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Sample records for genomic hybridisation acgh

  1. Microarray comparative genomic hybridisation analysis incorporating genomic organisation, and application to enterobacterial plant pathogens.

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    Leighton Pritchard

    2009-08-01

    Full Text Available Microarray comparative genomic hybridisation (aCGH provides an estimate of the relative abundance of genomic DNA (gDNA taken from comparator and reference organisms by hybridisation to a microarray containing probes that represent sequences from the reference organism. The experimental method is used in a number of biological applications, including the detection of human chromosomal aberrations, and in comparative genomic analysis of bacterial strains, but optimisation of the analysis is desirable in each problem domain.We present a method for analysis of bacterial aCGH data that encodes spatial information from the reference genome in a hidden Markov model. This technique is the first such method to be validated in comparisons of sequenced bacteria that diverge at the strain and at the genus level: Pectobacterium atrosepticum SCRI1043 (Pba1043 and Dickeya dadantii 3937 (Dda3937; and Lactococcus lactis subsp. lactis IL1403 and L. lactis subsp. cremoris MG1363. In all cases our method is found to outperform common and widely used aCGH analysis methods that do not incorporate spatial information. This analysis is applied to comparisons between commercially important plant pathogenic soft-rotting enterobacteria (SRE Pba1043, P. atrosepticum SCRI1039, P. carotovorum 193, and Dda3937.Our analysis indicates that it should not be assumed that hybridisation strength is a reliable proxy for sequence identity in aCGH experiments, and robustly extends the applicability of aCGH to bacterial comparisons at the genus level. Our results in the SRE further provide evidence for a dynamic, plastic 'accessory' genome, revealing major genomic islands encoding gene products that provide insight into, and may play a direct role in determining, variation amongst the SRE in terms of their environmental survival, host range and aetiology, such as phytotoxin synthesis, multidrug resistance, and nitrogen fixation.

  2. [Sotos syndrome diagnosed by comparative genomic hybridisation].

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    Saldarriaga, Wilmar; Molina-Barrera, Laura Camila; Ramírez-Cheyne, Julián

    2016-01-01

    Sotos Syndrome (SS) is a genetic disease with an autosomal dominant pattern caused by haplo-insufficiency of NSD1 gene secondary to point mutations or microdeletion of the 5q35 locus where the gene is located. It is a rare syndrome, occurring in 7 out of every 100,000 births. The objective of this report is to present the case of a 4 year-old patient with a global developmental delay, as well as specific physical findings suggesting a syndrome of genetic origin. Female patient, 4 years of age, thinning hair, triangular facie, long palpebral fissure, arched palate, prominent jaw, winged scapula and clinodactilia of the fifth finger both hands. The molecular test comparative genomic hybridisation test by microarray was subsequently performed, with the result showing 5q35.2 q35.3 region microdeletion of 2,082 MB, including the NSD1 gene. Finally, this article also proposes the performing of comparative genomic hybridisation as the first diagnostic option in cases where clinical findings are suggestive of SS. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. High resolution microarray comparative genomic hybridisation analysis using spotted oligonucleotides.

    NARCIS (Netherlands)

    Carvalho, B; Ouwerkerk, E; Meijer, G.A.; Ylstra, B.

    2004-01-01

    BACKGROUND: Currently, comparative genomic hybridisation array (array CGH) is the method of choice for studying genome wide DNA copy number changes. To date, either amplified representations of bacterial artificial chromosomes (BACs)/phage artificial chromosomes (PACs) or cDNAs have been spotted as

  4. [Comparative genomic hybridisation as a first option in genetic diagnosis: 1,000 cases and a cost-benefit analysis].

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    Castells-Sarret, Neus; Cueto-González, Anna M; Borregan, Mar; López-Grondona, Fermina; Miró, Rosa; Tizzano, Eduardo; Plaja, Alberto

    2017-09-25

    Conventional cytogenetics diagnoses 3-5% of patients with unexplained developmental delay/intellectual disability and/or multiple congenital anomalies. The Multiplex Ligation-dependent Probe Amplification increases diagnostic rates from between 2.4 to 5.8%. Currently the comparative genomic hybridisation array or aCGH is the highest performing diagnostic tool in patients with developmental delay/intellectual disability, congenital anomalies and autism spectrum disorders. Our aim is to evaluate the efficiency of the use of aCGH as first-line test in these and other indications (epilepsy, short stature). A total of 1000 patients referred due to one or more of the abovementioned disorders were analysed by aCGH. Pathogenic genomic imbalances were detected in 14% of the cases, with a variable distribution of diagnosis according to the phenotypes: 18.9% of patients with developmental delay/intellectual disability; 13.7% of multiple congenital anomalies, 9.76% of psychiatric pathologies, 7.02% of patients with epilepsy, and 13.3% of patients with short stature. Within the multiple congenital anomalies, central nervous system abnormalities and congenital heart diseases accounted for 14.9% and 10.6% of diagnoses, respectively. Among the psychiatric disorders, patients with autism spectrum disorders accounted for 8.9% of the diagnoses. Our results demonstrate the effectiveness and efficiency of the use of aCGH as the first line test in genetic diagnosis of patients suspected of genomic imbalances, supporting its inclusion within the National Health System. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  5. Detection of alien genetic introgressions in bread wheat using dot-blot genomic hybridisation.

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    Rey, María-Dolores; Prieto, Pilar

    2017-01-01

    Simple, reliable methods for the identification of alien genetic introgressions are required in plant breeding programmes. The use of genomic dot-blot hybridisation allows the detection of small Hordeum chilense genomic introgressions in the descendants of genetic crosses between wheat and H. chilense addition or substitution lines in wheat when molecular markers are difficult to use. Based on genomic in situ hybridisation, DNA samples from wheat lines carrying putatively H. chilense introgressions were immobilised on a membrane, blocked with wheat genomic DNA and hybridised with biotin-labelled H. chilense genomic DNA as a probe. This dot-blot screening reduced the number of plants necessary to be analysed by molecular markers or in situ hybridisation, saving time and money. The technique was sensitive enough to detect a minimum of 5 ng of total genomic DNA immobilised on the membrane or about 1/420 dilution of H. chilense genomic DNA in the wheat background. The robustness of the technique was verified by in situ hybridisation. In addition, the detection of other wheat relative species such as Hordeum vulgare , Secale cereale and Agropyron cristatum in the wheat background was also reported .

  6. Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridisation.

    NARCIS (Netherlands)

    Osoegawa, K.; Vessere, G.M.; Utami, K.H.; Mansilla, M.A.; Johnson, M.K.; Riley, B.M.; L'Heureux, J.; Pfundt, R.P.; Staaf, J.; Vliet, W.A. van der; Lidral, A.C.; Schoenmakers, E.F.P.M.; Borg, A.; Schutte, B.C.; Lammer, E.J.; Murray, J.C.; Jong, PJ de

    2008-01-01

    AIM AND METHOD: We analysed DNA samples isolated from individuals born with cleft lip and cleft palate to identify deletions and duplications of candidate gene loci using array comparative genomic hybridisation (array-CGH). RESULTS: Of 83 syndromic cases analysed we identified one subject with a

  7. A multi-sample based method for identifying common CNVs in normal human genomic structure using high-resolution aCGH data.

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    Chihyun Park

    Full Text Available BACKGROUND: It is difficult to identify copy number variations (CNV in normal human genomic data due to noise and non-linear relationships between different genomic regions and signal intensity. A high-resolution array comparative genomic hybridization (aCGH containing 42 million probes, which is very large compared to previous arrays, was recently published. Most existing CNV detection algorithms do not work well because of noise associated with the large amount of input data and because most of the current methods were not designed to analyze normal human samples. Normal human genome analysis often requires a joint approach across multiple samples. However, the majority of existing methods can only identify CNVs from a single sample. METHODOLOGY AND PRINCIPAL FINDINGS: We developed a multi-sample-based genomic variations detector (MGVD that uses segmentation to identify common breakpoints across multiple samples and a k-means-based clustering strategy. Unlike previous methods, MGVD simultaneously considers multiple samples with different genomic intensities and identifies CNVs and CNV zones (CNVZs; CNVZ is a more precise measure of the location of a genomic variant than the CNV region (CNVR. CONCLUSIONS AND SIGNIFICANCE: We designed a specialized algorithm to detect common CNVs from extremely high-resolution multi-sample aCGH data. MGVD showed high sensitivity and a low false discovery rate for a simulated data set, and outperformed most current methods when real, high-resolution HapMap datasets were analyzed. MGVD also had the fastest runtime compared to the other algorithms evaluated when actual, high-resolution aCGH data were analyzed. The CNVZs identified by MGVD can be used in association studies for revealing relationships between phenotypes and genomic aberrations. Our algorithm was developed with standard C++ and is available in Linux and MS Windows format in the STL library. It is freely available at: http://embio.yonsei.ac.kr/~Park/mgvd.php.

  8. A multi-sample based method for identifying common CNVs in normal human genomic structure using high-resolution aCGH data.

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    Park, Chihyun; Ahn, Jaegyoon; Yoon, Youngmi; Park, Sanghyun

    2011-01-01

    It is difficult to identify copy number variations (CNV) in normal human genomic data due to noise and non-linear relationships between different genomic regions and signal intensity. A high-resolution array comparative genomic hybridization (aCGH) containing 42 million probes, which is very large compared to previous arrays, was recently published. Most existing CNV detection algorithms do not work well because of noise associated with the large amount of input data and because most of the current methods were not designed to analyze normal human samples. Normal human genome analysis often requires a joint approach across multiple samples. However, the majority of existing methods can only identify CNVs from a single sample. We developed a multi-sample-based genomic variations detector (MGVD) that uses segmentation to identify common breakpoints across multiple samples and a k-means-based clustering strategy. Unlike previous methods, MGVD simultaneously considers multiple samples with different genomic intensities and identifies CNVs and CNV zones (CNVZs); CNVZ is a more precise measure of the location of a genomic variant than the CNV region (CNVR). We designed a specialized algorithm to detect common CNVs from extremely high-resolution multi-sample aCGH data. MGVD showed high sensitivity and a low false discovery rate for a simulated data set, and outperformed most current methods when real, high-resolution HapMap datasets were analyzed. MGVD also had the fastest runtime compared to the other algorithms evaluated when actual, high-resolution aCGH data were analyzed. The CNVZs identified by MGVD can be used in association studies for revealing relationships between phenotypes and genomic aberrations. Our algorithm was developed with standard C++ and is available in Linux and MS Windows format in the STL library. It is freely available at: http://embio.yonsei.ac.kr/~Park/mgvd.php.

  9. Genomic confirmation of hybridisation and recent inbreeding in a vector-isolated Leishmania population.

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    Rogers, Matthew B; Downing, Tim; Smith, Barbara A; Imamura, Hideo; Sanders, Mandy; Svobodova, Milena; Volf, Petr; Berriman, Matthew; Cotton, James A; Smith, Deborah F

    2014-01-01

    Although asexual reproduction via clonal propagation has been proposed as the principal reproductive mechanism across parasitic protozoa of the Leishmania genus, sexual recombination has long been suspected, based on hybrid marker profiles detected in field isolates from different geographical locations. The recent experimental demonstration of a sexual cycle in Leishmania within sand flies has confirmed the occurrence of hybridisation, but knowledge of the parasite life cycle in the wild still remains limited. Here, we use whole genome sequencing to investigate the frequency of sexual reproduction in Leishmania, by sequencing the genomes of 11 Leishmania infantum isolates from sand flies and 1 patient isolate in a focus of cutaneous leishmaniasis in the Çukurova province of southeast Turkey. This is the first genome-wide examination of a vector-isolated population of Leishmania parasites. A genome-wide pattern of patchy heterozygosity and SNP density was observed both within individual strains and across the whole group. Comparisons with other Leishmania donovani complex genome sequences suggest that these isolates are derived from a single cross of two diverse strains with subsequent recombination within the population. This interpretation is supported by a statistical model of the genomic variability for each strain compared to the L. infantum reference genome strain as well as genome-wide scans for recombination within the population. Further analysis of these heterozygous blocks indicates that the two parents were phylogenetically distinct. Patterns of linkage disequilibrium indicate that this population reproduced primarily clonally following the original hybridisation event, but that some recombination also occurred. This observation allowed us to estimate the relative rates of sexual and asexual reproduction within this population, to our knowledge the first quantitative estimate of these events during the Leishmania life cycle.

  10. Tomato genome mapping by fluorescence in situ hybridisation = Kartering van het tomatengenoom met behulp van fluorescentie in situ hybridisatie

    NARCIS (Netherlands)

    Zhong, X.B.

    1998-01-01

    The general introduction reviews the progress in tomato genome mapping using classical genetics, cytogenetics, and molecular genetics, emphasising the great potential of fluorescence in situ hybridisation (FISH) techniques.

    Chapter 2 describes how to

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

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

    2017-04-01

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

  12. High resolution array-based comparative genomic hybridisation of medulloblastomas and supra-tentorial primitive neuroectodermal tumours

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    McCabe, Martin Gerard; Ichimura, Koichi; Liu, Lu; Plant, Karen; Bäcklund, L Magnus; Pearson, Danita M; Collins, Vincent Peter

    2010-01-01

    Medulloblastomas and supratentorial primitive neuroectodermal tumours are aggressive childhood tumours. We report our findings using array comparative genomic hybridisation (CGH) on a whole-genome BAC/PAC/cosmid array with a median clone separation of 0.97Mb to study 34 medulloblastomas and 7 supratentorial primitive neuroectodermal tumours. Array CGH allowed identification and mapping of numerous novel small regions of copy number change to genomic sequence, in addition to the large regions already known from previous studies. Novel amplifications were identified, some encompassing oncogenes, MYCL1, PDGFRA, KIT and MYB, not previously reported to show amplification in these tumours. In addition, one supratentorial primitive neuroectodermal tumour had lost both copies of the tumour suppressor genes CDKN2A & CDKN2B. Ten medulloblastomas had findings suggestive of isochromosome 17q. In contrast to previous reports using conventional CGH, array CGH identified three distinct breakpoints in these cases: Ch 17: 17940393-19251679 (17p11.2, n=6), Ch 17: 20111990-23308272 (17p11.2-17q11.2, n=4) and Ch 17: 38425359-39091575 (17q21.31, n=1). Significant differences were found in the patterns of copy number change between medulloblastomas and supratentorial primitive neuroectodermal tumours, providing further evidence that these tumours are genetically distinct despite their morphological and behavioural similarities. PMID:16783165

  13. A robust Correntropy-based method for analyzing multisample aCGH data.

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    Mohammadi, Majid; Hodtani, Ghosheh Abed; Yassi, Maryam

    2015-11-01

    This paper presents a new method for analyzing array comparative genomic hybridization (aCGH) data based on Correntropy. A new formulation based on low-rank aCGH data and Correntropy is proposed and its solution is presented based on Half-Quadratic method. Compared to existing methods, the proposed method is more robust to high corruptions and various kinds of noise. Moreover, it analyzes all aCGH profiles relating to a data set simultaneously. Experimental results illustrate the robustness of the proposed method when the noise is non-Gaussian and show its excellent performance in other cases. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. The draft genome of the pest tephritid fruit fly Bactrocera tryoni: resources for the genomic analysis of hybridising species.

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    Gilchrist, Anthony Stuart; Shearman, Deborah C A; Frommer, Marianne; Raphael, Kathryn A; Deshpande, Nandan P; Wilkins, Marc R; Sherwin, William B; Sved, John A

    2014-12-20

    The tephritid fruit flies include a number of economically important pests of horticulture, with a large accumulated body of research on their biology and control. Amongst the Tephritidae, the genus Bactrocera, containing over 400 species, presents various species groups of potential utility for genetic studies of speciation, behaviour or pest control. In Australia, there exists a triad of closely-related, sympatric Bactrocera species which do not mate in the wild but which, despite distinct morphologies and behaviours, can be force-mated in the laboratory to produce fertile hybrid offspring. To exploit the opportunities offered by genomics, such as the efficient identification of genetic loci central to pest behaviour and to the earliest stages of speciation, investigators require genomic resources for future investigations. We produced a draft de novo genome assembly of Australia's major tephritid pest species, Bactrocera tryoni. The male genome (650-700 Mbp) includes approximately 150 Mb of interspersed repetitive DNA sequences and 60 Mb of satellite DNA. Assessment using conserved core eukaryotic sequences indicated 98% completeness. Over 16,000 MAKER-derived gene models showed a large degree of overlap with other Dipteran reference genomes. The sequence of the ribosomal RNA transcribed unit was also determined. Unscaffolded assemblies of B. neohumeralis and B. jarvisi were then produced; comparison with B. tryoni showed that the species are more closely related than any Drosophila species pair. The similarity of the genomes was exploited to identify 4924 potentially diagnostic indels between the species, all of which occur in non-coding regions. This first draft B. tryoni genome resembles other dipteran genomes in terms of size and putative coding sequences. For all three species included in this study, we have identified a comprehensive set of non-redundant repetitive sequences, including the ribosomal RNA unit, and have quantified the major satellite DNA

  15. Targeted array comparative genomic hybridisation (array CGH) identifies genomic imbalances associated with isolated congenital diaphragmatic hernia (CDH).

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    Srisupundit, Kasemsri; Brady, Paul D; Devriendt, Koenraad; Fryns, Jean-Pierre; Cruz-Martinez, Rogelio; Gratacos, Eduard; Deprest, Jan A; Vermeesch, Joris R

    2010-12-01

    Congenital diaphragmatic hernia (CDH) is a congenital birth defect affecting around 1/3000 births. We propose that a significant number of isolated CDH cases have an underlying genetic cause, and that a subset of these result from copy number variations (CNVs) identifiable by array CGH. We have designed a custom array targeted at genes and genomic loci associated with CDH. A total of 79 isolated CDH patients were screened using this targeted array. In three patients, we detected genomic imbalances associated with the observed diaphragmatic hernia; a deletion of 8p22-p23.3, 14.2 Mb in size, a 340 kb duplication of Xq13.1 including the ephrin-B1 gene (EFNB1), and mosaicism for trisomy 2. Using this approach, we detected genomic imbalances associated with CDH in 3/79 (4%) isolated CDH patients. Our findings further implicate 8p deletions as being associated with CDH. The duplication of EFNB1 further highlights this gene as a potential candidate involved in diaphragm development. Mosaicism for trisomy 2 is a rare event and unlikely to be a common cause of CDH. Further investigations of isolated CDH patients by array CGH will continue to identify novel submicroscopic loci and refine genomic regions associated with CDH. Copyright © 2010 John Wiley & Sons, Ltd.

  16. Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

    DEFF Research Database (Denmark)

    Staaf, Johan; Törngren, Therese; Rambech, Eva

    2008-01-01

    hybridization (CGH) platform of 60mer oligonucleotides. The 4 x 44 K array format provides high-resolution coverage (200-300 bp) of 400-700 kb genomic regions surrounding six cancer susceptibility genes. We evaluate its performance to accurately detect and precisely map earlier described or novel large germline...... of primers for sequence determination of the breakpoints. The array platform can be streamlined for a particular application, e.g., focusing on breast cancer susceptibility genes, with increased capacity using multiformat design, and represents a valuable new tool and complement for genetic screening...

  17. Deciphering the hybridisation history leading to the Lager lineage based on the mosaic genomes of Saccharomyces bayanus strains NBRC1948 and CBS380.

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    Huu-Vang Nguyen

    Full Text Available Saccharomyces bayanus is a yeast species described as one of the two parents of the hybrid brewing yeast S. pastorianus. Strains CBS380(T and NBRC1948 have been retained successively as pure-line representatives of S. bayanus. In the present study, sequence analyses confirmed and upgraded our previous finding: S. bayanus type strain CBS380(T harbours a mosaic genome. The genome of strain NBRC1948 was also revealed to be mosaic. Both genomes were characterized by amplification and sequencing of different markers, including genes involved in maltotriose utilization or genes detected by array-CGH mapping. Sequence comparisons with public Saccharomyces spp. nucleotide sequences revealed that the CBS380(T and NBRC1948 genomes are composed of: a predominant non-cerevisiae genetic background belonging to S. uvarum, a second unidentified species provisionally named S. lagerae, and several introgressed S. cerevisiae fragments. The largest cerevisiae-introgressed DNA common to both genomes totals 70kb in length and is distributed in three contigs, cA, cB and cC. These vary in terms of length and presence of MAL31 or MTY1 (maltotriose-transporter gene. In NBRC1948, two additional cerevisiae-contigs, cD and cE, totaling 12kb in length, as well as several smaller cerevisiae fragments were identified. All of these contigs were partially detected in the genomes of S. pastorianus lager strains CBS1503 (S. monacensis and CBS1513 (S. carlsbergensis explaining the noticeable common ability of S. bayanus and S. pastorianus to metabolize maltotriose. NBRC1948 was shown to be inter-fertile with S. uvarum CBS7001. The cross involving these two strains produced F1 segregants resembling the strains CBS380(T or NRRLY-1551. This demonstrates that these S. bayanus strains were the offspring of a cross between S. uvarum and a strain similar to NBRC1948. Phylogenies established with selected cerevisiae and non-cerevisiae genes allowed us to decipher the complex hybridisation

  18. A High-Throughput Computational Framework for Identifying Significant Copy Number Aberrations from Array Comparative Genomic Hybridisation Data

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    Ian Roberts

    2012-01-01

    Full Text Available Reliable identification of copy number aberrations (CNA from comparative genomic hybridization data would be improved by the availability of a generalised method for processing large datasets. To this end, we developed swatCGH, a data analysis framework and region detection heuristic for computational grids. swatCGH analyses sequentially displaced (sliding windows of neighbouring probes and applies adaptive thresholds of varying stringency to identify the 10% of each chromosome that contains the most frequently occurring CNAs. We used the method to analyse a published dataset, comparing data preprocessed using four different DNA segmentation algorithms, and two methods for prioritising the detected CNAs. The consolidated list of the most commonly detected aberrations confirmed the value of swatCGH as a simplified high-throughput method for identifying biologically significant CNA regions of interest.

  19. A robust aCGH data recovery framework based on half quadratic minimization.

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    Mohammadi, Majid; Abed Hodtani, Ghosheh

    2016-03-01

    This paper presents a general half quadratic framework for simultaneous analysis of the whole array comparative genomic hybridization (aCGH) profiles in a data set. The proposed framework accommodates different M-estimation loss functions and two underlying assumptions for aCGH profiles of a data set: sparsity and low rank. Using M-estimation loss functions, this framework is more robust to various types of noise and outliers. The solution of the proposed framework is given by half quadratic (HQ) minimization. To hasten this procedure, accelerated proximal gradient (APG) is utilized. Experimental results support the robustness of the proposed framework in comparison to the state-of-the-art algorithms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Measurement of locus copy number by hybridisation with amplifiable probes

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    Armour, John A. L.; Sismani, Carolina; Patsalis, Philippos C.; Cross, Gareth

    2000-01-01

    Despite its fundamental importance in genome analysis, it is only recently that systematic approaches have been developed to assess copy number at specific genetic loci, or to examine genomic DNA for submicroscopic deletions of unknown location. In this report we show that short probes can be recovered and amplified quantitatively following hybridisation to genomic DNA. This simple observation forms the basis of a new approach to determining locus copy number in complex genomes. The power and specificity of multiplex amplifiable probe hybridisation is demonstrated by the simultaneous assessment of copy number at a set of 40 human loci, including detection of deletions causing Duchenne muscular dystrophy and Prader–Willi/Angelman syndromes. Assembly of other probe sets will allow novel, technically simple approaches to a wide variety of genetic analyses, including the potential for extension to high resolution genome-wide screens for deletions and amplifications. PMID:10606661

  1. Array comparative genomic hybridisation-based identification of two imbalances of chromosome 1p in a 9-year-old girl with a monosomy 1p36 related phenotype and a family history of learning difficulties: a case report

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    Fitzgibbon Gregory J

    2008-11-01

    Full Text Available Abstract Introduction Monosomy 1p36 is one of the most common terminal deletion syndromes, with an approximate incidence of 1 in every 5000 live births. This syndrome is associated with several pronounced clinical features including characteristic facial features, cardiac abnormalities, seizures and mental retardation, all of which are believed to be due to haploinsufficiency of genes within the 1p36 region. The deletion size varies from approximately 1.5 Mb to 10 Mb with the most common breakpoints located at 1p36.13 to 1p36.33. Over 70% of 1p36 deletion patients have a true terminal deletion. A further 7% have interstitial deletions and a proportion have a derivative chromosome 1 where the 1p telomere is replaced by material from another chromosome, either as a result of a de-novo rearrangement or as a consequence of malsegregation of a balanced parental translocation at meiosis. Case presentation Array comparative genomic hybridisation analysis of a 9-year-old Caucasian girl presenting with dysmorphic facial features and learning difficulties, for whom previous routine karyotyping had been normal, identified two submicroscopic rearrangements within chromosome 1p. Detection of both an insertional duplication of a region of 1p32.3 into the subtelomeric region of the short arm of a chromosome 1 homologue and a deletion within 1p36.32 of the same chromosome instigated a search for candidate genes within these regions which could be responsible for the clinical phenotype of the patient. Several genes were identified by computer-based annotation, some of which have implications in neurological and physical development. Conclusion Array comparative genomic hybridisation is providing a robust method for pinpointing regions of candidate genes associated with clinical phenotypes that extend beyond the resolution of the light microscope. This case report provides an example of how this method of analysis and the subsequent reporting of findings have

  2. ADaCGH: A parallelized web-based application and R package for the analysis of aCGH data.

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    Ramón Díaz-Uriarte

    Full Text Available BACKGROUND: Copy number alterations (CNAs in genomic DNA have been associated with complex human diseases, including cancer. One of the most common techniques to detect CNAs is array-based comparative genomic hybridization (aCGH. The availability of aCGH platforms and the need for identification of CNAs has resulted in a wealth of methodological studies. METHODOLOGY/PRINCIPAL FINDINGS: ADaCGH is an R package and a web-based application for the analysis of aCGH data. It implements eight methods for detection of CNAs, gains and losses of genomic DNA, including all of the best performing ones from two recent reviews (CBS, GLAD, CGHseg, HMM. For improved speed, we use parallel computing (via MPI. Additional information (GO terms, PubMed citations, KEGG and Reactome pathways is available for individual genes, and for sets of genes with altered copy numbers. CONCLUSIONS/SIGNIFICANCE: ADACGH represents a qualitative increase in the standards of these types of applications: a all of the best performing algorithms are included, not just one or two; b we do not limit ourselves to providing a thin layer of CGI on top of existing BioConductor packages, but instead carefully use parallelization, examining different schemes, and are able to achieve significant decreases in user waiting time (factors up to 45x; c we have added functionality not currently available in some methods, to adapt to recent recommendations (e.g., merging of segmentation results in wavelet-based and CGHseg algorithms; d we incorporate redundancy, fault-tolerance and checkpointing, which are unique among web-based, parallelized applications; e all of the code is available under open source licenses, allowing to build upon, copy, and adapt our code for other software projects.

  3. Review of the Application of Modern Cytogenetic Methods (FISH/GISH to the Study of Reticulation (Polyploidy/Hybridisation

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    Michael Chester

    2010-07-01

    Full Text Available The convergence of distinct lineages upon interspecific hybridisation, including when accompanied by increases in ploidy (allopolyploidy, is a driving force in the origin of many plant species. In plant breeding too, both interspecific hybridisation and allopolyploidy are important because they facilitate introgression of alien DNA into breeding lines enabling the introduction of novel characters. Here we review how fluorescence in situ hybridisation (FISH and genomic in situ hybridisation (GISH have been applied to: 1 studies of interspecific hybridisation and polyploidy in nature, 2 analyses of phylogenetic relationships between species, 3 genetic mapping and 4 analysis of plant breeding materials. We also review how FISH is poised to take advantage of nextgeneration sequencing (NGS technologies, helping the rapid characterisation of the repetitive fractions of a genome in natural populations and agricultural plants.

  4. Introgression of tomato chromosomes into the potato genome : an analysis through molecular marker and in situ hybridisation techniques = [Introgressie van tomatenchromosomen in het aardappelgenoom : een analyse met behulp van moleculaire merker en in situ hybridisatie technieken

    NARCIS (Netherlands)

    Garriga Caldere, F.

    1998-01-01

    Transfer of alien chromosomes and genes across intergeneric boundaries can be useful not only for the introgression of desirable characters but also for fundamental genetic studies. The successful demonstration of hybridisation of potato ( Solanum tuberosum ) and tomato

  5. Findings from aCGH in patients with congenital diaphragmatic hernia (CDH): a possible locus for Fryns syndrome.

    Science.gov (United States)

    Kantarci, S; Casavant, D; Prada, C; Russell, M; Byrne, J; Haug, L Wilkins; Jennings, R; Manning, S; Boyd, T K; Fryns, J P; Holmes, L B; Donahoe, P K; Lee, C; Kimonis, V; Pober, B R

    2006-01-01

    Congenital diaphragmatic hernia (CDH) is a common and often devastating birth defect that can occur in isolation or as part of a malformation complex. Considerable progress is being made in the identification of genetic causes of CDH. We applied array-based comparative genomic hybridization (aCGH) of approximately 1Mb resolution to 29 CDH patients with prior normal karyotypes who had been recruited into our multi-site study. One patient, clinically diagnosed with Fryns syndrome, demonstrated a de novo 5Mb deletion at chromosome region 1q41-q42.12 that was confirmed by FISH. Given prior reports of CDH in association with cytogenetic abnormalities in this region, we propose that this represents a locus for Fryns syndrome, a Fryns syndrome phenocopy, or CDH. (c) 2005 Wiley-Liss, Inc.

  6. Mating, hybridisation and introgression in Lasius ants

    NARCIS (Netherlands)

    Have, van der T.M.; Pedersen, J.S.; Boomsma, J.J.

    2011-01-01

    Recent reviews have shown that hybridisation among ant species is likely to be more common than previously appreciated. but that documented cases of introgression remain rare. After molecular phylogenetic work had shown that European Lasius niger (LINNAEUS, 1758) and L. psammophilus SEIFERT, 1992

  7. Hybridisation between native Oreochromis species and introduced ...

    African Journals Online (AJOL)

    The Nile tilapia Oreochromis niloticus has been introduced throughout Africa outside its native range for aquaculture purposes. Hybridisation between escaped O. niloticus and native Oreochromis species is of concern due to potential negative effects on wild genetic resources for conservation, aquaculture and capture ...

  8. Asterias: A Parallelized Web-based Suite for the Analysis of Expression and aCGH Data

    Directory of Open Access Journals (Sweden)

    Ramón Díaz-Uriarte

    2007-01-01

    Full Text Available The analysis of expression and CGH arrays plays a central role in the study of complex diseases, especially cancer, including finding markers for early diagnosis and prognosis, choosing an optimal therapy, or increasing our understanding of cancer development and metastasis. Asterias (http://www.asterias.info is an integrated collection of freely-accessible web tools for the analysis of gene expression and aCGH data. Most of the tools use parallel computing (via MPI and run on a server with 60 CPUs for computation; compared to a desktop or server-based but not parallelized application, parallelization provides speed ups of factors up to 50. Most of our applications allow the user to obtain additional information for user-selected genes (chromosomal location, PubMed ids, Gene Ontology terms, etc. by using clickable links in tables and/or fi gures. Our tools include: normalization of expression and aCGH data (DNMAD; converting between different types of gene/clone and protein identifi ers (IDconverter/IDClight; fi ltering and imputation (preP; finding differentially expressed genes related to patient class and survival data (Pomelo II; searching for models of class prediction (Tnasas; using random forests to search for minimal models for class prediction or for large subsets of genes with predictive capacity (GeneSrF; searching for molecular signatures and predictive genes with survival data (SignS; detecting regions of genomic DNA gain or loss (ADaCGH. The capability to send results between different applications, access to additional functional information, and parallelized computation make our suite unique and exploit features only available to web-based applications.

