not only minimize harmful side effects and guarantee a more successful result, but can be less cost effective compared with a ‘trial-and-error’ approach to disease treatment. The less efficient non-PM (‘trial-and-error’) approach, which can lead to drug toxicity, severe side effects, reactive treatment and misdiagnosis continue to contribute to increasing healthcare costs. Increased patient stratification will allow for the enhanced application of PM and pro-active treatment regimens, resulting in reduced costs and quality of life enhancement. PMID:28685051

Genomic Analyses Reveal the Influence of Geographic Origin, Migration, and Hybridization on Modern Dog Breed Development.

PubMed

Parker, Heidi G; Dreger, Dayna L; Rimbault, Maud; Davis, Brian W; Mullen, Alexandra B; Carpintero-Ramirez, Gretchen; Ostrander, Elaine A

2017-04-25

There are nearly 400 modern domestic dog breeds with a unique histories and genetic profiles. To track the genetic signatures of breed development, we have assembled the most diverse dataset of dog breeds, reflecting their extensive phenotypic variation and heritage. Combining genetic distance, migration, and genome-wide haplotype sharing analyses, we uncover geographic patterns of development and independent origins of common traits. Our analyses reveal the hybrid history of breeds and elucidate the effects of immigration, revealing for the first time a suggestion of New World dog within some modern breeds. Finally, we used cladistics and haplotype sharing to show that some common traits have arisen more than once in the history of the dog. These analyses characterize the complexities of breed development, resolving longstanding questions regarding individual breed origination, the effect of migration on geographically distinct breeds, and, by inference, transfer of trait and disease alleles among dog breeds. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Mitochondrial DNA Profiling of Illegal Tortoiseshell Products Derived from Hawksbill Sea Turtles.

PubMed

Foran, David R; Ray, Rebecca L

2016-07-01

The hawksbill sea turtle (Eretmochelys imbricata) is a highly endangered species, commonly poached for its ornate shell. "Tortoiseshell" products made from the shell are widely, although illegally, available in many countries. Hawksbills have a circumglobal distribution; thus, determining their origin is difficult, although genetic differences exist geographically. In the research presented, a procedure was developed to extract and amplify mitochondrial DNA from tortoiseshell items, in an effort to better understand where the species is being poached. Confiscated tortoiseshell items were obtained from the U.S. Fish and Wildlife Service, and DNA from 56 of them was analyzed. Multiple mitochondrial haplotypes were identified, including five not previously reported. Only one tortoiseshell item proved to be of Atlantic origin, while all others corresponded to genetic stocks in the Indo-Pacific region. The developed methodology allows for unique, and previously unattainable, genetic information on the illegal poaching of sea turtles for the decorative tortoiseshell trade. © 2016 American Academy of Forensic Sciences.

Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci

PubMed Central

Ellinghaus, David; Jostins, Luke; Spain, Sarah L; Cortes, Adrian; Bethune, Jörn; Han, Buhm; Park, Yu Rang; Raychaudhuri, Soumya; Pouget, Jennie G; Hübenthal, Matthias; Folseraas, Trine; Wang, Yunpeng; Esko, Tonu; Metspalu, Andres; Westra, Harm-Jan; Franke, Lude; Pers, Tune H; Weersma, Rinse K; Collij, Valerie; D'Amato, Mauro; Halfvarson, Jonas; Jensen, Anders Boeck; Lieb, Wolfgang; Degenhardt, Franziska; Forstner, Andreas J; Hofmann, Andrea; Schreiber, Stefan; Mrowietz, Ulrich; Juran, Brian D; Lazaridis, Konstantinos N; Brunak, Søren; Dale, Anders M; Trembath, Richard C; Weidinger, Stephan; Weichenthal, Michael; Ellinghaus, Eva; Elder, James T; Barker, Jonathan NWN; Andreassen, Ole A; McGovern, Dermot P; Karlsen, Tom H; Barrett, Jeffrey C; Parkes, Miles; Brown, Matthew A; Franke, Andre

2016-01-01

We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European-ancestry we identified 244 independent multi-disease signals including 27 novel genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multi-disease signals with expression data sets from human, rat and mouse, and epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases that is genetically identical to another disease, possibly due to diagnostic misclassification, molecular subtypes, or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes. PMID:26974007

Population structure and infectious disease risk in southern Africa.

PubMed

Uren, Caitlin; Möller, Marlo; van Helden, Paul D; Henn, Brenna M; Hoal, Eileen G

2017-06-01

The KhoeSan populations are the earliest known indigenous inhabitants of southern Africa. The relatively recent expansion of Bantu-speaking agropastoralists, as well as European colonial settlement along the south-west coast, dramatically changed patterns of genetic diversity in a region which had been largely isolated for thousands of years. Owing to this unique history, population structure in southern Africa reflects both the underlying KhoeSan genetic diversity as well as differential recent admixture. This population structure has a wide range of biomedical and sociocultural implications; such as changes in disease risk profiles. Here, we consolidate information from various population genetic studies that characterize admixture patterns in southern Africa with an aim to better understand differences in adverse disease phenotypes observed among groups. Our review confirms that ancestry has a direct impact on an individual's immune response to infectious diseases. In addition, we emphasize the importance of collaborative research, especially for populations in southern Africa that have a high incidence of potentially fatal infectious diseases such as HIV and tuberculosis.

Use of Embryos Extracted from Individual Cannabis sativa Seeds for Genetic Studies and Forensic Applications.

PubMed

Soler, Salvador; Borràs, Dionís; Vilanova, Santiago; Sifres, Alicia; Andújar, Isabel; Figàs, Maria R; Llosa, Ernesto R; Prohens, Jaime

2016-03-01

Legal limits on the psychoactive tetrahydrocannabinol (THC) content in Cannabis sativa plants have complicated genetic and forensic studies in this species. However, Cannabis seeds present very low THC levels. We developed a method for embryo extraction from seeds and an improved protocol for DNA extraction and tested this method in four hemp and six marijuana varieties. This embryo extraction method enabled the recovery of diploid embryos from individual seeds. An improved DNA extraction protocol (CTAB3) was used to obtain DNA from individual embryos at a concentration and quality similar to DNA extracted from leaves. DNA extracted from embryos was used for SSR molecular characterization in individuals from the 10 varieties. A unique molecular profile for each individual was obtained, and a clear differentiation between hemp and marijuana varieties was observed. The combined embryo extraction-DNA extraction methodology and the new highly polymorphic SSR markers facilitate genetic and forensic studies in Cannabis. © 2015 American Academy of Forensic Sciences.

Molecular-genetic profiling and high-throughput in vitro drug screening in NUT midline carcinoma—an aggressive and fatal disease

PubMed Central

Stirnweiss, Anja; Oommen, Joyce; Kotecha, Rishi S.; Kees, Ursula R.; Beesley, Alex H.

2017-01-01

NUT midline carcinoma (NMC) is a rare and aggressive cancer, with survival typically less than seven months, that can arise in people of any age. Genetically, NMC is defined by the chromosomal fusion of NUTM1 with a chromatin-binding partner, typically the bromodomain-containing protein BRD4. However, little is known about other genetic aberrations in this disease. In this study, we used a unique panel of cell lines to describe the molecular-genetic features of NMC. Next-generation sequencing identified a recurring high-impact mutation in the DNA-helicase gene RECQL5 in 75% of lines studied, and biological signals from mutation-signature and network analyses consistent with a general failure in DNA-repair. A high-throughput drug screen confirmed that microtubule inhibitors, topoisomerase inhibitors and anthracyclines are highly cytotoxic in the majority of NMC lines, and that cell lines expressing the BRD4-NUTM1 (exon11:exon2) variant are an order of magnitude more responsive to bromodomain inhibitors (iBETs) on average than those with other BRD4-NUTM1 translocation variants. We also identified a highly significant correlation between iBET and aurora kinase inhibitor efficacy in this study. Integration of exome sequencing, transcriptome, and drug sensitivity profiles suggested that aberrant activity of the nuclear receptor co-activator NCOA3 may correlate with poor response to iBETs. In conclusion, our data emphasize the heterogeneity of NMC and highlights genetic aberrations that could be explored to improve therapeutic strategies. The novel finding of a recurring RECQL5 mutation, together with recent reports of chromoplexy in this disease, suggests that DNA-repair pathways are likely to play a central role in NMC tumorigenesis. PMID:29348827

Genetic diversity of thermotolerant Campylobacter spp. isolates from different stages of the poultry meat supply chain in Argentina.

PubMed

Zbrun, María V; Romero-Scharpen, Analía; Olivero, Carolina; Zimmermann, Jorge A; Rossler, Eugenia; Soto, Lorena P; Astesana, Diego M; Blajman, Jesica E; Berisvil, Ayelén; Frizzo, Laureano S; Signorini, Marcelo L

The objective of this study was to investigate a clonal relationship among thermotolerant Campylobacter spp. isolates from different stages of the poultry meat supply chain in Argentina. A total of 128 thermotolerant Campylobacter spp. (89 C. jejuni and 39 C. coli) isolates from six poultry meat chains were examined. These isolates were from: a) hens from breeder flocks, b) chickens on the farm (at ages 1 wk and 5 wk), c) chicken carcasses in the slaughterhouse, and d) chicken carcasses in the retail market. Chickens sampled along each food chain were from the same batch. Campylobacter spp. isolates were analyzed using pulsed-field gel electrophoresis to compare different profiles according to the source. Clustering of C. jejuni isolates resulted in 17 profiles, with four predominant genotypes and many small profiles with just a few isolates or unique patterns, showing a very high degree of heterogeneity among the C. jejuni isolates. Some clusters included isolates from different stages within the same chain, which would indicate a spread of strains along the same poultry meat chain. Moreover, twenty-two strains of C. coli clustered in seven groups and the remaining 17 isolates exhibited unique profiles. Evidence for transmission of thermotolerant Campylobacter spp. through the food chain and cross contamination in the slaughterhouses were obtained. This collective evidence should be considered as the scientific basis to implement risk management measures to protect the public health. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records.

PubMed

Jiang, Li; Edwards, Stefan M; Thomsen, Bo; Workman, Christopher T; Guldbrandtsen, Bernt; Sørensen, Peter

2014-09-24

Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic profile of genes with respect to their connection to disease phenotypes. The importance of protein-protein interaction networks in the genetic heterogeneity of common diseases or complex traits is becoming increasingly recognized. Thus, the development of a network-based approach combined with phenotypic profiling would be useful for disease gene prioritization. We developed a random-set scoring model and implemented it to quantify phenotype relevance in a network-based disease gene-prioritization approach. We validated our approach based on different gene phenotypic profiles, which were generated from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining of the phenotype data. Our method demonstrated good precision and sensitivity compared with those of two alternative complex-based prioritization approaches. We then conducted a global ranking of all human genes according to their relevance to a range of human diseases. The resulting accurate ranking of known causal genes supported the reliability of our approach. Moreover, these data suggest many promising novel candidate genes for human disorders that have a complex mode of inheritance. We have implemented and validated a network-based approach to prioritize genes for human diseases based on their phenotypic profile. We have devised a powerful and transparent tool to identify and rank candidate genes. Our global gene prioritization provides a unique resource for the biological interpretation of data from genome-wide association studies, and will help in the understanding of how the associated genetic variants influence disease or quantitative phenotypes.

A genetic dissection of breed composition and performance enhancement in the Alaskan sled dog

PubMed Central

2010-01-01

Background The Alaskan sled dog offers a rare opportunity to investigate the development of a dog breed based solely on performance, rather than appearance, thus setting the breed apart from most others. Several established breeds, many of which are recognized by the American Kennel Club (AKC), have been introduced into the sled dog population to enhance racing performance. We have used molecular methods to ascertain the constitutive breeds used to develop successful sled dog lines, and in doing so, determined the breed origins of specific performance-related behaviors. One hundred and ninety-nine Alaskan sled dogs were genotyped using 96 microsatellite markers that span the canine genome. These data were compared to that from 141 similarly genotyped purebred dog breeds. Sled dogs were evaluated for breed composition based on a variety of performance phenotypes including speed, endurance and work ethic, and the data stratified based on population structure. Results We observe that the Alaskan sled dog has a unique molecular signature and that the genetic profile is sufficient for identifying dogs bred for sprint versus distance. When evaluating contributions of existing breeds we find that the Alaskan Malamute and Siberian Husky contributions are associated with enhanced endurance; Pointer and Saluki are associated with enhanced speed and the Anatolian Shepherd demonstrates a positive influence on work ethic. Conclusion We have established a genetic breed profile for the Alaskan sled dog, identified profile variance between sprint and distance dogs, and established breeds associated with enhanced performance attributes. These data set the stage for mapping studies aimed at finding genes that are associated with athletic attributes integral to the high performing Alaskan sled dog. PMID:20649949

A combined analysis of genome-wide expression profiling of bipolar disorder in human prefrontal cortex.

PubMed

Wang, Jinglu; Qu, Susu; Wang, Weixiao; Guo, Liyuan; Zhang, Kunlin; Chang, Suhua; Wang, Jing

2016-11-01

Numbers of gene expression profiling studies of bipolar disorder have been published. Besides different array chips and tissues, variety of the data processes in different cohorts aggravated the inconsistency of results of these genome-wide gene expression profiling studies. By searching the gene expression databases, we obtained six data sets for prefrontal cortex (PFC) of bipolar disorder with raw data and combinable platforms. We used standardized pre-processing and quality control procedures to analyze each data set separately and then combined them into a large gene expression matrix with 101 bipolar disorder subjects and 106 controls. A standard linear mixed-effects model was used to calculate the differentially expressed genes (DEGs). Multiple levels of sensitivity analyses and cross validation with genetic data were conducted. Functional and network analyses were carried out on basis of the DEGs. In the result, we identified 198 unique differentially expressed genes in the PFC of bipolar disorder and control. Among them, 115 DEGs were robust to at least three leave-one-out tests or different pre-processing methods; 51 DEGs were validated with genetic association signals. Pathway enrichment analysis showed these DEGs were related with regulation of neurological system, cell death and apoptosis, and several basic binding processes. Protein-protein interaction network further identified one key hub gene. We have contributed the most comprehensive integrated analysis of bipolar disorder expression profiling studies in PFC to date. The DEGs, especially those with multiple validations, may denote a common signature of bipolar disorder and contribute to the pathogenesis of disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Whole-genome sequence, SNP chips and pedigree structure: building demographic profiles in domestic dog breeds to optimize genetic-trait mapping.

PubMed

Dreger, Dayna L; Rimbault, Maud; Davis, Brian W; Bhatnagar, Adrienne; Parker, Heidi G; Ostrander, Elaine A

2016-12-01

In the decade following publication of the draft genome sequence of the domestic dog, extraordinary advances with application to several fields have been credited to the canine genetic system. Taking advantage of closed breeding populations and the subsequent selection for aesthetic and behavioral characteristics, researchers have leveraged the dog as an effective natural model for the study of complex traits, such as disease susceptibility, behavior and morphology, generating unique contributions to human health and biology. When designing genetic studies using purebred dogs, it is essential to consider the unique demography of each population, including estimation of effective population size and timing of population bottlenecks. The analytical design approach for genome-wide association studies (GWAS) and analysis of whole-genome sequence (WGS) experiments are inextricable from demographic data. We have performed a comprehensive study of genomic homozygosity, using high-depth WGS data for 90 individuals, and Illumina HD SNP data from 800 individuals representing 80 breeds. These data were coupled with extensive pedigree data analyses for 11 breeds that, together, allowed us to compute breed structure, demography, and molecular measures of genome diversity. Our comparative analyses characterize the extent, formation and implication of breed-specific diversity as it relates to population structure. These data demonstrate the relationship between breed-specific genome dynamics and population architecture, and provide important considerations influencing the technological and cohort design of association and other genomic studies. © 2016. Published by The Company of Biologists Ltd.

Whole-genome sequence, SNP chips and pedigree structure: building demographic profiles in domestic dog breeds to optimize genetic-trait mapping

PubMed Central

Dreger, Dayna L.; Rimbault, Maud; Davis, Brian W.; Bhatnagar, Adrienne; Parker, Heidi G.

2016-01-01

ABSTRACT In the decade following publication of the draft genome sequence of the domestic dog, extraordinary advances with application to several fields have been credited to the canine genetic system. Taking advantage of closed breeding populations and the subsequent selection for aesthetic and behavioral characteristics, researchers have leveraged the dog as an effective natural model for the study of complex traits, such as disease susceptibility, behavior and morphology, generating unique contributions to human health and biology. When designing genetic studies using purebred dogs, it is essential to consider the unique demography of each population, including estimation of effective population size and timing of population bottlenecks. The analytical design approach for genome-wide association studies (GWAS) and analysis of whole-genome sequence (WGS) experiments are inextricable from demographic data. We have performed a comprehensive study of genomic homozygosity, using high-depth WGS data for 90 individuals, and Illumina HD SNP data from 800 individuals representing 80 breeds. These data were coupled with extensive pedigree data analyses for 11 breeds that, together, allowed us to compute breed structure, demography, and molecular measures of genome diversity. Our comparative analyses characterize the extent, formation and implication of breed-specific diversity as it relates to population structure. These data demonstrate the relationship between breed-specific genome dynamics and population architecture, and provide important considerations influencing the technological and cohort design of association and other genomic studies. PMID:27874836

Molecular & genetic characteristics of Mycobacterium tuberculosis strains circulating in the southern part of West Siberia

PubMed Central

Pasechnik, Oksana; Dymova, Maya Alexandrovna; Stasenko, Vladimir Leonidovich; Blokh, Aleksey Igorevich; Tatarintseva, Marina Petrovna; Kolesnikova, Lyubov Pavlovna; Filipenko, Maksim Leonidovich

2017-01-01

Background & objectives: A complicated epidemiological situation characterized by significantly high tuberculosis (TB) morbidity is observed in West Siberia. This study was aimed to investigate the genetic characteristics of Mycobacterium tuberculosis circulating in the southern part of West Siberia (in the Omsk region). Methods: From March 2013 to January 2015, 100 isolates of M. tuberculosis were obtained from patients with pulmonary TB living in the Omsk region. Drug susceptibility testing was performed on Lowenstein-Jensen medium (absolute concentration method). Genetic typing of isolates was carried out by variable number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) typing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The genetic types and characteristics of cluster strains were determined using 15 MIRU-VNTR loci. Results: Thirty six VNTR types were found. Twenty six (26.0%) isolates had a unique profile, and the remaining 74 were grouped in 10 clusters containing from 2 to 23 isolates. The Beijing genotype was found in 72 isolates, 61 (85.0%) of which were part of five clusters that included two large clusters containing 23 isolates. Other genetic families, such as Latin-American Mediterranean (LAM, 11.0%), S family (2.0%) and Haarlem (4.0%), were also detected. The genetic family of 11 isolates could not be determined. Six different VNTR profiles were found in these non-classified isolates. Only 16 per cent of isolates were sensitive to anti-TB drugs. The katG315 (94.8%) and rpoB531 (92.2%) mutations were identified in 77 multidrug-resistant M. tuberculosis isolates. Interpretation & conclusions: This study showed that the M. tuberculosis population in the Omsk region was heterogeneous. The Beijing genotype predominated and was actively spreading. The findings obtained point to the need for the implementation of more effective preventive measures to stop the spread of drug-resistant M. tuberculosis strains. PMID:29168460

Proteome profiling of exosomes derived from plasma of heifers with divergent genetic merit for fertility.

PubMed

Koh, Yong Qin; Peiris, Hassendrini N; Vaswani, Kanchan; Almughlliq, Fatema B; Meier, Susanne; Burke, Chris R; Roche, John R; Reed, Charlotte B; Arachchige, Buddhika J; Reed, Sarah; Mitchell, Murray D

2018-04-25

The current study evaluated exosomes isolated from plasma of heifers bred to have high or low fertility through developing extreme diversity in fertility breeding values, however, key animal traits (e.g., body weight, milk production, and percentage of North American genetics) remained similar between the 2 groups. The exosomes were isolated by a combined ultracentrifugation and size exclusion chromatography approach and characterized by their size distribution (nanoparticle tracking analysis), morphology (transmission electron microscopy), and presence of exosomal markers (immunoblotting). In addition, a targeted mass spectrometry approach was used to confirm the presence of 2 exosomal markers, tumor susceptibility gene 101 and flotillin 1. The number of exosomes from plasma of high fertility heifers was greater compared with low fertility heifers. Interestingly, the exosomal proteomic profile, evaluated using mass spectrometry, identified 89 and 116 proteins in the high and low fertility heifers respectively, of which 4 and 31 were unique, respectively. These include proteins associated with specific biological processes and molecular functions of fertility. Most notably, the tetratricopeptide repeat protein 41-related, glycodelin, and kelch-like protein 8 were identified in plasma exosomes unique to the low fertility heifers. These proteins are suggested to play a role in reproduction; however, the role of these proteins in dairy cow reproduction remains to be elucidated. Their identification underscores the potential for proteins within exosomes to provide information on the fertility status and physiological condition of the cow. This may potentially lead to the development of prognostic tools and interventions to improving dairy cow fertility. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

G-protein coupled receptor expression patterns delineate medulloblastoma subgroups

PubMed Central

2013-01-01

Background Medulloblastoma is the most common malignant brain tumor in children. Genetic profiling has identified four principle tumor subgroups; each subgroup is characterized by different initiating mutations, genetic and clinical profiles, and prognoses. The two most well-defined subgroups are caused by overactive signaling in the WNT and SHH mitogenic pathways; less is understood about Groups 3 and 4 medulloblastoma. Identification of tumor subgroup using molecular classification is set to become an important component of medulloblastoma diagnosis and staging, and will likely guide therapeutic options. However, thus far, few druggable targets have emerged. G-protein coupled receptors (GPCRs) possess characteristics that make them ideal targets for molecular imaging and therapeutics; drugs targeting GPCRs account for 30-40% of all current pharmaceuticals. While expression patterns of many proteins in human medulloblastoma subgroups have been discerned, the expression pattern of GPCRs in medulloblastoma has not been investigated. We hypothesized that analysis of GPCR expression would identify clear subsets of medulloblastoma and suggest distinct GPCRs that might serve as molecular targets for both imaging and therapy. Results Our study found that medulloblastoma tumors fall into distinct clusters based solely on GPCR expression patterns. Normal cerebellum clustered separately from the tumor samples. Further, two of the tumor clusters correspond with high fidelity to the WNT and SHH subgroups of medulloblastoma. Distinct over-expressed GPCRs emerge; for example, LGR5 and GPR64 are significantly and uniquely over-expressed in the WNT subgroup of tumors, while PTGER4 is over-expressed in the SHH subgroup. Uniquely under-expressed GPCRs were also observed. Our key findings were independently validated using a large international dataset. Conclusions Our results identify GPCRs with potential to act as imaging and therapeutic targets. Elucidating tumorigenic pathways is a secondary benefit to identifying differential GPCR expression patterns in medulloblastoma tumors. PMID:24252460

QUANTITATIVE GENETIC ACTIVITY GRAPHICAL PROFILES FOR USE IN CHEMICAL EVALUATION

EPA Science Inventory

A graphic approach termed a Genetic Activity Profile (GAP) has been developed to display a matrix of data on the genetic and related effects of selected chemical agents. he profiles provide a visual overview of the quantitative (doses) and qualitative (test results) data for each...

Cardiovascular risk after androgen deprivation therapy for prostate cancer: an Asian perspective.

PubMed

Teoh, Jeremy Yuen Chun; Ng, Chi-Fai

2016-09-01

Androgen deprivation therapy (ADT) plays an important role in managing prostate cancer. However, ADT may result in major cardiovascular events and potentially lead to fatal consequences. Cardiovascular disease is the leading cause of mortality and it is a very important health condition to look into. Asians and Caucasians differ both physiologically and genetically, and they may have display different cardiovascular profiles. In this article, we reviewed the literature focusing on the cardiovascular risk after ADT for prostate cancer in the Asian population. We would discuss about the pathogenesis of ADT leading to cardiovascular events, summarize the findings concerning cardiac and stroke risks after ADT, compare between the different modalities of ADT and also provide genetic basics which are unique to Asians. We hope this article would provide more insights into the cardiovascular risk after ADT for prostate cancer in an Asian perspective.

Genetic and Chemical Profiling of Gymnema sylvestre Accessions from Central India: Its Implication for Quality Control and Therapeutic Potential of Plant

PubMed Central

Verma, Ashutosh Kumar; Dhawan, Sunita Singh; Singh, Seema; Bharati, Kumar Avinash; Jyotsana

2016-01-01

Background: Gymnema sylvestre, a vulnerable plant species, is mentioned in Indian Pharmacopeia as an antidiabetic drug Objective: Study of genetic and chemical diversity and its implications in accessions of G. sylvestre Materials and Methods: Fourteen accessions of G. sylvestre collected from Central India and assessment of their genetic and chemical diversity were carried out using ISSR (inter simple sequence repeat) and HPLC (high performance liquid chromatography) fingerprinting methods Results: Among the screened 40 ISSR primers, 15 were found polymorphic and collectively produced nine unique accession-specific bands. The maximum and minimum numbers of amplicones were noted for ISSR-15 and ISSR-11, respectively. The ISSR -11 and ISSR-13 revealed 100% polymorphism. HPLC chromatograms showed that accessions possess the secondary metabolites of mid-polarity with considerable variability. Unknown peaks with retention time 2.63, 3.41, 23.83, 24.50, and 44.67 were found universal type. Comparative hierarchical clustering analysis based on foresaid fingerprints indicates that both techniques have equal potential to discriminate accessions according to percentage gymnemic acid in their leaf tissue. Second approach was noted more efficiently for separation of accessions according to their agro-climatic/collection site Conclusion: Highly polymorphic ISSRs could be utilized as molecular probes for further selection of high gymnemic acid yielding accessions. Observed accession specific bands may be used as a descriptor for plant accessions protection and converted into sequence tagged sites markers. Identified five universal type peaks could be helpful in identification of G. sylvestre-based various herbal preparations. SUMMARY Nine accession specific unique bandsFive marker peaks for G. sylvestre.Suitability of genetic and chemical fingerprinting Abbreviations used: HPLC: High Performance Liquid Chromatography, ISSR: Inter Simple Sequence Repeats, CTAB: Cetyl Trimethylammonium Bromide, DNTP: Deoxynucleotide Triphosphates PMID:27761067

Genetic and Chemical Profiling of Gymnema sylvestre Accessions from Central India: Its Implication for Quality Control and Therapeutic Potential of Plant.

PubMed

Verma, Ashutosh Kumar; Dhawan, Sunita Singh; Singh, Seema; Bharati, Kumar Avinash; Jyotsana

2016-07-01

Gymnema sylvestre , a vulnerable plant species, is mentioned in Indian Pharmacopeia as an antidiabetic drug. Study of genetic and chemical diversity and its implications in accessions of G. sylvestre . Fourteen accessions of G. sylvestre collected from Central India and assessment of their genetic and chemical diversity were carried out using ISSR (inter simple sequence repeat) and HPLC (high performance liquid chromatography) fingerprinting methods. Among the screened 40 ISSR primers, 15 were found polymorphic and collectively produced nine unique accession-specific bands. The maximum and minimum numbers of amplicones were noted for ISSR-15 and ISSR-11, respectively. The ISSR -11 and ISSR-13 revealed 100% polymorphism. HPLC chromatograms showed that accessions possess the secondary metabolites of mid-polarity with considerable variability. Unknown peaks with retention time 2.63, 3.41, 23.83, 24.50, and 44.67 were found universal type. Comparative hierarchical clustering analysis based on foresaid fingerprints indicates that both techniques have equal potential to discriminate accessions according to percentage gymnemic acid in their leaf tissue. Second approach was noted more efficiently for separation of accessions according to their agro-climatic/collection site. Highly polymorphic ISSRs could be utilized as molecular probes for further selection of high gymnemic acid yielding accessions. Observed accession specific bands may be used as a descriptor for plant accessions protection and converted into sequence tagged sites markers. Identified five universal type peaks could be helpful in identification of G. sylvestre -based various herbal preparations. Nine accession specific unique bandsFive marker peaks for G. sylvestre .Suitability of genetic and chemical fingerprinting Abbreviations used: HPLC: High Performance Liquid Chromatography, ISSR: Inter Simple Sequence Repeats, CTAB: Cetyl Trimethylammonium Bromide, DNTP: Deoxynucleotide Triphosphates.

An Underlying Common Factor, Influenced by Genetics and Unique Environment, Explains the Covariation Between Major Depressive Disorder, Generalized Anxiety Disorder, and Burnout: A Swedish Twin Study.

PubMed

Mather, Lisa; Blom, Victoria; Bergström, Gunnar; Svedberg, Pia

2016-12-01

Depression and anxiety are highly comorbid due to shared genetic risk factors, but less is known about whether burnout shares these risk factors. We aimed to examine whether the covariation between major depressive disorder (MDD), generalized anxiety disorder (GAD), and burnout is explained by common genetic and/or environmental factors. This cross-sectional study included 25,378 Swedish twins responding to a survey in 2005-2006. Structural equation models were used to analyze whether the trait variances and covariances were due to additive genetics, non-additive genetics, shared environment, and unique environment. Univariate analyses tested sex limitation models and multivariate analysis tested Cholesky, independent pathway, and common pathway models. The phenotypic correlations were 0.71 (0.69-0.74) between MDD and GAD, 0.58 (0.56-0.60) between MDD and burnout, and 0.53 (0.50-0.56) between GAD and burnout. Heritabilities were 45% for MDD, 49% for GAD, and 38% for burnout; no statistically significant sex differences were found. A common pathway model was chosen as the final model. The common factor was influenced by genetics (58%) and unique environment (42%), and explained 77% of the variation in MDD, 69% in GAD, and 44% in burnout. GAD and burnout had additive genetic factors unique to the phenotypes (11% each), while MDD did not. Unique environment explained 23% of the variability in MDD, 20% in GAD, and 45% in burnout. In conclusion, the covariation was explained by an underlying common factor, largely influenced by genetics. Burnout was to a large degree influenced by unique environmental factors not shared with MDD and GAD.

Genetic aspects of auto-immune profiles of healthy chickens.

PubMed

Parmentier, Henk K; van der Vaart, Priscilla S; Nieuwland, Mike G B; Savelkoul, Huub F J

2017-09-01

Auto-antibody profiles binding liver antigens differed between chicken lines divergently selected for specific antibody responses to SRBC, and were affected by ageing suggesting both genetic and environmental effects. Presence and levels of IgM and IgG antibodies binding chicken liver cell lysate (CLL) fragments in plasma at 5 weeks of age from 10 individual full sibs and their parents from 5 H srbc and 5 L srbc line families was studied to reveal genetic relations. Non-genetic maternal effects were studied by comparing auto-antibody profiles of 36 weeks old hens from 2 other unrelated lines with the profiles from their chicks at hatch. IgM and IgG antibodies from parents and progeny from both H srbc and L srbc lines bound CLL fragments. Significant line and generation differences and their interactions were found for both isotypes. Higher staining of CLL fragments was usually found for H srbc line birds. Lines were clustered by auto-antibody profiles, but staining by birds of both lines in both generations was very individual for IgG and IgM. The current data with full sibs therefore not supported a genetic basis for auto-antibody profiles. IgG but not IgM auto-antibody profiles of chicks correlated with maternal auto-antibody profiles. The results suggest that the auto-antibody repertoire of healthy chickens is largely stochastically initiated and may be affected by environmental challenges during ageing, but genetic mechanisms may underlie staining intensity of individual bound CLL fragments. The present results suggest that identification of fragments or profiles to be used at early age for genetic selection for health traits is not feasible yet. Secondly, the IgM profile of neonatal chickens seems non-organised independent of the maternal profile, but the neonatal IgG profile is much more related with the maternal profile. Consequences of these findings for disease susceptibility or breeding for optimal health are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical-genetic profile analysis of five inhibitory compounds in yeast.

PubMed

Alamgir, Md; Erukova, Veronika; Jessulat, Matthew; Azizi, Ali; Golshani, Ashkan

2010-08-06

Chemical-genetic profiling of inhibitory compounds can lead to identification of their modes of action. These profiles can help elucidate the complex interactions between small bioactive compounds and the cell machinery, and explain putative gene function(s). Colony size reduction was used to investigate the chemical-genetic profile of cycloheximide, 3-amino-1,2,4-triazole, paromomycin, streptomycin and neomycin in the yeast Saccharomyces cerevisiae. These compounds target the process of protein biosynthesis. More than 70,000 strains were analyzed from the array of gene deletion mutant yeast strains. As expected, the overall profiles of the tested compounds were similar, with deletions for genes involved in protein biosynthesis being the major category followed by metabolism. This implies that novel genes involved in protein biosynthesis could be identified from these profiles. Further investigations were carried out to assess the activity of three profiled genes in the process of protein biosynthesis using relative fitness of double mutants and other genetic assays. Chemical-genetic profiles provide insight into the molecular mechanism(s) of the examined compounds by elucidating their potential primary and secondary cellular target sites. Our follow-up investigations into the activity of three profiled genes in the process of protein biosynthesis provided further evidence concerning the usefulness of chemical-genetic analyses for annotating gene functions. We termed these genes TAE2, TAE3 and TAE4 for translation associated elements 2-4.

Demyelinating diseases in Asia.

PubMed

Ochi, Hirofumi; Fujihara, Kazuo

2016-06-01

The present review aims to discuss the recent advances in inflammatory demyelinating diseases of the central nervous system in Asia. Prevalence of multiple sclerosis (MS) in Asia is lower than that in Western countries, although it has been increasing recently. Meanwhile, there seems to be no major difference in neuromyelitis optica (NMO) prevalence in various regions or ethnicities. Thus, the ratios of NMO/NMO spectrum disorder (NMOSD) to MS are higher in Asia as compared with Western countries, indicating that the differential diagnosis between NMO/NMOSD and MS is a major challenge in Asia. Although the detection of aquaporin-4 (AQP4)-antibody is critical in distinguishing NMO/NMOSD from MS, some patients with NMO/NMOSD phenotype are seronegative for AQP4-antibody, and a fraction of those patients possess autoantibody against myelin oligodendrocyte glycoprotein. The clinical profile of Asian MS seems to be essentially similar to that in Western MS after careful exclusion of NMO/NMOSD, although some unique genetic and/or environmental factors may modify the disease in Asians. MS prevalence has been low but is increasing in Asia. In contrast, NMO/NMOSD prevalence seems relatively constant in the world. Asian MS is not fundamentally different from Western MS, but some genetic and/or environmental differences may cause some features unique to Asian patients.

Evidence for Gender-Dependent Genotype by Environment Interaction in Adult Depression.

PubMed

Molenaar, Dylan; Middeldorp, Christel M; Willemsen, Gonneke; Ligthart, Lannie; Nivard, Michel G; Boomsma, Dorret I

2015-10-14

Depression in adults is heritable with about 40 % of the phenotypic variance due to additive genetic effects and the remaining phenotypic variance due to unique (unshared) environmental effects. Common environmental effects shared by family members are rarely found in adults. One possible explanation for this finding is that there is an interaction between genes and the environment which may mask effects of the common environment. To test this hypothesis, we investigated genotype by environment interaction in a large sample of female and male adult twins aged 18-70 years. The anxious depression subscale of the Adult Self Report from the Achenbach System of Empirically Based Assessment (Achenbach and Rescorla in Manual for the ASEBA adult: forms and profiles, 2003) was completed by 13,022 twins who participate in longitudinal studies of the Netherlands Twin Register. In a single group analysis, we found genotype by unique environment interaction, but no genotype by common environment interaction. However, when conditioning on gender, we observed genotype by common environment interaction in men, with larger common environmental variance in men who are genetically less at risk to develop depression. Although the effect size of the interaction is characterized by large uncertainty, the results show that there is at least some variance due to the common environment in adult depression in men.

Genetically modified plants for law enforcement applications

NASA Astrophysics Data System (ADS)

Stewart, C. Neal, Jr.

2002-08-01

Plants are ubiquitous in the environment and have the unique ability to respond to their environment physiologically and through altered gene expression profiles (they cannot walk away). In addition, plant genetic transformation techniques and genomic information in plants are becoming increasingly advanced. We have been performing research to express the jellyfish green fluorescent protein (GFP) in plants. GFP emits green light when excited by blue or UV light. In addition, my group and collaborators have developed methods to detect GFP in plants by contact instruments and at a standoff. There are several law enforcement applications for this technology. One involves using tagging and perhaps modifying drug plants genetically. In one instance, we could tag them for destruction. In another, we could adulterate them directly. Another application is one that falls into the chemical terrorism and bioterrorism countermeasures category. We are developing plants to sense toxins and whole organisms covertly. Plants are well adapted to monitor large geographic areas; biosurveillance. Some examples of research being performed focus on plants with plant pathogen inducible promoters fused to GFP for disease sensing, and algae biosensors for chemicals.

DNA profiling of Tilapia guinasana, a species endemic to a single sinkhole, to determine the genetic divergence between color forms.

PubMed

Nxomani, C; Ribbink, A J; Kirby, R

1999-06-01

Northwestern South Africa and Namibia contain a number of sinkholes in the dolomitic rock formations found in this area. These contain isolated populations of Tilapia. Most contain Tilapia sparmanii, but the one in Namibia, Guinas, is of particular interest as it contains the endemic species, Tilapia guinasana, which exhibits none sex-limited polychromatisms, which is unique for Tilapia. This sinkhole is under environmental threat, particularly as a result of being a recreational diving site. This study, using randomly amplified polymorphic DNA sequences (RAPDs), when analyzed using analysis of variance (ANOVA), shows that the colour forms of Tilapia guinasana are genetically distinct. This confirms previous evidence that assortative mating between color forms takes place. The various possible hypotheses for the occurrence and genetic stability of the color polymorphism are discussed. Further, a new hypothesis is put forward based on a need to maximize outbreeding in fully isolated population with no possibility of increase in size above the maximum and limited carrying capacity of the sinkhole.

Nuclear, chloroplast, and mitochondrial data of a US cannabis DNA database.

PubMed

Houston, Rachel; Birck, Matthew; LaRue, Bobby; Hughes-Stamm, Sheree; Gangitano, David

2018-05-01

As Cannabis sativa (marijuana) is a controlled substance in many parts of the world, the ability to track biogeographical origin of cannabis could provide law enforcement with investigative leads regarding its trade and distribution. Population substructure and inbreeding may cause cannabis plants to become more genetically related. This genetic relatedness can be helpful for intelligence purposes. Analysis of autosomal, chloroplast, and mitochondrial DNA allows for not only prediction of biogeographical origin of a plant but also discrimination between individual plants. A previously validated, 13-autosomal STR multiplex was used to genotype 510 samples. Samples were analyzed from four different sites: 21 seizures at the US-Mexico border, Northeastern Brazil, hemp seeds purchased in the US, and the Araucania area of Chile. In addition, a previously reported multi-loci system was modified and optimized to genotype five chloroplast and two mitochondrial markers. For this purpose, two methods were designed: a homopolymeric STR pentaplex and a SNP triplex with one chloroplast (Cscp001) marker shared by both methods for quality control. For successful mitochondrial and chloroplast typing, a novel real-time PCR quantitation method was developed and validated to accurately estimate the quantity of the chloroplast DNA (cpDNA) using a synthetic DNA standard. Moreover, a sequenced allelic ladder was also designed for accurate genotyping of the homopolymeric STR pentaplex. For autosomal typing, 356 unique profiles were generated from the 425 samples that yielded full STR profiles and 25 identical genotypes within seizures were observed. Phylogenetic analysis and case-to-case pairwise comparisons of 21 seizures at the US-Mexico border, using the Fixation Index (F ST ) as genetic distance, revealed the genetic association of nine seizures that formed a reference population. For mitochondrial and chloroplast typing, subsampling was performed, and 134 samples were genotyped. Complete haplotypes (STRs and SNPs) were observed for 127 samples. As expected, extensive haplotype sharing was observed; five distinguishable haplotypes were detected. In the reference population, the same haplotype was observed 39 times and two unique haplotypes were also detected. Haplotype sharing was observed between the US border seizures, Brazil, and Chile, while the hemp samples generated a distinct haplotype. Phylogenetic analysis of the four populations was performed, and results revealed that both autosomal and lineage markers could discern population substructure.

Genetic architecture of the Delis-Kaplan Executive Function System Trail Making Test: evidence for distinct genetic influences on executive function.

PubMed

Vasilopoulos, Terrie; Franz, Carol E; Panizzon, Matthew S; Xian, Hong; Grant, Michael D; Lyons, Michael J; Toomey, Rosemary; Jacobson, Kristen C; Kremen, William S

2012-03-01

To examine how genes and environments contribute to relationships among Trail Making Test (TMT) conditions and the extent to which these conditions have unique genetic and environmental influences. Participants included 1,237 middle-aged male twins from the Vietnam Era Twin Study of Aging. The Delis-Kaplan Executive Function System TMT included visual searching, number and letter sequencing, and set-shifting components. Phenotypic correlations among TMT conditions ranged from 0.29 to 0.60, and genes accounted for the majority (58-84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. A common genetic factor, most likely representing a combination of speed and sequencing, accounted for most of the correlation among TMT 1-4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in nonpatient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes.

Reproductive cloning combined with genetic modification.

PubMed

Strong, C

2005-11-01

Although there is widespread opposition to reproductive cloning, some have argued that its use by infertile couples to have genetically related children would be ethically justifiable. Others have suggested that lesbian or gay couples might wish to use cloning to have genetically related children. Most of the main objections to human reproductive cloning are based on the child's lack of unique nuclear DNA. In the future, it may be possible safely to create children using cloning combined with genetic modifications, so that they have unique nuclear DNA. The genetic modifications could be aimed at giving such children genetic characteristics of both members of the couple concerned. Thus, cloning combined with genetic modification could be appealing to infertile, lesbian, or gay couples who seek genetically related children who have genetic characteristics of both members. In such scenarios, the various objections to human reproductive cloning that are based on the lack of genetic uniqueness would no longer be applicable. The author argues that it would be ethically justifiable for such couples to create children in this manner, assuming these techniques could be used safely.

Identification of unique repeated patterns, location of mutation in DNA finger printing using artificial intelligence technique.

PubMed

Mukunthan, B; Nagaveni, N

2014-01-01

In genetic engineering, conventional techniques and algorithms employed by forensic scientists to assist in identification of individuals on the basis of their respective DNA profiles involves more complex computational steps and mathematical formulae, also the identification of location of mutation in a genomic sequence in laboratories is still an exigent task. This novel approach provides ability to solve the problems that do not have an algorithmic solution and the available solutions are also too complex to be found. The perfect blend made of bioinformatics and neural networks technique results in efficient DNA pattern analysis algorithm with utmost prediction accuracy.

Genetic seascape of the threatened Caribbean elkhorn coral, Acropora palmata, on the Puerto Rico Shelf.

PubMed

Mège, Pascal; Schizas, Nikolaos V; Reyes, Joselyd García; Hrbek, Tomas

2015-06-01

It has been proposed that the elkhorn coral, Acropora palmata , is genetically separated into two distinct provinces in the Caribbean, an Eastern and a Western population admixing in western Puerto Rico and around the Mona Passage. In this study, the genetic structure of A. palmata sampled at 11 Puerto Rican localities and localities from Curaçao, the Bahamas and Guadeloupe were examined. Analyses using five microsatellite markers showed that 75% of sampled colonies had unique genotypes, the rest being clone mates. Genetic diversity among genets was high (H E = 0.761) and consistent across localities (0.685 to 0.844). F ST ranged from -0.011 to 0.047 supporting low but significant genetic differentiation between localities within the previously reported Eastern and Western genetic provinces. Plots of genetic per geographic distances and significant Mantel tests supported isolation-by-distance (IBD) within Puerto Rico. Analysis with the software Structure favored a scenario with weak differentiation between two populations, assigning eastern Puerto Rican locations (Fajardo and Culebra), Guadeloupe and Curaçao to the Caribbean Eastern population and western Puerto Rican locations (west of Vega Baja and Ponce), Mona and the Bahamas to the Caribbean Western population. Vieques and San Juan area harbored admixed profiles. Standardized F ST s per 1,000 km unit further supported higher differentiation between localities belonging to different Structure populations, with IBD being stronger within Puerto Rico than on larger regional scales. This stronger genetic transition seems to separate localities between putative Eastern and Western provinces in the eastern Puerto Rican region, not around the Mona Passage.

Genetic seascape of the threatened Caribbean elkhorn coral, Acropora palmata, on the Puerto Rico Shelf

PubMed Central

Mège, Pascal; Schizas, Nikolaos V.; Reyes, Joselyd García; Hrbek, Tomas

2014-01-01

It has been proposed that the elkhorn coral, Acropora palmata, is genetically separated into two distinct provinces in the Caribbean, an Eastern and a Western population admixing in western Puerto Rico and around the Mona Passage. In this study, the genetic structure of A. palmata sampled at 11 Puerto Rican localities and localities from Curaçao, the Bahamas and Guadeloupe were examined. Analyses using five microsatellite markers showed that 75% of sampled colonies had unique genotypes, the rest being clone mates. Genetic diversity among genets was high (HE = 0.761) and consistent across localities (0.685 to 0.844). FST ranged from −0.011 to 0.047 supporting low but significant genetic differentiation between localities within the previously reported Eastern and Western genetic provinces. Plots of genetic per geographic distances and significant Mantel tests supported isolation-by-distance (IBD) within Puerto Rico. Analysis with the software Structure favored a scenario with weak differentiation between two populations, assigning eastern Puerto Rican locations (Fajardo and Culebra), Guadeloupe and Curaçao to the Caribbean Eastern population and western Puerto Rican locations (west of Vega Baja and Ponce), Mona and the Bahamas to the Caribbean Western population. Vieques and San Juan area harbored admixed profiles. Standardized FSTs per 1,000 km unit further supported higher differentiation between localities belonging to different Structure populations, with IBD being stronger within Puerto Rico than on larger regional scales. This stronger genetic transition seems to separate localities between putative Eastern and Western provinces in the eastern Puerto Rican region, not around the Mona Passage. PMID:26085704

DNA mutations of the cat: the good, the bad and the ugly.

PubMed

Lyons, Leslie A

2015-03-01

The health of the cat is a complex interaction between its environment (nurture) and its genetics (nature). Over 70 genetic mutations (variants) have been defined in the cat, many involving diseases, structural abnormalities and clinically relevant health concerns. As more of the cat's genome is deciphered, less commonly will the term 'idiopathic' be used regarding the diagnosis of diseases and unique health conditions. State-of-the-art health care will include DNA profiling of the individual cat, and perhaps its tumor, to establish the best treatment approaches. Genetic testing and eventually whole genome sequencing should become routine diagnostics for feline health care. Cat breeds have disseminated around the world. Thus, practitioners should be aware of the breeds common to their region and the mutations found in those regional populations. Specific random-bred populations can also have defined genetic characteristics and mutations. This review of 'the good, the bad and the ugly' DNA variants provides the current state of knowledge for genetic testing and genetic health management for cats. It is aimed at feline and general practitioners wanting to update and review the basics of genetics, what tests are available for cats and sources for genetic testing. The tables are intended to be used as references in the clinic. Practitioners with a high proportion of cat breeder clientele will especially benefit from the review. The data presented is extracted from peer-reviewed publications pertaining to mutation identification, and relevant articles concerning the heritable trait and/or disease. The author also draws upon personal experience and expertise in feline genetics. © ISFM and AAFP 2015.

Chemical profiles of body surfaces and nests from six Bornean stingless bee species.

PubMed

Leonhardt, Sara Diana; Blüthgen, Nico; Schmitt, Thomas

2011-01-01

Stingless bees (Apidae: Meliponini) are the most diverse group of Apid bees and represent common pollinators in tropical ecosystems. Like honeybees they live in large eusocial colonies and rely on complex chemical recognition and communication systems. In contrast to honeybees, their ecology and especially their chemical ecology have received only little attention, particularly in the Old World. We previously have analyzed the chemical profiles of six paleotropical stingless bee species from Borneo and revealed the presence of species-specific cuticular terpenes- an environmentally derived compound class so far unique among social insects. Here, we compared the bees' surface profiles to the chemistry of their nest material. Terpenes, alkanes, and alkenes were the dominant compound groups on both body surfaces and nest material. However, bee profiles and nests strongly differed in their chemical composition. Body surfaces thus did not merely mirror nests, rendering a passive compound transfer from nests to bees unlikely. The difference between nests and bees was particularly pronounced when all resin-derived compounds (terpenes) were excluded and only genetically determined compounds were considered. When terpenes were included, bee profiles and nest material still differed, because whole groups of terpenes (e.g., sesquiterpenes) were found in nest material of some species, but missing in their chemical profile, indicating that bees are able to influence the terpene composition both in their nests and on their surfaces.

Genome-Wide Requirements for Resistance to Functionally Distinct DNA-Damaging Agents

PubMed Central

Proctor, Michael; Flaherty, Patrick; Jordan, Michael I; Arkin, Adam P; Davis, Ronald W; Nislow, Corey; Giaever, Guri

2005-01-01

The mechanistic and therapeutic differences in the cellular response to DNA-damaging compounds are not completely understood, despite intense study. To expand our knowledge of DNA damage, we assayed the effects of 12 closely related DNA-damaging agents on the complete pool of ~4,700 barcoded homozygous deletion strains of Saccharomyces cerevisiae. In our protocol, deletion strains are pooled together and grown competitively in the presence of compound. Relative strain sensitivity is determined by hybridization of PCR-amplified barcodes to an oligonucleotide array carrying the barcode complements. These screens identified genes in well-characterized DNA-damage-response pathways as well as genes whose role in the DNA-damage response had not been previously established. High-throughput individual growth analysis was used to independently confirm microarray results. Each compound produced a unique genome-wide profile. Analysis of these data allowed us to determine the relative importance of DNA-repair modules for resistance to each of the 12 profiled compounds. Clustering the data for 12 distinct compounds uncovered both known and novel functional interactions that comprise the DNA-damage response and allowed us to define the genetic determinants required for repair of interstrand cross-links. Further genetic analysis allowed determination of epistasis for one of these functional groups. PMID:16121259

Specific Medical Conditions Are Associated with Unique Behavioral Profiles in Autism Spectrum Disorders.

PubMed

Zachor, Ditza A; Ben-Itzchak, Esther

2016-01-01

Autism spectrum disorder (ASD) is a heterogeneous group of disorders which occurs with numerous medical conditions. In previous research, subtyping in ASD has been based mostly on cognitive ability and ASD symptom severity. The aim of the current study was to investigate whether specific medical conditions in ASD are associated with unique behavioral profiles. The medical conditions included in the study were macrocephaly, microcephaly, developmental regression, food selectivity, and sleep problems. The behavioral profile was composed of cognitive ability, adaptive skills, and autism severity, and was examined in each of the aforementioned medical conditions. The study population included 1224 participants, 1043 males and 181 females (M:F ratio = 5.8:1) with a mean age of 49.9 m (SD = 29.4) diagnosed with ASD using standardized tests. Groups with and without the specific medical conditions were compared on the behavioral measures. Developmental regression was present in 19% of the population and showed a more severe clinical presentation, with lower cognitive abilities, more severe ASD symptoms, and more impaired adaptive functioning. Microcephaly was observed in 6.3% of the population and was characterized by a lower cognitive ability and more impaired adaptive functioning in comparison to the normative head circumference (HC) group. Severe food selectivity was found in 9.8% and severe sleep problems in 5.1% of the ASD population. The food selectivity and sleep problem subgroups, both showed more severe autism symptoms only as described by the parents, but not per the professional assessment, and more impaired adaptive skills. Macrocephaly was observed in 7.9% of the ASD population and did not differ from the normative HC group in any of the examined behavioral measures. Based on these findings, two unique medical-behavioral subtypes in ASD that affect inherited traits of cognition and/or autism severity were suggested. The microcephaly phenotype occurred with more impaired cognition and the developmental regression phenotype with widespread, more severe impairments in cognition and autism severity. In contrast, severe food selectivity and sleep problems represent only comorbidities to ASD that affect functioning. Defining specific subgroups in ASD with a unique biological signature and specific behavioral phenotypes may help future genetic and neuroscience research.

Genetic Architecture of the Delis-Kaplan Executive Function System Trail Making Test: Evidence for Distinct Genetic Influences on Executive Function

PubMed Central

Vasilopoulos, Terrie; Franz, Carol E.; Panizzon, Matthew S.; Xian, Hong; Grant, Michael D.; Lyons, Michael J; Toomey, Rosemary; Jacobson, Kristen C.; Kremen, William S.

2012-01-01

Objective To examine how genes and environments contribute to relationships among Trail Making test conditions and the extent to which these conditions have unique genetic and environmental influences. Method Participants included 1237 middle-aged male twins from the Vietnam-Era Twin Study of Aging (VESTA). The Delis-Kaplan Executive Function System Trail Making test included visual searching, number and letter sequencing, and set-shifting components. Results Phenotypic correlations among Trails conditions ranged from 0.29 – 0.60, and genes accounted for the majority (58–84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set-shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. Conclusions A common genetic factor, most likely representing a combination of speed and sequencing accounted for most of the correlation among Trails 1–4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set-shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in non-patient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes. PMID:22201299

TEMPLE: analysing population genetic variation at transcription factor binding sites.

PubMed

Litovchenko, Maria; Laurent, Stefan

2016-11-01

Genetic variation occurring at the level of regulatory sequences can affect phenotypes and fitness in natural populations. This variation can be analysed in a population genetic framework to study how genetic drift and selection affect the evolution of these functional elements. However, doing this requires a good understanding of the location and nature of regulatory regions and has long been a major hurdle. The current proliferation of genomewide profiling experiments of transcription factor occupancies greatly improves our ability to identify genomic regions involved in specific DNA-protein interactions. Although software exists for predicting transcription factor binding sites (TFBS), and the effects of genetic variants on TFBS specificity, there are no tools currently available for inferring this information jointly with the genetic variation at TFBS in natural populations. We developed the software Transcription Elements Mapping at the Population LEvel (TEMPLE), which predicts TFBS, evaluates the effects of genetic variants on TFBS specificity and summarizes the genetic variation occurring at TFBS in intraspecific sequence alignments. We demonstrate that TEMPLE's TFBS prediction algorithms gives identical results to PATSER, a software distribution commonly used in the field. We also illustrate the unique features of TEMPLE by analysing TFBS diversity for the TF Senseless (SENS) in one ancestral and one cosmopolitan population of the fruit fly Drosophila melanogaster. TEMPLE can be used to localize TFBS that are characterized by strong genetic differentiation across natural populations. This will be particularly useful for studies aiming to identify adaptive mutations. TEMPLE is a java-based cross-platform software that easily maps the genetic diversity at predicted TFBSs using a graphical interface, or from the Unix command line. © 2016 John Wiley & Sons Ltd.

Current genetic methodologies in the identification of disaster victims and in forensic analysis.

PubMed

Ziętkiewicz, Ewa; Witt, Magdalena; Daca, Patrycja; Zebracka-Gala, Jadwiga; Goniewicz, Mariusz; Jarząb, Barbara; Witt, Michał

2012-02-01

This review presents the basic problems and currently available molecular techniques used for genetic profiling in disaster victim identification (DVI). The environmental conditions of a mass disaster often result in severe fragmentation, decomposition and intermixing of the remains of victims. In such cases, traditional identification based on the anthropological and physical characteristics of the victims is frequently inconclusive. This is the reason why DNA profiling became the gold standard for victim identification in mass-casualty incidents (MCIs) or any forensic cases where human remains are highly fragmented and/or degraded beyond recognition. The review provides general information about the sources of genetic material for DNA profiling, the genetic markers routinely used during genetic profiling (STR markers, mtDNA and single-nucleotide polymorphisms [SNP]) and the basic statistical approaches used in DNA-based disaster victim identification. Automated technological platforms that allow the simultaneous analysis of a multitude of genetic markers used in genetic identification (oligonucleotide microarray techniques and next-generation sequencing) are also presented. Forensic and population databases containing information on human variability, routinely used for statistical analyses, are discussed. The final part of this review is focused on recent developments, which offer particularly promising tools for forensic applications (mRNA analysis, transcriptome variation in individuals/populations and genetic profiling of specific cells separated from mixtures).

Value of genetic profiling for the prediction of coronary heart disease.

PubMed

van der Net, Jeroen B; Janssens, A Cecile J W; Sijbrands, Eric J G; Steyerberg, Ewout W

2009-07-01

Advances in high-throughput genomics facilitate the identification of novel genetic susceptibility variants for coronary heart disease (CHD). This may improve CHD risk prediction. The aim of the present simulation study was to investigate to what degree CHD risk can be predicted by testing multiple genetic variants (genetic profiling). We simulated genetic profiles for a population of 100,000 individuals with a 10-year CHD incidence of 10%. For each combination of model parameters (number of variants, genotype frequency and odds ratio [OR]), we calculated the area under the receiver operating characteristic curve (AUC) to indicate the discrimination between individuals who will and will not develop CHD. The AUC of genetic profiles could rise to 0.90 when 100 hypothetical variants with ORs of 1.5 and genotype frequencies of 50% were simulated. The AUC of a genetic profile consisting of 10 established variants, with ORs ranging from 1.13 to 1.42, was 0.59. When 2, 5, and 10 times as many identical variants would be identified, the AUCs were 0.63, 0.69, and 0.76. To obtain AUCs similar to those of conventional CHD risk predictors, a considerable number of additional common genetic variants need to be identified with preferably strong effects.

Asthma pharmacogenetics and the development of genetic profiles for personalized medicine

PubMed Central

Ortega, Victor E; Meyers, Deborah A; Bleecker, Eugene R

2015-01-01

Human genetics research will be critical to the development of genetic profiles for personalized or precision medicine in asthma. Genetic profiles will consist of gene variants that predict individual disease susceptibility and risk for progression, predict which pharmacologic therapies will result in a maximal therapeutic benefit, and predict whether a therapy will result in an adverse response and should be avoided in a given individual. Pharmacogenetic studies of the glucocorticoid, leukotriene, and β2-adrenergic receptor pathways have focused on candidate genes within these pathways and, in addition to a small number of genome-wide association studies, have identified genetic loci associated with therapeutic responsiveness. This review summarizes these pharmacogenetic discoveries and the future of genetic profiles for personalized medicine in asthma. The benefit of a personalized, tailored approach to health care delivery is needed in the development of expensive biologic drugs directed at a specific biologic pathway. Prior pharmacogenetic discoveries, in combination with additional variants identified in future studies, will form the basis for future genetic profiles for personalized tailored approaches to maximize therapeutic benefit for an individual asthmatic while minimizing the risk for adverse events. PMID:25691813

Genetic and Environmental Influences on Smoking Behavior across Adolescence and Young Adulthood in the Virginia Twin Study of Adolescent Behavioral Development and the Transitions to Substance Abuse Follow-Up

PubMed Central

Do, Elizabeth K.; Prom-Wormley, Elizabeth C.; Eaves, Lindon J.; Silberg, Judy L.; Miles, Donna R.; Maes, Hermine H.

2016-01-01

Little is known regarding the underlying relationship between smoking initiation and current quantity smoked during adolescence into young adulthood. It is possible that the influences of genetic and environmental factors on this relationship vary across sex and age. To investigate this further, the current study applied a common causal contingency model to data from a Virginia-based twin study to determine: (1) if the same genetic and environmental factors are contributing to smoking initiation and current quantity smoked; (2) whether the magnitude of genetic and environmental factor contributions are the same across adolescence and young adulthood; and (3) if qualitative and quantitative differences in the sources of variance between males and females exist. Study results found no qualitative or quantitative sex differences in the relationship between smoking initiation and current quantity smoked, though relative contributions of genetic and environmental factors changed across adolescence and young adulthood. More specifically, smoking initiation and current quantity smoked remain separate constructs until young adulthood, when liabilities are correlated. Smoking initiation is explained by genetic, shared, and unique environmental factors in early adolescence and by genetic and unique environmental factors in young adulthood; while current quantity smoked is explained by shared environmental and unique environmental factors until young adulthood, when genetic and unique environmental factors play a larger role. PMID:25662421

Genetic and Environmental Influences on Smoking Behavior across Adolescence and Young Adulthood in the Virginia Twin Study of Adolescent Behavioral Development and the Transitions to Substance Abuse Follow-Up.

PubMed

Do, Elizabeth K; Prom-Wormley, Elizabeth C; Eaves, Lindon J; Silberg, Judy L; Miles, Donna R; Maes, Hermine H

2015-02-01

Little is known regarding the underlying relationship between smoking initiation and current quantity smoked during adolescence into young adulthood. It is possible that the influences of genetic and environmental factors on this relationship vary across sex and age. To investigate this further, the current study applied a common causal contingency model to data from a Virginia-based twin study to determine: (1) if the same genetic and environmental factors are contributing to smoking initiation and current quantity smoked; (2) whether the magnitude of genetic and environmental factor contributions are the same across adolescence and young adulthood; and (3) if qualitative and quantitative differences in the sources of variance between males and females exist. Study results found no qualitative or quantitative sex differences in the relationship between smoking initiation and current quantity smoked, though relative contributions of genetic and environmental factors changed across adolescence and young adulthood. More specifically, smoking initiation and current quantity smoked remain separate constructs until young adulthood, when liabilities are correlated. Smoking initiation is explained by genetic, shared, and unique environmental factors in early adolescence and by genetic and unique environmental factors in young adulthood; while current quantity smoked is explained by shared environmental and unique environmental factors until young adulthood, when genetic and unique environmental factors play a larger role.

Fetal alcohol spectrum disorders: gene-environment interactions, predictive biomarkers, and the relationship between structural alterations in the brain and functional outcomes.

PubMed

Reynolds, James N; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2011-03-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. Copyright © 2011 Elsevier Inc. All rights reserved.

Fetal Alcohol Spectrum Disorders: Gene-Environment Interactions, Predictive Biomarkers, and the Relationship Between Structural Alterations in the Brain and Functional Outcomes

PubMed Central

Reynolds, James N.; Weinberg, Joanne; Clarren, Sterling; Beaulieu, Christian; Rasmussen, Carmen; Kobor, Michael; Dube, Marie-Pierre; Goldowitz, Daniel

2016-01-01

Prenatal alcohol exposure is a major, preventable cause of behavioral and cognitive deficits in children. Despite extensive research, a unique neurobehavioral profile for children affected by prenatal alcohol exposure remains elusive. A fundamental question that must be addressed is how genetic and environmental factors interact with gestational alcohol exposure to produce neurobehavioral and neurobiological deficits in children. The core objectives of the NeuroDevNet team in fetal alcohol spectrum disorders is to create an integrated research program of basic and clinical investigations that will (1) identify genetic and epigenetic modifications that may be predictive of the neurobehavioral and neurobiological dysfunctions in offspring induced by gestational alcohol exposure and (2) determine the relationship between structural alterations in the brain induced by gestational alcohol exposure and functional outcomes in offspring. The overarching hypothesis to be tested is that neurobehavioral and neurobiological dysfunctions induced by gestational alcohol exposure are correlated with the genetic background of the affected child and/or epigenetic modifications in gene expression. The identification of genetic and/or epigenetic markers that are predictive of the severity of behavioral and cognitive deficits in children affected by gestational alcohol exposure will have a profound impact on our ability to identify children at risk. PMID:21575841

Use of RAPD technique in evolution studies of four species in the family Canidae.

PubMed

Stepniak, Ewa; Zagalska, Maria M; Switoński, Marek

2002-01-01

The RAPD-PCR technique was applied to identify genetic markers able to distinguish between four canid species: the arctic fox (Alopex lagopus), red fox (Vulpes vulpes), Chinese raccoon dog (Nyctereutes procyonoides procyonoides) and six breeds of the domestic dog (Canis familiaris). A total of 29 ten-nucleotide arbitrary primers were screened for their potential use in the differentiation of these species. Ten primers amplified RAPD profiles that made it possible to distinguish between the investigated taxa. A number of species-specific bands was scored within RAPD profiles produced by these primers: 35.6% of all the polymorphic bands were unique to the Chinese raccoon dog, 29.6% were unique to the domestic dog, 21.2% were diagnostic for the red fox and 13.6% for the arctic fox. No breed-specific fragments were amplified from canine DNA; however, three primers produced bands characteristic for the dog, but not present in all of the investigated breeds. A Neighbor-Joining tree constructed on the basis of the analysis of RAPD profiles amplified by six primers revealed that the phylogenetic distance between the dog and the arctic fox is larger than the distance between the dog and the red fox. The phylogenetic branch of the Chinese raccoon dog was the most distinct on the dendrogram, suggesting that this species belongs to a different phylogenetic lineage. Obtained results make it possible to conclude that RAPD analysis can be a powerful tool for developing molecular markers useful in distinguishing between species of the family Canidae and for studying their phylogenetic relations.

Use of a genetic algorithm to improve the rail profile on Stockholm underground

NASA Astrophysics Data System (ADS)

Persson, Ingemar; Nilsson, Rickard; Bik, Ulf; Lundgren, Magnus; Iwnicki, Simon

2010-12-01

In this paper, a genetic algorithm optimisation method has been used to develop an improved rail profile for Stockholm underground. An inverted penalty index based on a number of key performance parameters was generated as a fitness function and vehicle dynamics simulations were carried out with the multibody simulation package Gensys. The effectiveness of each profile produced by the genetic algorithm was assessed using the roulette wheel method. The method has been applied to the rail profile on the Stockholm underground, where problems with rolling contact fatigue on wheels and rails are currently managed by grinding. From a starting point of the original BV50 and the UIC60 rail profiles, an optimised rail profile with some shoulder relief has been produced. The optimised profile seems similar to measured rail profiles on the Stockholm underground network and although initial grinding is required, maintenance of the profile will probably not require further grinding.

[HLA genetic markers and auto-antibody profile in a Mapuche family with a case affected of type 1 diabetes].

PubMed

Asenjo, Sylvia; Gleisner, Andrea; Pérez, Francisco

2004-01-01

Type 1 diabetes (DM1) is caused by an autoimmune process that destroys beta cells of pancreas. Not all carriers of susceptible HLA genes and positive for autoantibodies develop the disease. Environmental factors play a role in triggering the autoimmune process. To analyze an exceptional case of DM1 in a Mapuche family in the context of genetic, immunological and environmental factors. A study of a family with an affected female child was carried out in a Mapuche community in Southern Chile (VIII region). This is an unique and sporadic DM1 case with Mapuche heritage. Nutritional and viral infections data were collected by interview and clinical records. A genetic analysis by PCR was done to detect class I and II HLA genes by reverse dot blot. The proband, her mother and sister had positive islet cell antibodies (ICA). Her father and brother were negative. All thefamily was positive for anti glutamic decarboxylase antibodies (GAD65). All subjects had HLA-DRB1 0407/0407 and HLA-DQB1 0302/0302 alleles. The index case and her father were homozygotes for the HLA-A1:A*68012/A*68012 allele. Mean breastfeeding lapse was 18 months in all children. No evidences for viral infections such as rubella, mumps or measles were found in this family. There was an altered profile of autoantibodies in the family of the index case. All genotypes were comparable with the European population where the diabetogenic combination DR4/DQB1*0302 is the most prevalent. No environmental factors could be incriminated as triggers of the disease.

Hoarding in obsessive-compulsive disorder: clinical and genetic correlates.

PubMed

Lochner, Christine; Kinnear, Craig J; Hemmings, Sian M J; Seller, Cathlene; Niehaus, Dana J H; Knowles, James A; Daniels, Willie; Moolman-Smook, Johanna C; Seedat, Soraya; Stein, Dan J

2005-09-01

Hoarding may be an important symptom dimension in obsessive-compulsive disorder (OCD). Hoarding in OCD has been associated with poor insight, poorer response to selective serotonin reuptake inhibitors than other OCD symptom dimensions, and a distinctive psychobiological profile. The clinical and genetic correlates of hoarding in OCD therefore deserve additional investigation. Adult OCD patients (N = 315) underwent a comprehensive clinical assessment that included the Structured Clinical Interview for DSM-IV Axis I Disorders (Patient Edition) and for Diagnosis of Obsessive-Compulsive Spectrum Disorders. DNA extracted from venous blood (10-30 mL) in a Caucasian subset of the interviewed OCD patients (N = 204) and Caucasian controls (N = 169), including patients (N = 94) and controls (N = 138) of Afrikaner descent, was genotyped to investigate polymorphisms in genes involved in monoamine function and previously hypothesized to be relevant to OCD. Data were collected from 1998 through 2004. OCD patients with hoarding made up 18.1% of the total sample. Compared with nonhoarding OCD, OCD with hoarding was associated with a number of comorbid Axis I disorders, obsessive-compulsive personality disorder, significantly higher OCD severity scores, and more functional impairment. In subjects of Afrikaner descent, the L/L genotype of the COMT Val158Met polymorphism was significantly more common in the OCD hoarding group, with a preponderance of low activity alleles, compared with nonhoarding patients and controls. These data are consistent with the hypothesis that hoarding represents a unique symptom subtype in OCD with a distinctive clinical and psychobiological profile. Further work is needed to determine the psychobiological mechanisms responsible for hoarding and to replicate the genetic findings noted here.

Mouse Models as Predictors of Human Responses: Evolutionary Medicine.