  9. True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.

    Science.gov (United States)

    Brunelli, Matteo; Bria, Emilio; Nottegar, Alessia; Cingarlini, Sara; Simionato, Francesca; Caliò, Anna; Eccher, Albino; Parolini, Claudia; Iannucci, Antonio; Gilioli, Eliana; Pedron, Serena; Massari, Francesco; Tortora, Giampaolo; Borze, Ioana; Knuutila, Sakari; Gobbo, Stefano; Santo, Antonio; Tondulli, Luca; Calabrò, Francesco; Martignoni, Guido; Chilosi, Marco

    2012-01-01

    Squamous lung carcinoma lacks specific "ad hoc" therapies. Amplification of chromosome 3q is the most common genomic aberration and this region harbours genes having role as novel targets for therapeutics. There is no standard definition on how to score and report 3q amplification. False versus true 3q chromosomal amplification in squamous cell lung carcinoma may have tremendous impact on trials involving drugs which target DNA zones mapping on 3q. Forty squamous lung carcinomas were analyzed by FISH to assess chromosome 3q amplification. aCGH was performed as gold-standard to avoid false positive amplifications. Three clustered patterns of fluorescent signals were observed. Eight cases out of 40 (20%) showed ≥8 3q signals. Twenty out of 40 (50%) showed from 3 to 7 signals. The remaining showed two fluorescent signals (30%). When corrected by whole chromosome 3 signals, only cases with ≥8 signals maintained a LSI 3q/CEP3 ratio >2. Only the cases showing 3q amplification by aCGH (+3q25.3-3q27.3) showed ≥8 fluorescent signals at FISH evidencing a 3q/3 ratio >2. The remaining cases showed flat genomic portrait at aCGH on chromosome 3. We concluded that: 1) absolute copy number of 3q chromosomal region may harbour false positive interpretation of 3q amplification in squamous cell carcinoma; 2) a case results truly "amplified for chromosome 3q" when showing ≥8 fluorescent 3q signals; 3) trials involving drugs targeting loci on chromosome 3q in squamous lung carcinoma therapy have to consider false versus true 3q chromosomal amplification.

  10. True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.

    Directory of Open Access Journals (Sweden)

    Matteo Brunelli

    Full Text Available Squamous lung carcinoma lacks specific "ad hoc" therapies. Amplification of chromosome 3q is the most common genomic aberration and this region harbours genes having role as novel targets for therapeutics. There is no standard definition on how to score and report 3q amplification. False versus true 3q chromosomal amplification in squamous cell lung carcinoma may have tremendous impact on trials involving drugs which target DNA zones mapping on 3q. Forty squamous lung carcinomas were analyzed by FISH to assess chromosome 3q amplification. aCGH was performed as gold-standard to avoid false positive amplifications. Three clustered patterns of fluorescent signals were observed. Eight cases out of 40 (20% showed ≥8 3q signals. Twenty out of 40 (50% showed from 3 to 7 signals. The remaining showed two fluorescent signals (30%. When corrected by whole chromosome 3 signals, only cases with ≥8 signals maintained a LSI 3q/CEP3 ratio >2. Only the cases showing 3q amplification by aCGH (+3q25.3-3q27.3 showed ≥8 fluorescent signals at FISH evidencing a 3q/3 ratio >2. The remaining cases showed flat genomic portrait at aCGH on chromosome 3. We concluded that: 1 absolute copy number of 3q chromosomal region may harbour false positive interpretation of 3q amplification in squamous cell carcinoma; 2 a case results truly "amplified for chromosome 3q" when showing ≥8 fluorescent 3q signals; 3 trials involving drugs targeting loci on chromosome 3q in squamous lung carcinoma therapy have to consider false versus true 3q chromosomal amplification.

  11. A healthy HLA-matched baby born by using a combination of aCGH and Karyomapping: the first latin american case

    Science.gov (United States)

    Delgado, Andrea; Llerena, Guillermo; Lopez, Rosmary; Portella, Jimmy; Inoue, Naomi; Noriega-Hoces, Luis; Guzman, Luis

    2017-01-01

    PGD for HLA typing is a procedure that can be performed when an affected child requires a transplant to treat a non-hereditary disorder related to the hematopoietic and/or immune system. Hematopoietic stem cell transplantation from an HLA-identical donor provides the best treatment option. Three conventional ovarian stimulation procedures for IVF were performed in a couple with a 10-year-old child diagnosed with T-cell acute lymphoblastic leukemia of high risk. Trophectoderm biopsy and aCGH examination were performed on 15 blastocysts, three on the first IVF procedure, four on the second cycle, and eight on the third. Three euploid blastocysts HLA-compatible with the genome of the affected child were identified. One euploid blastocyst HLA-compatible with the affected child was warmed and transferred, resulting in an HLA-matched live birth. In conclusion, combined aCGH for aneuploidy screening and Karyomapping may be performed in a single biopsy procedure. PMID:29120571

  12. Bridging the gap from prenatal karyotyping to whole-genome array comparative genomic hybridization in Hong Kong: survey on knowledge and acceptance of health-care providers and pregnant women.

    Science.gov (United States)

    Cheng, Hiu Yee Heidi; Kan, Anita Sik-Yau; Hui, Pui Wah; Lee, Chin Peng; Tang, Mary Hoi Yin

    2017-12-01

    The use of array comparative genomic hybridization (aCGH) has been increasingly widespread. The challenge of integration of this technology into prenatal diagnosis was the interpretation of results and communicating findings of unclear clinical significance. This study assesses the knowledge and acceptance of prenatal aCGH in Hong Kong obstetricians and pregnant women. The aim is to identify the needs and gaps before implementing the replacement of karyotyping with aCGH. Questionnaires with aCGH information in the form of pamphlets were sent by post to obstetrics and gynecology doctors. For the pregnant women group, a video presentation, pamphlets on aCGH and a self-administered questionnaire were provided at the antenatal clinic. The perception of aCGH between doctors and pregnant women was similar. Doctors not choosing aCGH were more concerned about the difficulty in counseling of variants of unknown significance and adult-onset disease in pregnant women, whereas pregnant women not choosing aCGH were more concerned about the increased waiting time leading to increased anxiety. Prenatal aCGH is perceived as a better test by both doctors and patients. Counseling support, training, and better understanding and communication of findings of unclear clinical significance are necessary to improve doctor-patient experience.

  13. Ribonucleic acid from the higher plant Matthiola incana. Molecular weight measurements and DNA-RNA hybridisation studies.

    Science.gov (United States)

    Grierson, D; Hemleben, V

    1977-04-04

    The percentage of DNA from the crucifer Matthiola incana coding for different types of RNA was measured by filter saturation hybridisation experiments using RNA labelled in vivo. In addition, the melting curves of the various DNA - RNA hybrids formed and the buoyant densities of the DNA sequences complementary to different types of RNA were measured. 1. The RNA preparations used were 25, 18, and 5 S rRNA and 4 S RNA, purified by gel electrophoresis, and poly(A)-containing RNA purified by oligo-(dT)-cellulose chromatography. The molecular weights of the 25 S and 18 S rRNAs, calculated from the mobility in formamide-acrylamide gels relative to Escherichia coli RNA, are 1.25 - 10(6) and 0.64 - 10(6). The rRNA precursor has a molecular weight of approx. 2.1 - 10(6) and the average molecular weight of the poly(A)-containing RNA from both cotyledons and roots is 4 - 10(5). 2. The percentage of the genome, calculated on the basis of double-stranded DNA, coding for these RNAs and the estimated number of genes per haploid DNA amount are approximately 0.46% and 1100 for 25 S plus 18 S rRNA, 0.032% and 3600 for 5 S rRNA and 0.072% and 13 000 for 4 S RNA. In filter hybridisation experiments very little hybridisation of poly(A)-containing RNA was found. A rapidly-hybridising component is attributed to small amounts of contaminating rRNA. 3. M. incana DNA has a main band at 1.697 g - ml-1 in CsCl and a satellite constituting approximately 3% of the DNA, at 1.708 g - ml-1 - 25 and 18 S rRNA hybridise to DNA with a buoyant density of 1.701--2 g - ml-1. The buoyant density of 5 S DNA is slightly less at 1.700--1 g - ml-1. 4. S RNA hybridises to at least two separate regions, one within the main-band DNA and a second lighter component. None of the RNAs tested hybridised to the satellite DNA. The Tm of the DNA - RNA hybrids in 1 X SSC is 89 degrees C for 25 S rRNA, 85 degrees C for 5 S rRNA and 82 degrees C for 4 S RNA. 4. 5 and 4 S RNA preparations contain fragments which hybridise

  14. An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients

    NARCIS (Netherlands)

    Vollebergh, M. A.; Lips, E. H.; Nederlof, P. M.; Wessels, L. F. A.; Schmidt, M. K.; van Beers, E. H.; Cornelissen, S.; Holtkamp, M.; Froklage, F. E.; de Vries, E. G. E.; Schrama, J. G.; Wesseling, J.; van de Vijver, M. J.; van Tinteren, H.; de Bruin, Michiel; Hauptmann, M.; Rodenhuis, S.; Linn, S. C.

    2011-01-01

    Breast cancer cells deficient for BRCA1 are hypersensitive to agents inducing DNA double-strand breaks (DSB), such as bifunctional alkylators and platinum agents. Earlier, we had developed a comparative genomic hybridisation (CGH) classifier based on BRCA1-mutated breast cancers. We hypothesised

  15. Interspecific Hybridisation in Campanula

    DEFF Research Database (Denmark)

    Röper, Anna Catharina

    had an influence on the number of ovules and germination success in some cross combinations. In the second research part interspecific hybrids obtained from ovule culture were genotypically and phenotypically characterised by AFLP analysis, flow cytometry and biometrical parameters. Hybridity......In the present thesis, economically important Campanula species were selected for interspecific hybridisation to increase the genetic viability in plant breeding material. To reach this goal, ovule culture was established as an embryo rescue technique to overcome post-fertilisation barriers...... was confirmed for most of the interspecific hybrids. Intermediate phenotypes compared to the parental species were found for several interspecific hybrids. The results from this PhD study demonstrated that the genetic viability could be increased in Campanula and reveal valuable information for interspecific...

  16. The Hybridisation of Higher Education in Canada

    Directory of Open Access Journals (Sweden)

    Douglas Shale

    2002-01-01

    Full Text Available Canada's postsecondary institutions are becoming increasingly involved with technology enhanced learning, generally under the rubric of distance education. Growth and activity in distance education stems from rapid developments in communication and information technologies such as videoconferencing and the Internet. This case study focuses on the use of new technologies, primarily within the context of higher education institutions operating in Canada's English speaking provinces. Capitalising on the interactive capabilities of "new" learning technologies, some distance education providers are starting to behave more like conventional educational institutions in terms of forming study groups and student cohorts. Conversely, new telecommunications technologies are having a reverse impact on traditional classroom settings, and as a result conventional universities are beginning to establish administrative structures reflective of those used by distance education providers. When viewed in tandem, these trends reflect growing convergence between conventional and distance learning modes, leading to the hybridisation of higher education in Canada.

  17. High Quality Genomic Copy Number Data from Archival Formalin-Fixed Paraffin-Embedded Leiomyosarcoma: Optimisation of Universal Linkage System Labelling

    Science.gov (United States)

    Salawu, Abdulazeez; Ul-Hassan, Aliya; Hammond, David; Fernando, Malee; Reed, Malcolm; Sisley, Karen

    2012-01-01

    Most soft tissue sarcomas are characterized by genetic instability and frequent genomic copy number aberrations that are not subtype-specific. Oligonucleotide microarray-based Comparative Genomic Hybridisation (array CGH) is an important technique used to map genome-wide copy number aberrations, but the traditional requirement for high-quality DNA typically obtained from fresh tissue has limited its use in sarcomas. Although large archives of Formalin-fixed Paraffin-embedded (FFPE) tumour samples are available for research, the degradative effects of formalin on DNA from these tissues has made labelling and analysis by array CGH technically challenging. The Universal Linkage System (ULS) may be used for a one-step chemical labelling of such degraded DNA. We have optimised the ULS labelling protocol to perform aCGH on archived FFPE leiomyosarcoma tissues using the 180k Agilent platform. Preservation age of samples ranged from a few months to seventeen years and the DNA showed a wide range of degradation (when visualised on agarose gels). Consistently high DNA labelling efficiency and low microarray probe-to-probe variation (as measured by the derivative log ratio spread) was seen. Comparison of paired fresh and FFPE samples from identical tumours showed good correlation of CNAs detected. Furthermore, the ability to macro-dissect FFPE samples permitted the detection of CNAs that were masked in fresh tissue. Aberrations were visually confirmed using Fluorescence in situ Hybridisation. These results suggest that archival FFPE tissue, with its relative abundance and attendant clinical data may be used for effective mapping for genomic copy number aberrations in such rare tumours as leiomyosarcoma and potentially unravel clues to tumour origins, progression and ultimately, targeted treatment. PMID:23209738

  18. Cross-species comparison of aCGH data from mouse and human BRCA1- and BRCA2-mutated breast cancers

    International Nuclear Information System (INIS)

    Holstege, Henne; Wessels, Lodewyk FA; Nederlof, Petra M; Jonkers, Jos; Beers, Erik van; Velds, Arno; Liu, Xiaoling; Joosse, Simon A; Klarenbeek, Sjoerd; Schut, Eva; Kerkhoven, Ron; Klijn, Christiaan N

    2010-01-01

    Genomic gains and losses are a result of genomic instability in many types of cancers. BRCA1- and BRCA2-mutated breast cancers are associated with increased amounts of chromosomal aberrations, presumably due their functions in genome repair. Some of these genomic aberrations may harbor genes whose absence or overexpression may give rise to cellular growth advantage. So far, it has not been easy to identify the driver genes underlying gains and losses. A powerful approach to identify these driver genes could be a cross-species comparison of array comparative genomic hybridization (aCGH) data from cognate mouse and human tumors. Orthologous regions of mouse and human tumors that are commonly gained or lost might represent essential genomic regions selected for gain or loss during tumor development. To identify genomic regions that are associated with BRCA1- and BRCA2-mutated breast cancers we compared aCGH data from 130 mouse Brca1 Δ/Δ ;p53 Δ/Δ , Brca2 Δ/Δ ;p53 Δ/Δ and p53 Δ/Δ mammary tumor groups with 103 human BRCA1-mutated, BRCA2-mutated and non-hereditary breast cancers. Our genome-wide cross-species analysis yielded a complete collection of loci and genes that are commonly gained or lost in mouse and human breast cancer. Principal common CNAs were the well known MYC-associated gain and RB1/INTS6-associated loss that occurred in all mouse and human tumor groups, and the AURKA-associated gain occurred in BRCA2-related tumors from both species. However, there were also important differences between tumor profiles of both species, such as the prominent gain on chromosome 10 in mouse Brca2 Δ/Δ ;p53 Δ/Δ tumors and the PIK3CA associated 3q gain in human BRCA1-mutated tumors, which occurred in tumors from one species but not in tumors from the other species. This disparity in recurrent aberrations in mouse and human tumors might be due to differences in tumor cell type or genomic organization between both species. The selection of the oncogenome during

  19. BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1

    Directory of Open Access Journals (Sweden)

    Estivill Xavier

    2009-12-01

    Full Text Available Abstract Background Microdeletion of the chromosome 22q11.2 region is the most common genetic aberration among patients with velocardiofacial syndrome (VCFS but a subset of subjects do not show alterations of this chromosome region. Methods We analyzed 18 patients with VCFS-like features by comparative genomic hybridisation (aCGH array and performed a face-to-face slide hybridization with two different arrays: a whole genome and a chromosome 22-specific BAC array. Putative rearrangements were confirmed by FISH and MLPA assays. Results One patient carried a combination of rearrangements on 1q21.1, consisting in a microduplication of 212 kb and a close microdeletion of 1.15 Mb, previously reported in patients with variable phenotypes, including mental retardation, congenital heart defects (CHD and schizophrenia. While 326 control samples were negative for both 1q21.1 rearrangements, one of 73 patients carried the same 212-kb microduplication, reciprocal to TAR microdeletion syndrome. Also, we detected four copy number variants (CNVs inherited from one parent (a 744-kb duplication on 10q11.22; a 160 kb duplication and deletion on 22q11.21 in two cases; and a gain of 140 kb on 22q13.2, not present in control subjects, raising the potential role of these CNVs in the VCFS-like phenotype. Conclusions Our results confirmed aCGH as a successful strategy in order to characterize additional submicroscopic aberrations in patients with VCF-like features that fail to show alterations in 22q11.2 region. We report a 212-kb microduplication on 1q21.1, detected in two patients, which may contribute to CHD.

  20. Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer

    DEFF Research Database (Denmark)

    Carneiro, Ana; Isinger, Anna; Karlsson, Anna

    2008-01-01

    applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. METHODS: A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential......p13.3 independently predicted poor survival in multivariate analysis. CONCLUSION: aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict...

  1. Evaluation of Real-Time Quantitative PCR as a Standard Cytogenetic Diagnostic Tool for Confirmation of Microarray (aCGH) Results and Determination of Inheritance

    OpenAIRE

    Wang, Rubin; Carter, Jenny; Lench, Nicholas

    2013-01-01

    Aim: To evaluate the use of real-time quantitative PCR (qPCR) as a diagnostic tool for follow up of abnormal microarray (aCGH) results. Method: qPCR was performed on 207 samples with known aCGH results to detect chromosomal abnormality and determine the capability of qPCR. Eighty-four samples were processed and the results compared with the original aCGH result and with one or more of the alternative follow-up methods: aCGH, fluorescence in situ hybridization (FISH), or karyotyping. A separat...

  2. Climate change promotes hybridisation between deeply divergent species

    Directory of Open Access Journals (Sweden)

    Daniele Canestrelli

    2017-03-01

    Full Text Available Rare hybridisations between deeply divergent animal species have been reported for decades in a wide range of taxa, but have often remained unexplained, mainly considered chance events and reported as anecdotal. Here, we combine field observations with long-term data concerning natural hybridisations, climate, land-use, and field-validated species distribution models for two deeply divergent and naturally sympatric toad species in Europe (Bufo bufo and Bufotes viridis species groups. We show that climate warming and seasonal extreme temperatures are conspiring to set the scene for these maladaptive hybridisations, by differentially affecting life-history traits of both species. Our results identify and provide evidence of an ultimate cause for such events, and reveal that the potential influence of climate change on interspecific hybridisations goes far beyond closely related species. Furthermore, climate projections suggest that the chances for these events will steadily increase in the near future.

  3. Time-Resolved Fluorometry Based Sandwich Hybridisation Assay for HLA-DQA1 Typing

    Science.gov (United States)

    Sjöroos, Minna; Ilonen, Jorma; Reijonen, Helena; Lövgren, Timo

    1998-01-01

    A microtitration plate based time-resolved fluorescence (TRF) hybridisation assay was developed for HLA typing utilising biotinylated sequence-specific catching probes and europium (Eu) labelled gene locus-specific detection probe to allow time-resolved fluorometer reading of the reaction. In an application for HLA-DQA typing a 228 base pair long region of the polymorphic exon 2 of DQA1 gene was amplified and the denatured PCR product distributed into streptavidin-coated microtitration wells together with the detection probe and one of the catching probes. After incubation and washes, the enhancement solution was added and specific hybridisation signal detected by measuring the emitted light. A series of 100 isolated genomic DNA samples were studied using biotinylated probes specific for DQA1*01, *0101/0104, *0103/0201/0601, *0201, *03, *0401/0601, *05 and *0502 alleles with results demonstrating the capacity of the test to detect aimed alleles. A series of whole blood spot samples were also studied and the results confirmed the applicability of this modification of the test. PMID:9706458

  4. Time-Resolved Fluorometry Based Sandwich Hybridisation Assay for HLA-DQA1 Typing

    Directory of Open Access Journals (Sweden)

    Minna Sjöroos

    1998-01-01

    Full Text Available A microtitration plate based time-resolved fluorescence (TRF hybridisation assay was developed for HLA typing utilising biotinylated sequence-specific catching probes and europium (Eu labelled gene locus-specific detection probe to allow time-resolved fluorometer reading of the reaction. In an application for HLA-DQA typing a 228 base pair long region of the polymorphic exon 2 of DQA1 gene was amplified and the denatured PCR product distributed into streptavidin-coated microtitration wells together with the detection probe and one of the catching probes. After incubation and washes, the enhancement solution was added and specific hybridisation signal detected by measuring the emitted light. A series of 100 isolated genomic DNA samples were studied using biotinylated probes specific for DQA1*01, *0101/0104, *0103/0201/0601, *0201, *03, *0401/0601, *05 and *0502 alleles with results demonstrating the capacity of the test to detect aimed alleles. A series of whole blood spot samples were also studied and the results confirmed the applicability of this modification of the test.

  5. Analysis of the ABCA4 genomic locus in Stargardt disease

    DEFF Research Database (Denmark)

    Zernant, Jana; Xie, Yajing Angela; Ayuso, Carmen

    2014-01-01

    was designed to find the missing disease-causing ABCA4 variation by a combination of next-generation sequencing (NGS), array-Comparative Genome Hybridization (aCGH) screening, familial segregation and in silico analyses. The entire 140 kb ABCA4 genomic locus was sequenced in 114 STGD patients with one known...

  6. Genome-wide oligonucleotide-based array comparative genome hybridization analysis of non-isolated congenital diaphragmatic hernia

    NARCIS (Netherlands)

    D.A. Scott; M. Klaassens; A.M. Holder (Ashley); K.P. Lally (Kevin); C.J. Fernandes (Caraciolo); R-J.H. Galjaard (Robert-Jan); D. Tibboel (Dick); J.E.M.M. de Klein (Annelies); B. Lee (Brendan)

    2007-01-01

    textabstractNon-isolated congenital diaphragmatic hernia (CDH+) is a severe birth defect that is often caused by de novo chromosomal anomalies. In this report, we use genome-wide oligonucleotide-based array comparative genome hybridization (aCGH) followed by rapid real-time quantitative PCR analysis

  7. BRCA1-mutated and basal-like breast cancers have similar aCGH profiles and a high incidence of protein truncating TP53 mutations

    International Nuclear Information System (INIS)

    Holstege, Henne; Horlings, Hugo M; Velds, Arno; Langerød, Anita; Børresen-Dale, Anne-Lise; Vijver, Marc J van de; Nederlof, Petra M; Jonkers, Jos

    2010-01-01

    Basal-like breast cancers (BLBC) are aggressive breast cancers for which, so far, no targeted therapy is available because they typically lack expression of hormone receptors and HER2. Phenotypic features of BLBCs, such as clinical presentation and early age of onset, resemble those of breast tumors from BRCA1-mutation carriers. The genomic instability of BRCA1-mutated tumors can be effectively targeted with DNA-damaging agents and poly-(ADP-ribose) polymerase 1 (PARP1) inhibitors. Molecular similarities between BLBCs and BRCA1-mutated tumors may therefore provide predictive markers for therapeutic response of BLBCs. There are several known molecular features characteristic for BRCA1-mutated breast tumors: 1) increased numbers of genomic aberrations, 2) a distinct pattern of genomic aberrations, 3) a high frequency of TP53 mutations and 4) a high incidence of complex, protein-truncating TP53 mutations. We compared the frequency of TP53 mutations and the pattern and amount of genomic aberrations between BRCA1-mutated breast tumors, BLBCs and luminal breast tumors by TP53 gene sequencing and array-based comparative genomics hybridization (aCGH) analysis. We found that the high incidence of protein truncating TP53 mutations and the pattern and amount of genomic aberrations specific for BRCA1-mutated breast tumors are also characteristic for BLBCs and different from luminal breast tumors. Complex, protein truncating TP53 mutations in BRCA1-mutated tumors may be a direct consequence of genomic instability caused by BRCA1 loss, therefore, the presence of these types of TP53 mutations in sporadic BLBCs might be a hallmark of BRCAness and a potential biomarker for sensitivity to PARP inhibition. Also, our data suggest that a small subset of genomic regions may be used to identify BRCA1-like BLBCs. BLBCs share molecular features that were previously found to be specific for BRCA1-mutated breast tumors. These features might be useful for the identification of tumors with

  8. Mating, hybridisation and introgression in Lasius ants (Hymenoptera: Formicidae)

    DEFF Research Database (Denmark)

    Van der Have, Tom; Pedersen, Jes Søe; Boomsma, Jacobus Jan

    2011-01-01

    Recent reviews have shown that hybridisation among ant species is likely to be more common than previously appreci-ated, but that documented cases of introgression remain rare. After molecular phylogenetic work had shown that Euro-pean Lasius niger (LINNAEUS, 1758) and L. psammophilus SEIFERT, 1992...... (formerly L. alienus (FOERSTER, 1850)) are unlikely to be very closely related, we decided to analyse an old data set confirming the conclusion by PEARSON (1983) that these two ants can indeed form viable hybrids. We show that signatures of introgression can be detected in a Danish site...... sympatrically. This would imply that multiple accessible field sites are available to study the molecular details of hybridisation and in-trogression between two ant species that have variable degrees of sympatry throughout their distributional ranges...

  9. Radioactive probes for human gene localisation by in situ hybridisation

    International Nuclear Information System (INIS)

    Fennell, S.J.

    1980-07-01

    Radioactive probes of high specific activity have been used for human gene localisation on metaphase chromosome preparations. Human 5S ribosomal RNA was used as a model system, as a probe for the localisation of human 5S ribosomal genes. 125 I-labelled mouse 5S ribosomal RNA was used to study the 5S ribosomal gene content and arrangement in families with translocations on the long arm of chromosome 1 close to or containing the 5S ribosomal RNA locus, by in situ hybridisation to human metaphase chromosomes from peripheral blood cultures. This confirmed the chromosomal assignment of 5S ribosomal genes to 1q 42-43. In situ hybridisation probes were also prepared from recombinant plasmids containing Xenopus laevis oocyte 5S or 28S/18S gene sequences to give [ 3 H]-labelled cRNA and [ 3 H]-labelled nick-translated plasmid DNA. Studies on the kinetics of hybridisation of plasmid probes with and without ribosomal gene sequences questioned the role of plasmid DNA for amplification of signal during gene localisation. Gene localisation was obtained with nick-translated plasmid DNA containing the 28S/18S ribosomal DNA insert after short exposure times, but poor results were obtained using a [ 3 H]-labelled cRNA probe transcribed from the plasmid with the 5S gene insert. (author)

  10. Exome sequencing of germline DNA from non-BRCA1/2 familial breast cancer cases selected on the basis of aCGH tumor profiling.

    Directory of Open Access Journals (Sweden)

    Florentine S Hilbers

    Full Text Available The bulk of familial breast cancer risk (∼70% cannot be explained by mutations in the known predisposition genes, primarily BRCA1 and BRCA2. Underlying genetic heterogeneity in these cases is the probable explanation for the failure of all attempts to identify further high-risk alleles. While exome sequencing of non-BRCA1/2 breast cancer cases is a promising strategy to detect new high-risk genes, rational approaches to the rigorous pre-selection of cases are needed to reduce heterogeneity. We selected six families in which the tumours of multiple cases showed a specific genomic profile on array comparative genomic hybridization (aCGH. Linkage analysis in these families revealed a region on chromosome 4 with a LOD score of 2.49 under homogeneity. We then analysed the germline DNA of two patients from each family using exome sequencing. Initially focusing on the linkage region, no potentially pathogenic variants could be identified in more than one family. Variants outside the linkage region were then analysed, and we detected multiple possibly pathogenic variants in genes that encode DNA integrity maintenance proteins. However, further analysis led to the rejection of all variants due to poor co-segregation or a relatively high allele frequency in a control population. We concluded that using CGH results to focus on a sub-set of families for sequencing analysis did not enable us to identify a common genetic change responsible for the aggregation of breast cancer in these families. Our data also support the emerging view that non-BRCA1/2 hereditary breast cancer families have a very heterogeneous genetic basis.

  11. Pure partial monosomy 3p (3p25.3 → pter: Prenatal diagnosis and array comparative genomic hybridization characterization

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2012-09-01

    Conclusion: In this case, aCGH has characterized a 3p deleted region with haploinsufficiency of the neurodevelopmental genes associated with cognitive deficit and mental retardation but without involvement of the congenital heart disease susceptibility locus, and QF-PCR has determined a paternal origin of the deletion. aCGH and QF-PCR help to delineate the genomic imbalance in prenatally detected de novo chromosome aberration, and the information acquired is useful for genetic counseling.

  12. Fertilisation and early developmental barriers to hybridisation in field crickets.

    Science.gov (United States)

    Tyler, Frances; Rodríguez-Muñoz, Rolando; Tregenza, Tom

    2013-02-15

    Post-mating interactions between the reproductive traits and gametes of mating individuals and among their genes within zygotes are invariably complex, providing multiple opportunities for reproduction to go awry. These interactions have the potential to act as barriers to gene flow between species, and may be important in the process of speciation. There are multiple post-mating barriers to interbreeding between the hybridising field crickets Gryllus bimaculatus and G. campestris. Female G. bimaculatus preferentially store sperm from conspecific males when mated to both conspecific and heterospecific partners. Additionally, conspecific males sire an even greater proportion of offspring than would be predicted from their sperm's representation in the spermatheca. The nature of these post-sperm-storage barriers to hybridisation are unknown. We use a fluorescent staining technique to determine whether barriers occur prior to, or during embryo development. We show that eggs laid by G. bimaculatus females mated to G. campestris males are less likely to begin embryogenesis than eggs from conspecific mating pairs. Of the eggs that are successfully fertilised and start to develop, those from heterospecific mating pairs are more likely to arrest early, prior to blastoderm formation. We find evidence for bimodal variation among egg clutches in the number of developing embryos that subsequently arrest, indicating that there is genetic variation for incompatibility between mating individuals. In contrast to the pattern of early embryonic mortality, those hybrids reaching advanced stages of embryogenesis have survival rates equal to that of embryos from conspecific mating pairs. Post-sperm-storage barriers to hybridisation show evidence of genetic polymorphism. They are sufficiently large, that if the species interbreed where they are sympatric, these barriers could play a role in the maintenance of reproductive isolation between them. The number of eggs that fail to develop

  13. Synthesis and evaluation of phosphorescent oligonucleotide probes for hybridisation assays

    Science.gov (United States)

    O’Sullivan, Paul J.; Burke, Martina; Soini, Aleksi E.; Papkovsky, Dmitri B.

    2002-01-01

    Monofunctional, p-isothiocyanatophenyl-derivatives of platinum (II)-coproporphyrin-I (PtCP-NCS) were evaluated as phosphorescent labelling reagents for synthetic oligonucleotides containing a 3′- or 5′-amino modification. Synthesis and purification conditions were optimised to generate high yields and purity of PtCP-labelled oligonucleotide probes. Phosphorescent properties of the PtCP label have been shown to be largely unaffected by conjugation to oligonucleotides of various length, GC composition and label attachment site. 5′-PtCP-labelled oligonucleotides were shown to work efficiently as primers in a standard PCR. A dedicated 532 nm laser-based time-resolved fluorescence plate reader enabled highly sensitive detection of PtCP-labelled oligonucleotides and PCR products, both in solution and in agarose gels, with limits of detection in the order of 0.3 pM. A model system employing two complementary oligonucleotides labelled with PtCP and QSY® 7 dye (dark quencher) showed strong (∼20-fold) and specific proximity quenching of PtCP label upon hybridisation in solution. The potential applications of PtCP-labelled probes in hybridisation assays were discussed. PMID:12409473

  14. Hybridisation and crystal field in YbPd2Si2

    International Nuclear Information System (INIS)

    Bonville, P.; Hammann, J.; Hodges, J.A.; Imbert, P.; Jehanno, G.