PubMed

Uhl, Elizabeth W; Warner, Natalie J

Mice offer a number of advantages and are extensively used to model human diseases and drug responses. Selective breeding and genetic manipulation of mice have made many different genotypes and phenotypes available for research. However, in many cases, mouse models have failed to be predictive. Important sources of the prediction problem have been the failure to consider the evolutionary basis for species differences, especially in drug metabolism, and disease definitions that do not reflect the complexity of gene expression underlying disease phenotypes. Incorporating evolutionary insights into mouse models allow for unique opportunities to characterize the effects of diet, different gene expression profiles, and microbiomics underlying human drug responses and disease phenotypes.

Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures

PubMed Central

Park, Paul J.; Fuchs, Robert; Wei, Lai; Jorgensen, Brian G.; Redelman, Doug; Ward, Sean M.; Sanders, Kenton M.

2017-01-01

Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC), which serve as slow-wave electrical pacemakers for gastrointestinal (GI) smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome) based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies. PMID:28426719

Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation

PubMed Central

Pagliaccio, David; Luby, Joan L.; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Belden, Andrew C.; Botteron, Kelly N.; Harms, Michael P.; Barch, Deanna M.

2015-01-01

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9–14 year olds; N=120). Whole-brain regression analyses indicated that increasing genetic ‘risk’ predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic ‘risk’ and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. PMID:26595470

Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation.

PubMed

Pagliaccio, David; Luby, Joan L; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S; Belden, Andrew C; Botteron, Kelly N; Harms, Michael P; Barch, Deanna M

2015-11-01

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. (c) 2015 APA, all rights reserved).

Postdoctoral Fellows | Center for Cancer Research

Cancer.gov

The Oncogenomics section of the Genetics Branch is a multidisciplinary and interdisciplinary translational research programmatic effort with the goal of utilizing genomics to develop novel immunotherapies for cancer. Our group is applying high throughput applied genomics methods including single cell RNAseq, single cell TCR sequencing, DNA sequencing, CRISPR/Cas9, bioinformatics combined with T cell based therapeutics to identify and develop novel immunotherapeutics for human cancer. We work with other investigators within the intramural program as well as industrial and pharmaceutical partners to rapidly translate our findings to the clinic. The program takes advantage of the uniqueness of the National Cancer Institute, (NCI), Center for Cancer Research (CCR) intramural program in that it spans high-risk basic discovery research in immunology, genomics and tumor biology, through preclinical translational research, to paradigm-shifting clinical trials. The position is available immediately. The appointment duration is up to 5 years. Stipends are commensurate with education and experience. Additional information can be found on Dr. Khan’s profile page: https://ccr.cancer.gov/Genetics-Branch/javed-khan

Comparative transcriptional profiling of tildipirosin-resistant and sensitive Haemophilus parasuis.

PubMed

Lei, Zhixin; Fu, Shulin; Yang, Bing; Liu, Qianying; Ahmed, Saeed; Xu, Lei; Xiong, Jincheng; Cao, Jiyue; Qiu, Yinsheng

2017-08-08

Numerous studies have been conducted to examine the molecular mechanism of Haemophilus parasuis resistance to antibiotic, but rarely to tildipirosin. In the current study, transcriptional profiling was applied to analyse the variation in gene expression of JS0135 and tildipirosin-resistant JS32. The growth curves showed that JS32 had a higher growth rate but fewer bacteria than JS0135. The cell membranes of JS32 and a resistant clinical isolate (HB32) were observed to be smoother than those of JS0135. From the comparative gene expression profile 349 up- and 113 downregulated genes were observed, covering 37 GO and 63 KEGG pathways which are involved in biological processes (11), cellular components (17), molecular function (9), cellular processes (1), environmental information processing (4), genetic information processing (9) and metabolism (49) affected in JS32. In addition, the relative overexpression of genes of the metabolism pathway (HAPS_RS09315, HAPS_RS09320), ribosomes (HAPS_RS07815) and ABC transporters (HAPS_RS10945) was detected, particularly the metabolism pathway, and verified with RT-qPCR. Collectively, the gene expression profile in connection with tildipirosin resistance factors revealed unique and highly resistant determinants of H. parasuis to macrolides that warrant further attention due to the significant threat of bacterial resistance.

Multi-locus variable number tandem repeat analysis of 7th pandemic Vibrio cholerae

PubMed Central

2012-01-01

Background Seven pandemics of cholera have been recorded since 1817, with the current and ongoing pandemic affecting almost every continent. Cholera remains endemic in developing countries and is still a significant public health issue. In this study we use multilocus variable number of tandem repeats (VNTRs) analysis (MLVA) to discriminate between isolates of the 7th pandemic clone of Vibrio cholerae. Results MLVA of six VNTRs selected from previously published data distinguished 66 V. cholerae isolates collected between 1961–1999 into 60 unique MLVA profiles. Only 4 MLVA profiles consisted of more than 2 isolates. The discriminatory power was 0.995. Phylogenetic analysis showed that, except for the closely related profiles, the relationships derived from MLVA profiles were in conflict with that inferred from Single Nucleotide Polymorphism (SNP) typing. The six SNP groups share consensus VNTR patterns and two SNP groups contained isolates which differed by only one VNTR locus. Conclusions MLVA is highly discriminatory in differentiating 7th pandemic V. cholerae isolates and MLVA data was most useful in resolving the genetic relationships among isolates within groups previously defined by SNPs. Thus MLVA is best used in conjunction with SNP typing in order to best determine the evolutionary relationships among the 7th pandemic V. cholerae isolates and for longer term epidemiological typing. PMID:22624829

The first genetic map of pigeon pea based on diversity arrays technology (DArT) markers.

PubMed

Yang, Shi Ying; Saxena, Rachit K; Kulwal, Pawan L; Ash, Gavin J; Dubey, Anuja; Harper, John D I; Upadhyaya, Hari D; Gothalwal, Ragini; Kilian, Andrzej; Varshney, Rajeev K

2011-04-01

With an objective to develop a genetic map in pigeon pea (Cajanus spp.), a total of 554 diversity arrays technology (DArT) markers showed polymorphism in a pigeon pea F(2) mapping population of 72 progenies derived from an interspecific cross of ICP 28 (Cajanus cajan) and ICPW 94 (Cajanus scarabaeoides). Approximately 13% of markers did not conform to expected segregation ratio. The total number of DArT marker loci segregating in Mendelian manner was 405 with 73.1% (P > 0.001) of DArT markers having unique segregation patterns. Two groups of genetic maps were generated using DArT markers. While the maternal genetic linkage map had 122 unique DArT maternal marker loci, the paternal genetic linkage map has a total of 172 unique DArT paternal marker loci. The length of these two maps covered 270.0 cM and 451.6 cM, respectively. These are the first genetic linkage maps developed for pigeon pea, and this is the first report of genetic mapping in any grain legume using diversity arrays technology.

Gene-set analysis based on the pharmacological profiles of drugs to identify repurposing opportunities in schizophrenia.

PubMed

de Jong, Simone; Vidler, Lewis R; Mokrab, Younes; Collier, David A; Breen, Gerome

2016-08-01

Genome-wide association studies (GWAS) have identified thousands of novel genetic associations for complex genetic disorders, leading to the identification of potential pharmacological targets for novel drug development. In schizophrenia, 108 conservatively defined loci that meet genome-wide significance have been identified and hundreds of additional sub-threshold associations harbour information on the genetic aetiology of the disorder. In the present study, we used gene-set analysis based on the known binding targets of chemical compounds to identify the 'drug pathways' most strongly associated with schizophrenia-associated genes, with the aim of identifying potential drug repositioning opportunities and clues for novel treatment paradigms, especially in multi-target drug development. We compiled 9389 gene sets (2496 with unique gene content) and interrogated gene-based p-values from the PGC2-SCZ analysis. Although no single drug exceeded experiment wide significance (corrected p<0.05), highly ranked gene-sets reaching suggestive significance including the dopamine receptor antagonists metoclopramide and trifluoperazine and the tyrosine kinase inhibitor neratinib. This is a proof of principle analysis showing the potential utility of GWAS data of schizophrenia for the direct identification of candidate drugs and molecules that show polypharmacy. © The Author(s) 2016.

Automatic genetic optimization approach to two-dimensional blade profile design for steam turbines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trigg, M.A.; Tubby, G.R.; Sheard, A.G.

1999-01-01

In this paper a systematic approach to the optimization of two-dimensional blade profiles is presented. A genetic optimizer has been developed that modifies the blade profile and calculates its profile loss. This process is automatic, producing profile designs significantly faster and with significantly lower loss than has previously been possible. The optimizer developed uses a genetic algorithm to optimize a two-dimensional profile, defined using 17 parameters, for minimum loss with a given flow condition. The optimizer works with a population of two-dimensional profiles with varied parameters. A CFD mesh is generated for each profile, and the result is analyzed usingmore » a two-dimensional blade-to-blade solver, written for steady viscous compressible flow, to determine profile loss. The loss is used as the measure of a profile`s fitness. The optimizer uses this information to select the members of the next population, applying crossovers, mutations, and elitism in the process. Using this method, the optimizer tends toward the best values for the parameters defining the profile with minimum loss.« less

From genes to genomes: a new paradigm for studying fungal pathogenesis in Magnaporthe oryzae.

PubMed

Xu, Jin-Rong; Zhao, Xinhua; Dean, Ralph A

2007-01-01

Magnaporthe oryzae is the most destructive fungal pathogen of rice worldwide and because of its amenability to classical and molecular genetic manipulation, availability of a genome sequence, and other resources it has emerged as a leading model system to study host-pathogen interactions. This chapter reviews recent progress toward elucidation of the molecular basis of infection-related morphogenesis, host penetration, invasive growth, and host-pathogen interactions. Related information on genome analysis and genomic studies of plant infection processes is summarized under specific topics where appropriate. Particular emphasis is placed on the role of MAP kinase and cAMP signal transduction pathways and unique features in the genome such as repetitive sequences and expanded gene families. Emerging developments in functional genome analysis through large-scale insertional mutagenesis and gene expression profiling are detailed. The chapter concludes with new prospects in the area of systems biology, such as protein expression profiling, and highlighting remaining crucial information needed to fully appreciate host-pathogen interactions.

Bosutinib, dasatinib, imatinib, nilotinib, and ponatinib differentially affect the vascular molecular pathways and functionality of human endothelial cells.

PubMed

Gover-Proaktor, Ayala; Granot, Galit; Pasmanik-Chor, Metsada; Pasvolsky, Oren; Shapira, Saar; Raz, Oshrat; Raanani, Pia; Leader, Avi

2018-05-09

The tyrosine kinase inhibitors (TKIs), nilotinib, ponatinib, and dasatinib (but not bosutinib or imatinib), are associated with vascular adverse events (VAEs) in chronic myeloid leukemia (CML). Though the mechanism is inadequately understood, an effect on vascular cells has been suggested. We investigated the effect of imatinib, nilotinib, dasatinib, bosutinib, and ponatinib on tube formation, cell viability, and gene expression of human vascular endothelial cells (HUVECs). We found a distinct genetic profile in HUVECs treated with dasatinib, ponatinib, and nilotinib compared to bosutinib and imatinib, who resembled untreated samples. However, unique gene expression and molecular pathway alterations were detected between dasatinib, ponatinib, and nilotinib. Angiogenesis/blood vessel-related pathways and HUVEC function (tube formation/viability) were adversely affected by dasatinib, ponatinib, and nilotinib but not by imatinib or bosutinib. These results correspond to the differences in VAE profiles of these TKIs, support a direct effect on vascular cells, and provide direction for future research.

Comparison of bacteroides-prevotella 16S rRNA genetic markers for fecal samples from different animal species.

PubMed

Fogarty, Lisa R; Voytek, Mary A

2005-10-01

To effectively manage surface and ground waters it is necessary to improve our ability to detect and identify sources of fecal contamination. We evaluated the use of the anaerobic bacterial group Bacteroides-Prevotella as a potential fecal indicator. Terminal restriction length polymorphism (T-RFLP) of the 16S rRNA genes from this group was used to determine differences in populations and to identify any unique populations in chickens, cows, deer, dogs, geese, horses, humans, pigs, and seagulls. The group appears to be a good potential fecal indicator in all groups tested except for avians. Cluster analysis of Bacteroides-Prevotella community T-RFLP profiles indicates that Bacteroides-Prevotella populations from samples of the same host species are much more similar to each other than to samples from different source species. We were unable to identify unique peaks that were exclusive to any source species; however, for most host species, at least one T-RFLP peak was identified to be more commonly found in that species, and a combination of peaks could be used to identify the source. T-RFLP profiles obtained from water spiked with known-source feces contained the expected diagnostic peaks from the source. These results indicate that the approach of identifying Bacteroides-Prevotella molecular markers associated with host species might be useful in identifying sources of fecal contamination in the environment.

Comparison of Bacteroides-Prevotella 16S rRNA Genetic Markers for Fecal Samples from Different Animal Species

PubMed Central

Fogarty, Lisa R.; Voytek, Mary A.

2005-01-01

To effectively manage surface and ground waters it is necessary to improve our ability to detect and identify sources of fecal contamination. We evaluated the use of the anaerobic bacterial group Bacteroides-Prevotella as a potential fecal indicator. Terminal restriction length polymorphism (T-RFLP) of the 16S rRNA genes from this group was used to determine differences in populations and to identify any unique populations in chickens, cows, deer, dogs, geese, horses, humans, pigs, and seagulls. The group appears to be a good potential fecal indicator in all groups tested except for avians. Cluster analysis of Bacteroides-Prevotella community T-RFLP profiles indicates that Bacteroides-Prevotella populations from samples of the same host species are much more similar to each other than to samples from different source species. We were unable to identify unique peaks that were exclusive to any source species; however, for most host species, at least one T-RFLP peak was identified to be more commonly found in that species, and a combination of peaks could be used to identify the source. T-RFLP profiles obtained from water spiked with known-source feces contained the expected diagnostic peaks from the source. These results indicate that the approach of identifying Bacteroides-Prevotella molecular markers associated with host species might be useful in identifying sources of fecal contamination in the environment. PMID:16204514

Comparison of Bacteroides-Prevotella 16S rRNA genetic markers for fecal samples from different animal species

USGS Publications Warehouse

Fogarty, L.R.; Voytek, M.A.

2005-01-01

To effectively manage surface and ground waters it is necessary to improve our ability to detect and identify sources of fecal contamination. We evaluated the use of the anaerobic bacterial group Bacteroides-Prevotella as a potential fecal indicator. Terminal restriction length polymorphism (T-RFLP) of the 16S rRNA genes from this group was used to determine differences in populations and to identify any unique populations in chickens, cows, deer, dogs, geese, horses, humans, pigs, and seagulls. The group appears to be a good potential fecal indicator in all groups tested except for avians. Cluster analysis of Bacteroides-Prevotella community T-RFLP profiles indicates that Bacteroides-Prevotella populations from samples of the same host species are much more similar to each other than to samples from different source species. We were unable to identify unique peaks that were exclusive to any source species; however, for most host species, at least one T-RFLP peak was identified to be more commonly found in that species, and a combination of peaks could be used to identify the source. T-RFLP profiles obtained from water spiked with known-source feces contained the expected diagnostic peaks from the source. These results indicate that the approach of identifying Bacteroides-Prevotella molecular markers associated with host species might be useful in identifying sources of fecal contamination in the environment.

Functional annotation of chemical libraries across diverse biological processes.

PubMed

Piotrowski, Jeff S; Li, Sheena C; Deshpande, Raamesh; Simpkins, Scott W; Nelson, Justin; Yashiroda, Yoko; Barber, Jacqueline M; Safizadeh, Hamid; Wilson, Erin; Okada, Hiroki; Gebre, Abraham A; Kubo, Karen; Torres, Nikko P; LeBlanc, Marissa A; Andrusiak, Kerry; Okamoto, Reika; Yoshimura, Mami; DeRango-Adem, Eva; van Leeuwen, Jolanda; Shirahige, Katsuhiko; Baryshnikova, Anastasia; Brown, Grant W; Hirano, Hiroyuki; Costanzo, Michael; Andrews, Brenda; Ohya, Yoshikazu; Osada, Hiroyuki; Yoshida, Minoru; Myers, Chad L; Boone, Charles

2017-09-01

Chemical-genetic approaches offer the potential for unbiased functional annotation of chemical libraries. Mutations can alter the response of cells in the presence of a compound, revealing chemical-genetic interactions that can elucidate a compound's mode of action. We developed a highly parallel, unbiased yeast chemical-genetic screening system involving three key components. First, in a drug-sensitive genetic background, we constructed an optimized diagnostic mutant collection that is predictive for all major yeast biological processes. Second, we implemented a multiplexed (768-plex) barcode-sequencing protocol, enabling the assembly of thousands of chemical-genetic profiles. Finally, based on comparison of the chemical-genetic profiles with a compendium of genome-wide genetic interaction profiles, we predicted compound functionality. Applying this high-throughput approach, we screened seven different compound libraries and annotated their functional diversity. We further validated biological process predictions, prioritized a diverse set of compounds, and identified compounds that appear to have dual modes of action.

Mining natural variation for maize improvement: Selection on phenotypes and genes

USDA-ARS?s Scientific Manuscript database

Maize is highly genetically and phenotypically diverse. Tropical maize and teosinte are important genetic resources that harbor unique alleles not found in temperate maize hybrids. To access these resources, breeders must be able to extract favorable unique alleles from tropical maize and teosinte f...

Long-term genetic selection reduced prevalence of hip and elbow dysplasia in 60 dog breeds

PubMed Central

Keller, G. G.; Famula, T. R.

2017-01-01

Canine hip dysplasia (CHD) and elbow dysplasia (ED) impact the health and welfare of all dogs. The first formally organized assessment scheme to improve canine health centered on reducing the prevalence of these orthopedic disorders. Phenotypic screening of joint conformation remains the currently available strategy for breeders to make selection decisions. The present study evaluated the efficacy of employing phenotypic selection on breed improvement of hips and elbows using the Orthopedic Foundation for Animals complete database spanning the 1970–2015 time period. Sixty breeds having more than 1000 unique hip evaluations and 500 elbow evaluations (1,056,852 and 275,129 hip and elbow records, respectively) were interrogated to derive phenotypic improvement, sex and age at time of assessment effects, correlation between the two joints, heritability estimates, estimated breeding values (EBV), and effectiveness of maternal/paternal selection. The data demonstrated that there has been overall improvement in hip and elbow conformation with a reduction in EBV for disease liability, although the breeds differed in the magnitude of the response to selection. Heritabilities also differed substantially across the breeds as did the correlation of the joints; in the absence of a universal association of these differences with breed size, popularity, or participation in screening, it appears that the breeds themselves vary in genetic control. There was subtle, though again breed specific, impact of sex and older ages on CHD and ED. There was greater paternal impact on a reduction of CHD. In the absence of direct genetic tests for either of these two diseases, phenotypic selection has proven to be effective. Furthermore, the data underscore that selection schemes must be breed specific and that it is likely the genetic profiles will be unique across the breeds for these two conditions. Despite the advances achieved with phenotypic selection, incorporation of EBVs into selection schemes should accelerate advances in hip and elbow improvement. PMID:28234985

Long-term genetic selection reduced prevalence of hip and elbow dysplasia in 60 dog breeds.

PubMed

Oberbauer, A M; Keller, G G; Famula, T R

2017-01-01

Canine hip dysplasia (CHD) and elbow dysplasia (ED) impact the health and welfare of all dogs. The first formally organized assessment scheme to improve canine health centered on reducing the prevalence of these orthopedic disorders. Phenotypic screening of joint conformation remains the currently available strategy for breeders to make selection decisions. The present study evaluated the efficacy of employing phenotypic selection on breed improvement of hips and elbows using the Orthopedic Foundation for Animals complete database spanning the 1970-2015 time period. Sixty breeds having more than 1000 unique hip evaluations and 500 elbow evaluations (1,056,852 and 275,129 hip and elbow records, respectively) were interrogated to derive phenotypic improvement, sex and age at time of assessment effects, correlation between the two joints, heritability estimates, estimated breeding values (EBV), and effectiveness of maternal/paternal selection. The data demonstrated that there has been overall improvement in hip and elbow conformation with a reduction in EBV for disease liability, although the breeds differed in the magnitude of the response to selection. Heritabilities also differed substantially across the breeds as did the correlation of the joints; in the absence of a universal association of these differences with breed size, popularity, or participation in screening, it appears that the breeds themselves vary in genetic control. There was subtle, though again breed specific, impact of sex and older ages on CHD and ED. There was greater paternal impact on a reduction of CHD. In the absence of direct genetic tests for either of these two diseases, phenotypic selection has proven to be effective. Furthermore, the data underscore that selection schemes must be breed specific and that it is likely the genetic profiles will be unique across the breeds for these two conditions. Despite the advances achieved with phenotypic selection, incorporation of EBVs into selection schemes should accelerate advances in hip and elbow improvement.

Construction of the first compendium of chemical-genetic profiles in the fission yeast Schizosaccharomyces pombe and comparative compendium approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Sangjo; Lee, Minho; Chang, Hyeshik

Highlights: •The first compendium of chemical-genetic profiles form fission yeast was generated. •The first HTS of drug mode-of-action in fission yeast was performed. •The first comparative chemical genetic analysis between two yeasts was conducted. -- Abstract: Genome-wide chemical genetic profiles in Saccharomyces cerevisiae since the budding yeast deletion library construction have been successfully used to reveal unknown mode-of-actions of drugs. Here, we introduce comparative approach to infer drug target proteins more accurately using two compendiums of chemical-genetic profiles from the budding yeast S. cerevisiae and the fission yeast Schizosaccharomyces pombe. For the first time, we established DNA-chip based growth defectmore » measurement of genome-wide deletion strains of S. pombe, and then applied 47 drugs to the pooled heterozygous deletion strains to generate chemical-genetic profiles in S. pombe. In our approach, putative drug targets were inferred from strains hypersensitive to given drugs by analyzing S. pombe and S. cerevisiae compendiums. Notably, many evidences in the literature revealed that the inferred target genes of fungicide and bactericide identified by such comparative approach are in fact the direct targets. Furthermore, by filtering out the genes with no essentiality, the multi-drug sensitivity genes, and the genes with less eukaryotic conservation, we created a set of drug target gene candidates that are expected to be directly affected by a given drug in human cells. Our study demonstrated that it is highly beneficial to construct the multiple compendiums of chemical genetic profiles using many different species. The fission yeast chemical-genetic compendium is available at (http://pombe.kaist.ac.kr/compendium)« less

Molecular characterization of Streptococcus agalactiae strains isolated from fishes in Malaysia.

PubMed

Amal, M N A; Zamri-Saad, M; Siti-Zahrah, A; Zulkafli, A R; Nur-Nazifah, M

2013-07-01

The aim of this study was to characterize Streptococcus agalactiae strains that were isolated from fishes in Malaysia using random amplified polymorphic DNA (RAPD) and repetitive extragenic palindromic PCR (REP-PCR) techniques. A total of 181 strains of Strep. agalactiae isolated from red hybrid tilapia (Oreochromis sp.) and golden pompano (Trachinotus blochii) were characterized using RAPD and REP-PCR techniques. Both the fingerprinting techniques generated reproducible band patterns, differing in the number and molecular mass amplicons. The RAPD technique displayed greater discriminatory power by its production of more complex binding pattern and divided all the strains into 13 groups, compared to 9 by REP-PCR technique. Both techniques showed the availability to differentiate the genetic profiles of the strains according to their geographical location of origin. Three strains of Strep. agalactiae that were recovered from golden pompano showed a genetic dissimilarity from the strains isolated from red hybrid tilapia, while the strain of ATCC 27956 that recovered from bovine displayed a unique profile for both methods. Both techniques possess excellent discriminative capabilities and can be used as a rapid means of comparing Strep. agalactiae strains for future epidemiological investigation. Framework as the guideline in traceability of this disease and in the search for potential local vaccine candidates for streptococcosis in this country. Journal of Applied Microbiology © 2013 The Society for Applied Microbiology.

[Forensic hematology genetics--paternity testing].

PubMed

Kratzer, A; Bär, W

1997-05-01

In Switzerland paternity investigations are carried out using DNA analysis only since 1991. DNA patterns are inherited and only with the exception of genetically identical twins they are different in everyone and therefore unique to an individual. Hence DNA-systems are an excellent tool to resolve paternity disputes. DNA polymorphisms used for paternity diagnosis are length polymorphisms of the highly polymorphic VNTR loci [variable number of tandem repeats]. The most frequently applied systems are the DNA single locus systems. In addition to the DNA single locus systems the application of PCR (PCR = polymerase chain reaction) based DNA systems has increased particularly in difficult deficiency cases or in cases where only small evidential samples or partially degraded DNA are available. Normally four independent DNA single probes are used to produce a DNA profile from the mother, the child and the alleged father. A child inherits half the DNA patterns from its mother and the other half from its true biological father. If an alleged father doesn't possess the paternal specific DNA pattern in his DNA profile he is excluded from the paternity. In case of non-exclusion the probability for paternity is calculated according to Essen-Möller. When applying four highly polymorphic DNA single locus systems the biostatistical evaluation leads always to W-values exceeding 99.8% [= required value for positive proof of paternity]. DNA analysis is currently the best available method to achieve such effective conclusions in paternity investigations.

Coordinated transcriptional regulation patterns associated with infertility phenotypes in men

PubMed Central

Ellis, Peter J I; Furlong, Robert A; Conner, Sarah J; Kirkman‐Brown, Jackson; Afnan, Masoud; Barratt, Christopher; Griffin, Darren K; Affara, Nabeel A

2007-01-01

Introduction Microarray gene‐expression profiling is a powerful tool for global analysis of the transcriptional consequences of disease phenotypes. Understanding the genetic correlates of particular pathological states is important for more accurate diagnosis and screening of patients, and thus for suggesting appropriate avenues of treatment. As yet, there has been little research describing gene‐expression profiling of infertile and subfertile men, and thus the underlying transcriptional events involved in loss of spermatogenesis remain unclear. Here we present the results of an initial screen of 33 patients with differing spermatogenic phenotypes. Methods Oligonucleotide array expression profiling was performed on testis biopsies for 33 patients presenting for testicular sperm extraction. Significantly regulated genes were selected using a mixed model analysis of variance. Principle components analysis and hierarchical clustering were used to interpret the resulting dataset with reference to the patient history, clinical findings and histological composition of the biopsies. Results Striking patterns of coordinated gene expression were found. The most significant contains multiple germ cell‐specific genes and corresponds to the degree of successful spermatogenesis in each patient, whereas a second pattern corresponds to inflammatory activity within the testis. Smaller‐scale patterns were also observed, relating to unique features of the individual biopsies. PMID:17496197

Better together? Examining profiles of employee recovery experiences.

PubMed

Bennett, Andrew A; Gabriel, Allison S; Calderwood, Charles; Dahling, Jason J; Trougakos, John P

2016-12-01

Employees are exposed to a wide variety of job demands that deplete personal resources and necessitate recovery. In light of this need, research on work recovery has focused on how distinct recovery experiences during postwork time relate to employee well-being. However, investigators have largely tested the effects of these experiences in isolation, neglecting the possibility that profiles of recovery experiences may exist and influence the recovery process. The current set of studies adopted a person-centered approach using latent profile analysis to understand whether unique constellations of recovery experiences-psychological detachment, relaxation, mastery, control, and problem-solving pondering-emerged for 2 samples of full-time employees. In Study 1, which involved a single-time-point assessment, we identified 4 unique profiles of recovery experiences, tested whether job demands (i.e., time pressure, role ambiguity) and job resources (i.e., job control) differentiated profile membership, and evaluated whether each profile uniquely related to employee well-being outcomes (i.e., emotional exhaustion, engagement, somatic complaints). In Study 2, which involved 2 time points, we replicated 3 of the 4 profiles observed in Study 1, and tested 2 additional antecedents rated by employees' supervisors: leader-member exchange and supervisor support for recovery. Across both studies, unique differences emerged in regard to antecedents and outcomes tied to recovery experience profile membership. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Cancer genetic risk assessment and referral patterns in primary care.

PubMed

Vig, Hetal S; Armstrong, Joanne; Egleston, Brian L; Mazar, Carla; Toscano, Michele; Bradbury, Angela R; Daly, Mary B; Meropol, Neal J

2009-12-01

This study was undertaken to describe cancer risk assessment practices among primary care providers (PCPs). An electronic survey was sent to PCPs affiliated with a single insurance carrier. Demographic and practice characteristics associated with cancer genetic risk assessment and testing activities were described. Latent class analysis supported by likelihood ratio tests was used to define PCP profiles with respect to the level of engagement in genetic risk assessment and referral activity based on demographic and practice characteristics. 860 physicians responded to the survey (39% family practice, 29% internal medicine, 22% obstetrics/gynecology (OB/GYN), 10% other). Most respondents (83%) reported that they routinely assess hereditary cancer risk; however, only 33% reported that they take a full, three-generation pedigree for risk assessment. OB/GYN specialty, female gender, and physician access to a genetic counselor were independent predictors of referral to cancer genetics specialists. Three profiles of PCPs, based upon referral practice and extent of involvement in genetics evaluation, were defined. Profiles of physician characteristics associated with varying levels of engagement with cancer genetic risk assessment and testing can be identified. These profiles may ultimately be useful in targeting decision support tools and services.

Isolation and genetic analysis of pure cells from forensic biological mixtures: The precision of a digital approach.

PubMed

Fontana, F; Rapone, C; Bregola, G; Aversa, R; de Meo, A; Signorini, G; Sergio, M; Ferrarini, A; Lanzellotto, R; Medoro, G; Giorgini, G; Manaresi, N; Berti, A

2017-07-01

Latest genotyping technologies allow to achieve a reliable genetic profile for the offender identification even from extremely minute biological evidence. The ultimate challenge occurs when genetic profiles need to be retrieved from a mixture, which is composed of biological material from two or more individuals. In this case, DNA profiling will often result in a complex genetic profile, which is then subject matter for statistical analysis. In principle, when more individuals contribute to a mixture with different biological fluids, their single genetic profiles can be obtained by separating the distinct cell types (e.g. epithelial cells, blood cells, sperm), prior to genotyping. Different approaches have been investigated for this purpose, such as fluorescent-activated cell sorting (FACS) or laser capture microdissection (LCM), but currently none of these methods can guarantee the complete separation of different type of cells present in a mixture. In other fields of application, such as oncology, DEPArray™ technology, an image-based, microfluidic digital sorter, has been widely proven to enable the separation of pure cells, with single-cell precision. This study investigates the applicability of DEPArray™ technology to forensic samples analysis, focusing on the resolution of the forensic mixture problem. For the first time, we report here the development of an application-specific DEPArray™ workflow enabling the detection and recovery of pure homogeneous cell pools from simulated blood/saliva and semen/saliva mixtures, providing full genetic match with genetic profiles of corresponding donors. In addition, we assess the performance of standard forensic methods for DNA quantitation and genotyping on low-count, DEPArray™-isolated cells, showing that pure, almost complete profiles can be obtained from as few as ten haploid cells. Finally, we explore the applicability in real casework samples, demonstrating that the described approach provides complete separation of cells with outstanding precision. In all examined cases, DEPArray™ technology proves to be a groundbreaking technology for the resolution of forensic biological mixtures, through the precise isolation of pure cells for an incontrovertible attribution of the obtained genetic profiles. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The effect of quercetin on genetic expression of the commensal gut microbes Bifidobacterium catenulatum, Enterococcus caccae and Ruminococcus gauvreauii.

PubMed

Firrman, Jenni; Liu, LinShu; Zhang, Liqing; Arango Argoty, Gustavo; Wang, Minqian; Tomasula, Peggy; Kobori, Masuko; Pontious, Sherri; Xiao, Weidong

2016-12-01

Quercetin is one of the most abundant polyphenols found in fruits and vegetables. The ability of the gut microbiota to metabolize quercetin has been previously documented; however, the effect that quercetin may have on commensal gut microbes remains unclear. In the present study, the effects of quercetin on the commensal gut microbes Ruminococcus gauvreauii, Bifidobacterium catenulatum and Enterococcus caccae were determined through evaluation of growth patterns and cell morphology, and analysis of genetic expression profiles between quercetin treated and non-treated groups using Single Molecule RNA sequencing via Helicos technology. Results of this study revealed that phenotypically, quercetin did not prevent growth of Ruminococcus gauvreauii, mildly suppressed growth of Bifidobacterium catenulatum, and moderately inhibited growth of Enterococcus caccae. Genetic analysis revealed that in response to quercetin, Ruminococcus gauvreauii down regulated genes responsible for protein folding, purine synthesis and metabolism. Bifidobacterium catenulatum increased expression of the ABC transport pathway and decreased metabolic pathways and cell wall synthesis. Enterococcus caccae upregulated genes responsible for energy production and metabolism, and downregulated pathways of stress response, translation and sugar transport. For the first time, the effect of quercetin on the growth and genetic expression of three different commensal gut bacteria was documented. The data provides insight into the interactions between genetic regulation and growth. This is also a unique demonstration of how RNA single molecule sequencing can be used to study the gut microbiota. Published by Elsevier Ltd.

Molecular actions and clinical pharmacogenetics of lithium therapy

PubMed Central

Can, Adem; Schulze, Thomas G.; Gould, Todd D.

2014-01-01

Mood disorders, including bipolar disorder and depression, are relatively common human diseases for which pharmacological treatment options are often not optimal. Among existing pharmacological agents and mood stabilizers used for the treatment of mood disorders, lithium has a unique clinical profile. Lithium has efficacy in the treatment of bipolar disorder generally, and in particular mania, while also being useful in the adjunct treatment of refractory depression. In addition to antimanic and adjunct antidepressant efficacy, lithium is also proven effective in the reduction of suicide and suicidal behaviors. However, only a subset of patients manifests beneficial responses to lithium therapy and the underlying genetic factors of response are not exactly known. Here we discuss preclinical research suggesting mechanisms likely to underlie lithium’s therapeutic actions including direct targets inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) among others, as well as indirect actions including modulation of neurotrophic and neurotransmitter systems and circadian function. We follow with a discussion of current knowledge related to the pharmacogenetic underpinnings of effective lithium therapy in patients within this context. Progress in elucidation of genetic factors that may be involved in human response to lithium pharmacology has been slow, and there is still limited conclusive evidence for the role of a particular genetic factor. However, the development of new approaches such as genome-wide association studies (GWAS), and increased use of genetic testing and improved identification of mood disorder patients sub-groups will lead to improved elucidation of relevant genetic factors in the future. PMID:24534415

Population structure of the NPGS Senegalese sorghum collection and its evaluation to identify new disease resistant genes.

PubMed

Cuevas, Hugo E; Prom, Louis K; Rosa-Valentin, Giseiry

2018-01-01

Sorghum germplasm from West and Central Africa is cultivated in rainy and high humidity regions and is an important source of resistance genes to fungal diseases. Mold and anthracnose are two important biotic constraints to sorghum production in wet areas worldwide. Here, 158 National Plant Germplasm System (NPGS) accessions from Senegal were evaluated for agronomic traits, anthracnose, and grain mold resistance at two locations, and genetically characterized according to 20 simple sequence repeat markers. A total of 221 alleles were amplified with an average of 11 alleles per locus. Each accession had a unique genetic profile (i.e., no duplicates), and the average genetic distance between accessions was 0.42. Population structure and cluster analysis separated the collection into four populations with pairwise FST values >0.15. Three of the populations were composed of Guinea-race sorghum germplasm, and one included multiple races. Anthracnose resistant accessions were present at high frequency and evenly distributed among the three Guinea-race populations. Fourteen accessions showed resistance to grain mold, and eight were resistant to both diseases. These results indicated that the NPGS of Senegal is a genetically diverse collection with a high frequency of disease resistant accessions. Nevertheless, its population structure suggests the presence of few sources of resistance to both grain mold and anthracnose, which are fixed in the germplasm. The phenotypic and genotypic information for these accessions provides a valuable resource for its correct use to broaden the genetic base of breeding programs.

[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.

Genetic Comparison of B. Anthracis and its Close Relatives Using AFLP and PCR Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackson, P.J.; Hill, K.K.; Laker, M.T.

1999-02-01

Amplified Fragment length Polymorphism (AFLP) analysis allows a rapid, relatively simple analysis of a large portion of a microbial genome, providing information about the species and its phylogenetic relationship to other microbes (Vos, et al., 1995). The method simply surveys the genome for length and sequence polymorphisms. The pattern identified can be used for comparison to the genomes of other species. Unlike other methods, it does not rely on analysis of a single genetic locus that may bias the interpretation of results and it does not require any prior knowledge of the targeted organism. Moreover, a standard set of reagentsmore » can be applied to any species without using species-specific information or molecular probes. The authors are using AFLP's to rapidly identify different bacterial species. A comparison of AFLP profiles generated from a large battery of B. anthracis strains shows very little variability among different isolates (Keim, et al., 1997). By contrast, there is a significant difference between AFLP profiles generated for any B. anthracis strain and even the most closely related Bacillus species. Sufficient variability is apparent among all known microbial species to allow phylogenetic analysis based on large numbers of genetically unlinked loci. These striking differences among AFLP profiles allow unambiguous identification of previously identified species and phylogenetic placement of newly characterized isolates relative to known species based on a large number of independent genetic loci. Data generated thus far show that the method provides phylogenetic analyses that are consistent with other widely accepted phylogenetic methods. However, AFLP analysis provides a more detailed analysis of the targets and samples a much larger portion of the genome. Consequently, it provides an inexpensive, rapid means of characterizing microbial isolates to further differentiate among strains and closely related microbial species. Such information cannot be rapidly generated by other means. AFLP sample analysis quickly generates a very large amount of molecular information about microbial genomes. However, this information cannot be analyzed rapidly using manual methods. The authors are developing a large archive of electronic AFLP signatures that is being used to identify isolates collected from medical, veterinary, forensic and environmental samples. They are also developing the computational packages necessary to rapidly and unambiguously analyze the AFLP profiles and conduct a phylogenetic comparison of these data relative to information already in the database. They will use this archive and the associated algorithms to determine the species identity of previously uncharacterized isolates and place them phylogenetically relative to other microbes based on their AFLP signatures. This study provides significant new information about microbes with environmental, veterinary and medical significance. This information can be used in further studies to understand the relationships among these species and the factors that distinguish them from one another. It should also allow identification of unique factors that contribute to important microbial traits including pathogenicity and virulence. They are also using AFLP data to identify, isolate and sequence DNA fragments that are unique to particular microbial species and strains. The fragment patterns and sequence information provide insights into the complexity and organization of bacterial genomes relative to one another. They also provide the information necessary for development of species-specific PCR primers that can be used to interrogate complex samples for the presence of B. anthracis, other microbial pathogens or their remnants.« less

Decoding the non-coding genome: elucidating genetic risk outside the coding genome.

PubMed

Barr, C L; Misener, V L

2016-01-01

Current evidence emerging from genome-wide association studies indicates that the genetic underpinnings of complex traits are likely attributable to genetic variation that changes gene expression, rather than (or in combination with) variation that changes protein-coding sequences. This is particularly compelling with respect to psychiatric disorders, as genetic changes in regulatory regions may result in differential transcriptional responses to developmental cues and environmental/psychosocial stressors. Until recently, however, the link between transcriptional regulation and psychiatric genetic risk has been understudied. Multiple obstacles have contributed to the paucity of research in this area, including challenges in identifying the positions of remote (distal from the promoter) regulatory elements (e.g. enhancers) and their target genes and the underrepresentation of neural cell types and brain tissues in epigenome projects - the availability of high-quality brain tissues for epigenetic and transcriptome profiling, particularly for the adolescent and developing brain, has been limited. Further challenges have arisen in the prediction and testing of the functional impact of DNA variation with respect to multiple aspects of transcriptional control, including regulatory-element interaction (e.g. between enhancers and promoters), transcription factor binding and DNA methylation. Further, the brain has uncommon DNA-methylation marks with unique genomic distributions not found in other tissues - current evidence suggests the involvement of non-CG methylation and 5-hydroxymethylation in neurodevelopmental processes but much remains unknown. We review here knowledge gaps as well as both technological and resource obstacles that will need to be overcome in order to elucidate the involvement of brain-relevant gene-regulatory variants in genetic risk for psychiatric disorders. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Molecular genetic identification of skeletal remains from the Second World War Konfin I mass grave in Slovenia

PubMed Central

Gornjak Pogorelc, Barbara; Balažic, Jože

2010-01-01

This paper describes molecular genetic identification of one third of the skeletal remains of 88 victims of postwar (June 1945) killings found in the Konfin I mass grave in Slovenia. Living relatives were traced for 36 victims. We analyzed 84 right femurs and compared their genetic profiles to the genetic material of living relatives. We cleaned the bones, removed surface contamination, and ground the bones into powder. Prior to DNA isolation using Biorobot EZ1 (Qiagen), the powder was decalcified. The nuclear DNA of the samples was quantified using the real-time polymerase chain reaction method. We extracted 0.8 to 100 ng DNA/g of bone powder from 82 bones. Autosomal genetic profiles and Y-chromosome haplotypes were obtained from 98% of the bones, and mitochondrial DNA (mtDNA) haplotypes from 95% of the bones for the HVI region and from 98% of the bones for the HVII region. Genetic profiles of the nuclear and mtDNA were determined for reference persons. For traceability in the event of contamination, we created an elimination database including genetic profiles of the nuclear and mtDNA of all persons that had been in contact with the skeletal remains. When comparing genetic profiles, we matched 28 of the 84 bones analyzed with living relatives (brothers, sisters, sons, daughters, nephews, or cousins). The statistical analyses showed a high confidence of correct identification for all 28 victims in the Konfin I mass grave (posterior probability ranged from 99.9% to more than 99.999999%). PMID:20217112

Molecular genetic identification of skeletal remains from the Second World War Konfin I mass grave in Slovenia.

PubMed

Zupanic Pajnic, Irena; Gornjak Pogorelc, Barbara; Balazic, Joze

2010-07-01

This paper describes molecular genetic identification of one third of the skeletal remains of 88 victims of postwar (June 1945) killings found in the Konfin I mass grave in Slovenia. Living relatives were traced for 36 victims. We analyzed 84 right femurs and compared their genetic profiles to the genetic material of living relatives. We cleaned the bones, removed surface contamination, and ground the bones into powder. Prior to DNA isolation using Biorobot EZ1 (Qiagen), the powder was decalcified. The nuclear DNA of the samples was quantified using the real-time polymerase chain reaction method. We extracted 0.8 to 100 ng DNA/g of bone powder from 82 bones. Autosomal genetic profiles and Y-chromosome haplotypes were obtained from 98% of the bones, and mitochondrial DNA (mtDNA) haplotypes from 95% of the bones for the HVI region and from 98% of the bones for the HVII region. Genetic profiles of the nuclear and mtDNA were determined for reference persons. For traceability in the event of contamination, we created an elimination database including genetic profiles of the nuclear and mtDNA of all persons that had been in contact with the skeletal remains. When comparing genetic profiles, we matched 28 of the 84 bones analyzed with living relatives (brothers, sisters, sons, daughters, nephews, or cousins). The statistical analyses showed a high confidence of correct identification for all 28 victims in the Konfin I mass grave (posterior probability ranged from 99.9% to more than 99.999999%).

African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks.

PubMed

Erkizan, Hayriye Verda; Johnson, Kory; Ghimbovschi, Svetlana; Karkera, Deepa; Trachiotis, Gregory; Adib, Houtan; Hoffman, Eric P; Wadleigh, Robert G

2017-06-19

Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups. To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues. We found significant dysregulation of genes encoding drug-metabolizing enzymes and stress response components of the NRF2- mediated oxidative damage pathway, potentially representing key genes in African-American esophageal squamous carcinogenesis. Loss of activity of drug metabolizing enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence and aggressiveness of ESCC in this ethnic group. To determine whether certain genes are uniquely altered in African-American ESCC we performed a meta-analysis of ESCC expression profiles in our African-American samples and those of several Asian samples. Down-regulation of TP53 pathway components represented the most common feature in ESCC of all ethnic groups. Importantly, this analysis revealed a potential distinctive molecular underpinning of African-American ESCC, that is, a widespread and prominent involvement of the NRF2 pathway. Taken together, these findings highlight the remarkable interplay of genetic and environmental factors in the pathogenesis of African-American ESCC.

Overlapping Genetic and Child-Specific Nonshared Environmental Influences on Listening Comprehension, Reading Motivation, and Reading Comprehension

PubMed Central

Schenker, Victoria J.; Petrill, Stephen A.

2015-01-01

This study investigated the genetic and environmental influences on observed associations between listening comprehension, reading motivation, and reading comprehension. Univariate and multivariate quantitative genetic models were conducted in a sample of 284 pairs of twins at a mean age of 9.81 years. Genetic and nonshared environmental factors accounted for statistically significant variance in listening and reading comprehension, and nonshared environmental factors accounted for variance in reading motivation. Furthermore, listening comprehension demonstrated unique genetic and nonshared environmental influences but also had overlapping genetic influences with reading comprehension. Reading motivation and reading comprehension each had unique and overlapping nonshared environmental contributions. Therefore, listening comprehension appears to be related to reading primarily due to genetic factors whereas motivation appears to affect reading via child-specific, nonshared environmental effects. PMID:26321677

Overlapping genetic and child-specific nonshared environmental influences on listening comprehension, reading motivation, and reading comprehension.

PubMed

Schenker, Victoria J; Petrill, Stephen A

2015-01-01

This study investigated the genetic and environmental influences on observed associations between listening comprehension, reading motivation, and reading comprehension. Univariate and multivariate quantitative genetic models were conducted in a sample of 284 pairs of twins at a mean age of 9.81 years. Genetic and nonshared environmental factors accounted for statistically significant variance in listening and reading comprehension, and nonshared environmental factors accounted for variance in reading motivation. Furthermore, listening comprehension demonstrated unique genetic and nonshared environmental influences but also had overlapping genetic influences with reading comprehension. Reading motivation and reading comprehension each had unique and overlapping nonshared environmental contributions. Therefore, listening comprehension appears to be related to reading primarily due to genetic factors whereas motivation appears to affect reading via child-specific, nonshared environmental effects. Copyright © 2015 Elsevier Inc. All rights reserved.

Female choice for male cuticular hydrocarbon profile in decorated crickets is not based on similarity to their own profile.

PubMed

Steiger, S; Capodeanu-Nägler, A; Gershman, S N; Weddle, C B; Rapkin, J; Sakaluk, S K; Hunt, J

2015-12-01

Indirect genetic benefits derived from female mate choice comprise additive (good genes) and nonadditive genetic benefits (genetic compatibility). Although good genes can be revealed by condition-dependent display traits, the mechanism by which compatibility alleles are detected is unclear because evaluation of the genetic similarity of a prospective mate requires the female to assess the genotype of the male and compare it to her own. Cuticular hydrocarbons (CHCs), lipids coating the exoskeleton of most insects, influence female mate choice in a number of species and offer a way for females to assess genetic similarity of prospective mates. Here, we determine whether female mate choice in decorated crickets is based on male CHCs and whether it is influenced by females' own CHC profiles. We used multivariate selection analysis to estimate the strength and form of selection acting on male CHCs through female mate choice, and employed different measures of multivariate dissimilarity to determine whether a female's preference for male CHCs is based on similarity to her own CHC profile. Female mating preferences were significantly influenced by CHC profiles of males. Male CHC attractiveness was not, however, contingent on the CHC profile of the choosing female, as certain male CHC phenotypes were equally attractive to most females, evidenced by significant linear and stabilizing selection gradients. These results suggest that additive genetic benefits, rather than nonadditive genetic benefits, accrue to female mate choice, in support of earlier work showing that CHC expression of males, but not females, is condition dependent. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Different neurodevelopmental symptoms have a common genetic etiology.

PubMed

Pettersson, Erik; Anckarsäter, Henrik; Gillberg, Christopher; Lichtenstein, Paul

2013-12-01

Although neurodevelopmental disorders are demarcated as discrete entities in the Diagnostic Statistical Manual of mental disorders, empirical evidence indicates that there is a high degree of overlap among them. The first aim of this investigation was to explore if a single general factor could account for the large degree of observed overlap among neurodevelopmental problems, and explore whether this potential factor was primarily genetic or environmental in origin. The second aim was to explore whether there was systematic covariation, either genetic or environmental, over and above that contributed by the potential general factor, unique to each syndrome. Parents of all Swedish 9- and 12-year-old twin pairs born between 1992 and 2002 were targeted for interview regarding problems typical of autism spectrum disorders, ADHD and other neurodevelopmental conditions (response rate: 80 percent). Structural equation modeling was conducted on 6,595 pairs to examine the genetic and environmental structure of 53 neurodevelopmental problems. One general genetic factor accounted for a large proportion of the phenotypic covariation among the 53 symptoms. Three specific genetic subfactors identified 'impulsivity,' 'learning problems,' and 'tics and autism,' respectively. Three unique environment factors identified 'autism,' 'hyperactivity and impulsivity,' and 'inattention and learning problems,' respectively. One general genetic factor was responsible for the wide-spread phenotypic overlap among all neurodevelopmental symptoms, highlighting the importance of addressing broad patient needs rather than specific diagnoses. The unique genetic factors may help guide diagnostic nomenclature, whereas the unique environmental factors may highlight that neurodevelopmental symptoms are responsive to change at the individual level and may provide clues into different mechanisms and treatments. Future research would benefit from assessing the general factor separately from specific factors to better understand observed overlap among neurodevelopmental problems. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Understanding the Relation between Anorexia Nervosa and Bulimia Nervosa in a Swedish National Twin Sample

PubMed Central

Bulik, Cynthia M; Thornton, Laura; Root, Tammy L.; Pisetsky, Emily M.; Lichtenstein, Paul; Pedersen, Nancy L.

2010-01-01

Background We present a bivariate twin analysis of anorexia nervosa (AN) and bulimia nervosa (BN) to determine the extent to which shared genetic and environmental factors contribute to liability to these disorders. Method Focusing on females from the Swedish Twin study of Adults: Genes and Environment (STAGE) (N=7000), we calculated heritability estimates for narrow and broad AN and BN and estimated their genetic correlation. Results In the full model, the heritability estimate for narrow AN was (a2 = .57; 95% CI: .00, .81) and for narrow BN (a2 = .62; 95% CI: .08, .70) with the remaining variance accounted for by unique environmental factors. Shared environmental factors estimates were (c2 = .00; 95% CI: .00, .67) for AN and (c2 = .00; 95% CI: .00, .40) for BN. Moderate additive genetic (.46) and unique environmental (.42) correlations between AN and BN were observed. Heritability estimates for broad AN were lower (a2 = .29; 95% CI: .04, .43) than for narrow AN, but estimates for broad BN were similar to narrow BN. The genetic correlation for broad AN and BN was .79 and the unique environmental correlation was .44. Conclusions We highlight the contribution of additive genetic factors to both narrow and broad AN and BN and demonstrate a moderate overlap of both genetic and unique environmental factors that influence the two conditions. Common concurrent and sequential comorbidity of AN and BN can in part be accounted for by shared genetic and environmental influences on liability although independent factors also operative. PMID:19828139

Conditional clustering of temporal expression profiles

PubMed Central

Wang, Ling; Montano, Monty; Rarick, Matt; Sebastiani, Paola

2008-01-01

Background Many microarray experiments produce temporal profiles in different biological conditions but common cluster techniques are not able to analyze the data conditional on the biological conditions. Results This article presents a novel technique to cluster data from time course microarray experiments performed across several experimental conditions. Our algorithm uses polynomial models to describe the gene expression patterns over time, a full Bayesian approach with proper conjugate priors to make the algorithm invariant to linear transformations, and an iterative procedure to identify genes that have a common temporal expression profile across two or more experimental conditions, and genes that have a unique temporal profile in a specific condition. Conclusion We use simulated data to evaluate the effectiveness of this new algorithm in finding the correct number of clusters and in identifying genes with common and unique profiles. We also use the algorithm to characterize the response of human T cells to stimulations of antigen-receptor signaling gene expression temporal profiles measured in six different biological conditions and we identify common and unique genes. These studies suggest that the methodology proposed here is useful in identifying and distinguishing uniquely stimulated genes from commonly stimulated genes in response to variable stimuli. Software for using this clustering method is available from the project home page. PMID:18334028

Genetic profiling of two phenotypically distinct outbred rats derived from a colony of the Zucker fatty rats maintained at Tokyo Medical University

PubMed Central

Nakanishi, Satoshi; Kuramoto, Takashi; Kashiwazaki, Naomi; Yokoi, Norihide

2016-01-01

The Zucker fatty (ZF) rat is an outbred rat and a well-known model of obesity without diabetes, harboring a missense mutation (fatty, abbreviated as fa) in the leptin receptor gene (Lepr). Slc:Zucker (Slc:ZF) outbred rats exhibit obesity while Hos:ZFDM-Leprfa (Hos:ZFDM) outbred rats exhibit obesity and type 2 diabetes. Both outbred rats have been derived from an outbred ZF rat colony maintained at Tokyo Medical University. So far, genetic profiles of these outbred rats remain unknown. Here, we applied a simple genotyping method using Ampdirect reagents and FTA cards (Amp-FTA) in combination with simple sequence length polymorphisms (SSLP) markers to determine genetic profiles of Slc:ZF and Hos:ZFDM rats. Among 27 SSLP marker loci, 24 loci (89%) were fixed for specific allele at each locus in Slc:ZF rats and 26 loci (96%) were fixed in Hos:ZFDM rats, respectively. This indicates the low genetic heterogeneity in both colonies of outbred rats. Nine loci (33%) showed different alleles between the two outbred rats, suggesting considerably different genetic profiles between the two outbred rats in spite of the same origin. Additional analysis using 72 SSLP markers further supported these results and clarified the profiles in detail. This study revealed that genetic profiles of the Slc:ZF and Hos:ZFDM outbred rats are different for about 30% of the SSLP marker loci, which is the underlying basis for the phenotypic difference between the two outbred rats. PMID:27795491

Genetic and Biochemical Diversity among Isolates of Paenibacillus alvei Cultured from Australian Honeybee (Apis mellifera) Colonies

PubMed Central

Djordjevic, Steven P.; Forbes, Wendy A.; Smith, Lisa A.; Hornitzky, Michael A.

2000-01-01

Twenty-five unique CfoI-generated whole-cell DNA profiles were identified in a study of 30 Paenibacillus alvei isolates cultured from honey and diseased larvae collected from honeybee (Apis mellifera) colonies in geographically diverse areas in Australia. The fingerprint patterns were highly variable and readily discernible from one another, which highlighted the potential of this method for tracing the movement of isolates in epidemiological studies. 16S rRNA gene fragments (length, 1,416 bp) for all 30 isolates were enzymatically amplified by PCR and subjected to restriction analysis with DraI, HinfI, CfoI, AluI, FokI, and RsaI. With each enzyme the restriction profiles of the 16S rRNA genes from all 30 isolates were identical (one restriction fragment length polymorphism [RFLP] was observed in the HinfI profile of the 16S rRNA gene from isolate 17), which confirmed that the isolates belonged to the same species. The restriction profiles generated by using DraI, FokI, and HinfI differentiated P. alvei from the phylogenetically closely related species Paenibacillus macerans and Paenibacillus macquariensis. Alveolysin gene fragments (length, 1,555 bp) were enzymatically amplified from some of the P. alvei isolates (19 of 30 isolates), and RFLP were detected by using the enzymes CfoI, Sau3AI, and RsaI. Extrachromosomal DNA ranging in size from 1 to 10 kb was detected in 17 of 30 (57%) P. alvei whole-cell DNA profiles. Extensive biochemical heterogeneity was observed among the 28 P. alvei isolates examined with the API 50CHB system. All of these isolates were catalase, oxidase, and Voges-Proskauer positive and nitrate negative, and all produced acid when glycerol, esculin, and maltose were added. The isolates produced variable results for 16 of the 49 biochemical tests; negative reactions were recorded in the remaining 30 assays. The genetic and biochemical heterogeneity in P. alvei isolates may be a reflection of adaptation to the special habitats in which they originated. PMID:10698777

Genetic and biochemical diversity among isolates of Paenibacillus alvei cultured from Australian honeybee (Apis mellifera) colonies.

PubMed

Djordjevic, S P; Forbes, W A; Smith, L A; Hornitzky, M A

2000-03-01

Twenty-five unique CfoI-generated whole-cell DNA profiles were identified in a study of 30 Paenibacillus alvei isolates cultured from honey and diseased larvae collected from honeybee (Apis mellifera) colonies in geographically diverse areas in Australia. The fingerprint patterns were highly variable and readily discernible from one another, which highlighted the potential of this method for tracing the movement of isolates in epidemiological studies. 16S rRNA gene fragments (length, 1,416 bp) for all 30 isolates were enzymatically amplified by PCR and subjected to restriction analysis with DraI, HinfI, CfoI, AluI, FokI, and RsaI. With each enzyme the restriction profiles of the 16S rRNA genes from all 30 isolates were identical (one restriction fragment length polymorphism [RFLP] was observed in the HinfI profile of the 16S rRNA gene from isolate 17), which confirmed that the isolates belonged to the same species. The restriction profiles generated by using DraI, FokI, and HinfI differentiated P. alvei from the phylogenetically closely related species Paenibacillus macerans and Paenibacillus macquariensis. Alveolysin gene fragments (length, 1, 555 bp) were enzymatically amplified from some of the P. alvei isolates (19 of 30 isolates), and RFLP were detected by using the enzymes CfoI, Sau3AI, and RsaI. Extrachromosomal DNA ranging in size from 1 to 10 kb was detected in 17 of 30 (57%) P. alvei whole-cell DNA profiles. Extensive biochemical heterogeneity was observed among the 28 P. alvei isolates examined with the API 50CHB system. All of these isolates were catalase, oxidase, and Voges-Proskauer positive and nitrate negative, and all produced acid when glycerol, esculin, and maltose were added. The isolates produced variable results for 16 of the 49 biochemical tests; negative reactions were recorded in the remaining 30 assays. The genetic and biochemical heterogeneity in P. alvei isolates may be a reflection of adaptation to the special habitats in which they originated.

A Swedish national twin study of criminal behavior and its violent, white-collar and property subtypes.

PubMed

Kendler, K S; Maes, H H; Lönn, S L; Morris, N A; Lichtenstein, P; Sundquist, J; Sundquist, K

2015-08-01

We sought to clarify the etiological contribution of genetic and environmental factors to total criminal behavior (CB) measured as criminal convictions in men and women, and to violent (VCB), white-collar (WCCB) and property criminal behavior (PCB) in men only. In 21 603 twin pairs from the Swedish Twin Registry, we obtained information on all criminal convictions from 1973 to 2011 from the Swedish Crime Register. Twin modeling was performed using the OpenMx package. For all criminal convictions, heritability was estimated at around 45% in both sexes, with the shared environment accounting for 18% of the variance in liability in females and 27% in males. The correlation of these risk factors across sexes was estimated at +0.63. In men, the magnitudes of genetic and environmental influence were similar in the three criminal conviction subtypes. However, for violent and white-collar convictions, nearly half and one-third of the genetic effects were respectively unique to that criminal subtype. About half of the familial environmental effects were unique to property convictions. The familial aggregation of officially recorded CB is substantial and results from both genetic and familial environmental factors. These factors are moderately correlated across the sexes suggesting that some genetic and environmental influences on criminal convictions are unique to men and to women. Violent criminal behavior and property crime are substantially influenced respectively by genetic and shared environmental risk factors unique to that criminal subtype.

Alu polymorphic insertions reveal genetic structure of north Indian populations.

PubMed

Tripathi, Manorama; Tripathi, Piyush; Chauhan, Ugam Kumari; Herrera, Rene J; Agrawal, Suraksha

2008-10-01

The Indian subcontinent is characterized by the ancestral and cultural diversity of its people. Genetic input from several unique source populations and from the unique social architecture provided by the caste system has shaped the current genetic landscape of India. In the present study 200 individuals each from three upper-caste and four middle-caste Hindu groups and from two Muslim populations in North India were examined for 10 polymorphic Alu insertions (PAIs). The investigated PAIs exhibit high levels of polymorphism and average heterozygosity. Limited interpopulation variance and genetic flow in the present study suggest admixture. The results of this study demonstrate that, contrary to common belief, the caste system has not provided an impermeable barrier to genetic exchange among Indian groups.

Diversity amongst trigeminal neurons revealed by high throughput single cell sequencing

PubMed Central

Nguyen, Minh Q.; Wu, Youmei; Bonilla, Lauren S.; von Buchholtz, Lars J.

2017-01-01

The trigeminal ganglion contains somatosensory neurons that detect a range of thermal, mechanical and chemical cues and innervate unique sensory compartments in the head and neck including the eyes, nose, mouth, meninges and vibrissae. We used single-cell sequencing and in situ hybridization to examine the cellular diversity of the trigeminal ganglion in mice, defining thirteen clusters of neurons. We show that clusters are well conserved in dorsal root ganglia suggesting they represent distinct functional classes of somatosensory neurons and not specialization associated with their sensory targets. Notably, functionally important genes (e.g. the mechanosensory channel Piezo2 and the capsaicin gated ion channel Trpv1) segregate into multiple clusters and often are expressed in subsets of cells within a cluster. Therefore, the 13 genetically-defined classes are likely to be physiologically heterogeneous rather than highly parallel (i.e., redundant) lines of sensory input. Our analysis harnesses the power of single-cell sequencing to provide a unique platform for in silico expression profiling that complements other approaches linking gene-expression with function and exposes unexpected diversity in the somatosensory system. PMID:28957441

A critical appraisal of the scientific basis of commercial genomic profiles used to assess health risks and personalize health interventions.

PubMed

Janssens, A Cecile J W; Gwinn, Marta; Bradley, Linda A; Oostra, Ben A; van Duijn, Cornelia M; Khoury, Muin J

2008-03-01

Predictive genomic profiling used to produce personalized nutrition and other lifestyle health recommendations is currently offered directly to consumers. By examining previous meta-analyses and HuGE reviews, we assessed the scientific evidence supporting the purported gene-disease associations for genes included in genomic profiles offered online. We identified seven companies that offer predictive genomic profiling. We searched PubMed for meta-analyses and HuGE reviews of studies of gene-disease associations published from 2000 through June 2007 in which the genotypes of people with a disease were compared with those of a healthy or general-population control group. The seven companies tested at least 69 different polymorphisms in 56 genes. Of the 56 genes tested, 24 (43%) were not reviewed in meta-analyses. For the remaining 32 genes, we found 260 meta-analyses that examined 160 unique polymorphism-disease associations, of which only 60 (38%) were found to be statistically significant. Even the 60 significant associations, which involved 29 different polymorphisms and 28 different diseases, were generally modest, with synthetic odds ratios ranging from 0.54 to 0.88 for protective variants and from 1.04 to 3.2 for risk variants. Furthermore, genes in cardiogenomic profiles were more frequently associated with noncardiovascular diseases than with cardiovascular diseases, and though two of the five genes of the osteogenomic profiles did show significant associations with disease, the associations were not with bone diseases. There is insufficient scientific evidence to conclude that genomic profiles are useful in measuring genetic risk for common diseases or in developing personalized diet and lifestyle recommendations for disease prevention.

Genetics Home Reference: Williams syndrome

MedlinePlus

... Berman KF. Neural correlates of genetically abnormal social cognition in Williams syndrome. Nat Neurosci. 2005 Aug;8( ... syndrome: a unique window to genetic influences on cognition and behaviour. Nat Rev Neurosci. 2006 May;7( ...

Duality based direct resolution of unique profiles using zero concentration region information.

PubMed

Tavakkoli, Elnaz; Rajkó, Róbert; Abdollahi, Hamid

2018-07-01

Self Modeling Curve Resolution (SMCR) is a class of techniques concerned with estimating pure profiles underlying a set of measurements on chemical systems. In general, the estimated profiles are ambiguous (non-unique) except if some special conditions fulfilled. Implementing the adequate information can reduce the so-called rotational ambiguity effectively, and in the most desirable cases lead to the unique solution. Therefore, studies on circumstances resulting in unique solution are of particular importance. The conditions of unique solution can particularly be studied based on duality principle. In bilinear chemical (e.g., spectroscopic) data matrix, there is a natural duality between its row and column vector spaces using minimal constraints (non-negativity of concentrations and absorbances). In this article, the conditions of the unique solution according to duality concept and using zero concentration region information is intended to show. A simulated dataset of three components and an experimental system with synthetic mixtures containing three amino acids tyrosine, phenylalanine and tryptophan are analyzed. It is shown that in the presence of sufficient information, the reliable unique solution is obtained that is valuable in analytical qualification and for quantitative verification analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

Metabolome and fecal microbiota in monozygotic twin pairs discordant for weight: a Big Mac challenge.

PubMed

Bondia-Pons, Isabel; Maukonen, Johanna; Mattila, Ismo; Rissanen, Aila; Saarela, Maria; Kaprio, Jaakko; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Hyötyläinen, Tuulia; Pietiläinen, Kirsi H; Orešič, Matej

2014-09-01

Postprandial responses to food are complex, involving both genetic and environmental factors. We studied postprandial responses to a Big Mac meal challenge in monozygotic co-twins highly discordant for body weight. This unique design allows assessment of the contribution of obesity, independent of genetic liability. Comprehensive metabolic profiling using 3 analytical platforms was applied to fasting and postprandial serum samples from 16 healthy monozygotic twin pairs discordant for weight (body mass index difference >3 kg/m(2)). Nine concordant monozygotic pairs were examined as control pairs. Fecal samples were analyzed to assess diversity of the major bacterial groups by using 5 different validated bacterial group specific denaturing gradient gel electrophoresis methods. No differences in fecal bacterial diversity were detected when comparing co-twins discordant for weight (ANOVA, P<0.05). We found that within-pair similarity is a dominant factor in the metabolic postprandial response, independent of acquired obesity. Branched chain amino acids were increased in heavier as compared with leaner co-twins in the fasting state, but their levels converged postprandially (paired t tests, FDR q<0.05). We also found that specific bacterial groups were associated with postprandial changes of specific metabolites. Our findings underline important roles of genetic and early life factors in the regulation of postprandial metabolite levels. © FASEB.

Novel microsatellite markers acquired from Rubus coreanus Miq. and cross-amplification in other Rubus species.

PubMed

Lee, Gi-An; Song, Jae Young; Choi, Heh-Ran; Chung, Jong-Wook; Jeon, Young-Ah; Lee, Jung-Ro; Ma, Kyung-Ho; Lee, Myung-Chul

2015-04-10

The Rubus genus consists of more than 600 species that are distributed globally. Only a few Rubus species, including raspberries and blueberries, have been domesticated. Genetic diversity within and between Rubus species is an important resource for breeding programs. We developed genomic microsatellite markers using an SSR-enriched R. coreanus library to study the diversity of the Rubus species. Microsatellite motifs were discovered in 546 of 646 unique clones, and a dinucleotide repeat was the most frequent (75.3%) type of repeat. From 97 microsatellite loci with reproducible amplicons, we acquired 29 polymorphic microsatellite markers in the Rubus coreanus collection. The transferability values ranged from 59.8% to 84% across six Rubus species, and Rubus parvifolius had the highest transferability value (84%). The average number of alleles and the polymorphism information content were 5.7 and 0.541, respectively, in the R. coreanus collection. The diversity index of R. coreanus was similar to the values reported for other Rubus species. A phylogenetic dendrogram based on SSR profiles revealed that seven Rubus species could be allocated to three groups, and that R. coreanus was genetically close to Rubus crataegifolius (mountain berry). These new microsatellite markers might prove useful in studies of the genetic diversity, population structure, and evolutionary relationships among Rubus species.

Bilateral wilms tumor with TP53-related anaplasia.

PubMed

Popov, Sergey D; Vujanic, Gordan M; Sebire, Neil J; Chagtai, Tasnim; Williams, Richard; Vaidya, Sucheta; Pritchard-Jones, Kathy

2013-01-01

Wilms tumor (WT) with diffuse anaplasia has an unfavorable prognosis and is often (>70%) associated with mutations in the TP53 gene. Although most WTs are unilateral, 5-10% are bilateral, and they are almost always present with nephrogenic rests. The latter are considered a precursor of WT. Two cases of bilateral WTs with nephroblastomatosis, in which anaplastic changes were detected over a period of time, were analyzed using clinical, radiological, histopathological, and molecular-genetic data. TP53 was analyzed by direct sequencing of its full coding sequence and intron-exon boundaries in 11 fragments. DNA was extracted from paraffin-embedded or frozen specimens. High-resolution genomic copy number profiling was carried out by UCL Genomics on the Affymetrix Human Mapping 250K Nsp or Genome-Wide Human SNP Array 6.0 platform. Both cases demonstrated a strong association between the appearance of anaplastic clones and TP53 mutations. Synchronous ganglioneuroma was diagnosed in one case. Our cases are unique as they represent a long disease history and demonstrate the difficulties in managing rare cases of bilateral WT with anaplasia. These cases also emphasize the practical importance of modern molecular-genetic techniques and their clinical application. Moreover, they highlight the issue of the adequate sampling needed in order to gather comprehensive, efficient, and sufficient information about genetic events in a single tumor.

Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers

PubMed Central

Arashiro, Patricia; Eisenberg, Iris; Kho, Alvin T.; Cerqueira, Antonia M. P.; Canovas, Marta; Silva, Helga C. A.; Pavanello, Rita C. M.; Verjovski-Almeida, Sergio; Kunkel, Louis M.; Zatz, Mayana

2009-01-01

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disorder that has been associated with a contraction of 3.3-kb repeats on chromosome 4q35. FSHD is characterized by a wide clinical inter- and intrafamilial variability, ranging from wheelchair-bound patients to asymptomatic carriers. Our study is unique in comparing the gene expression profiles from related affected, asymptomatic carrier, and control individuals. Our results suggest that the expression of genes on chromosome 4q is altered in affected and asymptomatic individuals. Remarkably, the changes seen in asymptomatic samples are largely in products of genes encoding several chemokines, whereas the changes seen in affected samples are largely in genes governing the synthesis of GPI-linked proteins and histone acetylation. Besides this, the affected patient and related asymptomatic carrier share the 4qA161 haplotype. Thus, these polymorphisms by themselves do not explain the pathogenicity of the contracted allele. Interestingly, our results also suggest that the miRNAs might mediate the regulatory network in FSHD. Together, our results support the previous evidence that FSHD may be caused by transcriptional dysregulation of multiple genes, in cis and in trans, and suggest some factors potentially important for FSHD pathogenesis. The study of the gene expression profiles from asymptomatic carriers and related affected patients is a unique approach to try to enhance our understanding of the missing link between the contraction in D4Z4 repeats and muscle disease, while minimizing the effects of differences resulting from genetic background. PMID:19339494

Levetiracetam: the preclinical profile of a new class of antiepileptic drugs?

PubMed

Klitgaard, H

2001-01-01

Levetiracetam is a new antiepileptic drug (AED) devoid of anticonvulsant activity in the two classic screening models for AEDs, the maximal electroshock and pentylenetetrazol seizure tests in both mice and rats. This contrasts a potent seizure suppression in genetic and kindled mice and rats and against chemoconvulsants inducing partial seizures in rats. The highly selective action in "epileptic" animals distinguishes levetiracetam from classic and other new AEDs that have nearly equipotent effects in normal and "epileptic" animals. Levetiracetam induces minor behavioral alterations in normal and in kindled mice and rats. This results in an unusually high safety margin in animal models reflecting both partial and primary generalized epilepsy. Furthermore, experiments in the kindling model suggest that levetiracetam may possess antiepileptogenic properties due to a potent ability to prevent the development of kindling in mice and rats at doses devoid of adverse effects. Electrophysiologic recordings from different experimental models suggest that levetiracetam exerts a selective action against abnormal patterns of neuronal activity, which probably explains its selective protection in epileptic animals and its unique tolerability. This effect appears to derive from one or more novel mechanisms of action that do not involve a conventional interaction with traditional drug targets implicated in the modulation of inhibitory and excitatory neurotransmission. Instead, ligand-binding assays have disclosed a brain-specific binding site for levetiracetam. These studies reveal a unique preclinical profile of levetiracetam, distinct from that of all known AEDs, suggesting that levetiracetam could represent the first agent in a new class of AEDs.

Oncogene-induced senescence results in marked metabolic and bioenergetic alterations

PubMed Central

Quijano, Celia; Cao, Liu; Fergusson, Maria M; Romero, Hector; Liu, Jie; Gutkind, Sarah; Rovira, Ilsa I; Mohney, Robert P; Karoly, Edward D

2012-01-01

Oncogene-induced senescence (OIS) is characterized by permanent growth arrest and the acquisition of a secretory, pro-inflammatory state. Increasingly, OIS is viewed as an important barrier to tumorgenesis. Surprisingly, relatively little is known about the metabolic changes that accompany and therefore may contribute to OIS. Here, we have performed a metabolomic and bioenergetic analysis of Ras-induced senescence. Profiling approximately 300 different intracellular metabolites reveals that cells that have undergone OIS develop a unique metabolic signature that differs markedly from cells undergoing replicative senescence. A number of lipid metabolites appear uniquely increased in OIS cells, including a marked increase in the level of certain intracellular long chain fatty acids. Functional studies reveal that this alteration in the metabolome reflects substantial changes in overall lipid metabolism. In particular, Ras-induced senescent cells manifest a decline in lipid synthesis and a significant increase in fatty acid oxidation. Increased fatty acid oxidation results in an unexpectedly high rate of basal oxygen consumption in cells that have undergone OIS. Pharmacological or genetic inhibition of carnitine palmitoyltransferase 1, the rate-limiting step in mitochondrial fatty acid oxidation, restores a presenescent metabolic rate and, surprisingly, selectively inhibits the secretory, pro-inflammatory state that accompanies OIS. Thus, Ras-induced senescent cells demonstrate profound alterations in their metabolic and bioenergetic profiles, particularly with regards to the levels, synthesis and oxidation of free fatty acids. Furthermore, the inflammatory phenotype that accompanies OIS appears to be related to these underlying changes in cellular metabolism. PMID:22421146

Evaluating the genetic susceptibility to peer reported bullying behaviors.

PubMed

Musci, Rashelle J; Bettencourt, Amie F; Sisto, Danielle; Maher, Brion; Uhl, George; Ialongo, Nicholas; Bradshaw, Catherine P

2018-05-01

Bullying is a significant public health concern with lasting impacts on youth. Although environmental risk factors for bullying have been well-characterized, genetic influences on bullying are not well understood. This study explored the role of genetics on early childhood bullying behavior. Participants were 561 children who participated in a longitudinal randomized control trial of a preventive intervention beginning in first grade who were present for the first grade peer nominations used to measure early childhood bullying and who provided genetic data during the age 19-21 year follow-up in the form of blood or saliva. Measures included a polygenic risk score (PRS) derived from a conduct disorder genome wide association study. Latent profile analysis identified three profiles of bullying behaviors during early childhood. Results suggest that the PRS was significantly associated with class membership, with individuals in the moderate bully-victim profile having the highest levels of the PRS and those in the high bully-victim profile having the lowest levels. This line of research has important implications for understanding genetic vulnerability to bullying in early childhood. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

2011-04-01

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

Verna Wright Lecture: Psoriatic Arthritis: The Need for Early Intervention.

PubMed

McHugh, Neil J

2015-11-01

About 30% of individuals with skin psoriasis will develop an inflammatory disease of the peripheral or axial skeleton involving synovial and/or entheseal tissue termed psoriatic arthritis (PsA). In most cases psoriasis will precede PsA by several years. Hence skin psoriasis provides an opportune model to investigate genetic and environmental factors that interact and contribute to the development of a common form of inflammatory arthritis. Further, the preexisting presence of psoriasis represents a unique opportunity for the early detection of arthritis and the potential for more effective intervention. However, despite the presence of psoriasis, there may be delay in the diagnosis of PsA that is associated with adverse longterm outcome. Undiagnosed disease is not uncommon, as demonstrated by studies applying screening questionnaires to primary care and dermatology clinic populations. Other potential risk factors, such as obesity and smoking, the presence of certain genetic and biomarker profiles, combined with accurate imaging modalities, offer the potential for more targeted screening. So in future it should be possible to detect PsA at a much earlier stage and prevent significant joint damage and associated disability before it happens.

Comprehensive genetic study of fatty acids helps explain the role of noncoding inflammatory bowel disease associated SNPs and fatty acid metabolism in disease pathogenesis.

PubMed

Jezernik, Gregor; Potočnik, Uroš

2018-03-01

Fatty acids and their derivatives play an important role in inflammation. Diet and genetics influence fatty acid profiles. Abnormalities of fatty acid profiles have been observed in inflammatory bowel diseases (IBD), a group of complex diseases defined by chronic gastrointestinal inflammation. IBD associated fatty acid profile abnormalities were observed independently of nutritional status or disease activity, suggesting a common genetic background. However, no study so far has attempted to look for overlap between IBD loci and fatty acid associated loci or investigate the genetics of fatty acid profiles in IBD. To this end, we conducted a comprehensive genetic study of fatty acid profiles in IBD using iCHIP, a custom microarray platform designed for deep sequencing of immune-mediated disease associated loci. This study identifies 10 loci associated with fatty acid profiles in IBD. The most significant associations were a locus near CBS (p = 7.62 × 10 -8 ) and a locus in LRRK2 (p = 1.4 × 10 -7 ). Of note, this study replicates the FADS gene cluster locus, previously associated with both fatty acid profiles and IBD pathogenesis. Furthermore, we identify 18 carbon chain trans-fatty acids (p = 1.12 × 10 -3 ), total trans-fatty acids (p = 4.49 × 10 -3 ), palmitic acid (p = 5.85 × 10 -3 ) and arachidonic acid (p = 8.58 × 10 -3 ) as significantly associated with IBD pathogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Psychological aspects of human cloning and genetic manipulation: the identity and uniqueness of human beings.

PubMed

Morales, N M

2009-01-01

Human cloning has become one of the most controversial debates about reproduction in Western civilization. Human cloning represents asexual reproduction, but the critics of human cloning argue that the result of cloning is not a new individual who is genetically unique. There is also awareness in the scientific community, including the medical community, that human cloning and the creation of clones are inevitable. Psychology and other social sciences, together with the natural sciences, will need to find ways to help the healthcare system, to be prepared to face the new challenges introduced by the techniques of human cloning. One of those challenges is to help the healthcare system to find specific standards of behaviour that could be used to help potential parents to interact properly with cloned babies or children created through genetic manipulation. In this paper, the concepts of personality, identity and uniqueness are discussed in relationship to the contribution of twin studies in these areas. The author argues that an individual created by human cloning techniques or any other type of genetic manipulation will not show the donor's characteristics to the extent of compromising uniqueness. Therefore, claims to such an effect are needlessly alarmist.

Clusterons as a tool for monitoring populations of tick-borne encephalitis virus.

PubMed

Kovalev, Sergey Y; Mukhacheva, Tatyana A

2014-02-01

Tick-borne encephalitis (TBE) is a natural focal viral neuroinfection that is widespread in the temperate zone of Eurasia. Knowledge of the genetic structure of tick-borne encephalitis virus (TBEV) populations is important for understanding, not only the origin and evolution of the virus, but also the formation and maintenance of natural foci. A new approach to the differentiation of TBEV strains within subtype, with clusterons as the basis of analysis, has recently been proposed. In the present study, the genetic structure of TBEV-Sib populations has been investigated based on 387 strains isolated in the Middle Urals (Sverdlovsk region). Fourteen of the 18 currently known TBEV-Sib clusterons were identified. They belong to the Asian and Eastern European (Baltic) groups. It was shown that each TBE foci could be characterized by a unique clusteron profile. Three clusterons that emerged within the last 50 years have been identified which implies an active evolutionary process in the TBEV-Sib populations. The greatest diversity of clusterons was observed in the south of the Middle Urals along the Trans-Siberian Way. Such a pattern could reflect the history of colonization of the area and is closely related to the roads passing from Siberia to the European part of Russia through the Urals. In this article, the principles of continuous monitoring in the regional and local TBE foci are proposed, based on the quantitative and qualitative analysis of TBEV-Sib clusteron profiles. © 2013 Wiley Periodicals, Inc.

Interactions of OsMADS1 with Floral Homeotic Genes in Rice Flower Development.

PubMed

Hu, Yun; Liang, Wanqi; Yin, Changsong; Yang, Xuelian; Ping, Baozhe; Li, Anxue; Jia, Ru; Chen, Mingjiao; Luo, Zhijing; Cai, Qiang; Zhao, Xiangxiang; Zhang, Dabing; Yuan, Zheng

2015-09-01

During reproductive development, rice plants develop unique flower organs which determine the final grain yield. OsMADS1, one of SEPALLATA-like MADS-box genes, has been unraveled to play critical roles in rice floral organ identity specification and floral meristem determinacy. However, the molecular mechanisms underlying interactions of OsMADS1 with other floral homeotic genes in regulating flower development remains largely elusive. In this work, we studied the genetic interactions of OsMADS1 with B-, C-, and D-class genes along with physical interactions among their proteins. We show that the physical and genetic interactions between OsMADS1 and OsMADS3 are essential for floral meristem activity maintenance and organ identity specification; while OsMADS1 physically and genetically interacts with OsMADS58 in regulating floral meristem determinacy and suppressing spikelet meristem reversion. We provided important genetic evidence to support the neofunctionalization of two rice C-class genes (OsMADS3 and OsMADS58) during flower development. Gene expression profiling and quantitative RT-PCR analyses further revealed that OsMADS1 affects the expression of many genes involved in floral identity and hormone signaling, and chromatin immunoprecipitation (ChIP)-PCR assay further demonstrated that OsMADS17 is a direct target gene of OsMADS1. Taken together, these results reveal that OsMADS1 has diversified regulatory functions in specifying rice floral organ and meristem identity, probably through its genetic and physical interactions with different floral homeotic regulators. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Additive Genetic Risk from Five Serotonin System Polymorphisms Interacts with Interpersonal Stress to Predict Depression

PubMed Central

Vrshek-Schallhorn, Suzanne; Stroud, Catherine B.; Mineka, Susan; Zinbarg, Richard E.; Adam, Emma K.; Redei, Eva E.; Hammen, Constance; Craske, Michelle G.

2016-01-01

Behavioral genetic research supports polygenic models of depression in which many genetic variations each contribute a small amount of risk, and prevailing diathesis-stress models suggest gene-environment interactions (GxE). Multilocus profile scores of additive risk offer an approach that is consistent with polygenic models of depression risk. In a first demonstration of this approach in a GxE predicting depression, we created an additive multilocus profile score from five serotonin system polymorphisms (one each in the genes HTR1A, HTR2A, HTR2C, and two in TPH2). Analyses focused on two forms of interpersonal stress as environmental risk factors. Using five years of longitudinal diagnostic and life stress interviews from 387 emerging young adults in the Youth Emotion Project, survival analyses show that this multilocus profile score interacts with major interpersonal stressful life events to predict major depressive episode onsets (HR = 1.815, p = .007). Simultaneously, there was a significant protective effect of the profile score without a recent event (HR = 0.83, p = .030). The GxE effect with interpersonal chronic stress was not significant (HR = 1.15, p = .165). Finally, effect sizes for genetic factors examined ignoring stress suggested such an approach could lead to overlooking or misinterpreting genetic effects. Both the GxE effect and the protective simple main effect were replicated in a sample of early adolescent girls (N = 105). We discuss potential benefits of the multilocus genetic profile score approach and caveats for future research. PMID:26595467

Evaluating two-dimensional electrophoresis profiles of the protein phaseolin as markers of genetic differentiation and seed protein quality in common bean (Phaseolus vulgaris L.).

PubMed

López-Pedrouso, María; Bernal, Javier; Franco, Daniel; Zapata, Carlos

2014-07-23

High-resolution two-dimensional electrophoresis (2-DE) profiles of the protein phaseolin, the major seed storage protein of common bean, display great number of spots with differentially glycosylated and phosphorylated α- and β-type polypeptides. This work aims to test whether these complex profiles can be useful markers of genetic differentiation and seed protein quality in bean populations. The 2-DE phaseolin profile and the amino acid composition were examined in bean seeds from 18 domesticated and wild accessions belonging to the Mesoamerican and Andean gene pools. We found that proteomic distances based on 2-DE profiles were successful in identifying the accessions belonging to each gene pool and outliers distantly related. In addition, accessions identified as outliers from proteomic distances showed the highest levels of methionine content, an essential amino acid deficient in bean seeds. These findings suggest that 2-DE phaseolin profiles provide valuable information with potential of being used in common bean genetic improvement.

Characterization of Antimicrobial Resistance Patterns and Detection of Virulence Genes in Campylobacter Isolates in Italy

PubMed Central

Di Giannatale, Elisabetta; Di Serafino, Gabriella; Zilli, Katiuscia; Alessiani, Alessandra; Sacchini, Lorena; Garofolo, Giuliano; Aprea, Giuseppe; Marotta, Francesca

2014-01-01

Campylobacter has developed resistance to several antimicrobial agents over the years, including macrolides, quinolones and fluoroquinolones, becoming a significant public health hazard. A total of 145 strains derived from raw milk, chicken faeces, chicken carcasses, cattle faeces and human faeces collected from various Italian regions, were screened for antimicrobial susceptibility, molecular characterization (SmaI pulsed-field gel electrophoresis) and detection of virulence genes (sequencing and DNA microarray analysis). The prevalence of C. jejuni and C. coli was 62.75% and 37.24% respectively. Antimicrobial susceptibility revealed a high level of resistance for ciprofloxacin (62.76%), tetracycline (55.86%) and nalidixic acid (55.17%). Genotyping of Campylobacter isolates using PFGE revealed a total of 86 unique SmaI patterns. Virulence gene profiles were determined using a new microbial diagnostic microarray composed of 70-mer oligonucleotide probes targeting genes implicated in Campylobacter pathogenicity. Correspondence between PFGE and microarray clusters was observed. Comparisons of PFGE and virulence profiles reflected the high genetic diversity of the strains examined, leading us to speculate different degrees of pathogenicity inside Campylobacter populations. PMID:24556669

Characterization of antimicrobial resistance patterns and detection of virulence genes in Campylobacter isolates in Italy.

PubMed

Di Giannatale, Elisabetta; Di Serafino, Gabriella; Zilli, Katiuscia; Alessiani, Alessandra; Sacchini, Lorena; Garofolo, Giuliano; Aprea, Giuseppe; Marotta, Francesca

2014-02-19

Campylobacter has developed resistance to several antimicrobial agents over the years, including macrolides, quinolones and fluoroquinolones, becoming a significant public health hazard. A total of 145 strains derived from raw milk, chicken faeces, chicken carcasses, cattle faeces and human faeces collected from various Italian regions, were screened for antimicrobial susceptibility, molecular characterization (SmaI pulsed-field gel electrophoresis) and detection of virulence genes (sequencing and DNA microarray analysis). The prevalence of C. jejuni and C. coli was 62.75% and 37.24% respectively. Antimicrobial susceptibility revealed a high level of resistance for ciprofloxacin (62.76%), tetracycline (55.86%) and nalidixic acid (55.17%). Genotyping of Campylobacter isolates using PFGE revealed a total of 86 unique SmaI patterns. Virulence gene profiles were determined using a new microbial diagnostic microarray composed of 70-mer oligonucleotide probes targeting genes implicated in Campylobacter pathogenicity. Correspondence between PFGE and microarray clusters was observed. Comparisons of PFGE and virulence profiles reflected the high genetic diversity of the strains examined, leading us to speculate different degrees of pathogenicity inside Campylobacter populations.

Improved microarray methods for profiling the yeast knockout strain collection

PubMed Central

Yuan, Daniel S.; Pan, Xuewen; Ooi, Siew Loon; Peyser, Brian D.; Spencer, Forrest A.; Irizarry, Rafael A.; Boeke, Jef D.

2005-01-01

A remarkable feature of the Yeast Knockout strain collection is the presence of two unique 20mer TAG sequences in almost every strain. In principle, the relative abundances of strains in a complex mixture can be profiled swiftly and quantitatively by amplifying these sequences and hybridizing them to microarrays, but TAG microarrays have not been widely used. Here, we introduce a TAG microarray design with sophisticated controls and describe a robust method for hybridizing high concentrations of dye-labeled TAGs in single-stranded form. We also highlight the importance of avoiding PCR contamination and provide procedures for detection and eradication. Validation experiments using these methods yielded false positive (FP) and false negative (FN) rates for individual TAG detection of 3–6% and 15–18%, respectively. Analysis demonstrated that cross-hybridization was the chief source of FPs, while TAG amplification defects were the main cause of FNs. The materials, protocols, data and associated software described here comprise a suite of experimental resources that should facilitate the use of TAG microarrays for a wide variety of genetic screens. PMID:15994458

Categorizing Cells on the Basis of their Chemical Profiles: Progress in Single-Cell Mass Spectrometry.

PubMed

Comi, Troy J; Do, Thanh D; Rubakhin, Stanislav S; Sweedler, Jonathan V

2017-03-22

The chemical differences between individual cells within large cellular populations provide unique information on organisms' homeostasis and the development of diseased states. Even genetically identical cell lineages diverge due to local microenvironments and stochastic processes. The minute sample volumes and low abundance of some constituents in cells hinder our understanding of cellular heterogeneity. Although amplification methods facilitate single-cell genomics and transcriptomics, the characterization of metabolites and proteins remains challenging both because of the lack of effective amplification approaches and the wide diversity in cellular constituents. Mass spectrometry has become an enabling technology for the investigation of individual cellular metabolite profiles with its exquisite sensitivity, large dynamic range, and ability to characterize hundreds to thousands of compounds. While advances in instrumentation have improved figures of merit, acquiring measurements at high throughput and sampling from large populations of cells are still not routine. In this Perspective, we highlight the current trends and progress in mass-spectrometry-based analysis of single cells, with a focus on the technologies that will enable the next generation of single-cell measurements.

Supporting Asian patients with metastatic breast cancer during ixabepilone therapy.

PubMed

Bourdeanu, Laura; Wong, Siu-Fun

2010-05-01

Ixabepilone is currently FDA-approved in metastatic breast cancer, and most patients in the registrational trials were Caucasian. Studies in Asian populations receiving other cytotoxic agents have revealed differential pharmacokinetics and clinical outcomes. As such, clinicians should understand the possible contributions of Asian ethnicity and culture to the clinical profile of ixabepilone. Studies in Asian patients receiving other chemotherapeutics reported altered toxicity profiles for myelosuppression, neurotoxicity and gastrointestinal symptoms. Encouragingly, the limited clinical data in Asian patients receiving ixabepilone suggest that efficacy and toxicity in these women resemble those reported in the ixabepilone registrational trials. The reader will better understand how Asian genetics and culture may influence treatment outcomes and patient attitudes toward therapy and interaction with caregivers. Management of ixabepilone-related adverse events is also discussed with an emphasis on special considerations for Asian patients. Awareness of possible altered drug response in Asian patients will aid clinicians in monitoring for toxicity, recognizing the need for dose modification and educating patients. Sensitivity to cultural aspects that are unique to Asians may improve adherence, reporting of adverse events and trust among Asian patients receiving ixabepilone.

Metagenomic profiling of historic Colorado Front Range flood impact on distribution of riverine antibiotic resistance genes.

PubMed

Garner, Emily; Wallace, Joshua S; Argoty, Gustavo Arango; Wilkinson, Caitlin; Fahrenfeld, Nicole; Heath, Lenwood S; Zhang, Liqing; Arabi, Mazdak; Aga, Diana S; Pruden, Amy

2016-12-05

Record-breaking floods in September 2013 caused massive damage to homes and infrastructure across the Colorado Front Range and heavily impacted the Cache La Poudre River watershed. Given the unique nature of this watershed as a test-bed for tracking environmental pathways of antibiotic resistance gene (ARG) dissemination, we sought to determine the impact of extreme flooding on ARG reservoirs in river water and sediment. We utilized high-throughput DNA sequencing to obtain metagenomic profiles of ARGs before and after flooding, and investigated 23 antibiotics and 14 metals as putative selective agents during post-flood recovery. With 277 ARG subtypes identified across samples, total bulk water ARGs decreased following the flood but recovered to near pre-flood abundances by ten months post-flood at both a pristine site and at a site historically heavily influenced by wastewater treatment plants and animal feeding operations. Network analysis of de novo assembled sequencing reads into 52,556 scaffolds identified ARGs likely located on mobile genetic elements, with up to 11 ARGs per plasmid-associated scaffold. Bulk water bacterial phylogeny correlated with ARG profiles while sediment phylogeny varied along the river's anthropogenic gradient. This rare flood afforded the opportunity to gain deeper insight into factors influencing the spread of ARGs in watersheds.

Metagenomic profiling of historic Colorado Front Range flood impact on distribution of riverine antibiotic resistance genes

NASA Astrophysics Data System (ADS)

Garner, Emily; Wallace, Joshua S.; Argoty, Gustavo Arango; Wilkinson, Caitlin; Fahrenfeld, Nicole; Heath, Lenwood S.; Zhang, Liqing; Arabi, Mazdak; Aga, Diana S.; Pruden, Amy

2016-12-01

Record-breaking floods in September 2013 caused massive damage to homes and infrastructure across the Colorado Front Range and heavily impacted the Cache La Poudre River watershed. Given the unique nature of this watershed as a test-bed for tracking environmental pathways of antibiotic resistance gene (ARG) dissemination, we sought to determine the impact of extreme flooding on ARG reservoirs in river water and sediment. We utilized high-throughput DNA sequencing to obtain metagenomic profiles of ARGs before and after flooding, and investigated 23 antibiotics and 14 metals as putative selective agents during post-flood recovery. With 277 ARG subtypes identified across samples, total bulk water ARGs decreased following the flood but recovered to near pre-flood abundances by ten months post-flood at both a pristine site and at a site historically heavily influenced by wastewater treatment plants and animal feeding operations. Network analysis of de novo assembled sequencing reads into 52,556 scaffolds identified ARGs likely located on mobile genetic elements, with up to 11 ARGs per plasmid-associated scaffold. Bulk water bacterial phylogeny correlated with ARG profiles while sediment phylogeny varied along the river’s anthropogenic gradient. This rare flood afforded the opportunity to gain deeper insight into factors influencing the spread of ARGs in watersheds.

Genetics of the Framingham Heart Study Population

PubMed Central

Govindaraju, Diddahally R.; Cupples, L. Adrienne; Kannel, William B.; O’Donnell, Christopher J.; Atwood, Larry D.; D’Agostino, Ralph B.; Fox, Caroline S.; Larson, Marty; Levy, Daniel; Morabito, Joanne; Vasan, Ramachandran S.; Splansky, Greta Lee; Wolf, Philip A.; Benjamin, Emelia J.

2010-01-01

This article provides an introduction to the Framingham Heart Study (FHS) and the genetic research related to cardiovascular diseases conducted in this unique population1. It briefly describes the origins of the study, the risk factors that contribute to heart disease and the approaches taken to discover the genetic basis of some of these risk factors. The genetic architecture of several biological risk factors has been explained using family studies, segregation analysis, heritability, phenotypic and genetic correlations. Many quantitative trait loci underlying cardiovascular diseases have been discovered using different molecular markers. Additionally, results from genome-wide association studies using 100,000 markers, and the prospects of using 550,000 markers for association studies are presented. Finally, the use of this unique sample in genotype and environment interaction is described. PMID:19010253

Obesity management in Prader-Willi syndrome.

PubMed

Salehi, Parisa; Leavitt, Anne; Beck, Anita E; Chen, Maida L; Roth, Christian L

2015-03-01

Prader-Willi Syndrome (PWS) is one of the most common genetic causes of obesity. The phenotype of obesity in PWS is unique and characterized by hyperphagia, earlier meal initiation, delayed meal termination, reduced energy expenditure, abnormal gut hormone profiles, as well as irregular responses to food in areas of the brain associated with satiety and reward. Management of obesity is necessary to avoid major morbidity. The relentless food-seeking behavior associated with PWS such as stealing, hoarding food, eating inedibles, and lying about eating, can cause turmoil both inside and outside of the home. Management is challenging for both patients and caretakers, but at this time there are limited medical therapies available besides dietary restriction and behavior management. However, current research shows promise for discovery of additional treatment options for hyperphagia and obesity management in PWS.

Extensive genetic diversity, unique population structure and evidence of genetic exchange in the sexually transmitted parasite Trichomonas vaginalis.

PubMed

Conrad, Melissa D; Gorman, Andrew W; Schillinger, Julia A; Fiori, Pier Luigi; Arroyo, Rossana; Malla, Nancy; Dubey, Mohan Lal; Gonzalez, Jorge; Blank, Susan; Secor, William E; Carlton, Jane M

2012-01-01

Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection world-wide. Despite its prevalence, little is known about the genetic diversity and population structure of this haploid parasite due to the lack of appropriate tools. The development of a panel of microsatellite makers and SNPs from mining the parasite's genome sequence has paved the way to a global analysis of the genetic structure of the pathogen and association with clinical phenotypes. Here we utilize a panel of T. vaginalis-specific genetic markers to genotype 235 isolates from Mexico, Chile, India, Australia, Papua New Guinea, Italy, Africa and the United States, including 19 clinical isolates recently collected from 270 women attending New York City sexually transmitted disease clinics. Using population genetic analysis, we show that T. vaginalis is a genetically diverse parasite with a unique population structure consisting of two types present in equal proportions world-wide. Parasites belonging to the two types (type 1 and type 2) differ significantly in the rate at which they harbor the T. vaginalis virus, a dsRNA virus implicated in parasite pathogenesis, and in their sensitivity to the widely-used drug, metronidazole. We also uncover evidence of genetic exchange, indicating a sexual life-cycle of the parasite despite an absence of morphologically-distinct sexual stages. Our study represents the first robust and comprehensive evaluation of global T. vaginalis genetic diversity and population structure. Our identification of a unique two-type structure, and the clinically relevant phenotypes associated with them, provides a new dimension for understanding T. vaginalis pathogenesis. In addition, our demonstration of the possibility of genetic exchange in the parasite has important implications for genetic research and control of the disease.

The impact of shrimp farming effluent on bacterial communities in mangrove waters, Ceará, Brazil.

PubMed

Sousa, O V; Macrae, A; Menezes, F G R; Gomes, N C M; Vieira, R H S F; Mendonça-Hagler, L C S

2006-12-01

The effects of shrimp farm effluents on bacterial communities in mangroves have been infrequently reported. Classic and molecular biology methods were used to survey bacterial communities from four mangroves systems. Water temperature, salinity, pH, total heterotrophic bacteria and maximum probable numbers of Vibrio spp. were investigated. Genetic profiles of bacterial communities were also characterized by polymerase chain reaction (PCR) amplification of eubacterial and Vibrio 16S rDNA using denaturing gradient gel electrophoresis (DGGE). Highest heterotrophic counts were registered in the mangrove not directly polluted by shrimp farming. The Enterobacteriaceae and Chryseomonas luteola dominated the heterotrophic isolates. Vibrio spp. pathogenic to humans and shrimps were identified. Eubacterial genetic profiles suggest a shared community structure independent of mangrove system. Vibrio genetic profiles were mangrove specific. Neither microbial counts nor genetic profiling revealed a significant decrease in species richness associated with shrimp farm effluent. The complex nature of mangrove ecosystems and their microbial communities is discussed.

Genetic and Environmental Basis in Phenotype Correlation Between Physical Function and Cognition in Aging Chinese Twins.

PubMed

Xu, Chunsheng; Zhang, Dongfeng; Tian, Xiaocao; Wu, Yili; Pang, Zengchang; Li, Shuxia; Tan, Qihua

2017-02-01

Although the correlation between cognition and physical function has been well studied in the general population, the genetic and environmental nature of the correlation has been rarely investigated. We conducted a classical twin analysis on cognitive and physical function, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), handgrip strength, five-times-sit-to-stand test (FTSST), near visual acuity, and number of teeth lost in 379 complete twin pairs. Bivariate twin models were fitted to estimate the genetic and environmental correlation between physical and cognitive function. Bivariate analysis showed mildly positively genetic correlations between cognition and FEV1, r G = 0.23 [95% CI: 0.03, 0.62], as well as FVC, r G = 0.35 [95% CI: 0.06, 1.00]. We found that FTSST and cognition presented very high common environmental correlation, r C = -1.00 [95% CI: -1.00, -0.57], and low but significant unique environmental correlation, r E = -0.11 [95% CI: -0.22, -0.01], all in the negative direction. Meanwhile, near visual acuity and cognition also showed unique environmental correlation, r E = 0.16 [95% CI: 0.03, 0.27]. We found no significantly genetic correlation for cognition with handgrip strength, FTSST, near visual acuity, and number of teeth lost. Cognitive function was genetically related to pulmonary function. The FTSST and cognition shared almost the same common environmental factors but only part of the unique environmental factors, both with negative correlation. In contrast, near visual acuity and cognition may positively share part of the unique environmental factors.

Functional Connectivity and Genetic Profile of a “Double-Cortex”-Like Malformation

PubMed Central

Sprugnoli, Giulia; Vatti, Giampaolo; Rossi, Simone; Cerase, Alfonso; Renieri, Alessandra; Mencarelli, Maria A.; Zara, Federico; Rossi, Alessandro; Santarnecchi, Emiliano

2018-01-01

Laminar heterotopia is a rare condition consisting in an extra layer of gray matter under properly migrated cortex; it configures an atypical presentation of periventricular nodular heterotopia (PNH) or a double cortex (DC) syndrome. We conducted an original functional MRI (fMRI) analysis in a drug-resistant epilepsy patient with “double-cortex”-like malformation to reveal her functional connectivity (FC) as well as a wide genetic analysis to identify possible genetic substrates. Heterotopias were segmented into region of interests (ROIs), whose voxel-wise FC was compared to that of (i) its normally migrated counterpart, (ii) its contralateral homologous, and (iii) those of 30 age-matched healthy controls. Extensive genetic analysis was conducted to screen cortical malformations-associated genes. Compared to healthy controls, both laminar heterotopias and the overlying cortex showed significant reduction of FC with the contralateral hemisphere. Two heterozygous variants of uncertain clinical significance were found, involving autosomal recessive disease-causing genes, FAT4 and COL18A1. This first FC analysis of a unique case of “double-cortex”-like malformation revealed a hemispheric connectivity segregation both in the laminar cortex as in the correctly migrated one, with a new pattern of genes’ mutations. Our study suggests the altered FC could have an electrophysiological and functional impact on large-scale brain networks, and the involvement of not yet identified genes in “double-cortex”-like malformation with a possible role of rare variants in recessive genes as pathogenic cofactors. PMID:29946244

Understanding Genetic Toxicity Through Data Mining: The ...

EPA Pesticide Factsheets

This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in a weight-of-evidence approach to assess potential for genetic toxicity, and to guide the development of intelligent testing strategies. This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in a weight-of-evidence approach to assess potential for genetic toxicity, and to guide the development of intelligent testing strategies.

The Relationship Between the Genetic and Environmental Influences on Common Externalizing Psychopathology and Mental Wellbeing

PubMed Central

Kendler, Kenneth S.; Myers, John M.; Keyes, Corey L. M.

2012-01-01

To determine the relationship between the genetic and environmental risk factors for externalizing psychopathology and mental wellbeing, we examined detailed measures of emotional, social and psychological wellbeing, and a history of alcohol-related problems and smoking behavior in the last year in 1,386 individual twins from same-sex pairs from the MIDUS national US sample assessed in 1995. Cholesky decomposition analyses were performed with the Mx program. The best fit model contained one highly heritable common externalizing psychopathology factor for both substance use/abuse measures, and one strongly heritable common factor for the three wellbeing measures. Genetic and environmental risk factors for externalizing psychopathology were both negatively associated with levels of mental wellbeing and accounted for, respectively, 7% and 21% of its genetic and environmental influences. Adding internalizing psychopathology assessed in the last year to the model, genetic risk factors unique for externalizing psychopathology were now positively related to levels of mental wellbeing, although accounting for only 5% of the genetic variance. Environmental risk factors unique to externalizing psychopathology continued to be negatively associated with mental wellbeing, accounting for 26% of the environmental variance. When both internalizing psychopathology and externalizing psychopathology are associated with mental wellbeing, the strongest risk factors for low mental wellbeing are genetic factors that impact on both internalizing psychopathology and externalizing psychopathology, and environmental factors unique to externalizing psychopathology. In this model, genetic risk factors for externalizing psychopathology predict, albeit weakly, higher levels of mental wellbeing. PMID:22506307

Reducing uncertainties in the velocities determined by inversion of phase velocity dispersion curves using synthetic seismograms

NASA Astrophysics Data System (ADS)

Hosseini, Seyed Mehrdad

Characterizing the near-surface shear-wave velocity structure using Rayleigh-wave phase velocity dispersion curves is widespread in the context of reservoir characterization, exploration seismology, earthquake engineering, and geotechnical engineering. This surface seismic approach provides a feasible and low-cost alternative to the borehole measurements. Phase velocity dispersion curves from Rayleigh surface waves are inverted to yield the vertical shear-wave velocity profile. A significant problem with the surface wave inversion is its intrinsic non-uniqueness, and although this problem is widely recognized, there have not been systematic efforts to develop approaches to reduce the pervasive uncertainty that affects the velocity profiles determined by the inversion. Non-uniqueness cannot be easily studied in a nonlinear inverse problem such as Rayleigh-wave inversion and the only way to understand its nature is by numerical investigation which can get computationally expensive and inevitably time consuming. Regarding the variety of the parameters affecting the surface wave inversion and possible non-uniqueness induced by them, a technique should be established which is not controlled by the non-uniqueness that is already affecting the surface wave inversion. An efficient and repeatable technique is proposed and tested to overcome the non-uniqueness problem; multiple inverted shear-wave velocity profiles are used in a wavenumber integration technique to generate synthetic time series resembling the geophone recordings. The similarity between synthetic and observed time series is used as an additional tool along with the similarity between the theoretical and experimental dispersion curves. The proposed method is proven to be effective through synthetic and real world examples. In these examples, the nature of the non-uniqueness is discussed and its existence is shown. Using the proposed technique, inverted velocity profiles are estimated and effectiveness of this technique is evaluated; in the synthetic example, final inverted velocity profile is compared with the initial target velocity model, and in the real world example, final inverted shear-wave velocity profile is compared with the velocity model from independent measurements in a nearby borehole. Real world example shows that it is possible to overcome the non-uniqueness and distinguish the representative velocity profile for the site that also matches well with the borehole measurements.

Exploitation of molecular profiling techniques for GM food safety assessment.

PubMed

Kuiper, Harry A; Kok, Esther J; Engel, Karl-Heinz

2003-04-01

Several strategies have been developed to identify unintended alterations in the composition of genetically modified (GM) food crops that may occur as a result of the genetic modification process. These include comparative chemical analysis of single compounds in GM food crops and their conventional non-GM counterparts, and profiling methods such as DNA/RNA microarray technologies, proteomics and metabolite profiling. The potential of profiling methods is obvious, but further exploration of specificity, sensitivity and validation is needed. Moreover, the successful application of profiling techniques to the safety evaluation of GM foods will require linked databases to be built that contain information on variations in profiles associated with differences in developmental stages and environmental conditions.

Rice diversity panels available through the genetic stocks oryza collection

USDA-ARS?s Scientific Manuscript database

The Genetic Stocks Oryza (GSOR) Collection was established in 2004 at the USDA-ARS, Dale Bumpers National Rice Research Center (DBNRRC) located in Stuttgart, AR. The mission of GSOR is to provide unique genetic resources to the rice research community for genetic and genomics related research. GSOR ...

Characterization of the genetic profile of five Danish dog breeds.

PubMed

Pertoldi, C; Kristensen, T N; Loeschcke, V; Berg, P; Praebel, A; Stronen, A V; Proschowsky, H F; Fredholm, M

2013-11-01

This investigation presents results from a genetic characterization of 5 Danish dog breeds genotyped on the CanineHD BeadChip microarray with 170,000 SNP. The breeds investigated were 1) Danish Spitz (DS; n=8), 2) Danish-Swedish Farm Dog (DSF; n=18), 3) Broholmer (BR; n=22), 4) Old Danish Pointing Dog (ODP; n=24), and 5) Greenland Dog (GD; n=23). The aims of the investigation were to characterize the genetic profile of the abovementioned dog breeds by quantifying the genetic differentiation among them and the degree of genetic homogeneity within breeds. The genetic profile was determined by means of principal component analysis (PCA) and through a Bayesian clustering method. Both the PCA and the Bayesian clustering method revealed a clear genetic separation of the 5 breeds. The level of genetic variation within the breeds varied. The expected heterozygosity (HE) as well as the degree of polymorphism (P%) ranked the dog breeds in the order DS>DSF>BR>ODP>GD. Interestingly, the breed with a tenfold higher census population size compared to the other breeds, the Greenland Dog, had the lowest within-breed genetic variation, emphasizing that census size is a poor predictor of genetic variation. The observed differences in variation among and within dog breeds may be related to factors such as genetic drift, founder effects, genetic admixture, and population bottlenecks. We further examined whether the observed genetic patterns in the 5 dog breeds can be used to design breeding strategies for the preservation of the genetic pool of these dog breeds.

Additive genetic risk from five serotonin system polymorphisms interacts with interpersonal stress to predict depression.

PubMed

Vrshek-Schallhorn, Suzanne; Stroud, Catherine B; Mineka, Susan; Zinbarg, Richard E; Adam, Emma K; Redei, Eva E; Hammen, Constance; Craske, Michelle G

2015-11-01

Behavioral genetic research supports polygenic models of depression in which many genetic variations each contribute a small amount of risk, and prevailing diathesis-stress models suggest gene-environment interactions (G×E). Multilocus profile scores of additive risk offer an approach that is consistent with polygenic models of depression risk. In a first demonstration of this approach in a G×E predicting depression, we created an additive multilocus profile score from 5 serotonin system polymorphisms (1 each in the genes HTR1A, HTR2A, HTR2C, and 2 in TPH2). Analyses focused on 2 forms of interpersonal stress as environmental risk factors. Using 5 years of longitudinal diagnostic and life stress interviews from 387 emerging young adults in the Youth Emotion Project, survival analyses show that this multilocus profile score interacts with major interpersonal stressful life events to predict major depressive episode onsets (hazard ratio [HR] = 1.815, p = .007). Simultaneously, there was a significant protective effect of the profile score without a recent event (HR = 0.83, p = .030). The G×E effect with interpersonal chronic stress was not significant (HR = 1.15, p = .165). Finally, effect sizes for genetic factors examined ignoring stress suggested such an approach could lead to overlooking or misinterpreting genetic effects. Both the G×E effect and the protective simple main effect were replicated in a sample of early adolescent girls (N = 105). We discuss potential benefits of the multilocus genetic profile score approach and caveats for future research. (c) 2015 APA, all rights reserved).

Breast cancer: determining the genetic profile from ultrasound-guided percutaneous biopsy specimens obtained during the diagnostic workups.

PubMed

López Ruiz, J A; Zabalza Estévez, I; Mieza Arana, J A

2016-01-01

To evaluate the possibility of determining the genetic profile of primary malignant tumors of the breast from specimens obtained by ultrasound-guided percutaneous biopsies during the diagnostic imaging workup. This is a retrospective study in 13 consecutive patients diagnosed with invasive breast cancer by B-mode ultrasound-guided 12 G core needle biopsy. After clinical indication, the pathologist decided whether the paraffin block specimens seemed suitable (on the basis of tumor size, validity of the sample, and percentage of tumor cells) before sending them for genetic analysis with the MammaPrint® platform. The size of the tumors on ultrasound ranged from 0.6cm to 5cm. In 11 patients the preserved specimen was considered valid and suitable for use in determining the genetic profile. In 1 patient (with a 1cm tumor) the pathologist decided that it was necessary to repeat the core biopsy to obtain additional samples. In 1 patient (with a 5cm tumor) the specimen was not considered valid by the genetic laboratory. The percentage of tumor cells in the samples ranged from 60% to 70%. In 11/13 cases (84.62%) it was possible to do the genetic analysis on the previously diagnosed samples. In most cases, regardless of tumor size, it is possible to obtain the genetic profile from tissue specimens obtained with ultrasound-guided 12 G core biopsy preserved in paraffin blocks. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

GENETIC ACTIVITY PROFILES AND PATTERN RECOGNITION IN TEST BATTERY SELECTION (JOURNAL VERSION)

EPA Science Inventory

Computer-generated genetic activity profiles and pairwise matching procedures may aid in the selection of the most appropriate short-term bioassays to be used in test batteries for the evaluation of the genotoxicity of a given chemical or group of chemicals. Selection of test bat...

Genomic Expression Patterns in Menstrually-Related Migraine in Adolescents

PubMed Central

Hershey, Andrew; Horn, Paul; Kabbouche, Marielle; O'Brien, Hope; Powers, Scott

2011-01-01

Background Exacerbation of migraine with menses is common in adolescent girls and women with migraine, occurring in up to 60% of females with migraine. These migraines are oftentimes longer and more disabling and may be related to estrogen levels and hormonal fluctuations. Objective This study identifies the unique genomic expression pattern of menstrually-related migraine (MRM) in comparison to migraine occurring outside the menstrual period and headache free controls. Methods Whole blood samples were obtained from female subjects having an acute migraine during their menstrual period (MRM) or outside of their menstrual period (nonMRM) and controls (C) – females having a menstrual period without any history of headache. The mRNA was isolated from these samples and genomic profile was assessed. Affymetrix Human Exon ST 1.0 arrays were used to examine the genomic expression pattern differences between these three groups. Results Blood genomic expression patterns were obtained on 56 subjects (MRM = 18, nonMRM = 18 and C = 20). Unique genomic expression patterns were observed for both MRM and nonMRM. For MRM, 77 genes were identified that were unique to MRM, while 61 genes were commonly expressed for MRM and nonMRM and 127 genes appeared to have a unique expression pattern for nonMRM. In addition, there were 279 genes that differentially expressed for MRM compared to nonMRM that were not differentially expressed for nonMRM. Gene ontology of these samples indicated many of these groups of genes were functionally related and included categories of immunomodulation/inflammation, mitochondrial function and DNA homeostasis. Conclusions Blood genomic patterns can accurately differentiate MRM from nonMRM. These results indicate that MRM involves a unique molecular biology pathway that can be identified with a specific biomarker and suggest that individuals with MRM have a different underlying genetic etiology. PMID:22220971

The Genetic Interpretation of Area under the ROC Curve in Genomic Profiling

PubMed Central

Wray, Naomi R.; Yang, Jian; Goddard, Michael E.; Visscher, Peter M.

2010-01-01

Genome-wide association studies in human populations have facilitated the creation of genomic profiles which combine the effects of many associated genetic variants to predict risk of disease. The area under the receiver operator characteristic (ROC) curve is a well established measure for determining the efficacy of tests in correctly classifying diseased and non-diseased individuals. We use quantitative genetics theory to provide insight into the genetic interpretation of the area under the ROC curve (AUC) when the test classifier is a predictor of genetic risk. Even when the proportion of genetic variance explained by the test is 100%, there is a maximum value for AUC that depends on the genetic epidemiology of the disease, i.e. either the sibling recurrence risk or heritability and disease prevalence. We derive an equation relating maximum AUC to heritability and disease prevalence. The expression can be reversed to calculate the proportion of genetic variance explained given AUC, disease prevalence, and heritability. We use published estimates of disease prevalence and sibling recurrence risk for 17 complex genetic diseases to calculate the proportion of genetic variance that a test must explain to achieve AUC = 0.75; this varied from 0.10 to 0.74. We provide a genetic interpretation of AUC for use with predictors of genetic risk based on genomic profiles. We provide a strategy to estimate proportion of genetic variance explained on the liability scale from estimates of AUC, disease prevalence, and heritability (or sibling recurrence risk) available as an online calculator. PMID:20195508

Segmenting by Risk Perceptions: Predicting Young Adults’ Genetic-Belief Profiles with Health and Opinion-Leader Covariates

PubMed Central

Smith, Rachel A.; Greenberg, Marisa; Parrott, Roxanne L.

2014-01-01

With a growing interest in using genetic information to motivate young adults’ health behaviors, audience segmentation is needed for effective campaign design. Using latent class analysis, this study identifies segments based on young adults’ (N = 327) beliefs about genetic threats to their health and personal efficacy over genetic influences on their health. A four-class model was identified. The model indicators fit the risk perception attitude framework (Rimal & Real, 2003), but the covariates (e.g., current health behaviors) did not. In addition, opinion leader qualities covaried with one profile: those in this profile engaged in fewer preventative behaviors and more dangerous treatment options, and also liked to persuade others, making them a particularly salient group for campaign efforts. The implications for adult-onset disorders, like alpha-1 antitrypsin deficiency are discussed. PMID:24111749

Fatty Acid Diversity is Not Associated with Neutral Genetic Diversity in Native Populations of the Biodiesel Plant Jatropha curcas L.

PubMed

Martínez-Díaz, Yesenia; González-Rodríguez, Antonio; Rico-Ponce, Héctor Rómulo; Rocha-Ramírez, Víctor; Ovando-Medina, Isidro; Espinosa-García, Francisco J

2017-01-01

Jatropha curcas L. (Euphorbiaceae) is a shrub native to Mexico and Central America, which produces seeds with a high oil content that can be converted to biodiesel. The genetic diversity of this plant has been widely studied, but it is not known whether the diversity of the seed oil chemical composition correlates with neutral genetic diversity. The total seed oil content, the diversity of profiles of fatty acids and phorbol esters were quantified, also, the genetic diversity obtained from simple sequence repeats was analyzed in native populations of J. curcas in Mexico. Using the fatty acids profiles, a discriminant analysis recognized three groups of individuals according to geographical origin. Bayesian assignment analysis revealed two genetic groups, while the genetic structure of the populations could not be explained by isolation-by-distance. Genetic and fatty acid profile data were not correlated based on Mantel test. Also, phorbol ester content and genetic diversity were not associated. Multiple linear regression analysis showed that total oil content was associated with altitude and seasonality of temperature. The content of unsaturated fatty acids was associated with altitude. Therefore, the cultivation planning of J. curcas should take into account chemical variation related to environmental factors. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Genetic Diversity of Escherichia coli Isolated from Urban Rivers and Beach Water

PubMed Central

McLellan, Sandra L.

2004-01-01

Repetitive element anchored PCR was used to evaluate the genetic profiles of Escherichia coli isolated from surface water contaminated with urban stormwater, sanitary sewage, and gull feces to determine if strains found in environmental samples reflect the strain composition of E. coli obtained from host sources. Overall, there was less diversity in isolates collected from river and beach sites than with isolates obtained from human and nonhuman sources. Unique strain types comprised 28.8, 29.2, and 15.0% of the isolate data sets recovered from stormwater, river water, and beach water, respectively. In contrast, 50.4% of gull isolates and 41.2% of sewage isolates were unique strain types. River water, which is expected to contain E. coli strains from many diffuse sources of nonpoint source pollution, contained strains most closely associated with other river water isolates that were collected at different sites or on different days. However, river sites impacted by sewage discharge had approximately 20% more strains similar to sewage isolates than did sites impacted by stormwater alone. Beach sites with known gull fecal contamination contained E. coli most similar to other beach isolates rather than gull isolates collected at these same sites, indicating underrepresentation of possible gull strains. These results suggest large numbers of strains are needed to represent contributing host sources within a geographical location. Additionally, environmental survival may influence the composition of strains that can be recovered from contaminated waters. Understanding the ecology of indicator bacteria is important when interpreting fecal pollution assessments and developing source detection methodology. PMID:15294799

Characterization of local goat breeds using RAP-DNA markers

NASA Astrophysics Data System (ADS)

Al-Barzinji, Yousif M. S.; Hamad, Aram O.

2017-09-01

The present study was conducted on different colors of local goat breeds. A number of 216 does were sampled from the seven groups. Genomic DNA was extracted from the blood samples. From the twenty used RAPD primers 12 of them were amplified, and presence of bands. The total fragment number of 12 primers over all the goat breed samples was 485 fragments. Out of the 485 fragments, 90 of them were Polymorphic fragments numbers (PFN). From all bands obtained, 20 of them possessed unique bands. The highest unique band was found in locus RAP 6 which has 4 unique bands, three of them in the Maraz Brown and one in the local Koor. Nei's gene diversity and Shanon's information index in this study were averaged 0.38 and 0.60, respectively. The genetic distance among several goat breeds ranged from 9.11 to 43.33%. The highest genetic distance 43.33% recorded between Maraz goat and other goat breeds and between local Koor and other goat (except Maraz goats) breeds (37.79%). However, the lowest genetic distance recorded between local white and Pnok. The distance between (local Black and Pnok) and (local Black and local white) was 22.75%. In conclusions, the high distance among these goat breeds, polymorphism and high numbers of unique bands found in present study indicates that these goat breeds have the required amount of genetic variation to made genetic improvement. This study helps us to clarify the image of the genetic diversity of the local goat breeds and the breeders can used it for mating system when need to make the crossing among these goat breeds.

The SRAP based molecular diversity related to antifungal and antioxidant bioactive constituents for biocontrol potentials of Trichoderma against Sclerotium rolfsii Scc.

PubMed

Hirpara, Darshna G; Gajera, H P; Bhimani, R D; Golakiya, B A

2016-08-01

The study was performed to examine 11 isolates of Trichoderma for their bio-control potentials against Sclerotium rolfsii Sacc. causing stem rot in groundnut. The antagonists Trichoderma were subjected to sequence related amplified polymorphism (SRAP) based molecular diversity analysis and compared with their hardness to S. rolfsii with respect to secretary antifungal and antioxidant profile. T. virens NBAII Tvs 12 evident highest (87.91 %) growth inhibition of test pathogen followed by T. koningii MTCC 796 (67.03 %) at 7 days after inoculation (DAI). Microscopic study confirmed biocontrol mechanism as mycoparasitism for Tvs 12 and antibiosis for MTCC 796. The growth inhibition of test pathogen was significantly negatively correlated with sclerotia formation and lipid peroxidation during antagonism due to release of secretary bioactive antioxidants by antagonists to terminate oxidative burst generated by S. rolfsii and causing inhibition of sclerotium formation. The GC-MS profile identified antifungal and antioxidant constituents hexadecane, 1,2-benzenedicarboxylic acid, mono (2-ethylhexyl) ester, 1-hexadecanesulfonyl chloride, and octadecane in potent antagonists Tvs 12; and nonacosane and octadecane in MTCC 796 along with two novel compounds 1-pentadecene and 1-heneicosyl formate for biocontrol activity. Molecular diversity of Trichoderma isolates associated with antagonistic activity was assessed by SRAP markers. The 115 primer combinations generate total 1328 amplified products of which, 1095 are shared polymorphic and 199 are unique polymorphic. The 15 SRAP combinations produced 18 bands to diagnose best antagonist Tvs 12 and 13 SRAP combinations generated 19 unique bands for identification of MTCC 796. The mycoparasitic antagonist Tvs 12 would be the best antagonist and released unique antifungal and antioxidant constituents to combat pathogen infection. The SRAP based genetic diversity indicates Tvs12 strain clustered with T. viride NBAII Tv23 and shared only 52 % similarity with other isolates of Trichoderma. The SRAP similarities explained substantial diversity (19-68 %) across Trichoderma isolates.

Shared Genetic Contributions to Anxiety Disorders and Pathological Gambling in a Male Population

PubMed Central

Giddens, Justine L.; Xian, Hong; Scherrer, Jeffrey F.; Eisen, Seth A.; Potenza, Marc N.

2013-01-01

Background Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known. Method Data from the Vietnam Twin Registry (n=7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD). Results While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (ra =0.53). In contrast, substantial correlations were observed between both the genetic (ra=0.34) and unique environmental (re =0.31) contributions to PG and PD. Limitations Results may be limited to middle aged males. Conclusions The existence of shared genetic contributions between PG and both GAD and PD suggest that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women, adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences. PMID:21481943

Shared genetic contributions to anxiety disorders and pathological gambling in a male population.

PubMed

Giddens, Justine L; Xian, Hong; Scherrer, Jeffrey F; Eisen, Seth A; Potenza, Marc N

2011-08-01

Pathological gambling (PG) frequently co-occurs with anxiety disorders. However, the extent to which the co-occurrence is related to genetic or environmental factors across PG and anxiety disorders is not known. Data from the Vietnam Era Twin Registry (n=7869, male twins) were examined in bivariate models to estimate genetic and shared and unique environmental contributions to PG and generalized anxiety disorder (GAD) and PG and panic disorder (PD). While both genetic and unique environmental factors contributed individually to PG, GAD, and PD, the best fitting model indicated that the relationship between PG and GAD was attributable predominantly to shared genetic contributions (r(A)=0.53). In contrast, substantial correlations were observed between both the genetic (r(A)=0.34) and unique environmental (r(E)=0.31) contributions to PG and PD. Results may be limited to middle aged males. The existence of shared genetic contributions between PG and both GAD and PD suggests that specific genes, perhaps those involved in affect regulation or stress responsiveness, contribute to PG and anxiety disorders. Overlapping environmental contributions to the co-occurrence of PG and PD suggest that common life experiences (e.g., early life trauma) contribute to both PG and PD. Conversely, the data suggest that distinct environmental factors contribute to PG and GAD (e.g., early onset of gambling in PG). Future studies should examine the relationship between PG and anxiety disorders amongst other populations (women and adolescents) to identify specific genetic and environmental influences that account for the manifestation of these disorders and their co-occurrences. Copyright © 2011. Published by Elsevier B.V.

Genetic and environmental influences on conduct and antisocial personality problems in childhood, adolescence, and adulthood.

PubMed

Wesseldijk, Laura W; Bartels, Meike; Vink, Jacqueline M; van Beijsterveldt, Catharina E M; Ligthart, Lannie; Boomsma, Dorret I; Middeldorp, Christel M

2017-06-21

Conduct problems in children and adolescents can predict antisocial personality disorder and related problems, such as crime and conviction. We sought an explanation for such predictions by performing a genetic longitudinal analysis. We estimated the effects of genetic, shared environmental, and unique environmental factors on variation in conduct problems measured at childhood and adolescence and antisocial personality problems measured at adulthood and on the covariation across ages. We also tested whether these estimates differed by sex. Longitudinal data were collected in the Netherlands Twin Register over a period of 27 years. Age appropriate and comparable measures of conduct and antisocial personality problems, assessed with the Achenbach System of Empirically Based Assessment, were available for 9783 9-10-year-old, 6839 13-18-year-old, and 7909 19-65-year-old twin pairs, respectively; 5114 twins have two or more assessments. At all ages, men scored higher than women. There were no sex differences in the estimates of the genetic and environmental influences. During childhood, genetic and environmental factors shared by children in families explained 43 and 44% of the variance of conduct problems, with the remaining variance due to unique environment. During adolescence and adulthood, genetic and unique environmental factors equally explained the variation. Longitudinal correlations across age varied between 0.20 and 0.38 and were mainly due to stable genetic factors. We conclude that shared environment is mainly of importance during childhood, while genetic factors contribute to variation in conduct and antisocial personality problems at all ages, and also underlie its stability over age.

The degree of intratumor mutational heterogeneity varies by primary tumor sub-site

PubMed Central

Eterovic, Agda Karina; Wick, Jo; Chen, Ken; Zhao, Hao; Tazi, Loubna; Manna, Pradip; Kerley, Spencer; Joshi, Radhika; Wang, Lin; Chiosea, Simion I.; Garnett, James David; Tsue, Terance Ted; Chien, Jeremy; Mills, Gordon B.; Grandis, Jennifer Rubin; Thomas, Sufi Mary

2016-01-01

In an era where mutational profiles inform treatment options, it is critical to know the extent to which tumor biopsies represent the molecular profile of the primary and metastatic tumor. Head and neck squamous cell carcinoma (HNSCC) arise primarily in the mucosal lining of oral cavity and oropharynx. Despite aggressive therapy the 5-year survival rate is at 50%. The primary objective of this study is to characterize the degree of intratumor mutational heterogeneity in HNSCC. We used multi-region sequencing of paired primary and metastatic tumor DNA of 24 spatially distinct samples from seven patients with HNSCC of larynx, floor of the mouth (FOM) or oral tongue. Full length, in-depth sequencing of 202 genes implicated in cancer was carried out. Larynx and FOM tumors had more than 69.2% unique SNVs between the paired primary and metastatic lesions. In contrast, the oral tongue HNSCC had only 33.3% unique SNVs across multiple sites. In addition, HNSCC of the oral tongue had fewer mutations than larynx and FOM tumors. These findings were validated on the Affymetrix whole genome 6.0 array platform and were consistent with data from The Cancer Genome Atlas (TCGA). This is the first report demonstrating differences in mutational heterogeneity varying by subsite in HNSCC. The heterogeneity within laryngeal tumor specimens may lead to an underestimation of the genetic abnormalities within tumors and may foster resistance to standard treatment protocols. These findings are relevant to investigators and clinicians developing personalized cancer treatments based on identification of specific mutations in tumor biopsies. PMID:27034009

The degree of intratumor mutational heterogeneity varies by primary tumor sub-site.

PubMed

Ledgerwood, Levi G; Kumar, Dhruv; Eterovic, Agda Karina; Wick, Jo; Chen, Ken; Zhao, Hao; Tazi, Loubna; Manna, Pradip; Kerley, Spencer; Joshi, Radhika; Wang, Lin; Chiosea, Simion I; Garnett, James David; Tsue, Terance Ted; Chien, Jeremy; Mills, Gordon B; Grandis, Jennifer Rubin; Thomas, Sufi Mary

2016-05-10

In an era where mutational profiles inform treatment options, it is critical to know the extent to which tumor biopsies represent the molecular profile of the primary and metastatic tumor. Head and neck squamous cell carcinoma (HNSCC) arise primarily in the mucosal lining of oral cavity and oropharynx. Despite aggressive therapy the 5-year survival rate is at 50%. The primary objective of this study is to characterize the degree of intratumor mutational heterogeneity in HNSCC. We used multi-region sequencing of paired primary and metastatic tumor DNA of 24 spatially distinct samples from seven patients with HNSCC of larynx, floor of the mouth (FOM) or oral tongue. Full length, in-depth sequencing of 202 genes implicated in cancer was carried out. Larynx and FOM tumors had more than 69.2% unique SNVs between the paired primary and metastatic lesions. In contrast, the oral tongue HNSCC had only 33.3% unique SNVs across multiple sites. In addition, HNSCC of the oral tongue had fewer mutations than larynx and FOM tumors. These findings were validated on the Affymetrix whole genome 6.0 array platform and were consistent with data from The Cancer Genome Atlas (TCGA). This is the first report demonstrating differences in mutational heterogeneity varying by subsite in HNSCC. The heterogeneity within laryngeal tumor specimens may lead to an underestimation of the genetic abnormalities within tumors and may foster resistance to standard treatment protocols. These findings are relevant to investigators and clinicians developing personalized cancer treatments based on identification of specific mutations in tumor biopsies.

Understanding Genetic Toxicity Through Data Mining: The Process of Building Knowledge by Integrating Multiple Genetic Toxicity Databases

EPA Science Inventory

This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in...

Predicting human genetic interactions from cancer genome evolution.

PubMed

Lu, Xiaowen; Megchelenbrink, Wout; Notebaart, Richard A; Huynen, Martijn A

2015-01-01

Synthetic Lethal (SL) genetic interactions play a key role in various types of biological research, ranging from understanding genotype-phenotype relationships to identifying drug-targets against cancer. Despite recent advances in empirical measuring SL interactions in human cells, the human genetic interaction map is far from complete. Here, we present a novel approach to predict this map by exploiting patterns in cancer genome evolution. First, we show that empirically determined SL interactions are reflected in various gene presence, absence, and duplication patterns in hundreds of cancer genomes. The most evident pattern that we discovered is that when one member of an SL interaction gene pair is lost, the other gene tends not to be lost, i.e. the absence of co-loss. This observation is in line with expectation, because the loss of an SL interacting pair will be lethal to the cancer cell. SL interactions are also reflected in gene expression profiles, such as an under representation of cases where the genes in an SL pair are both under expressed, and an over representation of cases where one gene of an SL pair is under expressed, while the other one is over expressed. We integrated the various previously unknown cancer genome patterns and the gene expression patterns into a computational model to identify SL pairs. This simple, genome-wide model achieves a high prediction power (AUC = 0.75) for known genetic interactions. It allows us to present for the first time a comprehensive genome-wide list of SL interactions with a high estimated prediction precision, covering up to 591,000 gene pairs. This unique list can potentially be used in various application areas ranging from biotechnology to medical genetics.

Safe Genetic Modification of Cardiac Stem Cells Using a Site-Specific Integration Technique

PubMed Central

Lan, Feng; Liu, Junwei; Narsinh, Kazim H.; Hu, Shijun; Han, Leng; Lee, Andrew S.; Karow, Marisa; Nguyen, Patricia K.; Nag, Divya; Calos, Michele P.; Robbins, Robert C.; Wu, Joseph C.

2012-01-01

Background Human cardiac progenitor cells (hCPCs) are a promising cell source for regenerative repair after myocardial infarction. Exploitation of their full therapeutic potential may require stable genetic modification of the cells ex vivo. Safe genetic engineering of stem cells, using facile methods for site-specific integration of transgenes into known genomic contexts, would significantly enhance the overall safety and efficacy of cellular therapy in a variety of clinical contexts. Methods and Results We employed the phiC31 site-specific recombinase to achieve targeted integration of a triple fusion reporter gene into a known chromosomal context in hCPCs and human endothelial cells (hECs). Stable expression of the reporter gene from its unique chromosomal integration site resulted in no discernible genomic instability or adverse changes in cell phenotype. Namely, phiC31-modified hCPCs were unchanged in their differentiation propensity, cellular proliferative rate, and global gene expression profile when compared to unaltered control hCPCs. Expression of the triple fusion reporter gene enabled multimodal assessment of cell fate in vitro and in vivo using fluorescence microscopy, bioluminescence imaging (BLI), and positron emission tomography (PET). Intramyocardial transplantation of genetically modified hCPCs resulted in significant improvement in myocardial function two weeks after cell delivery, as assessed by echocardiography (P = 0.002) and magnetic resonance imaging (P = 0.001). We also demonstrated the feasibility and therapeutic efficacy of genetically modifying differentiated hECs, which enhanced hindlimb perfusion (P<0.05 at day 7 and 14 after transplantation) on laser Doppler imaging. Conclusions The phiC31 integrase genomic modification system is a safe, efficient tool to enable site-specific integration of reporter transgenes in progenitor and differentiated cell types. PMID:22965984

Safe genetic modification of cardiac stem cells using a site-specific integration technique.

PubMed

Lan, Feng; Liu, Junwei; Narsinh, Kazim H; Hu, Shijun; Han, Leng; Lee, Andrew S; Karow, Marisa; Nguyen, Patricia K; Nag, Divya; Calos, Michele P; Robbins, Robert C; Wu, Joseph C

2012-09-11

Human cardiac progenitor cells (hCPCs) are a promising cell source for regenerative repair after myocardial infarction. Exploitation of their full therapeutic potential may require stable genetic modification of the cells ex vivo. Safe genetic engineering of stem cells, using facile methods for site-specific integration of transgenes into known genomic contexts, would significantly enhance the overall safety and efficacy of cellular therapy in a variety of clinical contexts. We used the phiC31 site-specific recombinase to achieve targeted integration of a triple fusion reporter gene into a known chromosomal context in hCPCs and human endothelial cells. Stable expression of the reporter gene from its unique chromosomal integration site resulted in no discernible genomic instability or adverse changes in cell phenotype. Namely, phiC31-modified hCPCs were unchanged in their differentiation propensity, cellular proliferative rate, and global gene expression profile when compared with unaltered control hCPCs. Expression of the triple fusion reporter gene enabled multimodal assessment of cell fate in vitro and in vivo using fluorescence microscopy, bioluminescence imaging, and positron emission tomography. Intramyocardial transplantation of genetically modified hCPCs resulted in significant improvement in myocardial function 2 weeks after cell delivery, as assessed by echocardiography (P=0.002) and MRI (P=0.001). We also demonstrated the feasibility and therapeutic efficacy of genetically modifying differentiated human endothelial cells, which enhanced hind limb perfusion (P<0.05 at day 7 and 14 after transplantation) on laser Doppler imaging. The phiC31 integrase genomic modification system is a safe, efficient tool to enable site-specific integration of reporter transgenes in progenitor and differentiated cell types.

The KNOXI Transcription Factor SHOOT MERISTEMLESS Regulates Floral Fate in Arabidopsis.

PubMed

Roth, Ohad; Alvarez, John; Levy, Matan; Bowman, John L; Ori, Naomi; Shani, Eilon

2018-05-09

Plants have evolved a unique and conserved developmental program that enables the conversion of leaves into floral organs. Elegant genetic and molecular work has identified key regulators of flower meristem identity. However, further understanding of flower meristem specification has been hampered by redundancy and by pleiotropic effects. The KNOXI transcription factor SHOOT MERISTEMLESS (STM) is a well-characterized regulator of shoot apical meristem maintenance. Arabidopsis thaliana stm loss-of-function mutants arrest shortly after germination, and therefore the knowledge on later roles of STM in later processes, including flower development, is limited. Here, we uncover a role for STM in the specification of flower meristem identity. Silencing STM in the APETALA1 (AP1) expression domain in the ap1-4 mutant background resulted in a leafy-flower phenotype, and an intermediate stm-2 allele enhanced the flower meristem identity phenotype of ap1-4. Transcriptional profiling of STM perturbation suggested that STM activity affects multiple floral fate genes, among them the F-Box protein-encoding gene UNUSUAL FLORAL ORGANS (UFO). In agreement with this notion, stm-2 enhanced the ufo-2 floral fate phenotype, and ectopic UFO expression rescued the leafy flowers in genetic backgrounds with compromised AP1 and STM activities. This work suggests a genetic mechanism that underlies the activity of STM in the specification of flower meristem identity. © 2018 American Society of Plant Biologists. All rights reserved.