    1990-01-01

    Experimental data in the Kondo lattice YbPd 2 Si 2 is compared with the results of a hybridisation model, based on the large-degeneracy expansion approximation, which takes into account the crystal field level splittings of the Yb ion. We show that satisfactory agreement is obtained with a unique set of crystal field and hybridisation parameters

  15. Comprehensive identification of essential Staphylococcus aureus genes using Transposon-Mediated Differential Hybridisation (TMDH

    Directory of Open Access Journals (Sweden)

    Burgis Timothy A

    2009-07-01

    Full Text Available Abstract Background In recent years there has been an increasing problem with Staphylococcus aureus strains that are resistant to treatment with existing antibiotics. An important starting point for the development of new antimicrobial drugs is the identification of "essential" genes that are important for bacterial survival and growth. Results We have developed a robust microarray and PCR-based method, Transposon-Mediated Differential Hybridisation (TMDH, that uses novel bioinformatics to identify transposon inserts in genome-wide libraries. Following a microarray-based screen, genes lacking transposon inserts are re-tested using a PCR and sequencing-based approach. We carried out a TMDH analysis of the S. aureus genome using a large random mariner transposon library of around a million mutants, and identified a total of 351 S. aureus genes important for survival and growth in culture. A comparison with the essential gene list experimentally derived for Bacillus subtilis highlighted interesting differences in both pathways and individual genes. Conclusion We have determined the first comprehensive list of S. aureus essential genes. This should act as a useful starting point for the identification of potential targets for novel antimicrobial compounds. The TMDH methodology we have developed is generic and could be applied to identify essential genes in other bacterial pathogens.

  16. Clinical Utility of Array Comparative Genomic Hybridization for Detection of Chromosomal Abnormalities in Pediatric Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Rabin, Karen R.; Man, Tsz-Kwong; Yu, Alexander; Folsom, Matthew R.; Zhao, Yi-Jue; Rao, Pulivarthi H.; Plon, Sharon E.; Naeem, Rizwan C.

    2014-01-01

    Background Accurate detection of recurrent chromosomal abnormalities is critical to assign patients to risk-based therapeutic regimens for pediatric acute lymphoblastic leukemia (ALL). Procedure We investigated the utility of array comparative genomic hybridization (aCGH) for detection of chromosomal abnormalities compared to standard clinical evaluation with karyotype and fluorescent in-situ hybridization (FISH). Fifty pediatric ALL diagnostic bone marrows were analyzed by bacterial artificial chromosome (BAC) array, and findings compared to standard clinical evaluation. Results Sensitivity of aCGH was 79% to detect karyotypic findings other than balanced translocations, which cannot be detected by aCGH because they involve no copy number change. aCGH also missed abnormalities occurring in subclones constituting less than 25% of cells. aCGH detected 44 additional abnormalities undetected or misidentified by karyotype, 21 subsequently validated by FISH, including abnormalities in 4 of 10 cases with uninformative cytogenetics. aCGH detected concurrent terminal deletions of both 9p and 20q in three cases, in two of which the 20q deletion was undetected by karyotype. A narrow region of loss at 7p21 was detected in two cases. Conclusions An array with increased BAC density over regions important in ALL, combined with PCR for fusion products of balanced translocations, could minimize labor- and time-intensive cytogenetic assays and provide key prognostic information in the approximately 35% of cases with uninformative cytogenetics. PMID:18253961

  17. A genomic copy number signature predicts radiation exposure in post-Chernobyl breast cancer.

    Science.gov (United States)

    Wilke, Christina M; Braselmann, Herbert; Hess, Julia; Klymenko, Sergiy V; Chumak, Vadim V; Zakhartseva, Liubov M; Bakhanova, Elena V; Walch, Axel K; Selmansberger, Martin; Samaga, Daniel; Weber, Peter; Schneider, Ludmila; Fend, Falko; Bösmüller, Hans C; Zitzelsberger, Horst; Unger, Kristian

    2018-04-16

    Breast cancer is the second leading cause of cancer death among women worldwide and besides life-style, age and genetic risk factors, exposure to ionising radiation is known to increase the risk for breast cancer. Further, DNA copy number alterations (CNAs), which can result from radiation-induced double-strand breaks, are frequently occurring in breast cancer cells. We set out to identify a signature of CNAs discriminating breast cancers from radiation-exposed and non-exposed female patients. We analysed resected breast cancer tissues from 68 exposed female Chernobyl clean-up workers and evacuees and 68 matched non-exposed control patients for CNAs by array comparative genomic hybridisation analysis (aCGH). Using a stepwise forward-backward selection approach a non-complex CNA-signature, i.e. less than ten features, was identified in the training data set, which could be subsequently validated in the validation data set (p-value<0.05). The signature consisted of nine copy number regions located on chromosomal bands 7q11.22-11.23, 7q21.3, 16q24.3, 17q21.31, 20p11.23-11.21, 1p21.1, 2q35, 2q35, 6p22.2. The signature was independent of any clinical characteristics of the patients. In all, we identified a CNA-signature that has the potential to allow identification of radiation-associated breast cancer at the individual level. This article is protected by copyright. All rights reserved. © 2018 UICC.

  18. Comparison of chromosomal and array-based comparative genomic hybridization for the detection of genomic imbalances in primary prostate carcinomas

    Directory of Open Access Journals (Sweden)

    Berg Marianne

    2006-09-01

    Full Text Available Abstract Background In order to gain new insights into the molecular mechanisms involved in prostate cancer, we performed array-based comparative genomic hybridization (aCGH on a series of 46 primary prostate carcinomas using a 1 Mbp whole-genome coverage platform. As chromosomal comparative genomic hybridization (cCGH data was available for these samples, we compared the sensitivity and overall concordance of the two methodologies, and used the combined information to infer the best of three different aCGH scoring approaches. Results Our data demonstrate that the reliability of aCGH in the analysis of primary prostate carcinomas depends to some extent on the scoring approach used, with the breakpoint estimation method being the most sensitive and reliable. The pattern of copy number changes detected by aCGH was concordant with that of cCGH, but the higher resolution technique detected 2.7 times more aberrations and 15.2% more carcinomas with genomic imbalances. We additionally show that several aberrations were consistently overlooked using cCGH, such as small deletions at 5q, 6q, 12p, and 17p. The latter were validated by fluorescence in situ hybridization targeting TP53, although only one carcinoma harbored a point mutation in this gene. Strikingly, homozygous deletions at 10q23.31, encompassing the PTEN locus, were seen in 58% of the cases with 10q loss. Conclusion We conclude that aCGH can significantly improve the detection of genomic aberrations in cancer cells as compared to previously established whole-genome methodologies, although contamination with normal cells may influence the sensitivity and specificity of some scoring approaches. Our work delineated recurrent copy number changes and revealed novel amplified loci and frequent homozygous deletions in primary prostate carcinomas, which may guide future work aimed at identifying the relevant target genes. In particular, biallelic loss seems to be a frequent mechanism of inactivation

  19. Magnon-Phonon-Hybridisation in FeCl2

    DEFF Research Database (Denmark)

    Ziebeck, K. R. A.; Houmann, Jens Christian Gylden

    1976-01-01

    without an applied magnetic field established the splitting at the nominal point of intersection Kx=0.17 to be 0.32 meV. The application of a 8.9 KG field parallel to the c axis raised the degeneracy of the magnons enabling both polarisations to be identified. From the observed magnon energy gap at Kx=0...... the gyromagnetic ratio g was estimated to be 4.01±0.2 in close agreement with the value 4.14 obtained by resonance experiments. Detailed measurements made in the |100| direction showed that the hybridisation takes place only between the magnons and the low energy TA⊥ (Σ2) phonon in agreement with theory....

  20. Trisomy 7 mosaicism at amniocentesis: Interphase FISH, QF-PCR, and aCGH analyses on uncultured amniocytes for rapid distinguishing of true mosaicism from pseudomosaicism

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2012-03-01

    Conclusion: Interphase FISH, QF-PCR, and aCGH analyses on uncultured amniocytes are useful for rapid distinguishing of true mosaicism from pseudomosaicism for trisomy 7 at amniocentesis. Cord blood sampling for confirmation of fetal trisomy 7 mosaicism is not practical.

  1. Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer

    DEFF Research Database (Denmark)

    Carneiro, Ana; Isinger, Anna; Karlsson, Anna

    2008-01-01

    p13.3 independently predicted poor survival in multivariate analysis. CONCLUSION: aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict......BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We...... applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. METHODS: A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential...

  2. Microdeletion and microduplication analysis of chinese conotruncal defects patients with targeted array comparative genomic hybridization.

    Directory of Open Access Journals (Sweden)

    Xiaohui Gong

    Full Text Available OBJECTIVE: The current study aimed to develop a reliable targeted array comparative genomic hybridization (aCGH to detect microdeletions and microduplications in congenital conotruncal defects (CTDs, especially on 22q11.2 region, and for some other chromosomal aberrations, such as 5p15-5p, 7q11.23 and 4p16.3. METHODS: Twenty-seven patients with CTDs, including 12 pulmonary atresia (PA, 10 double-outlet right ventricle (DORV, 3 transposition of great arteries (TGA, 1 tetralogy of Fallot (TOF and one ventricular septal defect (VSD, were enrolled in this study and screened for pathogenic copy number variations (CNVs, using Agilent 8 x 15K targeted aCGH. Real-time quantitative polymerase chain reaction (qPCR was performed to test the molecular results of targeted aCGH. RESULTS: Four of 27 patients (14.8% had 22q11.2 CNVs, 1 microdeletion and 3 microduplications. qPCR test confirmed the microdeletion and microduplication detected by the targeted aCGH. CONCLUSION: Chromosomal abnormalities were a well-known cause of multiple congenital anomalies (MCA. This aCGH using arrays with high-density coverage in the targeted regions can detect genomic imbalances including 22q11.2 and other 10 kinds CNVs effectively and quickly. This approach has the potential to be applied to detect aneuploidy and common microdeletion/microduplication syndromes on a single microarray.

  3. Identification of chromosome aberrations in sporadic microsatellite stable and unstable colorectal cancers using array comparative genomic hybridization

    DEFF Research Database (Denmark)

    Jensen, Thomas Dyrsø; Li, Jian; Wang, Kai

    2011-01-01

    cancers constitute approximately 85% of sporadic cases, whereas microsatellite unstable (MSI) cases constitute the remaining 15%. In this study, we used array comparative genomic hybridization (aCGH) to identify genomic hotspot regions that harbor recurrent copy number changes. The study material...

  4. Can genome array screening replace FISH as a front-line test in multiple myeloma?

    Science.gov (United States)

    Boneva, Temenushka; Brazma, Diana; Gancheva, Katya; Howard-Reeves, Julie; Raynov, Julian; Grace, Colin; Nacheva, Elisabeth P

    2014-08-01

    Multiple myeloma (MM) is a malignant disorder characterized by neoplastic transformation of mature B cells in the bone marrow (BM), accompanied by complex genetic changes. The disease is heterogeneous at both the clinical and genomic levels. Molecular genetics and genomic investigations have demonstrated that disease evolution is associated with an accumulation of specific aberrations, mostly genome imbalances, which not only shed light on the disease pathogenesis but also allow risk assessment and treatment monitoring. We used a catalogue version of the Agilent 8x60K oligo-array with immuno-magnetically isolated CD138(+) cells from BM samples of 50 patients with myeloma to evaluate the merit of array comparative genomic hybridization (aCGH) as a diagnostic tool. We demonstrate the ability of aCGH to detect clonal imbalances to a level well below established clinically significant thresholds. aCGH, combined with target enrichment and complemented with tests for IGH rearrangements offers a cost neutral alternative to multiprobe fluorescence in situ hybridization screening. While we recognize the limitations of the standard version of the 8x60k array we demonstrate the value of aCGH as a first tier test in the diagnostic workup of MM. The array technology enables high-risk disease stratification with the added benefit of providing whole genome data to assist in establishing clinically relevant predicative markers. © 2014 Wiley Periodicals, Inc.

  5. Sensitive and reliable detection of genomic imbalances in human neuroblastomas using comparative genomic hybridisation analysis

    NARCIS (Netherlands)

    van Gele, M.; van Roy, N.; Jauch, A.; Laureys, G.; Benoit, Y.; Schelfhout, V.; de Potter, C. R.; Brock, P.; Uyttebroeck, A.; Sciot, R.; Schuuring, E.; Versteeg, R.; Speleman, F.

    1997-01-01

    Deletions of the short arm of chromosome 1, extra copies of chromosome 17q and MYCN amplification are the most frequently encountered genetic changes in neuroblastomas. Standard techniques for detection of one or more of these genetic changes are karyotyping, FISH analysis and LOH analysis by

  6. Genome wide array comparative genomic hybridisation analysis of premalignant lesions of the stomach.

    NARCIS (Netherlands)

    Weiss, M.M.; Kuipers, E.J.; Postma, C; Snijders, A.M.; Stolte, M.; Vieth, M; Pinkel, D; Meuwissen, SG; Albertson, D; Meijer, G.A.

    2003-01-01

    BACKGROUND: Gastric cancer is one of the most frequent malignancies in the world, ranking fifth in the Netherlands as a cause of cancer death. Surgery is the only curative treatment for advanced cases, but results of gastrectomy largely depend on the stage of the disease. A better understanding of

  7. Hybridisation among groupers (genus Cephalopholis) at the eastern Indian Ocean suture zone: taxonomic and evolutionary implications

    KAUST Repository

    Payet, Samuel D.

    2016-08-05

    Hybridisation is a significant evolutionary process that until recently was considered rare in the marine environment. A suture zone in the eastern Indian Ocean is home to numerous hybridising sister species, providing an ideal opportunity to determine how hybridisation affects speciation and biodiversity in coral reef fishes. At this location, hybridisation between two grouper (Epinephelidae) species: Cephalopholis urodeta (Pacific Ocean) and C. nigripinnis (Indian Ocean) was investigated to determine the genetic basis of hybridisation and to compare the ecology and life history of hybrids and their parent species. This approach aimed to provide insights into the taxonomic and evolutionary consequences of hybridisation. Despite clear phenotypic differences, multiple molecular markers revealed hybrids, and their parent species were genetically homogenous within and (thousands of kilometres) outside of the hybrid zone. Hybrids were at least as fit as their parent species (in terms of growth, reproduction, and abundance) and were observed in a broad range of intermediate phenotypes. The two species appear to be interbreeding at Christmas Island due to inherent biological and ecological compatibilities, and the lack of genetic structure may be explained by three potential scenarios: (1) hybridisation and introgression; (2) discordance between morphology and genetics; and (3) incomplete lineage sorting. Further molecular analyses are necessary to discriminate these scenarios. Regardless of which applies, C. urodeta and C. nigripinnis are unlikely to evolve in reproductive isolation as they cohabit where they are common (Christmas Island) and will source congeneric mates where they are rare (Cocos Keeling Islands). Our results add to the growing body of evidence that hybridisation among coral reef fishes is a dynamic evolutionary factor. © 2016 Springer-Verlag Berlin Heidelberg

  8. Sensitive in situ hybridisation technique using biotin-streptavidin-polyalkaline phosphatase complex.

    OpenAIRE

    Lewis, F A; Griffiths, S; Dunnicliff, R; Wells, M; Dudding, N; Bird, C C

    1987-01-01

    A sensitive in situ hybridisation technique, using a biotin-streptavidin-polyalkaline phosphatase complex detection system, was successfully applied to smears of fresh cultured cells, frozen sections, and formalin fixed paraffin processed tissue: the procedure was successful for DNA-DNA hybridizations using a variety of DNA probes. The detection method is rapid, reliable, and economical producing a purplish-blue precipitate at the site of hybridisation and clearly visible by low power light m...

  9. Array Comparative Genomic Hybridization as the First-line Investigation for Neonates with Congenital Heart Disease: Experience in a Single Tertiary Center.

    Science.gov (United States)

    Choi, Bo Geum; Hwang, Su Kyung; Kwon, Jung Eun; Kim, Yeo Hyang

    2018-03-01

    The purpose of the present study was to investigate the advantages and disadvantages of verifying genetic abnormalities using array comparative genomic hybridization (a-CGH) immediately after diagnosis of congenital heart disease (CHD). Among neonates under the age of 28 days who underwent echocardiography from January 1, 2014 to April 30, 2016, neonates whose chromosomal and genomic abnormalities were tested using a-CGH in cases of an abnormal finding on echocardiography were enrolled. Of the 166 patients diagnosed with CHD, 81 underwent a-CGH and 11 patients (11/81, 13.5%) had abnormal findings on a-CGH. 22q11.2 deletion syndrome was the most common (4/11, 36.4%). On the first a-CGH, 4 patients were negative (4/81, 5%). Three of them were finally diagnosed with Williams syndrome using fluorescent in situ hybridization (FISH), 1 patient was diagnosed with Noonan syndrome through exome sequencing. All of them exhibited diffuse pulmonary artery branch hypoplasia, as well as increased velocity of blood flow, on repeated echocardiography. Five patients started rehabilitation therapy at mean 6 months old age in outpatient clinics and epilepsy was diagnosed in 2 patients. Parents of 2 patients (22q11.2 deletion syndrome and Patau syndrome) refused treatment due to the anticipated prognosis. Screening tests for genetic abnormalities using a-CGH in neonates with CHD has the advantage of early diagnosis of genetic abnormality during the neonatal period in which there is no obvious symptom of genetic abnormality. However, there are disadvantages that some genetic abnormalities cannot be identified on a-CGH. Copyright © 2018. The Korean Society of Cardiology.

  10. Technological, mediatic and cultural hybridisation: Cultural mediations in the context of globalisation

    Directory of Open Access Journals (Sweden)

    Laan Mendes de Barros

    2009-12-01

    Full Text Available We live in a context of borders that are dissolving in many senses, of the convergence and hybridisation of technologies, mass media and cultures. The context is the resizing of practical time, of movements and links between the local and the global. In these times of interculturality, communication plays a very important role; not so much in its technological media dimension, but particularly in the dynamics of cultural mediations that are dividing off from mediatised relations. This article aims to reflect on the transformations in present-day communication processes, marked by strong movements of hybridisation, as well as examining how to consider interculturality in the context of cultural mediations, based on dialogue between Latin American and French authors. Also, using media material, the article presents illustrations of the Brazilian cultural scene, which is marked by a long history of hybridisation that is filled with intercultural dynamics.

  11. Genomic DNA extraction methods using formalin-fixed paraffin-embedded tissue.

    Science.gov (United States)

    Potluri, Keerti; Mahas, Ahmed; Kent, Michael N; Naik, Sameep; Markey, Michael

    2015-10-01

    As new technologies come within reach for the average cytogenetic laboratory, the study of chromosome structure has become increasingly more sophisticated. Resolution has improved from karyotyping (in which whole chromosomes are discernible) to fluorescence in situ hybridization and comparative genomic hybridization (CGH, with which specific megabase regions are visualized), array-based CGH (aCGH, examining hundreds of base pairs), and next-generation sequencing (providing single base pair resolution). Whole genome next-generation sequencing remains a cost-prohibitive method for many investigators. Meanwhile, the cost of aCGH has been reduced during recent years, even as resolution has increased and protocols have simplified. However, aCGH presents its own set of unique challenges. DNA of sufficient quantity and quality to hybridize to arrays and provide meaningful results is required. This is especially difficult for DNA from formalin-fixed paraffin-embedded (FFPE) tissues. Here, we compare three different methods for acquiring DNA of sufficient length, purity, and "amplifiability" for aCGH and other downstream applications. Phenol-chloroform extraction and column-based commercial kits were compared with adaptive focused acoustics (AFA). Of the three extraction methods, AFA samples showed increased amplicon length and decreased polymerase chain reaction (PCR) failure rate. These findings support AFA as an improvement over previous DNA extraction methods for FFPE tissues. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Karyotype analysis of Lilium longiflorum and Lilium rubellum by chromosome banding and fluorescence in situ hybridisation

    NARCIS (Netherlands)

    Lim, K.B.; Wennekes, J.; Jong, de J.H.S.G.M.; Jacobsen, E.; Tuyl, van J.M.

    2001-01-01

    Detailed karyotypes of Lilium longiflorum and L. rubellum were constructed on the basis of chromosome arm lengths, C-banding, AgNO3 staining, and PI-DAPI banding, together with fluorescence in situ hybridisation (FISH) with the 5S and 45S rDNA sequences as probes. The C-banding patterns that were

  13. Whole-genome array CGH evaluation for replacing prenatal karyotyping in Hong Kong.

    Directory of Open Access Journals (Sweden)

    Anita S Y Kan

    Full Text Available OBJECTIVE: To evaluate the effectiveness of whole-genome array comparative genomic hybridization (aCGH in prenatal diagnosis in Hong Kong. METHODS: Array CGH was performed on 220 samples recruited prospectively as the first-tier test study. In addition 150 prenatal samples with abnormal fetal ultrasound findings found to have normal karyotypes were analyzed as a 'further-test' study using NimbleGen CGX-135K oligonucleotide arrays. RESULTS: Array CGH findings were concordant with conventional cytogenetic results with the exception of one case of triploidy. It was found in the first-tier test study that aCGH detected 20% (44/220 clinically significant copy number variants (CNV, of which 21 were common aneuploidies and 23 had other chromosomal imbalances. There were 3.2% (7/220 samples with CNVs detected by aCGH but not by conventional cytogenetics. In the 'further-test' study, the additional diagnostic yield of detecting chromosome imbalance was 6% (9/150. The overall detection for CNVs of unclear clinical significance was 2.7% (10/370 with 0.9% found to be de novo. Eleven loci of common CNVs were found in the local population. CONCLUSION: Whole-genome aCGH offered a higher resolution diagnostic capacity than conventional karyotyping for prenatal diagnosis either as a first-tier test or as a 'further-test' for pregnancies with fetal ultrasound anomalies. We propose replacing conventional cytogenetics with aCGH for all pregnancies undergoing invasive diagnostic procedures after excluding common aneuploidies and triploidies by quantitative fluorescent PCR. Conventional cytogenetics can be reserved for visualization of clinically significant CNVs.

  14. How much do we know about the frequency of hybridisation and polyploidy in the Mediterranean region?

    Science.gov (United States)

    Marques, I; Loureiro, J; Draper, D; Castro, M; Castro, S

    2018-01-01

    Natural hybridisation and polyploidy are currently recognised as drivers of biodiversity, despite early scepticism about their importance. The Mediterranean region is a biodiversity hotspot where geological and climatic events have created numerous opportunities for speciation through hybridisation and polyploidy. Still, our knowledge on the frequency of these mechanisms in the region is largely limited, despite both phenomena are frequently cited in studies of Mediterranean plants. We reviewed information available from biodiversity and cytogenetic databases to provide the first estimates of hybridisation and polyploidy frequency in the Mediterranean region. We also inspected the most comprehensive modern Mediterranean Flora (Flora iberica) to survey the frequency and taxonomic distribution of hybrids and polyploids in Iberian Peninsula. We found that Mediterranean plants were hybrids, although a higher frequency was estimated for the Iberian Peninsula (13%). Hybrids were concentrated in few families and in even fewer genera. The overall frequency of polyploidy (36.5%) was comparable with previous estimates in other regions; however our estimates increased when analysing the Iberian Peninsula (48.8%). A surprisingly high incidence of species harbouring two or more ploidy levels was also observed (21.7%). A review of the available literature also showed that the ecological factors driving emergence and establishment of new entities are still poorly studied in the Mediterranean flora, although geographic barriers seem to play a major role in polyploid complexes. Finally, this study reveals several gaps and limitations in our current knowledge about the frequency of hybridisation and polyploidy in the Mediterranean region. The obtained estimates might change in the future with the increasing number of studies; still, rather than setting the complete reality, we hope that this work triggers future studies on hybridisation and polyploidy in the Mediterranean region.

  15. Climate as possible reproductive barrier in Pinus radiata (D. Don interspecific hybridisation

    Directory of Open Access Journals (Sweden)

    Hannél Ham

    2017-12-01

    Full Text Available Historically, interspecific hybridisation with Pinus radiata D. Don had limited success. The effect of environmental conditions and position of pollination bags in the tree were investigated as possible hybridisation barriers. The study was conducted in a P. radiata seed orchard in the Southern Cape (South Africa. Field data were compared to the climatic conditions at natural and commercial provenances of seven Mesoamerican Pinus species identified as possible hybrid partners. In vitro pollen studies were used to confirm whether interspecific crosses with P. radiata might be feasible within predefined climatic parameters. The temperature ranges for both top and northern side of P. radiata pine trees in the seed orchard was similar to the natural distribution of P. radiata, P. elliottii Engelm. and P. taeda L. in the USA. Results suggested that pollen of P. elliottii and P. taeda might be more suited to result in the successful pollination of P. radiata than the other Mesoamerican pine species tested in this study.  Furthermore, the combination of minimum temperature and precipitation also showed a closer correlation to successful hybridisation with P. radiata for both P. elliotii and P. taeda. However, pollen tube elongation studies did not support these results, suggesting that mean temperature might not be the only determining factor of hybridisation success. Three circadian temperature models that mimic natural conditions were developed for Karatara and Sabie (Tweefontein, Witklip and Spitskop.  These models will be tested in future in vitro studies to further evaluate temperature fluctuations between day and night regimes as a possible reproductive barrier limiting hybridisation success between P. radiata and other Mesoamerican pine species.

  16. Genomes

    National Research Council Canada - National Science Library

    Brown, T. A. (Terence A.)

    2002-01-01

    ... of genome expression and replication processes, and transcriptomics and proteomics. This text is richly illustrated with clear, easy-to-follow, full color diagrams, which are downloadable from the book's website...

  17. HER-2 gene amplification by chromogenic in situ hybridisation (CISH) compared with fluorescence in situ hybridisation (FISH) in breast cancer-A study of two hundred cases.

    Science.gov (United States)

    Sáez, A; Andreu, F J; Seguí, M A; Baré, M L; Fernández, S; Dinarés, C; Rey, M

    2006-08-01

    The purpose of the study was to compare two methods used to analyse HER-2 gene amplification (fluorescence in situ hybridisation (FISH) and chromogenic in situ hybridisation (CISH)), and determine the accuracy of the antibodies CB11 and HercepTest for immunohistochemical detection of HER-2 overexpression from archival breast cancer tissue. Additionally, interobserver variability in the interpretation of CISH and immunohistochemical tests was measured. Two hundred cases of invasive breast carcinoma diagnosed between 2000 and 2003 were selected. Immunohistochemistry (IHC) was performed with HercepTest and CB11, and gene amplification was determined by FISH (PathVision, Vysis) and CISH (Zymed) using tissue macroarrays. An excellent concordance (94.8%) was found between CISH and FISH. Considering FISH as gold standard, sensitivity of CISH was 97.5% and specificity 94%. Overall interobserver agreement of CISH was 97.5% and of IHC 84%. Both antibodies showed a sensitivity of 95.2% and a specificity of 70.7% (CB11) and 81.2% (HercepTest). Our results show that CISH is a highly accurate, reproducible and practical technique to determine HER-2 gene amplification. CB11 and HercepTest are good screening methods with a high sensitivity. The performance of tissue macroarrays to test HER-2 status by IHC, FISH and CISH has demonstrated to be an available and effective method to study large series of tumours.

  18. A tale of two doctoral students: social media tools and hybridised identities

    Directory of Open Access Journals (Sweden)

    Liz Bennett

    2014-05-01

    Full Text Available This paper explores the experiences of two doctoral students who embraced Web 2.0 tools in their digital scholarship practices. The paper gives an insider perspective of the challenges and potential of working with online tools, such as blogs, and participating in online communities, such as Twitter's #phdchat. We explore by drawing on our personal experiences as to how this participation was affected by our hybridised identity as both members of staff at a UK university and as PhD students. We argue that social media tools provide access to a community of doctoral students and knowledgeable others that reduce isolation and provide challenge and support along the challenging journey of undertaking a doctoral study. Whilst the tools involved exposure and risk in relation to managing our hybridised identities, our experience of their use was one we would recommend to others.

  19. Chromosomal positioning of human T-lymphotropic type 1 proviruses by fluorescence in situ hybridisation.

    Science.gov (United States)

    Richardson, J H; Rose, N J; Mann, S; Ferguson-Smith, M; Lever, A M

    2001-04-01

    Fluorescence in situ hybridisation (FISH) was employed to identify the chromosomal integration site of the human T-cell lymphotropic virus, type 1 (HTLV-1) present in T-cell clones derived from HTLV-1-infected individuals and a virally transformed cell line, C8166-45. Proviral sequences were detected in C8166-45 but not uninfected Jurkat cells. Integration sites were reliably detected in T-cell clones determined previously to be infected with HTLV-1. The results indicated that the transformed cell line and some of the T-cell clones possessed more than one proviral integration site. This hybridisation system is useful for determining the number of integration events and for localising proviruses to specific chromosomal regions.

  20. Cohen syndrome diagnosed using microarray comparative genomic hibridization

    Directory of Open Access Journals (Sweden)

    Saldarriaga-Gil, Wilmar

    2017-10-01

    Full Text Available Cohen syndrome (CS is an uncommon autosomal recessive genetic disorder attributed to damage on VPS13B gene, locus 8q22-q23. Characteristic phenotype consists of intellectual disability, microcephaly, facial dysmorphism, ophthalmic abnormalities, truncal obesity and hipotony. Worldwide, around 150 cases have been published, mostly in Finish patients. We report the case of a 3 year-old male, with short height, craniosynostosis, facial dysmorphism, hipotony, and developmental delay. He was diagnosed with Cohen syndrome using Microarray Comparative Genomic Hibridization (aCGH that showed homozygous deletion of 0.153 Mb on 8q22.2 including VPS13B gene, OMIM #216550. With this report we contribute to enlarge epidemiological databases on an uncommon genetic disorder. Besides, we illustrate on the contribution of aCGH to the etiological diagnosis of patients with unexplained intellectual disability, delayed psychomotor development, language difficulties, autism and multiple congenital anomalies.

  1. Chromogenic in situ hybridisation for the assessment of HER2 status in breast cancer: an international validation ring study

    OpenAIRE

    van de Vijver, Marc; Bilous, Michael; Hanna, Wedad; Hofmann, Manfred; Kristel, Petra; Penault-Llorca, Frédérique; Rüschoff, Josef

    2007-01-01

    Introduction Before any new methodology can be introduced into the routine diagnostic setting it must be technically validated against the established standards. To this end, a ring study involving five international pathology laboratories was initiated to validate chromogenic in situ hybridisation (CISH) against fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) as a test for assessing human epidermal growth factor receptor 2 (HER2) status in breast cancer. Methods Each...

  2. Application of fluorescence in situ hybridisation to chromosome analysis of aged bone marrow smears.

    Science.gov (United States)

    Hammond, D W; Hinchliffe, R F; Goyns, M H; Potter, A M; Lilleyman, J S

    1994-01-01

    AIMS--To evaluate the reliability of fluorescence in situ hybridisation (FISH) in the retrospective cytogenetic assessment of old bone marrow smears stored for periods of up to 20 years. METHODS--A series of bone marrow smears either Romanowsky stained, or frozen and unstained, and aged from one month to 20 years were hybridised with biotin labelled probes specific for the centromeric regions of human chromosomes X, 6, and 18. Sites of hybridisation were detected with fluoresceinated avidin. One hundred to 400 cells from each preparation were examined and the number of signals observed was recorded. RESULTS--All smears exhibited signals in most cells examined. In cytogenetically normal cases, an average 67.6% of cells (range 36%-90%) demonstrated the appropriate number of X centromere signals. In those samples known to contain extra chromosomes X, 6, or 18 the presence of cells with the abnormal copy number was clearly detected in each case. CONCLUSION--When applied in the way described, FISH can give consistent and accurate results with a variety of archival bone marrow smears, including aged prestained material. This will permit retrospective assessment of specific cytogenetic abnormalities in patients with leukaemia using their initial diagnostic slides even where these are several years old. Images PMID:8063931

  3. Positive Emotional Responses to Hybridised Writing about a Socio-Scientific Issue

    Science.gov (United States)

    Tomas, Louisa; Ritchie, Stephen M.

    2012-01-01

    In order to understand better the role of affect in learning about socio-scientific issues (SSI), this study investigated Year 12 students' emotional arousal as they participated in an online writing-to-learn science project about the socio-scientific issue of biosecurity. Students wrote a series of hybridised scientific narratives, or BioStories, that integrate scientific information about biosecurity with narrative storylines, and uploaded these to a dedicated website. Throughout their participation in the project, students recorded their emotional responses to the various activities ( N = 50). Four case students were also video recorded during selected science lessons as they researched, composed and uploaded their BioStories for peer review. Analysis of these data, as well as interview data obtained from the case students, revealed that pride, strength, determination, interest and alertness were among the positive emotions most strongly elicited by the project. These emotions reflected students' interest in learning about a new socio-scientific issue, and their enhanced feelings of self-efficacy in successfully writing hybridised scientific narratives in science. The results of this study suggest that the elicitation of positive emotional responses as students engage in hybridised writing about SSI with strong links to environmental education, such as biosecurity, can be valuable in engaging students in education for sustainability.

  4. On hybridising lettuce seedlings with nanoparticles and the resultant effects on the organisms' electrical characteristics.

    Science.gov (United States)

    Gizzie, Nina; Mayne, Richard; Patton, David; Kendrick, Paul; Adamatzky, Andrew

    2016-09-01

    Lettuce seedlings are attracting interest in the computing world due to their capacity to become hybrid circuit components, more specifically, in the creation of living 'wires'. Previous studies have shown that seedlings can be hybridised with gold nanoparticles and withstand mild electrical currents. In this study, lettuce seedlings were hybridised with a variety of metallic and non-metallic nanomaterials: carbon nanotubes, graphene oxide, aluminium oxide and calcium phosphate. Toxic effects and the following electrical properties were monitored: mean potential, resistance and capacitance. Macroscopic observations revealed only slight deleterious health effects after administration with one variety of particle, aluminium oxide. Mean potential in calcium phosphate-hybridised seedlings showed a considerable increase when compared with the control, whereas those administered with graphene oxide showed a small decrease; there were no notable variations across the remaining treatments. Electrical resistance decreased substantially in graphene oxide-treated seedlings whereas slight increases were shown following calcium phosphate and carbon nanotubes applications. Capacitance showed no considerable variation across treated seedlings. These results demonstrate that use of some nanomaterials, specifically graphene oxide and calcium phosphate, may be towards biohybridisation purposes including the generation of living 'wires'. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Comparison of Chromogenic In Situ Hybridisation with Fluorescence In Situ Hybridisation and Immunohistochemistry for the Assessment of Her-2/neu Oncogene in Archival Material of Breast Carcinoma

    International Nuclear Information System (INIS)

    Pothos, Alexios; Plastira, Konstantina; Plastiras, Aris; Vlachodimitropoulos, Dimitrios; Goutas, Nikolaos; Angelopoulou, Roxani

    2008-01-01

    The successful treatment of breast cancer is dependent upon a number of complex factors. Her-2/neu gene amplification is known to be one of the most common genetic alterations associated with breast cancer and its accurate determination has become necessary for the selection of patients for trastuzumab therapy. The aim of this study was to prove the consistency of chromogenic in situ hybridisation (CISH) technique after analyzing the overexpression of the Her-2/neu proto-oncogene in 100 invasive breast carcinomas and by comparing CISH results with immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). Moreover, it was done to evaluate the possible correlation of estrogen (ERs) and progesterone receptors (PRs), the proliferation marker Ki67 and the tumour suppressor gene p53 with HER-2/neu status of these breast carcinomas. Of the 100 breast carcinomas that were analysed, 22 cases showed HER-2/neu amplification, 66 cases showed no amplification, whereas 12 cases were non-interpretable in both assays (FISH and CISH). Consequently, the overall concordance between FISH and CISH was 100%. Additionally, it was observed that when HER-2/neu gene was overexpressed, there was an association with negative PRs and ERs status, negative p53 protein expression and high Ki67 labelling index. It is concluded that patients with tumours scoring 2+ with the CBE356 antibody (borderline immunohistochemistry-tested cases) would also benefit from CISH as it is shown to be highly accurate, practical and can be easily integrated into routine testing in any histopathology laboratory. Finally, CISH represents an important addition to the HER2 testing algorithm

  6. Aneuploidy screening by array comparative genomic hybridization improves success rates of in vitro fertilization: A multicenter Indian study

    Directory of Open Access Journals (Sweden)

    Aditi Kotdawala

    2016-01-01

    Full Text Available Objective: To evaluate the usefulness of preimplantation genetic screening (PGS using array comparative genomic hybridization (aCGH in the Indian population. Materials and Methods: This is a retrospective, multicenter study including 235 PGS cycles following intracytoplasmic sperm injection performed at six different infertility centers from September 2013 to June 2015. Patients were divided as per maternal age in several groups (40 years and as per indication for undergoing PGS. Indications for performing PGS were recurrent miscarriage, repetitive implantation failure, severe male factor, previous trisomic pregnancy, and advanced maternal age (≥35. Day 3 embryo biopsy was performed and analyzed by aCGH followed by day 5 embryo transfer in the same cycle or the following cycle. Outcomes such as pregnancy rates (PRs/transfer, implantation rates, miscarriage rates, percentage of abnormal embryos, and number of embryos with more than one aneuploidy and chaotic patterns were recorded for all the treated subjects based on different age and indication groups. Results: aCGH helped in identifying aneuploid embryos, thus leading to consistent implantation (range: 33.3%-42.9% and PRs per transfer (range: 31.8%-54.9% that were obtained for all the indications in all the age groups, after performing PGS. Conclusion: Aneuploidy is one of the major factors which affect embryo implantation. aCGH can be successfully employed for screening of aneuploid embryos. When euploid embryos are transferred, an increase in PRs can be achieved irrespective of the age or the indication.

  7. Comparative genomics of wild type yeast strains unveils important genome diversity

    Directory of Open Access Journals (Sweden)

    Pereira Patrícia M

    2008-11-01

    Full Text Available Abstract Background Genome variability generates phenotypic heterogeneity and is of relevance for adaptation to environmental change, but the extent of such variability in natural populations is still poorly understood. For example, selected Saccharomyces cerevisiae strains are variable at the ploidy level, have gene amplifications, changes in chromosome copy number, and gross chromosomal rearrangements. This suggests that genome plasticity provides important genetic diversity upon which natural selection mechanisms can operate. Results In this study, we have used wild-type S. cerevisiae (yeast strains to investigate genome variation in natural and artificial environments. We have used comparative genome hybridization on array (aCGH to characterize the genome variability of 16 yeast strains, of laboratory and commercial origin, isolated from vineyards and wine cellars, and from opportunistic human infections. Interestingly, sub-telomeric instability was associated with the clinical phenotype, while Ty element insertion regions determined genomic differences of natural wine fermentation strains. Copy number depletion of ASP3 and YRF1 genes was found in all wild-type strains. Other gene families involved in transmembrane transport, sugar and alcohol metabolism or drug resistance had copy number changes, which also distinguished wine from clinical isolates. Conclusion We have isolated and genotyped more than 1000 yeast strains from natural environments and carried out an aCGH analysis of 16 strains representative of distinct genotype clusters. Important genomic variability was identified between these strains, in particular in sub-telomeric regions and in Ty-element insertion sites, suggesting that this type of genome variability is the main source of genetic diversity in natural populations of yeast. The data highlights the usefulness of yeast as a model system to unravel intraspecific natural genome diversity and to elucidate how natural

  8. Comparative genomics of wild type yeast strains unveils important genome diversity.

    Science.gov (United States)

    Carreto, Laura; Eiriz, Maria F; Gomes, Ana C; Pereira, Patrícia M; Schuller, Dorit; Santos, Manuel A S

    2008-11-04

    Genome variability generates phenotypic heterogeneity and is of relevance for adaptation to environmental change, but the extent of such variability in natural populations is still poorly understood. For example, selected Saccharomyces cerevisiae strains are variable at the ploidy level, have gene amplifications, changes in chromosome copy number, and gross chromosomal rearrangements. This suggests that genome plasticity provides important genetic diversity upon which natural selection mechanisms can operate. In this study, we have used wild-type S. cerevisiae (yeast) strains to investigate genome variation in natural and artificial environments. We have used comparative genome hybridization on array (aCGH) to characterize the genome variability of 16 yeast strains, of laboratory and commercial origin, isolated from vineyards and wine cellars, and from opportunistic human infections. Interestingly, sub-telomeric instability was associated with the clinical phenotype, while Ty element insertion regions determined genomic differences of natural wine fermentation strains. Copy number depletion of ASP3 and YRF1 genes was found in all wild-type strains. Other gene families involved in transmembrane transport, sugar and alcohol metabolism or drug resistance had copy number changes, which also distinguished wine from clinical isolates. We have isolated and genotyped more than 1000 yeast strains from natural environments and carried out an aCGH analysis of 16 strains representative of distinct genotype clusters. Important genomic variability was identified between these strains, in particular in sub-telomeric regions and in Ty-element insertion sites, suggesting that this type of genome variability is the main source of genetic diversity in natural populations of yeast. The data highlights the usefulness of yeast as a model system to unravel intraspecific natural genome diversity and to elucidate how natural selection shapes the yeast genome.

  9. HER2 testing in the UK: recommendations for breast and gastric in-situ hybridisation methods

    LENUS (Irish Health Repository)

    Bartlett, J. M. S.

    2011-01-01

    These guidelines supplement existing guidelines on HER2 testing by immunohistochemistry and in-situ hybridisation(ISH) methods in the UK. They provide a specific focus on aspects of guidance relevant to HER2 ISH testing methods, both fluorescent and chromogenic. They are formulated to give advice on methodology, interpretation and quality control for ISH-based testing of HER2 status in common tumour types, including both breast and gastric tumours. The aim is to ensure that all ISH-based testing is accurate, reliable and timely.

  10. Establishing the Genome of ' Sukali Ndizi \\' | Pillay | African Crop ...

    African Journals Online (AJOL)

    Banana improvement programs make use of interspecific hybridisation for gene introgression. Consequently knowledge of the exact ploidy level and genome composition of a plant is important for breeding purposes. The ploidy level of a plant is generally determined in two ways: (1) by a physical count of its chromosomes, ...

  11. The draft genome of the pest tephritid fruit fly Bactrocera tryoni: resources for the genomic analysis of hybridising species

    OpenAIRE

    Gilchrist, Anthony Stuart; Shearman, Deborah CA; Frommer, Marianne; Raphael, Kathryn A; Deshpande, Nandan P; Wilkins, Marc R; Sherwin, William B; Sved, John A

    2014-01-01

    Background The tephritid fruit flies include a number of economically important pests of horticulture, with a large accumulated body of research on their biology and control. Amongst the Tephritidae, the genus Bactrocera, containing over 400 species, presents various species groups of potential utility for genetic studies of speciation, behaviour or pest control. In Australia, there exists a triad of closely-related, sympatric Bactrocera species which do not mate in the wild but which, despit...

  12. Chromosomal minimal critical regions in therapy-related leukemia appear different from those of de novo leukemia by high-resolution aCGH.

    Directory of Open Access Journals (Sweden)

    Nathalie Itzhar

    Full Text Available Therapy-related acute leukemia (t-AML, is a severe complication of cytotoxic therapy used for primary cancer treatment. The outcome of these patients is poor, compared to people who develop de novo acute leukemia (p-AML. Cytogenetic abnormalities in t-AML are similar to those found in p-AML but present more frequent unfavorable karyotypes depending on the inducting agent. Losses of chromosome 5 or 7 are observed after alkylating agents while balanced translocations are found after topoisomerase II inhibitors. This study compared t-AML to p-AML using high resolution array CGH in order to find copy number abnormalities (CNA at a higher resolution than conventional cytogenetics. More CNAs were observed in 30 t-AML than in 36 p-AML: 104 CNAs were observed with 63 losses and 41 gains (mean number 3.46 per case in t-AML, while in p-AML, 69 CNAs were observed with 32 losses and 37 gains (mean number of 1.9 per case. In primary leukemia with a previously "normal" karyotype, 18% exhibited a previously undetected CNA, whereas in the (few t-AML with a normal karyotype, the rate was 50%. Several minimal critical regions (MCRs were found in t-AML and p-AML. No common MCRs were found in the two groups. In t-AML a 40 kb deleted MCR pointed to RUNX1 on 21q22, a gene coding for a transcription factor implicated in frequent rearrangements in leukemia and in familial thrombocytopenia. In de novo AML, a 1 Mb MCR harboring ERG and ETS2 was observed from patients with complex aCGH profiles. High resolution cytogenomics obtained by aCGH and similar techniques already published allowed us to characterize numerous non random chromosome abnormalities. This work supports the hypothesis that they can be classified into several categories: abnormalities common to all AML; those more frequently found in t-AML and those specifically found in p-AML.

  13. A hybridised variable neighbourhood tabu search heuristic to increase security in a utility network

    International Nuclear Information System (INIS)

    Janssens, Jochen; Talarico, Luca; Sörensen, Kenneth

    2016-01-01

    We propose a decision model aimed at increasing security in a utility network (e.g., electricity, gas, water or communication network). The network is modelled as a graph, the edges of which are unreliable. We assume that all edges (e.g., pipes, cables) have a certain, not necessarily equal, probability of failure, which can be reduced by selecting edge-specific security strategies. We develop a mathematical programming model and a metaheuristic approach that uses a greedy random adaptive search procedure to find an initial solution and uses tabu search hybridised with iterated local search and a variable neighbourhood descend heuristic to improve this solution. The main goal is to reduce the risk of service failure between an origin and a destination node by selecting the right combination of security measures for each network edge given a limited security budget. - Highlights: • A decision model aimed at increasing security in a utility network is proposed. • The goal is to reduce the risk of service failure given a limited security budget. • An exact approach and a variable neighbourhood tabu search heuristic are developed. • A generator for realistic networks is built and used to test the solution methods. • The hybridised heuristic reduces the total risk on average with 32%.

  14. Oligo-based High-resolution aCGH Analysis Enhances Routine Cytogenetic Diagnostics in Haematological Malignancies.

    Science.gov (United States)

    Kjeldsen, Eigil

    2015-01-01

    The purpose of the present study was to evaluate the detection rate of genomic aberrations in haematological malignancies using oligobased array-CGH (oaCGH) analysis in combination with karyotyping and fluorescence in situ hybridization (FISH) analyses, and its feasibility in a clinical pragmatic approach. The 4x180K Cancer Cytochip array was applied in 96 patients with various haematological malignancies in a prospective setting and in 41 acute myeloid leukemia (AML) patients retrospectively. Combined use of oaCGH analysis and karyotyping improved the overall detection rate in comparison to karyotyping-alone and vice versa. In cases with normal karyotypes oaCGH analysis detected genomic aberrations in 66% (39/60) of cases. In the group of simple karyotypes oaCGH analysis extended karyotypic findings in 39% (12/31) while oaCGH analysis extended the karyotypic findings in 89% (39/44) of cases with complex karyotypes. In 7% (5/75) of cases oaCGH analysis failed in detecting the observed abnormalities by karyotyping. oaCGH analysis is a valuable asset in routine cytogenetics of haematological malignancies. Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

  15. Genome-Wide Screening of Cytogenetic Abnormalities in Multiple Myeloma Patients Using Array-CGH Technique: A Czech Multicenter Experience

    Directory of Open Access Journals (Sweden)

    Jan Smetana

    2014-01-01

    Full Text Available Characteristic recurrent copy number aberrations (CNAs play a key role in multiple myeloma (MM pathogenesis and have important prognostic significance for MM patients. Array-based comparative genomic hybridization (aCGH provides a powerful tool for genome-wide classification of CNAs and thus should be implemented into MM routine diagnostics. We demonstrate the possibility of effective utilization of oligonucleotide-based aCGH in 91 MM patients. Chromosomal aberrations associated with effect on the prognosis of MM were initially evaluated by I-FISH and were found in 93.4% (85/91. Incidence of hyperdiploidy was 49.5% (45/91; del(13(q14 was detected in 57.1% (52/91; gain(1(q21 occurred in 58.2% (53/91; del(17(p13 was observed in 15.4% (14/91; and t(4;14(p16;q32 was found in 18.6% (16/86. Genome-wide screening using Agilent 44K aCGH microarrays revealed copy number alterations in 100% (91/91. Most common deletions were found at 13q (58.9%, 1p (39.6%, and 8p (31.1%, whereas gain of whole 1q was the most often duplicated region (50.6%. Furthermore, frequent homozygous deletions of genes playing important role in myeloma biology such as TRAF3, BIRC1/BIRC2, RB1, or CDKN2C were observed. Taken together, we demonstrated the utilization of aCGH technique in clinical diagnostics as powerful tool for identification of unbalanced genomic abnormalities with prognostic significance for MM patients.

  16. Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

    DEFF Research Database (Denmark)

    Staaf, Johan; Törngren, Therese; Rambech, Eva

    2008-01-01

    deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged...... of primers for sequence determination of the breakpoints. The array platform can be streamlined for a particular application, e.g., focusing on breast cancer susceptibility genes, with increased capacity using multiformat design, and represents a valuable new tool and complement for genetic screening...

  17. Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

    DEFF Research Database (Denmark)

    Staaf, Johan; Törngren, Therese; Rambech, Eva

    2008-01-01

    deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged...

  18. Niche accumulation and hybridisation strategies in transition processes towards a sustainable energy system: An assessment of differences and pitfalls

    International Nuclear Information System (INIS)

    Raven, Rob

    2007-01-01

    This paper assesses two patterns in transition processes for using them as strategies towards a sustainable energy system, i.e., niche accumulation and hybridisation. Both play important but different roles in transitions. The expected success of these strategies depends on the innovation's history and the innovation context. The different strategies are illustrated with several examples from the energy domain

  19. Interspecific hybridisation and interaction with cultivars affect the genetic variation of Ulmus minor and U. glabra in Flanders

    NARCIS (Netherlands)

    Cox, K.; Broek, vanden A.; Mijnsbrugge, vander K.; Buiteveld, J.; Collin, R.W.J.; Heybroek, H.; Mergeay, J.

    2014-01-01

    Interspecific hybridisation and gene flow from cultivated plants may have profound effects on the evolution of wild species. Considering the cultural history and past use of Ulmus minor and Ulmus glabra trees in Flanders (northern Belgium), we investigated the extent of human impact on the genetic

  20. Application of fluorescent in situ hybridisation for demonstration of Coxiella burnetti in placentas from ruminant abortions

    DEFF Research Database (Denmark)

    Jensen, Tim Kåre; Montgomery, Donald L.; Jaeger, Paula T.

    2007-01-01

    A fluorescent in situ hybridisation (FISH) assay targeting 16S ribosomal RNA was developed for detection of the zoonotic bacterium Coxiella burnetii in formalin-fixed, paraffin-embedded tissue, and applied on placentas from ruminant abortions. The applicability of the FISH assay was compared...... to immunohistochemistry (IHC) using human positive control serum in 12 cases of C burnetii-associated placentitis as well as 7 negative control tissue samples. In all 12 cases the bacterium was detected within trophoblasts as well as free in the placental debris by both FISH and IHC. Extensive and significant infection...... by C. burnetii was revealed in 10 of the cases, whereas a slighter and focal distribution of the bacterium was observed in two cases. 90 aborted placentas from Danish ruminants were investigated by FISH. C burnetii was detected in one bovine case only, representing the first confirmation of C burnetii...

  1. Genetic Diversity and Hybridisation between Native and Introduced Salmonidae Fishes in a Swedish Alpine Lake.

    Directory of Open Access Journals (Sweden)

    Leanne Faulks

    Full Text Available Understanding the processes underlying diversification can aid in formulating appropriate conservation management plans that help maintain the evolutionary potential of taxa, particularly under human-induced activities and climate change. Here we assessed the microsatellite genetic diversity and structure of three salmonid species, two native (Arctic charr, Salvelinus alpinus and brown trout, Salmo trutta and one introduced (brook charr, Salvelinus fontinalis, from an alpine lake in sub-arctic Sweden, Lake Ånn. The genetic diversity of the three species was similar and sufficiently high from a conservation genetics perspective: corrected total heterozygosity, H'T = 0.54, 0.66, 0.60 and allelic richness, AR = 4.93, 5.53 and 5.26 for Arctic charr, brown trout and brook charr, respectively. There were indications of elevated inbreeding coefficients in brown trout (GIS = 0.144 and brook charr (GIS = 0.129 although sibling relationships were likely a confounding factor, as a high proportion of siblings were observed in all species within and among sampling locations. Overall genetic structure differed between species, Fst = 0.01, 0.02 and 0.04 in Arctic charr, brown trout and brook charr respectively, and there was differentiation at only a few specific locations. There was clear evidence of hybridisation between the native Arctic charr and the introduced brook charr, with 6% of individuals being hybrids, all of which were sampled in tributary streams. The ecological and evolutionary consequences of the observed hybridisation are priorities for further research and the conservation of the evolutionary potential of native salmonid species.

  2. Molecular detection of Schistosoma japonicum in infected snails and mouse faeces using a real-time PCR assay with FRET hybridisation probes.

    Science.gov (United States)

    Thanchomnang, Tongjit; Intapan, Pewpan; Sri-Aroon, Pusadee; Lulitanond, Viraphong; Janwan, Penchome; Sanpool, Oranuch; Maleewong, Wanchai

    2011-11-01

    A real-time polymerase chain reaction (PCR) assay with fluorescence resonance energy transfer (FRET) hybridisation probes combined with melting curve analysis was developed to detect Schistosoma japonicum in experimentally infected snails and in faecal samples of infected mice. This procedure is based on melting curve analysis of a hybrid between an amplicon from the S. japonicum internal transcribed spacer region 2 sequence, which is a 192-bp S. japonicum-specific sequence, and fluorophore-labelled specific probes. Real-time FRET PCR could detect as little as a single cercaria artificially introduced into a pool of 10 non-infected snails and a single egg inoculated in 100 mg of non-infected mouse faeces. All S. japonicum-infected snails and all faecal samples from infected mice were positive. Non-infected snails, non-infected mouse faeces and genomic DNA from other parasites were negative. This assay is rapid and has potential for epidemiological S. japonicum surveys in snails, intermediate hosts and faecal samples of final hosts.

  3. Hybridisation of solar and geothermal energy in both subcritical and supercritical Organic Rankine Cycles

    International Nuclear Information System (INIS)

    Zhou, Cheng

    2014-01-01

    Highlights: • Hybrid solar and geothermal energy conversion system was modelled using subcritical and supercritical ORCs. • Solar thermal and geothermal energy can be effectively hybridised. • Greater thermodynamic advantages and economic benefits can be achieved using the supercritical hybrid plant. • Hybrid plants can produce up to 19% more annual electricity than the two stand-alone plants. • Solar-to-electricity cost in the supercritical hybrid plant is about 4–19% less than in the subcritical plant. - Abstract: A supercritical Organic Rankine Cycle (ORC) is renowned for higher conversion efficiency than the conventional ORC due to a better thermal match (i.e. reduced irreversibility) presented in the heat exchanger unit. This improved thermal match is a result of the obscured liquid-to-vapor boundary of the organic working fluid at supercritical states. Stand-alone solar thermal power generation and stand-alone geothermal power generation using a supercritical ORC have been widely investigated. However, the power generation capability of a single supercritical ORC using combined solar and geothermal energy has not been examined. This paper thus investigates the hybridisation of solar and geothermal energy in a supercritical ORC to explore the benefit from the potential synergies of such a hybrid platform. Its performances were also compared with those of a subcritical hybrid plant, stand-alone solar and geothermal plants. All simulations and modelling of the power cycles were carried out using process simulation package Aspen HYSYS. The performances of the hybrid plant were then assessed using technical analysis, economic analysis, and the figure of merit analysis. The results of the technical analysis show that thermodynamically, the hybrid plant using a supercritical ORC outperforms the hybrid plant using a subcritical ORC if at least 66% of its exergy input is met by solar energy (i.e. a solar exergy fraction of >66%), namely producing 4–17

  4. Significance of genomic instability in breast cancer in atomic bomb survivors: analysis of microarray-comparative genomic hybridization

    International Nuclear Information System (INIS)

    Oikawa, Masahiro; Yoshiura, Koh-ichiro; Kondo, Hisayoshi; Miura, Shiro; Nagayasu, Takeshi; Nakashima, Masahiro

    2011-01-01

    It has been postulated that ionizing radiation induces breast cancers among atomic bomb (A-bomb) survivors. We have reported a higher incidence of HER2 and C-MYC oncogene amplification in breast cancers from A-bomb survivors. The purpose of this study was to clarify the effect of A-bomb radiation exposure on genomic instability (GIN), which is an important hallmark of carcinogenesis, in archival formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer by using microarray-comparative genomic hybridization (aCGH). Tumor DNA was extracted from FFPE tissues of invasive ductal cancers from 15 survivors who were exposed at 1.5 km or less from the hypocenter and 13 calendar year-matched non-exposed patients followed by aCGH analysis using a high-density oligonucleotide microarray. The total length of copy number aberrations (CNA) was used as an indicator of GIN, and correlation with clinicopathological factors were statistically tested. The mean of the derivative log ratio spread (DLRSpread), which estimates the noise by calculating the spread of log ratio differences between consecutive probes for all chromosomes, was 0.54 (range, 0.26 to 1.05). The concordance of results between aCGH and fluorescence in situ hybridization (FISH) for HER2 gene amplification was 88%. The incidence of HER2 amplification and histological grade was significantly higher in the A-bomb survivors than control group (P = 0.04, respectively). The total length of CNA tended to be larger in the A-bomb survivors (P = 0.15). Correlation analysis of CNA and clinicopathological factors revealed that DLRSpread was negatively correlated with that significantly (P = 0.034, r = -0.40). Multivariate analysis with covariance revealed that the exposure to A-bomb was a significant (P = 0.005) independent factor which was associated with larger total length of CNA of breast cancers. Thus, archival FFPE tissues from A-bomb survivors are useful for genome-wide aCGH analysis. Our results suggested that A

  5. One-day detection of PCR amplified Chlamydia trachomatis DNA in clinical samples: ELISA versus Southern blot hybridisation.

    OpenAIRE

    Roymans, R T; Onland, G; Postma, B H

    1996-01-01

    AIMS: To compare ELISA and Southern blot hybridisation for the detection of PCR amplified Chlamydia trachomatis DNA extracted from clinical samples; to assess the value of the ELISA method in a clinical setting. METHODS: DNA was extracted from urogenital samples of 508 patients, purified and amplified using C trachomatis specific primers, one of which was endlabelled with biotin. Amplification products were detected by Streptavidin biotin based ELISA and non-radioactive Southern blotting. RES...

  6. The assisted prediction modelling frame with hybridisation and ensemble for business risk forecasting and an implementation

    Science.gov (United States)

    Li, Hui; Hong, Lu-Yao; Zhou, Qing; Yu, Hai-Jie

    2015-08-01

    The business failure of numerous companies results in financial crises. The high social costs associated with such crises have made people to search for effective tools for business risk prediction, among which, support vector machine is very effective. Several modelling means, including single-technique modelling, hybrid modelling, and ensemble modelling, have been suggested in forecasting business risk with support vector machine. However, existing literature seldom focuses on the general modelling frame for business risk prediction, and seldom investigates performance differences among different modelling means. We reviewed researches on forecasting business risk with support vector machine, proposed the general assisted prediction modelling frame with hybridisation and ensemble (APMF-WHAE), and finally, investigated the use of principal components analysis, support vector machine, random sampling, and group decision, under the general frame in forecasting business risk. Under the APMF-WHAE frame with support vector machine as the base predictive model, four specific predictive models were produced, namely, pure support vector machine, a hybrid support vector machine involved with principal components analysis, a support vector machine ensemble involved with random sampling and group decision, and an ensemble of hybrid support vector machine using group decision to integrate various hybrid support vector machines on variables produced from principle components analysis and samples from random sampling. The experimental results indicate that hybrid support vector machine and ensemble of hybrid support vector machines were able to produce dominating performance than pure support vector machine and support vector machine ensemble.

  7. Y-SNPs do not indicate hybridisation between European aurochs and domestic cattle.

    Directory of Open Access Journals (Sweden)

    Ruth Bollongino

    Full Text Available BACKGROUND: Previous genetic studies of modern and ancient mitochondrial DNA have confirmed the Near Eastern origin of early European domestic cattle. However, these studies were not able to test whether hybridisation with male aurochs occurred post-domestication. To address this issue, Götherström and colleagues (2005 investigated the frequencies of two Y-chromosomal haplotypes in extant bulls. They found a significant influence of wild aurochs males on domestic populations thus challenging the common view on early domestication and Neolithic stock-rearing. To test their hypothesis, we applied these Y-markers on Neolithic bone specimens from various European archaeological sites. METHODS AND FINDINGS: Here, we have analysed the ancient DNA of 59 Neolithic skeletal samples. After initial molecular sexing, two segregating Y-SNPs were identified in 13 bulls. Strikingly, our results do not support the hypothesis that these markers distinguish European aurochs from domesticated cattle. CONCLUSIONS: The model of a rapid introduction of domestic cattle into Central Europe without significant crossbreeding with local wild cattle remains unchallenged.

  8. Medium Affect Desire: Hybridising Real Virtual and the Actualised through Affective Medium Ecology

    Directory of Open Access Journals (Sweden)

    Marc Boumeester

    2014-10-01

    Full Text Available Underneath the turbulent surface of the ubiquitous media-scape lies an even more agile and aggressive set of relations. A central figure in this turmoil of desires seems to be the asignifying sign, which has a hybridising liaison with both the realm of the real virtual and the realm of the actualised. The main question is what does it want? This new materialistic, non-anthropocentric liberty of affect is creating an arena of strange attractors and other topological vector fields in which our own unconscious drive is as effective as that of the steel ball in a pinball machine. Could we isolate the intrinsic drive of the medium from its subservient position in the aesthetic, freeing its desire from the anthropocentric dominion? What does it Yen for? Perhaps this gap is not meant to be filled, as it is this yearning what it yearns for. The asignifying sign cannot be isolated, it is neither here nor there, yet it is conditionally omnipresent, it inhibits the gap, its desire is to affect.

  9. Examination of equine glandular stomach lesions for bacteria, including Helicobacter spp by fluorescence in situ hybridisation

    Directory of Open Access Journals (Sweden)

    Olsen Susanne N

    2010-03-01

    Full Text Available Abstract Background The equine glandular stomach is commonly affected by erosion and ulceration. The aim of this study was to assess whether bacteria, including Helicobacter, could be involved in the aetiology of gastric glandular lesions seen in horses. Results Stomach lesions, as well as normal appearing mucosa were obtained from horses slaughtered for human consumption. All samples were tested for urease activity using the Pyloritek® assay, while mucosal bacterial content was evaluated using Fluorescence In Situ Hybridisation. In selected sub samples, bacteria characterisation was pursued further by cloning and sequencing. Mucosal lesions were found in 36/63 stomachs and included hyperplastic rugae, polypoid structures and focal erosions. None of the samples were tested positive for urease activity or for FISH using the Helicobacter genus specific probe. In samples of lesions, as well as normal samples, clones with 99% similarities to Lactobacillus salivarius and Sarcina ventriculi were found. Escherichia like bacterium clones and Enterococcus clones were demonstrated in one focal erosion. Based on a phylogenetic tree these clones had 100% similarity to Escherichia fergusonii and Enterococcus faecium. The Enterococcus were found colonising the mucosal surface, while E. fergusonii organisms were also demonstrated intraepithelial. Conclusion Gastric Helicobacter spp. could not be verified as being involved in lesions of the glandular stomach of the horse. Since E. fergusonii has been described as an emerging pathogen in both humans and animals, the finding of this bacterium in gastric erosion warrants further clarification to whether gastric infection with this type bacterium is important for horses.