Comparative evaluation of an automated repetitive-sequence-based PCR instrument versus pulsed-field gel electrophoresis in the setting of a Serratia marcescens nosocomial infection outbreak.

PubMed

Ligozzi, Marco; Fontana, Roberta; Aldegheri, Marco; Scalet, Giovanna; Lo Cascio, Giuliana

2010-05-01

A semiautomated, repetitive-sequence-based PCR (rep-PCR) instrument (DiversiLab system) was evaluated in comparison with pulsed-field gel electrophoresis (PFGE) to investigate an outbreak of Serratia marcescens infections in a neonatal intensive care unit (NICU). A selection of 36 epidemiologically related and 8 epidemiologically unrelated isolates was analyzed. Among the epidemiologically related isolates, PFGE identified five genetically unrelated patterns. Thirty-two isolates from patients and wet nurses showed the same PFGE profile (pattern A). Genetically unrelated PFGE patterns were found in one patient (pattern B), in two wet nurses (patterns C and D), and in an environmental isolate from the NICU (pattern G). Rep-PCR identified seven different patterns, three of which included the 32 isolates of PFGE type A. One or two band differences in isolates of these three types allowed isolates to be categorized as similar and included in a unique cluster. Isolates of different PFGE types were also of unrelated rep-PCR types. All of the epidemiologically unrelated isolates were of different PFGE and rep-PCR types. The level of discrimination exhibited by rep-PCR with the DiversiLab system allowed us to conclude that this method was able to identify genetic similarity in a spatio-temporal cluster of S. marcescens isolates.

Genetic and phenotypic diversity of geographically different isolates of Glomus mosseae.

PubMed

Avio, Luciano; Cristani, Caterina; Strani, Patrizia; Giovannetti, Manuela

2009-03-01

In this work, we combined morphological taxonomy and molecular methods to investigate the intraspecific diversity of Glomus mosseae, whose global distribution has been reviewed by a survey of scientific literature and Web-available records from international germplasm collections (International Culture Collection of Vesicular Arbuscular Mycorrhizal Fungi and International Bank of Glomeromycota). We surveyed 186 publications reporting the occurrence of G. mosseae from at least 474 different sites from 55 countries throughout all continents, producing a geographical map of their distribution. The relationships among G. mosseae isolates originating from Europe (United Kingdom), the United States (Arizona, Florida, and Indiana), Africa (Namibia), and West Asia (Syria) were analyzed. The level of resolution of internal transcribed spacer (ITS) sequences strongly supports the morphological species definition of G. mosseae. An ITS - restriction fragment length polymorphism assay with the enzyme HinfI yielded a unique profile for all G. mosseae isolates, allowing a straightforward identification of this morphospecies. Genetic variability among G. mosseae isolates was revealed by the inter-simple-sequence repeat (ISSR) - polymerase chain reaction: the magnitude of genetic divergence shown by the investigated geographical isolates was higher than 50%, consistent with previous data on vegetative compatibility and functional diversity. The variability of ISSR patterns suggests that intraspecific diversity is much higher than that foreseen by morphology and rDNA regions, and should be further investigated by using other genes, such as those related to functional diversity.

Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

PubMed Central

Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

2014-01-01

The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

Genetic and environmental influences on residential location in the U.S

PubMed Central

Duncan, Glen E.; Dansie, Elizabeth J.; Strachan, Eric; Munsell, Melissa; Huang, Ruizhu; Moudon, Anne Vernez; Goldberg, Jack; Buchwald, Dedra

2012-01-01

We used a classical twin design and measures of neighborhood walkability and social deprivation, using each twin’s street address, to examine genetic and environmental influences on the residential location of 1,389 same-sex pairs from a U.S. community-based twin registry. Within-pair correlations and structural equation models estimated these influences on walkability among younger (ages 18–24.9) and older (ages 25+) twins. Adjusting for social deprivation, walkability of residential location was primarily influenced by common environment with lesser contributions of unique environment and genetic factors among younger twins, while unique environment most strongly influenced walkability, with small genetic and common environment effects, among older twins. Thus, minimal variance in walkability was explained by shared genetic effects in younger and older twins, and confirms the importance of environmental factors in walkability of residential locations. PMID:22377617

The Genome Sequencer FLX System--longer reads, more applications, straight forward bioinformatics and more complete data sets.

PubMed

Droege, Marcus; Hill, Brendon

2008-08-31

The Genome Sequencer FLX System (GS FLX), powered by 454 Sequencing, is a next-generation DNA sequencing technology featuring a unique mix of long reads, exceptional accuracy, and ultra-high throughput. It has been proven to be the most versatile of all currently available next-generation sequencing technologies, supporting many high-profile studies in over seven applications categories. GS FLX users have pursued innovative research in de novo sequencing, re-sequencing of whole genomes and target DNA regions, metagenomics, and RNA analysis. 454 Sequencing is a powerful tool for human genetics research, having recently re-sequenced the genome of an individual human, currently re-sequencing the complete human exome and targeted genomic regions using the NimbleGen sequence capture process, and detected low-frequency somatic mutations linked to cancer.

Development of imaging biomarkers and generation of big data.

PubMed

Alberich-Bayarri, Ángel; Hernández-Navarro, Rafael; Ruiz-Martínez, Enrique; García-Castro, Fabio; García-Juan, David; Martí-Bonmatí, Luis

2017-06-01

Several image processing algorithms have emerged to cover unmet clinical needs but their application to radiological routine with a clear clinical impact is still not straightforward. Moving from local to big infrastructures, such as Medical Imaging Biobanks (millions of studies), or even more, Federations of Medical Imaging Biobanks (in some cases totaling to hundreds of millions of studies) require the integration of automated pipelines for fast analysis of pooled data to extract clinically relevant conclusions, not uniquely linked to medical imaging, but in combination to other information such as genetic profiling. A general strategy for the development of imaging biomarkers and their integration in the cloud for the quantitative management and exploitation in large databases is herein presented. The proposed platform has been successfully launched and is being validated nowadays among the early adopters' community of radiologists, clinicians, and medical imaging researchers.

Advanced Applications of Next-Generation Sequencing Technologies to Orchid Biology.

PubMed

Yeh, Chuan-Ming; Liu, Zhong-Jian; Tsai, Wen-Chieh

2018-01-01

Next-generation sequencing technologies are revolutionizing biology by permitting, transcriptome sequencing, whole-genome sequencing and resequencing, and genome-wide single nucleotide polymorphism profiling. Orchid research has benefited from this breakthrough, and a few orchid genomes are now available; new biological questions can be approached and new breeding strategies can be designed. The first part of this review describes the unique features of orchid biology. The second part provides an overview of the current next-generation sequencing platforms, many of which are already used in plant laboratories. The third part summarizes the state of orchid transcriptome and genome sequencing and illustrates current achievements. The genetic sequences currently obtained will not only provide a broad scope for the study of orchid biology, but also serves as a starting point for uncovering the mystery of orchid evolution.

Individualization and estimation of relatedness in crocodilians by DNA fingerprinting with a Bkm-derived probe.

PubMed

Lang, J W; Aggarwal, R K; Majumdar, K C; Singh, L

1993-04-01

Individual-specific DNA fingerprints of crocodilians were obtained by the use of Bkm-2(8) probe. Pedigree analyses of Crocodylus palustris, C. porosus and Caiman crocodilus revealed that the multiple bands (22-23 bands with Aludigest) thus obtained were inherited stably in a Mendelian fashion. Unique fingerprints permitted us to identify individuals, assign parentage, and reconstruct the DNA profile of a missing parent. Average band sharing between unrelated crocodiles was found to be 0.37. Band sharing between animals of known pedigrees increased predictably with relatedness and provided a basis for distinguishing relatives from non-relatives. Similar results obtained in other species/genera, using the same probe, suggest that this approach may be applicable to all species of crocodilians, and could facilitate genetic studies of wild and captive populations.

Genetic Testing for Deafness--GJB2 and SLC26A4 as Causes of Deafness.

ERIC Educational Resources Information Center

Smith, Richard J. H.; Robin, Nathaniel H.

2002-01-01

This article introduces the concept of genetic testing for deafness. Two genes that make appreciable contributions to the autosomal recessive non-syndromic deafness (ARNSD) genetic load are reviewed, GJB2 and SLC26A4. In addition, the unique aspects of genetic counseling for deafness and recurrence chance estimates are explained. (Contains…

Emerging Applications of Metabolomic and Genomic Profiling in Diabetic Clinical Medicine

PubMed Central

McKillop, Aine M.; Flatt, Peter R.

2011-01-01

Clinical and epidemiological metabolomics provides a unique opportunity to look at genotype-phenotype relationships as well as the body\\x{2019}s responses to environmental and lifestyle factors. Fundamentally, it provides information on the universal outcome of influencing factors on disease states and has great potential in the early diagnosis, therapy monitoring, and understanding of the pathogenesis of disease. Diseases, such as diabetes, with a complex set of interactions between genetic and environmental factors, produce changes in the body\\x{2019}s biochemical profile, thereby providing potential markers for diagnosis and initiation of therapies. There is clearly a need to discover new ways to aid diagnosis and assessment of glycemic status to help reduce diabetes complications and improve the quality of life. Many factors, including peptides, proteins, metabolites, nucleic acids, and polymorphisms, have been proposed as putative biomarkers for diabetes. Metabolomics is an approach used to identify and assess metabolic characteristics, changes, and phenotypes in response to influencing factors, such as environment, diet, lifestyle, and pathophysiological states. The specificity and sensitivity using metabolomics to identify biomarkers of disease have become increasingly feasible because of advances in analytical and information technologies. Likewise, the emergence of high-throughput genotyping technologies and genome-wide association studies has prompted the search for genetic markers of diabetes predisposition or susceptibility. In this review, we consider the application of key metabolomic and genomic methodologies in diabetes and summarize the established, new, and emerging metabolomic and genomic biomarkers for the disease. We conclude by summarizing future insights into the search for improved biomarkers for diabetes research and human diagnostics. PMID:22110171

Met-Activating Genetically Improved Chimeric Factor-1 Promotes Angiogenesis and Hypertrophy in Adult Myogenesis.

PubMed

Ronzoni, Flavio; Ceccarelli, Gabriele; Perini, Ilaria; Benedetti, Laura; Galli, Daniela; Mulas, Francesca; Balli, Martina; Magenes, Giovanni; Bellazzi, Riccardo; De Angelis, Gabriella C; Sampaolesi, Maurilio

2017-01-01

Myogenic progenitor cells (activated satellite cells) are able to express both HGF and its receptor cMet. After muscle injury, HGF-Met stimulation promotes activation and primary division of satellite cells. MAGIC-F1 (Met-Activating Genetically Improved Chimeric Factor-1) is an engineered protein that contains two human Met-binding domains that promotes muscle hypertrophy. MAGIC-F1 protects myogenic precursors against apoptosis and increases their fusion ability enhancing muscle differentiation. Hemizygous and homozygous Magic-F1 transgenic mice displayed constitutive muscle hypertrophy. Here we describe microarray analysis on Magic-F1 myogenic progenitor cells showing an altered gene signatures on muscular hypertrophy and angiogenesis compared to wild-type cells. In addition, we performed a functional analysis on Magic-F1+/+ transgenic mice versus controls using treadmill test. We demonstrated that Magic-F1+/+ mice display an increase in muscle mass and cross-sectional area leading to an improvement in running performance. Moreover, the presence of MAGIC-F1 affected positively the vascular network, increasing the vessel number in fast twitch fibers. Finally, the gene expression profile analysis of Magic-F1+/+ satellite cells evidenced transcriptomic changes in genes involved in the control of muscle growth, development and vascularisation. We showed that MAGIC-F1-induced muscle hypertrophy affects positively vascular network, increasing vessel number in fast twitch fibers. This was due to unique features of mammalian skeletal muscle and its remarkable ability to adapt promptly to different physiological demands by modulating the gene expression profile in myogenic progenitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Prevalence and Genetic Profile of Duchene and Becker Muscular Dystrophy in Puerto Rico.

PubMed

Ramos, Edwardo; Conde, José G; Berrios, Rafael Arias; Pardo, Sherly; Gómez, Omar; Mas Rodríguez, Manuel F

2016-05-27

Duchenne and Becker Muscular Dystrophy (DMD and BMD, respectively), are common forms of inherited muscle disease. Information regarding the epidemiology of these conditions, including genotype, is still sparse. To establish the prevalence and genetic profile of DMD and BMD in Puerto Rico. We collected data from medical records in all Muscular Dystrophy Association (MDA) clinics in Puerto Rico in order to estimate the prevalence of DMD and BMD and to describe the genotypic profile of these patients. Patients selected for data analysis matched "definite", "probable" and "possible" case definitions as established by MD STARnet. A total of 141 patients matched the inclusion criteria, with 64.5% and 35.5% being categorized into DMD and BMD, respectively. DMD and BMD prevalence in Puerto Rico was estimated at 5.18 and 2.84 per 100,000 males, respectively. Deletion was the most common form of mutation (66.7%) in the dystrophin gene, with exons in segment 45 to 47 being the most frequently affected. This is the first report of the prevalence and genetic profile characteristics of DMD and BMD in Puerto Rico. Prevalence of DMD was similar to that reported worldwide, while prevalence of BMD was higher. Genetic profile was consistent with that reported in the literature.

Defining the Genomic Signature of Totipotency and Pluripotency during Early Human Development

PubMed Central

Galan, Amparo; Diaz-Gimeno, Patricia; Poo, Maria Eugenia; Valbuena, Diana; Sanchez, Eva; Ruiz, Veronica; Dopazo, Joaquin; Montaner, David; Conesa, Ana; Simon, Carlos

2013-01-01

The genetic mechanisms governing human pre-implantation embryo development and the in vitro counterparts, human embryonic stem cells (hESCs), still remain incomplete. Previous global genome studies demonstrated that totipotent blastomeres from day-3 human embryos and pluripotent inner cell masses (ICMs) from blastocysts, display unique and differing transcriptomes. Nevertheless, comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. To understand early human stages evolution, we developed an undifferentiation network signature (UNS) and applied it to a differential gene expression profile between single blastomeres from day-3 embryos, ICMs and hESCs. This allowed us to establish a unique signature composed of highly interconnected genes characteristic of totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro pluripotency (107 genes), and which are also proprietary according to functional analysis. This systems biology approach has led to an improved understanding of the molecular and signaling processes governing human pre-implantation embryo development, as well as enabling us to comprehend how hESCs might adapt to in vitro culture conditions. PMID:23614026

Expanding the foundation for personalized medicine: implications and challenges for dentistry.

PubMed

Garcia, I; Kuska, R; Somerman, M J

2013-07-01

Personalized medicine aims to individualize care based on a person's unique genetic, environmental, and clinical profile. Dentists and physicians have long recognized variations between and among patients, and have customized care based on each individual's health history, environment, and behavior. However, the sequencing of the human genome in 2003 and breakthroughs in regenerative medicine, imaging, and computer science redefined "personalized medicine" as clinical care that takes advantage of new molecular tools to facilitate highly precise health care based on an individual's unique genomic and molecular characteristics. Major investments in science bring a new urgency toward realizing the promise of personalized medicine; yet, many challenges stand in the way. In this article, we present an overview of the opportunities and challenges that influence the oral health community's full participation in personalized medicine. We highlight selected research advances that are solidifying the foundation of personalized oral health care, elaborate on their impact on dentistry, and explore obstacles toward their adoption into practice. It is our view that now is the time for oral health professionals, educators, students, researchers, and patients to engage fully in preparations for the arrival of personalized medicine as a means to provide quality, customized, and effective oral health care for all.

Extensive Genetic Diversity, Unique Population Structure and Evidence of Genetic Exchange in the Sexually Transmitted Parasite Trichomonas vaginalis

PubMed Central

Conrad, Melissa D.; Gorman, Andrew W.; Schillinger, Julia A.; Fiori, Pier Luigi; Arroyo, Rossana; Malla, Nancy; Dubey, Mohan Lal; Gonzalez, Jorge; Blank, Susan; Secor, William E.; Carlton, Jane M.

2012-01-01

Background Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection world-wide. Despite its prevalence, little is known about the genetic diversity and population structure of this haploid parasite due to the lack of appropriate tools. The development of a panel of microsatellite makers and SNPs from mining the parasite's genome sequence has paved the way to a global analysis of the genetic structure of the pathogen and association with clinical phenotypes. Methodology/Principal Findings Here we utilize a panel of T. vaginalis-specific genetic markers to genotype 235 isolates from Mexico, Chile, India, Australia, Papua New Guinea, Italy, Africa and the United States, including 19 clinical isolates recently collected from 270 women attending New York City sexually transmitted disease clinics. Using population genetic analysis, we show that T. vaginalis is a genetically diverse parasite with a unique population structure consisting of two types present in equal proportions world-wide. Parasites belonging to the two types (type 1 and type 2) differ significantly in the rate at which they harbor the T. vaginalis virus, a dsRNA virus implicated in parasite pathogenesis, and in their sensitivity to the widely-used drug, metronidazole. We also uncover evidence of genetic exchange, indicating a sexual life-cycle of the parasite despite an absence of morphologically-distinct sexual stages. Conclusions/Significance Our study represents the first robust and comprehensive evaluation of global T. vaginalis genetic diversity and population structure. Our identification of a unique two-type structure, and the clinically relevant phenotypes associated with them, provides a new dimension for understanding T. vaginalis pathogenesis. In addition, our demonstration of the possibility of genetic exchange in the parasite has important implications for genetic research and control of the disease. PMID:22479659

Role of genetic testing in patients undergoing percutaneous coronary intervention.

PubMed

Moon, Jae Youn; Franchi, Francesco; Rollini, Fabiana; Rivas Rios, Jose R; Kureti, Megha; Cavallari, Larisa H; Angiolillo, Dominick J

2018-02-01

Variability in individual response profiles to antiplatelet therapy, in particular clopidogrel, is a well-established phenomenon. Genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key determinant in clopidogrel metabolism, have been associated with clopidogrel response profiles. Moreover, the presence of a CYP2C19 loss-of-function allele is associated with an increased risk of atherothrombotic events among clopidogrel-treated patients undergoing percutaneous coronary interventions (PCI), prompting studies evaluating the use of genetic tests to identify patients who may be potential candidates for alternative platelet P2Y 12 receptor inhibiting therapies (prasugrel or ticagrelor). Areas covered: The present manuscript provides an overview of genetic factors associated with response profiles to platelet P2Y 12 receptor inhibitors and their clinical implications, as well as the most recent developments and future considerations on the role of genetic testing in patients undergoing PCI. Expert commentary: The availability of more user-friendly genetic tests has contributed towards the development of many ongoing clinical trials and personalized medicine programs for patients undergoing PCI. Results of pilot investigations have shown promising results, which however need to be confirmed in larger-scale studies to support the routine use of genetic testing as a strategy to personalize antiplatelet therapy and improve clinical outcomes.

Molecular and Genomic Alterations in Glioblastoma Multiforme.

PubMed

Crespo, Ines; Vital, Ana Louisa; Gonzalez-Tablas, María; Patino, María del Carmen; Otero, Alvaro; Lopes, María Celeste; de Oliveira, Catarina; Domingues, Patricia; Orfao, Alberto; Tabernero, Maria Dolores

2015-07-01

In recent years, important advances have been achieved in the understanding of the molecular biology of glioblastoma multiforme (GBM); thus, complex genetic alterations and genomic profiles, which recurrently involve multiple signaling pathways, have been defined, leading to the first molecular/genetic classification of the disease. In this regard, different genetic alterations and genetic pathways appear to distinguish primary (eg, EGFR amplification) versus secondary (eg, IDH1/2 or TP53 mutation) GBM. Such genetic alterations target distinct combinations of the growth factor receptor-ras signaling pathways, as well as the phosphatidylinositol 3-kinase/phosphatase and tensin homolog/AKT, retinoblastoma/cyclin-dependent kinase (CDK) N2A-p16(INK4A), and TP53/mouse double minute (MDM) 2/MDM4/CDKN2A-p14(ARF) pathways, in cells that present features associated with key stages of normal neurogenesis and (normal) central nervous system cell types. This translates into well-defined genomic profiles that have been recently classified by The Cancer Genome Atlas Consortium into four subtypes: classic, mesenchymal, proneural, and neural GBM. Herein, we review the most relevant genetic alterations of primary versus secondary GBM, the specific signaling pathways involved, and the overall genomic profile of this genetically heterogeneous group of malignant tumors. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Role of Genetic Testing in Patients undergoing Percutaneous Coronary Intervention

PubMed Central

Moon, Jae Youn; Franchi, Francesco; Rollini, Fabiana; Rios, Jose R. Rivas; Kureti, Megha; Cavallari, Larisa H.; Angiolillo, Dominick J.

2017-01-01

Introduction Variability in individual response profiles to antiplatelet therapy, in particular clopidogrel, is a well-established phenomenon. Genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key determinant in clopidogrel metabolism, have been associated with clopidogrel response profiles. Moreover, the presence of a CYP2C19 loss-of-function allele is associated with an increased risk of atherothrombotic events among clopidogrel-treated patients undergoing percutaneous coronary interventions (PCI), prompting studies evaluating the use of genetic tests to identify patients who may be potential candidates for alternative platelet P2Y12 receptor inhibiting therapies (prasugrel or ticagrelor). Areas covered The present manuscript provides an overview of genetic factors associated with response profiles to platelet P2Y12 receptor inhibitors and their clinical implications, as well as the most recent developments and future considerations on the role of genetic testing in patients undergoing PCI. Expert Commentary The availability of more user-friendly genetic tests has contributed towards the development of many ongoing clinical trials and personalized medicine programs for patients undergoing PCI. Results of pilot investigations have shown promising results, which however need to be confirmed in larger-scale studies to support the routine use of genetic testing as a strategy to personalize antiplatelet therapy and improve clinical outcomes. PMID:28689434

The ABCs of Math: A Genetic Analysis of Mathematics and Its Links With Reading Ability and General Cognitive Ability

PubMed Central

Hart, Sara A.; Petrill, Stephen A.; Thompson, Lee A.; Plomin, Robert

2009-01-01

The goal of this first major report from the Western Reserve Reading Project Math component is to explore the etiology of the relationship among tester-administered measures of mathematics ability, reading ability, and general cognitive ability. Data are available on 314 pairs of monozygotic and same-sex dizygotic twins analyzed across 5 waves of assessment. Univariate analyses provide a range of estimates of genetic (h2 = .00 –.63) and shared (c2 = .15–.52) environmental influences across math calculation, fluency, and problem solving measures. Multivariate analyses indicate genetic overlap between math problem solving with general cognitive ability and reading decoding, whereas math fluency shares significant genetic overlap with reading fluency and general cognitive ability. Further, math fluency has unique genetic influences. In general, math ability has shared environmental overlap with general cognitive ability and decoding. These results indicate that aspects of math that include problem solving have different genetic and environmental influences than math calculation. Moreover, math fluency, a timed measure of calculation, is the only measured math ability with unique genetic influences. PMID:20157630

Atlantic salmon Salmo salar in the chalk streams of England are genetically unique.

PubMed

Ikediashi, C; Paris, J R; King, R A; Beaumont, W R C; Ibbotson, A; Stevens, J R

2018-03-01

Recent research has identified genetic groups of Atlantic salmon Salmo salar that show association with geological and environmental boundaries. This study focuses on one particular subgroup of the species inhabiting the chalk streams of southern England, U.K. These fish are genetically distinct from other British and European S. salar populations and have previously demonstrated markedly low admixture with populations in neighbouring regions. The genetic population structure of S. salar occupying five chalk streams was explored using 16 microsatellite loci. The analysis provides evidence of the genetic distinctiveness of chalk-stream S. salar in southern England, in comparison with populations from non-chalk regions elsewhere in western Europe. Little genetic differentiation exists between the chalk-stream populations and a pattern of isolation by distance was evident. Furthermore, evidence of temporal stability of S. salar populations across the five chalk streams was found. This work provides new insights into the temporal stability and lack of genetic population sub-structuring within a unique component of the species' range of S. salar. © 2018 The Fisheries Society of the British Isles.

DEPRESSION AND INTERNALLY DIRECTED AGGRESSION: GENETIC AND ENVIRONMENTAL CONTRIBUTIONS

PubMed Central

Haddad, Suzanne K.; Neiderhiser, Jenae M.; Spotts, Erica L.; Ganiban, Jody; Lichtenstein, Paul; Reiss, David

2013-01-01

This study uses behavior genetic (BG) methodology to investigate Freud’s theory of depression as aggression directed toward the self (1930) and the extent to which genetically and environmentally influenced aggressive tendencies contribute to depressive symptoms. Data from the Twin and Offspring Study in Sweden (TOSS) is used to demonstrate how, in estimating shared and unique environmental influences, BG methods can inform psychoanalytic theory and practice, particularly because of their shared emphasis on the importance of individual experience in development. The TOSS sample consists of 909 pairs of adult twins, their partners, and one adolescent child per couple. The Center for Epidemiologic Studies Depression Scale (Radloff 1977) was used to measure depressive symptoms and the Karolinska Scales of Personality (Schalling and Edman 1993) to measure internally directed aggression. Genetic analyses indicated that for both men and women, their unique experiences as well as genetic factors contributed equally to the association between internally directed aggression and depressive symptoms. These findings support Freud’s theory that constitutionally based differences in aggression, along with individual experiences, contribute to a person’s depressive symptoms. Establishing that an individual’s unique, not shared, experiences and perceptions contribute to depressive symptoms and internally directed aggression reinforces the use of patient-specific treatment approaches implemented in psychoanalytic psychotherapy or psychoanalysis. PMID:18515705

Chemical characteristics and volatile profile of genetically modified peanut cultivars.

PubMed

Ng, Ee Chin; Dunford, Nurhan T; Chenault, Kelly

2008-10-01

Genetic engineering has been used to modify peanut cultivars for improving agronomic performance and pest resistance. Food products developed through genetic engineering have to be assessed for their safety before approval for human consumption. Preservation of desirable chemical, flavor and aroma attributes of the peanut cultivars during the genetic modifications is critical for acceptance of genetically modified peanuts (GMP) by the food industry. Hence, the main objective of this study is to examine chemical characteristics and volatile profile of GMP. The genetically modified peanut cultivars, 188, 540 and 654 were obtained from the USDA-ARS in Stillwater, Oklahoma. The peanut variety Okrun was examined as a control. The volatile analysis was performed using a gas chromatograph/mass spectrometer (GC/MS) equipped with an olfactory detector. The peanut samples were also analyzed for their moisture, ash, protein, sugar and oil compositions. Experimental results showed that the variations in nutritional composition of peanut lines examined in this study were within the values reported for existing cultivars. There were minor differences in volatile profile among the samples. The implication of this study is significant, since it shows that peanut cultivars with greater pest and fungal resistance were successfully developed without major changes in their chemical characteristics.

Web-Based Analysis for Student-Generated Complex Genetic Profiles

ERIC Educational Resources Information Center

Kass, David H.; LaRoe, Robert

2007-01-01

A simple, rapid method for generating complex genetic profiles using Alu-based markers was recently developed for students primarily at the undergraduate level to learn more about forensics and paternity analysis. On the basis of the Cold Spring Harbor Allele Server, which provides an excellent tool for analyzing a single Alu variant, we present a…

Cytogenetic Profile of Down Syndrome Cases Seen by a General Genetics Outpatient Service in Brazil

ERIC Educational Resources Information Center

Biselli, Joice; Goloni-Bertollo, Eny; Ruiz, Mariangela; Pavarino-Bertelli, Erika

2009-01-01

Down syndrome or trisomy 21 can be caused by three types of chromosomal abnormalities: free trisomy 21, translocation or mosaicism. The cytogenetic diagnosis, made through karyotypic examination, is important mainly to determine recurrence risks to assist genetic counselling. The object of this work was to carry out a cytogenetic profile of…

Isolation and biological and molecular characterization of Neospora caninum (NC-SP1) from a naturally infected adult asymptomatic cattle (Bos taurus) in the state of São Paulo, Brazil.

PubMed

Oliveira, Solange; Soares, Rodrigo Martins; Aizawa, Juliana; Soares, Herbert Sousa; Chiebao, Daniela Pontes; Ortega-Mora, Luis Miguel; Regidor-Cerrillo, Javier; Silva, Natália Quadros Bressa; Gennari, Solange Maria; Pena, Hilda Fátima Jesus

2017-05-01

The biological and genetic diversity of Neospora caninum is very limited because of availability of only a few viable isolates worldwide. This study describes the isolation and biological and molecular characterization of a new viable isolate of N. caninum (NC-SP1), from a cattle in Brazil. Approximately 400 g of brain from a naturally infected adult male cattle from an abattoir was fed to a 2-month-old dog. Neospora-like oocysts were observed on day 7 post-inoculation (PI) and the duration of oocyst shedding was 14 days. The DNA obtained from oocysts was characterized molecularly and the final sequence was 99% identical to homologous sequences of N. caninum available in GenBank®. For bioassay, gerbils (Meriones unguiculatus) were orally inoculated with 10 100 and 1000 oocysts; all gerbils remained clinically normal but developed N. caninum antibodies 14 days PI. Cell culture isolation was successful using the brain homogenate from one of the gerbils and tachyzoites were observed 24 days PI. Microsatellite genotyping revealed a unique genetic profile for this new reference isolate.

Isolation of Neospora caninum from kidney and brain of a bovine foetus and molecular characterization in Brazil.

PubMed

Locatelli Dittrich, Rosangela; Regidor-Cerrillo, Javier; Ortega-Mora, Luis Miguel; Oliveira Koch, Marília de; Busch, Ana Paula B; Gonçalves, Kamila Alcalá; Cruz, Amilcar A

2018-02-01

Bovine neosporosis has become a disease of international concern as it is among the main causes of abortion in cattle. Viable N. caninum has been isolated from brains of fetuses and neonatal calves, and there is no report of isolation of tachyzoites from kidney. Also, detailed information about the genetic diversity of N. caninum is scarce. N. caninum tachyzoites were isolated from the kidney and the brain of an aborted 4-month-old bovine foetus. The parasite was confirmed to be N. caninum by PCR. The tachyzoites of the new isolate, named BNC-PR4, were propagated in Vero cell cultures. Pathogenicity of the parasite was examined in BALB/c mice. Mice inoculated intraperitoneally with BNC-PR4 failed to yield clinical signs of disease and did not induce severe brain lesions, suggesting a bovine isolate with low virulence. The N. caninum-positive DNA sample was further analyzed by multilocus microsatellite (MS) genotyping for MS4, MS5, MS6A, MS6B, MS7, MS8, MS10, MS12, and MS21. Multilocus-microsatellite genotyping revealed a unique genetic profile that differed from previously reported isolates. Published by Elsevier Inc.

Mutation Analysis of the Common Deafness Genes in Patients with Nonsyndromic Hearing Loss in Linyi by SNPscan Assay.

PubMed

Zhang, Fengguo; Xiao, Yun; Xu, Lei; Zhang, Xue; Zhang, Guodong; Li, Jianfeng; Lv, Huaiqing; Bai, Xiaohui; Wang, Haibo

2016-01-01

Hearing loss is a common sensory disorder, and at least 50% of cases are due to a genetic etiology. Although hundreds of genes have been reported to be associated with nonsyndromic hearing loss, GJB2, SLC26A4, and mtDNA12SrRNA are the major contributors. However, the mutation spectrum of these common deafness genes varies among different ethnic groups. The present work summarized mutations in these three genes and their prevalence in 339 patients with nonsyndromic hearing loss at three different special education schools and one children's hospital in Linyi, China. A new multiplex genetic screening system "SNPscan assay" was employed to detect a total of 115 mutations of the above three genes. Finally, 48.67% of the patients were identified with hereditary hearing loss caused by mutations in GJB2, SLC26A4, and mtDNA12SrRNA. The carrying rate of mutations in the three genes was 37.76%, 19.75%, and 4.72%, respectively. This mutation profile in our study is distinct from other parts of China, with high mutation rate of GJB2 suggesting a unique mutation spectrum in this area.

Human metabolic profiles are stably controlled by genetic and environmental variation

PubMed Central

Nicholson, George; Rantalainen, Mattias; Maher, Anthony D; Li, Jia V; Malmodin, Daniel; Ahmadi, Kourosh R; Faber, Johan H; Hallgrímsdóttir, Ingileif B; Barrett, Amy; Toft, Henrik; Krestyaninova, Maria; Viksna, Juris; Neogi, Sudeshna Guha; Dumas, Marc-Emmanuel; Sarkans, Ugis; The MolPAGE Consortium; Silverman, Bernard W; Donnelly, Peter; Nicholson, Jeremy K; Allen, Maxine; Zondervan, Krina T; Lindon, John C; Spector, Tim D; McCarthy, Mark I; Holmes, Elaine; Baunsgaard, Dorrit; Holmes, Chris C

2011-01-01

1H Nuclear Magnetic Resonance spectroscopy (1H NMR) is increasingly used to measure metabolite concentrations in sets of biological samples for top-down systems biology and molecular epidemiology. For such purposes, knowledge of the sources of human variation in metabolite concentrations is valuable, but currently sparse. We conducted and analysed a study to create such a resource. In our unique design, identical and non-identical twin pairs donated plasma and urine samples longitudinally. We acquired 1H NMR spectra on the samples, and statistically decomposed variation in metabolite concentration into familial (genetic and common-environmental), individual-environmental, and longitudinally unstable components. We estimate that stable variation, comprising familial and individual-environmental factors, accounts on average for 60% (plasma) and 47% (urine) of biological variation in 1H NMR-detectable metabolite concentrations. Clinically predictive metabolic variation is likely nested within this stable component, so our results have implications for the effective design of biomarker-discovery studies. We provide a power-calculation method which reveals that sample sizes of a few thousand should offer sufficient statistical precision to detect 1H NMR-based biomarkers quantifying predisposition to disease. PMID:21878913

Single-cell mRNA sequencing identifies subclonal heterogeneity in anti-cancer drug responses of lung adenocarcinoma cells.

PubMed

Kim, Kyu-Tae; Lee, Hye Won; Lee, Hae-Ock; Kim, Sang Cheol; Seo, Yun Jee; Chung, Woosung; Eum, Hye Hyeon; Nam, Do-Hyun; Kim, Junhyong; Joo, Kyeung Min; Park, Woong-Yang

2015-06-19

Intra-tumoral genetic and functional heterogeneity correlates with cancer clinical prognoses. However, the mechanisms by which intra-tumoral heterogeneity impacts therapeutic outcome remain poorly understood. RNA sequencing (RNA-seq) of single tumor cells can provide comprehensive information about gene expression and single-nucleotide variations in individual tumor cells, which may allow for the translation of heterogeneous tumor cell functional responses into customized anti-cancer treatments. We isolated 34 patient-derived xenograft (PDX) tumor cells from a lung adenocarcinoma patient tumor xenograft. Individual tumor cells were subjected to single cell RNA-seq for gene expression profiling and expressed mutation profiling. Fifty tumor-specific single-nucleotide variations, including KRAS(G12D), were observed to be heterogeneous in individual PDX cells. Semi-supervised clustering, based on KRAS(G12D) mutant expression and a risk score representing expression of 69 lung adenocarcinoma-prognostic genes, classified PDX cells into four groups. PDX cells that survived in vitro anti-cancer drug treatment displayed transcriptome signatures consistent with the group characterized by KRAS(G12D) and low risk score. Single-cell RNA-seq on viable PDX cells identified a candidate tumor cell subgroup associated with anti-cancer drug resistance. Thus, single-cell RNA-seq is a powerful approach for identifying unique tumor cell-specific gene expression profiles which could facilitate the development of optimized clinical anti-cancer strategies.

Cohort profile: the Western Australian Sleep Health Study.

PubMed

Mukherjee, Sutapa; Hillman, David; Lee, Jessica; Fedson, Annette; Simpson, Laila; Ward, Kim; Love, Gregory; Edwards, Cass; Szegner, Bernadett; Palmer, Lyle John

2012-03-01

Epidemiologic and genetic studies of obstructive sleep apnoea (OSA) are limited by a lack of large-scale, well-characterized OSA cohorts. These studies require large sample size to provide adequate power to detect differences between groups. This study describes the development of such a cohort (The Western Australian Sleep Health Study) in OSA patients of Caucasian-European origin attending the only public sleep clinic in Western Australia (WA). The main aim of the study is to phenotype 4,000 OSA patients in order to define the genetics of OSA and its co-morbidities. Almost all underwent laboratory-based attended polysomnography (PSG). Currently complete data (questionnaire, biochemistry, DNA, and PSG) has been obtained on over 3,000 individuals and will reach the target of 4,000 individuals by the end of 2010. In a separate but related study, we have developed a sleep study database containing data from all patients who have undergone PSG at the sleep laboratory since its inception in 1988 until the present day (over 30,000 PSG studies representing data from approximately 20,000 individuals). In addition, data from both cohorts have been linked prospectively to statutory health data collected by the WA Department of Health. This study will be the largest sleep clinic cohort database internationally with access to genetic and epidemiological data. It is unique among sleep clinic cohorts because of its size, the breadth of data collected and the ability to link prospectively to statutory health data. It will be a major tool to comprehensively assess genetic and epidemiologic factors determining OSA and its co-morbidities.

Genetic Biodiversity of Italian Olives (Olea europaea) Germplasm Analyzed by SSR Markers

PubMed Central

Vendramin, Giuseppe Giovanni; Chiappetta, Adriana

2014-01-01

The olive is an important fruit species cultivated for oil and table olives in Italy and the Mediterranean basin. The conservation of cultivated plants in ex situ collections is essential for the optimal management and use of their genetic resources. The largest ex situ olive germplasm collection consists of approximately 500 Italian olive varieties and corresponding to 85% of the total Italian olive germplasm is maintained at the Consiglio per la Ricerca e sperimentazione per l'Agricoltura, Centro di Ricerca per l'Olivicoltura e l'Industria Olearia (CRA-OLI), in Italy. In this work, eleven preselected nuclear microsatellite markers were used to assess genetic diversity, population structure, and gene flows with the aim of assembling a core collection. The dendrogram obtained utilizing the unweighted pair group method highlights the presence of homonymy and synonymy in olive tree datasets analyzed in this study. 439 different unique genotype profiles were obtained with this combination of 11 loci nSSR, representing 89.8% of the varieties analyzed. The remaining 10.2% comprises different variety pairs in which both accessions are genetically indistinguishable. Clustering analysis performed using BAPS software detected seven groups in Italian olive germplasm and gene flows were determined among identified clusters. We proposed an Italian core collection of 23 olive varieties capturing all detected alleles at microsatellites. The information collected in this study regarding the CRA-OLI ex situ collection can be used for breeding programs, for germplasm conservation, and for optimizing a strategy for the management of olive gene pools. PMID:24723801

Linking Genes to Cardiovascular Diseases: Gene Action and Gene–Environment Interactions

PubMed Central

2016-01-01

A unique myocardial characteristic is its ability to grow/remodel in order to adapt; this is determined partly by genes and partly by the environment and the milieu intérieur. In the “post-genomic” era, a need is emerging to elucidate the physiologic functions of myocardial genes, as well as potential adaptive and maladaptive modulations induced by environmental/epigenetic factors. Genome sequencing and analysis advances have become exponential lately, with escalation of our knowledge concerning sometimes controversial genetic underpinnings of cardiovascular diseases. Current technologies can identify candidate genes variously involved in diverse normal/abnormal morphomechanical phenotypes, and offer insights into multiple genetic factors implicated in complex cardiovascular syndromes. The expression profiles of thousands of genes are regularly ascertained under diverse conditions. Global analyses of gene expression levels are useful for cataloging genes and correlated phenotypes, and for elucidating the role of genes in maladies. Comparative expression of gene networks coupled to complex disorders can contribute insights as to how “modifier genes” influence the expressed phenotypes. Increasingly, a more comprehensive and detailed systematic understanding of genetic abnormalities underlying, for example, various genetic cardiomyopathies is emerging. Implementing genomic findings in cardiology practice may well lead directly to better diagnosing and therapeutics. There is currently evolving a strong appreciation for the value of studying gene anomalies, and doing so in a non-disjointed, cohesive manner. However, it is challenging for many—practitioners and investigators—to comprehend, interpret, and utilize the clinically increasingly accessible and affordable cardiovascular genomics studies. This survey addresses the need for fundamental understanding in this vital area. PMID:26545598

Statistically Derived Subtypes and Associations with Cerebrospinal Fluid and Genetic Biomarkers in Mild Cognitive Impairment: A Latent Profile Analysis.

PubMed

Eppig, Joel S; Edmonds, Emily C; Campbell, Laura; Sanderson-Cimino, Mark; Delano-Wood, Lisa; Bondi, Mark W

2017-08-01

Research demonstrates heterogeneous neuropsychological profiles among individuals with mild cognitive impairment (MCI). However, few studies have included visuoconstructional ability or used latent mixture modeling to statistically identify MCI subtypes. Therefore, we examined whether unique neuropsychological MCI profiles could be ascertained using latent profile analysis (LPA), and subsequently investigated cerebrospinal fluid (CSF) biomarkers, genotype, and longitudinal clinical outcomes between the empirically derived classes. A total of 806 participants diagnosed by means of the Alzheimer's Disease Neuroimaging Initiative (ADNI) MCI criteria received a comprehensive neuropsychological battery assessing visuoconstructional ability, language, attention/executive function, and episodic memory. Test scores were adjusted for demographic characteristics using standardized regression coefficients based on "robust" normal control performance (n=260). Calculated Z-scores were subsequently used in the LPA, and CSF-derived biomarkers, genotype, and longitudinal clinical outcome were evaluated between the LPA-derived MCI classes. Statistical fit indices suggested a 3-class model was the optimal LPA solution. The three-class LPA consisted of a mixed impairment MCI class (n=106), an amnestic MCI class (n=455), and an LPA-derived normal class (n=245). Additionally, the amnestic and mixed classes were more likely to be apolipoprotein e4+ and have worse Alzheimer's disease CSF biomarkers than LPA-derived normal subjects. Our study supports significant heterogeneity in MCI neuropsychological profiles using LPA and extends prior work (Edmonds et al., 2015) by demonstrating a lower rate of progression in the approximately one-third of ADNI MCI individuals who may represent "false-positive" diagnoses. Our results underscore the importance of using sensitive, actuarial methods for diagnosing MCI, as current diagnostic methods may be over-inclusive. (JINS, 2017, 23, 564-576).

Unique genetic variation at a species' rear edge is under threat from global climate change

PubMed Central

Provan, Jim; Maggs, Christine A.

2012-01-01

Global climate change is having a significant effect on the distributions of a wide variety of species, causing both range shifts and population extinctions. To date, however, no consensus has emerged on how these processes will affect the range-wide genetic diversity of impacted species. It has been suggested that species that recolonized from low-latitude refugia might harbour high levels of genetic variation in rear-edge populations, and that loss of these populations could cause a disproportionately large reduction in overall genetic diversity in such taxa. In the present study, we have examined the distribution of genetic diversity across the range of the seaweed Chondrus crispus, a species that has exhibited a northward shift in its southern limit in Europe over the last 40 years. Analysis of 19 populations from both sides of the North Atlantic using mitochondrial single nucleotide polymorphisms (SNPs), sequence data from two single-copy nuclear regions and allelic variation at eight microsatellite loci revealed unique genetic variation for all marker classes in the rear-edge populations in Iberia, but not in the rear-edge populations in North America. Palaeodistribution modelling and statistical testing of alternative phylogeographic scenarios indicate that the unique genetic diversity in Iberian populations is a result not only of persistence in the region during the last glacial maximum, but also because this refugium did not contribute substantially to the recolonization of Europe after the retreat of the ice. Consequently, loss of these rear-edge populations as a result of ongoing climate change will have a major effect on the overall genetic diversity of the species, particularly in Europe, and this could compromise the adaptive potential of the species as a whole in the face of future global warming. PMID:21593035

Farmers prevailing perception profiles regarding GM crops: A classification proposal.

PubMed

Almeida, Carla; Massarani, Luisa

2018-04-01

Genetically modified organisms have been at the centre of a major public controversy, involving different interests and actors. While much attention has been devoted to consumer views on genetically modified food, there have been few attempts to understand the perceptions of genetically modified technology among farmers. By investigating perceptions of genetically modified organisms among Brazilian farmers, we intend to contribute towards filling this gap and thereby add the views of this stakeholder group to the genetically modified debate. A comparative analysis of our data and data from other studies indicate there is a complex variety of views on genetically modified organisms among farmers. Despite this diversity, we found variations in such views occur within limited parameters, concerned principally with expectations or concrete experiences regarding the advantages of genetically modified crops, perceptions of risks associated with them, and ethical questions they raise. We then propose a classification of prevailing profiles to represent the spectrum of perceptions of genetically modified organisms among farmers.

Genetic and environmental influences on growth from late childhood to adulthood: a longitudinal study of two Finnish twin cohorts.

PubMed

Jelenkovic, Aline; Ortega-Alonso, Alfredo; Rose, Richard J; Kaprio, Jaakko; Rebato, Esther; Silventoinen, Karri

2011-01-01

Human growth is a complex process that remains insufficiently understood. We aimed to analyze genetic and environmental influences on growth from late childhood to early adulthood. Two cohorts of monozygotic and dizygotic (same sex and opposite sex) Finnish twin pairs were studied longitudinally using self-reported height at 11-12, 14, and 17 years and adult age (FinnTwin12) and at 16, 17, and 18 years and adult age (FinnTwin16). Univariate and multivariate variance component models for twin data were used. From childhood to adulthood, genetic differences explained 72-81% of the variation of height in boys and 65-86% in girls. Environmental factors common to co-twins explained 5-23% of the variation of height, with the residual variation explained by environmental factors unique to each twin individual. Common environmental factors affecting height were highly correlated between the analyzed ages (0.72-0.99 and 0.91-1.00 for boys and girls, respectively). Genetic (0.58-0.99 and 0.70-0.99, respectively) and unique environmental factors (0.32-0.78 and 0.54-0.82, respectively) affecting height at different ages were more weakly, but still substantially, correlated. The genetic contribution to height is strong during adolescence. The high genetic correlations detected across the ages encourage further efforts to identify genes affecting growth. Common and unique environmental factors affecting height during adolescence are also important, and further studies are necessary to identify their nature and test whether they interact with genetic factors. Copyright © 2011 Wiley-Liss, Inc.

Ethnopsychopharmacology considerations for Asians and Asian Americans.

PubMed

Wong, Felicia K; Pi, Edmond H

2012-03-01

Asians comprise more than 60% of the world's population and are the fastest growing minority group in the United States. Today's psychiatrist must learn to recognize and appreciate the unique factors that influence mental health outcomes in this group. Asian Americans are affected by psychiatric disorders at similar rates as non-Asians, but are significantly underrepresented in psychiatric clinics. When Asians and Asian Americans do present for psychiatric treatment, they often do so with higher severity of illness, and variable levels of compliance. Studies over the past three decades have suggested that pharmacokinetic and pharmacodynamic profiles of various psychotropic medications may be different in Asians, leading to differences in dosage requirements and side-effect profiles. These variations appear to be largely determined by genetic predisposition, but are also influenced by other factors such as environment, social support, cultural perceptions, and physicians' prescribing habits. In this paper, we provide an overview of biological and socio-cultural issues as they relate to psychopharmacology in Asians and Asian Americans, with the hope that a better understanding of these issues will lead to improved mental health care delivery to this population both in the United States, as well as in Asian countries. Copyright © 2012 Elsevier B.V. All rights reserved.

Practical relevance of pattern uniqueness in forensic science.

PubMed

Jayaprakash, Paul T

2013-09-10

Uniqueness being unprovable, it has recently been argued that individualization in forensic science is irrelevant and, probability, as applied for DNA profiles, should be applied for all identifications. Critiques against uniqueness have omitted physical matching, a realistic and tangible individualization that supports uniqueness. Describing case examples illustrating pattern matches including physical matching, it is indicated that individualizations are practically relevant for forensic science as they establish facts on a definitive basis providing firm leads benefitting criminal investigation. As a tenet of forensic identification, uniqueness forms a fundamental paradigm relevant for individualization. Evidence on the indeterministic and stochastic causal pathways of characteristics in patterns available in the related fields of science sufficiently supports the proposition of uniqueness. Characteristics involved in physical matching and matching achieved in patterned evidence existing in the state of nature are not events amenable for counting; instead these are ensemble of visible units occupying the entire pattern area stretching the probability of re-occurrence of a verisimilitude pattern into infinity offering epistemic support to uniqueness. Observational methods are as respectable as instrumental or statistical methods since they are capable of generating results that are tangible and obviously valid as in physical matching. Applying the probabilistic interpretation used for DNA profiles to the other patterns would be unbefitting since these two are disparate, the causal pathways of the events, the loci, in the manipulated DNA profiles being determinable. While uniqueness enables individualizations, it does not vouch for eliminating errors. Instead of dismissing uniqueness and individualization, accepting errors as human or system failures and seeking remedial measures would benefit forensic science practice and criminal investigation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Digging up the recent Spanish memory: genetic identification of human remains from mass graves of the Spanish Civil War and posterior dictatorship.

PubMed

Baeta, Miriam; Núñez, Carolina; Cardoso, Sergio; Palencia-Madrid, Leire; Herrasti, Lourdes; Etxeberria, Francisco; de Pancorbo, Marian M

2015-11-01

The Spanish Civil War (1936-1939) and posterior dictatorship (until 1970s) stands as one of the major conflicts in the recent history of Spain. It led to nearly two hundred thousand men and women executed or murdered extra-judicially or after dubious legal procedures. Nowadays, most of them remain unidentified or even buried in irretraceable mass graves across Spain. Here, we present the genetic identification of human remains found in 26 mass graves located in Northern Spain. A total of 252 post-mortem remains were analyzed and compared to 186 relatives, allowing the identification of 87 victims. Overall, a significant success of DNA profiling was reached, since informative profiles (≥ 12 STRs and/or mitochondrial DNA profile) were obtained in 85.71% of the remains. This high performance in DNA profiling from challenging samples demonstrated the efficacy of DNA extraction and amplification methods used herein, given that only around 14.29% of the samples did not provide an informative genetic profile for the analysis performed, probably due to the presence of degraded and/or limited DNA in these remains. However, this study shows a partial identification success rate, which is clearly a consequence of the lack of both appropriate family members for genetic comparisons and accurate information about the victims' location. Hence, further perseverance in the exhumation of other intact graves as well as in the search of more alleged relatives is crucial in order to facilitate and increase the number of genetic identifications. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Enzyme markers in inbred rat strains: genetics of new markers and strain profiles.

PubMed

Adams, M; Baverstock, P R; Watts, C H; Gutman, G A

1984-08-01

Twenty-six inbred strains of the laboratory rat (Rattus norvegicus) were examined for electrophoretic variation at an estimated 97 genetic loci. In addition to previously documented markers, variation was observed for the enzymes aconitase, aldehyde dehydrogenase, and alkaline phosphatase. The genetic basis of these markers (Acon-1, Ahd-2, and Akp-1) was confirmed. Linkage analysis between 35 pairwise comparisons revealed that the markers Fh-1 and Pep-3 are linked. The strain profiles of the 25 inbred strains at 11 electrophoretic markers are given.

The five-factor model of personality and borderline personality disorder: a genetic analysis of comorbidity.

PubMed

Distel, Marijn A; Trull, Timothy J; Willemsen, Gonneke; Vink, Jacqueline M; Derom, Catherine A; Lynskey, Michael; Martin, Nicholas G; Boomsma, Dorret I

2009-12-15

Recently, the nature of personality disorders and their relationship with normal personality traits has received extensive attention. The five-factor model (FFM) of personality, consisting of the personality traits neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness, is one of the proposed models to conceptualize personality disorders as maladaptive variants of continuously distributed personality traits. The present study examined the phenotypic and genetic association between borderline personality and FFM personality traits. Data were available for 4403 monozygotic twins, 4425 dizygotic twins, and 1661 siblings from 6140 Dutch, Belgian, and Australian families. Broad-sense heritability estimates for neuroticism, agreeableness, conscientiousness, extraversion, openness to experience, and borderline personality were 43%, 36%, 43%, 47%, 54%, and 45%, respectively. Phenotypic correlations between borderline personality and the FFM personality traits ranged from .06 for openness to experience to .68 for neuroticism. Multiple regression analyses showed that a combination of high neuroticism and low agreeableness best predicted borderline personality. Multivariate genetic analyses showed the genetic factors that influence individual differences in neuroticism, agreeableness, conscientiousness, and extraversion account for all genetic liability to borderline personality. Unique environmental effects on borderline personality, however, were not completely shared with those for the FFM traits (33% is unique to borderline personality). Borderline personality shares all genetic variation with neuroticism, agreeableness, conscientiousness, and extraversion. The unique environmental influences specific to borderline personality may cause individuals with a specific pattern of personality traits to cross a threshold and develop borderline personality.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waters, M.D.; Stack, H.F.; Garrett, N.E.

A graphic approach, terms a Genetic Activity Profile (GAP), was developed to display a matrix of data on the genetic and related effects of selected chemical agents. The profiles provide a visual overview of the quantitative (doses) and qualitative (test results) data for each chemical. Either the lowest effective dose or highest ineffective dose is recorded for each agent and bioassay. Up to 200 different test systems are represented across the GAP. Bioassay systems are organized according to the phylogeny of the test organisms and the end points of genetic activity. The methodology for producing and evaluating genetic activity profilemore » was developed in collaboration with the International Agency for Research on Cancer (IARC). Data on individual chemicals were compiles by IARC and by the US Environmental Protection Agency (EPA). Data are available on 343 compounds selected from volumes 1-53 of the IARC Monographs and on 115 compounds identified as Superfund Priority Substances. Software to display the GAPs on an IBM-compatible personal computer is available from the authors. Structurally similar compounds frequently display qualitatively and quantitatively similar profiles of genetic activity. Through examination of the patterns of GAPs of pairs and groups of chemicals, it is possible to make more informed decisions regarding the selection of test batteries to be used in evaluation of chemical analogs. GAPs provided useful data for development of weight-of-evidence hazard ranking schemes. Also, some knowledge of the potential genetic activity of complex environmental mixtures may be gained from an assessment of the genetic activity profiles of component chemicals. The fundamental techniques and computer programs devised for the GAP database may be used to develop similar databases in other disciplines. 36 refs., 2 figs.« less

Links between Genetic Groups, Indole Alkaloid Profiles and Ecology within the Grass-Parasitic Claviceps purpurea Species Complex.

PubMed

Negård, Mariell; Uhlig, Silvio; Kauserud, Håvard; Andersen, Tom; Høiland, Klaus; Vrålstad, Trude

2015-04-28

The grass parasitic fungus Claviceps purpurea sensu lato produces sclerotia with toxic indole alkaloids. It constitutes several genetic groups with divergent habitat preferences that recently were delimited into separate proposed species. We aimed to 1) analyze genetic variation of C. purpurea sensu lato in Norway, 2) characterize the associated indole alkaloid profiles, and 3) explore relationships between genetics, alkaloid chemistry and ecology. Approximately 600 sclerotia from 14 different grass species were subjected to various analyses including DNA sequencing and HPLC-MS. Molecular results, supported by chemical and ecological data, revealed one new genetic group (G4) in addition to two of the three known; G1 (C. purpurea sensu stricto) and G2 (C. humidiphila). G3 (C. spartinae) was not found. G4, which was apparently con-specific with the recently described C. arundinis sp. nov, was predominantly found in very wet habitats on Molinia caerulea and infrequently in saline habitats on Leymus arenarius. Its indole-diterpene profile resembled G2, while its ergot alkaloid profile differed from G2 in high amounts of ergosedmam. In contrast to G1, indole-diterpenes were consistently present in G2 and G4. Our study supports and complements the newly proposed species delimitation of the C. purpurea complex, but challenges some species characteristics including host spectrum, habitat preferences and sclerotial floating ability.

Links between Genetic Groups, Indole Alkaloid Profiles and Ecology within the Grass-Parasitic Claviceps purpurea Species Complex

PubMed Central

Negård, Mariell; Uhlig, Silvio; Kauserud, Håvard; Andersen, Tom; Høiland, Klaus; Vrålstad, Trude

2015-01-01

The grass parasitic fungus Claviceps purpurea sensu lato produces sclerotia with toxic indole alkaloids. It constitutes several genetic groups with divergent habitat preferences that recently were delimited into separate proposed species. We aimed to 1) analyze genetic variation of C. purpurea sensu lato in Norway, 2) characterize the associated indole alkaloid profiles, and 3) explore relationships between genetics, alkaloid chemistry and ecology. Approximately 600 sclerotia from 14 different grass species were subjected to various analyses including DNA sequencing and HPLC-MS. Molecular results, supported by chemical and ecological data, revealed one new genetic group (G4) in addition to two of the three known; G1 (C. purpurea sensu stricto) and G2 (C. humidiphila). G3 (C. spartinae) was not found. G4, which was apparently con-specific with the recently described C. arundinis sp. nov, was predominantly found in very wet habitats on Molinia caerulea and infrequently in saline habitats on Leymus arenarius. Its indole-diterpene profile resembled G2, while its ergot alkaloid profile differed from G2 in high amounts of ergosedmam. In contrast to G1, indole-diterpenes were consistently present in G2 and G4. Our study supports and complements the newly proposed species delimitation of the C. purpurea complex, but challenges some species characteristics including host spectrum, habitat preferences and sclerotial floating ability. PMID:25928134

Steroid profiles of professional soccer players: an international comparative study.

PubMed

Strahm, E; Sottas, P-E; Schweizer, C; Saugy, M; Dvorak, J; Saudan, C

2009-12-01

Urinary steroid profiling is used in doping controls to detect testosterone abuse. A testosterone over epitestosterone (T/E) ratio exceeding 4.0 is considered as suspicious of testosterone administration, irrespectively of individual heterogeneous factors such as the athlete's ethnicity. A deletion polymorphism in the UGT2B17 gene was demonstrated to account for a significant part of the interindividual variability in the T/E between Caucasians and Asians. Here, the variability of urinary steroid profiles was examined in a widely heterogeneous cohort of professional soccer players. The steroid profile of 57 Africans, 32 Asians, 50 Caucasians and 32 Hispanics was determined by gas chromatography-mass spectrometry. Significant differences have been observed between all ethnic groups. After estimation of the prevalence of the UGT2B17 deletion/deletion genotype (African: 22%; Asian: 81%; Caucasian: 10%; Hispanic: 7%), ethnic-specific thresholds were developed for a specificity of 99% for the T/E (African: 5.6; Asian: 3.8; Caucasian: 5.7; Hispanic: 5.8). Finally, another polymorphism could be hypothesised in Asians based on specific concentration ratio of 5alpha-/5beta-androstane-3alpha,17beta-diol in urine. These results demonstrate that a unique and non-specific threshold to evidence testosterone misuse is not fit for purpose. An athlete's endocrinological passport consisting of a longitudinal follow-up together with the ethnicity and/or the genotype would strongly enhance the detection of testosterone abuse. Finally, additional genotyping studies should be undertaken to determine whether the remaining unexplained disparities have an environmental or a genetic origin.

Genomic analysis of CD8+ NK/T cell line, ‘SRIK-NKL’, with array-based CGH (aCGH), SKY/FISH and molecular mapping

PubMed Central

Rossi, Michael; LaDuca, Jeff; Cowell, John; Srivastava, Bejai I.S.; Matsui, Sei-ichi

2010-01-01

We performed aCGH, SKY /FISH, molecular mapping and expression analyses on a permanent CD8+ NK/T cell line, ‘SRIK-NKL’ established from a lymphoma (ALL) patient, in attempt to define the fundamental genetic profile of its unique NK phenotypes. aCGH revealed hemizygous deletion of 6p containing genes responsible for hematopoietic functions. The SKY demonstrated that a constitutive reciprocal translocation, rcpt(5;14)(p13.2;q11) is a stable marker. Using somatic hybrids containing der(5) derived from SRIK-NKL, we found that the breakpoint in one homologue of no. 5 is located upstream of IL7R and also that the breakpoint in no. 14 is located within TRA@. The FISH analysis using BAC which contains TRA@ and its flanking region further revealed a ~231 kb deletion within 14q11 in the der(5) but not in the normal homologue of no. 14. The RT-PCR analysis detected mRNA for TRA@ transcripts which were extending across, but not including, the deleted region. IL7R was detected at least at mRNA levels. These findings were consistent with the immunological findings that TRA@ and IL7R are both expressed at mRNA levels and TRA@ at cytoplasmic protein levels in SRIK-NKL cells. In addition to rept(5;14), aCGH identified novel copy number abnormalities suggesting that the unique phenotype of the SRIK-NKL cell line is not solely due to the TRA@ rearrangement. These findings provide supportive evidence for the notion that SRIK-NKL cells may be useful for studying not only the function of NK cells but also genetic deregulations associated with leukemiogenesis. PMID:17640729

Genome-scale analysis of aberrant DNA methylation in colorectal cancer

PubMed Central

Hinoue, Toshinori; Weisenberger, Daniel J.; Lange, Christopher P.E.; Shen, Hui; Byun, Hyang-Min; Van Den Berg, David; Malik, Simeen; Pan, Fei; Noushmehr, Houtan; van Dijk, Cornelis M.; Tollenaar, Rob A.E.M.; Laird, Peter W.

2012-01-01

Colorectal cancer (CRC) is a heterogeneous disease in which unique subtypes are characterized by distinct genetic and epigenetic alterations. Here we performed comprehensive genome-scale DNA methylation profiling of 125 colorectal tumors and 29 adjacent normal tissues. We identified four DNA methylation–based subgroups of CRC using model-based cluster analyses. Each subtype shows characteristic genetic and clinical features, indicating that they represent biologically distinct subgroups. A CIMP-high (CIMP-H) subgroup, which exhibits an exceptionally high frequency of cancer-specific DNA hypermethylation, is strongly associated with MLH1 DNA hypermethylation and the BRAFV600E mutation. A CIMP-low (CIMP-L) subgroup is enriched for KRAS mutations and characterized by DNA hypermethylation of a subset of CIMP-H-associated markers rather than a unique group of CpG islands. Non-CIMP tumors are separated into two distinct clusters. One non-CIMP subgroup is distinguished by a significantly higher frequency of TP53 mutations and frequent occurrence in the distal colon, while the tumors that belong to the fourth group exhibit a low frequency of both cancer-specific DNA hypermethylation and gene mutations and are significantly enriched for rectal tumors. Furthermore, we identified 112 genes that were down-regulated more than twofold in CIMP-H tumors together with promoter DNA hypermethylation. These represent ∼7% of genes that acquired promoter DNA methylation in CIMP-H tumors. Intriguingly, 48/112 genes were also transcriptionally down-regulated in non-CIMP subgroups, but this was not attributable to promoter DNA hypermethylation. Together, we identified four distinct DNA methylation subgroups of CRC and provided novel insight regarding the role of CIMP-specific DNA hypermethylation in gene silencing. PMID:21659424

African Indigenous Cattle: Unique Genetic Resources in a Rapidly Changing World

PubMed Central

Mwai, Okeyo; Hanotte, Olivier; Kwon, Young-Jun; Cho, Seoae

2015-01-01

At least 150 indigenous African cattle breeds have been named, but the majority of African cattle populations remain largely uncharacterized. As cattle breeds and populations in Africa adapted to various local environmental conditions, they acquired unique features. We know now that the history of African cattle was particularly complex and while several of its episodes remain debated, there is no doubt that African cattle population evolved dramatically over time. Today, we find a mosaic of genetically diverse population from the purest Bos taurus to the nearly pure Bos indicus. African cattle are now found all across the continent, with the exception of the Sahara and the river Congo basin. They are found on the rift valley highlands as well as below sea level in the Afar depression. These unique livestock genetic resources are in danger to disappear rapidly following uncontrolled crossbreeding and breed replacements with exotic breeds. Breeding improvement programs of African indigenous livestock remain too few while paradoxically the demand of livestock products is continually increasing. Many African indigenous breeds are endangered now, and their unique adaptive traits may be lost forever. This paper reviews the unique known characteristics of indigenous African cattle populations while describing the opportunities, the necessity and urgency to understand and utilize these resources to respond to the needs of the people of the continent and to the benefit of African farmers. PMID:26104394

Effect of Cultivar and Cultivation Year on the Metabolite Profile of Onion Bulbs ( Allium cepa L.).

PubMed

Böttcher, Christoph; Krähmer, Andrea; Stürtz, Melanie; Widder, Sabine; Schulz, Hartwig

2018-03-28

This study investigated the variation of metabolite profiles of onion bulbs ( Allium cepa L.) depending on genetic and environmental factors. Nine onion cultivars ("Corrado", "Cupido", "Forum", "Hytech", "Picador", "Redlight", "Snowpack", "Stardust", "Sturon") with different scale color and dry matter content were grown in a two-year field trial. Using a recently established metabolite profiling approach based on liquid chromatography-coupled electrospray ionization quadrupole time-of-flight mass spectrometry, 106 polar and semipolar metabolites which belong to compound classes determining nutritional, sensory, and technological quality of onion bulbs such as saccharides, flavonoids, S-substitued cysteine conjugates, amino acids, and derived γ-glutamyl peptides were relatively quantitated in parallel. Statistical analyses of the obtained data indicated that depending on the compound class genetic and environmental factors differently contributed to variation of metabolite levels. For saccharides and flavonoids the genetic factor was the major source of variation, whereas for cysteine sulfoxides, amino acids, and peptides both genetic and environmental factors had a significant impact on corresponding metabolite levels.

Learning directed acyclic graphs from large-scale genomics data.

PubMed

Nikolay, Fabio; Pesavento, Marius; Kritikos, George; Typas, Nassos

2017-09-20

In this paper, we consider the problem of learning the genetic interaction map, i.e., the topology of a directed acyclic graph (DAG) of genetic interactions from noisy double-knockout (DK) data. Based on a set of well-established biological interaction models, we detect and classify the interactions between genes. We propose a novel linear integer optimization program called the Genetic-Interactions-Detector (GENIE) to identify the complex biological dependencies among genes and to compute the DAG topology that matches the DK measurements best. Furthermore, we extend the GENIE program by incorporating genetic interaction profile (GI-profile) data to further enhance the detection performance. In addition, we propose a sequential scalability technique for large sets of genes under study, in order to provide statistically significant results for real measurement data. Finally, we show via numeric simulations that the GENIE program and the GI-profile data extended GENIE (GI-GENIE) program clearly outperform the conventional techniques and present real data results for our proposed sequential scalability technique.

Genetic and caregiving-based contributions to infant attachment: unique associations with distress reactivity and attachment security.

PubMed

Raby, K Lee; Cicchetti, Dante; Carlson, Elizabeth A; Cutuli, J J; Englund, Michelle M; Egeland, Byron

2012-09-01

In the longitudinal study reported here, we examined genetic and caregiving-based contributions to individual differences in infant attachment classifications. For 154 mother-infant pairs, we rated mothers' responsiveness to their 6-month-old infants during naturalistic interactions and classified infants' attachment organization at 12 and 18 months using the Strange Situation procedure. These infants were later genotyped with respect to the serotonin-transporter-linked polymorphic region (5-HTTLPR). Maternal responsiveness uniquely predicted infants' attachment security. Infants' 5-HTTLPR variation uniquely predicted their subtype of attachment security at 12 months and their subtype of attachment insecurity at 12 and 18 months. The short allele for 5-HTTLPR was associated with attachment classifications characterized by higher emotional distress. These findings suggest that 5-HTTLPR variation contributes to infants' emotional reactivity and that the degree to which caregivers are responsive influences how effectively infants use their caregivers for emotion regulation. Theoretical implications for the study of genetic and caregiving influences are discussed.

Unique disease heritage of the Dutch-German Mennonite population.

PubMed

Orton, Noelle C; Innes, A Micheil; Chudley, Albert E; Bech-Hansen, N Torben

2008-04-15

The Dutch-German Mennonites are a religious isolate with foundational roots in the 16th century. A tradition of endogamy, large families, detailed genealogical records, and a unique disease history all contribute to making this a valuable population for genetic studies. Such studies in the Dutch-German Mennonite population have already contributed to the identification of the causative genes in several conditions such as the incomplete form of X-linked congenital stationary night blindness (CSNB2; previously iCSNB) and hypophosphatasia (HOPS), as well as the discovery of founder mutations within established disease genes (MYBPC1, CYP17alpha). The Dutch-German Mennonite population provides a strong resource for gene discovery and could lead to the identification of additional disease genes with relevance to the general population. In addition, further research developments should enhance delivery of clinical genetic services to this unique community. In the current review we discuss 31 genetic conditions, including 17 with identified gene mutations, within the Dutch-German Mennonite population. Copyright 2008 Wiley-Liss, Inc.

Maternal Sensitivity and Overt Aggression in Young Children with Down Syndrome

ERIC Educational Resources Information Center

Niccols, Alison; Milligan, Karen; Chisholm, Vivienne; Atkinson, Leslie

2011-01-01

Children with genetic syndromes offer a unique opportunity to combine genetic and environmental approaches to the study of aggression. Children with genetic syndromes associated with developmental delay are at increased risk for behavior problems, but little is known about risk and resilience factors. In this study, we examined maternal…

Measurement and Associations of Pregnancy Risk Factors with Genetic Influences, Postnatal Environmental Influences, and Toddler Behavior

ERIC Educational Resources Information Center

Marceau, Kristine; Hajal, Nastassia; Leve, Leslie D.; Reiss, David; Shaw, Daniel S.; Ganiban, Jody M.; Mayes, Linda C.; Neiderhiser, Jenae M.