  10. Prognostic Impact of Array-based Genomic Profiles in Esophageal Squamous Cell Cancer

    International Nuclear Information System (INIS)

    Carneiro, Ana; Isinger, Anna; Karlsson, Anna; Johansson, Jan; Jönsson, Göran; Bendahl, Pär-Ola; Falkenback, Dan; Halvarsson, Britta; Nilbert, Mef

    2008-01-01

    Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival. Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis. aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC

  11. Genomic hypomethylation in the human germline associates with selective structural mutability in the human genome.

    Directory of Open Access Journals (Sweden)

    Jian Li

    Full Text Available The hotspots of structural polymorphisms and structural mutability in the human genome remain to be explained mechanistically. We examine associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination (NAHR mediated by low-copy repeats (LCRs. Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability. Specifically, methylation deserts, the ~1% fraction of the human genome with the lowest methylation in the germline, show a tenfold enrichment for structural rearrangements that occurred in the human genome since the branching of chimpanzee and are highly enriched for fast-evolving loci that regulate tissue-specific gene expression. Analysis of copy number variants (CNVs from 400 human samples identified using a custom-designed array comparative genomic hybridization (aCGH chip, combined with publicly available structural variation data, indicates that association of structural mutability with germline hypomethylation is comparable in magnitude to the association of structural mutability with LCR-mediated NAHR. Moreover, rare CNVs occurring in the genomes of individuals diagnosed with schizophrenia, bipolar disorder, and developmental delay and de novo CNVs occurring in those diagnosed with autism are significantly more concentrated within hypomethylated regions. These findings suggest a new connection between the epigenome, selective mutability, evolution, and human disease.

  12. Analysis of genomic imbalances and gene expression changes in transformed follicular lymphoma (FL)

    DEFF Research Database (Denmark)

    Obel, G.; Farinha, P.; Lam, W.

    2005-01-01

    American patients with transformed FL. Methods: High-resolution BAC-array comparative genomic hybridisation (CGH) was used to detect genomic imbalances. Gene expression profiling was performed using cDNA microarrays (Affymetrix). Results: Of 9 biopsy pairs identified so far, analysis results of the first 4......: The combined use of array-CGH and gene expression analysis will provide a more comprehensive picture of the transformation process in FL....

  13. Isolation and characterization of repeat elements of the oak genome and their application in population analysis

    International Nuclear Information System (INIS)

    Fluch, S.; Burg, K.

    1998-01-01

    Four minisatellite sequence elements have been identified and isolated from the genome of the oak species Quercus petraea and Quercus robur. Minisatellites 1 and 2 are putative members of repeat families, while minisatellites 3 and 4 show repeat length variation among individuals of test populations. A 590 base pair (bp) long element has also been identified which reveals individual-specific autoradiographic patterns when used as probe in Southern hybridisations of genomic oak DNA. (author)

  14. Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH)

    NARCIS (Netherlands)

    Maas, N. M. C.; Van Buggenhout, G.; Hannes, F.; Thienpont, B.; Sanlaville, D.; Kok, K.; Midro, A.; Andrieux, J.; Anderlid, B-M; Schoumans, J.; Hordijk, R.; Devriendt, K.; Fryns, J-P; Vermeesch, J. R.

    Background: The Wolf-Hirschhorn syndrome (WHS) is usually caused by terminal deletions of the short arm of chromosome 4 and is phenotypically defined by growth and mental retardation, seizures, and specific craniofacial manifestations. Large variation is observed in phenotypic expression of these

  15. Identification of genome-wide copy number variations among diverse pig breeds by array CGH

    Directory of Open Access Journals (Sweden)

    Li Yan

    2012-12-01

    Full Text Available Abstract Background Recent studies have shown that copy number variation (CNV in mammalian genomes contributes to phenotypic diversity, including health and disease status. In domestic pigs, CNV has been catalogued by several reports, but the extent of CNV and the phenotypic effects are far from clear. The goal of this study was to identify CNV regions (CNVRs in pigs based on array comparative genome hybridization (aCGH. Results Here a custom-made tiling oligo-nucleotide array was used with a median probe spacing of 2506 bp for screening 12 pigs including 3 Chinese native pigs (one Chinese Erhualian, one Tongcheng and one Yangxin pig, 5 European pigs (one Large White, one Pietrain, one White Duroc and two Landrace pigs, 2 synthetic pigs (Chinese new line DIV pigs and 2 crossbred pigs (Landrace × DIV pigs with a Duroc pig as the reference. Two hundred and fifty-nine CNVRs across chromosomes 1–18 and X were identified, with an average size of 65.07 kb and a median size of 98.74 kb, covering 16.85 Mb or 0.74% of the whole genome. Concerning copy number status, 93 (35.91% CNVRs were called as gains, 140 (54.05% were called as losses and the remaining 26 (10.04% were called as both gains and losses. Of all detected CNVRs, 171 (66.02% and 34 (13.13% CNVRs directly overlapped with Sus scrofa duplicated sequences and pig QTLs, respectively. The CNVRs encompassed 372 full length Ensembl transcripts. Two CNVRs identified by aCGH were validated using real-time quantitative PCR (qPCR. Conclusions Using 720 K array CGH (aCGH we described a map of porcine CNVs which facilitated the identification of structural variations for important phenotypes and the assessment of the genetic diversity of pigs.

  16. Validity of whole slide images for scoring HER2 chromogenic in situ hybridisation in breast cancer.

    Science.gov (United States)

    Al-Janabi, Shaimaa; Horstman, Anja; van Slooten, Henk-Jan; Kuijpers, Chantal; Lai-A-Fat, Clifton; van Diest, Paul J; Jiwa, Mehdi

    2016-05-09

    Whole slide images (WSIs) have stimulated a paradigm shift from conventional to digital pathology in several applications within pathology. Due to the fact that WSIs have not yet been approved for primary diagnostics, validating their use for different diagnostic purposes is still mandatory. The aim of this study was to test the validity of WSI in assessing human epidermal growth factor receptor 2 (HER2) status in breast cancer specimens using chromogenic in situ hybridisation (CISH). Ninety-six HER2 CISH slides were scored by two observers on a light microscope (400× viewing magnification) and on WSI (40× scanning magnification, one focus plane) with a minimum of 6 weeks washout period. The concordance between digital and microscopic HER2 scores was assessed. Digitally, 93/96 cases could be assessed (96.8%). Microscopic and digital evaluation of HER2 amplification status were concordant in 68/93 cases ((73.1%, 95% CI: 0.639 -0.823), κ 0.588). CISH underscoring was most noticeable in the amplified and equivocal categories while the highest level concordance was seen in cases with a normal copy number. Additionally there was a noticeable tendency to underestimate the average HER2 scores on WSI: lower in 59 and higher in 11 cases. There was no major difference in time spent for microscopic scoring (86.9 s) and digital scoring (81.7 s). There was a reasonable concordance between microscopic scoring and WSI-based scoring of HER2 copy number of CISH slides. Nevertheless, WSIs scanned on a single focal plane are insufficient to assess HER2 gene amplification status by scoring CISH due to the noticeable tendency towards digitally underestimating the number of HER2 spots. Scanning at multiple focus planes may offer better resolution for improved digital CISH spot counting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. Introducing a New Breed of Wine Yeast: Interspecific Hybridisation between a Commercial Saccharomyces cerevisiae Wine Yeast and Saccharomyces mikatae

    Science.gov (United States)

    Bellon, Jennifer R.; Schmid, Frank; Capone, Dimitra L.; Dunn, Barbara L.; Chambers, Paul J.

    2013-01-01

    Interspecific hybrids are commonplace in agriculture and horticulture; bread wheat and grapefruit are but two examples. The benefits derived from interspecific hybridisation include the potential of generating advantageous transgressive phenotypes. This paper describes the generation of a new breed of wine yeast by interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast strain and Saccharomyces mikatae, a species hitherto not associated with industrial fermentation environs. While commercially available wine yeast strains provide consistent and reliable fermentations, wines produced using single inocula are thought to lack the sensory complexity and rounded palate structure obtained from spontaneous fermentations. In contrast, interspecific yeast hybrids have the potential to deliver increased complexity to wine sensory properties and alternative wine styles through the formation of novel, and wider ranging, yeast volatile fermentation metabolite profiles, whilst maintaining the robustness of the wine yeast parent. Screening of newly generated hybrids from a cross between a S. cerevisiae wine yeast and S. mikatae (closely-related but ecologically distant members of the Saccharomyces sensu stricto clade), has identified progeny with robust fermentation properties and winemaking potential. Chemical analysis showed that, relative to the S. cerevisiae wine yeast parent, hybrids produced wines with different concentrations of volatile metabolites that are known to contribute to wine flavour and aroma, including flavour compounds associated with non-Saccharomyces species. The new S. cerevisiae x S. mikatae hybrids have the potential to produce complex wines akin to products of spontaneous fermentation while giving winemakers the safeguard of an inoculated ferment. PMID:23614011

  18. Fluorescence (FISH) and chromogenic (CISH) in situ hybridisation in prostate carcinoma cell lines: comparison and use of virtual microscopy.

    Science.gov (United States)

    Elliott, K; Hamilton, P W; Maxwell, P

    2008-01-01

    Chromogenic in situ hybridisation (CISH) has become an attractive alternative to fluorescence in situ hybridisation (FISH) due to its permanent stain which is more familiar to pathologists and because it can be viewed using light microscopy. The aim of the present study is to examine reproducibility in the assessment of abnormal chromosome number by CISH in comparison to FISH. Using three prostate cell lines--PNT1A (derived from normal epithelium), LNCAP and DU145 (derived from prostatic carcinoma), chromosomes 7 and 8 were counted in 40 nuclei in FISH preparations (x100 oil immersion) and 100 nuclei in CISH preparations (x40) by two independent observers. The CISH slides were examined using standard light microscopy and virtual microscopy. Reproducibility was examined using paired Student's t-test (PCISH. No significant differences in chromosome count were seen between the techniques. Chromosomes 7 and 8 showed disomic status for each cell line except LNCAP, which proved to be heterogeneous (disomic/aneusomic), particularly for chromosome 8. Virtual microscopy proved to be easy to use and gave no significant differences from standard light microscopy. These results support the hypothesis that there is no significant difference between FISH and CISH techniques.

  19. Agreement between chromogenic in situ hybridisation (CISH) and FISH in the determination of HER2 status in breast cancer.

    Science.gov (United States)

    Arnould, L; Denoux, Y; MacGrogan, G; Penault-Llorca, F; Fiche, M; Treilleux, I; Mathieu, M C; Vincent-Salomon, A; Vilain, M O; Couturier, J

    2003-05-19

    Determination of the HER2/neu (HER2) status in breast carcinoma has become necessary for the selection of breast cancer patients for trastuzumab therapy. Amplification of the gene analysed by fluorescence in situ hybridisation (FISH) or overexpression of the protein determined by immunohistochemistry (IHC) are the two major methods to establish this status. A strong correlation has been previously demonstrated between these two methods. However, FISH is not always feasible in routine practice and weakly positive IHC tumours (2+) do not always correspond to a gene amplification. Our study was performed in order to evaluate the contribution of chromogenic in situ hybridisation (CISH), which enables detection of the gene copies through an immunoperoxidase reaction. CISH was performed in 79 breast carcinomas for which the HER2 status was previously determined by IHC and FISH. The results of IHC, FISH and CISH were compared for each tumour. CISH procedures were successful in 95% of our cases. Whatever the IHC results, we found a very good concordance (96%) between CISH and FISH. Our study confirms that CISH may be an alternative to FISH for the determination of the gene amplification status in 2+ tumours. Our results allow us to think that, in many laboratories, CISH may also be an excellent method to calibrate the IHC procedures or, as a quality control test, to check regularly that the IHC signal is in agreement with the gene status.

  20. Introducing a new breed of wine yeast: interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast and Saccharomyces mikatae.

    Directory of Open Access Journals (Sweden)

    Jennifer R Bellon

    Full Text Available Interspecific hybrids are commonplace in agriculture and horticulture; bread wheat and grapefruit are but two examples. The benefits derived from interspecific hybridisation include the potential of generating advantageous transgressive phenotypes. This paper describes the generation of a new breed of wine yeast by interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast strain and Saccharomyces mikatae, a species hitherto not associated with industrial fermentation environs. While commercially available wine yeast strains provide consistent and reliable fermentations, wines produced using single inocula are thought to lack the sensory complexity and rounded palate structure obtained from spontaneous fermentations. In contrast, interspecific yeast hybrids have the potential to deliver increased complexity to wine sensory properties and alternative wine styles through the formation of novel, and wider ranging, yeast volatile fermentation metabolite profiles, whilst maintaining the robustness of the wine yeast parent. Screening of newly generated hybrids from a cross between a S. cerevisiae wine yeast and S. mikatae (closely-related but ecologically distant members of the Saccharomyces sensu stricto clade, has identified progeny with robust fermentation properties and winemaking potential. Chemical analysis showed that, relative to the S. cerevisiae wine yeast parent, hybrids produced wines with different concentrations of volatile metabolites that are known to contribute to wine flavour and aroma, including flavour compounds associated with non-Saccharomyces species. The new S. cerevisiae x S. mikatae hybrids have the potential to produce complex wines akin to products of spontaneous fermentation while giving winemakers the safeguard of an inoculated ferment.

  1. Localisation and quantification of alkali-labile sites in human spermatozoa by DNA breakage detection-fluorescence in situ hybridisation.

    Science.gov (United States)

    Cortés-Gutiérrez, E I; Dávila-Rodríguez, M I; Cerda-Flores, R M; Fernández, J L; López-Fernández, C; Aragón Tovar, A R; Gosálvez, J

    2015-03-01

    The localisation and quantification of constitutive alkali-labile sites (ALSs) were investigated using a protocol of DNA breakage detection plus fluorescence in situ hybridisation (DBD-FISH) and alkaline single-cell gel electrophoresis (SCGE or comet assay), in spermatozoa of infertile and fertile men. Semen samples from 10 normozoospermic patients undergoing infertility treatment and 10 fertile men were included in this study. ALSs were localised and quantified by DBD-FISH. The region most sensitive to alkali treatment in human spermatozoa was located in the basal region of the head. ALSs were more frequent in spermatozoa of infertile men than in those of fertile men. These results were confirmed by SCGE comet assays. In conclusion, the most intense localisation of hybridisation signals in human spermatozoa, representing the highest density of constitutive ALSs, was not randomly distributed and was predominantly located in the base of the head. Moreover, infertile men presented with an increase in ALS frequency. Further studies are necessary to determine the association between ALS, sperm chromatin organisation and infertility. © 2014 Blackwell Verlag GmbH.

  2. Long tandem repeats as a form of genomic copy number variation: structure and length polymorphism of a chromosome 5p repeat in control and schizophrenia populations

    Science.gov (United States)

    Bruce, Heather A.; Sachs, Nancy A.; Rudnicki, Dobrila D.; Lin, Stephanie G.; Willour, Virginia L.; Cowell, John K.; Conroy, Jeffrey; McQuaid, Devin E.; Rossi, Michael; Gaile, Daniel P; Nowak, Norma J.; Holmes, Susan E.; Sklar, Pamela; Ross, Christopher A.; DeLisi, Lynn E.; Margolis, Russell L.

    2016-01-01

    Objectives Genomic copy number variations (CNVs) are a major form of variation in the human genome and play an etiologic role in several neuropsychiatric diseases. Tandem repeats, particularly with long (> 50bp) repeat units, are a relatively common yet underexplored type of CNV that may significantly contribute to human genomic variation and disease risk. We therefore performed a pilot experiment to explore the potential role of long tandem repeats as risk factors in psychiatric disorders. Methods A bacterial artificial chromosome (BAC)-based array comparative genomic hybridization (aCGH) platform was used to examine CNVs in genomic DNA from 34 probands with schizophrenia or schizoaffective disorder. Results The aCGH screen detected an apparent deletion on 5p15.1 in two probands, caused by the presence in each proband of two low copy number (short) alleles of a tandem repeat that ranges in length from 50 3.4 kb units in the population examined. Short alleles partially segregate with schizophrenia in a small number of families, though linkage was not significant. An association study showed no significant difference in repeat length between 406 schizophrenia cases and 392 controls. Conclusion Though we did not demonstrate a relationship between the 5p15.1 repeat and schizophrenia, our results illustrate that long tandem repeats represent an intriguing type of genetic variation that have not been previously studied in connection with psychiatric illness. aCGH can detect a small subset of these repeats, but systematic investigation will require the development of specific arrays and improved analytic methods. PMID:19672138

  3. Effects of willow hybridisation and simulated browsing on the development and survival of the leaf beetle Phratora vitellinae

    Directory of Open Access Journals (Sweden)

    Hallgren Per

    2003-06-01

    Full Text Available Abstract Background Interspecific hybridisation is common between many plant species and causes rapid changes in a variety of plant characters. This may pose problems for herbivores because changes in recognition characters may be poorly correlated with changes in quality characters. Many studies have examined different systems of hybrids and herbivores in attempts to understand the role of hybridisation in the evolution of plant resistance. The results from different systems are variable. Studies of hybrids between Salix caprea (L., Salicaceae and S. repens show that they are intermediate between the two parental species in most resistence characters. However, a plants herbivore resistence depends also on its biotic and abiotic environment. Important biotic factors that may influence plant growth and plant chemistry include the interactions between different herbivores that occur through their exploitation of common host plants. Although the effects on plants of previous herbivory are likely to be strongly affected by environmental conditions, they are also species-specific. Damage may therefore have different effects on hybrids than on their parental species, and this could influence the performance of herbivores on pure and hybrid species of plants. To evaluate the effects of hybridisation on insect performance, the development and survival rates of Phratora vitellinae (L. 1758, Coleoptera: Chrysomelidae larvae on pure S. repens, pure S. caprea and Fl hybrids of the two species was monitored. Further, to examine the effect of herbivorous mammals on the performance of the larvae, plants were damaged to simulate winter foraging by voles or spring leaf stripping by moose. Results The results show that development rates were highest on S. repens and equally low on S. caprea and the Fl hybrid. In addition, development of the plants treated to simulate mammalian herbivore damage was slower than that of corresponding controls. Conclusions The

  4. Chromogenic in situ hybridisation for the assessment of HER2 status in breast cancer: an international validation ring study

    Science.gov (United States)

    van de Vijver, Marc; Bilous, Michael; Hanna, Wedad; Hofmann, Manfred; Kristel, Petra; Penault-Llorca, Frédérique; Rüschoff, Josef

    2007-01-01

    Introduction Before any new methodology can be introduced into the routine diagnostic setting it must be technically validated against the established standards. To this end, a ring study involving five international pathology laboratories was initiated to validate chromogenic in situ hybridisation (CISH) against fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) as a test for assessing human epidermal growth factor receptor 2 (HER2) status in breast cancer. Methods Each laboratory performed CISH, FISH and IHC on its own samples. Unstained sections from each case were also sent to another participating laboratory for blinded retesting by CISH ('outside CISH'). Results A total of 211 invasive breast carcinoma cases were tested. In 76 cases with high amplification (HER2/CEP17 ratio >4.0) by FISH, 73 cases (96%) scored positive (scores ≥ 6) by 'outside CISH'. For FISH-negative cases (HER2/CEP17 ratio CISH scores indicating no amplification (score ≤ 5), and only three cases were positive by CISH; in the three remaining cases, no CISH result could be obtained. For cases with low-level amplification using FISH (HER2/CEP17 ratio 2.0–4.0), 20 of 35 had CISH scores indicating gene amplification. Inter-laboratory concordance was also very high: 95% for normal HER2 copy number (1–5 copies); and 92% for cases with HER2 copy numbers ≥ 6. CISH intra-laboratory concordance with IHC was 92% for IHC-negative cases (IHC 0/1+) and 91% for IHC 3+ cases. Among IHC 2+ cases, CISH was 100% concordant with samples showing high amplification by FISH, and 94% concordant with FISH-negative samples. Conclusion These results show that CISH inter- and intra-laboratory concordance to FISH and IHC is very high, even in equivocal IHC 2+ cases. Therefore, we conclude that CISH is a methodology that is a viable alternative to FISH in the HER2 testing algorithm. PMID:17922920

  5. Chromogenic in situ hybridisation (CISH) is a powerful method to detect ALK-positive non-small cell lung carcinomas.

    Science.gov (United States)

    Wagner, F; Streubel, A; Roth, A; Stephan-Falkenau, S; Mairinger, T

    2014-05-01

    We assessed the potential of a chromogenic in situ hybridisation (CISH) assay in comparison with quantitative reverse transcription (RT)-PCR (qPCR) to detect anaplastic lymphoma kinase (ALK) break apart-positive lung carcinomas. Dual-colour CISH using a break apart probe for the ALK gene on 2p23 was performed with 181 formalin-fixed, paraffin-embedded tissue and agar block sections from 175 cases of non-small cell lung carcinomas (NSCLC). Stained slides were analysed with a standard bright-field microscope at 1000× magnification by counting signals from 60 non-overlapping nuclei from three different tumour areas. Samples with ≥15% of positive nuclei were judged as ALK break apart-positive. All samples were simultaneously analysed by qPCR for EML4-ALK to validate CISH results, and positive samples were subject to Sanger sequencing. CISH was successful with 173 of 181 hybridised samples (96%), and seven ALK break apart-positive cases were detected. CISH signals were specific and distinct for both colours. All positive cases were confirmed by qPCR and Sanger sequencing, and concordance between CISH and qPCR was 100%. Nearly all samples (9/10) which failed by qPCR were accessible to CISH analysis. CISH is a very reliable, convenient and inexpensive method to detect ALK-positive NSCLC. CISH success rate is comparably high as with qPCR, and it detects all ALK break apart events in a single assay. It is of special value when RNA quality is poor, or when small biopsies with a very limited amount of tumour cells have to be analysed.

  6. Comparative genomics for biodiversity conservation

    Directory of Open Access Journals (Sweden)

    Catherine E. Grueber

    2015-01-01

    Full Text Available Genomic approaches are gathering momentum in biology and emerging opportunities lie in the creative use of comparative molecular methods for revealing the processes that influence diversity of wildlife. However, few comparative genomic studies are performed with explicit and specific objectives to aid conservation of wild populations. Here I provide a brief overview of comparative genomic approaches that offer specific benefits to biodiversity conservation. Because conservation examples are few, I draw on research from other areas to demonstrate how comparing genomic data across taxa may be used to inform the characterisation of conservation units and studies of hybridisation, as well as studies that provide conservation outcomes from a better understanding of the drivers of divergence. A comparative approach can also provide valuable insight into the threatening processes that impact rare species, such as emerging diseases and their management in conservation. In addition to these opportunities, I note areas where additional research is warranted. Overall, comparing and contrasting the genomic composition of threatened and other species provide several useful tools for helping to preserve the molecular biodiversity of the global ecosystem.

  7. Microarray MAPH: accurate array-based detection of relative copy number in genomic DNA.

    Science.gov (United States)

    Gibbons, Brian; Datta, Parikkhit; Wu, Ying; Chan, Alan; Al Armour, John

    2006-06-30

    Current methods for measurement of copy number do not combine all the desirable qualities of convenience, throughput, economy, accuracy and resolution. In this study, to improve the throughput associated with Multiplex Amplifiable Probe Hybridisation (MAPH) we aimed to develop a modification based on the 3-Dimensional, Flow-Through Microarray Platform from PamGene International. In this new method, electrophoretic analysis of amplified products is replaced with photometric analysis of a probed oligonucleotide array. Copy number analysis of hybridised probes is based on a dual-label approach by comparing the intensity of Cy3-labelled MAPH probes amplified from test samples co-hybridised with similarly amplified Cy5-labelled reference MAPH probes. The key feature of using a hybridisation-based end point with MAPH is that discrimination of amplified probes is based on sequence and not fragment length. In this study we showed that microarray MAPH measurement of PMP22 gene dosage correlates well with PMP22 gene dosage determined by capillary MAPH and that copy number was accurately reported in analyses of DNA from 38 individuals, 12 of which were known to have Charcot-Marie-Tooth disease type 1A (CMT1A). Measurement of microarray-based endpoints for MAPH appears to be of comparable accuracy to electrophoretic methods, and holds the prospect of fully exploiting the potential multiplicity of MAPH. The technology has the potential to simplify copy number assays for genes with a large number of exons, or of expanded sets of probes from dispersed genomic locations.

  8. Comparative analysis of copy number detection by whole-genome BAC and oligonucleotide array CGH

    Directory of Open Access Journals (Sweden)

    Bejjani Bassem A

    2010-06-01

    Full Text Available Abstract Background Microarray-based comparative genomic hybridization (aCGH is a powerful diagnostic tool for the detection of DNA copy number gains and losses associated with chromosome abnormalities, many of which are below the resolution of conventional chromosome analysis. It has been presumed that whole-genome oligonucleotide (oligo arrays identify more clinically significant copy-number abnormalities than whole-genome bacterial artificial chromosome (BAC arrays, yet this has not been systematically studied in a clinical diagnostic setting. Results To determine the difference in detection rate between similarly designed BAC and oligo arrays, we developed whole-genome BAC and oligonucleotide microarrays and validated them in a side-by-side comparison of 466 consecutive clinical specimens submitted to our laboratory for aCGH. Of the 466 cases studied, 67 (14.3% had a copy-number imbalance of potential clinical significance detectable by the whole-genome BAC array, and 73 (15.6% had a copy-number imbalance of potential clinical significance detectable by the whole-genome oligo array. However, because both platforms identified copy number variants of unclear clinical significance, we designed a systematic method for the interpretation of copy number alterations and tested an additional 3,443 cases by BAC array and 3,096 cases by oligo array. Of those cases tested on the BAC array, 17.6% were found to have a copy-number abnormality of potential clinical significance, whereas the detection rate increased to 22.5% for the cases tested by oligo array. In addition, we validated the oligo array for detection of mosaicism and found that it could routinely detect mosaicism at levels of 30% and greater. Conclusions Although BAC arrays have faster turnaround times, the increased detection rate of oligo arrays makes them attractive for clinical cytogenetic testing.

  9. High frequency of submicroscopic genomic aberrations detected by tiling path array comparative genome hybridisation in patients with isolated congenital heart disease

    DEFF Research Database (Denmark)

    Erdogan, F; Larsen, Lars Allan; Zhang, L

    2008-01-01

    BACKGROUND: Congenital heart disease (CHD) is the most common birth defect and affects nearly 1% of newborns. The aetiology of CHD is largely unknown and only a small percentage can be assigned to environmental risk factors such as maternal diseases or exposure to mutagenic agents during pregnanc...

  10. Prenatal diagnosis and array comparative genomic hybridization characterization of interstitial deletions of 8q23.3-q24.11 and 8q24.13 associated with Langer-Giedion syndrome, Cornelia de Lange syndrome and haploinsufficiency of TRPS1, RAD21 and EXT1.

    Science.gov (United States)

    Chen, Chih-Ping; Lin, Ming-Huei; Chen, Yi-Yung; Chern, Schu-Rern; Chen, Yen-Ni; Wu, Peih-Shan; Pan, Chen-Wen; Lee, Meng-Shan; Wang, Wayseen

    2015-10-01

    The aim of this research was to present prenatal diagnosis of Langer-Giedion syndrome (LGS/TRPS type II) and Cornelia de Lange syndrome-4 (CDLS4). A 36-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Conventional cytogenetic analysis of amniocentesis revealed an interstitial deletion of chromosome 8q or del(8)(q23.3q24.13). Level II prenatal ultrasound examination revealed craniofacial dysmorphism. The pregnancy was terminated, and a malformed fetus was delivered with characteristic craniofacial dysmorphism of LGS/TRPS type II and CDLS4. Whole-genome array comparative genomic hybridization (aCGH) on the DNA extracted from cultured amniocytes was performed. The analysis by aCGH revealed a result of arr 8q23.3q24.11 (116,087,006-118,969,399)×1, 8q24.13 (123,086,851-124,470,847)×1 (NCBI build 37) with a 2.88-Mb deletion of 8q23.3-q24.11 encompassing six OMIM genes, TRPS1, EIF3H, RAD21, SLC30A8, MED30, and EXT1, and a 1.383-Mb deletion of 8q24.13 encompassing four OMIM genes, ZHX2, DERL1, ZHX1, and ATAD2. In the present case, the conventional cytogenetic analysis of cultured amniocytes revealed del(8)(q23.3q24.13), whereas aCGH analysis of cultured amniocytes showed the deletions of 8q23.3-q24.11 and 8q24.13 with the presence of the segment 8q24.12. Therefore, aCGH provides the advantage of better understanding of the nature of interstitial deletion and genotype-phenotype correlation in this case. Copyright © 2015. Published by Elsevier B.V.

  11. Reconstructing the Evolution of Brachypodium Genomes Using Comparative Chromosome Painting.

    Directory of Open Access Journals (Sweden)

    Alexander Betekhtin

    Full Text Available Brachypodium distachyon is a model for the temperate cereals and grasses and has a biology, genomics infrastructure and cytogenetic platform fit for purpose. It is a member of a genus with fewer than 20 species, which have different genome sizes, basic chromosome numbers and ploidy levels. The phylogeny and interspecific relationships of this group have not to date been resolved by sequence comparisons and karyotypical studies. The aims of this study are not only to reconstruct the evolution of Brachypodium karyotypes to resolve the phylogeny, but also to highlight the mechanisms that shape the evolution of grass genomes. This was achieved through the use of comparative chromosome painting (CCP which hybridises fluorescent, chromosome-specific probes derived from B. distachyon to homoeologous meiotic chromosomes of its close relatives. The study included five diploids (B. distachyon 2n = 10, B. sylvaticum 2n = 18, B. pinnatum 2n = 16; 2n = 18, B. arbuscula 2n = 18 and B. stacei 2n = 20 three allotetraploids (B. pinnatum 2n = 28, B. phoenicoides 2n = 28 and B. hybridum 2n = 30, and two species of unknown ploidy (B. retusum 2n = 38 and B. mexicanum 2n = 40. On the basis of the patterns of hybridisation and incorporating published data, we propose two alternative, but similar, models of karyotype evolution in the genus Brachypodium. According to the first model, the extant genome of B. distachyon derives from B. mexicanum or B. stacei by several rounds of descending dysploidy, and the other diploids evolve from B. distachyon via ascending dysploidy. The allotetraploids arise by interspecific hybridisation and chromosome doubling between B. distachyon and other diploids. The second model differs from the first insofar as it incorporates an intermediate 2n = 18 species between the B. mexicanum or B. stacei progenitors and the dysploidic B. distachyon.

  12. The genetic architecture of hybridisation between two lineages of greenshell mussels.

    Science.gov (United States)

    Gardner, J P A; Wei, K-J

    2015-03-01

    A multidisciplinary approach has identified sigmoidal genetic clines on the east and west coasts in central New Zealand where low-density ecological interactions occur between northern and southern lineages of the endemic greenshell mussel, Perna canaliculus. The sigmoidal clines indicate the existence of a mussel hybrid zone in a region of genetic discontinuities for many continuously distributed coastal taxa, in particular marine invertebrates. Examination of the genetic architecture of the hybrid zone revealed the differential contribution of individual microsatellite loci and/or alleles to defining the zone of interaction and no evidence of increased allelic richness or heterozygosity inside versus outside the hybrid zone. Genomics cline analysis identified one locus in particular (Pcan1-27) as being different from neutral expectations, thereby contributing to lineage differentiation. Estimates of contemporary gene flow revealed very high levels of within-lineage self-recruitment and a hybrid zone composed mostly (~85%) of northern immigrants. Broad scale interpretation of these results is consistent with a zone of genetic interaction that was generated between 0.3 and 1.3 million years before present at a time of pronounced global sea-level change. At that time, the continuous distribution of the greenshell mussel was split into northern and southern groups, which differentiated to become distinct lineages, and which have subsequently been reunited (secondary contact) resulting in the generation of the hybrid zone at ~42°S.

  13. Hybridising Medicine: Illness, Healing and the Dynamics of Reciprocal Exchange on the Upper Guinea Coast (West Africa).

    Science.gov (United States)

    Havik, Philip J

    2016-04-01

    The present article seeks to fill a number of lacunae with regard to the study of the circulation and assimilation of different bodies of medical knowledge in an important cultural contact zone, that is the Upper Guinea Coast. Building upon ongoing research on trade and cultural brokerage in the area, it focuses upon shifting attitudes and practices with regard to health and healing as a result of cultural interaction and hybridisation against the background of growing intra-African and Afro-Atlantic interaction from the fifteenth to the late seventeenth century. Largely based upon travel accounts, missionary reports and documents produced by the Portuguese Inquisition, it shows how forms of medical knowledge shifted and circulated between littoral areas and their hinterland, as well as between the coast, the Atlantic and beyond. It shows that the changing patterns of trade, migration and settlement associated with Mandé influence and Afro-Atlantic exchange had a decisive impact on changing notions of illness and therapeutic trajectories. Over the centuries, cross-cultural, reciprocal borrowing contributed to the development of healing kits employed by Africans and non-African outsiders alike, which were used and brokered by local communities in different locations in the region.

  14. Suppressive subtractive hybridisation transcriptomics provides a novel insight into the functional role of the hypobranchial gland in a marine mollusc.

    Science.gov (United States)

    Laffy, Patrick W; Benkendorff, Kirsten; Abbott, Catherine A

    2013-06-01

    The hypobranchial gland present in gastropods is an organ whose function is not clearly understood. Involved in mucus production, within members of the family Muricidae it is also the source of the ancient dye Tyrian purple and its bioactive precursors. To gain further insights into hypobranchial gland biology, suppressive subtractive hybridisation was performed on hypobranchial gland and mantle tissue from the marine snail Dicathais orbita creating a differentially expressed cDNA library. 437 clones were randomly sequenced, analysed and annotated and 110 sequences had their functions putatively identified. Importantly this approach identified a putative gene involved in Tyrian purple biosynthesis, an arylsulphatase gene. Confirmation of the upregulation of arylsulphatase in the hypobranchial gland compared to the mantle was demonstrated using quantitative real-time PCR. Other genes identified as playing an important role in the hypobranchial gland were those involved in mucus protein synthesis, choline ester regulation, protein and energy production. This study confirms that the hypobranchial gland is involved in the production of mucus secretion and also identifies it as a site of chemical interaction and biosynthesis. This study lays the foundation for a better understanding of the enzymatic production of Tyrian purple precursors within the gland. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Hybridisation mix synthesis in a spiral lab-on-chip device for fast-track microarray genotyping of human pathogens

    Science.gov (United States)

    Peham, Johannes R.; Recnik, Lisa-Maria; Grienauer, Walter; Vellekoop, Michael J.; Nöhammer, Christa; Wiesinger-Mayr, Herbert

    2011-05-01

    DNA microarrays can provide bacterial identification, which is crucial for targeted therapy. However they lack rapidness, because of multiple analysis steps. Therefore a fast one-step method for synthesising a hybridisation-ready reagent out of initial bacterial DNA is required. This work presents the combination and acceleration of PCR and fluorescent labelling within a disposable microfluidic chip, fabricated by injection moulding. The utilised geometry consists of a spiral meander with 40 turns, representing a cyclic-flow PCR system. The used reaction chemistry includes Cy3-conjugated primers and a high-yield polymerase leading to a one-step process accelerated by cyclic-flow PCR. Three different bacterial samples (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) were processed and the bacterial DNA was successfully amplified and labelled with detection limits down to 102 cells per reaction. The specificity of species identification was comparable to the approach of separate PCR and labelling. Furthermore the overall processing time was decreased from 6 hours to 1.5 hours. We showed that a disposable polycarbonate chip, fabricated by injection moulding is suitable for the significant acceleration of DNA microarray assays. The reaction output lead to high-sensitivity bacterial identification in a short time, which is crucial for an early and targeted therapy against infectious diseases.

  16. New Tools for Embryo Selection: Comprehensive Chromosome Screening by Array Comparative Genomic Hybridization

    Directory of Open Access Journals (Sweden)

    Lorena Rodrigo

    2014-01-01

    Full Text Available The objective of this study was to evaluate the usefulness of comprehensive chromosome screening (CCS using array comparative genomic hybridization (aCGH. The study included 1420 CCS cycles for recurrent miscarriage (n=203; repetitive implantation failure (n=188; severe male factor (n=116; previous trisomic pregnancy (n=33; and advanced maternal age (n=880. CCS was performed in cycles with fresh oocytes and embryos (n=774; mixed cycles with fresh and vitrified oocytes (n=320; mixed cycles with fresh and vitrified day-2 embryos (n=235; and mixed cycles with fresh and vitrified day-3 embryos (n=91. Day-3 embryo biopsy was performed and analyzed by aCGH followed by day-5 embryo transfer. Consistent implantation (range: 40.5–54.2% and pregnancy rates per transfer (range: 46.0–62.9% were obtained for all the indications and independently of the origin of the oocytes or embryos. However, a lower delivery rate per cycle was achieved in women aged over 40 years (18.1% due to the higher percentage of aneuploid embryos (85.3% and lower number of cycles with at least one euploid embryo available per transfer (40.3%. We concluded that aneuploidy is one of the major factors which affect embryo implantation.

  17. Gene expression profile and genomic alterations in colonic tumours induced by 1,2-dimethylhydrazine (DMH) in rats

    International Nuclear Information System (INIS)

    Femia, Angelo Pietro; Luceri, Cristina; Toti, Simona; Giannini, Augusto; Dolara, Piero; Caderni, Giovanna

    2010-01-01

    Azoxymethane (AOM) or 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats shares many phenotypical similarities with human sporadic colon cancer and is a reliable model for identifying chemopreventive agents. Genetic mutations relevant to human colon cancer have been described in this model, but comprehensive gene expression and genomic analysis have not been reported so far. Therefore, we applied genome-wide technologies to study variations in gene expression and genomic alterations in DMH-induced colon cancer in F344 rats. For gene expression analysis, 9 tumours (TUM) and their paired normal mucosa (NM) were hybridized on 4 × 44K Whole rat arrays (Agilent) and selected genes were validated by semi-quantitative RT-PCR. Functional analysis on microarray data was performed by GenMAPP/MappFinder analysis. Array-comparative genomic hybridization (a-CGH) was performed on 10 paired TUM-NM samples hybridized on Rat genome arrays 2 × 105K (Agilent) and the results were analyzed by CGH Analytics (Agilent). Microarray gene expression analysis showed that Defcr4, Igfbp5, Mmp7, Nos2, S100A8 and S100A9 were among the most up-regulated genes in tumours (Fold Change (FC) compared with NM: 183, 48, 39, 38, 36 and 32, respectively), while Slc26a3, Mptx, Retlna and Muc2 were strongly down-regulated (FC: -500; -376, -167, -79, respectively). Functional analysis showed that pathways controlling cell cycle, protein synthesis, matrix metalloproteinases, TNFα/NFkB, and inflammatory responses were up-regulated in tumours, while Krebs cycle, the electron transport chain, and fatty acid beta oxidation were down-regulated. a-CGH analysis showed that four TUM out of ten had one or two chromosomal aberrations. Importantly, one sample showed a deletion on chromosome 18 including Apc. The results showed complex gene expression alterations in adenocarcinomas encompassing many altered pathways. While a-CGH analysis showed a low degree of genomic imbalance, it is interesting to

  18. A new method for real-time evaluation of pepsin digestion of paraffin-embedded tissue sections, prior to fluorescence in situ hybridisation.

    Science.gov (United States)

    Teng, Xiaojing; Zhang, Shuhong; Liu, Wei; Bi, Kuo; Zhang, Lei

    2017-05-01

    Fluorescence in situ hybridisation (FISH) is a molecular cytogenetic technique, which is regularly applied to formalin-fixed paraffin-embedded (FFPE) tissue sections of a variety of cancers to assess chromosomal aberrations. However, high-quality FISH requires optimal enzymatic digestion, and insufficient digestion is not noted until the hybridisation signals are evaluated in the fluorescence microscope. As a consequence, FISH results may be unreliable, and the experiment might have to be repeated. To solve this problem, we developed a new method for real-time evaluation of enzymatic tissue digestion. Termination of enzyme activity at the proper time facilitates successful hybridisation, and experiments do not have to be repeated. We first performed FISH on 20 FFPE samples, which had been pepsin digested for different times, and this revealed distinct morphological changes within the nucleus and perinuclear space that were detectable by light microscopy. These observations suggested that the presence of intact and clear bare nuclei, surrounded by a translucent perinuclear space, might serve as an indicator of adequate digestion. We developed a protocol for assessment of this indicator, based on morphological features, and applied this to a collection of 400 tissue samples, partly of breast cancer and partly of different types of lymphoma, prior to FISH. The FISH success rate was 99.5% (398/400), which was significantly higher than that of the conventional method. In all successful cases, morphological signs of adequate digestion were paralleled by easily interpretable FISH signals. This new method for the real-time assessment of digestion quality improved the success rate of FISH and in addition was simple and rapid.

  19. Hybridisation of Education

    DEFF Research Database (Denmark)

    Tække, Jesper; Paulsen, Michael

    in the action research project Socio Media Education. We argue that the new cyborg-reality – i.e. complex of digital technology and human beings - turns education into a social hybrid. The main feature of this hybrid is a new nexus of the community (the social system), social networks (the social environment......This paper presents a new systems theoretical model about how we adequately can describe education on the level of the classroom after the introduction of digital media and wireless networks. For centuries school-classes has worked as walled educational interaction-systems, but now under influence...... of the digital revolution, they are populated with – and invaded by - cyborgs who can interrupt, contribute to, or initiate interaction systems that transcends the room’s four walls, making the educational situation more fragile, vulnerable and complex than ever. The paper discusses the phenomena with departure...

  20. Hybridisation of Education

    DEFF Research Database (Denmark)

    Tække, Jesper; Paulsen, Michael

    of the digital revolution, they are populated with – and invaded by - cyborgs who can interrupt, contribute to, or initiate interaction systems that transcends the room’s four walls, making the educational situation more fragile, vulnerable and complex than ever. The paper discusses the phenomena with departure......This paper presents a new systems theoretical model about how we adequately can describe education on the level of the classroom after the introduction of digital media and wireless networks. For centuries school-classes has worked as walled educational interaction-systems, but now under influence...... in the action research project Socio Media Education. We argue that the new cyborg-reality – i.e. complex of digital technology and human beings - turns education into a social hybrid. The main feature of this hybrid is a new nexus of the community (the social system), social networks (the social environment...

  1. ROCK: a breast cancer functional genomics resource.

    Science.gov (United States)

    Sims, David; Bursteinas, Borisas; Gao, Qiong; Jain, Ekta; MacKay, Alan; Mitsopoulos, Costas; Zvelebil, Marketa

    2010-11-01

    The clinical and pathological heterogeneity of breast cancer has instigated efforts to stratify breast cancer sub-types according to molecular profiles. These profiling efforts are now being augmented by large-scale functional screening of breast tumour cell lines, using approaches such as RNA interference. We have developed ROCK ( rock.icr.ac.uk ) to provide a unique, publicly accessible resource for the integration of breast cancer functional and molecular profiling datasets. ROCK provides a simple online interface for the navigation and cross-correlation of gene expression, aCGH and RNAi screen data. It enables the interrogation of gene lists in the context of statistically analysed functional genomic datasets, interaction networks, pathways, GO terms, mutations and drug targets. The interface also provides interactive visualisations of datasets and interaction networks. ROCK collates data from a wealth of breast cancer molecular profiling and functional screening studies into a single portal, where analysed and annotated results can be accessed at the level of a gene, sample or study. We believe that portals such as ROCK will not only afford researchers rapid access to profiling data, but also aid the integration of different data types, thus enhancing the discovery of novel targets and biomarkers for breast cancer.

  2. Genome-wide mapping of copy number variation in humans: comparative analysis of high resolution array platforms.

    Directory of Open Access Journals (Sweden)

    Rajini R Haraksingh

    Full Text Available Accurate and efficient genome-wide detection of copy number variants (CNVs is essential for understanding human genomic variation, genome-wide CNV association type studies, cytogenetics research and diagnostics, and independent validation of CNVs identified from sequencing based technologies. Numerous, array-based platforms for CNV detection exist utilizing array Comparative Genome Hybridization (aCGH, Single Nucleotide Polymorphism (SNP genotyping or both. We have quantitatively assessed the abilities of twelve leading genome-wide CNV detection platforms to accurately detect Gold Standard sets of CNVs in the genome of HapMap CEU sample NA12878, and found significant differences in performance. The technologies analyzed were the NimbleGen 4.2 M, 2.1 M and 3×720 K Whole Genome and CNV focused arrays, the Agilent 1×1 M CGH and High Resolution and 2×400 K CNV and SNP+CGH arrays, the Illumina Human Omni1Quad array and the Affymetrix SNP 6.0 array. The Gold Standards used were a 1000 Genomes Project sequencing-based set of 3997 validated CNVs and an ultra high-resolution aCGH-based set of 756 validated CNVs. We found that sensitivity, total number, size range and breakpoint resolution of CNV calls were highest for CNV focused arrays. Our results are important for cost effective CNV detection and validation for both basic and clinical applications.

  3. Genomic Testing

    Science.gov (United States)

    ... Events and Multimedia Implementation Genetics 101 Family Health History Genomics and Diseases Genetic Counseling Genomic Testing Epidemiology Pathogen Genomics Resources Genomic Testing Recommend on Facebook Tweet Share Compartir Fact Sheet: Identifying Opportunities to ...

  4. Iso-Seq analysis ofNepenthes ampullaria,Nepenthes rafflesianaandNepenthes × hookerianafor hybridisation study in pitcher plants.

    Science.gov (United States)

    Zulkapli, Muhammad Mu'izzuddin; Rosli, Muhammad Aqil Fitri; Salleh, Faris Imadi Mohd; Mohd Noor, Normah; Aizat, Wan Mohd; Goh, Hoe-Han

    2017-06-01

    Tropical pitcher plants in the species-rich Nepenthaceae family of carnivorous plants possess unique pitcher organs. Hybridisation, natural or artificial, in this family is extensive resulting in pitchers with diverse features. The pitcher functions as a passive insect trap with digestive fluid for nutrient acquisition in nitrogen-poor habitats. This organ shows specialisation according to the dietary habit of different Nepenthes species. In this study, we performed the first single-molecule real-time isoform sequencing (Iso-Seq) analysis of full-length cDNA from Nepenthes ampullaria which can feed on leaf litter, compared to carnivorous Nepenthes rafflesiana , and their carnivorous hybrid Nepenthes  ×  hookeriana . This allows the comparison of pitcher transcriptomes from the parents and the hybrid to understand how hybridisation could shape the evolution of dietary habit in Nepenthes. Raw reads have been deposited to SRA database with the accession numbers SRX2692198 ( N. ampullaria ), SRX2692197 ( N. rafflesiana ), and SRX2692196 ( N.  ×  hookeriana ).

  5. Development of a real-time RT-PCR and Reverse Line probe Hybridisation assay for the routine detection and genotyping of Noroviruses in Ireland.

    LENUS (Irish Health Repository)

    Menton, John F

    2007-01-01

    BACKGROUND: Noroviruses are the most common cause of non-bacterial gastroenteritis. Improved detection methods have seen a large increase in the number of human NoV genotypes in the last ten years. The objective of this study was to develop a fast method to detect, quantify and genotype positive NoV samples from Irish hospitals. RESULTS: A real-time RT-PCR assay and a Reverse Line Blot Hybridisation assay were developed based on the ORF1-ORF2 region. The sensitivity and reactivity of the two assays used was validated using a reference stool panel containing 14 NoV genotypes. The assays were then used to investigate two outbreaks of gastroenteritis in two Irish hospitals. 56 samples were screened for NoV using a real-time RT-PCR assay and 26 samples were found to be positive. Genotyping of these positive samples found that all positives belonged to the GII\\/4 variant of NoV. CONCLUSION: The combination of the Real-time assay and the reverse line blot hybridisation assay provided a fast and accurate method to investigate a NoV associated outbreak. It was concluded that the predominant genotype circulating in these Irish hospitals was GII\\/4 which has been associated with the majority of NoV outbreaks worldwide. The assays developed in this study are useful tools for investigating NoV infection.

  6. Iso-Seq analysis of Nepenthes ampullaria, Nepenthes rafflesiana and Nepenthes × hookeriana for hybridisation study in pitcher plants

    Directory of Open Access Journals (Sweden)

    Muhammad Mu'izzuddin Zulkapli

    2017-06-01

    Full Text Available Tropical pitcher plants in the species-rich Nepenthaceae family of carnivorous plants possess unique pitcher organs. Hybridisation, natural or artificial, in this family is extensive resulting in pitchers with diverse features. The pitcher functions as a passive insect trap with digestive fluid for nutrient acquisition in nitrogen-poor habitats. This organ shows specialisation according to the dietary habit of different Nepenthes species. In this study, we performed the first single-molecule real-time isoform sequencing (Iso-Seq analysis of full-length cDNA from Nepenthes ampullaria which can feed on leaf litter, compared to carnivorous Nepenthes rafflesiana, and their carnivorous hybrid Nepenthes × hookeriana. This allows the comparison of pitcher transcriptomes from the parents and the hybrid to understand how hybridisation could shape the evolution of dietary habit in Nepenthes. Raw reads have been deposited to SRA database with the accession numbers SRX2692198 (N. ampullaria, SRX2692197 (N. rafflesiana, and SRX2692196 (N. × hookeriana.

  7. Microarray MAPH: accurate array-based detection of relative copy number in genomic DNA

    Directory of Open Access Journals (Sweden)

    Chan Alan

    2006-06-01

    Full Text Available Abstract Background Current methods for measurement of copy number do not combine all the desirable qualities of convenience, throughput, economy, accuracy and resolution. In this study, to improve the throughput associated with Multiplex Amplifiable Probe Hybridisation (MAPH we aimed to develop a modification based on the 3-Dimensional, Flow-Through Microarray Platform from PamGene International. In this new method, electrophoretic analysis of amplified products is replaced with photometric analysis of a probed oligonucleotide array. Copy number analysis of hybridised probes is based on a dual-label approach by comparing the intensity of Cy3-labelled MAPH probes amplified from test samples co-hybridised with similarly amplified Cy5-labelled reference MAPH probes. The key feature of using a hybridisation-based end point with MAPH is that discrimination of amplified probes is based on sequence and not fragment length. Results In this study we showed that microarray MAPH measurement of PMP22 gene dosage correlates well with PMP22 gene dosage determined by capillary MAPH and that copy number was accurately reported in analyses of DNA from 38 individuals, 12 of which were known to have Charcot-Marie-Tooth disease type 1A (CMT1A. Conclusion Measurement of microarray-based endpoints for MAPH appears to be of comparable accuracy to electrophoretic methods, and holds the prospect of fully exploiting the potential multiplicity of MAPH. The technology has the potential to simplify copy number assays for genes with a large number of exons, or of expanded sets of probes from dispersed genomic locations.

  8. Species and gene divergence in Littorina snails detected by array comparative genomic hybridization.

    Science.gov (United States)

    Panova, Marina; Johansson, Tomas; Canbäck, Björn; Bentzer, Johan; Rosenblad, Magnus Alm; Johannesson, Kerstin; Tunlid, Anders; André, Carl

    2014-08-18

    Array comparative genomic hybridization (aCGH) is commonly used to screen different types of genetic variation in humans and model species. Here, we performed aCGH using an oligonucleotide gene-expression array for a non-model species, the intertidal snail Littorina saxatilis. First, we tested what types of genetic variation can be detected by this method using direct re-sequencing and comparison to the Littorina genome draft. Secondly, we performed a genome-wide comparison of four closely related Littorina species: L. fabalis, L. compressa, L. arcana and L. saxatilis and of populations of L. saxatilis found in Spain, Britain and Sweden. Finally, we tested whether we could identify genetic variation underlying "Crab" and "Wave" ecotypes of L. saxatilis. We could reliably detect copy number variations, deletions and high sequence divergence (i.e. above 3%), but not single nucleotide polymorphisms. The overall hybridization pattern and number of significantly diverged genes were in close agreement with earlier phylogenetic reconstructions based on single genes. The trichotomy of L. arcana, L. compressa and L. saxatilis could not be resolved and we argue that these divergence events have occurred recently and very close in time. We found evidence for high levels of segmental duplication in the Littorina genome (10% of the transcripts represented on the array and up to 23% of the analyzed genomic fragments); duplicated genes and regions were mostly the same in all analyzed species. Finally, this method discriminated geographically distant populations of L. saxatilis, but we did not detect any significant genome divergence associated with ecotypes of L. saxatilis. The present study provides new information on the sensitivity and the potential use of oligonucleotide arrays for genotyping of non-model organisms. Applying this method to Littorina species yields insights into genome evolution following the recent species radiation and supports earlier single-gene based

  9. Array-komparativ genomisk hybridisering er en ny og lovende metode til prænatal kromosomundersøgelse

    DEFF Research Database (Denmark)

    Nørgaard, Lone Nikoline; Ekelund, Charlotte; Fagerberg, Christina

    2014-01-01

    Array-comparative genomic hybridization (array-CGH) is a very sensitive method for identifying chromosomal imbalances and is now used on a clinical basis for prenatal diagnosis. This article reviews the advantages and disadvantages of the method, the ethical considerations and the current...

  10. Alteration of the genomic composition of Solanum nigrum (+) potato backcross derivatives by somatic hybridisation: selection of fusion hybrids by DNA measurements and GISH

    NARCIS (Netherlands)

    Horsman, K.; Gavrilenko, T.; Bergervoet, M.; Huigen, D.J.; Tjin Wong Joe, A.; Jacobsen, E.

    2001-01-01

    Fusion experiments were performed with a first (BC1-6738) and a second (BC2-9017) generation backcross hybrid of 6x Solanum nigrum (+) 2x potato somatic hybrids with potato cultivars. Because no progeny was obtained from the BC2 genotypes, alternative approaches were sought to overcome the sexual

  11. Non-invasive preimplantation genetic screening using array comparative genomic hybridization on spent culture media: a proof-of-concept pilot study.

    Science.gov (United States)

    Feichtinger, Michael; Vaccari, Enrico; Carli, Luca; Wallner, Elisabeth; Mädel, Ulrike; Figl, Katharina; Palini, Simone; Feichtinger, Wilfried

    2017-06-01

    The aim of this pilot study was to assess if array comparative genomic hybridization (aCGH), non-invasive preimplantation genetic screening (PGS) on blastocyst culture media is feasible. Therefore, aCGH analysis was carried out on 22 spent blastocyst culture media samples after polar body PGS because of advanced maternal age. All oocytes were fertilized by intracytoplasmic sperm injection and all embryos underwent assisted hatching. Concordance of polar body analysis and culture media genetic results was assessed. Thirteen out of 18 samples (72.2%) revealed general concordance of ploidy status (euploid or aneuploid). At least one chromosomal aberration was found concordant in 10 out of 15 embryos found to be aneuploid by both polar body and culture media analysis. Overall, 17 out of 35 (48.6%) single chromosomal aneuploidies were concordant between the culture media and polar body analysis. By analysing negative controls (oocytes with fertilization failure), notable maternal contamination was observed. Therefore, non-invasive PGS could serve as a second matrix after polar body or cleavage stage PGS; however, in euploid results, maternal contamination needs to be considered and results interpreted with caution. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  12. Prenatal diagnosis of Wolf-Hirschhorn syndrome confirmed by comparative genomic hybridization array: report of two cases and review of the literature

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    Sifakis Stavros

    2012-02-01

    Full Text Available Abstract Wolf-Hirschhorn syndrome (WHS is a well known genetic condition caused by a partial deletion of the short arm of chromosome 4. The great variability in the extent of the 4p deletion and the possible contribution of additional genetic rearrangements lead to a wide spectrum of clinical manifestations. The majority of the reports of prenatally diagnosed WHS cases are associated with large 4p deletions identified by conventional chromosome analysis; however, the widespread clinical use of novel molecular techniques such as array comparative genomic hybridization (a-CGH has increased the detection rate of submicroscopic chromosomal aberrations associated with WHS phenotype. We provide a report of two fetuses with WHS presenting with intrauterine growth restriction as an isolated finding or combined with oligohydramnios and abnormal Doppler waveform in umbilical artery and uterine arteries. Standard karyotyping demonstrated a deletion on chromosome 4 in both cases [del(4(p15.33 and del(4(p15.31, respectively] and further application of a-CGH confirmed the diagnosis and offered a precise characterization of the genetic defect. A detailed review of the currently available literature on the prenatal diagnostic approach of WHS in terms of fetal sonographic assessment and molecular cytogenetic investigation is also provided.

  13. In situ hybridisation for identification and differentiation of Mycoplasma hyopneumoniae, Mycoplasma hyosynoviae and Mycoplasma hyorhinis in formalin-fixed porcine tissue sections

    DEFF Research Database (Denmark)

    Boye, Mette; Jensen, Tim Kåre; Ahrens, Peter

    2001-01-01

    Oligonucleotide probes targeting 16S ribosomal RNA were designed for species-specific identification of the porcine mycoplasmas Mycoplasma hyopneumoniae, Mycoplasma hyorhinis and Mycoplasma hyosynoviae using a fluorescent in situ hybridisation assay. The specificity of the probes was evaluated...... using pure cultures as well as porcine tissue sections with artificial presence of mycoplasma, and the probes were found specific for the target organisms. The assay was applied on sections of 28 tissue samples from pigs infected with one or more of the three Mycoplasma species as determined...... by cultivation. M. hyopneumoniae and M. hyorhinis were identified in accordance with cultivation in lung sections, from nine pigs affected by catarrhal to purulent bronchopneumonia. Likewise, in eight cases of fibrinous pericarditis, M. hyopneumoniae, M. hyorhinis and M. hyosynoviae were the infectious agents...

  14. Quantitative multiplex quantum dot in-situ hybridisation based gene expression profiling in tissue microarrays identifies prognostic genes in acute myeloid leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Tholouli, Eleni [Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); MacDermott, Sarah [The Medical School, The University of Manchester, Oxford Road, M13 9PT Manchester (United Kingdom); Hoyland, Judith [School of Biomedicine, Faculty of Medical and Human Sciences, The University of Manchester, Oxford Road, M13 9PT Manchester (United Kingdom); Yin, John Liu [Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); Byers, Richard, E-mail: richard.byers@cmft.nhs.uk [School of Cancer and Enabling Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Stopford Building, Oxford Road, M13 9PT Manchester (United Kingdom)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Development of a quantitative high throughput in situ expression profiling method. Black-Right-Pointing-Pointer Application to a tissue microarray of 242 AML bone marrow samples. Black-Right-Pointing-Pointer Identification of HOXA4, HOXA9, Meis1 and DNMT3A as prognostic markers in AML. -- Abstract: Measurement and validation of microarray gene signatures in routine clinical samples is problematic and a rate limiting step in translational research. In order to facilitate measurement of microarray identified gene signatures in routine clinical tissue a novel method combining quantum dot based oligonucleotide in situ hybridisation (QD-ISH) and post-hybridisation spectral image analysis was used for multiplex in-situ transcript detection in archival bone marrow trephine samples from patients with acute myeloid leukaemia (AML). Tissue-microarrays were prepared into which white cell pellets were spiked as a standard. Tissue microarrays were made using routinely processed bone marrow trephines from 242 patients with AML. QD-ISH was performed for six candidate prognostic genes using triplex QD-ISH for DNMT1, DNMT3A, DNMT3B, and for HOXA4, HOXA9, Meis1. Scrambled oligonucleotides were used to correct for background staining followed by normalisation of expression against the expression values for the white cell pellet standard. Survival analysis demonstrated that low expression of HOXA4 was associated with poorer overall survival (p = 0.009), whilst high expression of HOXA9 (p < 0.0001), Meis1 (p = 0.005) and DNMT3A (p = 0.04) were associated with early treatment failure. These results demonstrate application of a standardised, quantitative multiplex QD-ISH method for identification of prognostic markers in formalin-fixed paraffin-embedded clinical samples, facilitating measurement of gene expression signatures in routine clinical samples.

  15. When Anthropogenic River Disturbance Decreases Hybridisation between Non-Native and Endemic Cyprinids and Drives an Ecomorphological Displacement towards Juvenile State in Both Species.

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    Emmanuel Corse

    Full Text Available Understanding the impact of non-native species on native species is a major challenge in molecular ecology, particularly for genetically compatible fish species. Invasions are generally difficult to study because their effects may be confused with those of environmental or human disturbances. Colonized ecosystems are differently impacted by human activities, resulting in diverse responses and interactions between native and non-native species. We studied the dynamics between two Cyprinids species (invasive Chondrostoma nasus and endemic Parachondrostoma toxostoma and their hybrids in 16 populations (from allopatric to sympatric situations and from little to highly fragmented areas corresponding to 2,256 specimens. Each specimen was assigned to a particular species or to a hybrid pool using molecular identification (cytochrome b and 41 microsatellites. We carried out an ecomorphological analysis based on size, age, body shape, and diet (gut vacuity and molecular fecal contents. Our results contradicted our initial assumptions on the pattern of invasion and the rate of introgression. There was no sign of underperformance for the endemic species in areas where hybridisation occurred. In the unfragmented zone, the introduced species was found mostly downstream, with body shapes similar to those in allopatric populations while both species were found to be more insectivorous than the reference populations. However, high level of hybridisation was detected, suggesting interactions between the two species during spawning and/or the existence of hybrid swarm. In the disturbed zone, introgression was less frequent and slender body shape was associated with diatomivorous behaviour, smaller size (juvenile characteristics and greater gut vacuity. Results suggested that habitat degradation induced similar ecomorphological trait changes in the two species and their hybrids (i.e. a transition towards a pedomorphic state where the invasive species is more

  16. Genomic patterns resembling BRCA1- and BRCA2-mutated breast cancers predict benefit of intensified carboplatin-based chemotherapy

    Science.gov (United States)

    2014-01-01

    Introduction BRCA-mutated breast cancer cells lack the DNA-repair mechanism homologous recombination that is required for error-free DNA double-strand break (DSB) repair. Homologous recombination deficiency (HRD) may cause hypersensitivity to DNA DSB-inducing agents, such as bifunctional alkylating agents and platinum salts. HRD can be caused by BRCA mutations, and by other mechanisms. To identify HRD, studies have focused on triple-negative (TN) breast cancers as these resemble BRCA1-mutated breast cancer closely and might also share this hypersensitivity. However, ways to identify HRD in non-BRCA-mutated, estrogen receptor (ER)-positive breast cancers have remained elusive. The current study provides evidence that genomic patterns resembling BRCA1- or BRCA2-mutated breast cancers can identify breast cancer patients with TN as well as ER-positive, HER2-negative tumors that are sensitive to intensified, DSB-inducing chemotherapy. Methods Array comparative genomic hybridization (aCGH) was used to classify breast cancers. Patients with tumors with similar aCGH patterns as BRCA1- and/or BRCA2-mutated breast cancers were defined as having a BRCA-likeCGH status, others as non-BCRA-likeCGH. Stage-III patients (n = 249) had participated in a randomized controlled trial of adjuvant high-dose (HD) cyclophosphamide-thiotepa-carboplatin (CTC) versus 5-fluorouracil-epirubicin-cyclophosphamide (FE90C) chemotherapy. Results Among patients with BRCA-likeCGH tumors (81/249, 32%), a significant benefit of HD-CTC compared to FE90C was observed regarding overall survival (adjusted hazard ratio 0.19, 95% CI: 0.08 to 0.48) that was not seen for patients with non-BRCA-likeCGH tumors (adjusted hazard ratio 0.90, 95% CI: 0.53 to 1.54) (P = 0.004). Half of all BRCA-likeCGH tumors were ER-positive. Conclusions Distinct aCGH patterns differentiated between HER2-negative patients with a markedly improved outcome after adjuvant treatment with an intensified DNA-DSB-inducing regimen

  17. Comparative genomics in chicken and Pekin duck using FISH mapping and microarray analysis

    Directory of Open Access Journals (Sweden)

    Fowler Katie E

    2009-08-01

    Full Text Available Abstract Background The availability of the complete chicken (Gallus gallus genome sequence as well as a large number of chicken probes for fluorescent in-situ hybridization (FISH and microarray resources facilitate comparative genomic studies between chicken and other bird species. In a previous study, we provided a comprehensive cytogenetic map for the turkey (Meleagris gallopavo and the first analysis of copy number variants (CNVs in birds. Here, we extend this approach to the Pekin duck (Anas platyrhynchos, an obvious target for comparative genomic studies due to its agricultural importance and resistance to avian flu. Results We provide a detailed molecular cytogenetic map of the duck genome through FISH assignment of 155 chicken clones. We identified one inter- and six intrachromosomal rearrangements between chicken and duck macrochromosomes and demonstrated conserved synteny among all microchromosomes analysed. Array comparative genomic hybridisation revealed 32 CNVs, of which 5 overlap previously designated "hotspot" regions between chicken and turkey. Conclusion Our results suggest extensive conservation of avian genomes across 90 million years of evolution in both macro- and microchromosomes. The data on CNVs between chicken and duck extends previous analyses in chicken and turkey and supports the hypotheses that avian genomes contain fewer CNVs than mammalian genomes and that genomes of evolutionarily distant species share regions of copy number variation ("CNV hotspots". Our results will expedite duck genomics, assist marker development and highlight areas of interest for future evolutionary and functional studies.