2013-01-01

This study demonstrates the unique contributions of perinatal risk and genetic and environmental influences on child behavior using data from 561 domestic US adoption triads (birth mothers, adopted child, and adoptive parents). Findings show distinct patterns of associations among genetic (birth mother psychopathology), prenatal (six maternal…

Applications of landscape genetics to connectivity research in terrestrial animals [Chapter 12

Treesearch

Lisette P. Waits; Samuel A. Cushman; Steve F. Spear

2016-01-01

Landscape genetic studies have focused on terrestrial animals more than any other taxonomic group. This chapter focuses on applications of landscape genetics for understanding connectivity of terrestrial animal populations. It starts with a general introduction covering unique characteristics and challenges of the terrestrial study system. This is followed by...

A Behaviour-Genetic Analysis of Orthographic Learning, Spelling and Decoding

ERIC Educational Resources Information Center

Byrne, Brian; Coventry, William L.; Olson, Richard K.; Hulslander, Jacqueline; Wadsworth, Sally; DeFries, John C.; Corley, Robin; Willcutt, Erik G.; Samuelsson, Stefan

2008-01-01

As part of a longitudinal twin study of literacy and language, we conducted a behaviour-genetic analysis of orthographic learning, spelling and decoding in Grade 2 children (225 identical and 214 fraternal twin pairs) in the United States and Australia. Each variable showed significant genetic and unique environment influences. Multivariate…

Genetic Determinism in School Textbooks: A Comparative Study Conducted among Sixteen Countries

ERIC Educational Resources Information Center

Castera, Jeremy; Clement, Pierre; Abrougui, Mondher; Nisiforou, Olympia; Valanides, Nicos; Turcinaviciene, Jurga; Sarapuu, Tago; Agorram, Boujemaa; Calado, Florbela; Bogner, Franz; Carvalho, Graca

2008-01-01

Genetic concepts have significantly evolved over the last ten years, and are now less connected to innate ideas and reductionism. Unique reference to genetic determinism has been replaced by the interaction between the genes and their environment (epigenetics). Our analyses relate to how current school biology textbooks present this new paradigm…

Genetic management of endangered species at the Patuxent Wildlife Research Center

USGS Publications Warehouse

Gabel, R.R.; Gee, G.F.

1987-01-01

Summary: The Patuxent Wildlife Research Center conducts one of the world's largest and best-known research programs for captive propagation of endangered wildlife. In order to be effective and to ensure the long-term survival of species, researchers at Patuxent attempt to manage captive populations according to the principles of population genetics. This includes the use of estimated inbreeding levels for mate selections in Masked Bobwhites and biochemical analyses to measure extant genetic material and determine relationships among Whooping Cranes. As added insurance against catastrophic losses, or even random losses of key individuals representing unique lineages, cryopreservation of semen has been studied and used for some species. Artificial insemination, using either stored or fresh semen, is used to improve fertility rates, thereby increasing the chances for survival of unique genetic lines. Finally, a periodic influx of unrelated stock occurs, when feasible, in order to enhance the genetic base of captive populations. The application of these techniques will ensure that future releases utilize genetically viable animals, thereby improving the potential for successful reintroductions into the wild.

A better coefficient of determination for genetic profile analysis.

PubMed

Lee, Sang Hong; Goddard, Michael E; Wray, Naomi R; Visscher, Peter M

2012-04-01

Genome-wide association studies have facilitated the construction of risk predictors for disease from multiple Single Nucleotide Polymorphism markers. The ability of such "genetic profiles" to predict outcome is usually quantified in an independent data set. Coefficients of determination (R(2) ) have been a useful measure to quantify the goodness-of-fit of the genetic profile. Various pseudo-R(2) measures for binary responses have been proposed. However, there is no standard or consensus measure because the concept of residual variance is not easily defined on the observed probability scale. Unlike other nongenetic predictors such as environmental exposure, there is prior information on genetic predictors because for most traits there are estimates of the proportion of variation in risk in the population due to all genetic factors, the heritability. It is this useful ability to benchmark that makes the choice of a measure of goodness-of-fit in genetic profiling different from that of nongenetic predictors. In this study, we use a liability threshold model to establish the relationship between the observed probability scale and underlying liability scale in measuring R(2) for binary responses. We show that currently used R(2) measures are difficult to interpret, biased by ascertainment, and not comparable to heritability. We suggest a novel and globally standard measure of R(2) that is interpretable on the liability scale. Furthermore, even when using ascertained case-control studies that are typical in human disease studies, we can obtain an R(2) measure on the liability scale that can be compared directly to heritability. © 2012 Wiley Periodicals, Inc.

An Assessment of Host Associations, Geographic Distributions, and Genetic Diversity of Avian Chewing Lice (Insecta: Phthiraptera) from Benin.

PubMed

Takano, Oona M; Mitchell, Preston S; Gustafsson, Daniel R; Adite, Alphonse; Voelker, Gary; Light, Jessica E

2017-04-01

Host associations of highly host-specific chewing lice (Insecta: Phthiraptera) across multiple avian species remains fairly undocumented in the West African country of Benin. Two hundred and seventeen bird specimens collected from multiple localities across Benin and housed at the Texas A&M University Biodiversity Research and Teaching Collections were examined for lice. Lice were identified and genetic data (mitochondrial COI and nuclear EF-1α genes) were obtained and phylogenetically analyzed. In total, we found 15 host associations, 7 of which were new to science. Genetically, most lice from Benin were unique and could represent new species. Based on host associations and unique genetic lineages, we estimate we discovered a minimum of 4 and possibly as many as 8 new chewing louse species. Given the lack of current data on chewing louse species distributions in Benin, this study adds to the knowledge of host associations, geographic distribution, and genetic variability of avian chewing louse species in West Africa.

A New Look at Genetic and Environmental Architecture on Lipids Using Non-Normal Structural Equation Modeling in Male Twins: The NHLBI Twin Study.

PubMed

Wu, Sheng-Hui; Ozaki, Koken; Reed, Terry; Krasnow, Ruth E; Dai, Jun

2017-07-01

This study examined genetic and environmental influences on the lipid concentrations of 1028 male twins using the novel univariate non-normal structural equation modeling (nnSEM) ADCE and ACE models. In the best fitting nnSEM ADCE model that was also better than the nnSEM ACE model, additive genetic factors (A) explained 4%, dominant genetic factors (D) explained 17%, and common (C) and unique (E) environmental factors explained 47% and 33% of the total variance of high-density lipoprotein cholesterol (HDL-C). The percentage of variation explained for other lipids was 0% (A), 30% (D), 34% (C) and 37% (E) for low-density lipoprotein cholesterol (LDL-C); 30, 0, 31 and 39% for total cholesterol; and 0, 31, 12 and 57% for triglycerides. It was concluded that additive and dominant genetic factors simultaneously affected HDL-C concentrations but not other lipids. Common and unique environmental factors influenced concentrations of all lipids.

Identification of cognitive profiles among women considering BRCA1/2 testing through the utilisation of cluster analytic techniques.

PubMed

Roussi, Pagona; Sherman, Kerry A; Miller, Suzanne M; Hurley, Karen; Daly, Mary B; Godwin, Andrew; Buzaglo, Joanne S; Wen, Kuang-Yi

2011-10-01

Based on the cognitive-social health information processing model, we identified cognitive profiles of women at risk for breast and ovarian cancer. Prior to genetic counselling, participants (N = 171) completed a study questionnaire concerning their cognitive and affective responses to being at genetic risk. Using cluster analysis, four cognitive profiles were generated: (a) high perceived risk/low coping; (b) low value of screening/high expectancy of cancer; (c) moderate perceived risk/moderate efficacy of prevention/low informativeness of test result; and (d) high efficacy of prevention/high coping. The majority of women in Clusters One, Two and Three had no personal history of cancer, whereas Cluster Four consisted almost entirely of women affected with cancer. Women in Cluster One had the highest number of affected relatives and experienced higher levels of distress than women in the other three clusters. These results highlight the need to consider the psychological profile of women undergoing genetic testing when designing counselling interventions and messages.

Conservation of genetic uniqueness of populations may increase extinction likelihood of endangered species: the case of Australian mammals.

PubMed

Weeks, Andrew R; Stoklosa, Jakub; Hoffmann, Ary A

2016-01-01

As increasingly fragmented and isolated populations of threatened species become subjected to climate change, invasive species and other stressors, there is an urgent need to consider adaptive potential when making conservation decisions rather than focussing on past processes. In many cases, populations identified as unique and currently managed separately suffer increased risk of extinction through demographic and genetic processes. Other populations currently not at risk are likely to be on a trajectory where declines in population size and fitness soon appear inevitable. Using datasets from natural Australian mammal populations, we show that drift processes are likely to be driving uniqueness in populations of many threatened species as a result of small population size and fragmentation. Conserving and managing such remnant populations separately will therefore often decrease their adaptive potential and increase species extinction risk. These results highlight the need for a paradigm shift in conservation biology practise; strategies need to focus on the preservation of genetic diversity at the species level, rather than population, subspecies or evolutionary significant unit. The introduction of new genetic variants into populations through in situ translocation needs to be considered more broadly in conservation programs as a way of decreasing extinction risk by increasing neutral genetic diversity which may increase the adaptive potential of populations if adaptive variation is also increased.

Profiling of Intracellular Metabolites: An Approach to Understanding the Characteristic Physiology of Mycobacterium leprae

PubMed Central

Miyamoto, Yuji; Mukai, Tetsu; Matsuoka, Masanori; Kai, Masanori; Maeda, Yumi; Makino, Masahiko

2016-01-01

Mycobacterium leprae is the causative agent of leprosy and also known to possess unique features such as inability to proliferate in vitro. Among the cellular components of M. leprae, various glycolipids present on the cell envelope are well characterized and some of them are identified to be pathogenic factors responsible for intracellular survival in host cells, while other intracellular metabolites, assumed to be associated with basic physiological feature, remain largely unknown. In the present study, to elucidate the comprehensive profile of intracellular metabolites, we performed the capillary electrophoresis-mass spectrometry (CE-MS) analysis on M. leprae and compared to that of M. bovis BCG. Interestingly, comparison of these two profiles showed that, in M. leprae, amino acids and their derivatives are significantly accumulated, but most of intermediates related to central carbon metabolism markedly decreased, implying that M. leprae possess unique metabolic features. The present study is the first report demonstrating the unique profiles of M. leprae metabolites and these insights might contribute to understanding undefined metabolism of M. leprae as well as pathogenic characteristics related to the manifestation of the disease. PMID:27479467

Profiling of Intracellular Metabolites: An Approach to Understanding the Characteristic Physiology of Mycobacterium leprae.

PubMed

Miyamoto, Yuji; Mukai, Tetsu; Matsuoka, Masanori; Kai, Masanori; Maeda, Yumi; Makino, Masahiko

2016-08-01

Mycobacterium leprae is the causative agent of leprosy and also known to possess unique features such as inability to proliferate in vitro. Among the cellular components of M. leprae, various glycolipids present on the cell envelope are well characterized and some of them are identified to be pathogenic factors responsible for intracellular survival in host cells, while other intracellular metabolites, assumed to be associated with basic physiological feature, remain largely unknown. In the present study, to elucidate the comprehensive profile of intracellular metabolites, we performed the capillary electrophoresis-mass spectrometry (CE-MS) analysis on M. leprae and compared to that of M. bovis BCG. Interestingly, comparison of these two profiles showed that, in M. leprae, amino acids and their derivatives are significantly accumulated, but most of intermediates related to central carbon metabolism markedly decreased, implying that M. leprae possess unique metabolic features. The present study is the first report demonstrating the unique profiles of M. leprae metabolites and these insights might contribute to understanding undefined metabolism of M. leprae as well as pathogenic characteristics related to the manifestation of the disease.

Working with the Hmong Population in a Genetics Setting: an Interpreter Perspective.

PubMed

Krieger, Meghan; Agather, Aime; Douglass, Kathryn; Reiser, Catherine A; Petty, Elizabeth M

2018-06-01

The aim of this pilot qualitative study was to describe the experiences and beliefs of medical interpreters when working with genetic counselors and other genetic providers caring for Hmong patients who are not native English speakers. Specific goals were to identify interpreters' thoughts and perceptions on (a) their roles during sessions, (b) unique challenges in a genetics session, (c) knowledge genetics providers need when working with Hmong patients and interpreters, and (d) supports and training needed to effectively interpret in a genetics setting. Hmong medical interpreters from Wisconsin and Minnesota were invited by email to participate in the study. Six were interviewed by telephone. Participants had worked with a variety of providers including geneticists, genetic counselors, primary care physicians, and oncologists. Factors identified by Hmong interpreters that made interpretation of content difficult in clinical genetics sessions included: time constraints, technical terms, and unique cultural perspectives of Hmong patients. While all respondents felt their primary role was to interpret session content as close to verbatim as possible, there was notable variation in the description of their interpretation style and other perceived roles in the genetic counseling session. Cultural issues genetics providers could consider when working with Hmong patients and different style issues when working with Hmong interpreters are discussed. Ideas for future studies and suggestions to improve communication with Hmong patients are explored.

Identifying Genetic Hotspots by Mapping Molecular Diversity of Widespread Trees: When Commonness Matters.

PubMed

Souto, Cintia P; Mathiasen, Paula; Acosta, María Cristina; Quiroga, María Paula; Vidal-Russell, Romina; Echeverría, Cristian; Premoli, Andrea C

2015-01-01

Conservation planning requires setting priorities at the same spatial scale at which decision-making processes are undertaken considering all levels of biodiversity, but current methods for identifying biodiversity hotspots ignore its genetic component. We developed a fine-scale approach based on the definition of genetic hotspots, which have high genetic diversity and unique variants that represent their evolutionary potential and evolutionary novelties. Our hypothesis is that wide-ranging taxa with similar ecological tolerances, yet of phylogenetically independent lineages, have been and currently are shaped by ecological and evolutionary forces that result in geographically concordant genetic patterns. We mapped previously published genetic diversity and unique variants of biparentally inherited markers and chloroplast sequences for 9 species from 188 and 275 populations, respectively, of the 4 woody dominant families of the austral temperate forest, an area considered a biodiversity hotspot. Spatial distribution patterns of genetic polymorphisms differed among taxa according to their ecological tolerances. Eight genetic hotspots were detected and we recommend conservation actions for some in the southern Coastal Range in Chile. Existing spatially explicit genetic data from multiple populations and species can help to identify biodiversity hotspots and guide conservation actions to establish science-based protected areas that will preserve the evolutionary potential of key habitats and species. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Giraffe genome sequence reveals clues to its unique morphology and physiology

PubMed Central

Agaba, Morris; Ishengoma, Edson; Miller, Webb C.; McGrath, Barbara C.; Hudson, Chelsea N.; Bedoya Reina, Oscar C.; Ratan, Aakrosh; Burhans, Rico; Chikhi, Rayan; Medvedev, Paul; Praul, Craig A.; Wu-Cavener, Lan; Wood, Brendan; Robertson, Heather; Penfold, Linda; Cavener, Douglas R.

2016-01-01

The origins of giraffe's imposing stature and associated cardiovascular adaptations are unknown. Okapi, which lacks these unique features, is giraffe's closest relative and provides a useful comparison, to identify genetic variation underlying giraffe's long neck and cardiovascular system. The genomes of giraffe and okapi were sequenced, and through comparative analyses genes and pathways were identified that exhibit unique genetic changes and likely contribute to giraffe's unique features. Some of these genes are in the HOX, NOTCH and FGF signalling pathways, which regulate both skeletal and cardiovascular development, suggesting that giraffe's stature and cardiovascular adaptations evolved in parallel through changes in a small number of genes. Mitochondrial metabolism and volatile fatty acids transport genes are also evolutionarily diverged in giraffe and may be related to its unusual diet that includes toxic plants. Unexpectedly, substantial evolutionary changes have occurred in giraffe and okapi in double-strand break repair and centrosome functions. PMID:27187213

Characterizing the biocompatibility and tumor-imaging capability of Cu2S nanocrystals in vivo

NASA Astrophysics Data System (ADS)

Poulose, Aby Cheruvathoor; Veeranarayanan, Srivani; Mohamed, M. Sheikh; Sakamoto, Yasushi; Hirosawa, Narumi; Suzuki, Yuko; Zhang, Minfang; Yudasaka, Masako; Radhakrishnan, Neelima; Maekawa, Toru; Mohanan, P. V.; Sakthi Kumar, D.

2015-07-01

Multifunctional nanomaterial-based probes have had key impacts on high-resolution and high-sensitivity bioimaging and therapeutics. Typically, NIR-absorbing metal sulfide-based nanocrystals (NCs) are highly assuring due to their unique optical properties. Yet, their in vivo behavior remains undetermined, which in turn undermines their potential bioapplications. Herein, we have examined the application of PEGylated Cu2S NCs as tumor contrast optical nanoprobes as well as investigated the short- and long-term in vivo compatibility focusing on anti-oxidant defense mechanism, genetic material, immune system, and vital organs. The studies revealed an overall safe profile of the NCs with no apparent toxicity even at longer exposure periods. The acquired observations culminate into a set of primary safety data of this nanomaterial and the use of PEGylated Cu2S NCs as promising optical nanoprobes with immense futuristic bioapplications.

Is the New Variant RHDV Replacing Genogroup 1 in Portuguese Wild Rabbit Populations?

PubMed Central

Lopes, Ana M.; Correia, Jorge; Abrantes, Joana; Melo, Pedro; Ramada, Margarida; Magalhães, Maria J.; Alves, Paulo C.; Esteves, Pedro J.

2014-01-01

The Lagovirus rabbit hemorrhagic disease virus (RHDV), a member of the family Caliciviridae, severely affects European rabbit (Oryctolagus cuniculus) populations by causing rabbit hemorrhagic disease (RHD). RHDV is subdivided in six genogroups but, more recently, a new RHDV variant with a unique genetic and antigenic profile emerged. We performed a study in rabbits found dead in the field during 2013 and 2014 in Portugal to determine the prevalence of this new variant versus the classical RHDV. Fifty-seven liver samples were screened for the presence of RHDV and positive samples were genotyped. All cases of RHDV infection were caused by the new variant. The only former genogroup circulating in Portugal, G1, was not detected. We hence conclude that the new RHDV variant is replacing G1 in Portugal, probably due to a selective advantage. This sudden and rapid replacement emphasizes the necessity of continued monitoring of wild rabbit populations. PMID:25559218

Serrated pathway: Alternative route to colorectal cancer

PubMed Central

Patai, Árpád V; Molnár, Béla; Tulassay, Zsolt; Sipos, Ferenc

2013-01-01

Serrated polyps have been an area of intense focus for gastroenterologists over the past several years. Contrary to what was thought before, a growing body of literature indicates that these polyps can be precursors of colorectal cancer (CRC). Most of these lesions, particularly those in the proximal colon, have so far been under-recognized and missed during colonoscopy, qualifying these lesions to be the main cause of interval cancers. It is estimated that 10%-20% of CRCs evolve through this alternative, serrated pathway, with a distinct genetic and epigenetic profile. Aberrant DNA methylation plays a central role in the development of this CRC subtype. This characteristic molecular background is reflected in a unique pathological and clinical manifestation different from cancers arising via the traditional pathway. In this review we would like to highlight morphological, molecular and clinical features of this emerging pathway that are essential for gastroenterologists and may influence their everyday practice. PMID:23431044

G-cimp status prediction of glioblastoma samples using mRNA expression data.

PubMed

Baysan, Mehmet; Bozdag, Serdar; Cam, Margaret C; Kotliarova, Svetlana; Ahn, Susie; Walling, Jennifer; Killian, Jonathan K; Stevenson, Holly; Meltzer, Paul; Fine, Howard A

2012-01-01

Glioblastoma Multiforme (GBM) is a tumor with high mortality and no known cure. The dramatic molecular and clinical heterogeneity seen in this tumor has led to attempts to define genetically similar subgroups of GBM with the hope of developing tumor specific therapies targeted to the unique biology within each of these subgroups. Recently, a subset of relatively favorable prognosis GBMs has been identified. These glioma CpG island methylator phenotype, or G-CIMP tumors, have distinct genomic copy number aberrations, DNA methylation patterns, and (mRNA) expression profiles compared to other GBMs. While the standard method for identifying G-CIMP tumors is based on genome-wide DNA methylation data, such data is often not available compared to the more widely available gene expression data. In this study, we have developed and evaluated a method to predict the G-CIMP status of GBM samples based solely on gene expression data.

G-Cimp Status Prediction Of Glioblastoma Samples Using mRNA Expression Data

PubMed Central

Baysan, Mehmet; Bozdag, Serdar; Cam, Margaret C.; Kotliarova, Svetlana; Ahn, Susie; Walling, Jennifer; Killian, Jonathan K.; Stevenson, Holly; Meltzer, Paul; Fine, Howard A.

2012-01-01

Glioblastoma Multiforme (GBM) is a tumor with high mortality and no known cure. The dramatic molecular and clinical heterogeneity seen in this tumor has led to attempts to define genetically similar subgroups of GBM with the hope of developing tumor specific therapies targeted to the unique biology within each of these subgroups. Recently, a subset of relatively favorable prognosis GBMs has been identified. These glioma CpG island methylator phenotype, or G-CIMP tumors, have distinct genomic copy number aberrations, DNA methylation patterns, and (mRNA) expression profiles compared to other GBMs. While the standard method for identifying G-CIMP tumors is based on genome-wide DNA methylation data, such data is often not available compared to the more widely available gene expression data. In this study, we have developed and evaluated a method to predict the G-CIMP status of GBM samples based solely on gene expression data. PMID:23139755

[Paternity study in Chilean families using DNA fingerprints and erythrocyte blood markers].

PubMed

Aguirre, R; Blanco, R; Cifuentes, L; Chiffelle, I; Armanet, L; Vargas, J; Jara, L

1992-10-01

In the last decade, the electromorphic phenotype corresponding to extremely polymorphic zones of DNA, that include variable number of tandem repeat loci (VNTR) of oligonucleotide sequences, have been added to classical markers to elucidate the problems of parenthood identification and ascription in human beings. Using VNTR of several loci, a band profile practically unique for each individual is obtained (DNA-fingerprints). Since the pattern of VNTR electrophoretic bands is inherited from parents in a proportion of 50% from each one, this system is extremely useful for paternity ascription or exclusion. Nine nuclear families were studied, randomly selected from a group of 170 families that were analyzed using 5 erythrocyte genetic markers and with VNTRs detected using the multi locus probe (CAC)5, aiming to explore the concordance of both methods. Results were similar for both methods; however for VNTR, there is no information available on population frequency of polymorphisms.

Heritability of high sugar consumption through drinks and the genetic correlation with substance use.

PubMed

Treur, Jorien L; Boomsma, Dorret I; Ligthart, Lannie; Willemsen, Gonneke; Vink, Jacqueline M

2016-10-01

High sugar consumption contributes to the rising prevalence of obesity. Sugar can have rewarding effects that are similar to, but less strong than, the effects of addictive substances. People who consume large amounts of sugar also tend to use more addictive substances, but it is unclear whether this is due to shared genetic or environmental risk factors. We examined whether there are genetic influences on the consumption of sugar-containing drinks and whether genetic factors can explain the association with substance use. The frequency of consumption of sugar-containing drinks (e.g., cola, soft drinks, and energy drinks) and addictive substances (nicotine, caffeine, alcohol, cannabis, and illicit drugs) was obtained for 8586 twins who were registered at the Netherlands Twin Register (women: 68.7%; mean ± SD age: 33.5 ± 15.3 y). Participants were categorized as high or low sugar consumers (>1 compared with ≤1 SD above daily consumption in grams) and as high or low substance users (≥2 compared with <2 substances). Through bivariate genetic modeling, genetic and environmental influences on sugar consumption, substance use, and their association were estimated. Genetic factors explained 48% of the variation in high sugar consumption, whereas unique environmental factors explained 52%. For high substance use, these values were 62% and 38%, respectively. There was a moderate phenotypic association between high sugar consumption and high substance use (r = 0.2), which was explained by genetic factors (59%) and unique environmental factors (41%). The positive association between high sugar consumption and high substance use was partly due to unique environmental factors (e.g., social situations). Genetic factors were also of influence, suggesting that neuronal circuits underlying the development of addiction and obesity are related. Further research is needed to identify genes that influence sugar consumption and those that overlap with substance use. © 2016 American Society for Nutrition.

Application of genetic algorithm in the evaluation of the profile error of archimedes helicoid surface

NASA Astrophysics Data System (ADS)

Zhu, Lianqing; Chen, Yunfang; Chen, Qingshan; Meng, Hao

2011-05-01

According to minimum zone condition, a method for evaluating the profile error of Archimedes helicoid surface based on Genetic Algorithm (GA) is proposed. The mathematic model of the surface is provided and the unknown parameters in the equation of surface are acquired through least square method. Principle of GA is explained. Then, the profile error of Archimedes Helicoid surface is obtained through GA optimization method. To validate the proposed method, the profile error of an Archimedes helicoid surface, Archimedes Cylindrical worm (ZA worm) surface, is evaluated. The results show that the proposed method is capable of correctly evaluating the profile error of Archimedes helicoid surface and satisfy the evaluation standard of the Minimum Zone Method. It can be applied to deal with the measured data of profile error of complex surface obtained by three coordinate measurement machines (CMM).

Molecular Evolution and Functional Diversification of Replication Protein A1 in Plants

PubMed Central

Aklilu, Behailu B.; Culligan, Kevin M.

2016-01-01

Replication protein A (RPA) is a heterotrimeric, single-stranded DNA binding complex required for eukaryotic DNA replication, repair, and recombination. RPA is composed of three subunits, RPA1, RPA2, and RPA3. In contrast to single RPA subunit genes generally found in animals and yeast, plants encode multiple paralogs of RPA subunits, suggesting subfunctionalization. Genetic analysis demonstrates that five Arabidopsis thaliana RPA1 paralogs (RPA1A to RPA1E) have unique and overlapping functions in DNA replication, repair, and meiosis. We hypothesize here that RPA1 subfunctionalities will be reflected in major structural and sequence differences among the paralogs. To address this, we analyzed amino acid and nucleotide sequences of RPA1 paralogs from 25 complete genomes representing a wide spectrum of plants and unicellular green algae. We find here that the plant RPA1 gene family is divided into three general groups termed RPA1A, RPA1B, and RPA1C, which likely arose from two progenitor groups in unicellular green algae. In the family Brassicaceae the RPA1B and RPA1C groups have further expanded to include two unique sub-functional paralogs RPA1D and RPA1E, respectively. In addition, RPA1 groups have unique domains, motifs, cis-elements, gene expression profiles, and pattern of conservation that are consistent with proposed functions in monocot and dicot species, including a novel C-terminal zinc-finger domain found only in plant RPA1C-like sequences. These results allow for improved prediction of RPA1 subunit functions in newly sequenced plant genomes, and potentially provide a unique molecular tool to improve classification of Brassicaceae species. PMID:26858742

Burkitt lymphoma is molecularly distinct from other lymphomas

Cancer.gov

Scientists have uncovered a number of molecular signatures in Burkitt lymphoma, including unique genetic alterations that promote cell survival, that are not found in other lymphomas. These findings provide the first genetic evidence that Burkitt lymphoma

Contributions of Genes and Environment to Developmental Change in Alcohol Use.

PubMed

Long, E C; Verhulst, B; Aggen, S H; Kendler, K S; Gillespie, N A

2017-09-01

The precise nature of how genetic and environmental risk factors influence changes in alcohol use (AU) over time has not yet been investigated. Therefore, the aim of the present study is to examine the nature of longitudinal changes in these risk factors to AU from mid-adolescence through young adulthood. Using a large sample of male twins, we compared five developmental models that each makes different predictions regarding the longitudinal changes in genetic and environmental risks for AU. The best-fitting model indicated that genetic influences were consistent with a gradual growth in the liability to AU, whereas unique environmental risk factors were consistent with an accumulation of risks across time. These results imply that two distinct processes influence adolescent AU between the ages of 15-25. Genetic effects influence baseline levels of AU and rates of change across time, while unique environmental effects are more cumulative.

Genetic barcodes

DOEpatents

Weier, Heinz -Ulrich G

2015-08-04

Herein are described multicolor FISH probe sets termed "genetic barcodes" targeting several cancer or disease-related loci to assess gene rearrangements and copy number changes in tumor cells. Two, three or more different fluorophores are used to detect the genetic barcode sections thus permitting unique labeling and multilocus analysis in individual cell nuclei. Gene specific barcodes can be generated and combined to provide both numerical and structural genetic information for these and other pertinent disease associated genes.

A rangewide population genetic study of trumpeter swans

USGS Publications Warehouse

Oyler-McCance, S.J.; Ransler, F.A.; Berkman, L.K.; Quinn, T.W.

2007-01-01

For management purposes, the range of naturally occurring trumpeter swans (Cygnus buccinator) has been divided into two populations, the Pacific Coast Population (PP) and the Rocky Mountain Population (RMP). Little is known about the distribution of genetic variation across the species' range despite increasing pressure to make difficult management decisions regarding the two populations and flocks within them. To address this issue, we used rapidly evolving genetic markers (mitochondrial DNA sequence and 17 nuclear microsatellite loci) to elucidate the underlying genetic structure of the species. Data from both markers revealed a significant difference between the PP and RMP with the Yukon Territory as a likely area of overlap. Additionally, we found that the two populations have somewhat similar levels of genetic diversity (PP is slightly higher) suggesting that the PP underwent a population bottleneck similar to a well-documented one in the RMP. Both genetic structure and diversity results reveal that the Tri-State flock, a suspected unique, non-migratory flock, is not genetically different from the Canadian flock of the RMP and need not be treated as a unique population from a genetic standpoint. Finally, trumpeter swans appear to have much lower mitochondrial DNA variability than other waterfowl studied thus far which may suggest a previous, species-wide bottleneck. ?? 2007 Springer Science+Business Media, Inc.

Genotype x environment interactions for fatty acid profiles in Bos indicus and Bos taurus finished on pasture or grain.

PubMed

Bressan, M C; Rossato, L V; Rodrigues, E C; Alves, S P; Bessa, R J B; Ramos, E M; Gama, L T

2011-01-01

A study was conducted to characterize lipid profiles in the M. longissimus thoracis of commercial Brazilian beef and to assess how those profiles are influenced by finishing system, genetic group, and their interaction. Intramuscular fat (IMF) and fatty acid (FA) profiles were determined in 160 bulls of the Bos taurus (n = 75) and Bos indicus (n = 85) genetic groups, finished on pasture (n = 46) or with grain supplementation (n = 114) and slaughtered in a commercial abattoir. Finishing system had a major impact on the deposition of IMF, as well as on the concentration of SFA, PUFA, and their ratio, but genetic groups showed important differences in the ability to convert SFA into cis-9 MUFA and to convert 16:0 into 18:0. When compared with pasture-finished animals, those finished with grain had greater content of IMF and SFA (P < 0.01), similar amounts of MUFA (P > 0.05), and about one-half the amount of PUFA (P < 0.01). Except for MUFA, differences in FA profiles among finishing systems were mostly mediated through their effect on IMF, even though the relationship of IMF with groups of FA differed among finishing systems. Under grain finishing, B. taurus had less SFA and greater MUFA than B. indicus (P < 0.01), but no differences were observed in PUFA (P > 0.05). With pasture-finishing, no differences were observed among the 2 genetic groups in SFA and MUFA (P > 0.05), but PUFA were decreased in B. taurus (P < 0.01). When genetic groups were compared in grain-finishing, B. taurus had a decreased ability for elongation and B. indicus had a decreased aptitude for desaturation of FA. On the other hand, with pasture-finishing a greater deposition of intermediate FA from ruminal biohydrogenation was observed in B. indicus than in B. taurus. Overall, FA profiles were affected more by finishing system in B. indicus than in B. taurus.

Educational and Demographic Profile: Madera County

ERIC Educational Resources Information Center

California Postsecondary Education Commission, 2004

2004-01-01

This profile uniquely presents a variety of educational and socioeconomic information for Madera County, nearby counties, and the state. The profile highlights the relationship between various factors that affect the economic well-being of individuals and communities. This presentation of information provides a framework for enhanced…

Educational and Demographic Profile: Sonoma County.

ERIC Educational Resources Information Center

California Postsecondary Education Commission, 2004

2004-01-01

This profile uniquely presents a variety of educational and socioeconomic information for Sonoma County, nearby counties, and the state. The profile highlights the relationship between various factors that affect the economic well-being of individuals and communities. The information provides a framework for enhanced communication and…

Educational and Demographic Profile: Humboldt County.

ERIC Educational Resources Information Center

California Postsecondary Education Commission, 2004

2004-01-01

This profile uniquely presents a variety of educational and socioeconomic information for Humboldt County, nearby counties, and the state. The profile highlights the relationship between various factors that affect the economic well-being of individuals and communities. This presentation of information provides a framework for enhanced…

Educational and Demographic Profile: Mariposa County.

ERIC Educational Resources Information Center

California Postsecondary Education Commission, 2004

2004-01-01

This profile uniquely presents a variety of educational and socioeconomic information for Mariposa County, nearby counties, and the state. The profile highlights the relationship between various factors that affect the economic well-being of individuals and communities. This presentation of information provides a framework for enhanced…

Advances in the molecular genetics of gliomas - implications for classification and therapy.

PubMed

Reifenberger, Guido; Wirsching, Hans-Georg; Knobbe-Thomsen, Christiane B; Weller, Michael

2017-07-01

Genome-wide molecular-profiling studies have revealed the characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine glioma classification, to improve prediction of patient outcomes, and to guide individualized treatment. Thus, the WHO Classification of Tumours of the Central Nervous System was revised in 2016 to incorporate molecular biomarkers - together with classic histological features - in an integrated diagnosis, in order to define distinct glioma entities as precisely as possible. This paradigm shift is markedly changing how glioma is diagnosed, and has important implications for future clinical trials and patient management in daily practice. Herein, we highlight the developments in our understanding of the molecular genetics of gliomas, and review the current landscape of clinically relevant molecular biomarkers for use in classification of the disease subtypes. Novel approaches to the genetic characterization of gliomas based on large-scale DNA-methylation profiling and next-generation sequencing are also discussed. In addition, we illustrate how advances in the molecular genetics of gliomas can promote the development and clinical translation of novel pathogenesis-based therapeutic approaches, thereby paving the way towards precision medicine in neuro-oncology.

Genetic tumor profiling and genetically targeted cancer therapy.

PubMed

Goetsch, Cathleen M

2011-02-01

To discuss how understanding and manipulation of tumor genetics information and technology shapes cancer care today and what changes might be expected in the near future. Published articles, web resources, clinical practice. Advances in our understanding of genes and their regulation provide a promise of more personalized cancer care, allowing selection of the most safe and effective therapy in an individual situation. Rapid progress in the technology of tumor profiling and targeted cancer therapies challenges nurses to keep up-to-date to provide quality patient education and care. Copyright © 2011 Elsevier Inc. All rights reserved.

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

PubMed

Jácome, Alexandre Andrade Dos Anjos; Lima, Enaldo Melo de; Kazzi, Ana Izabela; Chaves, Gabriela Freitas; Mendonça, Diego Cavalheiro de; Maciel, Marina Mara; Santos, José Sebastião Dos

2016-04-01

Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

ZMYND10--Mutation Analysis in Slavic Patients with Primary Ciliary Dyskinesia.

PubMed

Kurkowiak, Małgorzata; Ziętkiewicz, Ewa; Greber, Agnieszka; Voelkel, Katarzyna; Wojda, Alina; Pogorzelski, Andrzej; Witt, Michał

2016-01-01

Primary ciliary dyskinesia (PCD) is a rare recessive disease with a prevalence of 1/10,000; its symptoms are caused by a kinetic dysfunction of motile cilia in the respiratory epithelium, flagella in spermatozoids, and primary cilia in the embryonic node. PCD is genetically heterogeneous: genotyping the already known PCD-related genes explains the genetic basis in 60-65% of the cases, depending on the population. While identification of new genes involved in PCD pathogenesis remains crucial, the search for new, population-specific mutations causative for PCD is equally important. The Slavs remain far less characterized in this respect compared to West European populations, which significantly limits diagnostic capability. The main goal of this study was to characterize the profile of causative genetic defects in one of the PCD-causing genes, ZMYND10, in the cohort of PCD patients of Slavic origin. The study was carried out using biological material from 172 unrelated PCD individuals of Polish origin, with no causative mutation found in nine major PCD genes. While none of the previously described mutations was found using the HRM-based screening, a novel frameshift mutation (c.367delC) in ZMYND10, unique for Slavic PCD population, was found in homozygous state in two unrelated PCD patients. Immunofluorescence analysis confirmed the absence of outer and inner dynein arms from the ciliary axoneme, consistent with the already published ZMYND10-mutated phenotype; cDNA analysis revealed the lack of ZMYND10 mRNA, indicating nonsense-mediated decay of the truncated transcript.

Polymorphisms of genes encoding P2X7R, IL-1B, OPG and RANK in orthodontic-induced apical root resorption.

PubMed

Pereira, S; Lavado, N; Nogueira, L; Lopez, M; Abreu, J; Silva, H

2014-10-01

Orthodontic-induced external apical root resorption (EARR) is a complex phenotype determined by poorly defined mechanical and patient intrinsic factors. The aim of this work was to construct a multifactorial integrative model, including clinical and genetic susceptibility factors, to analyze the risk of developing this common orthodontic complication. This retrospective study included 195 orthodontic patients. Using a multiple-linear regression model, where the dependent variable was the maximum% of root resorption (%EARRmax) for each patient, we assessed the contribution of nine clinical variables and four polymorphisms of genes involved in bone and tooth root remodeling (rs1718119 from P2RX7, rs1143634 from IL1B, rs3102735 from TNFRSF11B, encoding OPG, and rs1805034 from TNFRSF11A, encoding RANK). Clinical and genetic variables explained 30% of%EARRmax variability. The variables with the most significant unique contribution to the model were: gender (P < 0.05), treatment duration (P < 0.001), premolar extractions (P < 0.01), Hyrax appliance (P < 0.001) and GG genotype of rs1718119 from P2RX7 gene (P < 0.01). Age, overjet, tongue thrust, skeletal class II and the other polymorphisms made minor contributions. This study highlights the P2RX7 gene as a possible factor of susceptibility to EARR. A more extensive genetic profile may improve this model. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Metabolic risk factors in mice divergently selected for BMR fed high fat and high carb diets.

PubMed

Sadowska, Julita; Gębczyński, Andrzej K; Konarzewski, Marek

2017-01-01

Factors affecting contribution of spontaneous physical activity (SPA; activity associated with everyday tasks) to energy balance of humans are not well understood, as it is not clear whether low activity is related to dietary habits, precedes obesity or is a result of thereof. In particular, human studies on SPA and basal metabolic rates (BMR, accounting for >50% of human energy budget) and their associations with diet composition, metabolic thrift and obesity are equivocal. To clarify these ambiguities we used a unique animal model-mice selected for divergent BMR rates (the H-BMR and L-BMR line type) presenting a 50% between-line type difference in the primary selected trait. Males of each line type were divided into three groups and fed either a high fat, high carb or a control diet. They then spent 4 months in individual cages under conditions emulating human "sedentary lifestyle", with SPA followed every month and measurements of metabolic risk indicators (body fat mass %, blood lipid profile, fasting blood glucose levels and oxidative damage in the livers, kidneys and hearts) taken at the end of study. Mice with genetically determined high BMR assimilated more energy and had higher SPA irrespective of type of diet. H-BMR individuals were characterized by lower dry body fat mass %, better lipid profile and lower fasting blood glucose levels, but higher oxidative damage in the livers and hearts. Genetically determined high BMR may be a protective factor against diet-induced obesity and most of the metabolic syndrome indicators. Elevated spontaneous activity is correlated with high BMR, and constitutes an important factor affecting individual capability to sustain energy balance even under energy dense diets.

Genes versus environment: geography and phylogenetic relationships shape the chemical profiles of stingless bees on a global scale

PubMed Central

Leonhardt, Sara D.; Rasmussen, Claus; Schmitt, Thomas

2013-01-01

Chemical compounds are highly important in the ecology of animals. In social insects, compounds on the body surface represent a particularly interesting trait, because they comprise different compound classes that are involved in different functions, such as communication, recognition and protection, all of which can be differentially affected by evolutionary processes. Here, we investigate the widely unknown and possibly antagonistic influence of phylogenetic and environmental factors on the composition of the cuticular chemistry of tropical stingless bees. We chose stingless bees because some species are unique in expressing not only self-produced compounds, but also compounds that are taken up from the environment. By relating the cuticular chemistry of 40 bee species from all over the world to their molecular phylogeny and geographical occurrence, we found that distribution patterns of different groups of compounds were differentially affected by genetic relatedness and biogeography. The ability to acquire environmental compounds was, for example, highly correlated with the bees' phylogeny and predominated in evolutionarily derived species. Owing to the presence of environmentally derived compounds, those species further expressed a higher chemical and thus functional diversity. In Old World species, chemical similarity of both environmentally derived and self-produced compounds was particularly high among sympatric species, even when they were less related to each other than to allopatric species, revealing a strong environmental effect even on largely genetically determined compounds. Thus, our findings do not only reveal an unexpectedly strong influence of the environment on the cuticular chemistry of stingless bees, but also demonstrate that even within one morphological trait (an insect's cuticular profile), different components (compound classes) can be differentially affected by different drivers (relatedness and biogeography), depending on the functional context. PMID:23658202

Bodies of science and law: forensic DNA profiling, biological bodies, and biopower.

PubMed

Toom, Victor

2012-01-01

How is jurisdiction transferred from an individual's biological body to agents of power such as the police, public prosecutors, and the judiciary, and what happens to these biological bodies when transformed from private into public objects? These questions are examined by analysing bodies situated at the intersection of science and law. More specifically, the transformation of ‘private bodies’ into ‘public bodies’ is analysed by going into the details of forensic DNA profiling in the Dutch jurisdiction. It will be argued that various ‘forensic genetic practices’ enact different forensic genetic bodies'. These enacted forensic genetic bodies are connected with various infringements of civil rights, which become articulated in exploring these forensic genetic bodies’‘normative registers’.

Conservation priorities for the different lines of Dutch Red and White Friesian cattle change when relationships with other breeds are taken into account.

PubMed

Hulsegge, B; Calus, M P L; Oldenbroek, J K; Windig, J J

2017-02-01

From a genetic point of view, the selection of breeds and animals within breeds for conservation in a national gene pool can be based on a maximum diversity strategy. This implies that priority is given to conservation of breeds and animals that diverge most and overlap of conserved diversity is minimized. This study investigated the genetic diversity in the Dutch Red and White Friesian (DFR) cattle breed and its contribution to the total genetic diversity in the pool of the Dutch dairy breeds. All Dutch cattle breeds are clearly distinct, except for Dutch Friesian breed (DF) and DFR and have their own specific genetic identity. DFR has a small but unique contribution to the total genetic diversity of Dutch cattle breeds and is closely related to the Dutch Friesian breed. Seven different lines are distinguished within the DFR breed and all contribute to the diversity of the DFR breed. Two lines show the largest contributions to the genetic diversity in DFR. One of these lines comprises unique diversity both within the breed and across all cattle breeds. The other line comprises unique diversity for the DFR but overlaps with the Holstein Friesian breed. There seems to be no necessity to conserve the other five lines separately, because their level of differentiation is very low. This study illustrates that, when taking conservation decisions for a breed, it is worthwhile to take into account the population structure of the breed itself and the relationships with other breeds. © 2016 Blackwell Verlag GmbH.

Injury Profile SIMulator, a Qualitative Aggregative Modelling Framework to Predict Crop Injury Profile as a Function of Cropping Practices, and the Abiotic and Biotic Environment. I. Conceptual Bases

PubMed Central

Aubertot, Jean-Noël; Robin, Marie-Hélène

2013-01-01

The limitation of damage caused by pests (plant pathogens, weeds, and animal pests) in any agricultural crop requires integrated management strategies. Although significant efforts have been made to i) develop, and to a lesser extent ii) combine genetic, biological, cultural, physical and chemical control methods in Integrated Pest Management (IPM) strategies (vertical integration), there is a need for tools to help manage Injury Profiles (horizontal integration). Farmers design cropping systems according to their goals, knowledge, cognition and perception of socio-economic and technological drivers as well as their physical, biological, and chemical environment. In return, a given cropping system, in a given production situation will exhibit a unique injury profile, defined as a dynamic vector of the main injuries affecting the crop. This simple description of agroecosystems has been used to develop IPSIM (Injury Profile SIMulator), a modelling framework to predict injury profiles as a function of cropping practices, abiotic and biotic environment. Due to the tremendous complexity of agroecosystems, a simple holistic aggregative approach was chosen instead of attempting to couple detailed models. This paper describes the conceptual bases of IPSIM, an aggregative hierarchical framework and a method to help specify IPSIM for a given crop. A companion paper presents a proof of concept of the proposed approach for a single disease of a major crop (eyespot on wheat). In the future, IPSIM could be used as a tool to help design ex-ante IPM strategies at the field scale if coupled with a damage sub-model, and a multicriteria sub-model that assesses the social, environmental, and economic performances of simulated agroecosystems. In addition, IPSIM could also be used to help make diagnoses on commercial fields. It is important to point out that the presented concepts are not crop- or pest-specific and that IPSIM can be used on any crop. PMID:24019908

Injury Profile SIMulator, a qualitative aggregative modelling framework to predict crop injury profile as a function of cropping practices, and the abiotic and biotic environment. I. Conceptual bases.

PubMed

Aubertot, Jean-Noël; Robin, Marie-Hélène

2013-01-01

The limitation of damage caused by pests (plant pathogens, weeds, and animal pests) in any agricultural crop requires integrated management strategies. Although significant efforts have been made to i) develop, and to a lesser extent ii) combine genetic, biological, cultural, physical and chemical control methods in Integrated Pest Management (IPM) strategies (vertical integration), there is a need for tools to help manage Injury Profiles (horizontal integration). Farmers design cropping systems according to their goals, knowledge, cognition and perception of socio-economic and technological drivers as well as their physical, biological, and chemical environment. In return, a given cropping system, in a given production situation will exhibit a unique injury profile, defined as a dynamic vector of the main injuries affecting the crop. This simple description of agroecosystems has been used to develop IPSIM (Injury Profile SIMulator), a modelling framework to predict injury profiles as a function of cropping practices, abiotic and biotic environment. Due to the tremendous complexity of agroecosystems, a simple holistic aggregative approach was chosen instead of attempting to couple detailed models. This paper describes the conceptual bases of IPSIM, an aggregative hierarchical framework and a method to help specify IPSIM for a given crop. A companion paper presents a proof of concept of the proposed approach for a single disease of a major crop (eyespot on wheat). In the future, IPSIM could be used as a tool to help design ex-ante IPM strategies at the field scale if coupled with a damage sub-model, and a multicriteria sub-model that assesses the social, environmental, and economic performances of simulated agroecosystems. In addition, IPSIM could also be used to help make diagnoses on commercial fields. It is important to point out that the presented concepts are not crop- or pest-specific and that IPSIM can be used on any crop.

Integrative genomic profiling reveals conserved genetic mechanisms for tumorigenesis in common entities of non-Hodgkin's lymphoma.

PubMed

Green, Michael R; Aya-Bonilla, Carlos; Gandhi, Maher K; Lea, Rod A; Wellwood, Jeremy; Wood, Peter; Marlton, Paula; Griffiths, Lyn R

2011-05-01

Recent developments in genomic technologies have resulted in increased understanding of pathogenic mechanisms and emphasized the importance of central survival pathways. Here, we use a novel bioinformatic based integrative genomic profiling approach to elucidate conserved mechanisms of lymphomagenesis in the three commonest non-Hodgkin's lymphoma (NHL) entities: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia. By integrating genome-wide DNA copy number analysis and transcriptome profiling of tumor cohorts, we identified genetic lesions present in each entity and highlighted their likely target genes. This revealed a significant enrichment of components of both the apoptosis pathway and the mitogen activated protein kinase pathway, including amplification of the MAP3K12 locus in all three entities, within the set of genes targeted by genetic alterations in these diseases. Furthermore, amplification of 12p13.33 was identified in all three entities and found to target the FOXM1 oncogene. Amplification of FOXM1 was subsequently found to be associated with an increased MYC oncogenic signaling signature, and siRNA-mediated knock-down of FOXM1 resulted in decreased MYC expression and induced G2 arrest. Together, these findings underscore genetic alteration of the MAPK and apoptosis pathways, and genetic amplification of FOXM1 as conserved mechanisms of lymphomagenesis in common NHL entities. Integrative genomic profiling identifies common central survival mechanisms and highlights them as attractive targets for directed therapy. 2011 Wiley-Liss, Inc.

Genomic profiles of low-grade murine gliomas evolve during progression to glioblastoma. | Office of Cancer Genomics

Cancer.gov

Background: Gliomas are diverse neoplasms with multiple molecular subtypes. How tumor-initiating mutations relate to molecular subtypes as these tumors evolve during malignant progression remains unclear.Methods: We used genetically engineered mouse models, histopathology, genetic lineage tracing, expression profiling, and copy number analyses to examine how genomic tumor diversity evolves during the course of malignant progression from low- to high-grade disease.

USE OF GENOTOXIC ACTIVITY PROFILES IN ASSESSMENT OF CARCINOGENESIS AND TRANSMISSIBLE GENETIC EFFECTS

EPA Science Inventory

A methodology has been developed to display and evaluate multiple test quantitative information on genetic toxicants for purposes of assessing carcinogenesis and transmissible genetic effects. ose Information is collected from the open literature: either the lowest effective dose...

Association between prepulse inhibition of the startle response and latent inhibition of two-way avoidance acquisition: A study with heterogeneous NIH-HS rats.

PubMed

Sánchez-González, Ana; Esnal, Aitor; Río-Álamos, Cristóbal; Oliveras, Ignasi; Cañete, Toni; Blázquez, Gloria; Tobeña, Adolf; Fernández-Teruel, Alberto

2016-03-01

This study presents the first evaluation of the associations between responses in two paradigms related to schizophrenia in the genetically heterogeneous NIH-HS rat stock. NIH-HS rats are a stock of genetically heterogeneous animals that have been derived from eight different inbred strains. A rotational breeding schedule has been followed for more than eighty generations, leading to a high level of genetic recombination that makes the NIH-HS rats a unique tool for studying the genetic basis of (biological, behavioral, disease-related) complex traits. Previous work has dealt with the characterization of coping styles, cognitive and anxiety/fear-related profiles of NIH-HS rats. In the present study we have completed their characterization in two behavioral models, prepulse inhibition (PPI) and latent inhibition (LI) of the two-way active avoidance response, that appear to be related to schizophrenia or to schizophrenia-relevant symptoms. We have found that these rats display PPI for each of the four prepulse intensities tested, allowing their stratification in high, medium and low PPI subgroups. When testing these three subgroups for LI of two-way active avoidance acquisition it has been observed that the LowPPI and MediumPPI subgroups present impaired LI, which, along with the fact that the HighPPI group presents significant LI, allows us to hypothesize that responses in these two paradigms are somehow related and that selection of NIH-HS rats for Low vs HighPPI could make a promising animal model for the study of clusters of schizophrenia-relevant symptoms and their underlying neurobiological mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Seroprevalence and first multilocus microsatellite genotyping of Neospora caninum in dairy cattle in Henan, central China.

PubMed

Qian, Weifeng; Wang, Tianqi; Yan, Wenchao; Zhang, Min; Han, Lifang; Xue, Rui; Song, Shaofu; Lv, Chaochao

2017-09-15

Neospora caninum is one of the important causes of abortion in cattle worldwide, and losses due to neosporosis to the cattle industry are considerable. However, the knowledge of genetic characterization of this parasite is limited. The aim of the present study is to determine the prevalence and genetic characterization of N. caninum from dairy cows in Henan Province, central China. A total of 510 blood samples and 7 aborted fetuses were collected from 8 dairy farms in Henan Province. Serum antibodies to N. caninum were examined by ELISA using a recombinant tNcSRS2 protein as the coating antigen. The overall seroprevalence of N. caninum in dairy cows was 41.2% (210/510). The seropositivity rate of N. caninum in aborting cows (49.3%) was statistically significant higher than that (29.3%) in non-aborting cows (p<0.05) with an odds ratio of 2.44 (95% CI, 1.61-3.41). Statistical association was also found between farm type and the seropositivity rate of N. caninum infection in cows (p<0.01).N. caninum DNA was detected from 6 of 396 blood samples (1.5%) and 4 of 7 aborted fetuses by nested PCR based on NC5 gene, and the 10N. caninum positive DNA samples were further analyzed by multilocus microsatellite (MS) genotyping for MS4, MS5, MS6A, MS7, MS8, MS10, and MS12. Only 2 samples were successfully genotyped at all genetic loci, and two unique profiles including two novel allelic patterns were identified. To our knowledge, this study is the first report of genetic characterization of N. caninum isolates from naturally infected dairy cows based on multilocus microsatellites (more than 2 loci) in China. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic Evolution of Mycobacterium bovis Causing Tuberculosis in Livestock and Wildlife in France since 1978

PubMed Central

Hauer, Amandine; De Cruz, Krystel; Cochard, Thierry; Godreuil, Sylvain; Karoui, Claudine; Henault, Sylvie; Bulach, Tabatha; Bañuls, Anne-Laure; Biet, Franck; Boschiroli, María Laura

2015-01-01

To study the dynamics of bovine tuberculosis (bTB) in France, 4,654 M. bovis strains isolated mainly from livestock and wildlife since 1978 were characterized by spoligotyping and MLVA based on MIRU-VNTR. In our study spoligotyping allowed the discrimination of 176 types although 3 spoligotypes are predominant and account for more than half of the total strain population: SB0120 (26%), SB0134 (11%) and SB0121 (6%). In addition, 11% of the isolates, principally from Southern France, showing close spoligotypes and MIRU-VNTR types have been gathered in a family designated as the “F4-family”. MLVA typing allowed extensive discrimination, particularly for strains with predominant spoligotypes, with a total of 498 genotypes, several of which were highly regionalized. The similarity of the strains’ genetic relationships based on spoligotyping and MIRU-VNTR markers supports the co-existence of different clonal populations within the French M. bovis population. A genetic evolution of the strains was observed both geographically and in time. Indeed, as a result of the reduction of bTB due to the national control campaigns, a large reduction of the strains’ genetic variability took place in the last ten years. However, in the regions were bTB is highly prevalent at present, cases in both livestock and in wildlife are due to the spread of unique local genotype profiles. Our results show that the highly discriminating genotyping tools used in this study for molecular studies of bTB are useful for addressing pending questions, which would lead to a better insight into the epidemiology of the disease, and for finding proper solutions for its sustainable control in France. PMID:25658691

Phylogenetic evidence for the ancient Himalayan wolf: towards a clarification of its taxonomic status based on genetic sampling from western Nepal

PubMed Central

Kaden, Jennifer; Joshi, Jyoti; Bhattarai, Susmita; Kusi, Naresh; Sillero-Zubiri, Claudio; Macdonald, David W.

2017-01-01

Wolves in the Himalayan region form a monophyletic lineage distinct from the present-day Holarctic grey wolf Canis lupus spp. (Linnaeus 1758) found across Eurasia and North America. Here, we analyse phylogenetic relationships and the geographic distribution of mitochondrial DNA haplotypes of the contemporary Himalayan wolf (proposed in previous studies as Canis himalayensis) found in Central Asia. We combine genetic data from a living Himalayan wolf population collected in northwestern Nepal in this study with already published genetic data, and confirm the Himalayan wolf lineage based on mitochondrial genomic data (508 bp cytochrome b and 242 bp D-loop), and X- and Y-linked zinc-finger protein gene (ZFX and ZFY) sequences. We then compare the genetic profile of the Himalayan wolf lineage found in northwestern Nepal with canid reference sequences from around the globe with maximum likelihood and Bayesian phylogeny building methods to demonstrate that the Himalayan wolf forms a distinct monophyletic clade supported by posterior probabilities/bootstrap for D-loop of greater than 0.92/85 and cytochrome b greater than 0.99/93. The Himalayan wolf shows a unique Y-chromosome (ZFY) haplotype, and shares an X-chromosome haplotype (ZFX) with the newly postulated African wolf. Our results imply that the Himalayan wolf distribution range extends from the Himalayan range north across the Tibetan Plateau up to the Qinghai Lakes region in Qinghai Province in the People's Republic of China. Based on its phylogenetic distinction and its older age of divergence relative to the Holarctic grey wolf, the Himalayan wolf merits formal classification as a distinct taxon of special conservation concern. PMID:28680672

Genetic profile based upon 15 microsatellites of four caste groups of the eastern Indian state, Bihar.

PubMed

Ashma, R; Kashyap, V K

2003-01-01

The formation of caste groups among the Hindu community and the practice of endogamy exert a great impact on the genetic structure and diversity of the Indian population. Allele frequency data of 15 microsatellite loci clearly portray the genetic diversity and relatedness among four socio-culturally advanced caste groups: Brahmin, Bhumihar, Rajput and Kayasth of Caucasoid ethnicity of Bihar. The study seeks to understand the impact of the man-made caste system on the genetic profile of the four major caste groups of Bihar. Computation of average heterozygosity, most frequent allele, allele diversity and coefficient of gene differentiation (Gst), along with genetic distance (DA)and principal coordinate analysis were performed to assess intra-population and inter-population diversity. The average Gst value for all the loci was 0.012 +/- 0.0033, and the level of average heterozygosity was approximately 75.5%, indicating genetic similarity and intra-population diversity. Genetic distance (DA) values and the phylogenetic tree along with other higher caste groups of India indicate the relative distance between them. The present study clearly depicts the genetic profile of these caste groups, their inherent closeness in the past, and the impact of the imposed caste system that later restricted the gene flow. The study highlights the status of Bhumihar and Kayasth in the Hindu caste system. The former was found clustering with the Brahmin group (as expected, since Bhumihar is known to be a subclass of Brahmin), whereas the distance between the Brahmin and Kayasth caste groups was found to be large. North-eastern Indian Mongoloids form a separate cluster.

Defining a Contemporary Ischemic Heart Disease Genetic Risk Profile Using Historical Data.

PubMed

Mosley, Jonathan D; van Driest, Sara L; Wells, Quinn S; Shaffer, Christian M; Edwards, Todd L; Bastarache, Lisa; McCarty, Catherine A; Thompson, Will; Chute, Christopher G; Jarvik, Gail P; Crosslin, David R; Larson, Eric B; Kullo, Iftikhar J; Pacheco, Jennifer A; Peissig, Peggy L; Brilliant, Murray H; Linneman, James G; Denny, Josh C; Roden, Dan M

2016-12-01

Continued reductions in morbidity and mortality attributable to ischemic heart disease (IHD) require an understanding of the changing epidemiology of this disease. We hypothesized that we could use genetic correlations, which quantify the shared genetic architectures of phenotype pairs and extant risk factors from a historical prospective study to define the risk profile of a contemporary IHD phenotype. We used 37 phenotypes measured in the ARIC study (Atherosclerosis Risk in Communities; n=7716, European ancestry subjects) and clinical diagnoses from an electronic health record (EHR) data set (n=19 093). All subjects had genome-wide single-nucleotide polymorphism genotyping. We measured pairwise genetic correlations (rG) between the ARIC and EHR phenotypes using linear mixed models. The genetic correlation estimates between the ARIC risk factors and the EHR IHD were modestly linearly correlated with hazards ratio estimates for incident IHD in ARIC (Pearson correlation [r]=0.62), indicating that the 2 IHD phenotypes had differing risk profiles. For comparison, this correlation was 0.80 when comparing EHR and ARIC type 2 diabetes mellitus phenotypes. The EHR IHD phenotype was most strongly correlated with ARIC metabolic phenotypes, including total:high-density lipoprotein cholesterol ratio (rG=-0.44, P=0.005), high-density lipoprotein (rG=-0.48, P=0.005), systolic blood pressure (rG=0.44, P=0.02), and triglycerides (rG=0.38, P=0.02). EHR phenotypes related to type 2 diabetes mellitus, atherosclerotic, and hypertensive diseases were also genetically correlated with these ARIC risk factors. The EHR IHD risk profile differed from ARIC and indicates that treatment and prevention efforts in this population should target hypertensive and metabolic disease. © 2016 American Heart Association, Inc.

Genetic modification and genetic determinism

PubMed Central

Resnik, David B; Vorhaus, Daniel B

2006-01-01

In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

Salmonella enterica isolates from pasture-raised poultry exhibit antimicrobial resistance and class I integrons.

PubMed

Melendez, S N; Hanning, I; Han, J; Nayak, R; Clement, A R; Wooming, A; Hererra, P; Jones, F T; Foley, S L; Ricke, S C

2010-12-01

While considerable foodborne pathogen research has been conducted on conventionally produced broilers and turkeys, few studies have focused on free-range (organic) or pastured poultry. The current surveillance study was designed to isolate, identify and genetically characterize Salmonella from pastured poultry farm environment and from retail samples. In this study, 59 isolates were collected from two pastured poultry farms (n = 164; pens, feed, water and insect traps) and retail carcasses (n = 36) from a local natural foods store and a local processing plant. All isolates were serotyped and analysed phenotypically (antimicrobial resistance profiles) and genotypically (DNA fingerprints, plasmid profiles and integron analysis). Salmonella enterica was detected using standard microbiological methods. Salmonella Kentucky was the most prevalent serotype detected from the sampled sources (53%), followed by Salmonella Enteritidis (24%), Bareilly (10%), Mbandaka (7%), Montevideo (5%) or Newport (2%). All isolates were resistant to sulfisoxazole and novobiocin, and the majority (40/59) possessed class I integrons shown by PCR detection. Each Salmonella serotype elicited a distinct pulsed-field gel electrophoresis fingerprint profile, and unique differences were observed among the serotypes.  The findings of this study show that Salmonella serotypes isolated from pasture-raised poultry exhibit antimicrobial resistance and class I integrons.  This study demonstrates that despite the cessation of antibiotic usage in poultry production, antibiotic resistant Salmonella may still be recovered from the environment and poultry products. © 2010 The Authors. Journal of Applied Microbiology © 2010 The Society for Applied Microbiology.

Morphological characterization and molecular fingerprinting of Nostoc strains by multiplex RAPD.

PubMed

Hillol, Chakdar; Pabbi, Sunil

2012-01-01

Morphological parameters studied for the twenty selected Nostoc strains were mostly found to be consistent with the earlier reports. But the shape of akinetes observed in this study was a little deviation from the existing descriptions and heterocyst frequency was also found to be different in different strains in spite of growing in the same nitrogen free media. Multiplex RAPD produced reproducible and completely polymorphic amplification profiles for all the strains including some strain specific unique bands which are intended to be useful for identification of those strains. At least one to a maximum of two unique bands was produced by different dual primer combinations. For ten strains out of twenty, strain specific bands were found to be generated. Cluster analysis revealed a vast heterogeneity among these Nostoc strains and no specific clustering based on geographical origin was found except a few strains. It was also observed that morphological data may not necessarily correspond to the genetic data in most of the cases. CCC92 (Nostoc muscorum) and CCC48 (Nostoc punctiforme) showed a high degree of similarity which was well supported by high bootstrap value. The level of similarity of the strains ranged from 0.15 to 0.94. Cluster analysis based on multiplex RAPD showed a good fit revealing the discriminatory power of this technique.

Individual-specific antibody identification methods

DOEpatents

Francoeur, Ann -Michele

1989-11-14

An identification method, applicable to the identification of animals or inanimate objects, is described. The method takes advantage of a hithertofore unknown set of individual-specific, or IS antibodies, that are part of the unique antibody repertoire present in animals, by reacting an effective amount of IS antibodies with a particular panel, or n-dimensional array (where n is typically one or two) consisting of an effective amount of many different antigens (typically greater than one thousand), to give antibody-antigen complexes. The profile or pattern formed by the antigen-antibody complexes, termed an antibody fingerprint, when revealed by an effective amount of an appropriate detector molecule, is uniquely representative of a particular individual. The method can similarly by used to distinguish genetically, or otherwise similar individuals, or their body parts containing IS antibodies. Identification of inanimate objects, particularly security documents, is similarly affected by associating with the documents, an effective amount of a particular individual's IS antibodies, or conversely, a particular panel of antigens, and forming antibody-antigen complexes with a particular panel of antigens, or a particular individual's IS antibodies, respectively. One embodiment of the instant identification method, termed the blocked fingerprint assay, has applications in the area of allergy testing, autoimmune diagnostics and therapeutics, and the detection of environmental antigens such as pathogens, chemicals, and toxins.

Metagenomic insights into the rumen microbial fibrolytic enzymes in Indian crossbred cattle fed finger millet straw.

PubMed

Jose, V Lyju; Appoothy, Thulasi; More, Ravi P; Arun, A Sha

2017-12-01

The rumen is a unique natural habitat, exhibiting an unparalleled genetic resource of fibrolytic enzymes of microbial origin that degrade plant polysaccharides. The objectives of this study were to identify the principal plant cell wall-degrading enzymes and the taxonomic profile of rumen microbial communities that are associated with it. The cattle rumen microflora and the carbohydrate-active enzymes were functionally classified through a whole metagenomic sequencing approach. Analysis of the assembled sequences by the Carbohydrate-active enzyme analysis Toolkit identified the candidate genes encoding fibrolytic enzymes belonging to different classes of glycoside hydrolases(11,010 contigs), glycosyltransferases (6366 contigs), carbohydrate esterases (4945 contigs), carbohydrate-binding modules (1975 contigs), polysaccharide lyases (480 contigs), and auxiliary activities (115 contigs). Phylogenetic analysis of CAZyme encoding contigs revealed that a significant proportion of CAZymes were contributed by bacteria belonging to genera Prevotella, Bacteroides, Fibrobacter, Clostridium, and Ruminococcus. The results indicated that the cattle rumen microbiome and the CAZymes are highly complex, structurally similar but compositionally distinct from other ruminants. The unique characteristics of rumen microbiota and the enzymes produced by resident microbes provide opportunities to improve the feed conversion efficiency in ruminants and serve as a reservoir of industrially important enzymes for cellulosic biofuel production.

Depression is not a consistent syndrome: An investigation of unique symptom patterns in the STAR*D study.

PubMed

Fried, Eiko I; Nesse, Randolph M

2015-02-01

The DSM-5 encompasses a wide range of symptoms for Major Depressive Disorder (MDD). Symptoms are commonly added up to sum-scores, and thresholds differentiate between healthy and depressed individuals. The underlying assumption is that all patients diagnosed with MDD have a similar condition, and that sum-scores accurately reflect the severity of this condition. To test this assumption, we examined the number of DSM-5 depression symptom patterns in the "Sequenced Treatment Alternatives to Relieve Depression" (STAR*D) study. We investigated the number of unique symptom profiles reported by 3703 depressed outpatients at the beginning of the first treatment stage of STAR*D. Overall, we identified 1030 unique symptom profiles. Of these profiles, 864 profiles (83.9%) were endorsed by five or fewer subjects, and 501 profiles (48.6%) were endorsed by only one individual. The most common symptom profile exhibited a frequency of only 1.8%. Controlling for overall depression severity did not reduce the amount of observed heterogeneity. Symptoms were dichotomized to construct symptom profiles. Many subjects enrolled in STAR*D reported medical conditions for which prescribed medications may have affected symptom presentation. The substantial symptom variation among individuals who all qualify for one diagnosis calls into question the status of MDD as a specific consistent syndrome and offers a potential explanation for the difficulty in documenting treatment efficacy. We suggest that the analysis of individual symptoms, their patterns, and their causal associations will provide insights that could not be discovered in studies relying on only sum-scores. Copyright © 2014 Elsevier B.V. All rights reserved.

Classroom Behaviour and Academic Achievement: How Classroom Behaviour Categories Relate to Gender and Academic Performance

ERIC Educational Resources Information Center

Borg, Elin

2015-01-01

Latent profile analysis was used to identify different categories of students having different "profiles" using self-reported classroom behaviour. Four categories of students with unique classroom behaviour profiles were identified among secondary school students in Oslo, Norway (n = 1570). Analyses examined how classroom behaviour…

Owning genetic information and gene enhancement techniques: why privacy and property rights may undermine social control of the human genome.

PubMed

Moore, A D

2000-04-01

In this article I argue that the proper subjects of intangible property claims include medical records, genetic profiles, and gene enhancement techniques. Coupled with a right to privacy these intangible property rights allow individuals a zone of control that will, in most cases, justifiably exclude governmental or societal invasions into private domains. I argue that the threshold for overriding privacy rights and intangible property rights is higher, in relation to genetic enhancement techniques and sensitive personal information, than is commonly suggested. Once the bar is raised, so-to-speak, the burden of overriding it is formidable. Thus many policy decisions that have been recently proposed or enacted--citywide audio and video surveillance, law enforcement DNA sweeps, genetic profiling, national bans on genetic testing and enhancement of humans, to name a few--will have to be backed by very strong arguments.