  18. Genome profiling of chronic myelomonocytic leukemia: frequent alterations of RAS and RUNX1 genes

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    Olschwang Sylviane

    2008-10-01

    Full Text Available Abstract Background Chronic myelomonocytic leukemia (CMML is a hematological disease close to, but separate from both myeloproliferative disorders (MPD and myelodysplastic syndromes and may show either myeloproliferative (MP-CMML or myelodysplastic (MD-CMML features. Not much is known about the molecular biology of this disease. Methods We studied a series of 30 CMML samples (13 MP- and 11 MD-CMMLs, and 6 acutely transformed cases from 29 patients by using Agilent high density array-comparative genomic hybridization (aCGH and sequencing of 12 candidate genes. Results Two-thirds of samples did not show any obvious alteration of aCGH profiles. In one-third we observed chromosome abnormalities (e.g. trisomy 8, del20q and gain or loss of genes (e.g. NF1, RB1 and CDK6. RAS mutations were detected in 4 cases (including an uncommon codon 146 mutation in KRAS and PTPN11 mutations in 3 cases. We detected 11 RUNX1 alterations (9 mutations and 2 rearrangements. The rearrangements were a new, cryptic inversion of chromosomal region 21q21-22 leading to break and fusion of RUNX1 to USP16. RAS and RUNX1 alterations were not mutually exclusive. RAS pathway mutations occurred in MP-CMMLs (~46% but not in MD-CMMLs. RUNX1 alterations (mutations and cryptic rearrangement occurred in both MP and MD classes (~38%. Conclusion We detected RAS pathway mutations and RUNX1 alterations. The latter included a new cryptic USP16-RUNX1 fusion. In some samples, two alterations coexisted already at this early chronic stage.

  19. Genome profiling of chronic myelomonocytic leukemia: frequent alterations of RAS and RUNX1 genes

    International Nuclear Information System (INIS)

    Gelsi-Boyer, Véronique; Bentires-Alj, Mohamed; Olschwang, Sylviane; Vey, Norbert; Mozziconacci, Marie-Joëlle; Birnbaum, Daniel; Chaffanet, Max; Trouplin, Virginie; Adélaïde, José; Aceto, Nicola; Remy, Virginie; Pinson, Stephane; Houdayer, Claude; Arnoulet, Christine; Sainty, Danielle

    2008-01-01

    Chronic myelomonocytic leukemia (CMML) is a hematological disease close to, but separate from both myeloproliferative disorders (MPD) and myelodysplastic syndromes and may show either myeloproliferative (MP-CMML) or myelodysplastic (MD-CMML) features. Not much is known about the molecular biology of this disease. We studied a series of 30 CMML samples (13 MP- and 11 MD-CMMLs, and 6 acutely transformed cases) from 29 patients by using Agilent high density array-comparative genomic hybridization (aCGH) and sequencing of 12 candidate genes. Two-thirds of samples did not show any obvious alteration of aCGH profiles. In one-third we observed chromosome abnormalities (e.g. trisomy 8, del20q) and gain or loss of genes (e.g. NF1, RB1 and CDK6). RAS mutations were detected in 4 cases (including an uncommon codon 146 mutation in KRAS) and PTPN11 mutations in 3 cases. We detected 11 RUNX1 alterations (9 mutations and 2 rearrangements). The rearrangements were a new, cryptic inversion of chromosomal region 21q21-22 leading to break and fusion of RUNX1 to USP16. RAS and RUNX1 alterations were not mutually exclusive. RAS pathway mutations occurred in MP-CMMLs (~46%) but not in MD-CMMLs. RUNX1 alterations (mutations and cryptic rearrangement) occurred in both MP and MD classes (~38%). We detected RAS pathway mutations and RUNX1 alterations. The latter included a new cryptic USP16-RUNX1 fusion. In some samples, two alterations coexisted already at this early chronic stage

  20. Spectrum of Cytogenomic Abnormalities Revealed by Array Comparative Genomic Hybridization on Products of Conception Culture Failure and Normal Karyotype Samples.

    Science.gov (United States)

    Zhou, Qinghua; Wu, Shen-Yin; Amato, Katherine; DiAdamo, Autumn; Li, Peining

    2016-03-20

    Approximately 30% of pregnancies after implantation end up in spontaneous abortions, and 50% of them are caused by chromosomal abnormalities. However, the spectrum of genomic copy number variants (CNVs) in products of conception (POC) and the underlying gene-dosage-sensitive mechanisms causing spontaneous abortions remain largely unknown. In this study, array comparative genomic hybridization (aCGH) analysis was performed as a salvage procedure for 128 POC culture failure (POC-CF) samples and as a supplemental procedure for 106 POC normal karyotype (POC-NK) samples. Chromosomal abnormalities were detected in 10% of POC-CF and pathogenic CNVs were detected in 3.9% of POC-CF and 5.7% of POC-NK samples. Compiled results from this study and relevant case series through a literature review demonstrated an abnormality detection rate (ADR) of 35% for chromosomal abnormalities in POC-CF samples, 3.7% for pathogenic CNVs in POC-CF samples, and 4.6% for pathogenic CNVs in POC-NK samples. Ingenuity Pathway Analysis (IPA) was performed on the genes from pathogenic CNVs found in POC samples. The denoted primary gene networks suggested that apoptosis and cell proliferation pathways are involved in miscarriage. In summary, a similar spectrum of cytogenomic abnormalities was observed in POC culture success and POC-CF samples. A threshold effect correlating the number of dosage-sensitive genes in a chromosome with the observed frequency of autosomal trisomy is proposed. A rationalized approach using firstly fluorescence in situ hybridization (FISH) testing with probes of chromosomes X/Y/18, 13/21, and 15/16/22 for common aneuploidies and polyploidies and secondly aCGH for other cytogenomic abnormalities is recommended for POC-CF samples. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  1. Inferring the evolution of the major histocompatibility complex of wild pigs and peccaries using hybridisation DNA capture-based sequencing.

    Science.gov (United States)

    Lee, Carol; Moroldo, Marco; Perdomo-Sabogal, Alvaro; Mach, Núria; Marthey, Sylvain; Lecardonnel, Jérôme; Wahlberg, Per; Chong, Amanda Y; Estellé, Jordi; Ho, Simon Y W; Rogel-Gaillard, Claire; Gongora, Jaime

    2017-12-18

    The major histocompatibility complex (MHC) is a key genomic model region for understanding the evolution of gene families and the co-evolution between host and pathogen. To date, MHC studies have mostly focused on species from major vertebrate lineages. The evolution of MHC classical (Ia) and non-classical (Ib) genes in pigs has attracted interest because of their antigen presentation roles as part of the adaptive immune system. The pig family Suidae comprises over 18 extant species (mostly wild), but only the domestic pig has been extensively sequenced and annotated. To address this, we used a DNA-capture approach, with probes designed from the domestic pig genome, to generate MHC data for 11 wild species of pigs and their closest living family, Tayassuidae. The approach showed good efficiency for wild pigs (~80% reads mapped, ~87× coverage), compared to tayassuids (~12% reads mapped, ~4× coverage). We retrieved 145 MHC loci across both families. Phylogenetic analyses show that the class Ia and Ib genes underwent multiple duplications and diversifications before suids and tayassuids diverged from their common ancestor. The histocompatibility genes mostly form orthologous groups and there is genetic differentiation for most of these genes between Eurasian and sub-Saharan African wild pigs. Tests of selection showed that the peptide-binding region of class Ib genes was under positive selection. These findings contribute to better understanding of the evolutionary history of the MHC, specifically, the class I genes, and provide useful data for investigating the immune response of wild populations against pathogens.

  2. Whole genome amplification and its impact on CGH array profiles

    Directory of Open Access Journals (Sweden)

    Meldrum Cliff

    2008-07-01

    Full Text Available Abstract Background Some array comparative genomic hybridisation (array CGH platforms require a minimum of micrograms of DNA for the generation of reliable and reproducible data. For studies where there are limited amounts of genetic material, whole genome amplification (WGA is an attractive method for generating sufficient quantities of genomic material from miniscule amounts of starting material. A range of WGA methods are available and the multiple displacement amplification (MDA approach has been shown to be highly accurate, although amplification bias has been reported. In the current study, WGA was used to amplify DNA extracted from whole blood. In total, six array CGH experiments were performed to investigate whether the use of whole genome amplified DNA (wgaDNA produces reliable and reproducible results. Four experiments were conducted on amplified DNA compared to unamplified DNA and two experiments on unamplified DNA compared to unamplified DNA. Findings All the experiments involving wgaDNA resulted in a high proportion of losses and gains of genomic material. Previously, amplification bias has been overcome by using amplified DNA in both the test and reference DNA. Our data suggests that this approach may not be effective, as the gains and losses introduced by WGA appears to be random and are not reproducible between different experiments using the same DNA. Conclusion In light of these findings, the use of both amplified test and reference DNA on CGH arrays may not provide an accurate representation of copy number variation in the DNA.

  3. Regulation of gene expression by low levels of ultraviolet-B radiation in Pisum sativum: Isolation of novel genes by suppression subtractive hybridisation

    International Nuclear Information System (INIS)

    Sävenstrand, H.; Brosché, M.; Strid, A.

    2002-01-01

    Suppression subtractive hybridisation was used to isolate genes differentially regulated by low levels (UV-B BE,300 0.13 W m -2 ) of ultraviolet-B radiation (UV-B; 290–320 nm) in Pisum sativum. Six genes were regulated, two of which were novel. The mRNA levels for these two (PsTSDC and PsUOS1) were increased and depressed by UV-B treatment, respectively. Domains in the PsTSDC translation product was similar to TIR (Toll-Interleukin-1 receptor-similar) domains and a NB-ARC domain (nucleotide-binding domain in APAF-1, R gene products and CED-4). The PsUOS1 translation product was similar to an open reading frame in Arabidopsis. Genes encoding embryo-abundant protein (PsEMB) and S-adenosyl-l-methionine synthase (PsSAMS) were induced by UV-B, whereas the transcript levels for genes encoding sucrose transport protein (PsSUT) or ribulose-5-phosphate 3-epimerase (PsR5P3E) were decreased. These regulation patterns are novel, and the PsEMB and PsR5P3E sequences are reported for the first time. The stress-specificity of regulation of these genes were tested by ozone fumigation (100 ppb O 3 ). Qualitatively, the similarity of expression after both UV-B and ozone exposure suggests that, for these genes, similar stress-response pathways are in action. (author)

  4. Suppression substractive hybridisation (SSH) and real time PCR reveal differential gene expression in the Pacific cupped oyster, Crassostrea gigas, challenged with Ostreid herpesvirus 1.

    Science.gov (United States)

    Renault, T; Faury, N; Barbosa-Solomieu, V; Moreau, K

    2011-07-01

    Virus-induced genes were identified using suppression subtractive hybridisation (SSH) from Pacific cupped oyster, Crassostrea gigas, haemocytes challenged by OsHV-1. A total of 304 clones from SSH forward library were sequenced. Among these sequences, some homologues corresponded to (i) immune related genes (macrophage express protein, IK cytokine, interferon-induced protein 44 or multicopper oxidase), (ii) apoptosis related genes (Bcl-2) and (iii) cell signalling and virus receptor genes (glypican). Molecular characterization and phylogenic analysis of 3 immune-related genes (macrophage expressed protein, multicopper oxidase and immunoglobulin domain cell adhesion molecule) were performed. Finally, quantitative PCR revealed significant changes in the expression of immune related genes (multicopper oxidase, macrophage expressed protein, myeloid differentiation factor 88 and interferon-induced protein 44) in oysters experimentally challenged with OsHV-1. These findings provide a first basis for studying the role of innate immunity in response to viruses in bivalves and identified genes may serve as markers of interest in breeding programs in order to obtain selected oysters presenting OsHV-1 resistance. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Deep Sequencing of Suppression Subtractive Hybridisation Drought and Recovery Libraries of the Non-model Crop Trifolium repens L.

    Science.gov (United States)

    Bisaga, Maciej; Lowe, Matthew; Hegarty, Matthew; Abberton, Michael; Ravagnani, Adriana

    2017-01-01

    White clover is a short-lived perennial whose persistence is greatly affected by abiotic stresses, particularly drought. The aim of this work was to characterize its molecular response to water deficit and recovery following re-hydration to identify targets for the breeding of tolerant varieties. We created a white clover reference transcriptome of 16,193 contigs by deep sequencing (mean base coverage 387x) four Suppression Subtractive Hybridization (SSH) libraries (a forward and a reverse library for each treatment) constructed from young leaf tissue of white clover at the onset of the response to drought and recovery. Reads from individual libraries were then mapped to the reference transcriptome and processed comparing expression level data. The pipeline generated four robust sets of transcripts induced and repressed in the leaves of plants subjected to water deficit stress (6,937 and 3,142, respectively) and following re-hydration (6,695 and 4,897, respectively). Semi-quantitative polymerase chain reaction was used to verify the expression pattern of 16 genes. The differentially expressed transcripts were functionally annotated and mapped to biological processes and pathways. In agreement with similar studies in other crops, the majority of transcripts up-regulated in response to drought belonged to metabolic processes, such as amino acid, carbohydrate, and lipid metabolism, while transcripts involved in photosynthesis, such as components of the photosystem and the biosynthesis of photosynthetic pigments, were up-regulated during recovery. The data also highlighted the role of raffinose family oligosaccharides (RFOs) and the possible delayed response of the flavonoid pathways in the initial response of white clover to water withdrawal. The work presented in this paper is to our knowledge the first large scale molecular analysis of the white clover response to drought stress and re-hydration. The data generated provide a valuable genomic resource for marker

  6. Cancer genomics

    DEFF Research Database (Denmark)

    Norrild, Bodil; Guldberg, Per; Ralfkiær, Elisabeth Methner

    2007-01-01

    Almost all cells in the human body contain a complete copy of the genome with an estimated number of 25,000 genes. The sequences of these genes make up about three percent of the genome and comprise the inherited set of genetic information. The genome also contains information that determines when...

  7. Cancer genomics

    DEFF Research Database (Denmark)

    Norrild, Bodil; Guldberg, Per; Ralfkiær, Elisabeth Methner

    2007-01-01

    Almost all cells in the human body contain a complete copy of the genome with an estimated number of 25,000 genes. The sequences of these genes make up about three percent of the genome and comprise the inherited set of genetic information. The genome also contains information that determines whe...

  8. Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC and its application for DNA methylation analysis

    Directory of Open Access Journals (Sweden)

    Ottaviani Diego

    2008-05-01

    Full Text Available Abstract Background The major histocompatibility complex (MHC is essential for human immunity and is highly associated with common diseases, including cancer. While the genetics of the MHC has been studied intensively for many decades, very little is known about the epigenetics of this most polymorphic and disease-associated region of the genome. Methods To facilitate comprehensive epigenetic analyses of this region, we have generated a genomic tiling array of 2 Kb resolution covering the entire 4 Mb MHC region. The array has been designed to be compatible with chromatin immunoprecipitation (ChIP, methylated DNA immunoprecipitation (MeDIP, array comparative genomic hybridization (aCGH and expression profiling, including of non-coding RNAs. The array comprises 7832 features, consisting of two replicates of both forward and reverse strands of MHC amplicons and appropriate controls. Results Using MeDIP, we demonstrate the application of the MHC array for DNA methylation profiling and the identification of tissue-specific differentially methylated regions (tDMRs. Based on the analysis of two tissues and two cell types, we identified 90 tDMRs within the MHC and describe their characterisation. Conclusion A tiling array covering the MHC region was developed and validated. Its successful application for DNA methylation profiling indicates that this array represents a useful tool for molecular analyses of the MHC in the context of medical genomics.

  9. Large-scale genetic variation of the symbiosis-required megaplasmid pSymA revealed by comparative genomic analysis of Sinorhizobium meliloti natural strains

    Directory of Open Access Journals (Sweden)

    Landry Christian R

    2005-11-01

    Full Text Available Abstract Background Sinorhizobium meliloti is a soil bacterium that forms nitrogen-fixing nodules on the roots of leguminous plants such as alfalfa (Medicago sativa. This species occupies different ecological niches, being present as a free-living soil bacterium and as a symbiont of plant root nodules. The genome of the type strain Rm 1021 contains one chromosome and two megaplasmids for a total genome size of 6 Mb. We applied comparative genomic hybridisation (CGH on an oligonucleotide microarrays to estimate genetic variation at the genomic level in four natural strains, two isolated from Italian agricultural soil and two from desert soil in the Aral Sea region. Results From 4.6 to 5.7 percent of the genes showed a pattern of hybridisation concordant with deletion, nucleotide divergence or ORF duplication when compared to the type strain Rm 1021. A large number of these polymorphisms were confirmed by sequencing and Southern blot. A statistically significant fraction of these variable genes was found on the pSymA megaplasmid and grouped in clusters. These variable genes were found to be mainly transposases or genes with unknown function. Conclusion The obtained results allow to conclude that the symbiosis-required megaplasmid pSymA can be considered the major hot-spot for intra-specific differentiation in S. meliloti.

  10. Tiling array-CGH for the assessment of genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs

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    Ringnér Markus

    2008-07-01

    Full Text Available Abstract Background Today, no objective criteria exist to differentiate between individual primary tumors and intra- or intermammary dissemination respectively, in patients diagnosed with two or more synchronous breast cancers. To elucidate whether these tumors most likely arise through clonal expansion, or whether they represent individual primary tumors is of tumor biological interest and may have clinical implications. In this respect, high resolution genomic profiling may provide a more reliable approach than conventional histopathological and tumor biological factors. Methods 32 K tiling microarray-based comparative genomic hybridization (aCGH was used to explore the genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs, and was compared with histopathological and tumor biological parameters. Results Based on global copy number profiles and unsupervised hierarchical clustering, five of ten (p = 1.9 × 10-5 unilateral tumor pairs displayed similar genomic profiles within the pair, while only one of eight bilateral tumor pairs (p = 0.29 displayed pair-wise genomic similarities. DNA index, histological type and presence of vessel invasion correlated with the genomic analyses. Conclusion Synchronous unilateral tumor pairs are often genomically similar, while synchronous bilateral tumors most often represent individual primary tumors. However, two independent unilateral primary tumors can develop synchronously and contralateral tumor spread can occur. The presence of an intraductal component is not informative when establishing the independence of two tumors, while vessel invasion, the presence of which was found in clustering tumor pairs but not in tumor pairs that did not cluster together, supports the clustering outcome. Our data suggest that genomically similar unilateral tumor pairs may represent a more aggressive disease that requires the addition of more severe treatment modalities, and

  11. Using genomic DNA-based probe-selection to improve the sensitivity of high-density oligonucleotide arrays when applied to heterologous species

    Directory of Open Access Journals (Sweden)

    Townsend Henrik J

    2005-11-01

    Full Text Available Abstract High-density oligonucleotide (oligo arrays are a powerful tool for transcript profiling. Arrays based on GeneChip® technology are amongst the most widely used, although GeneChip® arrays are currently available for only a small number of plant and animal species. Thus, we have developed a method to improve the sensitivity of high-density oligonucleotide arrays when applied to heterologous species and tested the method by analysing the transcriptome of Brassica oleracea L., a species for which no GeneChip® array is available, using a GeneChip® array designed for Arabidopsis thaliana (L. Heynh. Genomic DNA from B. oleracea was labelled and hybridised to the ATH1-121501 GeneChip® array. Arabidopsis thaliana probe-pairs that hybridised to the B. oleracea genomic DNA on the basis of the perfect-match (PM probe signal were then selected for subsequent B. oleracea transcriptome analysis using a .cel file parser script to generate probe mask files. The transcriptional response of B. oleracea to a mineral nutrient (phosphorus; P stress was quantified using probe mask files generated for a wide range of gDNA hybridisation intensity thresholds. An example probe mask file generated with a gDNA hybridisation intensity threshold of 400 removed > 68 % of the available PM probes from the analysis but retained >96 % of available A. thaliana probe-sets. Ninety-nine of these genes were then identified as significantly regulated under P stress in B. oleracea, including the homologues of P stress responsive genes in A. thaliana. Increasing the gDNA hybridisation intensity thresholds up to 500 for probe-selection increased the sensitivity of the GeneChip® array to detect regulation of gene expression in B. oleracea under P stress by up to 13-fold. Our open-source software to create probe mask files is freely available http://affymetrix.arabidopsis.info/xspecies/ and may be used to facilitate transcriptomic analyses of a wide range of plant and animal

  12. Population Differentiation and Hybridisation of Australian Snubfin (Orcaella heinsohni) and Indo-Pacific Humpback (Sousa chinensis) Dolphins in North-Western Australia

    Science.gov (United States)

    Brown, Alexander M.; Kopps, Anna M.; Allen, Simon J.; Bejder, Lars; Littleford-Colquhoun, Bethan; Parra, Guido J.; Cagnazzi, Daniele; Thiele, Deborah; Palmer, Carol; Frère, Celine H.

    2014-01-01

    Little is known about the Australian snubfin (Orcaella heinsohni) and Indo-Pacific humpback (Sousa chinensis) dolphins (‘snubfin’ and ‘humpback dolphins’, hereafter) of north-western Australia. While both species are listed as ‘near threatened’ by the IUCN, data deficiencies are impeding rigorous assessment of their conservation status across Australia. Understanding the genetic structure of populations, including levels of gene flow among populations, is important for the assessment of conservation status and the effective management of a species. Using nuclear and mitochondrial DNA markers, we assessed population genetic diversity and differentiation between snubfin dolphins from Cygnet (n = 32) and Roebuck Bays (n = 25), and humpback dolphins from the Dampier Archipelago (n = 19) and the North West Cape (n = 18). All sampling locations were separated by geographic distances >200 km. For each species, we found significant genetic differentiation between sampling locations based on 12 (for snubfin dolphins) and 13 (for humpback dolphins) microsatellite loci (F ST = 0.05–0.09; PAustralia, providing valuable information towards the assessment of their conservation status in this rapidly developing region. Our results suggest that north-western Australian snubfin and humpback dolphins may exist as metapopulations of small, largely isolated population fragments, and should be managed accordingly. Management plans should seek to maintain effective population size and gene flow. Additionally, while interactions of a socio-sexual nature between these two species have been observed previously, here we provide strong evidence for the first documented case of hybridisation between a female snubfin dolphin and a male humpback dolphin. PMID:24988113

  13. Viable circulating tumour cell detection using multiplex RNA in situ hybridisation predicts progression-free survival in metastatic breast cancer patients.

    Science.gov (United States)

    Payne, R E; Wang, F; Su, N; Krell, J; Zebrowski, A; Yagüe, E; Ma, X-J; Luo, Y; Coombes, R C

    2012-05-22

    Current approaches for detecting circulating tumour cells (CTCs) in blood are dependent on CTC enrichment and are based either on surface epithelial markers on CTCs or on cell size differences. The objectives of this study were to develop and characterise an ultrasensitive multiplex fluorescent RNA in situ hybridisation (ISH)-based CTC detection system called CTCscope. This method detects a multitude of tumour-specific markers at single-cell level in blood. Healthy blood samples spiked with tumour cell lines were used as a model system for the development and initial characterisation of CTCscope. To demonstrate the feasibility of CTC detection in patient blood, duplicate blood samples were drawn from 45 metastatic breast cancer patients for analysis by CTCscope and the CellSearch system. The association of CTCs with the tumour marker CA15-3 and progression-free survival (PFS) were assessed. CTCscope detected CTC transcripts of eight epithelial markers and three epithelial-mesenchymal-transition (EMT) markers for increased sensitivity. CTCscope was used to detect CTCs with minimal enrichment, and did not detect apoptotic or dead cells. In patient blood samples, CTCs detected by CellSearch, but not CTCscope, were positively correlated with CA15-3 levels. Circulating tumour cells detected by either CTCscope or CellSearch predicted PFS (CTCscope, HR (hazard ratio) 2.26, 95% CI 1.18-4.35, P=0.014; CellSearch, HR 2.50, 95% CI 1.27-4.90, P=0.008). CTCscope offers unique advantages over existing CTC detection approaches. By enumerating and characterising only viable CTCs, CTCscope provides additional prognostic and predictive information in therapy monitoring. © 2012 Cancer Research UK

  14. Population differentiation and hybridisation of Australian snubfin (Orcaella heinsohni) and Indo-Pacific humpback (Sousa chinensis) dolphins in north-western Australia.

    Science.gov (United States)

    Brown, Alexander M; Kopps, Anna M; Allen, Simon J; Bejder, Lars; Littleford-Colquhoun, Bethan; Parra, Guido J; Cagnazzi, Daniele; Thiele, Deborah; Palmer, Carol; Frère, Celine H

    2014-01-01

    Little is known about the Australian snubfin (Orcaella heinsohni) and Indo-Pacific humpback (Sousa chinensis) dolphins ('snubfin' and 'humpback dolphins', hereafter) of north-western Australia. While both species are listed as 'near threatened' by the IUCN, data deficiencies are impeding rigorous assessment of their conservation status across Australia. Understanding the genetic structure of populations, including levels of gene flow among populations, is important for the assessment of conservation status and the effective management of a species. Using nuclear and mitochondrial DNA markers, we assessed population genetic diversity and differentiation between snubfin dolphins from Cygnet (n = 32) and Roebuck Bays (n = 25), and humpback dolphins from the Dampier Archipelago (n = 19) and the North West Cape (n = 18). All sampling locations were separated by geographic distances >200 km. For each species, we found significant genetic differentiation between sampling locations based on 12 (for snubfin dolphins) and 13 (for humpback dolphins) microsatellite loci (FST = 0.05-0.09; Pdolphins in Western Australia, providing valuable information towards the assessment of their conservation status in this rapidly developing region. Our results suggest that north-western Australian snubfin and humpback dolphins may exist as metapopulations of small, largely isolated population fragments, and should be managed accordingly. Management plans should seek to maintain effective population size and gene flow. Additionally, while interactions of a socio-sexual nature between these two species have been observed previously, here we provide strong evidence for the first documented case of hybridisation between a female snubfin dolphin and a male humpback dolphin.

  15. The Diagnostic Yield of Array Comparative Genomic Hybridization Is High Regardless of Severity of Intellectual Disability/Developmental Delay in Children.

    Science.gov (United States)

    D'Arrigo, Stefano; Gavazzi, Francesco; Alfei, Enrico; Zuffardi, Orsetta; Montomoli, Cristina; Corso, Barbara; Buzzi, Erika; Sciacca, Francesca L; Bulgheroni, Sara; Riva, Daria; Pantaleoni, Chiara

    2016-05-01

    Microarray-based comparative genomic hybridization is a method of molecular analysis that identifies chromosomal anomalies (or copy number variants) that correlate with clinical phenotypes. The aim of the present study was to apply a clinical score previously designated by de Vries to 329 patients with intellectual disability/developmental disorder (intellectual disability/developmental delay) referred to our tertiary center and to see whether the clinical factors are associated with a positive outcome of aCGH analyses. Another goal was to test the association between a positive microarray-based comparative genomic hybridization result and the severity of intellectual disability/developmental delay. Microarray-based comparative genomic hybridization identified structural chromosomal alterations responsible for the intellectual disability/developmental delay phenotype in 16% of our sample. Our study showed that causative copy number variants are frequently found even in cases of mild intellectual disability (30.77%). We want to emphasize the need to conduct microarray-based comparative genomic hybridization on all individuals with intellectual disability/developmental delay, regardless of the severity, because the degree of intellectual disability/developmental delay does not predict the diagnostic yield of microarray-based comparative genomic hybridization. © The Author(s) 2015.

  16. Genomic copy number analysis of Chernobyl papillary thyroid carcinoma in the Ukrainian–American Cohort

    Science.gov (United States)

    Selmansberger, Martin; Braselmann, Herbert; Hess, Julia; Bogdanova, Tetiana; Abend, Michael; Tronko, Mykola; Brenner, Alina; Zitzelsberger, Horst; Unger, Kristian

    2015-01-01

    One of the major consequences of the 1986 Chernobyl reactor accident was a dramatic increase in papillary thyroid carcinoma (PTC) incidence, predominantly in patients exposed to the radioiodine fallout at young age. The present study is the first on genomic copy number alterations (CNAs) of PTCs of the Ukrainian–American cohort (UkrAm) generated by array comparative genomic hybridization (aCGH). Unsupervised hierarchical clustering of CNA profiles revealed a significant enrichment of a subgroup of patients with female gender, long latency (>17 years) and negative lymph node status. Further, we identified single CNAs that were significantly associated with latency, gender, radiation dose and BRAF V600E mutation status. Multivariate analysis revealed no interactions but additive effects of parameters gender, latency and dose on CNAs. The previously identified radiation-associated gain of the chromosomal bands 7q11.22-11.23 was present in 29% of cases. Moreover, comparison of our radiation-associated PTC data set with the TCGA data set on sporadic PTCs revealed altered copy numbers of the tumor driver genes NF2 and CHEK2. Further, we integrated the CNA data with transcriptomic data that were available on a subset of the herein analyzed cohort and did not find statistically significant associations between the two molecular layers. However, applying hierarchical clustering on a ‘BRAF-like/RAS-like’ transcriptome signature split the cases into four groups, one of which containing all BRAF-positive cases validating the signature in an independent data set. PMID:26320103

  17. Genomic characterisation of acral melanoma cell lines.

    Science.gov (United States)

    Furney, Simon J; Turajlic, Samra; Fenwick, Kerry; Lambros, Maryou B; MacKay, Alan; Ricken, Gerda; Mitsopoulos, Costas; Kozarewa, Iwanka; Hakas, Jarle; Zvelebil, Marketa; Lord, Christopher J; Ashworth, Alan; Reis-Filho, Jorge S; Herlyn, Meenhard; Murata, Hiroshi; Marais, Richard

    2012-07-01

    Acral melanoma is a rare melanoma subtype with distinct epidemiological, clinical and genetic features. To determine if acral melanoma cell lines are representative of this melanoma subtype, six lines were analysed by whole-exome sequencing and array comparative genomic hybridisation. We demonstrate that the cell lines display a mutation rate that is comparable to that of published primary and metastatic acral melanomas and observe a mutational signature suggestive of UV-induced mutagenesis in two of the cell lines. Mutations were identified in oncogenes and tumour suppressors previously linked to melanoma including BRAF, NRAS, KIT, PTEN and TP53, in cancer genes not previously linked to melanoma and in genes linked to DNA repair such as BRCA1 and BRCA2. Our findings provide strong circumstantial evidence to suggest that acral melanoma cell lines and acral tumours share genetic features in common and that these cells are therefore valuable tools to investigate the biology of this aggressive melanoma subtype. Data are available at: http://rock.icr.ac.uk/collaborations/Furney_et_al_2012/. © 2012 John Wiley & Sons A/S.