Comparative genomic analysis of Lactobacillus plantarum ZJ316 reveals its genetic adaptation and potential probiotic profiles* #

PubMed Central

Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-yu; Zhang, Xiao-mei; Song, Da-feng; Zhang, Chen

2016-01-01

Objective: In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. Methods: The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs). Results: We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. Conclusions: Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate. PMID:27487802

Comparative genomic analysis of Lactobacillus plantarum ZJ316 reveals its genetic adaptation and potential probiotic profiles.

PubMed

Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-Yu; Zhang, Xiao-Mei; Song, Da-Feng; Zhang, Chen

2016-08-01

In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs). We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate.

Hierarchical spatial genetic structure in a distinct population segment of greater sage-grouse

USGS Publications Warehouse

Oyler-McCance, Sara J.; Casazza, Michael L.; Fike, Jennifer A.; Coates, Peter S.

2014-01-01

Greater sage-grouse (Centrocercus urophasianus) within the Bi-State Management Zone (area along the border between Nevada and California) are geographically isolated on the southwestern edge of the species’ range. Previous research demonstrated that this population is genetically unique, with a high proportion of unique mitochondrial DNA (mtDNA) haplotypes and with significant differences in microsatellite allele frequencies compared to populations across the species’ range. As a result, this population was considered a distinct population segment (DPS) and was recently proposed for listing as threatened under the U.S. Endangered Species Act. A more comprehensive understanding of the boundaries of this genetically unique population (where the Bi-State population begins) and an examination of genetic structure within the Bi-State is needed to help guide effective management decisions. We collected DNA from eight sampling locales within the Bi-State (N = 181) and compared those samples to previously collected DNA from the two most proximal populations outside of the Bi-State DPS, generating mtDNA sequence data and amplifying 15 nuclear microsatellites. Both mtDNA and microsatellite analyses support the idea that the Bi-State DPS represents a genetically unique population, which has likely been separated for thousands of years. Seven mtDNA haplotypes were found exclusively in the Bi-State population and represented 73 % of individuals, while three haplotypes were shared with neighboring populations. In the microsatellite analyses both STRUCTURE and FCA separate the Bi-State from the neighboring populations. We also found genetic structure within the Bi-State as both types of data revealed differences between the northern and southern part of the Bi-State and there was evidence of isolation-by-distance. STRUCTURE revealed three subpopulations within the Bi-State consisting of the northern Pine Nut Mountains (PNa), mid Bi-State, and White Mountains (WM) following a north–south gradient. This genetic subdivision within the Bi-State is likely the result of habitat loss and fragmentation that has been exacerbated by recent human activities and the encroachment of singleleaf pinyon (Pinus monophylla) and juniper (Juniperus spp.) trees. While genetic concerns may be only one of many priorities for the conservation and management of the Bi-State greater sage-grouse, we believe that they warrant attention along with other issues (e.g., quality of sagebrush habitat, preventing future loss of habitat). Management actions that promote genetic connectivity, especially with respect to WM and PNa, may be critical to the long-term viability of the Bi-State DPS.

FitSearch: a robust way to interpret a yeast fitness profile in terms of drug's mode-of-action.

PubMed

Lee, Minho; Han, Sangjo; Chang, Hyeshik; Kwak, Youn-Sig; Weller, David M; Kim, Dongsup

2013-01-01

Yeast deletion-mutant collections have been successfully used to infer the mode-of-action of drugs especially by profiling chemical-genetic and genetic-genetic interactions on a genome-wide scale. Although tens of thousands of those profiles are publicly available, a lack of an accurate method for mining such data has been a major bottleneck for more widespread use of these useful resources. For general usage of those public resources, we designed FitRankDB as a general repository of fitness profiles, and developed a new search algorithm, FitSearch, for identifying the profiles that have a high similarity score with statistical significance for a given fitness profile. We demonstrated that our new repository and algorithm are highly beneficial to researchers who attempting to make hypotheses based on unknown modes-of-action of bioactive compounds, regardless of the types of experiments that have been performed using yeast deletion-mutant collection in various types of different measurement platforms, especially non-chip-based platforms. We showed that our new database and algorithm are useful when attempting to construct a hypothesis regarding the unknown function of a bioactive compound through small-scale experiments with a yeast deletion collection in a platform independent manner. The FitRankDB and FitSearch enhance the ease of searching public yeast fitness profiles and obtaining insights into unknown mechanisms of action of drugs. FitSearch is freely available at http://fitsearch.kaist.ac.kr.

FitSearch: a robust way to interpret a yeast fitness profile in terms of drug's mode-of-action

PubMed Central

2013-01-01

Background Yeast deletion-mutant collections have been successfully used to infer the mode-of-action of drugs especially by profiling chemical-genetic and genetic-genetic interactions on a genome-wide scale. Although tens of thousands of those profiles are publicly available, a lack of an accurate method for mining such data has been a major bottleneck for more widespread use of these useful resources. Results For general usage of those public resources, we designed FitRankDB as a general repository of fitness profiles, and developed a new search algorithm, FitSearch, for identifying the profiles that have a high similarity score with statistical significance for a given fitness profile. We demonstrated that our new repository and algorithm are highly beneficial to researchers who attempting to make hypotheses based on unknown modes-of-action of bioactive compounds, regardless of the types of experiments that have been performed using yeast deletion-mutant collection in various types of different measurement platforms, especially non-chip-based platforms. Conclusions We showed that our new database and algorithm are useful when attempting to construct a hypothesis regarding the unknown function of a bioactive compound through small-scale experiments with a yeast deletion collection in a platform independent manner. The FitRankDB and FitSearch enhance the ease of searching public yeast fitness profiles and obtaining insights into unknown mechanisms of action of drugs. FitSearch is freely available at http://fitsearch.kaist.ac.kr. PMID:23368702

Challenges of Pre- and Post-Test Counseling for Orthodox Jewish Individuals in the Premarital Phase.

PubMed

Rose, E; Schreiber-Agus, N; Bajaj, K; Klugman, S; Goldwaser, T

2016-02-01

The Jewish community has traditionally taken ownership of its health, and has taken great strides to raise awareness about genetic issues that affect the community, such as Tay-Sachs disease and Hereditary Breast and Ovarian Cancer syndrome. Thanks in part to these heightened awareness efforts, many Orthodox Jewish individuals are now using genetics services as they begin to plan their families. Due to unique cultural and religious beliefs and perceptions, the Orthodox Jewish patients who seek genetic counseling face many barriers to a successful counseling session, and often seek the guidance of programs such as the Program for Jewish Genetic Health (PJGH). In this article, we present clinical vignettes from the PJGH's clinical affiliate, the Reproductive Genetics practice at the Montefiore Medical Center. These cases highlight unique features of contemporary premarital counseling and screening within the Orthodox Jewish Community, including concerns surrounding stigma, disclosure, "marriageability," the use of reproductive technologies, and the desire to include a third party in decision making. Our vignettes demonstrate the importance of culturally-sensitive counseling. We provide strategies and points to consider when addressing the challenges of pre- and post-test counseling as it relates to genetic testing in this population.

Oppositional Defiant Disorder dimensions: genetic influences and risk for later psychopathology

PubMed Central

Mikolajewski, Amy J.; Taylor, Jeanette; Iacono, William G.

2016-01-01

Background This study was undertaken to determine how well two Oppositional Defiant Disorder (ODD) dimensions (irritable and headstrong/hurtful) assessed in childhood predict late adolescent psychopathology and the degree to which these outcomes can be attributed to genetic influences shared with ODD dimensions. Methods Psychopathology was assessed via diagnostic interviews of 1225 twin pairs at ages 11 and 17. Results Consistent with hypotheses, the irritable dimension uniquely predicted overall internalizing problems, whereas the headstrong/hurtful dimension uniquely predicted substance use disorder symptoms. Both dimensions were predictive of antisocial behavior, and overall externalizing problems. The expected relationships between the irritable dimension and specific internalizing disorders were not found. Twin modeling showed the irritable and headstrong/hurtful dimensions were related to late adolescent psychopathology symptoms through common genetic influences. Conclusions Symptoms of ODD in childhood pose a significant risk for various mental health outcomes in late adolescence. Further, common genetic influences underlie the covariance between irritable symptoms in childhood and overall internalizing problems in late adolescence, whereas headstrong/hurtful symptoms share genetic influences with substance use disorder symptoms. Antisocial behavior and overall externalizing share common genetic influences with both the irritable and headstrong/hurtful dimensions. PMID:28059443

Oppositional defiant disorder dimensions: genetic influences and risk for later psychopathology.

PubMed

Mikolajewski, Amy J; Taylor, Jeanette; Iacono, William G

2017-06-01

This study was undertaken to determine how well two oppositional defiant disorder (ODD) dimensions (irritable and headstrong/hurtful) assessed in childhood predict late adolescent psychopathology and the degree to which these outcomes can be attributed to genetic influences shared with ODD dimensions. Psychopathology was assessed via diagnostic interviews of 1,225 twin pairs at ages 11 and 17. Consistent with hypotheses, the irritable dimension uniquely predicted overall internalizing problems, whereas the headstrong/hurtful dimension uniquely predicted substance use disorder symptoms. Both dimensions were predictive of antisocial behavior and overall externalizing problems. The expected relationships between the irritable dimension and specific internalizing disorders were not found. Twin modeling showed that the irritable and headstrong/hurtful dimensions were related to late adolescent psychopathology symptoms through common genetic influences. Symptoms of ODD in childhood pose a significant risk for various mental health outcomes in late adolescence. Further, common genetic influences underlie the covariance between irritable symptoms in childhood and overall internalizing problems in late adolescence, whereas headstrong/hurtful symptoms share genetic influences with substance use disorder symptoms. Antisocial behavior and overall externalizing share common genetic influences with both the irritable and headstrong/hurtful dimensions. © 2017 Association for Child and Adolescent Mental Health.

[DNAStat, version 1.2 -- a software package for processing genetic profile databases and biostatistical calculations].

PubMed

Berent, Jarosław

2007-01-01

This paper presents the new DNAStat version 1.2 for processing genetic profile databases and biostatistical calculations. This new version contains, besides all the options of its predecessor 1.0, a calculation-results file export option in .xls format for Microsoft Office Excel, as well as the option of importing/exporting the population base of systems as .txt files for processing in Microsoft Notepad or EditPad

A behavioral-genetic investigation of bulimia nervosa and its relationship with alcohol use disorder

PubMed Central

Trace, Sara Elizabeth; Thornton, Laura Marie; Baker, Jessica Helen; Root, Tammy Lynn; Janson, Lauren Elizabeth; Lichtenstein, Paul; Pedersen, Nancy Lee; Bulik, Cynthia Marie

2013-01-01

Bulimia nervosa (BN) and alcohol use disorder (AUD) frequently co-occur and may share genetic factors; however, the nature of their association is not fully understood. We assessed the extent to which the same genetic and environmental factors contribute to liability to BN and AUD. A bivariate structural equation model using a Cholesky decomposition was fit to data from 7,241 women who participated in the Swedish Twin study of Adults: Genes and Environment. The proportion of variance accounted for by genetic and environmental factors for BN and AUD and the genetic and environmental correlations between these disorders were estimated. In the best-fitting model, the heritability estimates were 0.55 (95% CI: 0.37; 0.70) for BN and 0.62 (95% CI: 0.54; 0.70) for AUD. Unique environmental factors accounted for the remainder of variance for BN. The genetic correlation between BN and AUD was 0.23 (95% CI: 0.01; 0.44), and the correlation between the unique environmental factors for the two disorders was 0.35 (95% CI: 0.08; 0.61), suggesting moderate overlap in these factors. Findings from this investigation provide additional support that some of the same genetic factors may influence liability to both BN and AUD. PMID:23790978

Spatial gene drives and pushed genetic waves.

PubMed

Tanaka, Hidenori; Stone, Howard A; Nelson, David R

2017-08-08

Gene drives have the potential to rapidly replace a harmful wild-type allele with a gene drive allele engineered to have desired functionalities. However, an accidental or premature release of a gene drive construct to the natural environment could damage an ecosystem irreversibly. Thus, it is important to understand the spatiotemporal consequences of the super-Mendelian population genetics before potential applications. Here, we use a reaction-diffusion model for sexually reproducing diploid organisms to study how a locally introduced gene drive allele spreads to replace the wild-type allele, although it possesses a selective disadvantage s > 0. Using methods developed by Barton and collaborators, we show that socially responsible gene drives require 0.5 < s < 0.697, a rather narrow range. In this "pushed wave" regime, the spatial spreading of gene drives will be initiated only when the initial frequency distribution is above a threshold profile called "critical propagule," which acts as a safeguard against accidental release. We also study how the spatial spread of the pushed wave can be stopped by making gene drives uniquely vulnerable ("sensitizing drive") in a way that is harmless for a wild-type allele. Finally, we show that appropriately sensitized drives in two dimensions can be stopped, even by imperfect barriers perforated by a series of gaps.

Somatic Genetic Variation in Solid Pseudopapillary Tumor of the Pancreas by Whole Exome Sequencing

PubMed Central

Guo, Meng; Luo, Guopei; Jin, Kaizhou; Long, Jiang; Cheng, He; Lu, Yu; Wang, Zhengshi; Yang, Chao; Xu, Jin; Ni, Quanxing; Yu, Xianjun; Liu, Chen

2017-01-01

Solid pseudopapillary tumor of the pancreas (SPT) is a rare pancreatic disease with a unique clinical manifestation. Although CTNNB1 gene mutations had been universally reported, genetic variation profiles of SPT are largely unidentified. We conducted whole exome sequencing in nine SPT patients to probe the SPT-specific insertions and deletions (indels) and single nucleotide polymorphisms (SNPs). In total, 54 SNPs and 41 indels of prominent variations were demonstrated through parallel exome sequencing. We detected that CTNNB1 mutations presented throughout all patients studied (100%), and a higher count of SNPs was particularly detected in patients with older age, larger tumor, and metastatic disease. By aggregating 95 detected variation events and viewing the interconnections among each of the genes with variations, CTNNB1 was identified as the core portion in the network, which might collaborate with other events such as variations of USP9X, EP400, HTT, MED12, and PKD1 to regulate tumorigenesis. Pathway analysis showed that the events involved in other cancers had the potential to influence the progression of the SNPs count. Our study revealed an insight into the variation of the gene encoding region underlying solid-pseudopapillary neoplasm tumorigenesis. The detection of these variations might partly reflect the potential molecular mechanism. PMID:28054945

Familial temporal lobe epilepsy due to focal cortical dysplasia type IIIa.

PubMed

Fabera, Petr; Krijtova, Hana; Tomasek, Martin; Krysl, David; Zamecnik, Josef; Mohapl, Milan; Jiruska, Premysl; Marusic, Petr

2015-09-01

Focal cortical dysplasia (FCD) represents a common cause of refractory epilepsy. It is considered a sporadic disorder, but its occasional familial occurrence suggests the involvement of genetic mechanisms. Siblings with intractable epilepsy were referred for epilepsy surgery evaluation. Both patients were examined using video-EEG monitoring, MRI examination and PET imaging. They underwent left anteromedial temporal lobe resection. Electroclinical features pointed to left temporal lobe epilepsy and MRI examination revealed typical signs of left-sided hippocampal sclerosis and increased white matter signal intensity in the left temporal pole. PET examination confirmed interictal hypometabolism in the left temporal lobe. Histopathological examination of resected tissue demonstrated the presence FCD type IIIa, i.e. hippocampal sclerosis and focal cortical dysplasia in the left temporal pole. We present a unique case of refractory mesial temporal lobe epilepsy in siblings, characterized by an identical clinical profile and histopathology of FCD type IIIa, who were successfully treated by epilepsy surgery. The presence of such a high concordance between the clinical and morphological data, together with the occurrence of epilepsy and febrile seizures in three generations of the family pedigree points towards a possible genetic nature of the observed FCD type IIIa. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Spatial gene drives and pushed genetic waves

PubMed Central

Tanaka, Hidenori; Stone, Howard A.; Nelson, David R.

2017-01-01

Gene drives have the potential to rapidly replace a harmful wild-type allele with a gene drive allele engineered to have desired functionalities. However, an accidental or premature release of a gene drive construct to the natural environment could damage an ecosystem irreversibly. Thus, it is important to understand the spatiotemporal consequences of the super-Mendelian population genetics before potential applications. Here, we use a reaction–diffusion model for sexually reproducing diploid organisms to study how a locally introduced gene drive allele spreads to replace the wild-type allele, although it possesses a selective disadvantage s > 0. Using methods developed by Barton and collaborators, we show that socially responsible gene drives require 0.5 < s < 0.697, a rather narrow range. In this “pushed wave” regime, the spatial spreading of gene drives will be initiated only when the initial frequency distribution is above a threshold profile called “critical propagule,” which acts as a safeguard against accidental release. We also study how the spatial spread of the pushed wave can be stopped by making gene drives uniquely vulnerable (“sensitizing drive”) in a way that is harmless for a wild-type allele. Finally, we show that appropriately sensitized drives in two dimensions can be stopped, even by imperfect barriers perforated by a series of gaps. PMID:28743753

Clonal selection in xenografted TAM recapitulates the evolutionary process of myeloid leukemia in Down syndrome.

PubMed

Saida, Satoshi; Watanabe, Ken-ichiro; Sato-Otsubo, Aiko; Terui, Kiminori; Yoshida, Kenichi; Okuno, Yusuke; Toki, Tsutomu; Wang, RuNan; Shiraishi, Yuichi; Miyano, Satoru; Kato, Itaru; Morishima, Tatsuya; Fujino, Hisanori; Umeda, Katsutsugu; Hiramatsu, Hidefumi; Adachi, Souichi; Ito, Etsuro; Ogawa, Seishi; Ito, Mamoru; Nakahata, Tatsutoshi; Heike, Toshio

2013-05-23

Transient abnormal myelopoiesis (TAM) is a clonal preleukemic disorder that progresses to myeloid leukemia of Down syndrome (ML-DS) through the accumulation of genetic alterations. To investigate the mechanism of leukemogenesis in this disorder, a xenograft model of TAM was established using NOD/Shi-scid, interleukin (IL)-2Rγ(null) mice. Serial engraftment after transplantation of cells from a TAM patient who developed ML-DS a year later demonstrated their self-renewal capacity. A GATA1 mutation and no copy number alterations (CNAs) were detected in the primary patient sample by conventional genomic sequencing and CNA profiling. However, in serial transplantations, engrafted TAM-derived cells showed the emergence of divergent subclones with another GATA1 mutation and various CNAs, including a 16q deletion and 1q gain, which are clinically associated with ML-DS. Detailed genomic analysis identified minor subclones with a 16q deletion or this distinct GATA1 mutation in the primary patient sample. These results suggest that genetically heterogeneous subclones with varying leukemia-initiating potential already exist in the neonatal TAM phase, and ML-DS may develop from a pool of such minor clones through clonal selection. Our xenograft model of TAM may provide unique insight into the evolutionary process of leukemia.

Heritability of personality disorder traits: a twin study.

PubMed

Jang, K L; Livesley, W J; Vernon, P A; Jackson, D N

1996-12-01

Genetic and non-genetic influences on the hierarchy of traits that delineate personality disorder as measured by the Dimensional Assessment of Personality Problems (DAPP-DQ) scale were examined using data from a sample of 483 volunteer twin pairs (236 monozygotic pairs and 247 dizygotic pairs). The DAPP-DQ assesses four higher-order factors, 18 basic dimensions and 69 facet traits of personality disorder. The correlation coefficients for monozygotic and dizygotic twin pairs ranged from 0.26 to 0.56 and from 0.03 to 0.41, respectively. Broad heritability estimates ranged from 0 to 58% (median value 45%). Additive genetic effects and unique environmental effects emerged as the primary influences on these scales, with unique environmental influences accounting for the largest proportion of the variance for most traits at all levels of the hierarchy.

Standards for gene therapy clinical trials based on pro-active risk assessment in a London NHS Teaching Hospital Trust.

PubMed

Bamford, K B; Wood, S; Shaw, R J

2005-02-01

Conducting gene therapy clinical trials with genetically modified organisms as the vectors presents unique safety and infection control issues. The area is governed by a range of legislation and guidelines, some unique to this field, as well as those pertinent to any area of clinical work. The relevant regulations covering gene therapy using genetically modified vectors are reviewed and illustrated with the approach taken by a large teaching hospital NHS Trust. Key elements were Trust-wide communication and involvement of staff in a pro-active approach to risk management, with specific emphasis on staff training and engagement, waste management, audit and record keeping. This process has led to the development of proposed standards for clinical trials involving genetically modified micro-organisms.

Overlapping genetic and environmental influences among men's alcohol consumption and problems, romantic quality and social support.

PubMed

Salvatore, J E; Prom-Wormley, E; Prescott, C A; Kendler, K S

2015-08-01

Alcohol consumption and problems are associated with interpersonal difficulties. We used a twin design to assess in men the degree to which genetic or environmental influences contributed to the covariance between alcohol consumption and problems, romantic quality and social support. The sample included adult male-male twin pairs (697 monozygotic and 487 dizygotic) for whom there were interview-based data on: alcohol consumption (average monthly alcohol consumption in the past year); alcohol problems (lifetime alcohol dependence symptoms); romantic conflict and warmth; friend problems and support; and relative problems and support. Key findings were that genetic and unique environmental factors contributed to the covariance between alcohol consumption and romantic conflict; genetic factors contributed to the covariance between alcohol problems and romantic conflict; and common and unique environmental factors contributed to the covariance between alcohol problems and friend problems. Recognizing and addressing the overlapping genetic and environmental influences that alcohol consumption and problems share with romantic quality and other indicators of social support may have implications for substance use prevention and intervention efforts.

Does the seed bank contribute to the build-up of a genetic extinction debt in the grassland perennial Campanula rotundifolia?

PubMed

Plue, Jan; Vandepitte, Katrien; Honnay, Olivier; Cousins, Sara A O

2017-09-01

Habitat fragmentation threatens global biodiversity. Many plant species persist in habitat fragments via persistent life cycle stages such as seed banks, generating a species extinction debt. Here, seed banks are hypothesized to cause a temporal delay in the expected loss of genetic variation, which can be referred to as a genetic extinction debt, as a possible mechanism behind species extinction debts. Fragmented grassland populations of Campanula rotundifolia were examined for evidence of a genetic extinction debt, investigating if the seed bank contributed to the extinction debt build-up. The genetic make-up of 15 above- and below-ground populations was analysed in relation to historical and current levels of habitat fragmentation, both separately and combined. Genetic diversity was highest in above-ground populations, though below-ground populations contained 8 % of unique alleles that were absent above-ground. Above-ground genetic diversity and composition were related to historical patch size and connectivity, but not current patch characteristics, suggesting the presence of a genetic extinction debt in the above-ground populations. No such relationships were found for the below-ground populations. Genetic diversity measures still showed a response to historical but not present landscape characteristics when combining genetic diversity of the above- and below-ground populations. The fragmented C. rotundifolia populations exhibited a genetic extinction debt. However, the role of the seed banks in the build-up of this extinction debt is probably small, since the limited, unique genetic diversity of the seed bank alone seems unable to counter the detrimental effects of habitat fragmentation on the population genetic structure of C. rotundifolia. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Putative and unique gene sequence utilization for the design of species specific probes as modeled by Lactobacillus plantarum

USDA-ARS?s Scientific Manuscript database

The concept of utilizing putative and unique gene sequences for the design of species specific probes was tested. The abundance profile of assigned functions within the Lactobacillus plantarum genome was used for the identification of the putative and unique gene sequence, csh. The targeted gene (cs...

Proteomic analysis of hair shafts from monozygotic twins: Expression profiles and genetically variant peptides.

PubMed

Wu, Pei-Wen; Mason, Katelyn E; Durbin-Johnson, Blythe P; Salemi, Michelle; Phinney, Brett S; Rocke, David M; Parker, Glendon J; Rice, Robert H

2017-07-01

Forensic association of hair shaft evidence with individuals is currently assessed by comparing mitochondrial DNA haplotypes of reference and casework samples, primarily for exclusionary purposes. Present work tests and validates more recent proteomic approaches to extract quantitative transcriptional and genetic information from hair samples of monozygotic twin pairs, which would be predicted to partition away from unrelated individuals if the datasets contain identifying information. Protein expression profiles and polymorphic, genetically variant hair peptides were generated from ten pairs of monozygotic twins. Profiling using the protein tryptic digests revealed that samples from identical twins had typically an order of magnitude fewer protein expression differences than unrelated individuals. The data did not indicate that the degree of difference within twin pairs increased with age. In parallel, data from the digests were used to detect genetically variant peptides that result from common nonsynonymous single nucleotide polymorphisms in genes expressed in the hair follicle. Compilation of the variants permitted sorting of the samples by hierarchical clustering, permitting accurate matching of twin pairs. The results demonstrate that genetic differences are detectable by proteomic methods and provide a framework for developing quantitative statistical estimates of personal identification that increase the value of hair shaft evidence. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nuclear and Mitochondrial DNA Analyses of Golden Eagles (Aquila chrysaetos canadensis) from Three Areas in Western North America; Initial Results and Conservation Implications

PubMed Central

Craig, Erica H.; Adams, Jennifer R.; Waits, Lisette P.; Fuller, Mark R.; Whittington, Diana M.

2016-01-01

Understanding the genetics of a population is a critical component of developing conservation strategies. We used archived tissue samples from golden eagles (Aquila chrysaetos canadensis) in three geographic regions of western North America to conduct a preliminary study of the genetics of the North American subspecies, and to provide data for United States Fish and Wildlife Service (USFWS) decision-making for golden eagle management. We used a combination of mitochondrial DNA (mtDNA) D-loop sequences and 16 nuclear DNA (nDNA) microsatellite loci to investigate the extent of gene flow among our sampling areas in Idaho, California and Alaska and to determine if we could distinguish birds from the different geographic regions based on their genetic profiles. Our results indicate high genetic diversity, low genetic structure and high connectivity. Nuclear DNA Fst values between Idaho and California were low but significantly different from zero (0.026). Bayesian clustering methods indicated a single population, and we were unable to distinguish summer breeding residents from different regions. Results of the mtDNA AMOVA showed that most of the haplotype variation (97%) was within the geographic populations while 3% variation was partitioned among them. One haplotype was common to all three areas. One region-specific haplotype was detected in California and one in Idaho, but additional sampling is required to determine if these haplotypes are unique to those geographic areas or a sampling artifact. We discuss potential sources of the high gene flow for this species including natal and breeding dispersal, floaters, and changes in migratory behavior as a result of environmental factors such as climate change and habitat alteration. Our preliminary findings can help inform the USFWS in development of golden eagle management strategies and provide a basis for additional research into the complex dynamics of the North American subspecies. PMID:27783687

Immunological Change in a Parasite-Impoverished Environment: Divergent Signals from Four Island Taxa

PubMed Central

Beadell, Jon S.; Atkins, Colm; Cashion, Erin; Jonker, Michelle; Fleischer, Robert C.

2007-01-01

Dramatic declines of native Hawaiian avifauna due to the human-mediated emergence of avian malaria and pox prompted an examination of whether island taxa share a common altered immunological signature, potentially driven by reduced genetic diversity and reduced exposure to parasites. We tested this hypothesis by characterizing parasite prevalence, genetic diversity and three measures of immune response in two recently-introduced species (Neochmia temporalis and Zosterops lateralis) and two island endemics (Acrocephalus aequinoctialis and A. rimitarae) and then comparing the results to those observed in closely-related mainland counterparts. The prevalence of blood parasites was significantly lower in 3 of 4 island taxa, due in part to the absence of certain parasite lineages represented in mainland populations. Indices of genetic diversity were unchanged in the island population of N. temporalis; however, allelic richness was significantly lower in the island population of Z. lateralis while both allelic richness and heterozygosity were significantly reduced in the two island-endemic species examined. Although parasite prevalence and genetic diversity generally conformed to expectations for an island system, we did not find evidence for a pattern of uniformly altered immune responses in island taxa, even amongst endemic taxa with the longest residence times. The island population of Z. lateralis exhibited a significantly reduced inflammatory cell-mediated response while levels of natural antibodies remained unchanged for this and the other recently introduced island taxon. In contrast, the island endemic A. rimitarae exhibited a significantly increased inflammatory response as well as higher levels of natural antibodies and complement. These measures were unchanged or lower in A. aequinoctialis. We suggest that small differences in the pathogenic landscape and the stochastic history of mutation and genetic drift are likely to be important in shaping the unique immunological profiles of small isolated populations. Consequently, predicting the impact of introduced disease on the many other endemic faunas of the remote Pacific will remain a challenge. PMID:17878931

Nuclear and Mitochondrial DNA Analyses of Golden Eagles (Aquila chrysaetos canadensis) from Three Areas in Western North America; Initial Results and Conservation Implications.

PubMed

Craig, Erica H; Adams, Jennifer R; Waits, Lisette P; Fuller, Mark R; Whittington, Diana M

2016-01-01

Understanding the genetics of a population is a critical component of developing conservation strategies. We used archived tissue samples from golden eagles (Aquila chrysaetos canadensis) in three geographic regions of western North America to conduct a preliminary study of the genetics of the North American subspecies, and to provide data for United States Fish and Wildlife Service (USFWS) decision-making for golden eagle management. We used a combination of mitochondrial DNA (mtDNA) D-loop sequences and 16 nuclear DNA (nDNA) microsatellite loci to investigate the extent of gene flow among our sampling areas in Idaho, California and Alaska and to determine if we could distinguish birds from the different geographic regions based on their genetic profiles. Our results indicate high genetic diversity, low genetic structure and high connectivity. Nuclear DNA Fst values between Idaho and California were low but significantly different from zero (0.026). Bayesian clustering methods indicated a single population, and we were unable to distinguish summer breeding residents from different regions. Results of the mtDNA AMOVA showed that most of the haplotype variation (97%) was within the geographic populations while 3% variation was partitioned among them. One haplotype was common to all three areas. One region-specific haplotype was detected in California and one in Idaho, but additional sampling is required to determine if these haplotypes are unique to those geographic areas or a sampling artifact. We discuss potential sources of the high gene flow for this species including natal and breeding dispersal, floaters, and changes in migratory behavior as a result of environmental factors such as climate change and habitat alteration. Our preliminary findings can help inform the USFWS in development of golden eagle management strategies and provide a basis for additional research into the complex dynamics of the North American subspecies.

Haplotype analysis of the polymorphic 40 Y-STR markers in Chinese populations.

PubMed

Ou, Xueling; Wang, Ying; Liu, Chao; Yang, Donggui; Zhang, Chuchu; Deng, Shujiao; Sun, Hongyu

2015-11-01

Forty Y-STR loci were analyzed in 1128 males from the following six Chinese ethnic populations: Han (n=300), Hui (n=244), Korean (n=100), Mongolian (n=100), Uighur (n=284) and Tibetan (n=100), utilizing two new generation multiplex Y-STR systems, AGCU Y24 STR and GFS Y24 STR genotyping kits, which allow for the genotyping of 24 loci from a single amplification reaction in each system. The lowest estimates of genetic diversity (below 0.5) correspond to markers DYS391 (0.441658) and DYS437 (0.496977), and the greatest diversity corresponds to markers DYS385a/b (0.969919) and DYS527a/b (0.94676). A considerable number of duplicate and off-ladder alleles were also revealed. Additionally, there were 1111 different haplotypes identified from the total 1128 samples, of which 1095 were unique. Notably, no shared haplotypes between populations were observed. The estimated overall haplotype diversity (HD) was 0.999085, and its discrimination capacity (DC) was 0.970745. An MDS plot based on the genetic distances between populations showed the genetic similarity of the southern Han population to the Northern populations of Hui, Korean, Mongolian and Uighur and a clear genetic departure of the Tibetan population from other populations. For the Y STR markers, population substructure correction was considered when calculating the rarity of the Y STR profile. However, because the haplotype based Fst values are extremely small within the present data (0.000153 with 40 Y-STRs), no substructure correction is required to estimate the rarity of a haplotype comprising 40 markers. In summary, the results of our study indicate that the 40 Y-STRs have a high level of polymorphism in Chinese ethnic groups and could therefore be a powerful tool for forensic applications and population genetic studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Nuclear and mitochondrial DNA analyses of golden eagles (Aquila chrysaetos canadensis) from three areas in western North America; initial results and conservation implications

USGS Publications Warehouse

Craig, Erica H; Adams, Jennifer R.; Waits, Lisette P.; Fuller, Mark R.; Whittington, Diana M.

2016-01-01

Understanding the genetics of a population is a critical component of developing conservation strategies. We used archived tissue samples from golden eagles (Aquila chrysaetos canadensis) in three geographic regions of western North America to conduct a preliminary study of the genetics of the North American subspecies, and to provide data for United States Fish and Wildlife Service (USFWS) decision-making for golden eagle management. We used a combination of mitochondrial DNA (mtDNA) D-loop sequences and 16 nuclear DNA (nDNA) microsatellite loci to investigate the extent of gene flow among our sampling areas in Idaho, California and Alaska and to determine if we could distinguish birds from the different geographic regions based on their genetic profiles. Our results indicate high genetic diversity, low genetic structure and high connectivity. Nuclear DNA Fst values between Idaho and California were low but significantly different from zero (0.026). Bayesian clustering methods indicated a single population, and we were unable to distinguish summer breeding residents from different regions. Results of the mtDNA AMOVA showed that most of the haplotype variation (97%) was within the geographic populations while 3% variation was partitioned among them. One haplotype was common to all three areas. One region-specific haplotype was detected in California and one in Idaho, but additional sampling is required to determine if these haplotypes are unique to those geographic areas or a sampling artifact. We discuss potential sources of the high gene flow for this species including natal and breeding dispersal, floaters, and changes in migratory behavior as a result of environmental factors such as climate change and habitat alteration. Our preliminary findings can help inform the USFWS in development of golden eagle management strategies and provide a basis for additional research into the complex dynamics of the North American subspecies.

Memory in Intellectually Matched Groups of Young Participants with 22q11.2 Deletion Syndrome and Those with Schizophrenia

ERIC Educational Resources Information Center

Kravariti, Eugenia; Jacobson, Clare; Morris, Robin; Frangou, Sophia; Murray, Robin M.; Tsakanikos, Elias; Habel, Alex; Shearer, Jo

2010-01-01

The 22q11.2 deletion syndrome (22qDS) and schizophrenia have genetic and neuropsychological similarities, but are likely to differ in memory profile. Confirming differences in memory function between the two disorders, and identifying their genetic determinants, can help to define genetic subtypes in both syndromes, identify genetic risk factors…

Systems genetics: a paradigm to improve discovery of candidate genes and mechanisms underlying complex traits.

PubMed

Feltus, F Alex

2014-06-01

Understanding the control of any trait optimally requires the detection of causal genes, gene interaction, and mechanism of action to discover and model the biochemical pathways underlying the expressed phenotype. Functional genomics techniques, including RNA expression profiling via microarray and high-throughput DNA sequencing, allow for the precise genome localization of biological information. Powerful genetic approaches, including quantitative trait locus (QTL) and genome-wide association study mapping, link phenotype with genome positions, yet genetics is less precise in localizing the relevant mechanistic information encoded in DNA. The coupling of salient functional genomic signals with genetically mapped positions is an appealing approach to discover meaningful gene-phenotype relationships. Techniques used to define this genetic-genomic convergence comprise the field of systems genetics. This short review will address an application of systems genetics where RNA profiles are associated with genetically mapped genome positions of individual genes (eQTL mapping) or as gene sets (co-expression network modules). Both approaches can be applied for knowledge independent selection of candidate genes (and possible control mechanisms) underlying complex traits where multiple, likely unlinked, genomic regions might control specific complex traits. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Genetic and environmental influences on last-year major depression in adulthood: a highly heritable stable liability but strong environmental effects on 1-year prevalence.

PubMed

Kendler, K S; Gardner, C O

2017-07-01

This study seeks to clarify the contribution of temporally stable and occasion-specific genetic and environmental influences on risk for major depression (MD). Our sample was 2153 members of female-female twin pairs from the Virginia Twin Registry. We examined four personal interview waves conducted over an 8-year period with MD in the last year defined by DSM-IV criteria. We fitted a structural equation model to the data using classic Mx. The model included genetic and environmental risk factors for a latent, stable vulnerability to MD and for episodes in each of the four waves. The best-fit model was simple and included genetic and unique environmental influences on the latent liability to MD and unique wave-specific environmental effects. The path from latent liability to MD in the last year was constant over time, moderate in magnitude (+0.65) and weaker than the impact of occasion-specific environmental effects (+0.76). Heritability of the latent stable liability to MD was much higher (78%) than that estimated for last-year MD (32%). Of the total unique environmental influences on MD, 13% reflected enduring consequences of earlier environmental insults, 17% diagnostic error and 70% wave-specific short-lived environmental stressors. Both genetic influences on MD and MD heritability are stable over middle adulthood. However, the largest influence on last-year MD is short-lived environmental effects. As predicted by genetic theory, the heritability of MD is increased substantially by measurement at multiple time points largely through the reduction of the effects of measurement error and short-term environmental risk factors.

From Wolves to Dogs, and Back: Genetic Composition of the Czechoslovakian Wolfdog.

PubMed

Smetanová, Milena; Černá Bolfíková, Barbora; Randi, Ettore; Caniglia, Romolo; Fabbri, Elena; Galaverni, Marco; Kutal, Miroslav; Hulva, Pavel

2015-01-01

The Czechoslovakian Wolfdog is a unique dog breed that originated from hybridization between German Shepherds and wild Carpathian wolves in the 1950s as a military experiment. This breed was used for guarding the Czechoslovakian borders during the cold war and is currently kept by civilian breeders all round the world. The aim of our study was to characterize, for the first time, the genetic composition of this breed in relation to its known source populations. We sequenced the hypervariable part of the mtDNA control region and genotyped the Amelogenin gene, four sex-linked microsatellites and 39 autosomal microsatellites in 79 Czechoslovakian Wolfdogs, 20 German Shepherds and 28 Carpathian wolves. We performed a range of population genetic analyses based on both empirical and simulated data. Only two mtDNA and two Y-linked haplotypes were found in Czechoslovakian Wolfdogs. Both mtDNA haplotypes were of domestic origin, while only one of the Y-haplotypes was shared with German Shepherds and the other was unique to Czechoslovakian Wolfdogs. The observed inbreeding coefficient was low despite the small effective population size of the breed, possibly due to heterozygote advantages determined by introgression of wolf alleles. Moreover, Czechoslovakian Wolfdog genotypes were distinct from both parental populations, indicating the role of founder effect, drift and/or genetic hitchhiking. The results revealed the peculiar genetic composition of the Czechoslovakian Wolfdog, showing a limited introgression of wolf alleles within a higher proportion of the dog genome, consistent with the reiterated backcrossing used in the pedigree. Artificial selection aiming to keep wolf-like phenotypes but dog-like behavior resulted in a distinctive genetic composition of Czechoslovakian Wolfdogs, which provides a unique example to study the interactions between dog and wolf genomes.

Application of next-generation sequencing technology to study genetic diversity and identify unique SNP markers in bread wheat from Kazakhstan.

PubMed

Shavrukov, Yuri; Suchecki, Radoslaw; Eliby, Serik; Abugalieva, Aigul; Kenebayev, Serik; Langridge, Peter

2014-09-28

New SNP marker platforms offer the opportunity to investigate the relationships between wheat cultivars from different regions and assess the mechanism and processes that have led to adaptation to particular production environments. Wheat breeding has a long history in Kazakhstan and the aim of this study was to explore the relationship between key varieties from Kazakhstan and germplasm from breeding programs for other regions. The study revealed 5,898 polymorphic markers amongst ten cultivars, of which 2,730 were mapped in the consensus genetic map. Mapped SNP markers were distributed almost equally across the A and B genomes, with between 279 and 484 markers assigned to each chromosome. Marker coverage was approximately 10-fold lower in the D genome. There were 863 SNP markers identified as unique to specific cultivars, and clusters of these markers (regions containing more than three closely mapped unique SNPs) showed specific patterns on the consensus genetic map for each cultivar. Significant intra-varietal genetic polymorphism was identified in three cultivars (Tzelinnaya 3C, Kazakhstanskaya rannespelaya and Kazakhstanskaya 15). Phylogenetic analysis based on inter-varietal polymorphism showed that the very old cultivar Erythrospermum 841 was the most genetically distinct from the other nine cultivars from Kazakhstan, falling in a clade together with the American cultivar Sonora and genotypes from Central and South Asia. The modern cultivar Kazakhstanskaya 19 also fell into a separate clade, together with the American cultivar Thatcher. The remaining eight cultivars shared a single sub-clade but were categorised into four clusters. The accumulated data for SNP marker polymorphisms amongst bread wheat genotypes from Kazakhstan may be used for studying genetic diversity in bread wheat, with potential application for marker-assisted selection and the preparation of a set of genotype-specific markers.

The Genetics of Bene Israel from India Reveals Both Substantial Jewish and Indian Ancestry

PubMed Central

Davidson, Natalie R.; Billing-Ross, Paul; Dubrovsky, Maya; Campbell, Christopher L.; Oddoux, Carole; Friedman, Eitan; Atzmon, Gil; Halperin, Eran; Ostrer, Harry; Keinan, Alon

2016-01-01

The Bene Israel Jewish community from West India is a unique population whose history before the 18th century remains largely unknown. Bene Israel members consider themselves as descendants of Jews, yet the identity of Jewish ancestors and their arrival time to India are unknown, with speculations on arrival time varying between the 8th century BCE and the 6th century CE. Here, we characterize the genetic history of Bene Israel by collecting and genotyping 18 Bene Israel individuals. Combining with 486 individuals from 41 other Jewish, Indian and Pakistani populations, and additional individuals from worldwide populations, we conducted comprehensive genome-wide analyses based on FST, principal component analysis, ADMIXTURE, identity-by-descent sharing, admixture linkage disequilibrium decay, haplotype sharing and allele sharing autocorrelation decay, as well as contrasted patterns between the X chromosome and the autosomes. The genetics of Bene Israel individuals resemble local Indian populations, while at the same time constituting a clearly separated and unique population in India. They are unique among Indian and Pakistani populations we analyzed in sharing considerable genetic ancestry with other Jewish populations. Putting together the results from all analyses point to Bene Israel being an admixed population with both Jewish and Indian ancestry, with the genetic contribution of each of these ancestral populations being substantial. The admixture took place in the last millennium, about 19–33 generations ago. It involved Middle-Eastern Jews and was sex-biased, with more male Jewish and local female contribution. It was followed by a population bottleneck and high endogamy, which can lead to increased prevalence of recessive diseases in this population. This study provides an example of how genetic analysis advances our knowledge of human history in cases where other disciplines lack the relevant data to do so. PMID:27010569

The Genetics of Bene Israel from India Reveals Both Substantial Jewish and Indian Ancestry.

PubMed

Waldman, Yedael Y; Biddanda, Arjun; Davidson, Natalie R; Billing-Ross, Paul; Dubrovsky, Maya; Campbell, Christopher L; Oddoux, Carole; Friedman, Eitan; Atzmon, Gil; Halperin, Eran; Ostrer, Harry; Keinan, Alon

2016-01-01

The Bene Israel Jewish community from West India is a unique population whose history before the 18th century remains largely unknown. Bene Israel members consider themselves as descendants of Jews, yet the identity of Jewish ancestors and their arrival time to India are unknown, with speculations on arrival time varying between the 8th century BCE and the 6th century CE. Here, we characterize the genetic history of Bene Israel by collecting and genotyping 18 Bene Israel individuals. Combining with 486 individuals from 41 other Jewish, Indian and Pakistani populations, and additional individuals from worldwide populations, we conducted comprehensive genome-wide analyses based on FST, principal component analysis, ADMIXTURE, identity-by-descent sharing, admixture linkage disequilibrium decay, haplotype sharing and allele sharing autocorrelation decay, as well as contrasted patterns between the X chromosome and the autosomes. The genetics of Bene Israel individuals resemble local Indian populations, while at the same time constituting a clearly separated and unique population in India. They are unique among Indian and Pakistani populations we analyzed in sharing considerable genetic ancestry with other Jewish populations. Putting together the results from all analyses point to Bene Israel being an admixed population with both Jewish and Indian ancestry, with the genetic contribution of each of these ancestral populations being substantial. The admixture took place in the last millennium, about 19-33 generations ago. It involved Middle-Eastern Jews and was sex-biased, with more male Jewish and local female contribution. It was followed by a population bottleneck and high endogamy, which can lead to increased prevalence of recessive diseases in this population. This study provides an example of how genetic analysis advances our knowledge of human history in cases where other disciplines lack the relevant data to do so.

Gene Expression Profiles of Sporadic Canine Hemangiosarcoma Are Uniquely Associated with Breed

PubMed Central

Tamburini, Beth A.; Trapp, Susan; Phang, Tzu Lip; Schappa, Jill T.; Hunter, Lawrence E.; Modiano, Jaime F.

2009-01-01

The role an individual's genetic background plays on phenotype and biological behavior of sporadic tumors remains incompletely understood. We showed previously that lymphomas from Golden Retrievers harbor defined, recurrent chromosomal aberrations that occur less frequently in lymphomas from other dog breeds, suggesting spontaneous canine tumors provide suitable models to define how heritable traits influence cancer genotypes. Here, we report a complementary approach using gene expression profiling in a naturally occurring endothelial sarcoma of dogs (hemangiosarcoma). Naturally occurring hemangiosarcomas of Golden Retrievers clustered separately from those of non-Golden Retrievers, with contributions from transcription factors, survival factors, and from pro-inflammatory and angiogenic genes, and which were exclusively present in hemangiosarcoma and not in other tumors or normal cells (i.e., they were not due simply to variation in these genes among breeds). Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) was among genes preferentially enriched within known pathways derived from gene set enrichment analysis when characterizing tumors from Golden Retrievers versus other breeds. Heightened VEGFR1 expression in these tumors also was apparent at the protein level and targeted inhibition of VEGFR1 increased proliferation of hemangiosarcoma cells derived from tumors of Golden Retrievers, but not from other breeds. Our results suggest heritable factors mold gene expression phenotypes, and consequently biological behavior in sporadic, naturally occurring tumors. PMID:19461996

Metabolomic tools for secondary metabolite discovery from marine microbial symbionts.

PubMed

Macintyre, Lynsey; Zhang, Tong; Viegelmann, Christina; Martinez, Ignacio Juarez; Cheng, Cheng; Dowdells, Catherine; Abdelmohsen, Usama Ramadam; Gernert, Christine; Hentschel, Ute; Edrada-Ebel, RuAngelie

2014-06-05

Marine invertebrate-associated symbiotic bacteria produce a plethora of novel secondary metabolites which may be structurally unique with interesting pharmacological properties. Selection of strains usually relies on literature searching, genetic screening and bioactivity results, often without considering the chemical novelty and abundance of secondary metabolites being produced by the microorganism until the time-consuming bioassay-guided isolation stages. To fast track the selection process, metabolomic tools were used to aid strain selection by investigating differences in the chemical profiles of 77 bacterial extracts isolated from cold water marine invertebrates from Orkney, Scotland using liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Following mass spectrometric analysis and dereplication using an Excel macro developed in-house, principal component analysis (PCA) was employed to differentiate the bacterial strains based on their chemical profiles. NMR 1H and correlation spectroscopy (COSY) were also employed to obtain a chemical fingerprint of each bacterial strain and to confirm the presence of functional groups and spin systems. These results were then combined with taxonomic identification and bioassay screening data to identify three bacterial strains, namely Bacillus sp. 4117, Rhodococcus sp. ZS402 and Vibrio splendidus strain LGP32, to prioritize for scale-up based on their chemically interesting secondary metabolomes, established through dereplication and interesting bioactivities, determined from bioassay screening.

BloodSpot: a database of gene expression profiles and transcriptional programs for healthy and malignant haematopoiesis

PubMed Central

Bagger, Frederik Otzen; Sasivarevic, Damir; Sohi, Sina Hadi; Laursen, Linea Gøricke; Pundhir, Sachin; Sønderby, Casper Kaae; Winther, Ole; Rapin, Nicolas; Porse, Bo T.

2016-01-01

Research on human and murine haematopoiesis has resulted in a vast number of gene-expression data sets that can potentially answer questions regarding normal and aberrant blood formation. To researchers and clinicians with limited bioinformatics experience, these data have remained available, yet largely inaccessible. Current databases provide information about gene-expression but fail to answer key questions regarding co-regulation, genetic programs or effect on patient survival. To address these shortcomings, we present BloodSpot (www.bloodspot.eu), which includes and greatly extends our previously released database HemaExplorer, a database of gene expression profiles from FACS sorted healthy and malignant haematopoietic cells. A revised interactive interface simultaneously provides a plot of gene expression along with a Kaplan–Meier analysis and a hierarchical tree depicting the relationship between different cell types in the database. The database now includes 23 high-quality curated data sets relevant to normal and malignant blood formation and, in addition, we have assembled and built a unique integrated data set, BloodPool. Bloodpool contains more than 2000 samples assembled from six independent studies on acute myeloid leukemia. Furthermore, we have devised a robust sample integration procedure that allows for sensitive comparison of user-supplied patient samples in a well-defined haematopoietic cellular space. PMID:26507857

Screening of miRNA profiles and construction of regulation networks in early and late lactation of dairy goat mammary glands.

PubMed

Ji, Zhibin; Liu, Zhaohua; Chao, Tianle; Hou, Lei; Fan, Rui; He, Rongyan; Wang, Guizhi; Wang, Jianmin

2017-09-20

In recent years, studies related to the expression profiles of miRNAs in the dairy goat mammary gland were performed, but regulatory mechanisms in the physiological environment and the dynamic homeostasis of mammary gland development and lactation are not clear. In the present study, sequencing data analysis of early and late lactation uncovered a total of 1,487 unique miRNAs, including 45 novel miRNA candidates and 1,442 known and conserved miRNAs, of which 758 miRNAs were co-expressed and 378 differentially expressed with P < 0.05. Moreover, 76 non-redundant target genes were annotated in 347 GO consortiums, with 3,143 candidate target genes grouped into 33 pathways. Additionally, 18 predicted target genes of 214 miRNAs were directly annotated in mammary gland development and used to construct regulatory networks based on GO annotation and the KEGG pathway. The expression levels of seven known miRNAs and three novel miRNAs were examined using quantitative real-time PCR. The results showed that miRNAs might play important roles in early and late lactation during dairy goat mammary gland development, which will be helpful to obtain a better understanding of the genetic control of mammary gland lactation and development.

Expression profiling of cardiovascular disease

PubMed Central

2004-01-01

Cardiovascular disease is the most important cause of morbidity and mortality in developed countries, causing twice as many deaths as cancer in the USA. The major cardiovascular diseases, including coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF) and common congenital heart disease (CHD), are caused by multiple genetic and environmental factors, as well as the interactions between them. The underlying molecular pathogenic mechanisms for these disorders are still largely unknown, but gene expression may play a central role in the development and progression of cardiovascular disease. Microarrays are high-throughput genomic tools that allow the comparison of global expression changes in thousands of genes between normal and diseased cells/tissues. Microarrays have recently been applied to CAD/MI, CHF and CHD to profile changes in gene expression patterns in diseased and non-diseased patients. This same technology has also been used to characterise endothelial cells, vascular smooth muscle cells and inflammatory cells, with or without various treatments that mimic disease processes involved in CAD/MI. These studies have led to the identification of unique subsets of genes associated with specific diseases and disease processes. Ongoing microarray studies in the field will provide insights into the molecular mechanism of cardiovascular disease and may generate new diagnostic and therapeutic markers. PMID:15588496

Metabolic profiles are principally different between cancers of the liver, pancreas and breast.

PubMed

Budhu, Anuradha; Terunuma, Atsushi; Zhang, Geng; Hussain, S Perwez; Ambs, Stefan; Wang, Xin Wei

2014-01-01

Molecular profiling of primary tumors may facilitate the classification of patients with cancer into more homogenous biological groups to aid clinical management. Metabolomic profiling has been shown to be a powerful tool in characterizing the biological mechanisms underlying a disease but has not been evaluated for its ability to classify cancers by their tissue of origin. Thus, we assessed metabolomic profiling as a novel tool for multiclass cancer characterization. Global metabolic profiling was employed to identify metabolites in paired tumor and non-tumor liver (n=60), breast (n=130) and pancreatic (n=76) tissue specimens. Unsupervised principal component analysis showed that metabolites are principally unique to each tissue and cancer type. Such a difference can also be observed even among early stage cancers, suggesting a significant and unique alteration of global metabolic pathways associated with each cancer type. Our global high-throughput metabolomic profiling study shows that specific biochemical alterations distinguish liver, pancreatic and breast cancer and could be applied as cancer classification tools to differentiate tumors based on tissue of origin.

Radial pressure profiles in a cold‐flow gas‐solid vortex reactor

PubMed Central

Pantzali, Maria N.; Kovacevic, Jelena Z.; Marin, Guy B.; Shtern, Vladimir N.

2015-01-01

A unique normalized radial pressure profile characterizes the bed of a gas‐solid vortex reactor over a range of particle densities and sizes, solid capacities, and gas flow rates: 950–1240 kg/m3, 1–2 mm, 2 kg to maximum solids capacity, and 0.4–0.8 Nm3/s (corresponding to gas injection velocities of 55–110 m/s), respectively. The combined momentum conservation equations of both gas and solid phases predict this pressure profile when accounting for the corresponding measured particle velocities. The pressure profiles for a given type of particles and a given solids loading but for different gas injection velocities merge into a single curve when normalizing the pressures with the pressure value downstream of the bed. The normalized—with respect to the overall pressure drop—pressure profiles for different gas injection velocities in particle‐free flow merge in a unique profile. © 2015 The Authors AIChE Journal published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers AIChE J, 61: 4114–4125, 2015 PMID:27667827

76 FR 37771 - Monsanto Co.; Availability of Petition, Plant Pest Risk Assessment, and Environmental Assessment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

... Determination of Nonregulated Status for Soybean Genetically Engineered To Have a Modified Fatty Acid Profile... soybean designated as MON 87705, which has been genetically engineered to have a modified fatty acid... our regulations concerning the introduction of certain genetically engineered organisms and products...

Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY).

PubMed

Lee, Nancy Raitano; Anand, Payal; Will, Elizabeth; Adeyemi, Elizabeth I; Clasen, Liv S; Blumenthal, Jonathan D; Giedd, Jay N; Daunhauer, Lisa A; Fidler, Deborah J; Edgin, Jamie O

2015-01-01

Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X (n = 30), and a TD group (n = 30), ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD (n = 43), ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups.

Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY)

PubMed Central

Lee, Nancy Raitano; Anand, Payal; Will, Elizabeth; Adeyemi, Elizabeth I.; Clasen, Liv S.; Blumenthal, Jonathan D.; Giedd, Jay N.; Daunhauer, Lisa A.; Fidler, Deborah J.; Edgin, Jamie O.

2015-01-01

Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X (n = 30), and a TD group (n = 30), ages 5–18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD (n = 43), ages 4–24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups. PMID:26539087

Profiling depression in childhood and adolescence: the role of conduct problems.

PubMed

Riglin, Lucy; Thapar, Anita; Shelton, Katherine H; Langley, Kate; Frederickson, Norah; Rice, Frances

2016-04-01

Depression is typically more common in females and rates rise around puberty. However, studies of children and adolescents suggest that depression accompanied by conduct problems may represent a different subtype not characterised by a female preponderance, with differing risk factors and genetic architecture compared to pure-depression. This study aimed to identify aetiologically distinct profiles of depressive symptoms, distinguished by the presence or absence of co-occurring conduct problems. Latent profile analysis was conducted on a school sample of 1648 children (11-12 years) and replicated in a sample of 2006 twins (8-17 years). In both samples pure-depressive and conduct-depressive profiles were identified. The pure-depressive profile was associated with female gender, while the conduct-depressive profile was associated with lower cognitive ability but not with gender. Twin analyses indicated possible differences in genetic aetiology. There was evidence for aetiologically heterogeneous depression symptom profiles based on the presence or absence of co-occurring conduct problems. © 2015 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

Systematic profiling of Caenorhabditis elegans locomotive behaviors reveals additional components in G-protein Gαq signaling.

PubMed

Yu, Hui; Aleman-Meza, Boanerges; Gharib, Shahla; Labocha, Marta K; Cronin, Christopher J; Sternberg, Paul W; Zhong, Weiwei

2013-07-16

Genetic screens have been widely applied to uncover genetic mechanisms of movement disorders. However, most screens rely on human observations of qualitative differences. Here we demonstrate the application of an automatic imaging system to conduct a quantitative screen for genes regulating the locomotive behavior in Caenorhabditis elegans. Two hundred twenty-seven neuronal signaling genes with viable homozygous mutants were selected for this study. We tracked and recorded each animal for 4 min and analyzed over 4,400 animals of 239 genotypes to obtain a quantitative, 10-parameter behavioral profile for each genotype. We discovered 87 genes whose inactivation causes movement defects, including 50 genes that had never been associated with locomotive defects. Computational analysis of the high-content behavioral profiles predicted 370 genetic interactions among these genes. Network partition revealed several functional modules regulating locomotive behaviors, including sensory genes that detect environmental conditions, genes that function in multiple types of excitable cells, and genes in the signaling pathway of the G protein Gαq, a protein that is essential for animal life and behavior. We developed quantitative epistasis analysis methods to analyze the locomotive profiles and validated the prediction of the γ isoform of phospholipase C as a component in the Gαq pathway. These results provided a system-level understanding of how neuronal signaling genes coordinate locomotive behaviors. This study also demonstrated the power of quantitative approaches in genetic studies.

Comparative study of sickle cell anemia and hemoglobin SC disease: clinical characterization, laboratory biomarkers and genetic profiles.

PubMed

Aleluia, Milena Magalhães; Fonseca, Teresa Cristina Cardoso; Souza, Regiana Quinto; Neves, Fábia Idalina; da Guarda, Caroline Conceição; Santiago, Rayra Pereira; Cunha, Bruna Laís Almeida; Figueiredo, Camylla Villas Boas; Santana, Sânzio Silva; da Paz, Silvana Sousa; Ferreira, Júnia Raquel Dutra; Cerqueira, Bruno Antônio Veloso; Gonçalves, Marilda de Souza

2017-01-01

In this study, we evaluate the association of different clinical profiles, laboratory and genetic biomarkers in patients with sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in attempt to characterize the sickle cell disease (SCD) genotypes. We conducted a cross-sectional study from 2013 to 2014 in 200 SCD individuals (141 with SCA; 59 with HbSC) and analyzed demographic data to characterize the study population. In addition, we determined the association of hematological, biochemical and genetic markers including the β S -globin gene haplotypes and the 3.7 Kb deletion of α-thalassemia (-α 3.7Kb -thal), as well as the occurrence of clinical events in both SCD genotypes. Laboratory parameters showed a hemolytic profile associated with endothelial dysfunction in SCA individuals; however, the HbSC genotype was more associated with increased blood viscosity and inflammatory conditions. The BEN haplotype was the most frequently observed and was associated with elevated fetal hemoglobin (HbF) and low S hemoglobin (HbS). The -α 3.7Kb -thal prevalence was 0.09 (9%), and it was associated with elevated hemoglobin and hematocrit concentrations. Clinical events were more frequent in SCA patients. Our data emphasize the differences between SCA and HbSC patients based on laboratory parameters and the clinical and genetic profile of both genotypes.

Leading-edge forensic DNA analyses and the necessity of including crime scene investigators, police officers and technicians in a DNA elimination database.

PubMed

Lapointe, Martine; Rogic, Anita; Bourgoin, Sarah; Jolicoeur, Christine; Séguin, Diane

2015-11-01

In recent years, sophisticated technology has significantly increased the sensitivity and analytical power of genetic analyses so that very little starting material may now produce viable genetic profiles. This sensitivity however, has also increased the risk of detecting unknown genetic profiles assumed to be that of the perpetrator, yet originate from extraneous sources such as from crime scene workers. These contaminants may mislead investigations, keeping criminal cases active and unresolved for long spans of time. Voluntary submission of DNA samples from crime scene workers is fairly low, therefore we have created a promotional method for our staff elimination database that has resulted in a significant increase in voluntary samples since 2011. Our database enforces privacy safeguards and allows for optional anonymity to all staff members. We also offer information sessions at various police precincts to advise crime scene workers of the importance and success of our staff elimination database. This study, a pioneer in its field, has obtained 327 voluntary submissions from crime scene workers to date, of which 46 individual profiles (14%) have been matched to 58 criminal cases. By implementing our methods and respect for individual privacy, forensic laboratories everywhere may see similar growth and success in explaining unidentified genetic profiles in stagnate criminal cases. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

Tumoural specimens for forensic purposes: comparison of genetic alterations in frozen and formalin-fixed paraffin-embedded tissues.

PubMed

Ananian, Viviana; Tozzo, Pamela; Ponzano, Elena; Nitti, Donato; Rodriguez, Daniele; Caenazzo, Luciana

2011-05-01

In certain circumstances, tumour tissue specimens are the only DNA resource available for forensic DNA analysis. However, cancer tissues can show microsatellite instability and loss of heterozygosity which, if concerning the short tandem repeats (STRs) used in the forensic field, can cause misinterpretation of the results. Moreover, though formalin-fixed paraffin-embedded tissues (FFPET) represent a large resource for these analyses, the quality of the DNA obtained from this kind of specimen can be an important limit. In this study, we evaluated the use of tumoural tissue as biological material for the determination of genetic profiles in the forensic field, highlighting which STR polymorphisms are more susceptible to tumour genetic alterations and which of the analysed tumours show a higher genetic variability. The analyses were conducted on samples of the same tissues conserved in different storage conditions, to compare genetic profiles obtained by frozen tissues and formalin-fixed paraffin-embedded tissues. The importance of this study is due to the large number of specimens analysed (122), the large number of polymorphisms analysed for each specimen (39), and the possibility to compare, many years after storage, the same tissue frozen and formalin-fixed paraffin-embedded. In the comparison between the genetic profiles of frozen tumour tissues and FFPET, the same genetic alterations have been reported in both kinds of specimens. However, FFPET showed new alterations. We conclude that the use of FFPET requires greater attention than frozen tissues in the results interpretation and great care in both pre-extraction and extraction processes.

Changes in composition of cuticular biochemicals of the facultatively polygynous ant Petalomyrmex phylax during range expansion in Cameroon with respect to social, spatial and genetic variation.

PubMed

Dalecky, Ambroise; Renucci, Marielle; Tirard, Alain; Debout, Gabriel; Roux, Maurice; Kjellberg, Finn; Provost, Erick

2007-09-01

In social insects, biochemicals found at the surface of the cuticle are involved in the recognition process and in protection against desiccation and pathogens. However, the relative contribution of evolutionary forces in shaping diversity of these biochemicals remains largely unresolved in ants. We determined the composition of epicuticular biochemicals for workers sampled in 12 populations of the ant Petalomyrmex phylax from Cameroon. Genetic variation at 12 microsatellite markers was used to infer population history and to provide null expectations under the neutrality hypothesis. Genetic data suggest a recent southward range expansion of this ant species. Furthermore, there is a decline southward in the numbers of queens present in mature colonies. Here, we contrast the pattern of biochemical variation against genetic, social and spatial parameters. We thus provide the first estimates of the relative contribution of neutral and selective processes on variation of ant cuticular profile. Populations in migration-drift disequilibrium showed reduction of within-population variation for genetic markers as well as for cuticular profiles. In these populations, the cuticular profile became biased towards a limited number of high molecular weight molecules. Within- and among-population biochemical variation was explained by both genetic and social variation and by the spatial distribution of populations. We therefore propose that during range expansion of P. phylax, the composition of epicuticular compounds has been affected by a combination of neutral processes - genetic drift and spatially limited dispersal - and spatially varying selection, social organization and environmental effects.

Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer

PubMed Central

Shen, Lanlan; Toyota, Minoru; Kondo, Yutaka; Lin, E; Zhang, Li; Guo, Yi; Hernandez, Natalie Supunpong; Chen, Xinli; Ahmed, Saira; Konishi, Kazuo; Hamilton, Stanley R.; Issa, Jean-Pierre J.

2007-01-01

Colon cancer has been viewed as the result of progressive accumulation of genetic and epigenetic abnormalities. However, this view does not fully reflect the molecular heterogeneity of the disease. We have analyzed both genetic (mutations of BRAF, KRAS, and p53 and microsatellite instability) and epigenetic alterations (DNA methylation of 27 CpG island promoter regions) in 97 primary colorectal cancer patients. Two clustering analyses on the basis of either epigenetic profiling or a combination of genetic and epigenetic profiling were performed to identify subclasses with distinct molecular signatures. Unsupervised hierarchical clustering of the DNA methylation data identified three distinct groups of colon cancers named CpG island methylator phenotype (CIMP) 1, CIMP2, and CIMP negative. Genetically, these three groups correspond to very distinct profiles. CIMP1 are characterized by MSI (80%) and BRAF mutations (53%) and rare KRAS and p53 mutations (16% and 11%, respectively). CIMP2 is associated with 92% KRAS mutations and rare MSI, BRAF, or p53 mutations (0, 4, and 31% respectively). CIMP-negative cases have a high rate of p53 mutations (71%) and lower rates of MSI (12%) or mutations of BRAF (2%) or KRAS (33%). Clustering based on both genetic and epigenetic parameters also identifies three distinct (and homogeneous) groups that largely overlap with the previous classification. The three groups are independent of age, gender, or stage, but CIMP1 and 2 are more common in proximal tumors. Together, our integrated genetic and epigenetic analysis reveals that colon cancers correspond to three molecularly distinct subclasses of disease. PMID:18003927

Demonstration: Genetic Jewelry

ERIC Educational Resources Information Center

Atkins, Thomas; Roderick, Joyce

2006-01-01

In order for students to understand genetics and evolution, they must first understand the structure of the DNA molecule. The function of DNA proceeds from its unique structure, a structure beautifully adapted for information storage, transcription, translation into amino acid sequences, replication, and time travel. The activity described in this…

Genetic Screening: A Unique Game of Survival

ERIC Educational Resources Information Center

Kurvink, Karen; Bowser, Jessica

2004-01-01

A creative learning game that helps students reinforce basic genetic information and facilitate the identification and understanding of the more subtle issues is presented. The basic framework of the game was conceived by a business major taking non-biology major course 'heredity and society-intertwining legacy.

The National Plant Germplasm System and GRIN-Global

USDA-ARS?s Scientific Manuscript database

The National Plant Germplasm System (NPGS) is a cooperative effort by public and private organizations to preserve plant genetic diversity. Federal and State personnel at 20 sites are responsible for approximately 547,000 unique accessions of a wide array of plant genetic resources (PGR) representi...

Aging, Genetic Variations, and Ethnopharmacology: Building Cultural Competence Through Awareness of Drug Responses in Ethnic Minority Elders.

PubMed

Woods, Diana Lynn; Mentes, Janet C; Cadogan, Mary; Phillips, Linda R

2017-01-01

Unique drug responses that may result in adverse events are among the ethnocultural differences described by the Agency for Healthcare Research and Quality. These differences, often attributed to a lack of adherence on the part of the older adult, may be linked to genetic variations that influence drug responses in different ethnic groups. The paucity of research coupled with a lack of knowledge among health care providers compound the problem, contributing to further disparities, especially in this era of personalized medicine and pharmacogenomics. This article examines how age-related changes and genetic differences influence variations in drug responses among older adults in unique ethnocultural groups. The article starts with an overview of age-related changes and ethnopharmacology, moves to describing genetic differences that affect drug responses, with a focus on medications commonly prescribed for older adults, and ends with application of these issues to culturally congruent health care. © The Author(s) 2015.

Consanguinity in Saudi Arabia: a unique opportunity for pediatric kidney research.

PubMed

Kari, Jameela A; Bockenhauer, Detlef; Stanescu, Horia; Gari, Mamdooh; Kleta, Robert; Singh, Ajay K

2014-02-01

Identification of disease-related genes is a critical step in understanding the molecular basis of disease and developing targeted therapies. The genetic study of diseases occurring in the offspring of consanguineous unions is a powerful way to discover new disease genes. Pediatric nephrology provides an excellent example because ∼70% of cases of kidney disease in childhood are congenital with a likely genetic basis. This percentage is likely to be even higher in countries with a high consanguinity rate, such as the Kingdom of Saudi Arabia. However, there are a number of challenges, such as cultural, legal, and religious restrictions, that should be appreciated before carrying out genetic research in a tradition-bound country. In this article, we discuss the background, opportunities, and challenges involved with this unique opportunity to conduct studies of such genetic disorders. Keys to success include collaboration and an understanding of local traditions and laws. Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.

Heterogeneity of clonal patterns among patches of kudzu, Pueraria montana var. lobata, an invasive plant

PubMed Central

Kartzinel, Tyler R.; Hamrick, J. L.; Wang, Chongyun; Bowsher, Alan W.; Quigley, Bryan G. P.

2015-01-01

Background and Aims Viny species are among the most serious invasive plants, and better knowledge of how vines grow to dominate landscapes is needed. Patches may contain a single genotype (i.e. genet), a competitively dominant genet or many independent but interacting genets, yet the clonal structure of vining species is often not apparent. Molecular markers can discriminate among the genetic identities of entwined vines to reveal the number and spatial distribution of genets. This study investigated how genets are spatially distributed within and among discrete patches of the invasive vine kudzu, Pueraria montana var. lobata, in the United States. It was expected that ramets of genets would be spatially clustered within patches, and that an increase in the number of genets within a patch would be associated with a decrease in the average size of each genet. Methods Six discrete kudzu patches were sampled across 2 years, and 1257 samples were genotyped at 21 polymorphic allozyme loci. Variation in genotypic and genetic diversity among patches was quantified and patterns of genet interdigitation were analysed. Key Results Substantial genotypic and genetic variation occurred within and among patches. As few as ten overlapping genets spanned up to 68 m2 in one patch, while >90 % of samples were genetically unique in another patch. Genotypic diversity within patches increased as mean clone size decreased, although spatially widespread genets did not preclude interdigitation. Eight genets were shared across ≥2 patches, suggesting that vegetative dispersal can occur among patches. Conclusions Genetically unique kudzu vines are highly interdigitated. Multiple vegetative propagules have become established in spatially discrete patches, probably through the movement of highway construction or maintenance machinery. The results suggest that common methods for controlling invasive vines (e.g. mowing) may inadvertently increase genotypic diversity. Thus, understanding vine architecture and growth has practical implications. PMID:26229064

Transcriptional profiling of the pea shoot apical meristem reveals processes underlying its function and maintenance

PubMed Central

Wong, Chui E; Bhalla, Prem L; Ottenhof, Harald; Singh, Mohan B

2008-01-01

Background Despite the importance of the shoot apical meristem (SAM) in plant development and organ formation, our understanding of the molecular mechanisms controlling its function is limited. Genomic tools have the potential to unravel the molecular mysteries of the SAM, and legume systems are increasingly being used in plant-development studies owing to their unique characteristics such as nitrogen fixation, secondary metabolism, and pod development. Garden pea (Pisum sativum) is a well-established classic model species for genetics studies that has been used since the Mendel era. In addition, the availability of a plethora of developmental mutants makes pea an ideal crop legume for genomics studies. This study aims to utilise genomics tools in isolating genes that play potential roles in the regulation of SAM activity. Results In order to identify genes that are differentially expressed in the SAM, we generated 2735 ESTs from three cDNA libraries derived from freshly micro-dissected SAMs from 10-day-old garden peas (Pisum sativum cv Torsdag). Custom-designed oligonucleotide arrays were used to compare the transcriptional profiles of pea SAMs and non-meristematic tissues. A total of 184 and 175 transcripts were significantly up- or down-regulated in the pea SAM, respectively. As expected, close to 61% of the transcripts down-regulated in the SAM were found in the public database, whereas sequences from the same source only comprised 12% of the genes that were expressed at higher levels in the SAM. This highlights the under-representation of transcripts from the meristematic tissues in the current public pea protein database, and demonstrates the utility of our SAM EST collection as an essential genetic resource for revealing further information on the regulation of this developmental process. In addition to unknowns, many of the up-regulated transcripts are known to encode products associated with cell division and proliferation, epigenetic regulation, auxin-mediated responses and microRNA regulation. Conclusion The presented data provide a picture of the transcriptional profile of the pea SAM, and reveal possible roles of differentially expressed transcripts in meristem function and maintenance. PMID:18590528

Mapping in an apple (Malus x domestica) F1 segregating population based on physical clustering of differentially expressed genes.

PubMed

Jensen, Philip J; Fazio, Gennaro; Altman, Naomi; Praul, Craig; McNellis, Timothy W

2014-04-04

Apple tree breeding is slow and difficult due to long generation times, self-incompatibility, and complex genetics. The identification of molecular markers linked to traits of interest is a way to expedite the breeding process. In the present study, we aimed to identify genes whose steady-state transcript abundance was associated with inheritance of specific traits segregating in an apple (Malus × domestica) rootstock F1 breeding population, including resistance to powdery mildew (Podosphaera leucotricha) disease and woolly apple aphid (Eriosoma lanigerum). Transcription profiling was performed for 48 individual F1 apple trees from a cross of two highly heterozygous parents, using RNA isolated from healthy, actively-growing shoot tips and a custom apple DNA oligonucleotide microarray representing 26,000 unique transcripts. Genome-wide expression profiles were not clear indicators of powdery mildew or woolly apple aphid resistance phenotype. However, standard differential gene expression analysis between phenotypic groups of trees revealed relatively small sets of genes with trait-associated expression levels. For example, thirty genes were identified that were differentially expressed between trees resistant and susceptible to powdery mildew. Interestingly, the genes encoding twenty-four of these transcripts were physically clustered on chromosome 12. Similarly, seven genes were identified that were differentially expressed between trees resistant and susceptible to woolly apple aphid, and the genes encoding five of these transcripts were also clustered, this time on chromosome 17. In each case, the gene clusters were in the vicinity of previously identified major quantitative trait loci for the corresponding trait. Similar results were obtained for a series of molecular traits. Several of the differentially expressed genes were used to develop DNA polymorphism markers linked to powdery mildew disease and woolly apple aphid resistance. Gene expression profiling and trait-associated transcript analysis using an apple F1 population readily identified genes physically linked to powdery mildew disease resistance and woolly apple aphid resistance loci. This result was especially useful in apple, where extreme levels of heterozygosity make the development of reliable DNA markers quite difficult. The results suggest that this approach could prove effective in crops with complicated genetics, or for which few genomic information resources are available.

Use of the maximum entropy method to retrieve the vertical atmospheric ozone profile and predict atmospheric ozone content

NASA Technical Reports Server (NTRS)

Turner, B. Curtis

1992-01-01

A method is developed for prediction of ozone levels in planetary atmospheres. This method is formulated in terms of error covariance matrices, and is associated with both direct measurements, a priori first guess profiles, and a weighting function matrix. This is described by the following linearized equation: y = A(matrix) x X + eta, where A is the weighting matrix and eta is noise. The problems to this approach are: (1) the A matrix is near singularity; (2) the number of unknowns in the profile exceeds the number of data points, therefore, the solution may not be unique; and (3) even if a unique solution exists, eta may cause the solution to be ill conditioned.

Trans-dimensional Bayesian inversion of airborne electromagnetic data for 2D conductivity profiles

NASA Astrophysics Data System (ADS)

Hawkins, Rhys; Brodie, Ross C.; Sambridge, Malcolm

2018-02-01

This paper presents the application of a novel trans-dimensional sampling approach to a time domain airborne electromagnetic (AEM) inverse problem to solve for plausible conductivities of the subsurface. Geophysical inverse field problems, such as time domain AEM, are well known to have a large degree of non-uniqueness. Common least-squares optimisation approaches fail to take this into account and provide a single solution with linearised estimates of uncertainty that can result in overly optimistic appraisal of the conductivity of the subsurface. In this new non-linear approach, the spatial complexity of a 2D profile is controlled directly by the data. By examining an ensemble of proposed conductivity profiles it accommodates non-uniqueness and provides more robust estimates of uncertainties.

A Decade of Genetic and Metabolomic Contributions to Type 2 Diabetes Risk Prediction

PubMed Central

Merino, Jordi; Leong, Aaron; Meigs, James B.

2018-01-01

Purpose of Review The purpose of this review was to summarize and reflect on advances over the past decade in human genetic and metabolomic discovery with particular focus on their contributions to type 2 diabetes (T2D) risk prediction. Recent Findings In the past 10 years, a combination of advances in genotyping efficiency, metabolomic profiling, bio-informatics approaches, and international collaboration have moved T2D genetics and metabolomics from a state of frustration to an abundance of new knowledge. Summary Efforts to control and prevent T2D have failed to stop this global epidemic. New approaches are needed, and although neither genetic nor metabolomic profiling yet have a clear clinical role, the rapid pace of accumulating knowledge offers the possibility for “multi-omic” prediction to improve health. PMID:29103096

Differentiation of mixed biological traces in sexual assaults using DNA fragment analysis

PubMed Central

Apostolov, Аleksandar

2014-01-01

During the investigation of sexual abuse, it is not rare that mixed genetic material from two or more persons is detected. In such cases, successful profiling can be achieved using DNA fragment analysis, resulting in individual genetic profiles of offenders and their victims. This has led to an increase in the percentage of identified perpetrators of sexual offenses. The classic and modified genetic models used, allowed us to refine and implement appropriate extraction, polymerase chain reaction and electrophoretic procedures with individual assessment and approach to conducting research. Testing mixed biological traces using DNA fragment analysis appears to be the only opportunity for identifying perpetrators in gang rapes. PMID:26019514

Heritability of neural reactions to social exclusion and prosocial compensation in middle childhood.

PubMed

van der Meulen, Mara; Steinbeis, Nikolaus; Achterberg, Michelle; van IJzendoorn, Marinus H; Crone, Eveline A

2018-06-07

Experiencing and observing social exclusion and inclusion, as well as prosocial behavior, are important aspects of social relationships in childhood. However, it is currently unknown to what extent these processes and their neural correlates differ in heritability. We investigated influences of genetics and environment on experiencing social exclusion and compensating for social exclusion of others with the Prosocial Cyberball Game using fMRI in a twin sample (aged 7-9; N = 500). Neuroimaging analyses (N = 283) revealed that experiencing possible self-exclusion resulted in activity in inferior frontal gyrus and medial prefrontal cortex, which was influenced by genetics and unique environment. Experiencing self-inclusion was associated with activity in anterior cingulate cortex, insula and striatum, but this was not significantly explained by genetics or shared environment. We found that children show prosocial compensating behavior when observing social exclusion. Prosocial compensating behavior was associated with activity in posterior cingulate cortex/precuneus, and showed unique environmental effects or measurement error at both behavioral and neural level. Together, these findings show that in children neural activation for experiencing possible self-exclusion and self-inclusion, and for displaying prosocial compensating behavior, is accounted for by unique environmental factors and measurement error, with a small genetic effect on possible self-exclusion. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Quantitative trait loci associated with anthracnose resistance in sorghum

USDA-ARS?s Scientific Manuscript database

With an aim to develop a durable resistance to the fungal disease anthracnose, two unique genetic sources of resistance were selected to create genetic mapping populations to identify regions of the sorghum genome that encode anthracnose resistance. A series of quantitative trait loci were identifi...

A modern amplelography: A genetic basis for leaf shape and venation patterning in grape

USDA-ARS?s Scientific Manuscript database

Terroir, the unique interaction between genotype, environment, and culture, is highly refined in domesticated grape (Vitis vinifera). Toward cultivating terroir, the science of ampelography tried to distinguish thousands of grape cultivars without the aid of genetics. This led to sophisticated pheno...

A modern ampelography: A genetic basis for leaf shape and venation patterning in grape

USDA-ARS?s Scientific Manuscript database

Terroir, the unique interaction between genotype, environment, and culture, is highly refined in domesticated grape (Vitis vinifera). Toward cultivating terroir, the science of ampelography tried to distinguish thousands of grape cultivars without the aid of genetics. This led to sophisticated pheno...

Genetic Testing for Autism Spectrum Disorders

ERIC Educational Resources Information Center

Bauer, Sarah C.; Msall, Michael E.

2011-01-01

Children with autism spectrum disorders (ASD) have unique developmental and behavioral phenotypes, and they have specific challenges with communication, social skills, and repetitive behaviors. At this time, no single etiology for ASD has been identified. However, evidence from family studies and linkage analyses suggests that genetic factors play…

Differential Susceptibility to Prevention: GABAergic, Dopaminergic, and Multilocus Effects

ERIC Educational Resources Information Center

Brody, Gene H.; Chen, Yi-fu; Beach, Steven R. H.

2013-01-01

Background: Randomized prevention trials provide a unique opportunity to test hypotheses about the interaction of genetic predispositions with contextual processes to create variations in phenotypes over time. Methods: Using two longitudinal, randomized prevention trials, molecular genetic and alcohol use outcome data were gathered from more than…

Analysis of MYB oncogene in transformed adenoid cystic carcinomas reveals distinct pathways of tumor progression.

PubMed

Costa, Ana F; Altemani, Albina; García-Inclán, Cristina; Fresno, Florentino; Suárez, Carlos; Llorente, José L; Hermsen, Mario

2014-06-01

Adenoid cystic carcinomas can occasionally undergo dedifferentiation, a phenomenon also referred to as high-grade transformation. However, cases of adenoid cystic carcinomas have been described showing transformation to adenocarcinomas that are not poorly differentiated, indicating that high-grade transformation may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form, which may encompass a wide spectrum of carcinomas in terms of aggressiveness. The aim of this study was to gain more insight in the biology of this pathological phenomenon by means of genetic profiling of both histological components. Using microarray comparative genomic hybridization, we compared the genome-wide DNA copy-number changes of the conventional and transformed area of eight adenoid cystic carcinomas with high-grade transformation, comprising four with transformation into moderately differentiated adenocarcinomas and four into poorly differentiated carcinomas. In general, the poorly differentiated carcinoma cases showed a higher total number of copy-number changes than the moderately differentiated adenocarcinoma cases, and this correlated with a worse clinical course. Special attention was given to chromosomal translocation and protein expression of MYB, recently being considered to be an early and major oncogenic event in adenoid cystic carcinomas. Our data showed that the process of high-grade transformation is not always accompanied by an accumulation of genetic alterations; both conventional and transformed components harbored unique genetic alterations, which indicate a parallel progression. Our data further demonstrated that the MYB/NFIB translocation is not necessarily an early event or fundamental for the progression to adenoid cystic carcinoma with high-grade transformation.

Microbial and genomic characterization of Geobacillus thermodenitrificans OS27, a marine thermophile that degrades diverse raw seaweeds.

PubMed

Fujii, Kenta; Tominaga, Yurie; Okunaka, Jyumpei; Yagi, Hisashi; Ohshiro, Takashi; Suzuki, Hirokazu

2018-06-01

Seaweeds are a nonlignocellulosic biomass, but they are often abundant in unique polysaccharides that common microbes can hardly utilize; therefore, polysaccharide degradation is key for the full utilization of seaweed biomass. Here, we isolated 13 thermophiles from seaweed homogenates that had been incubated at high temperature. All of the isolates were Gram-positive and preferentially grew at 60-70 °C. Most formed endospores and were tolerant to seawater salinity. Despite different sources, all isolates were identical regarding 16S rRNA gene sequences and were categorized as Geobacillus thermodenitrificans. Their growth occurred on seaweed polysaccharides with different profiles but required amino acids and/or vitamins, implying that they existed as proliferative cells by utilizing nutrients on seaweed viscous surfaces. Among 13 isolates, strain OS27 was further characterized to show that it can utilize a diverse range of seaweed polysaccharides and hemicelluloses. Notably, strain OS27 degraded raw seaweeds while releasing soluble saccharides. The degradation seemed to depend on enzymes that were extracellularly produced in an inducible manner. The strain could be genetically modified to produce heterologous endoglucanase, providing a transformant that degrades more diverse seaweeds with higher efficiency. The draft sequences of the OS27 genome contained 3766 coding sequences, which included intact genes for 28 glycoside hydrolases and many hypothetical proteins unusual among G. thermodenitrificans. These results suggest that G. thermodenitrificans OS27 serves as a genetic resource for thermostable enzymes to degrade seaweeds and potentially as a microbial platform for high temperature seaweed biorefinery via genetic modification.

Biography Today: Profiles of People of Interest to Young Readers, 1992-1993.

ERIC Educational Resources Information Center

Harris, Laurie Lanzen, Ed.

1992-01-01

This publication presents biographical profiles of people of interest to young readers. The concept is unique in that the subjects profiled are not necessarily people of great or lasting stature. Many are noted writers or public figures who have made important contributions to the current world, but a goodly number of entries are biographies of…

The Uniqueness of Speech among Motor Systems

ERIC Educational Resources Information Center

Kent, Ray

2004-01-01

This paper considers evidence that the speech muscles are unique in their genetic, developmental, functional and phenotypical properties. The literature was reviewed using PubMed, ScienceDirect, ComDisDome and other literature-retrieval systems to identify studies reporting on the craniofacial and laryngeal muscles. Particular emphasis was given…

The relationship between genetic and chemotypic diversity in American ginseng (Panax quinquefolius L.).

PubMed

Schlag, Erin M; McIntosh, Marla S

2013-09-01

Ginseng is one of the world's most important herbals used as an adaptogen and a cure for an impressively large range of ailments. Differences in the medicinal properties of ginseng roots have been attributed to variation in ginsenoside composition. In this study, the association between genetic and chemotypic profiles of wild and cultivated American ginseng (Panax quinquefolius L.) roots grown in Maryland was investigated. Ginseng roots were classified into chemotypes based on their relative composition of Re and Rg1. Genetic profiles of these roots were determined from the analysis of 38 polymorphic RAPD markers and used for a cluster analysis of genetic similarities. The close correspondence between chemotype and genetic cluster provides the first DNA-based evidence for the genetic basis of ginsenoside composition. Results of this research are significant for plant breeding and conservation, phytochemical research, and clinical and pharmacological studies. Also, the correlation between RAPD markers and chemotype indicates the potential to use RAPD markers as a reliable and practical method for identification and certification of ginseng roots. Copyright © 2013 Elsevier Ltd. All rights reserved.

Assessing the genome level diversity of Listeria monocytogenes from contaminated ice cream and environmental samples linked to a listeriosis outbreak in the United States.

PubMed

Chen, Yi; Luo, Yan; Curry, Phillip; Timme, Ruth; Melka, David; Doyle, Matthew; Parish, Mickey; Hammack, Thomas S; Allard, Marc W; Brown, Eric W; Strain, Errol A

2017-01-01

A listeriosis outbreak in the United States implicated contaminated ice cream produced by one company, which operated 3 facilities. We performed single nucleotide polymorphism (SNP)-based whole genome sequencing (WGS) analysis on Listeria monocytogenes from food, environmental and clinical sources, identifying two clusters and a single branch, belonging to PCR serogroup IIb and genetic lineage I. WGS Cluster I, representing one outbreak strain, contained 82 food and environmental isolates from Facility I and 4 clinical isolates. These isolates differed by up to 29 SNPs, exhibited 9 pulsed-field gel electrophoresis (PFGE) profiles and multilocus sequence typing (MLST) sequence type (ST) 5 of clonal complex 5 (CC5). WGS Cluster II contained 51 food and environmental isolates from Facility II, 4 food isolates from Facility I and 5 clinical isolates. Among them the isolates from Facility II and clinical isolates formed a clade and represented another outbreak strain. Isolates in this clade differed by up to 29 SNPs, exhibited 3 PFGE profiles and ST5. The only isolate collected from Facility III belonged to singleton ST489, which was in a single branch separate from Clusters I and II, and was not associated with the outbreak. WGS analyses clustered together outbreak-associated isolates exhibiting multiple PFGE profiles, while differentiating them from epidemiologically unrelated isolates that exhibited outbreak PFGE profiles. The complete genome of a Cluster I isolate allowed the identification and analyses of putative prophages, revealing that Cluster I isolates differed by the gain or loss of three putative prophages, causing the banding pattern differences among all 3 AscI-PFGE profiles observed in Cluster I isolates. WGS data suggested that certain ice cream varieties and/or production lines might have contamination sources unique to them. The SNP-based analysis was able to distinguish CC5 as a group from non-CC5 isolates and differentiate among CC5 isolates from different outbreaks/incidents.

Assessing the genome level diversity of Listeria monocytogenes from contaminated ice cream and environmental samples linked to a listeriosis outbreak in the United States

PubMed Central

Chen, Yi; Luo, Yan; Curry, Phillip; Timme, Ruth; Melka, David; Doyle, Matthew; Parish, Mickey; Hammack, Thomas S.; Allard, Marc W.; Brown, Eric W.; Strain, Errol A.

2017-01-01

A listeriosis outbreak in the United States implicated contaminated ice cream produced by one company, which operated 3 facilities. We performed single nucleotide polymorphism (SNP)-based whole genome sequencing (WGS) analysis on Listeria monocytogenes from food, environmental and clinical sources, identifying two clusters and a single branch, belonging to PCR serogroup IIb and genetic lineage I. WGS Cluster I, representing one outbreak strain, contained 82 food and environmental isolates from Facility I and 4 clinical isolates. These isolates differed by up to 29 SNPs, exhibited 9 pulsed-field gel electrophoresis (PFGE) profiles and multilocus sequence typing (MLST) sequence type (ST) 5 of clonal complex 5 (CC5). WGS Cluster II contained 51 food and environmental isolates from Facility II, 4 food isolates from Facility I and 5 clinical isolates. Among them the isolates from Facility II and clinical isolates formed a clade and represented another outbreak strain. Isolates in this clade differed by up to 29 SNPs, exhibited 3 PFGE profiles and ST5. The only isolate collected from Facility III belonged to singleton ST489, which was in a single branch separate from Clusters I and II, and was not associated with the outbreak. WGS analyses clustered together outbreak-associated isolates exhibiting multiple PFGE profiles, while differentiating them from epidemiologically unrelated isolates that exhibited outbreak PFGE profiles. The complete genome of a Cluster I isolate allowed the identification and analyses of putative prophages, revealing that Cluster I isolates differed by the gain or loss of three putative prophages, causing the banding pattern differences among all 3 AscI-PFGE profiles observed in Cluster I isolates. WGS data suggested that certain ice cream varieties and/or production lines might have contamination sources unique to them. The SNP-based analysis was able to distinguish CC5 as a group from non-CC5 isolates and differentiate among CC5 isolates from different outbreaks/incidents. PMID:28166293

PDE Nozzle Optimization Using a Genetic Algorithm

NASA Technical Reports Server (NTRS)

Billings, Dana; Turner, James E. (Technical Monitor)

2000-01-01

Genetic algorithms, which simulate evolution in natural systems, have been used to find solutions to optimization problems that seem intractable to standard approaches. In this study, the feasibility of using a GA to find an optimum, fixed profile nozzle for a pulse detonation engine (PDE) is demonstrated. The objective was to maximize impulse during the detonation wave passage and blow-down phases of operation. Impulse of each profile variant was obtained by using the CFD code Mozart/2.0 to simulate the transient flow. After 7 generations, the method has identified a nozzle profile that certainly is a candidate for optimum solution. The constraints on the generality of this possible solution remain to be clarified.

Genetic contributions to antisocial personality and behavior: a meta-analytic review from an evolutionary perspective.

PubMed

Ferguson, Christopher J

2010-01-01

Evidence from behavioral genetics supports the conclusion that a significant amount of the variance in antisocial personality and behavior (APB) is due to genetic contributions. Many scientific fields such as psychology, medicine, and criminal justice struggle to incorporate this information with preexisting paradigms that focused exclusively on external or learned etiology of antisocial behavior. The current paper presents a meta-analytic review of behavioral genetic etiological studies of APB. Results indicated that 56% of the variance in APB can be explained through genetic influences, with 11% due to shared non-genetic influences, and 31% due to unique non-genetic influences. This data is discussed in relation to evolutionary psychological theory.

SPECIATION IN MAMMALS AND THE GENETIC SPECIES CONCEPT

PubMed Central

Baker, Robert J.; Bradley, Robert D.

2009-01-01

We define a genetic species as a group of genetically compatible interbreeding natural populations that is genetically isolated from other such groups. This focus on genetic isolation rather than reproductive isolation distinguishes the Genetic Species Concept from the Biological Species Concept. Recognition of species that are genetically isolated (but not reproductively isolated) results in an enhanced understanding of biodiversity and the nature of speciation as well as speciation-based issues and evolution of mammals. We review criteria and methods for recognizing species of mammals and explore a theoretical scenario, the Bateson–Dobzhansky–Muller (BDM) model, for understanding and predicting genetic diversity and speciation in mammals. If the BDM model is operating in mammals, then genetically defined phylogroups would be predicted to occur within species defined by morphology, and phylogroups experiencing stabilizing selection will evolve genetic isolation without concomitant morphological diversification. Such species will be undetectable using classical skin and skull morphology (Morphological Species Concept). Using cytochrome-b data from sister species of mammals recognized by classical morphological studies, we estimated the number of phylogroups that exist within mammalian species and hypothesize that there will be >2,000 currently unrecognized species of mammals. Such an underestimation significantly affects conclusions on the nature of speciation in mammals, barriers associated with evolution of genetic isolation, estimates of biodiversity, design of conservation initiatives, zoonoses, and so on. A paradigm shift relative to this and other speciation-based issues will be needed. Data that will be effective in detecting these “morphologically cryptic genetic species” are genetic, especially DNA-sequence data. Application of the Genetic Species Concept uses genetic data from mitochondrial and nuclear genomes to identify species and species boundaries, the extent to which the integrity of the gene pool is protected, nature of hybridization (if present), and introgression. Genetic data are unique in understanding species because the use of genetic data 1) can quantify genetic divergence from different aspects of the genome (mitochondrial and nuclear genes, protein coding genes, regulatory genes, mobile DNA, microsatellites, chromosomal rearrangements, heterochromatin, etc.); 2) can provide divergence values that increase with time, providing an estimate of time since divergence; 3) can provide a population genetics perspective; 4) is less subject to convergence and parallelism relative to other sets of characters; 5) can identify monophyly, sister taxa, and presence or absence of introgression; and 6) can accurately identify hybrid individuals (kinship and source of hybrid individuals, F1s, backcrosses, direction of hybridization, and in concert with other data identify which hybrids are sterile or fertile). The proposed definition of the Genetic Species Concept is more compatible with a description of biodiversity of mammals than is “reproductively isolated species.” Genetic profiles of mammalian species will result in a genetic description of species and mammalian diversity, and such studies are being accelerated by technological advances that reduce cost and increase speed and efficiency of generating genetic data. We propose that this genetic revolution remain museum- and voucher specimen–based and that new names are based on a holotype (including associated tissues) deposited in an accredited museum. PMID:19890476

Genetic profile for five common variants associated with age-related macular degeneration in densely affected families: a novel analytic approach

PubMed Central

Sobrin, Lucia; Maller, Julian B; Neale, Benjamin M; Reynolds, Robyn C; Fagerness, Jesen A; Daly, Mark J; Seddon, Johanna M

2010-01-01

About 40% of the genetic variance of age-related macular degeneration (AMD) can be explained by a common variation at five common single-nucleotide polymorphisms (SNPs). We evaluated the degree to which these known variants explain the clustering of AMD in a group of densely affected families. We sought to determine whether the actual number of risk alleles at the five variants in densely affected families matched the expected number. Using data from 322 families with AMD, we used a simulation strategy to generate comparison groups of families and determined whether their genetic profile at the known AMD risk loci differed from the observed genetic profile, given the density of disease observed. Overall, the genotypic loads for the five SNPs in the families did not deviate significantly from the genotypic loads predicted by the simulation. However, for a subset of densely affected families, the mean genotypic load in the families was significantly lower than the expected load determined from the simulation. Given that these densely affected families may harbor rare, more penetrant variants for AMD, linkage analyses and resequencing targeting these families may be an effective approach to finding additional implicated genes. PMID:19844262

Behavioral phenotypes of genetic syndromes with intellectual disability: comparison of adaptive profiles.

PubMed

Di Nuovo, Santo; Buono, Serafino

2011-10-30

The study of distinctive and consistent behaviors in the most common genetic syndromes with intellectual disability is useful to explain abnormalities or associated psychiatric disorders. The behavioral phenotypes revealed outcomes totally or partially specific for each syndrome. The aim of our study was to compare similarities and differences in the adaptive profiles of the five most frequent genetic syndromes, i.e. Down syndrome, Williams syndrome, Angelman syndrome, Prader-Willi syndrome, and Fragile-X syndrome (fully mutated), taking into account the relation with chronological age and the overall IQ level. The research was carried out using the Vineland Adaptive Behavior Scale (beside the Wechsler Intelligence scales to obtain IQ) with a sample of 181 persons (107 males and 74 females) showing genetic syndromes and mental retardation. Syndrome-based groups were matched for chronological age and mental age (excluding the Angelman group, presenting with severe mental retardation). Similarities and differences in the adaptive profiles are described, relating them to IQs and maladaptive behaviors. The results might be useful in obtaining a global index of adjustment for the assessment of intellectual disability level as well as for educational guidance and rehabilitative plans. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Molecular and genetic analyses of geographic variation in isolates of Phoma macrostoma used for biological weed control.

PubMed

Zhou, Lecong; Bailey, K L; Chen, C Y; Keri, Mario

2005-01-01

Molecular and genetic approaches were used to evaluate the genetic relatedness among isolates of the fungus Phoma macrostoma Montagne originating from Canada and Europe and to other species in the genus Phoma. Distinct differences were observed in genetic variation among nine species of the genus Phoma. Randomly amplified polymorphic DNA (RAPD) revealed the presence of intraspecific genetic variation among the isolates of P. macrostoma, with the isolates being used for biological weed control being distributed in a distinct phylogenetic cluster. Additional variation within the biocontrol isolate cluster in P. macrostoma was revealed by pulsed field gel electrophoresis (PFGE), which showed that biocontrol isolates generated two different chromosomal profiles, however the profiles did not relate to their Canadian ecozone origin. Mating studies showed that biocontrol isolates of P. macrostoma from Canada did not produce sexual reproductive structures and were incapable of crossing. These studies also confirmed that no obvious differentiation exists among the biocontrol isolates of P. macrostoma from Canadian Ecozones 3 and 4.

Deducing noninductive current profile from surface voltage evolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Litwin, C.; Wukitch, S.; Hershkowitz, N.

Solving the resistive diffusion equation in the presence of a noninductive current source determines the time-evolution of the surface voltage. By inverting the problem the current drive profile can be determined from the surface voltage evolution. We show that under wide range of conditions the deduced profile is unique. If the conductivity profile is known, this method can be employed to infer the noninductive current profile, and, ipso facto, the profile of the total current. We discuss the application of this method to analyze the Alfven wave current drive experiments in Phaedrus-T.

Dissecting Complex Diseases in Complex Populations

PubMed Central

Choudhry, Shweta; Seibold, Max A.; Borrell, Luisa N.; Tang, Hua; Serebrisky, Denise; Chapela, Rocio; Rodriguez-Santana, José R.; Avila, Pedro C.; Ziv, Elad; Rodriguez-Cintron, William; Risch, Neil J.; Burchard, Esteban González

2007-01-01

Asthma is a common but complex respiratory ailment; current data indicate that interaction of genetic and environmental factors lead to its clinical expression. In the United States, asthma prevalence, morbidity, and mortality vary widely among different Latino ethnic groups. The prevalence of asthma is highest in Puerto Ricans, intermediate in Dominicans and Cubans, and lowest in Mexicans and Central Americans. Independently, known socioeconomic, environmental, and genetic differences do not fully account for this observation. One potential explanation is that there may be unique and ethnic-specific gene–environment interactions that can differentially modify risk for asthma in Latino ethnic groups. These gene–environment interactions can be tested using genetic ancestry as a surrogate for genetic risk factors. Latinos are admixed and share varying proportions of African, Native American, and European ancestry. Most Latinos are unaware of their precise ancestry and report their ancestry based on the national origin of their family and their physical appearance. The unavailability of precise ancestry and the genetic complexity among Latinos may complicate asthma research studies in this population. On the other hand, precisely because of this rich mixture of ancestry, Latinos present a unique opportunity to disentangle the clinical, social, environmental, and genetic underpinnings of population differences in asthma prevalence, severity, and bronchodilator drug responsiveness. PMID:17607004

Life-history and habitat features influence the within-river genetic structure of Atlantic salmon.

PubMed

Vähä, Juha-Pekka; Erkinaro, Jaakko; Niemelä, Eero; Primmer, Craig R

2007-07-01

Defining populations and identifying ecological and life-history characteristics affecting genetic structure is important for understanding species biology and hence, for managing threatened or endangered species or populations. In this study, populations of the world's largest indigenous Atlantic salmon (Salmo salar) stock were first inferred using model-based clustering methods, following which life-history and habitat variables best predicting the genetic diversity of populations were identified. This study revealed that natal homing of Atlantic salmon within the Teno River system is accurate at least to the tributary level. Generally, defining populations by main tributaries was observed to be a reasonable approach in this large river system, whereas in the mainstem of the river, the number of inferred populations was fewer than the number of distinct sampling sites. Mainstem and headwater populations were genetically more diverse and less diverged, while each tributary fostered a distinct population with high genetic differentiation and lower genetic diversity. Population structure and variation in genetic diversity among populations were poorly explained by geographical distance. In contrast, age-structure, as estimated by the proportion of multisea-winter spawners, was the most predictive variable in explaining the variation in the genetic diversity of the populations. This observation, being in agreement with theoretical predictions, emphasizes the essence of large multisea-winter females in maintaining the genetic diversity of populations. In addition, the unique genetic diversity of populations, as estimated by private allele richness, was affected by the ease of accessibility of a site, with more difficult to access sites having lower unique genetic diversity. Our results show that despite this species' high capacity for migration, tributaries foster relatively closed populations with little gene flow which will be important to consider when developing management strategies for the system.

Phlebotomy and the Amish Inspired this Geneticist - TCGA

Cancer.gov

Dr. Stacey Gabriel began her career in genetics while working on a rare disease in the Amish. Learn more about her experience witnessing the human element of genetics in this TCGA in Action Researcher Profile.

Tissue-Specific Profiling Reveals Transcriptome Alterations in Arabidopsis Mutants Lacking Morphological Phenotypes[C][W

PubMed Central

Simon, Marissa; Bruex, Angela; Kainkaryam, Raghunandan M.; Zheng, Xiaohua; Huang, Ling; Woolf, Peter J.; Schiefelbein, John

2013-01-01

Traditional genetic analysis relies on mutants with observable phenotypes. Mutants lacking visible abnormalities may nevertheless exhibit molecular differences useful for defining gene function. To examine this, we analyzed tissue-specific transcript profiles from Arabidopsis thaliana transcription factor gene mutants with known roles in root epidermis development, but lacking a single-gene mutant phenotype due to genetic redundancy. We discovered substantial transcriptional changes in each mutant, preferentially affecting root epidermal genes in a manner consistent with the known double mutant effects. Furthermore, comparing transcript profiles of single and double mutants, we observed remarkable variation in the sensitivity of target genes to the loss of one or both paralogous genes, including preferential effects on specific branches of the epidermal gene network, likely reflecting the pathways of paralog subfunctionalization during evolution. In addition, we analyzed the root epidermal transcriptome of the transparent testa glabra2 mutant to clarify its role in the network. These findings provide insight into the molecular basis of genetic redundancy and duplicate gene diversification at the level of a specific gene regulatory network, and they demonstrate the usefulness of tissue-specific transcript profiling to define gene function in mutants lacking informative visible changes in phenotype. PMID:24014549

Same genetic components underlie different measures of sweet taste preference.

PubMed

Keskitalo, Kaisu; Tuorila, Hely; Spector, Tim D; Cherkas, Lynn F; Knaapila, Antti; Silventoinen, Karri; Perola, Markus

2007-12-01

Sweet taste preferences are measured by several often correlated measures. We examined the relative proportions of genetic and environmental effects on sweet taste preference indicators and their mutual correlations. A total of 663 female twins (324 complete pairs, 149 monozygous and 175 dizygous pairs) aged 17-80 y rated the liking and intensity of a 20% (wt/vol) sucrose solution, reported the liking and the use-frequency of 6 sweet foods (sweet desserts, sweets, sweet pastry, ice cream, hard candy, and chocolate), and completed a questionnaire on cravings of sweet foods. The estimated contributions of genetic factors, environmental factors shared by a twin pair, and environmental factors unique to each twin individual to the variance and covariance of the traits were obtained with the use of linear structural equation modeling. Approximately half of the variation in liking for sweet solution and liking and use-frequency of sweet foods (49-53%) was explained by genetic factors, whereas the rest of the variation was due to environmental factors unique to each twin individual. Sweet taste preference-related traits were correlated. Tetravariate modeling showed that the correlation between liking for the sweet solution and liking for sweet foods was due to genetic factors (genetic r = 0.27). Correlations between liking, use-frequency, and craving for sweet foods were due to both genetic and unshared environmental factors. Detailed information on the associations between preference measures is an important intermediate goal in the determination of the genetic components affecting sweet taste preferences.

Utilizing cattle genetic trends to evaluate the robust nature of gene bank collections

USDA-ARS?s Scientific Manuscript database

The National Animal Germplasm Program has developed substantial germplasm collections (>800,000 samples) for more than 300 unique livestock populations or breeds. Gene bank utilization is relatively new to the livestock sector and the long term genetic relevance of such collections has not been docu...

BEGIN Partnership: Using Problem-Based Learning to Teach Genetics & Bioethics

ERIC Educational Resources Information Center

Markowitz, Dina; DuPre, Michael J.; Holt, Susan; Chen, Shaw-Ree; Wischnowski, Michael

2008-01-01

A science education center at a university medical school had grant funding to develop a genetics curriculum unit, but needed a dissemination plan. A statewide science teacher organization that provided professional development training was facing decreased funding. These two groups combined their efforts, and created a unique partnership, called…

Genetic Characterization of Providence Virus Isolated from Bat Guano in Hungary

PubMed Central

Kemenesi, Gábor; Földes, Fanni; Zana, Brigitta; Kurucz, Kornélia; Estók, Péter; Boldogh, Sándor; Görföl, Tamás; Bányai, Krisztián; Oldal, Miklós

2016-01-01

We report the complete genome sequence and genetic characterization of a novel strain of Providence virus, detected in Barbastella barbastellus bat guano, collected in Hungary in 2014. Our data may facilitate the understanding of the evolutionary processes of this unique viral family of Carmotetraviridae. PMID:27198029

Molecular Characterization of Cultivated Pawpaw (Asimina triloba) Using RAPD Markers

Treesearch

Hongwen Huang; Desmond R. Layne; Thomas L. Kubisiak

2003-01-01

Thirty-four extant pawpaw [Asimina triloba (L.) Dunal] cultivars and advanced selections representing a large portion of the gene pool of cultivated pawpaws were investigated using 71 randomly amplified polymorphic DNA (RAPD) markers to establish genetic identities and evaluate genetic relatedness. All 34 cultivated pawpaws were uniquely...

Important Hawaiian tree species in need of genetic conservation

Treesearch

Robert D. Hauff

2017-01-01

Resource managers in Hawaii face unique forest conservation challenges. Invasive species continue to inundate the remote island archipelago, directly threatening its forest resources. Hawaii has the largest number (> 400) of endangered plants in the United States, and managers use genetic approaches to preserve these small populations which are often island...

Chemical-genetic profile analysis in yeast suggests that a previously uncharacterized open reading frame, YBR261C, affects protein synthesis

PubMed Central

Alamgir, Md; Eroukova, Veronika; Jessulat, Matthew; Xu, Jianhua; Golshani, Ashkan

2008-01-01

Background Functional genomics has received considerable attention in the post-genomic era, as it aims to identify function(s) for different genes. One way to study gene function is to investigate the alterations in the responses of deletion mutants to different stimuli. Here we investigate the genetic profile of yeast non-essential gene deletion array (yGDA, ~4700 strains) for increased sensitivity to paromomycin, which targets the process of protein synthesis. Results As expected, our analysis indicated that the majority of deletion strains (134) with increased sensitivity to paromomycin, are involved in protein biosynthesis. The remaining strains can be divided into smaller functional categories: metabolism (45), cellular component biogenesis and organization (28), DNA maintenance (21), transport (20), others (38) and unknown (39). These may represent minor cellular target sites (side-effects) for paromomycin. They may also represent novel links to protein synthesis. One of these strains carries a deletion for a previously uncharacterized ORF, YBR261C, that we term TAE1 for Translation Associated Element 1. Our focused follow-up experiments indicated that deletion of TAE1 alters the ribosomal profile of the mutant cells. Also, gene deletion strain for TAE1 has defects in both translation efficiency and fidelity. Miniaturized synthetic genetic array analysis further indicates that TAE1 genetically interacts with 16 ribosomal protein genes. Phenotypic suppression analysis using TAE1 overexpression also links TAE1 to protein synthesis. Conclusion We show that a previously uncharacterized ORF, YBR261C, affects the process of protein synthesis and reaffirm that large-scale genetic profile analysis can be a useful tool to study novel gene function(s). PMID:19055778

Chemical-genetic profile analysis in yeast suggests that a previously uncharacterized open reading frame, YBR261C, affects protein synthesis.

PubMed

Alamgir, Md; Eroukova, Veronika; Jessulat, Matthew; Xu, Jianhua; Golshani, Ashkan

2008-12-03

Functional genomics has received considerable attention in the post-genomic era, as it aims to identify function(s) for different genes. One way to study gene function is to investigate the alterations in the responses of deletion mutants to different stimuli. Here we investigate the genetic profile of yeast non-essential gene deletion array (yGDA, approximately 4700 strains) for increased sensitivity to paromomycin, which targets the process of protein synthesis. As expected, our analysis indicated that the majority of deletion strains (134) with increased sensitivity to paromomycin, are involved in protein biosynthesis. The remaining strains can be divided into smaller functional categories: metabolism (45), cellular component biogenesis and organization (28), DNA maintenance (21), transport (20), others (38) and unknown (39). These may represent minor cellular target sites (side-effects) for paromomycin. They may also represent novel links to protein synthesis. One of these strains carries a deletion for a previously uncharacterized ORF, YBR261C, that we term TAE1 for Translation Associated Element 1. Our focused follow-up experiments indicated that deletion of TAE1 alters the ribosomal profile of the mutant cells. Also, gene deletion strain for TAE1 has defects in both translation efficiency and fidelity. Miniaturized synthetic genetic array analysis further indicates that TAE1 genetically interacts with 16 ribosomal protein genes. Phenotypic suppression analysis using TAE1 overexpression also links TAE1 to protein synthesis. We show that a previously uncharacterized ORF, YBR261C, affects the process of protein synthesis and reaffirm that large-scale genetic profile analysis can be a useful tool to study novel gene function(s).

Generation of novel pharmacogenomic candidates in the response to methotrexate in juvenile idiopathic arthritis: correlation between gene expression and genotype

PubMed Central

Moncrieffe, Halima; Hinks, Anne; Ursu, Simona; Kassoumeri, Laura; Etheridge, Angela; Hubank, Mike; Martin, Paul; Weiler, Tracey; Glass, David N; Thompson, Susan D.; Thomson, Wendy; Wedderburn, Lucy R

2010-01-01

Objectives Little is known about mechanisms of efficacy of methotrexate (MTX) in childhood arthritis, or genetic influences upon response to MTX. The aims of this study were to use gene expression profiling to identify novel pathways/genes altered by MTX and then investigate these genes for genotype associations with response to MTX treatment. Methods Gene expression profiling before and after MTX treatment was performed on 11 children with juvenile idiopathic arthritis (JIA) treated with MTX, in whom response at 6 months of treatment was defined. Genes showing the most differential gene expression after treatment were selected for SNP genotyping. Genotype frequencies were compared between non-responders and responders (ACR-Ped70). An independent cohort was available for validation. Results Gene expression profiling before and after MTX treatment revealed 1222 differentially expressed probes sets (fold change >1.7, p< 0.05) and 1065 when restricted to full responder cases only. Six highly differentially expressed genes were analysed for genetic association to response to MTX. Three SNPs in the SLC16A7 gene showed significant association with MTX response. One SNP showed validated association in an independent cohort. Conclusions This study is the first, to our knowledge, to evaluate gene expression profiles in children with JIA before and after MTX, and to analyse genetic variation in differentially expressed genes. We have identified a gene which may contribute to genetic variability in MTX response in JIA, and established as proof of principle that genes which are differentially expressed at mRNA level after drug administration may also be good candidates for genetic analysis. PMID:20827233

Leishmania major: Genetic Profiles of the Parasites Isolated from Chabahar, Southeastern Iran by PPIP-PCR

PubMed Central

SHARIFI-RAD, Mehdi; DABIRZADEH, Mansour; SHARIFI, Iraj; BABAEI, Zahra

2016-01-01

Background: Leishmaniasis is important vector-borne parasitic disease worldwide, caused by the genus Leishmania. The objective of the current study was to identify genetic polymorphism in L. major, one of the species causing cutaneous leishmaniasis (CL), isolated from southeastern Iran, using Permissively Primed Intergenic Polymorphic-Polymerase Chain Reaction (PPIP-PCR) method. Methods: Overall, 340 patients with suspected CL were examined. They referred to the Central Laboratory in Chabahar, Iran during Apr 2013 to Feb 2014. Microscopic examination of Giemsa-stained slides from lesions as well as aspirates cultured in Novy- Mac Neal-Nicolle (NNN) Media was employed in order to diagnose CL in these patients. Our analyses detected 86 suspected subjects as having CL from which 35 isolates were cultured successfully. PPIP-PCR method was performed on extracted genomic DNA from selected isolates in order to determine the genetic polymorphism among L. major isolates. Results: The electrophoresis patterns demonstrated two genetic profiles including A or A1 patterns between all samples tested. Frequency of A and A1 sub-types were 33 (94.3%) and two (5.7%), respectively. Conclusion: Both host and parasite factors may contribute to the clinical profile of human leishmaniasis in the endemic foci of the disease. Here we showed that genetic variations pertaining to the Leishmania parasites might determine, in part, the clinical outcomes of human leishmaniasis. PMID:28127333

Common Genetic Variants Alter Metabolism and Influence Dietary Choline Requirements.

PubMed

Ganz, Ariel B; Klatt, Kevin C; Caudill, Marie A

2017-08-04

Nutrient needs, including those of the essential nutrient choline, are a population wide distribution. Adequate Intake (AI) recommendations for dietary choline (put forth by the National Academies of Medicine to aid individuals and groups in dietary assessment and planning) are grouped to account for the recognized unique needs associated with age, biological sex, and reproductive status (i.e., pregnancy or lactation). Established and emerging evidence supports the notion that common genetic variants are additional factors that substantially influence nutrient requirements. This review summarizes the genetic factors that influence choline requirements and metabolism in conditions of nutrient deprivation, as well as conditions of nutrient adequacy, across biological sexes and reproductive states. Overall, consistent and strong associative evidence demonstrates that common genetic variants in choline and folate pathway enzymes impact the metabolic handling of choline and the risk of nutrient inadequacy across varied dietary contexts. The studies characterized in this review also highlight the substantial promise of incorporating common genetic variants into choline intake recommendations to more precisely target the unique nutrient needs of these subgroups within the broader population. Additional studies are warranted to facilitate the translation of this evidence to nutrigenetics-based dietary approaches.

Common Genetic Variants Alter Metabolism and Influence Dietary Choline Requirements

PubMed Central

Ganz, Ariel B.; Klatt, Kevin C.; Caudill, Marie A.

2017-01-01

Nutrient needs, including those of the essential nutrient choline, are a population wide distribution. Adequate Intake (AI) recommendations for dietary choline (put forth by the National Academies of Medicine to aid individuals and groups in dietary assessment and planning) are grouped to account for the recognized unique needs associated with age, biological sex, and reproductive status (i.e., pregnancy or lactation). Established and emerging evidence supports the notion that common genetic variants are additional factors that substantially influence nutrient requirements. This review summarizes the genetic factors that influence choline requirements and metabolism in conditions of nutrient deprivation, as well as conditions of nutrient adequacy, across biological sexes and reproductive states. Overall, consistent and strong associative evidence demonstrates that common genetic variants in choline and folate pathway enzymes impact the metabolic handling of choline and the risk of nutrient inadequacy across varied dietary contexts. The studies characterized in this review also highlight the substantial promise of incorporating common genetic variants into choline intake recommendations to more precisely target the unique nutrient needs of these subgroups within the broader population. Additional studies are warranted to facilitate the translation of this evidence to nutrigenetics-based dietary approaches. PMID:28777294

Design of a Family Study Among High-Risk Caribbean Hispanics: The Northern Manhattan Family Study

PubMed Central

Sacco, Ralph L.; Sabala, Edison A.; Rundek, Tanja; Juo, Suh-Hang Hank; Huang, Jinaping Sam; DiTullio, Marco; Homma, Shunichi; Almonte, Katihurka; Lithgow, Carlos García; Boden-Albala, Bernadette

2008-01-01

Stroke continues to kill disproportionately more Blacks and Hispanics than Whites in the United States. Racial/ethnic variations in the incidence of stroke and prevalence of stroke risk factors are probably explained by both genetic and environmental influences. Family studies can help identify genetic predisposition to stroke and potential stroke precursors. Few studies have evaluated the heritability of these stroke risk factors among non-White populations, and none have focused on Caribbean Hispanic populations. The aim of the Northern Manhattan Family Study (NOMAFS) is to investigate the gene-environment interaction of stroke risk factors among Caribbean Hispanics. The unique recruitment and methodologic approaches used in this study are relevant to the design and conduct of genetic aggregation studies to investigate complex genetic disorders in non-White populations. The aim of this paper is to describe the NOMAFS and report enrollment and characteristics of the participants. The NO-MAFS will provide a data resource for the exploration of the genetic determinants of highly heritable stroke precursor phenotypes that are less complex than the stroke phenotype. Understanding the gene environment interaction is the critical next step toward the development of new and unique approaches to disease prevention and interventions. PMID:17682370

Molecular Characterization and Phylogenetic Analysis of Pseudomonas aeruginosa Isolates Recovered from Greek Aquatic Habitats Implementing the Double-Locus Sequence Typing Scheme.

PubMed

Pappa, Olga; Beloukas, Apostolos; Vantarakis, Apostolos; Mavridou, Athena; Kefala, Anastasia-Maria; Galanis, Alex

2017-07-01

The recently described double-locus sequence typing (DLST) scheme implemented to deeply characterize the genetic profiles of 52 resistant environmental Pseudomonas aeruginosa isolates deriving from aquatic habitats of Greece. DLST scheme was able not only to assign an already known allelic profile to the majority of the isolates but also to recognize two new ones (ms217-190, ms217-191) with high discriminatory power. A third locus (oprD) was also used for the molecular typing, which has been found to be fundamental for the phylogenetic analysis of environmental isolates given the resulted increased discrimination between the isolates. Additionally, the circulation of acquired resistant mechanisms in the aquatic habitats according to their genetic profiles was proved to be more extent. Hereby, we suggest that the combination of the DLST to oprD typing can discriminate phenotypically and genetically related environmental P. aeruginosa isolates providing reliable phylogenetic analysis at a local level.

Genetic Relationships among Different Chemotypes of Lupinus sulphureus.

PubMed

Cook, Daniel; Mott, Ivan W; Larson, Steven R; Lee, Stephen T; Johnson, Robert; Stonecipher, Clinton A

2018-02-28

Lupines (Lupinus spp.) are a common plant legume species found on western U.S. rangelands. Lupinus spp. may contain quinolizidine and/or piperidine alkaloids that can be toxic and/or teratogenic to grazing livestock. Alkaloid profiles may vary between and within a species. The objectives of this study were to (1) further explore the characteristic alkaloid profiles of Lupinus sulphureus using field collections and (2) explore the phylogenetic relationship of the different populations and chemotypes of L. sulphureus using the amplified fragment length polymorphism method of DNA fingerprinting, thus providing possible explanations to the phenomena of multiple chemotypes within a species. A total of 49 accessions of L. sulphureus were classified into seven chemotypes. The DNA profiles showed that one L. sulphureus chemotype, chemotype A, is genetically divergent from the other chemotypes of L. sulphureus, suggesting that it represents an unresolved lupine taxon, possibly a new lupine species. Additionally, the different chemotypes of L. sulphureus represented different genetic groups, as shown by Bayesian cluster analysis and principle component analysis.

Unique Trichomonas vaginalis gene sequences identified in multinational regions of Northwest China.

PubMed

Liu, Jun; Feng, Meng; Wang, Xiaolan; Fu, Yongfeng; Ma, Cailing; Cheng, Xunjia

2017-07-24

Trichomonas vaginalis (T. vaginalis) is a flagellated protozoan parasite that infects humans worldwide. This study determined the sequence of the 18S ribosomal RNA gene of T. vaginalis infecting both females and males in Xinjiang, China. Samples from 73 females and 28 males were collected and confirmed for infection with T. vaginalis, a total of 110 sequences were identified when the T. vaginalis 18S ribosomal RNA gene was sequenced. These sequences were used to prepare a phylogenetic network. The rooted network comprised three large clades and several independent branches. Most of the Xinjiang sequences were in one group. Preliminary results suggest that Xinjiang T. vaginalis isolates might be genetically unique, as indicated by the sequence of their 18S ribosomal RNA gene. Low migration rate of local people in this province may contribute to a genetic conservativeness of T. vaginalis. The unique genetic feature of our isolates may suggest a different clinical presentation of trichomoniasis, including metronidazole susceptibility, T. vaginalis virus or Mycoplasma co-infection characteristics. The transmission and evolution of Xinjiang T. vaginalis is of interest and should be studied further. More attention should be given to T. vaginalis infection in both females and males in Xinjiang.

Protein-based forensic identification using genetically variant peptides in human bone.

PubMed

Mason, Katelyn Elizabeth; Anex, Deon; Grey, Todd; Hart, Bradley; Parker, Glendon

2018-04-22

Bone tissue contains organic material that is useful for forensic investigations and may contain preserved endogenous protein that can persist in the environment for extended periods of time over a range of conditions. Single amino acid polymorphisms in these proteins reflect genetic information since they result from non-synonymous single nucleotide polymorphisms (SNPs) in DNA. Detection of genetically variant peptides (GVPs) - those peptides that contain amino acid polymorphisms - in digests of bone proteins allows for the corresponding SNP alleles to be inferred. Resulting genetic profiles can be used to calculate statistical measures of association between a bone sample and an individual. In this study proteomic analysis on rib cortical bone samples from 10 recently deceased individuals demonstrates this concept. A straight-forward acidic demineralization protocol yielded proteins that were digested with trypsin. Tryptic digests were analyzed by liquid chromatography mass spectrometry. A total of 1736 different proteins were identified across all resulting datasets. On average, individual samples contained 454±121 (x¯±σ) proteins. Thirty-five genetically variant peptides were identified from 15 observed proteins. Overall, 134 SNP inferences were made based on proteomically detected GVPs, which were confirmed by sequencing of subject DNA. Inferred individual SNP genetic profiles ranged in random match probability (RMP) from 1/6 to 1/42,472 when calculated with European population frequencies in the 1000 Genomes Project, Phase 3. Similarly, RMPs based on African population frequencies were calculated for each SNP genetic profile and likelihood ratios (LR) were obtained by dividing each European RMP by the corresponding African RMP. Resulting LR values ranged from 1.4 to 825 with a median value of 16. GVP markers offer a basis for the identification of compromised skeletal remains independent of the presence of DNA template. Published by Elsevier B.V.

Genetic analysis of predicted fatty acid profiles of milk from Danish Holstein and Danish Jersey cattle populations.

PubMed

Hein, L; Sørensen, L P; Kargo, M; Buitenhuis, A J

2018-03-01

The objective of this study was to assess the genetic variability of the detailed fatty acid (FA) profiles of Danish Holstein (DH) and Danish Jersey (DJ) cattle populations. We estimated genetic parameters for 11 FA or groups of FA in milk samples from the Danish milk control system between May 2015 and October 2016. Concentrations of different FA and FA groups in milk samples were measured by mid-infrared spectroscopy. Data used for parameter estimation were from 132,732 first-parity DH cows and 21,966 first-parity DJ cows. We found the highest heritabilities for test day measurements in both populations for short-chain FA (DH = 0.16; DJ = 0.16) and C16:0 (DH = 0.14; DJ = 0.16). In DH, the highest heritabilities were also found for saturated FA and monounsaturated FA (both populations: 0.15). Genetic correlations between the fatty acid traits showed large differences between DH and DJ for especially short-chain FA with the other FA traits measured. Furthermore, genetic correlations of total fat with monounsaturated FA, polyunsaturated FA, short-chain FA, and C16:0 differed markedly between DH and DJ populations. In conclusion, we found genetic variation in the mid-infrared spectroscopy-predicted FA and FA groups of the DH and DJ cattle populations. This finding opens the possibility of using genetic selection to change the FA profiles of dairy cattle. The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Climate-driven range shifts explain the distribution of extant gene pools and predict future loss of unique lineages in a marine brown alga.

PubMed

Assis, J; Serrão, E A; Claro, B; Perrin, C; Pearson, G A

2014-06-01

The climate-driven dynamics of species ranges is a critical research question in evolutionary ecology. We ask whether present intraspecific diversity is determined by the imprint of past climate. This is an ongoing debate requiring interdisciplinary examination of population genetic pools and persistence patterns across global ranges. Previously, contrasting inferences and predictions have resulted from distinct genomic coverage and/or geographical information. We aim to describe and explain the causes of geographical contrasts in genetic diversity and their consequences for the future baseline of the global genetic pool, by comparing present geographical distribution of genetic diversity and differentiation with predictive species distribution modelling (SDM) during past extremes, present time and future climate scenarios for a brown alga, Fucus vesiculosus. SDM showed that both atmospheric and oceanic variables shape the global distribution of intertidal species, revealing regions of persistence, extinction and expansion during glacial and postglacial periods. These explained the distribution and structure of present genetic diversity, consisting of differentiated genetic pools with maximal diversity in areas of long-term persistence. Most of the present species range comprises postglacial expansion zones and, in contrast to highly dispersive marine organisms, expansions involved only local fronts, leaving distinct genetic pools at rear edges. Besides unravelling a complex phylogeographical history and showing congruence between genetic diversity and persistent distribution zones, supporting the hypothesis of niche conservatism, range shifts and loss of unique genetic diversity at the rear edge were predicted for future climate scenarios, impoverishing the global gene pool. © 2014 John Wiley & Sons Ltd.

Genetic Algorithm for Opto-thermal Skin Hydration Depth Profiling Measurements

NASA Astrophysics Data System (ADS)

Cui, Y.; Xiao, Perry; Imhof, R. E.

2013-09-01

Stratum corneum is the outermost skin layer, and the water content in stratum corneum plays a key role in skin cosmetic properties as well as skin barrier functions. However, to measure the water content, especially the water concentration depth profile, within stratum corneum is very difficult. Opto-thermal emission radiometry, or OTTER, is a promising technique that can be used for such measurements. In this paper, a study on stratum corneum hydration depth profiling by using a genetic algorithm (GA) is presented. The pros and cons of a GA compared against other inverse algorithms such as neural networks, maximum entropy, conjugate gradient, and singular value decomposition will be discussed first. Then, it will be shown how to use existing knowledge to optimize a GA for analyzing the opto-thermal signals. Finally, these latest GA results on hydration depth profiling of stratum corneum under different conditions, as well as on the penetration profiles of externally applied solvents, will be shown.

Sampling Soil for Characterization and Site Description

NASA Technical Reports Server (NTRS)

Levine, Elissa

1999-01-01

The sampling scheme for soil characterization within the GLOBE program is uniquely different from the sampling methods of the other protocols. The strategy is based on an understanding of the 5 soil forming factors (parent material, climate, biota, topography, and time) at each study site, and how each of these interact to produce a soil profile with unique characteristics and unique input and control into the atmospheric, biological, and hydrological systems. Soil profile characteristics, as opposed to soil moisture and temperature, vegetative growth, and atmospheric and hydrologic conditions, change very slowly, depending on the parameter being measured, ranging from seasonally to many thousands of years. Thus, soil information, including profile description and lab analysis, is collected only one time for each profile at a site. These data serve two purposes: 1) to supplement existing spatial information about soil profile characteristics across the landscape at local, regional, and global scales, and 2) to provide specific information within a given area about the basic substrate to which elements within the other protocols are linked. Because of the intimate link between soil properties and these other environmental elements, the static soil properties at a given site are needed to accurately interpret and understand the continually changing dynamics of soil moisture and temperature, vegetation growth and phenology, atmospheric conditions, and chemistry and turbidity in surface waters. Both the spatial and specific soil information can be used for modeling purposes to assess and make predictions about global change.

The clinical genetics of phaeochromocytoma and paraganglioma.

PubMed

Kavinga Gunawardane, P T; Grossman, Ashley

2017-10-01

Phaeochromocytoma and paraganglioma are rare catecholamine-producing tumours, recognised to have one of the richest hereditary backgrounds of all neoplasms, with germline mutations seen in approximately 30% of patients. They can be a part of genetic syndromes such as MEN 2 or Neurofibromatosis type 1, or can be found as apparently sporadic tumours. Germline mutations are almost always found in syndromic patients. Nonetheless, apparently sporadic phaeochromocytoma too show high germline mutation rates. Early detection of a genetic mutation can lead to early diagnosis of further tumours via surveillance, early treatment and better prognosis. Apart from this, the genetic profile has important relevance for tumour location and biochemical profile, and can be a useful predictor of future tumour behaviour. It also enables family screening and surveillance. Moreover, recent studies have demonstrated significant driver somatic mutations in up to 75% of all tumours. Arch Endocrinol Metab. 2017;61(5):490-500.

Unique autosomal recessive variant of palmoplantar keratoderma associated with hearing loss not caused by known mutations*

PubMed Central

Hegazi, Moustafa Abdelaal; Manou, Sommen; Sakr, Hazem; Camp, Guy Van

2017-01-01

Inherited Palmoplantar Keratodermas are rare disorders of genodermatosis that are conventionally regarded as autosomal dominant in inheritance with extensive clinical and genetic heterogeneity. This is the first report of a unique autosomal recessive Inherited Palmoplantar keratoderma - sensorineural hearing loss syndrome which has not been reported before in 3 siblings of a large consanguineous family. The patients presented unique clinical features that were different from other known Inherited Palmoplantar Keratodermas - hearing loss syndromes. Mutations in GJB2 or GJB6 and the mitochondrial A7445G mutation, known to be the major causes of diverse Inherited Palmoplantar Keratodermas -hearing loss syndromes were not detected by Sanger sequencing. Moreover, the pathogenic mutation could not be identified using whole exome sequencing. Other known Inherited Palmoplantar keratoderma syndromes were excluded based on both clinical criteria and genetic analysis. PMID:29267478

Modular assembly of transposable element arrays by microsatellite targeting in the guayule and rice genomes.

PubMed

Valdes Franco, José A; Wang, Yi; Huo, Naxin; Ponciano, Grisel; Colvin, Howard A; McMahan, Colleen M; Gu, Yong Q; Belknap, William R

2018-04-19

Guayule (Parthenium argentatum A. Gray) is a rubber-producing desert shrub native to Mexico and the United States. Guayule represents an alternative to Hevea brasiliensis as a source for commercial natural rubber. The efficient application of modern molecular/genetic tools to guayule improvement requires characterization of its genome. The 1.6 Gb guayule genome was sequenced, assembled and annotated. The final 1.5 Gb assembly, while fragmented (N 50  = 22 kb), maps > 95% of the shotgun reads and is essentially complete. Approximately 40,000 transcribed, protein encoding genes were annotated on the assembly. Further characterization of this genome revealed 15 families of small, microsatellite-associated, transposable elements (TEs) with unexpected chromosomal distribution profiles. These SaTar (Satellite Targeted) elements, which are non-autonomous Mu-like elements (MULEs), were frequently observed in multimeric linear arrays of unrelated individual elements within which no individual element is interrupted by another. This uniformly non-nested TE multimer architecture has not been previously described in either eukaryotic or prokaryotic genomes. Five families of similarly distributed non-autonomous MULEs (microsatellite associated, modularly assembled) were characterized in the rice genome. Families of TEs with similar structures and distribution profiles were identified in sorghum and citrus. The sequencing and assembly of the guayule genome provides a foundation for application of current crop improvement technologies to this plant. In addition, characterization of this genome revealed SaTar elements with distribution profiles unique among TEs. Satar targeting appears based on an alternative MULE recombination mechanism with the potential to impact gene evolution.

A Specific Pathway Can Be Identified between Genetic Characteristics and Behaviour Profiles in Prader-Willi Syndrome via Cognitive, Environmental and Physiological Mechanisms

ERIC Educational Resources Information Center

Woodcock, K. A.; Oliver, C.; Humphreys, G. W.

2009-01-01

Background: Behavioural phenotypes associated with genetic syndromes have been extensively investigated in order to generate rich descriptions of phenomenology, determine the degree of specificity of behaviours for a particular syndrome, and examine potential interactions between genetic predispositions for behaviour and environmental influences.…

Profiling Lipid Metabolites Yields Unique Information on Sex- and Time-dependent Responses of Fathead Minnows (Pimephales promelas) Exposed to 17α-Ethynylestradiol

EPA Science Inventory

Alterations in hepatic lipid profiles of fathead minnows (FHM) exposed to the synthetic estrogen 17α-ethynylestradiol (EE2) were determined using 1H-NMR spectroscopy-based metabolite profiling. The exposures were conducted using either 10 ng/l or 100 ng/l EE2 via a continuous flo...

Phosphodiesterase type 5 and cancers: progress and challenges

PubMed Central

Barone, Ines; Giordano, Cinzia; Bonofiglio, Daniela; Andò, Sebastiano; Catalano, Stefania

2017-01-01

Cancers are an extraordinarily heterogeneous collection of diseases with distinct genetic profiles and biological features that directly influence response patterns to various treatment strategies as well as clinical outcomes. Nevertheless, our growing understanding of cancer cell biology and tumor progression is gradually leading towards rational, tailored medical treatments designed to destroy cancer cells by exploiting the unique cellular pathways that distinguish them from normal healthy counterparts. Recently, inhibition of the activity of phosphodiesterase type 5 (PDE5) is emerging as a promising approach to restore normal intracellular cyclic guanosine monophosphate (cGMP) signalling, and thereby resulting into the activation of various downstream molecules to inhibit proliferation, motility and invasion of certain cancer cells. In this review, we present an overview of the experimental and clinical evidences highlighting the role of PDE5 in the pathogenesis and prevention of various malignancies. Current data are still not sufficient to draw conclusive statements for cancer patient management, but could provide further rational for testing PDE5-targeting drugs as anticancer agents in clinical settings. PMID:29228762

What the Aspergillus genomes have told us.

PubMed

Nierman, W C; May, G; Kim, H S; Anderson, M J; Chen, D; Denning, D W

2005-05-01

The sequencing and annotation of the genomes of the first strains of Aspergillus nidulans, Aspergillus oryzae, and Aspergillus fumigatus will be seen in retrospect as a transformational event in Aspergillus biology. With this event the entire genetic composition of A. nidulans, the sexual experimental model organism of the genus Aspergillus, A. oryzae, the food biotechnology organism which is the product of centuries of cultivation, and A. fumigatus, the most common causative agent of invasive aspergillosis is now revealed to the extent that we are at present able to understand. Each genome exhibits a large set of genes common to the three as well as a much smaller set of genes unique to each. Moreover, these sequences serve as resources providing the major tool to expanding our understanding of the biology of each. Transcription profiling of A. fumigatus at high temperatures and comparative genomic hybridization between A. fumigatus and a closely related Aspergillus species provides microarray based examples of the beginning of functional analysis of the genomes of these organisms going forward from the genome sequence.

klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis

PubMed Central

Steed, Emily; Faggianelli, Nathalie; Roth, Stéphane; Ramspacher, Caroline; Concordet, Jean-Paul; Vermot, Julien

2016-01-01

The heartbeat and blood flow signal to endocardial cell progenitors through mechanosensitive proteins that modulate the genetic program controlling heart valve morphogenesis. To date, the mechanism by which mechanical forces coordinate tissue morphogenesis is poorly understood. Here we use high-resolution imaging to uncover the coordinated cell behaviours leading to heart valve formation. We find that heart valves originate from progenitors located in the ventricle and atrium that generate the valve leaflets through a coordinated set of endocardial tissue movements. Gene profiling analyses and live imaging reveal that this reorganization is dependent on extracellular matrix proteins, in particular on the expression of fibronectin1b. We show that blood flow and klf2a, a major endocardial flow-responsive gene, control these cell behaviours and fibronectin1b synthesis. Our results uncover a unique multicellular layering process leading to leaflet formation and demonstrate that endocardial mechanotransduction and valve morphogenesis are coupled via cellular rearrangements mediated by fibronectin synthesis. PMID:27221222

Stakeholder views on returning research results.

PubMed

Haga, Susanne B; Zhao, Jennifer Q

2013-01-01

While the disclosure of research findings is relevant to all types of biomedical research, it has garnered particular attention with respect to genetics and genomics research due to some of the unique aspects of the data and the high public profile of the field. In this chapter, we review the attitudes of stakeholders (research participants, policymakers, and researchers) to define areas of consensus regarding the issue of returning research results across and within groups. In addition to stakeholder attitudes about obligations and interest in research results, other major related issues related to returning research results, such as informed consent, communication of research results, and cost, are discussed. Given the consensus between stakeholders to return summary reports of a study's outcomes and individual research results of clinical significance, we conclude that the time has come to encourage, if not require, researchers to consider these issues in the developmental planning stages of a project and to plan and budget accordingly. © 2013 Elsevier Inc. All rights reserved.

Systems Biology-Based Identification of Mycobacterium tuberculosis Persistence Genes in Mouse Lungs

PubMed Central

Dutta, Noton K.; Bandyopadhyay, Nirmalya; Veeramani, Balaji; Lamichhane, Gyanu; Karakousis, Petros C.; Bader, Joel S.

2014-01-01

ABSTRACT Identifying Mycobacterium tuberculosis persistence genes is important for developing novel drugs to shorten the duration of tuberculosis (TB) treatment. We developed computational algorithms that predict M. tuberculosis genes required for long-term survival in mouse lungs. As the input, we used high-throughput M. tuberculosis mutant library screen data, mycobacterial global transcriptional profiles in mice and macrophages, and functional interaction networks. We selected 57 unique, genetically defined mutants (18 previously tested and 39 untested) to assess the predictive power of this approach in the murine model of TB infection. We observed a 6-fold enrichment in the predicted set of M. tuberculosis genes required for persistence in mouse lungs relative to randomly selected mutant pools. Our results also allowed us to reclassify several genes as required for M. tuberculosis persistence in vivo. Finally, the new results implicated additional high-priority candidate genes for testing. Experimental validation of computational predictions demonstrates the power of this systems biology approach for elucidating M. tuberculosis persistence genes. PMID:24549847

Films of Bacteria at Interfaces (FBI): Remodeling of Fluid Interfaces by Pseudomonas aeruginosa.

PubMed

Niepa, Tagbo H R; Vaccari, Liana; Leheny, Robert L; Goulian, Mark; Lee, Daeyeon; Stebe, Kathleen J

2017-12-19

Bacteria at fluid interfaces endure physical and chemical stresses unique to these highly asymmetric environments. The responses of Pseudomonas aeruginosa PAO1 and PA14 to a hexadecane-water interface are compared. PAO1 cells form elastic films of bacteria, excreted polysaccharides and proteins, whereas PA14 cells move actively without forming an elastic film. Studies of PAO1 mutants show that, unlike solid-supported biofilms, elastic interfacial film formation occurs in the absence of flagella, pili, or certain polysaccharides. Highly induced genes identified in transcriptional profiling include those for putative enzymes and a carbohydrate metabolism enzyme, alkB2; this latter gene is not upregulated in PA14 cells. Notably, PAO1 mutants lacking the alkB2 gene fail to form an elastic layer. Rather, they form an active film like that formed by PA14. These findings demonstrate that genetic expression is altered by interfacial confinement, and suggest that the ability to metabolize alkanes may play a role in elastic film formation at oil-water interfaces.

Virology and Molecular Pathogenesis of Human Papillomavirus (HPV)-Associated Oropharyngeal Squamous Cell Carcinoma

PubMed Central

Miller, Daniel L.; Puricelli, Michael D.; Stack, M. Sharon

2012-01-01

Current literature fully supports HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) as a unique clinical entity. It affects an unambiguous patient population with defined risk factors, has a genetic expression pattern more similar to cervical squamous cell carcinoma than non-HPV-associated head and neck squamous cell carcinoma (HNSCC), and may warrant divergent clinical management compared to HNSCC associated with traditional risk factors. However, a detailed understanding of the molecular mechanisms driving these differences and the ability to exploit this knowledge to improve clinical management of OPSCC has not yet come to fruition. This review summarizes the etiology of HPV positive (HPV+) OPSCC and provides a detailed overview of HPV virology and molecular pathogenesis relevant to infection of oropharyngeal tissues. Methods of detection and differential gene expression analyses are also summarized. Future research into mechanisms that mediate tropism of HPV to oropharyngeal tissues, improved detection strategies, and the pathophysiologic significance of altered gene and microRNA expression profiles is warranted. PMID:22452816

Neurogliaform cortical interneurons derive from cells in the preoptic area

PubMed Central

Cadilhac, Christelle; Prados, Julien; Holtmaat, Anthony

2018-01-01

Delineating the basic cellular components of cortical inhibitory circuits remains a fundamental issue in order to understand their specific contributions to microcircuit function. It is still unclear how current classifications of cortical interneuron subtypes relate to biological processes such as their developmental specification. Here we identified the developmental trajectory of neurogliaform cells (NGCs), the main effectors of a powerful inhibitory motif recruited by long-range connections. Using in vivo genetic lineage-tracing in mice, we report that NGCs originate from a specific pool of 5-HT3AR-expressing Hmx3+ cells located in the preoptic area (POA). Hmx3-derived 5-HT3AR+ cortical interneurons (INs) expressed the transcription factors PROX1, NR2F2, the marker reelin but not VIP and exhibited the molecular, morphological and electrophysiological profile of NGCs. Overall, these results indicate that NGCs are a distinct class of INs with a unique developmental trajectory and open the possibility to study their specific functional contribution to cortical inhibitory microcircuit motifs. PMID:29557780

Quinoa starch: Structure, properties, and applications.

PubMed

Li, Guantian; Zhu, Fan

2018-02-01

Quinoa (Chenopodium quinoa Willd.) has gained popularity worldwide largely due to the attractive nutritional profile. It also has much potential for food security due to the great genetic diversity. Starch is the main component of quinoa grain and makes up to 70% of the dry matter. The starch plays a crucial role in functional properties of quinoa and related food products. The starch granules are rather small (∼1-3μm) with relatively low amylose contents as compared with most of the other starches. Quinoa amylopectin has significant amounts of short chains and super-long chains. These unique features have generated research interest in using the starch for food and other applications such as creating Pickering emulsions. This review summarizes the present knowledge of the isolation, composition, granular and molecular structures, physicochemical properties, modifications, and applications of quinoa starch. It becomes obvious that this starch has great potential for food and nonfood applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys.

PubMed

Chen, Yongchang; Yu, Juehua; Niu, Yuyu; Qin, Dongdong; Liu, Hailiang; Li, Gang; Hu, Yingzhou; Wang, Jiaojian; Lu, Yi; Kang, Yu; Jiang, Yong; Wu, Kunhua; Li, Siguang; Wei, Jingkuan; He, Jing; Wang, Junbang; Liu, Xiaojing; Luo, Yuping; Si, Chenyang; Bai, Raoxian; Zhang, Kunshan; Liu, Jie; Huang, Shaoyong; Chen, Zhenzhen; Wang, Shuang; Chen, Xiaoying; Bao, Xinhua; Zhang, Qingping; Li, Fuxing; Geng, Rui; Liang, Aibin; Shen, Dinggang; Jiang, Tianzi; Hu, Xintian; Ma, Yuanye; Ji, Weizhi; Sun, Yi Eve

2017-05-18

Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT. Moreover, blood transcriptome profiling revealed that mutant monkeys resembled RTT patients in immune gene dysregulation. Taken together, the stark similarity in phenotype and/or endophenotype between monkeys and patients suggested that gene-edited RTT founder monkeys would be of value for disease mechanistic studies as well as development of potential therapeutic interventions for RTT. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of an autonomous, wireless pH and temperature sensing system for monitoring pig meat quality.

PubMed

Frisby, June; Raftery, Declan; Kerry, Joe P; Diamond, Dermot

2005-06-01

This paper focuses on the development of a unique wireless pH and temperature monitoring system to assess pig meat quality. Pale, soft and exudative (PSE) pig meat continues to be a major problem in the pig meat industry today. The PSE condition in pork is related to a number of factors including genetics, pre-slaughter stress and insufficient chilling of pig carcasses, which cause a rapid rate of glycolysis post-mortem (<1h). As a result the pH drops to low levels while the muscle temperature is still high. A wireless dual channel system that monitors pH and temperature simultaneously has been developed to provide pH and temperature data of the carcass during the first 24h after slaughter. We have demonstrated that this approach can distinguish in real time, pH and temperature profiles that are 'non-normal', and identify carcasses that are PSE positive quickly and easily.

The science and complexity of bitter taste.

PubMed

Drewnowski, A

2001-06-01

Food choices and eating habits are largely influenced by how foods taste. Without being the dominant taste sensation, bitter taste contributes to the complexity and enjoyment of beverages and foods. Compounds that are perceived as bitter do not share a similar chemical structure. In addition to peptides and salts, bitter compounds in foods may include plant-derived phenols and polyphenols, flavonoids, catechins, and caffeine. Recent studies have shown that humans possess a multitude of bitter taste receptors and that the transduction of bitter taste may differ between one compound and another. Studies of mixture interactions suggest further that bitter compounds suppress or enhance sweet and sour tastes and interact with volatile flavor molecules. Caffeine, a natural ingredient of tea, coffee, and chocolate, has a unique flavor profile. Used as a flavoring agent, it enhances the sensory appeal of beverages. Research developments on the genetics and perception of bitter taste add to our understanding of the role of bitterness in relation to food preference.

Advancing epilepsy treatment through personalized genetic zebrafish models.

PubMed

Griffin, A; Krasniak, C; Baraban, S C

2016-01-01

With an increase in the number of disease causing genetic mutations identified from epilepsy cohorts, zebrafish are proving to be an attractive vertebrate model for functional analysis of these allele variants. Not only do zebrafish have conserved gene functions, but larvae harboring mutations in identified human epileptic genes show spontaneous seizure activity and mimic the convulsive behavioral movements observed in humans. With zebrafish being compatible with medium to high-throughput screening, they are also proving to be a unique and powerful system for early preclinical drug screening, including novel target identification, pharmacology, and toxicology. Additionally, with recent advances in genomic engineering technologies, it is now possible to study the precise pathophysiology of patient-specific gene mutations in zebrafish. The following sections highlight how the unique attributes of zebrafish, in combination with genetic modifications, are continuing to transform our understanding of epilepsy and help identify personalized therapeutics for specific patient cohorts. © 2016 Elsevier B.V. All rights reserved.

Forensic timber identification: a case study of a CITES listed species, Gonystylus bancanus (Thymelaeaceae).

PubMed

Ng, Kevin Kit Siong; Lee, Soon Leong; Tnah, Lee Hong; Nurul-Farhanah, Zakaria; Ng, Chin Hong; Lee, Chai Ting; Tani, Naoki; Diway, Bibian; Lai, Pei Sing; Khoo, Eyen

2016-07-01

Illegal logging and smuggling of Gonystylus bancanus (Thymelaeaceae) poses a serious threat to this fragile valuable peat swamp timber species. Using G. bancanus as a case study, DNA markers were used to develop identification databases at the species, population and individual level. The species level database for Gonystylus comprised of an rDNA (ITS2) and two cpDNA (trnH-psbA and trnL) markers based on a 20 Gonystylus species database. When concatenated, taxonomic species recognition was achieved with a resolution of 90% (18 out of the 20 species). In addition, based on 17 natural populations of G. bancanus throughout West (Peninsular Malaysia) and East (Sabah and Sarawak) Malaysia, population and individual identification databases were developed using cpDNA and STR markers respectively. A haplotype distribution map for Malaysia was generated using six cpDNA markers, resulting in 12 unique multilocus haplotypes, from 24 informative intraspecific variable sites. These unique haplotypes suggest a clear genetic structuring of West and East regions. A simulation procedure based on the composition of the samples was used to test whether a suspected sample conformed to a given regional origin. Overall, the observed type I and II errors of the databases showed good concordance with the predicted 5% threshold which indicates that the databases were useful in revealing provenance and establishing conformity of samples from West and East Malaysia. Sixteen STRs were used to develop the DNA profiling databases for individual identification. Bayesian clustering analyses divided the 17 populations into two main genetic clusters, corresponding to the regions of West and East Malaysia. Population substructuring (K=2) was observed within each region. After removal of bias resulting from sampling effects and population subdivision, conservativeness tests showed that the West and East Malaysia databases were conservative. This suggests that both databases can be used independently for random match probability estimation within respective regions. The reliability of the databases was further determined by independent self-assignment tests based on the likelihood of each individual's multilocus genotype occurring in each identified population, genetic cluster and region with an average percentage of correctly assigned individuals of 54.80%, 99.60% and 100% respectively. Thus, after appropriate validation, the genetic identification databases developed for G. bancanus in this study could support forensic applications and help safeguard this valuable species into the future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Identification of kin structure among Guam rail founders: a comparison of pedigrees and DNA profiles

USGS Publications Warehouse

Haig, Susan M.; Ballou, J.D.; Casna, N.J.

1994-01-01

Kin structure among founders can have a significant effect on subsequent population structure. Here we use the correlation between DNA profile similarity and relatedness calculated from pedigrees to test hypotheses regarding kin structure among founders to the captive Guam rail (Rallus owstoni) population. Five different pedigrees were generated under the following hypotheses: (i) founders are unrelated; (ii) founders are unrelated except for same-nest chicks; (iii) founders from the same major site are siblings; (iv) founders from the same local site are siblings; and (v) founders are related as defined by a UPGMA cluster analysis of DNA similarity data. Relatedness values from pedigrees 1, 2 and 5 had the highest correlation with DNA similarity but the correlation between relatedness and similarity were not significantly different among pedigrees. Pedigree 5 resulted in the highest correlation overall when using only relatedness values that changed as a result of different founder hypotheses. Thus, founders were assigned relatedness based on pedigree 5 because it had the highest correlations with DNA similarity, was the most conservative approach, and incorporated all field data. The analyses indicated that estimating relatedness using DNA profiles remains problematic, therefore we compared mean kinship, a measure of genetic importance, with mean DNA profile similarity to determine if genetic importance among individuals could be determined via use of DNA profiles alone. The significant correlation suggests this method may provide more information about population structure than was previously thought. Thus, DNA profiles can provide a reasonable explanation for founder relatedness and mean DNA profile similarity may be helpful in determining relative genetic importance of individuals when detailed pedigrees are absent.

Investigation of major genetic alterations in neuroblastoma.

PubMed

Costa, Régis Afonso; Seuánez, Héctor N

2018-06-01

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. This malignancy shows a wide spectrum of clinical outcome and its prognosis is conditioned by manifold biological and genetic factors. We investigated the tumor genetic profile and clinical data of 29 patients with NB by multiplex ligation-dependent probe amplification (MLPA) to assess therapeutic risk. In 18 of these tumors, MYCN status was assessed by fluorescence in situ hybridization (FISH). Copy number variation was also determined for confirming MLPA findings in two 6p loci. We found 2p, 7q and 17q gains, and 1p and 11q losses as the most frequent chromosome alterations in this cohort. FISH confirmed all cases of MYCN amplification detected by MLPA. In view of unexpected 6p imbalance, copy number variation of two 6p loci was assessed for validating MLPA findings. Based on clinical data and genetic profiles, patients were stratified in pretreatment risk groups according to international consensus. MLPA proved to be effective for detecting multiple genetic alterations in all chromosome regions as requested by the International Neuroblastoma Risk Group (INRG) for therapeutic stratification. Moreover, this technique proved to be cost effective, reliable, only requiring standard PCR equipment, and attractive for routine analysis. However, the observed 6p imbalances made PKHD1 and DCDC2 inadequate for control loci. This must be considered when designing commercial MLPA kits for NB. Finally, four patients showed a normal MLPA profile, suggesting that NB might have a more complex genetic pattern than the one assessed by presently available MLPA kits.

Genetic overlap between diagnostic subtypes of ischemic stroke.

PubMed

Holliday, Elizabeth G; Traylor, Matthew; Malik, Rainer; Bevan, Steve; Falcone, Guido; Hopewell, Jemma C; Cheng, Yu-Ching; Cotlarciuc, Ioana; Bis, Joshua C; Boerwinkle, Eric; Boncoraglio, Giorgio B; Clarke, Robert; Cole, John W; Fornage, Myriam; Furie, Karen L; Ikram, M Arfan; Jannes, Jim; Kittner, Steven J; Lincz, Lisa F; Maguire, Jane M; Meschia, James F; Mosley, Thomas H; Nalls, Mike A; Oldmeadow, Christopher; Parati, Eugenio A; Psaty, Bruce M; Rothwell, Peter M; Seshadri, Sudha; Scott, Rodney J; Sharma, Pankaj; Sudlow, Cathie; Wiggins, Kerri L; Worrall, Bradford B; Rosand, Jonathan; Mitchell, Braxton D; Dichgans, Martin; Markus, Hugh S; Levi, Christopher; Attia, John; Wray, Naomi R

2015-03-01

Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10(-4)) and profile scores (rg=0.72; 95% confidence interval, 0.52-0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (P=1×10(-7)) for single nucleotide polymorphisms near the opioid receptor μ1 (OPRM1) gene. Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes. © 2015 American Heart Association, Inc.

Profiles of Types of Central Auditory Processing Disorders in Children with Learning Disabilities.

ERIC Educational Resources Information Center

Musiek, Frank E.; And Others

1985-01-01

The article profiles five cases of children (8-17 years old) with learning disabilities and auditory processing problems. Possible correlations between the presumed etiology and the unique audiological pattern on the central test battery are analyzed. (Author/CL)

Gene Expression Profiling Differentiates Autism Case–Controls and Phenotypic Variants of Autism Spectrum Disorders: Evidence for Circadian Rhythm Dysfunction in Severe Autism

PubMed Central

Hu, Valerie W.; Sarachana, Tewarit; Kim, Kyung Soon; Nguyen, AnhThu; Kulkarni, Shreya; Steinberg, Mara E.; Luu, Truong; Lai, Yinglei; Lee, Norman H.

2009-01-01

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests. The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders. DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into three phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls. Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity. Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups. Among the findings unique to the most severely affected ASD group are 15 genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism. Among the genes common to all three subgroups of ASD are 20 novel genes mostly in putative noncoding regions, which appear to associate with androgen sensitivity and which may underlie the strong 4:1 bias toward affected males. PMID:19418574

Seahorse Brood Pouch Transcriptome Reveals Common Genes Associated with Vertebrate Pregnancy.

PubMed

Whittington, Camilla M; Griffith, Oliver W; Qi, Weihong; Thompson, Michael B; Wilson, Anthony B

2015-12-01

Viviparity (live birth) has evolved more than 150 times in vertebrates, and represents an excellent model system for studying the evolution of complex traits. There are at least 23 independent origins of viviparity in fishes, with syngnathid fishes (seahorses and pipefish) unique in exhibiting male pregnancy. Male seahorses and pipefish have evolved specialized brooding pouches that provide protection, gas exchange, osmoregulation, and limited nutrient provisioning to developing embryos. Pouch structures differ widely across the Syngnathidae, offering an ideal opportunity to study the evolution of reproductive complexity. However, the physiological and genetic changes facilitating male pregnancy are largely unknown. We used transcriptome profiling to examine pouch gene expression at successive gestational stages in a syngnathid with the most complex brood pouch morphology, the seahorse Hippocampus abdominalis. Using a unique time-calibrated RNA-seq data set including brood pouch at key stages of embryonic development, we identified transcriptional changes associated with brood pouch remodeling, nutrient and waste transport, gas exchange, osmoregulation, and immunological protection of developing embryos at conception, development and parturition. Key seahorse transcripts share homology with genes of reproductive function in pregnant mammals, reptiles, and other live-bearing fish, suggesting a common toolkit of genes regulating pregnancy in divergent evolutionary lineages. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Market niche analysis in the casino gaming industry.

PubMed

Dandurand, L

1990-03-01

This article discusses the nature of market niche analysis in the casino gaming industry. It presents four approaches for conducting market niche analysis. An an example of one approach, the Las Vegas Visitor Profile Study is used to identify a premium niche in the Las Vegas Slot Target Market. A detailed examination of the premium niche profile provides a description of the typical premium slot player. The description of the typical premium player leads to hypotheses regarding needs (the unique preference set) of the premium player. An analysis of the unique preference set suggests an appropriate enhanced marketing program.

GENETIC ACTIVITY PROFILES AND HAZARD ASSESSMENT

EPA Science Inventory

A methodology has been developed to display and evaluate multiple test quantitative information on genetic toxicants for purposes of hazard/risk assessment. ose information is collected from the open literature: either the lowest effective dose (LED) or the highest ineffective do...

Ethical dimensions of genetics in pediatric neurology: a look into the future.

PubMed

Avard, Denise M; Knoppers, Bartha M

2002-03-01

Health care providers and families with children who participate in genetic research or who need specialized genetic services, including genetic testing, will encounter not only medical but difficult social, ethical, and legal questions surrounding pediatric genetic neurology. Children are often at the center of much of the genetic revolution and their unique needs raise special concerns about the risks and benefits associated with genetic research, particularly the issues of consent, the use of genetic databases, and gene therapy. Moreover, genetic research and testing raise important psychosocial risks. In this article we discuss some of the benefits and consequences of genetic technologies for children in relation to national and international guidelines. In particular, physicians, policy-makers, and families should be knowledgeable about the guidelines and have a good understanding of the psychosocial and ethical issues associated with genetics in pediatric neurology.

MHC ANTIGEN-BINDING LOCUS SHOWS STRONG SIGNAL OF SELECTION AND HIGH VARIABILITY IN FUNDULUS HETEROCLITUS POPULATIONS

EPA Science Inventory

The major histocompatibility system provides a unique genetic locus in vertebrates to assess genetic diversity and to look for the effects of selecti.on on the immune system. Fish population studies using MHC are fairly new, and thus far they have focused on endangered population...

Genetic Characterization of Providence Virus Isolated from Bat Guano in Hungary.

PubMed

Kemenesi, Gábor; Földes, Fanni; Zana, Brigitta; Kurucz, Kornélia; Estók, Péter; Boldogh, Sándor; Görföl, Tamás; Bányai, Krisztián; Oldal, Miklós; Jakab, Ferenc

2016-05-19

We report the complete genome sequence and genetic characterization of a novel strain of Providence virus, detected in Barbastella barbastellus bat guano, collected in Hungary in 2014. Our data may facilitate the understanding of the evolutionary processes of this unique viral family of Carmotetraviridae. Copyright © 2016 Kemenesi et al.

MHC ANTIGEN BINDING LOCUS DRB1 SHOWS STRONG SIGNAL OF SELECTION AND HIGH VARIABILITY IN FUNDULUS HETERCLITUS POPULATIONS

EPA Science Inventory

The major histocompatibility system provides a unique complex of genetic loci in vertebrates to assess genetic diversity and to look for the effects of selection on the adaptive immune system. Studies using mammals and birds
have demonstrated relationships between MHC genotyp...

A Quasi-Experimental Analysis of Second Graders with Dyslexia Using the Motor Markers in the Cerebellar Deficit Hypothesis

ERIC Educational Resources Information Center

Stark, Sandra Kathleen

2013-01-01

Developmental dyslexia is a specific impairment of reading ability in the presence of normal intelligence and adequate reading instruction. Current research has linked dyslexia to genetic underpinnings, which are identifiable. Furthermore, there are cognitive processes that are influenced by unique genetically programmed neural networks that…

Genetic evidence of hybridization between Onothera wolfii (Wolf's evening primrose) and O. glaziovana, a garden escape

Treesearch

Jennifer DeWoody; Leonel Arguello; David Imper; Robert D. Westfall; Valerie D. Hipkins

2008-01-01

Isozyme analysis of the rare Oenothera wolfii (Wolf's evening primrose) and the garden escape, O. glazioviana, indicates that hybridization between these species may be more widespread than morphological evidence indicates. Although both species contained low amounts of genetic variation, unique alleles were identified in...

Evidence of evolutionary history and selective sweeps in the genome of Meishan pig reveals its genetic and phenotypic characterization

USDA-ARS?s Scientific Manuscript database

Meishan is a famous Chinese indigenous pig breed known for its extremely high fecundity. To explore if Meishan has unique evolutionary process and genome characteristics differing from other pig breeds, we systematically analyzed its genetic divergence, and demographic history by large-scale reseque...

Genetic fingerprinting of longleaf pine seed orchard clones following Hurricane Hugo

Treesearch

K. D. Jermstad; P.A. Guge; E.R. Carroll; S.T. Friedman; D.B. Neale

1993-01-01

Isozyme and restriction fragment length polymorphism (RFLP) markers were used to determine the genetic identities of 12 longleaf pine (Pinus palustrus Mill.) ramets whose identities came into question after Hurricane Hugo. Isozyme assays were performed for 12 enzyme systems representing 15 loci. Variation at 6 loci revealed unique identities for 6...

Genetic Counseling for the 22q11.2 Deletion

ERIC Educational Resources Information Center

McDonald-McGinn, Donna M.; Zackai, Elaine H.

2008-01-01

Because of advances in palliative medical care, children with the 22q11.2 deletion syndrome are surviving into adulthood. An increase in reproductive fitness will likely follow necessitating enhanced access to genetic counseling for these patients and their families. Primary care physicians/obstetric practitioners are in a unique position to…

Comparative genomic analysis of clinical and environmental Vibrio vulnificus isolates revealed biotype 3 evolutionary relationships.

PubMed

Koton, Yael; Gordon, Michal; Chalifa-Caspi, Vered; Bisharat, Naiel

2014-01-01

In 1996 a common-source outbreak of severe soft tissue and bloodstream infections erupted among Israeli fish farmers and fish consumers due to changes in fish marketing policies. The causative pathogen was a new strain of Vibrio vulnificus, named biotype 3, which displayed a unique biochemical and genotypic profile. Initial observations suggested that the pathogen erupted as a result of genetic recombination between two distinct populations. We applied a whole genome shotgun sequencing approach using several V. vulnificus strains from Israel in order to study the pan genome of V. vulnificus and determine the phylogenetic relationship of biotype 3 with existing populations. The core genome of V. vulnificus based on 16 draft and complete genomes consisted of 3068 genes, representing between 59 and 78% of the whole genome of 16 strains. The accessory genome varied in size from 781 to 2044 kbp. Phylogenetic analysis based on whole, core, and accessory genomes displayed similar clustering patterns with two main clusters, clinical (C) and environmental (E), all biotype 3 strains formed a distinct group within the E cluster. Annotation of accessory genomic regions found in biotype 3 strains and absent from the core genome yielded 1732 genes, of which the vast majority encoded hypothetical proteins, phage-related proteins, and mobile element proteins. A total of 1916 proteins (including 713 hypothetical proteins) were present in all human pathogenic strains (both biotype 3 and non-biotype 3) and absent from the environmental strains. Clustering analysis of the non-hypothetical proteins revealed 148 protein clusters shared by all human pathogenic strains; these included transcriptional regulators, arylsulfatases, methyl-accepting chemotaxis proteins, acetyltransferases, GGDEF family proteins, transposases, type IV secretory system (T4SS) proteins, and integrases. Our study showed that V. vulnificus biotype 3 evolved from environmental populations and formed a genetically distinct group within the E-cluster. The unique epidemiological circumstances facilitated disease outbreak and brought this genotype to the attention of the scientific community.

Induced Mutagenesis in UGT74S1 Gene Leads to Stable New Flax Lines with Altered Secoisolariciresinol Diglucoside (SDG) Profiles.

PubMed

Fofana, Bourlaye; Ghose, Kaushik; Somalraju, Ashok; McCallum, Jason; Main, David; Deyholos, Michael K; Rowland, Gordon G; Cloutier, Sylvie

2017-01-01

Flax secoisolariciresinol (SECO) diglucoside (SDG) lignan is an emerging natural product purported to prevent chronic diseases in humans. SECO, the aglycone form of SDG, has shown higher intestinal cell absorption but it is not accumulated naturally in planta . Recently, we have identified and characterized a UDP-glucosyltransferase gene, UGT74S1 , that glucosylates SECO into its monoglucoside (SMG) and SDG forms when expressed in yeast. However, whether this gene is unique in controlling SECO glucosylation into SDG in planta is unclear. Here, we report on the use of UGT74S1 in reverse and forward genetics to characterize an ethyl methane sulfonate (EMS) mutagenized flax population from cultivar CDC Bethune and consisting of 1996 M2 families. EMS mutagenesis generated 73 SNP variants causing 79 mutational events in the UGT74S1 exonic regions of 93 M2 families. The mutation frequency in the exonic regions was determined to be one per 28 Kb. Of these mutations, 13 homozygous missense mutations and two homozygous nonsense mutations were observed and all were transmitted into the M3 and M4 generations. Forward genetics screening of the population showed homozygous nonsense mutants completely lacking SDG biosynthesis while the production of SMG was observed only in a subset of the M4 lines. Heterozygous or homozygous M4 missense mutants displayed a wide range of SDG levels, some being greater than those of CDC Bethune. No additional deleterious mutations were detected in these mutant lines using a panel of 10 other genes potentially involved in the lignan biosynthesis. This study provides further evidence that UGT74S1 is unique in controlling SDG formation from SECO and this is the first report of non-transgenic flax germplasm with simultaneous knockout of SDG and presence of SMG in planta .

Induced Mutagenesis in UGT74S1 Gene Leads to Stable New Flax Lines with Altered Secoisolariciresinol Diglucoside (SDG) Profiles

PubMed Central

Fofana, Bourlaye; Ghose, Kaushik; Somalraju, Ashok; McCallum, Jason; Main, David; Deyholos, Michael K.; Rowland, Gordon G.; Cloutier, Sylvie

2017-01-01

Flax secoisolariciresinol (SECO) diglucoside (SDG) lignan is an emerging natural product purported to prevent chronic diseases in humans. SECO, the aglycone form of SDG, has shown higher intestinal cell absorption but it is not accumulated naturally in planta. Recently, we have identified and characterized a UDP-glucosyltransferase gene, UGT74S1, that glucosylates SECO into its monoglucoside (SMG) and SDG forms when expressed in yeast. However, whether this gene is unique in controlling SECO glucosylation into SDG in planta is unclear. Here, we report on the use of UGT74S1 in reverse and forward genetics to characterize an ethyl methane sulfonate (EMS) mutagenized flax population from cultivar CDC Bethune and consisting of 1996 M2 families. EMS mutagenesis generated 73 SNP variants causing 79 mutational events in the UGT74S1 exonic regions of 93 M2 families. The mutation frequency in the exonic regions was determined to be one per 28 Kb. Of these mutations, 13 homozygous missense mutations and two homozygous nonsense mutations were observed and all were transmitted into the M3 and M4 generations. Forward genetics screening of the population showed homozygous nonsense mutants completely lacking SDG biosynthesis while the production of SMG was observed only in a subset of the M4 lines. Heterozygous or homozygous M4 missense mutants displayed a wide range of SDG levels, some being greater than those of CDC Bethune. No additional deleterious mutations were detected in these mutant lines using a panel of 10 other genes potentially involved in the lignan biosynthesis. This study provides further evidence that UGT74S1 is unique in controlling SDG formation from SECO and this is the first report of non-transgenic flax germplasm with simultaneous knockout of SDG and presence of SMG in planta. PMID:28983308

Development of a practical NF1 genetic testing method through the pilot analysis of five Japanese families with neurofibromatosis type 1.

PubMed

Okumura, Akiko; Ozaki, Mamoru; Niida, Yo

2015-08-01

Mutation analysis of NF1, the responsible gene for neurofibromatosis type 1 (NF1), is still difficult due to its large size, lack of mutational hotspots, the presence of many pseudogenes, and its wide spectrum of mutations. To develop a simple and inexpensive NF1 genetic testing for clinical use, we analyzed five Japanese families with NF1 as a pilot study. Our original method, CEL endonuclease mediated heteroduplex incision with polyacrylamide gel electrophoresis and silver staining (CHIPS) was optimized for NF1 mutation screening, and reverse transcription polymerase chain reaction (RT-PCR) was performed to determine the effect of transcription. Also, we employed DNA microarray analysis to evaluate the break points of the large deletion. A new nonsense mutation, p.Gln209(∗), was detected in family 1 and the splicing donor site mutation, c.2850+1G>T, was detected in family 2. In family 3, c.4402A>G was detected in exon 34 and the p.Ser1468Gly missense mutation was predicted. However mRNA analysis revealed that this substitution created an aberrant splicing acceptor site, thereby causing the p.Phe1457(∗) nonsense mutation. In the other two families, type-1 and unique NF1 microdeletions were detected by DNA microarray analysis. Our results show that the combination of CHIPS and RT-PCR effectively screen and characterize NF1 point mutations, and both DNA and RNA level analysis are required to understand the nature of the NF1 mutation. Our results also suggest the possibility of a higher incidence and unique profile of NF1 large deletions in the Japanese population as compared to previous studies performed in Europe. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Diurnal Cortisol Profile in Williams Syndrome in Novel and Familiar Settings

ERIC Educational Resources Information Center

Lense, Miriam Diane; Tomarken, Andrew J.; Dykens, Elisabeth M.

2013-01-01

Williams syndrome (WS) is a neurodevelopmental genetic disorder associated with high rates of anxiety and social issues. We examined diurnal cortisol, a biomarker of the stress response, in adults with WS in novel and familiar settings, and compared these profiles to typically developing (TD) adults. WS and TD participants had similar profiles in…

Genetic testing: medico-legal issues.

PubMed

Bird, Sara

2014-07-01

The availability and frequency of genetic testing is increasing. Genetic testing poses some unique ethical and legal issues for medical practitioners because of the potential to identify genetic variants that carry implications for the risk of disease in the future for the patient and their relatives. The regulatory framework within which genetic testing is provided in Australia is also changing. This article examines some medico-legal issues associated with genetic testing that general practitioners (GPs) are likely encounter in their practices. There is inevitable involvement of the GP in the long term care of a patient (and possibly their family) following genetic testing, regardless of whether or not the GP has ordered the testing. Cases are presented to illustrate some of the medico-legal issues that may arise from direct-to-consumer genetic testing, information disclosure to genetic relatives and requests for parentage testing.

A Multistate Toggle Switch Defines Fungal Cell Fates and Is Regulated by Synergistic Genetic Cues

PubMed Central

Anderson, Matthew Z.; Porman, Allison M.; Wang, Na; Mancera, Eugenio; Bennett, Richard J.

2016-01-01

Heritable epigenetic changes underlie the ability of cells to differentiate into distinct cell types. Here, we demonstrate that the fungal pathogen Candida tropicalis exhibits multipotency, undergoing stochastic and reversible switching between three cellular states. The three cell states exhibit unique cellular morphologies, growth rates, and global gene expression profiles. Genetic analysis identified six transcription factors that play key roles in regulating cell differentiation. In particular, we show that forced expression of Wor1 or Efg1 transcription factors can be used to manipulate transitions between all three cell states. A model for tristability is proposed in which Wor1 and Efg1 are self-activating but mutually antagonistic transcription factors, thereby forming a symmetrical self-activating toggle switch. We explicitly test this model and show that ectopic expression of WOR1 can induce white-to-hybrid-to-opaque switching, whereas ectopic expression of EFG1 drives switching in the opposite direction, from opaque-to-hybrid-to-white cell states. We also address the stability of induced cell states and demonstrate that stable differentiation events require ectopic gene expression in combination with chromatin-based cues. These studies therefore experimentally test a model of multistate stability and demonstrate that transcriptional circuits act synergistically with chromatin-based changes to drive cell state transitions. We also establish close mechanistic parallels between phenotypic switching in unicellular fungi and cell fate decisions during stem cell reprogramming. PMID:27711197

Anterior segment dysgenesis associated with Williams-Beuren syndrome: a case report and review of the literature.

PubMed

Todorova, Margarita G; Grieshaber, Matthias C; Cámara, Rafael J A; Miny, Peter; Palmowski-Wolfe, Anja M

2014-05-21

Williams-Beuren syndrome is characterized by mild mental retardation, specific neurocognitive profile, hypercalcemia during infancy, distinctive facial features and cardiovascular diseases. We report on complete ophthalmologic, sonographic and genetic evaluation of a girl with a clinical phenotype of Williams-Beuren syndrome, associated with unilateral anterior segment dysgenesis and bilateral cleft of the soft and hard palate. These phenotypic features have not been linked to the haploinsufficiency of genes involved in the microdeletion. A term born girl presented at the initial examination with clouding of the right cornea. On ultrasound biomicroscopy the anterior chamber structures were difficult to differentiate, showing severe adhesions from the opacified cornea to the iris with a kerato-irido-lenticular contact to the remnant lens, a finding consistent with Peters' anomaly. Genetic analyses including FISH confirmed a loss of the critical region 7q11.23, usually associated with the typical Williams-Beuren syndrome. Microsatellite analysis showed a loss of about 2.36 Mb. A diagnosis of Williams-Beuren syndrome was made based on the microdeletion of 7q11.23. The unique features, including unilateral microphthalmia and anterior segment dysgenesis, were unlikely to be caused by the microdeletion. Arguments in favor of the latter are unilateral manifestation, as well as the fact that numerous patients with deletions of comparable or microscopically visible size have not shown similar manifestations.

Morphometric variation between two morphotypes within the Astyanax Baird and Girard, 1854 (Actinopterygii: Characidae) genus, from a Mexican tropical lake.

PubMed

Ornelas-García, Claudia P; Bastir, Markus; Doadrio, Ignacio

2014-07-01

Phenotypic variation is important for evolutionary processes because it can allow local adaptation, promote genetic segregation, and ultimately give rise to speciation. Lacustrine systems provide a unique opportunity to study the mechanisms by which sister species can co-occur by means of ecological segregation. The fish genus Astyanax is characterized by high levels of phenotypic variability, providing an excellent model for the study of local specialization. Here, we analyze the morphological specializations through geometric morphometrics of two sympatric species described as different genera: Bramocharax caballeroi endemic to Lake Catemaco, and the widely distributed Astyanax aeneus. Additionally, we assess the correlation between phenotypic and genetic structure, and the phylogenetic signal of morphological variation. We examined body size and shape variation in 196 individuals and analyzed mitochondrial cytochrome b sequences in 298 individuals. Our results confirm the striking morphological divergence among the sympatric characids. Differences between them were mainly found in the body depth and profile and orientation of the head, where B. caballeroi in contrast with the A. aeneus, presented a fusiform body and an upward mouth. Moreover, different growth trajectories were observed among morphotypes, suggesting that a heterochronic process could be involved in the diversification of our study system. Morphological differences did not correspond with the molecular differentiation, suggesting high levels of homoplasy among the lineages of B. caballeroi morphs. © 2014 Wiley Periodicals, Inc.

Abundance and Genetic Diversity of nifH Gene Sequences in Anthropogenically Affected Brazilian Mangrove Sediments

PubMed Central

Dias, Armando Cavalcante Franco; Pereira e Silva, Michele de Cassia; Cotta, Simone Raposo; Dini-Andreote, Francisco; Soares, Fábio Lino; Salles, Joana Falcão; Azevedo, João Lúcio; van Elsas, Jan Dirk

2012-01-01

Although mangroves represent ecosystems of global importance, the genetic diversity and abundance of functional genes that are key to their functioning scarcely have been explored. Here, we present a survey based on the nifH gene across transects of sediments of two mangrove systems located along the coast line of São Paulo state (Brazil) which differed by degree of disturbance, i.e., an oil-spill-affected and an unaffected mangrove. The diazotrophic communities were assessed by denaturing gradient gel electrophoresis (DGGE), quantitative PCR (qPCR), and clone libraries. The nifH gene abundance was similar across the two mangrove sediment systems, as evidenced by qPCR. However, the nifH-based PCR-DGGE profiles revealed clear differences between the mangroves. Moreover, shifts in the nifH gene diversities were noted along the land-sea transect within the previously oiled mangrove. The nifH gene diversity depicted the presence of nitrogen-fixing bacteria affiliated with a wide range of taxa, encompassing members of the Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Firmicutes, and also a group of anaerobic sulfate-reducing bacteria. We also detected a unique mangrove-specific cluster of sequences denoted Mgv-nifH. Our results indicate that nitrogen-fixing bacterial guilds can be partially endemic to mangroves, and these communities are modulated by oil contamination, which has important implications for conservation strategies. PMID:22941088

Abundance and genetic diversity of nifH gene sequences in anthropogenically affected Brazilian mangrove sediments.

PubMed

Dias, Armando Cavalcante Franco; Pereira e Silva, Michele de Cassia; Cotta, Simone Raposo; Dini-Andreote, Francisco; Soares, Fábio Lino; Salles, Joana Falcão; Azevedo, João Lúcio; van Elsas, Jan Dirk; Andreote, Fernando Dini

2012-11-01

Although mangroves represent ecosystems of global importance, the genetic diversity and abundance of functional genes that are key to their functioning scarcely have been explored. Here, we present a survey based on the nifH gene across transects of sediments of two mangrove systems located along the coast line of São Paulo state (Brazil) which differed by degree of disturbance, i.e., an oil-spill-affected and an unaffected mangrove. The diazotrophic communities were assessed by denaturing gradient gel electrophoresis (DGGE), quantitative PCR (qPCR), and clone libraries. The nifH gene abundance was similar across the two mangrove sediment systems, as evidenced by qPCR. However, the nifH-based PCR-DGGE profiles revealed clear differences between the mangroves. Moreover, shifts in the nifH gene diversities were noted along the land-sea transect within the previously oiled mangrove. The nifH gene diversity depicted the presence of nitrogen-fixing bacteria affiliated with a wide range of taxa, encompassing members of the Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Firmicutes, and also a group of anaerobic sulfate-reducing bacteria. We also detected a unique mangrove-specific cluster of sequences denoted Mgv-nifH. Our results indicate that nitrogen-fixing bacterial guilds can be partially endemic to mangroves, and these communities are modulated by oil contamination, which has important implications for conservation strategies.

Refining the tobacco dependence phenotype using the Wisconsin Inventory of Smoking Dependence Motives (WISDM)

PubMed Central

Piper, Megan E.; Bolt, Daniel M.; Kim, Su-Young; Japuntich, Sandra J.; Smith, Stevens S.; Niederdeppe, Jeff; Cannon, Dale S.; Baker, Timothy B.

2008-01-01

The construct of tobacco dependence is important from both scientific and public health perspectives, but it is poorly understood. The current research integrates person-centered analyses (e.g., latent profile analysis) and variable-centered analyses (e.g., exploratory factor analysis) to understand better the latent structure of dependence and to guide distillation of the phenotype. Using data from four samples of smokers (including treatment and non-treatment samples), latent profiles were derived using the Wisconsin Inventory of Smoking Dependence Motives (WISDM) subscale scores. Across all four samples, results revealed a unique latent profile that had relative elevations on four dependence motive subscales (Automaticity, Craving, Loss of Control, and Tolerance). Variable-centered analyses supported the uniqueness of these four subscales both as measures of a common factor distinct from that underlying the other nine subscales, and as the strongest predictors of relapse, withdrawal and other dependence criteria. Conversely, the remaining nine motives carried little unique predictive validity regarding dependence. Applications of a factor mixture model further support the presence of a unique class of smokers in relation to a common factor underlying the four subscales. The results illustrate how person-centered analyses may be useful as a supplement to variable-centered analyses for uncovering variables that are necessary and/or sufficient predictors of disorder criteria, as they may uncover small segments of a population in which the variables are uniquely distributed. The results also suggest that severe dependence is associated with a pattern of smoking that is heavy, pervasive, automatic and relatively unresponsive to instrumental contingencies. PMID:19025223

Anorexia Nervosa, Major Depression, and Suicide Attempts: Shared Genetic Factors

PubMed Central

Thornton, Laura M.; Welch, Elisabeth; Munn-Chernoff, Melissa A.; Lichtenstein, Paul; Bulik, Cynthia M.

2015-01-01

We evaluated the extent to which genetic and environmental factors influenced anorexia nervosa (AN), major depressive disorder (MDD), and suicide attempts (SA). Participants were 6,899 women from the Swedish Twin study of Adults Genes and Environment. A Cholesky decomposition assessed independent and overlapping genetic and environmental contributions to AN, MDD, and SA. Genetic factors accounted for a substantial amount of liability to all three traits; unique environmental factors accounted for most of the remaining liability. Shared genetic factors may underlie the co-expression of these traits. Results underscore the importance of assessing for signs of suicide among individuals with AN. PMID:26916469

Anorexia Nervosa, Major Depression, and Suicide Attempts: Shared Genetic Factors.

PubMed

Thornton, Laura M; Welch, Elisabeth; Munn-Chernoff, Melissa A; Lichtenstein, Paul; Bulik, Cynthia M

2016-10-01

The extent to which genetic and environmental factors influenced anorexia nervosa (AN), major depressive disorder (MDD), and suicide attempts (SA) were evaluated. Participants were 6,899 women from the Swedish Twin Study of Adults: Genes and Environment. A Cholesky decomposition assessed independent and overlapping genetic and environmental contributions to AN, MDD, and SA. Genetic factors accounted for a substantial amount of liability to all three traits; unique environmental factors accounted for most of the remaining liability. Shared genetic factors may underlie the coexpression of these traits. Results underscore the importance of assessing for signs of suicide among individuals with AN. © 2016 The American Association of Suicidology.

Genetically distinct genogroup IV norovirus strains identified in wastewater.

PubMed

Kitajima, Masaaki; Rachmadi, Andri T; Iker, Brandon C; Haramoto, Eiji; Gerba, Charles P

2016-12-01

We investigated the prevalence and genetic diversity of genogroup IV norovirus (GIV NoV) strains in wastewater in Arizona, United States, over a 13-month period. Among 50 wastewater samples tested, GIV NoVs were identified in 13 (26 %) of the samples. A total of 47 different GIV NoV strains were identified, which were classified into two genetically distinct clusters: the GIV.1 human cluster and a unique genetic cluster closely related to strains previously identified in Japanese wastewater. The results provide additional evidence of the considerable genetic diversity among GIV NoV strains through the analysis of wastewater containing virus strains shed from all populations.

Genetic and Environmental Regulation on Longitudinal Change of Metabolic Phenotypes in Danish and Chinese Adult Twins

PubMed Central

Li, Shuxia; Kyvik, Kirsten Ohm; Pang, Zengchang; Zhang, Dongfeng; Duan, Haiping; Tan, Qihua; Hjelmborg, Jacob; Kruse, Torben; Dalgård, Christine

2016-01-01

Objective The rate of change in metabolic phenotypes can be highly indicative of metabolic disorders and disorder-related modifications. We analyzed data from longitudinal twin studies on multiple metabolic phenotypes in Danish and Chinese twins representing two populations of distinct ethnic, cultural, social-economic backgrounds and geographical environments. Materials and Methods The study covered a relatively large sample of 502 pairs of Danish adult twins followed up for a long period of 12 years with a mean age at intake of 38 years (range: 18–65) and a total of 181 Chinese adult twin pairs traced for about 7 years with a mean baseline age of 39.5 years (range: 23–64). The classical twin models were fitted to the longitudinal change in each phenotype (Δphenotype) to estimate the genetic and environmental contributions to the variation in Δphenotype. Results Moderate to high contributions by the unique environment were estimated for all phenotypes in both Danish (from 0.51 for low density lipoprotein cholesterol up to 0.72 for triglycerides) and Chinese (from 0.41 for triglycerides up to 0.73 for diastolic blood pressure) twins; low to moderate genetic components were estimated for long-term change in most of the phenotypes in Danish twins except for triglycerides and hip circumference. Compared with Danish twins, the Chinese twins tended to have higher genetic control over the longitudinal changes in lipids (except high density lipoprotein cholesterol) and glucose, higher unique environmental contribution to blood pressure but no genetic contribution to longitudinal change in body mass traits. Conclusion Our results emphasize the major contribution of unique environment to the observed intra-individual variation in all metabolic phenotypes in both samples, and meanwhile reveal differential patterns of genetic and common environmental regulation on changes over time in metabolic phenotypes across the two samples. PMID:26862898

Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications

PubMed Central

Nugoli, Mélanie; Chuchana, Paul; Vendrell, Julie; Orsetti, Béatrice; Ursule, Lisa; Nguyen, Catherine; Birnbaum, Daniel; Douzery, Emmanuel JP; Cohen, Pascale; Theillet, Charles

2003-01-01

Background Both phenotypic and cytogenetic variability have been reported for clones of breast carcinoma cell lines but have not been comprehensively studied. Despite this, cell lines such as MCF-7 cells are extensively used as model systems. Methods In this work we documented, using CGH and RNA expression profiles, the genetic variability at the genomic and RNA expression levels of MCF-7 cells of different origins. Eight MCF-7 sublines collected from different sources were studied as well as 3 subclones isolated from one of the sublines by limit dilution. Results MCF-7 sublines showed important differences in copy number alteration (CNA) profiles. Overall numbers of events ranged from 28 to 41. Involved chromosomal regions varied greatly from a subline to another. A total of 62 chromosomal regions were affected by either gains or losses in the 11 sublines studied. We performed a phylogenetic analysis of CGH profiles using maximum parsimony in order to reconstruct the putative filiation of the 11 MCF-7 sublines. The phylogenetic tree obtained showed that the MCF-7 clade was characterized by a restricted set of 8 CNAs and that the most divergent subline occupied the position closest to the common ancestor. Expression profiles of 8 MCF-7 sublines were analyzed along with those of 19 unrelated breast cancer cell lines using home made cDNA arrays comprising 720 genes. Hierarchical clustering analysis of the expression data showed that 7/8 MCF-7 sublines were grouped forming a cluster while the remaining subline clustered with unrelated breast cancer cell lines. These data thus showed that MCF-7 sublines differed at both the genomic and phenotypic levels. Conclusions The analysis of CGH profiles of the parent subline and its three subclones supported the heteroclonal nature of MCF-7 cells. This strongly suggested that the genetic plasticity of MCF-7 cells was related to their intrinsic capacity to generate clonal heterogeneity. We propose that MCF-7, and possibly the breast tumor it was derived from, evolved in a node like pattern, rather than according to a linear progression model. Due to their capacity to undergo rapid genetic changes MCF-7 cells could represent an interesting model for genetic evolution of breast tumors. PMID:12713671

The genomic landscape of acute lymphoblastic leukemia in children and young adults.

PubMed

Mullighan, Charles G

2014-12-05

Our understanding of the genetic basis of childhood acute lymphoblastic leukemia (ALL) has been greatly advanced by genomic profiling and sequencing studies. These efforts have characterized the genetic basis of recently described and poorly understood subtypes of ALL, including early T-cell precursor ALL, Philadelphia chromosome-like (Ph-like) ALL, and ALL with intrachromosomal amplification of chromosome 21, and have identified several rational therapeutic targets in high-risk ALL, notably ABL1-class and JAK-STAT inhibitors in Ph-like ALL. Deep sequencing studies are also refining our understanding of the genetic basis of clonal heterogeneity and relapse. These studies have elucidated the nature of clonal evolution during disease progression and identified genetic changes that confer resistance to specific therapeutic agents, including CREBBP and NT5C2. Genomic profiling has also identified common and rare inherited genetic variants that influence the risk of developing leukemia. These efforts are now being extended to ALL in adolescents and adults with the goal of fully defining the genetic landscape of ALL to further improve treatment outcomes in high-risk populations. © 2014 by The American Society of Hematology. All rights reserved.

Who is at risk for compassion fatigue? An investigation of genetic counselor demographics, anxiety, compassion satisfaction, and burnout.

PubMed

Lee, Whiwon; Veach, Patricia McCarthy; MacFarlane, Ian M; LeRoy, Bonnie S

2015-04-01

Compassion fatigue is a state of detachment and isolation experienced when healthcare providers repeatedly engage with patients in distress. Compassion fatigue can hinder empathy and cause extreme tension. Prior research suggests 73.8 % of genetic counselors are at moderate to high risk for compassion fatigue and approximately 1 in 4 have considered leaving the field as a result Injeyan et al. (Journal of Genetic Counseling, 20, 526-540, 2011). Empirical data to establish a reliable profile of genetic counselors at risk for compassion fatigue are limited. Thus the purpose of this study was to establish a profile by assessing relationships between state and trait anxiety, burnout, compassion satisfaction, selected demographics and compassion fatigue risk in practicing genetic counselors. Practicing genetic counselors (n = 402) completed an anonymous, online survey containing demographic questions, the State-Trait Anxiety Inventory, and the Professional Quality of Life scale. Multiple regression analysis yielded four significant predictors which increase compassion fatigue risk (accounting for 48 % of the variance): higher levels of trait anxiety, burnout, and compassion satisfaction, and ethnicity other than Caucasian. Additional findings, study limitations, practice implications, and research recommendations are provided.

Evaluation of the genetic distinctiveness of Greater Sage-grouse in the Bi-State Planning Area

USGS Publications Warehouse

Oyler-McCance, Sara J.; Casazza, Michael L.

2011-01-01

The purpose of this study was to further characterize a distinct population of Greater Sage-grouse: the population located along the border between Nevada and California (Bi-State Planning Area) and centered around the Mono Basin. This population was previously determined to be genetically distinct from other Greater Sage-grouse populations across their range. Previous genetic work focused on characterizing genetic variation across the species' range and thereby used a coarse sampling approach for species characterization. The goal of this study was to investigate this population further by obtaining samples from breeding locations within the population and analyzing those samples with the same mitochondrial and microsatellite loci used in previous studies. Blood samples were collected in six locations within the Bi-State Planning Area. Genetic data from subpopulations were then compared with each other and also with two populations outside of the Bi-State Planning Area. Particular attention was paid to subpopulation boundaries and internal dynamics by drawing comparisons among particular regions within the Bi-State Planning Area and regions proximal to it. All newly sampled subpopulations contained mitochondrial haplotypes and allele frequencies that were consistent with the genetically unique Bi-State (Mono Basin) Greater Sage-grouse described previously. This reinforces the fact that this group of Greater Sage-grouse is genetically unique and warrants special attention. Maintaining the genetic integrity of this population could protect the evolutionary potential of this population of Greater Sage-grouse. Additionally, the White Mountains subpopulation was found to be significantly distinct from all other Bi-State subpopulations.

Genetic Pedagogical Content Knowledge (PCK) Ability Profile of Prospective Biology Teacher

NASA Astrophysics Data System (ADS)

Purwianingsih, W.; Muthmainnah, E.; Hidayat, T.

2017-02-01

Genetics is one of the topics or subject matter in biology that are considered difficult. Student difficulties of understanding genetics, can be caused by lack of understanding this concept and the way of teachers teach. Pedagogical Content Knowledge (PCK) is a way to understand the complex relationships between teaching and content taught through the use of specific teaching approaches. The aims of study was to analyze genetic PCK ability profile of prospective biology teacher.13 student of sixth semester Biology education department who learned Kapita Selekta Biologi SMA course, participated in this study. PCK development was measured by CoRes (Content Representation). Before students fill CoRes, students are tested mastery genetic concepts through a multiple-choice test with three tier-test. Data was obtained from the prior CoRes and its revisions, as well as the mastery concept in pre and post test. Results showed that pre-test of genetic mastery concepts average on 55.4% (low category) and beginning of the writing CoRes, student get 43.2% (Pra PCK). After students get lecture and simulating learning, the post-test increased to 63.8% (sufficient category) and PCK revision is also increase 58.1% (growing PCK). It can be concluded that mastery of subject matter could affects the ability of genetic PCK.

The CRISPR-Cas9 system in Neisseria spp.

PubMed Central

2017-01-01

Abstract Bacteria and archaea possess numerous defense systems to combat viral infections and other mobile genetic elements. Uniquely among these, CRISPR-Cas (clustered, regularly interspaced short palindromic repeats-CRISPR associated) provides adaptive genetic interference against foreign nucleic acids. Here we review recent advances on the CRISPR-Cas9 system in Neisseria spp, with a focus on its biological functions in genetic transfer, its mechanistic features that establish new paradigms and its technological applications in eukaryotic genome engineering. PMID:28369433

The genetic basis for cognitive ability, memory, and depression symptomatology in middle-aged and elderly chinese twins.

PubMed

Xu, Chunsheng; Sun, Jianping; Ji, Fuling; Tian, Xiaocao; Duan, Haiping; Zhai, Yaoming; Wang, Shaojie; Pang, Zengchang; Zhang, Dongfeng; Zhao, Zhongtang; Li, Shuxia; Hjelmborg, Jacob V B; Christensen, Kaare; Tan, Qihua

2015-02-01

The genetic influences on aging-related phenotypes, including cognition and depression, have been well confirmed in the Western populations. We performed the first twin-based analysis on cognitive performance, memory and depression status in middle-aged and elderly Chinese twins, representing the world's largest and most rapidly aging population. The sample consisted of 384 twin pairs with a median age of 50 years. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) scale; memory was assessed using the revised Wechsler Adult Intelligence scale; depression symptomatology was evaluated by the self-reported 30-item Geriatric Depression (GDS-30)scale. Both univariate and multivariate twin models were fitted to the three phenotypes with full and nested models and compared to select the best fitting models. Univariate analysis showed moderate-to-high genetic influences with heritability 0.44 for cognition and 0.56 for memory. Multivariate analysis by the reduced Cholesky model estimated significant genetic (rG = 0.69) and unique environmental (rE = 0.25) correlation between cognitive ability and memory. The model also estimated weak but significant inverse genetic correlation for depression with cognition (-0.31) and memory (-0.28). No significant unique environmental correlation was found for depression with other two phenotypes. In conclusion, there can be a common genetic architecture for cognitive ability and memory that weakly correlates with depression symptomatology, but in the opposite direction.

Heritability of insomnia symptoms in youth and their relationship to depression and anxiety.

PubMed

Gehrman, Philip R; Meltzer, Lisa J; Moore, Melisa; Pack, Allan I; Perlis, Michael L; Eaves, Lindon J; Silberg, Judy L

2011-12-01

Insomnia is a highly prevalent sleep disorder yet little is known about the role of genetic factors in its pathophysiology. The aim of this study was to examine the relative contributions of genetic and environmental factors in explaining variability in insomnia symptoms. Traditional twin design. Academic medical center. 1412 twin pairs aged 8-16 years (48.8% MZ, 47.2% DZ, 4.0% indeterminate). None. Ratings of insomnia symptoms, depression, and overanxious disorder were made by trained interviewers based on DSM-III-R criteria. ACE models were conducted using Mx statistical software. Insomnia symptoms were prevalent in this sample based both on parental (6.6%) and youth (19.5%) reports. The overall heritability of insomnia symptoms was modest (30.7%), with the remaining variance attributed to unique environmental effects. There was no evidence of sex differences in the prevalence of insomnia symptoms or in the contribution of genetic and environmental effects. In multivariate models, there was support for insomnia-specific unique environmental effects over and above overlapping effects with depression and overanxious disorder, but no evidence for insomnia-specific genetic effects. Genetic factors play a modest role in the etiology of insomnia symptoms in 8-16 year-olds. These effects overlap with the genetics of depression and overanxious disorder. Further work is needed to determine which genes confer risk for all three disorders.

Unique patterns of organization and migration of FGF-expressing cells during Drosophila morphogenesis.

PubMed

Du, Lijuan; Zhou, Amy; Patel, Akshay; Rao, Mishal; Anderson, Kelsey; Roy, Sougata

2017-07-01

Fibroblast growth factors (FGF) are essential signaling proteins that regulate diverse cellular functions in developmental and metabolic processes. In Drosophila, the FGF homolog, branchless (bnl) is expressed in a dynamic and spatiotemporally restricted pattern to induce branching morphogenesis of the trachea, which expresses the Bnl-receptor, breathless (btl). Here we have developed a new strategy to determine bnl- expressing cells and study their interactions with the btl-expressing cells in the range of tissue patterning during Drosophila development. To enable targeted gene expression specifically in the bnl expressing cells, a new LexA based bnl enhancer trap line was generated using CRISPR/Cas9 based genome editing. Analyses of the spatiotemporal expression of the reporter in various embryonic stages, larval or adult tissues and in metabolic hypoxia, confirmed its target specificity and versatility. With this tool, new bnl expressing cells, their unique organization and functional interactions with the btl-expressing cells were uncovered in a larval tracheoblast niche in the leg imaginal discs, in larval photoreceptors of the developing retina, and in the embryonic central nervous system. The targeted expression system also facilitated live imaging of simultaneously labeled Bnl sources and tracheal cells, which revealed a unique morphogenetic movement of the embryonic bnl- source. Migration of bnl- expressing cells may create a dynamic spatiotemporal pattern of the signal source necessary for the directional growth of the tracheal branch. The genetic tool and the comprehensive profile of expression, organization, and activity of various types of bnl-expressing cells described in this study provided us with an important foundation for future research investigating the mechanisms underlying Bnl signaling in tissue morphogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Provision of genetics services on Guam.

PubMed

McWalter, Kirsty; Hasegawa, Lianne; Au, Sylvia Mann

2013-12-01

Guam's geographic isolation and lack of community resources have resulted in unique healthcare needs. In 2006, the Western States Genetic Services Collaborative (WSGSC) conducted a genetics needs assessment and found that professional development is limited, families lack access to genetic services, and improved coverage of genetic testing is needed. With funding from the WSGSC, a Guam genetics outreach clinic was established and staffed by genetic counselors and a medical geneticist from Hawaii. Four clinics have been held to date. Although several challenges have been encountered, including minimal coverage of genetic testing by Guam insurance companies, limited referrals for families with private insurance, and inappropriate referral indications, the outreach clinic has been successful at increasing access to genetic services and improving professional development. With more collaborative work by staff from Guam, Hawaii, and the WSGSC, provision and reimbursement of genetic services and testing will continue to improve.

Fruit metabolite networks in engineered and non-engineered tomato genotypes reveal fluidity in a hormone and agroecosystem specific manner.

PubMed

Fatima, Tahira; Sobolev, Anatoly P; Teasdale, John R; Kramer, Matthew; Bunce, Jim; Handa, Avtar K; Mattoo, Autar K

Metabolomics provides a view of endogenous metabolic patterns not only during plant growth, development and senescence but also in response to genetic events, environment and disease. The effects of the field environment on plant hormone-specific metabolite profiles are largely unknown. Few studies have analyzed useful phenotypes generated by introducing single or multiple gene events alongside the non-engineered wild type control at field scale to determine the robustness of the genetic trait and its modulation in the metabolome as a function of specific agroecosystem environments. We evaluated the influence of genetic background (high polyamine lines; low methyl jasmonate line; low ethylene line; and isogenic genotypes carrying double transgenic events) and environments (hairy vetch, rye, plastic black mulch and bare soil mulching systems) on the metabolomic profile of isogenic reverse genetic mutations and selected mulch based cropping systems in tomato fruit. Net photosynthesis and fruit yield were also determined. NMR spectroscopy was used for quantifying metabolites that are central to primary metabolism. We analyzed both the first moment (means) of metabolic response to genotypes and agroecosystems by traditional univariate/multivariate methods, and the second moment (covariances) of responses by creating networks that depicted changes in correlations of paired metabolites. This particular approach is novel and was necessary because our experimental material yielded highly variable metabolic responses that could not be easily understood using the traditional analytical approaches for first moment statistics. High endogenous spermidine and spermine content exhibited strong effects on amino acids, Krebs cycle intermediates and energy molecules (ADP + ATP) in ripening fruits of plants grown under different agroecosystem environments. The metabolic response to high polyamine genotypes was similar to the response to hairy vetch cover crop mulch; supported by the pattern of changes in correlation between metabolites. Changes in primary metabolites of genotypes mutated for the deficiency of ethylene or methyl jasmonate were unique under all growth conditions and opposite of high polyamine genotype results. The high polyamine trait was found to dominate the low ethylene and low jasmonate mutations under field conditions. For several metabolites low ethylene and low methyl jasmonate genotypes had an inverse relationship. Collectively, these results affirm that interactions between metabolite pathways and growth environments are affected by genotype, and influence the metabolite quality of a crop. This study portrays how metabolite relationships change, both in mean and in correlation, under different genotypic and environmental conditions. Although these networks are surprisingly dynamic, we also find examples of selectively conserved associations.

Genome-Wide Mutagenesis of Dengue Virus Reveals Plasticity of the NS1 Protein and Enables Generation of Infectious Tagged Reporter Viruses

PubMed Central

Johnson, Stephen M.; Eltahla, Auda A.; Aloi, Maria; Aloia, Amanda L.; McDevitt, Christopher A.; Bull, Rowena A.

2017-01-01

ABSTRACT Dengue virus (DENV) is a major global pathogen that causes significant morbidity and mortality in tropical and subtropical areas worldwide. An improved understanding of the regions within the DENV genome and its encoded proteins that are required for the virus replication cycle will expedite the development of urgently required therapeutics and vaccines. We subjected an infectious DENV genome to unbiased insertional mutagenesis and used next-generation sequencing to identify sites that tolerate 15-nucleotide insertions during the virus replication cycle in hepatic cell culture. This revealed that the regions within capsid, NS1, and the 3′ untranslated region were the most tolerant of insertions. In contrast, prM- and NS2A-encoding regions were largely intolerant of insertions. Notably, the multifunctional NS1 protein readily tolerated insertions in regions within the Wing, connector, and β-ladder domains with minimal effects on viral RNA replication and infectious virus production. Using this information, we generated infectious reporter viruses, including a variant encoding the APEX2 electron microscopy tag in NS1 that uniquely enabled high-resolution imaging of its localization to the surface and interior of viral replication vesicles. In addition, we generated a tagged virus bearing an mScarlet fluorescent protein insertion in NS1 that, despite an impact on fitness, enabled live cell imaging of NS1 localization and traffic in infected cells. Overall, this genome-wide profile of DENV genome flexibility may be further dissected and exploited in reporter virus generation and antiviral strategies. IMPORTANCE Regions of genetic flexibility in viral genomes can be exploited in the generation of reporter virus tools and should arguably be avoided in antiviral drug and vaccine design. Here, we subjected the DENV genome to high-throughput insertional mutagenesis to identify regions of genetic flexibility and enable tagged reporter virus generation. In particular, the viral NS1 protein displayed remarkable tolerance of small insertions. This genetic flexibility enabled generation of several novel NS1-tagged reporter viruses, including an APEX2-tagged virus that we used in high-resolution imaging of NS1 localization in infected cells by electron microscopy. For the first time, this analysis revealed the localization of NS1 within viral replication factories known as “vesicle packets” (VPs), in addition to its acknowledged localization to the luminal surface of these VPs. Together, this genetic profile of DENV may be further refined and exploited in the identification of antiviral targets and the generation of reporter virus tools. PMID:28956770

Unique sleep disorders profile of a population-based sample of 747 Hmong immigrants in Wisconsin

PubMed Central

Young, Eric; Xiong, Se; Finn, Laurel; Young, Terry

2013-01-01

Concerns regarding sleep disorders in Hmong immigrants in the US emerged when an astonishingly high mortality rate of Sudden Unexplained Nocturnal Death Syndrome (SUNDS) was documented in Hmong men. Stress, genetics, and cardiac abnormalities interacting with disordered sleep were hypothesized as contributing factors to SUNDS. Most recently, sleep apnea has been implicated in nighttime deaths of Brugada Syndrome. This syndrome is thought to comprise a spectrum of sudden cardiac death disorders, including SUNDS. However, little research since has placed SUNDS in its context of Hmong cultural beliefs, health, or the prevalence of other sleep disorders. Because the epidemiology of sleep disorders and terrifying nighttime experiences in Hmong is poorly documented, we investigated the prevalence and correlates of sleep apnea, rapid eye movement (REM) sleep stage related disorders, and insomnia in 3 population-based samples (collected from 1996 to 2001) comprising 747 Hmong immigrants in Wisconsin. Participants were questioned on sleep problems, cultural beliefs, health, and other factors. A random subsample (n = 37) underwent in-home polysomnography to investigate sleep apnea prevalence. Self-report and laboratory findings were compared with similarly collected data from the Wisconsin Sleep Cohort (WSC) study (n = 1170), a population-based longitudinal study of sleep. The results inform a unique Hmong sleep disorder profile of a high prevalence of sleep apnea, sleep paralysis, and other REM-related sleep abnormalities as well the interaction of culturally related nighttime stressors with these sleep problems. For example, experiences of dab tsog (frightening night spirit pressing on chest) was prevalent and related to sleep apnea indicators, sleep paralysis, nightmares, hypnogogic hallucinations, and insomnia. Understanding the role of sleep disorders and the cultural mechanisms that may trigger or condition response to them could ultimately provide a basis for screening and intervention to reduce the adverse health and emotional consequences of these conditions in Hmong. PMID:22832325

Genetic diversity and domestication origin of tea plant Camellia taliensis (Theaceae) as revealed by microsatellite markers

PubMed Central

2014-01-01

Background Tea is one of the most popular beverages in the world. Many species in the Thea section of the Camellia genus can be processed for drinking and have been domesticated. However, few investigations have focused on the genetic consequence of domestication and geographic origin of landraces on tea plants using credible wild and planted populations of a single species. Here, C. taliensis provides us with a unique opportunity to explore these issues. Results Fourteen nuclear microsatellite loci were employed to determine the genetic diversity and domestication origin of C. taliensis, which were represented by 587 individuals from 25 wild, planted and recently domesticated populations. C. taliensis showed a moderate high level of overall genetic diversity. The greater reduction of genetic diversity and stronger genetic drift were detected in the wild group than in the recently domesticated group, indicating the loss of genetic diversity of wild populations due to overexploitation and habitat fragmentation. Instead of the endangered wild trees, recently domesticated individuals were used to compare with the planted trees for detecting the genetic consequence of domestication. A little and non-significant reduction in genetic diversity was found during domestication. The long life cycle, selection for leaf traits and gene flow between populations will delay the emergence of bottleneck in planted trees. Both phylogenetic and assignment analyses suggested that planted trees may have been domesticated from the adjacent central forest of western Yunnan and dispersed artificially to distant places. Conclusions This study contributes to the knowledge about levels and distribution of genetic diversity of C. taliensis and provides new insights into genetic consequence of domestication and geographic origin of planted trees of this species. As an endemic tea source plant, wild, planted and recently domesticated C. taliensis trees should all be protected for their unique genetic characteristics, which are valuable for tea breeding. PMID:24405939