  18. Comparative Genomics

    Indian Academy of Sciences (India)

    An important hallmark of biological research is the aspect of 'comparisons'. As the complete genome sequences of numerous organisms have become available, the emphasis in biology has shifted to comparisons at the genome level. Indeed, the last few years have witnessed an exponential rise in the number of ...

  19. Comparative Genomics

    Indian Academy of Sciences (India)

    structions of the tree of life, drug discovery programs, func- tion predictions of hypothetical proteins and genes, regula- tory motifs and other non-coding DNA motifs, and genome ... expertise in assembling sequences. Beginning with the complete genome sequence of the bacterial pathogen Haemophilus influenzae that was ...

  20. Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast.

    Science.gov (United States)

    Natrajan, Rachael; Wilkerson, Paul M; Marchiò, Caterina; Piscuoglio, Salvatore; Ng, Charlotte K Y; Wai, Patty; Lambros, Maryou B; Samartzis, Eleftherios P; Dedes, Konstantin J; Frankum, Jessica; Bajrami, Ilirjana; Kopec, Alicja; Mackay, Alan; A'hern, Roger; Fenwick, Kerry; Kozarewa, Iwanka; Hakas, Jarle; Mitsopoulos, Costas; Hardisson, David; Lord, Christopher J; Kumar-Sinha, Chandan; Ashworth, Alan; Weigelt, Britta; Sapino, Anna; Chinnaiyan, Arul M; Maher, Christopher A; Reis-Filho, Jorge S

    2014-04-01

    Micropapillary carcinoma (MPC) is a rare histological special type of breast cancer, characterized by an aggressive clinical behaviour and a pattern of copy number aberrations (CNAs) distinct from that of grade- and oestrogen receptor (ER)-matched invasive carcinomas of no special type (IC-NSTs). The aims of this study were to determine whether MPCs are underpinned by a recurrent fusion gene(s) or mutations in 273 genes recurrently mutated in breast cancer. Sixteen MPCs were subjected to microarray-based comparative genomic hybridization (aCGH) analysis and Sequenom OncoCarta mutation analysis. Eight and five MPCs were subjected to targeted capture and RNA sequencing, respectively. aCGH analysis confirmed our previous observations about the repertoire of CNAs of MPCs. Sequencing analysis revealed a spectrum of mutations similar to those of luminal B IC-NSTs, and recurrent mutations affecting mitogen-activated protein kinase family genes and NBPF10. RNA-sequencing analysis identified 17 high-confidence fusion genes, eight of which were validated and two of which were in-frame. No recurrent fusions were identified in an independent series of MPCs and IC-NSTs. Forced expression of in-frame fusion genes (SLC2A1-FAF1 and BCAS4-AURKA) resulted in increased viability of breast cancer cells. In addition, genomic disruption of CDK12 caused by out-of-frame rearrangements was found in one MPC and in 13% of HER2-positive breast cancers, identified through a re-analysis of publicly available massively parallel sequencing data. In vitro analyses revealed that CDK12 gene disruption results in sensitivity to PARP inhibition, and forced expression of wild-type CDK12 in a CDK12-null cell line model resulted in relative resistance to PARP inhibition. Our findings demonstrate that MPCs are neither defined by highly recurrent mutations in the 273 genes tested, nor underpinned by a recurrent fusion gene. Although seemingly private genetic events, some of the fusion transcripts found in

  1. Cardiovascular genomics.

    Science.gov (United States)

    Wung, Shu-Fen; Hickey, Kathleen T; Taylor, Jacquelyn Y; Gallek, Matthew J

    2013-03-01

    This article provides an update on cardiovascular genomics using three clinically relevant exemplars, including myocardial infarction (MI) and coronary artery disease (CAD), stroke, and sudden cardiac death (SCD). ORGANIZATIONAL CONSTRUCT: Recent advances in cardiovascular genomic research, testing, and clinical implications are presented. Genomic nurse experts reviewed and summarized recent salient literature to provide updates on three selected cardiovascular genomic conditions. Research is ongoing to discover comprehensive genetic markers contributing to many common forms of cardiovascular disease (CVD), including MI and stroke. However, genomic technologies are increasingly being used clinically, particularly in patients with long QT syndrome (LQTS) or hypertrophic cardiomyopathy (HCM) who are at risk for SCD. Currently, there are no clinically recommended genetic tests for many common forms of CVD even though direct-to-consumer genetic tests are being marketed to healthcare providers and the general public. On the other hand, genetic testing for patients with certain single gene conditions, including channelopathies (e.g., LQTS) and cardiomyopathies (e.g., HCM), is recommended clinically. Nurses play a pivotal role in cardiogenetics and are actively engaged in direct clinical care of patients and families with a wide variety of heritable conditions. It is important for nurses to understand current development of cardiovascular genomics and be prepared to translate the new genomic knowledge into practice. © 2013 Sigma Theta Tau International.

  2. DNA capture and next-generation sequencing can recover whole mitochondrial genomes from highly degraded samples for human identification.

    Science.gov (United States)

    Templeton, Jennifer E L; Brotherton, Paul M; Llamas, Bastien; Soubrier, Julien; Haak, Wolfgang; Cooper, Alan; Austin, Jeremy J

    2013-12-02

    Mitochondrial DNA (mtDNA) typing can be a useful aid for identifying people from compromised samples when nuclear DNA is too damaged, degraded or below detection thresholds for routine short tandem repeat (STR)-based analysis. Standard mtDNA typing, focused on PCR amplicon sequencing of the control region (HVS I and HVS II), is limited by the resolving power of this short sequence, which misses up to 70% of the variation present in the mtDNA genome. We used in-solution hybridisation-based DNA capture (using DNA capture probes prepared from modern human mtDNA) to recover mtDNA from post-mortem human remains in which the majority of DNA is both highly fragmented (DNA in valuable extracts as DNA libraries, which is followed by the targeted enrichment of endogenous mtDNA sequences and characterisation by next-generation sequencing (NGS). We sequenced whole mitochondrial genomes for human identification from samples where standard nuclear STR typing produced only partial profiles or demonstrably failed and/or where standard mtDNA hypervariable region sequences lacked resolving power. Multiple rounds of enrichment can substantially improve coverage and sequencing depth of mtDNA genomes from highly degraded samples. The application of this method has led to the reliable mitochondrial sequencing of human skeletal remains from unidentified World War Two (WWII) casualties approximately 70 years old and from archaeological remains (up to 2,500 years old). This approach has potential applications in forensic science, historical human identification cases, archived medical samples, kinship analysis and population studies. In particular the methodology can be applied to any case, involving human or non-human species, where whole mitochondrial genome sequences are required to provide the highest level of maternal lineage discrimination. Multiple rounds of in-solution hybridisation-based DNA capture can retrieve whole mitochondrial genome sequences from even the most challenging

  3. Genome-wide Studies of Mycolic Acid Bacteria: Computational Identification and Analysis of a Minimal Genome

    KAUST Repository

    Kamanu, Frederick Kinyua

    2012-12-01

    The mycolic acid bacteria are a distinct suprageneric group of asporogenous Grampositive, high GC-content bacteria, distinguished by the presence of mycolic acids in their cell envelope. They exhibit great diversity in their cell and morphology; although primarily non-pathogens, this group contains three major pathogens Mycobacterium leprae, Mycobacterium tuberculosis complex, and Corynebacterium diphtheria. Although the mycolic acid bacteria are a clearly defined group of bacteria, the taxonomic relationships between its constituent genera and species are less well defined. Two approaches were tested for their suitability in describing the taxonomy of the group. First, a Multilocus Sequence Typing (MLST) experiment was assessed and found to be superior to monophyletic (16S small ribosomal subunit) in delineating a total of 52 mycolic acid bacterial species. Phylogenetic inference was performed using the neighbor-joining method. To further refine phylogenetic analysis and to take advantage of the widespread availability of bacterial genome data, a computational framework that simulates DNA-DNA hybridisation was developed and validated using multiscale bootstrap resampling. The tool classifies microbial genomes based on whole genome DNA, and was deployed as a web-application using PHP and Javascript. It is accessible online at http://cbrc.kaust.edu.sa/dna_hybridization/ A third study was a computational and statistical methods in the identification and analysis of a putative minimal mycolic acid bacterial genome so as to better understand (1) the genomic requirements to encode a mycolic acid bacterial cell and (2) the role and type of genes and genetic elements that lead to the massive increase in genome size in environmental mycolic acid bacteria. Using a reciprocal comparison approach, a total of 690 orthologous gene clusters forming a putative minimal genome were identified across 24 mycolic acid bacterial species. In order to identify new potential drug

  4. Genomic Imprinting

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 9. Genomic Imprinting - Some Interesting Implications for the Evolution of Social Behaviour. Raghavendra Gadagkar. General Article Volume 5 Issue 9 September 2000 pp 58-68 ...

  5. Genome-wide detection of copy number variations among diverse horse breeds by array CGH.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available Recent studies have found that copy number variations (CNVs are widespread in human and animal genomes. CNVs are a significant source of genetic variation, and have been shown to be associated with phenotypic diversity. However, the effect of CNVs on genetic variation in horses is not well understood. In the present study, CNVs in 6 different breeds of mare horses, Mongolia horse, Abaga horse, Hequ horse and Kazakh horse (all plateau breeds and Debao pony and Thoroughbred, were determined using aCGH. In total, seven hundred CNVs were identified ranging in size from 6.1 Kb to 0.57 Mb across all autosomes, with an average size of 43.08 Kb and a median size of 15.11 Kb. By merging overlapping CNVs, we found a total of three hundred and fifty-three CNV regions (CNVRs. The length of the CNVRs ranged from 6.1 Kb to 1.45 Mb with average and median sizes of 38.49 Kb and 13.1 Kb. Collectively, 13.59 Mb of copy number variation was identified among the horses investigated and accounted for approximately 0.61% of the horse genome sequence. Five hundred and eighteen annotated genes were affected by CNVs, which corresponded to about 2.26% of all horse genes. Through the gene ontology (GO, genetic pathway analysis and comparison of CNV genes among different breeds, we found evidence that CNVs involving 7 genes may be related to the adaptation to severe environment of these plateau horses. This study is the first report of copy number variations in Chinese horses, which indicates that CNVs are ubiquitous in the horse genome and influence many biological processes of the horse. These results will be helpful not only in mapping the horse whole-genome CNVs, but also to further research for the adaption to the high altitude severe environment for plateau horses.

  6. [Nutrition genomics].

    Science.gov (United States)

    Sedová, L; Seda, O

    2004-01-01

    The importance of nutrition for human health and its influence on the onset and course of many diseases are nowadays considered as proven. Only the recent development of molecular biology and biochemical methods allows the elucidation of the molecular mechanisms of diet constituent actions and their subsequent effect on homeostatic mechanisms in health and disease states. The availability of the draft human genome sequence as well as the genome sequences of model organisms, combined with the functional and integrative genomics approaches of systems biology, bring about the possibility to identify alleles and haplotypes responsible for specific reaction to the dietary challenge in susceptible individuals. Such complex interactions are studied within the newly conceived field, the nutrition genomics (nutrigenomics). Using the tools of highly parallel analyses of transcriptome, proteome and metabolome, the nutrition genomics pursues its ultimate goal, i.e. the individualized diet, respecting not only quantitative and qualitative nutritional needs and the actual health status, but also the genetic predispositions of an individual. This approach should lead to prevention of the onset of such diseases as obesity, hypertension or type 2 diabetes, or enhance the efficiency of their therapy.

  7. A customized high-resolution array-comparative genomic hybridization to explore copy number variations in Parkinson's disease.

    Science.gov (United States)

    La Cognata, Valentina; Morello, Giovanna; Gentile, Giulia; D'Agata, Velia; Criscuolo, Chiara; Cavalcanti, Francesca; Cavallaro, Sebastiano

    2016-10-01

    Parkinson's disease (PD), the second most common progressive neurodegenerative disorder, was long believed to be a non-genetic sporadic syndrome. Today, only a small percentage of PD cases with genetic inheritance patterns are known, often complicated by reduced penetrance and variable expressivity. The few well-characterized Mendelian genes, together with a number of risk factors, contribute to the major sporadic forms of the disease, thus delineating an intricate genetic profile at the basis of this debilitating and incurable condition. Along with single nucleotide changes, gene-dosage abnormalities and copy number variations (CNVs) have emerged as significant disease-causing mutations in PD. However, due to their size variability and to the quantitative nature of the assay, CNV genotyping is particularly challenging. For this reason, innovative high-throughput platforms and bioinformatics algorithms are increasingly replacing classical CNV detection methods. Here, we report the design strategy, development, validation and implementation of NeuroArray, a customized exon-centric high-resolution array-based comparative genomic hybridization (aCGH) tailored to detect single/multi-exon deletions and duplications in a large panel of PD-related genes. This targeted design allows for a focused evaluation of structural imbalances in clinically relevant PD genes, combining exon-level resolution with genome-wide coverage. The NeuroArray platform may offer new insights in elucidating inherited potential or de novo structural alterations in PD patients and investigating new candidate genes.

  8. Genomic and transcriptome profiling identified both human and HBV genetic variations and their interactions in Chinese hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Hua Dong

    2015-12-01

    Full Text Available Interaction between HBV and host genome integrations in hepatocellular carcinoma (HCC development is a complex process and the mechanism is still unclear. Here we described in details the quality controls and data mining of aCGH and transcriptome sequencing data on 50 HCC samples from the Chinese patients, published by Dong et al. (2015 (GEO#: GSE65486. In additional to the HBV-MLL4 integration discovered, we also investigated the genetic aberrations of HBV and host genes as well as their genetic interactions. We reported human genome copy number changes and frequent transcriptome variations (e.g. TP53, CTNNB1 mutation, especially MLL family mutations in this cohort of the patients. For HBV genotype C, we identified a novel linkage disequilibrium region covering HBV replication regulatory elements, including basal core promoter, DR1, epsilon and poly-A regions, which is associated with HBV core antigen over-expression and almost exclusive to HBV-MLL4 integration.

  9. Marine genomics

    DEFF Research Database (Denmark)

    Oliveira Ribeiro, Ângela Maria; Foote, Andrew David; Kupczok, Anne

    2017-01-01

    evolutionary biology of non-model organisms to species of commercial relevance for fishing, aquaculture and biomedicine. Instead of providing an exhaustive list of available genomic data, we rather set to present contextualized examples that best represent the current status of the field of marine genomics.......Marine ecosystems occupy 71% of the surface of our planet, yet we know little about their diversity. Although the inventory of species is continually increasing, as registered by the Census of Marine Life program, only about 10% of the estimated two million marine species are known. This lag......-throughput sequencing approaches have been helping to improve our knowledge of marine biodiversity, from the rich microbial biota that forms the base of the tree of life to a wealth of plant and animal species. In this review, we present an overview of the applications of genomics to the study of marine life, from...

  10. Listeria Genomics

    Science.gov (United States)

    Cabanes, Didier; Sousa, Sandra; Cossart, Pascale

    The opportunistic intracellular foodborne pathogen Listeria monocytogenes has become a paradigm for the study of host-pathogen interactions and bacterial adaptation to mammalian hosts. Analysis of L. monocytogenes infection has provided considerable insight into how bacteria invade cells, move intracellularly, and disseminate in tissues, as well as tools to address fundamental processes in cell biology. Moreover, the vast amount of knowledge that has been gathered through in-depth comparative genomic analyses and in vivo studies makes L. monocytogenes one of the most well-studied bacterial pathogens. This chapter provides an overview of progress in the exploration of genomic, transcriptomic, and proteomic data in Listeria spp. to understand genome evolution and diversity, as well as physiological aspects of metabolism used by bacteria when growing in diverse environments, in particular in infected hosts.

  11. Cephalopod genomics

    DEFF Research Database (Denmark)

    Albertin, Caroline B.; Bonnaud, Laure; Brown, C. Titus

    2012-01-01

    The Cephalopod Sequencing Consortium (CephSeq Consortium) was established at a NESCent Catalysis Group Meeting, ``Paths to Cephalopod Genomics-Strategies, Choices, Organization,'' held in Durham, North Carolina, USA on May 24-27, 2012. Twenty-eight participants representing nine countries (Austri...... in this white paper......., Australia, China, Denmark, France, Italy, Japan, Spain and the USA) met to address the pressing need for genome sequencing of cephalopod mollusks. This group, drawn from cephalopod biologists, neuroscientists, developmental and evolutionary biologists, materials scientists, bioinformaticians and researchers...

  12. Widespread horizontal genomic exchange does not erode species barriers among sympatric ducks

    Directory of Open Access Journals (Sweden)

    Kraus Robert HS

    2012-04-01

    Full Text Available Abstract Background The study of speciation and maintenance of species barriers is at the core of evolutionary biology. During speciation the genome of one population becomes separated from other populations of the same species, which may lead to genomic incompatibility with time. This separation is complete when no fertile offspring is produced from inter-population matings, which is the basis of the biological species concept. Birds, in particular ducks, are recognised as a challenging and illustrative group of higher vertebrates for speciation studies. There are many sympatric and ecologically similar duck species, among which fertile hybrids occur relatively frequently in nature, yet these species remain distinct. Results We show that the degree of shared single nucleotide polymorphisms (SNPs between five species of dabbling ducks (genus Anas is an order of magnitude higher than that previously reported between any pair of eukaryotic species with comparable evolutionary distances. We demonstrate that hybridisation has led to sustained exchange of genetic material between duck species on an evolutionary time scale without disintegrating species boundaries. Even though behavioural, genetic and ecological factors uphold species boundaries in ducks, we detect opposing forces allowing for viable interspecific hybrids, with long-term evolutionary implications. Based on the superspecies concept we here introduce the novel term "supra-population" to explain the persistence of SNPs identical by descent within the studied ducks despite their history as distinct species dating back millions of years. Conclusions By reviewing evidence from speciation theory, palaeogeography and palaeontology we propose a fundamentally new model of speciation to accommodate our genetic findings in dabbling ducks. This model, we argue, may also shed light on longstanding unresolved general speciation and hybridisation patterns in higher organisms, e.g. in other bird

  13. High density, genome-wide markers and intra-specific replication yield an unprecedented phylogenetic reconstruction of a globally significant, speciose lineage of Eucalyptus.

    Science.gov (United States)

    Jones, Rebecca C; Nicolle, Dean; Steane, Dorothy A; Vaillancourt, René E; Potts, Brad M

    2016-12-01

    We used genome-wide markers and an unprecedented scale of sampling to construct a phylogeny for a globally significant Eucalyptus lineage that has been impacted by hybridisation, recent radiation and morphological convergence. Our approach, using 3109 DArT markers distributed throughout the genome and 540 samples covering 185 terminal taxa in sections Maidenaria, Exsertaria, Latoangulatae and related smaller sections, with multiple geographically widespread samples per terminal taxon, produced a phylogeny that largely matched the morphological treatment of sections, though sections Exsertaria and Latoangulatae were polyphyletic. At lower levels there were numerous inconsistencies between the morphological treatment and the molecular phylogeny, and taxa within the three main sections were generally not monophyletic at the series (at least 62% polyphyly) or species (at least 52% polyphyly) level. Some of the discrepancies appear to be the result of morphological convergence or misclassifications, and we propose some taxonomic reassessments to address this. However, many inconsistencies appear to be the products of incomplete speciation and/or hybridisation. Our analysis represents a significant advance on previous phylogenies of these important eucalypt sections (which have mainly used single samples to represent each species), thus providing a robust phylogenetic framework for evolutionary and ecological studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Genome Imprinting

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 9. Genome Imprinting - The Silencing of ... General Article Volume 5 Issue 9 September 2000 pp 49-57 ... M T Tanuja1. Drosophila Stock Centre, Department of Studies in Zoology, University of Mysore Manasagangotri Mysore 570 006, India.

  15. Genome Imprinting

    Indian Academy of Sciences (India)

    ring pathological condition cystic fibrosis is due to inheritance of both copies of chromosome 7 from the mother. Similarly,. Prader-Willi syndrome in humans is due to the inheritance of both copies of chromosome 15 from the mother. Human Triploids. The triploid (Le. 3 copies of the haploid genome are present instead of the ...

  16. genome editing

    Indian Academy of Sciences (India)

    2016-02-11

    Feb 11, 2016 ... What history tells us. XL. The success story of the expression 'genome editing'. MICHEL MORANGE. Centre Cavaillès, République des Savoirs: Lettres, Sciences, Philosophie USR 3608, Ecole. Normale Supérieure, 29 Rue d'Ulm, 75230, Paris Cedex 05, France. (Fax, 33-144-323941; Email, ...

  17. Ancient genomics

    DEFF Research Database (Denmark)

    Der Sarkissian, Clio; Allentoft, Morten Erik; Avila Arcos, Maria del Carmen

    2015-01-01

    The past decade has witnessed a revolution in ancient DNA (aDNA) research. Although the field's focus was previously limited to mitochondrial DNA and a few nuclear markers, whole genome sequences from the deep past can now be retrieved. This breakthrough is tightly connected to the massive sequen...

  18. Comparative Genomics

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 11; Issue 8. Comparative Genomics - A Powerful New Tool in Biology. Anand K Bachhawat. General Article Volume 11 Issue 8 August 2006 pp 22-40. Fulltext. Click here to view fulltext PDF. Permanent link:

  19. A 1.37-Mb 12p11.22-p11.21 deletion coincident with a 367-kb 22q11.2 duplication detected by array comparative genomic hybridization in an adolescent girl with autism and difficulty in self-care of menstruation.

    Science.gov (United States)

    Chen, Chih-Ping; Lin, Shuan-Pei; Chern, Schu-Rern; Wu, Peih-Shan; Su, Jun-Wei; Lee, Chen-Chi; Wang, Wayseen

    2014-03-01

    To present an array comparative genomic hybridization (aCGH) characterization of a 12p11.22-p11.21 microdeletion and 22q11.2 microduplication in an adolescent girl with autism, mental retardation, facial dysmorphism, microcephaly, behavior problems, and an apparently balanced reciprocal translocation of t(8;12)(q24.3;p11.2). A 13-year-old girl was referred to the hospital because of autism, mental retardation, and difficulty in the self-care of her menstruation. Cytogenetic analysis revealed an apparently balanced reciprocal translocation and a karyotype of 46,XX,t(8;12) (q24.3;p11.2)dn. The girl manifested microcephaly, hypertelorism, flat facial profile, prominent forehead, thick scalp hair, upslanting palpebral fissures, broad nasal bridge, bulbous nose, right simian crease, bilateral clinodactyly of the fifth fingers, bilateral pes cavus, learning difficulties, mental retardation, emotional instability, cognitive impairment, behavior problems, jumping-like gaits, and autistic spectrum disorder. aCGH was performed to evaluate genomic imbalance in this patient. aCGH analysis revealed a 1.37-Mb 12p11.22-p11.21 microdeletion or arr [hg 19] 12p11.22-p11.21 (30,645,008-32,014,774)×1 and a 367-kb 22q11.21 microduplication or arr [hg 19] 22q11.21 (18,657,470-19,024,306)×3. The 1.37-Mb 12p11.22-p11.21 microdeletion encompassed 26 genes including IPO8, CAPRIN2, and DDX11, and the 367-kb 22q11.21 microduplication encompassed 20 genes including USP18, DGCR6, PRODH, and DGCR2. An apparently balanced translocation may be in fact affected by concurrent deletion and duplication in two different chromosomal regions. Our presentation provides information on diagnostic phenotype of 12p11.22-p11.21 microdeletion and 22q11.2 microduplication. Copyright © 2014. Published by Elsevier B.V.

  20. Robust group fused lasso for multisample copy number variation detection under uncertainty.

    Science.gov (United States)

    Sharifi Noghabi, Hossein; Mohammadi, Majid; Tan, Yao-Hua

    2016-12-01

    One of the most important needs in the post-genome era is providing the researchers with reliable and efficient computational tools to extract and analyse this huge amount of biological data, in which DNA copy number variation (CNV) is a vitally important one. Array-based comparative genomic hybridisation (aCGH) is a common approach in order to detect CNVs. Most of methods for this purpose were proposed for one-dimensional profiles. However, slightly this focus has moved from one- to multi-dimensional signals. In addition, since contamination of these profiles with noise is always an issue, it is highly important to have a robust method for analysing multi-sample aCGH profiles. In this study, the authors propose robust group fused lasso which utilises the robust group total variations. Instead of l 2,1 norm, the l 1 - l 2 M-estimator is used which is more robust in dealing with non-Gaussian noise and high corruption. More importantly, Correntropy (Welsch M-estimator) is also applied for fitting error. Extensive experiments indicate that the proposed method outperforms the state-of-the art algorithms and techniques under a wide range of scenarios with diverse noises.

  1. Genomic profiling of myeloma: the best approach, a comparison of cytogenetics, FISH and array-CGH of 112 myeloma cases.

    Science.gov (United States)

    Rack, Katrina; Vidrequin, Sébastien; Dargent, Jean-Louis

    2016-01-01

    Chromosome abnormalities are important prognostic factors in myeloma allowing risk stratification of patients. Different techniques are available for their detection including cytogenetics, Fluorescent In Situ Hybridisation (FISH) and array Competitive Genomic Hybridisation (CGH). This study aimed to assess the validity and usefulness of each technique in a diagnostic setting. 112 myeloma cases were analysed by whole bone marrow cytogenetics and by FISH and array CGH performed on purified plasma cell populations. Clonal abnormalities were identified in 30% of cases by cytogenetics and 97% by FISH and array CGH. By combining array and FISH results abnormalities were detected in 99% of cases and, if cytogenetic analysis was also considered, abnormalities were detected in 100% of cases. Cytogenetic analysis is of limited value in myeloma. Array CGH and FISH are highly specific tests allowing the identification of aberrations in virtually all cases. The two techniques are complementary and need to be combined in order to provide a comprehensive analysis of all clinically relevant aberrations in myeloma. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Direct detection of chicken genomic DNA for gender determination by thymine-DNA glycosylase.

    Science.gov (United States)

    Porat, N; Bogdanov, K; Danielli, A; Arie, A; Samina, I; Hadani, A

    2011-02-01

    1. Birds, especially nestlings, are generally difficult to sex by morphology and early detection of chick gender in ovo in the hatchery would facilitate removal of unwanted chicks and diminish welfare objections regarding culling after hatch. 2. We describe a method to determine chicken gender without the need for PCR via use of Thymine-DNA Glycosylase (TDG). TDG restores thymine (T)/guanine (G) mismatches to cytosine (C)/G. We show here, that like DNA Polymerase, TDG can recognise, bind and function on a primer hybridised to chicken genomic DNA. 3. The primer contained a T to mismatch a G in a chicken genomic template and the T/G was cleaved with high fidelity by TDG. Thus, the chicken genomic DNA can be identified without PCR amplification via direct and linear detection. Sensitivity was increased using gender specific sequences from the chicken genome. 4. Currently, these are laboratory results, but we anticipate that further development will allow this method to be used in non-laboratory settings, where PCR cannot be employed.

  3. Personal genomics services: whose genomes?

    Science.gov (United States)

    Gurwitz, David; Bregman-Eschet, Yael

    2009-07-01

    New companies offering personal whole-genome information services over the internet are dynamic and highly visible players in the personal genomics field. For fees currently ranging from US$399 to US$2500 and a vial of saliva, individuals can now purchase online access to their individual genetic information regarding susceptibility to a range of chronic diseases and phenotypic traits based on a genome-wide SNP scan. Most of the companies offering such services are based in the United States, but their clients may come from nearly anywhere in the world. Although the scientific validity, clinical utility and potential future implications of such services are being hotly debated, several ethical and regulatory questions related to direct-to-consumer (DTC) marketing strategies of genetic tests have not yet received sufficient attention. For example, how can we minimize the risk of unauthorized third parties from submitting other people's DNA for testing? Another pressing question concerns the ownership of (genotypic and phenotypic) information, as well as the unclear legal status of customers regarding their own personal information. Current legislation in the US and Europe falls short of providing clear answers to these questions. Until the regulation of personal genomics services catches up with the technology, we call upon commercial providers to self-regulate and coordinate their activities to minimize potential risks to individual privacy. We also point out some specific steps, along the trustee model, that providers of DTC personal genomics services as well as regulators and policy makers could consider for addressing some of the concerns raised below.

  4. Nutritional genomics.

    Science.gov (United States)

    Ordovas, Jose M; Corella, Dolores

    2004-01-01

    Nutritional genomics has tremendous potential to change the future of dietary guidelines and personal recommendations. Nutrigenetics will provide the basis for personalized dietary recommendations based on the individual's genetic make up. This approach has been used for decades for certain monogenic diseases; however, the challenge is to implement a similar concept for common multifactorial disorders and to develop tools to detect genetic predisposition and to prevent common disorders decades before their manifestation. The preliminary results involving gene-diet interactions for cardiovascular diseases and cancer are promising, but mostly inconclusive. Success in this area will require the integration of different disciplines and investigators working on large population studies designed to adequately investigate gene-environment interactions. Despite the current difficulties, preliminary evidence strongly suggests that the concept should work and that we will be able to harness the information contained in our genomes to achieve successful aging using behavioral changes; nutrition will be the cornerstone of this endeavor.

  5. Visualization for genomics: the Microbial Genome Viewer.

    NARCIS (Netherlands)

    Kerkhoven, R.; Enckevort, F.H.J. van; Boekhorst, J.; Molenaar, D; Siezen, R.J.

    2004-01-01

    SUMMARY: A Web-based visualization tool, the Microbial Genome Viewer, is presented that allows the user to combine complex genomic data in a highly interactive way. This Web tool enables the interactive generation of chromosome wheels and linear genome maps from genome annotation data stored in a

  6. Exploring the zoonotic potential of Mycobacterium avium subspecies paratuberculosis through comparative genomics.

    Directory of Open Access Journals (Sweden)

    James W Wynne

    Full Text Available A comparative genomics approach was utilised to compare the genomes of Mycobacterium avium subspecies paratuberculosis (MAP isolated from early onset paediatric Crohn's disease (CD patients as well as Johne's diseased animals. Draft genome sequences were produced for MAP isolates derived from four CD patients, one ulcerative colitis (UC patient, and two non-inflammatory bowel disease (IBD control individuals using Illumina sequencing, complemented by comparative genome hybridisation (CGH. MAP isolates derived from two bovine and one ovine host were also subjected to whole genome sequencing and CGH. All seven human derived MAP isolates were highly genetically similar and clustered together with one bovine type isolate following phylogenetic analysis. Three other sequenced isolates (including the reference bovine derived isolate K10 were genetically distinct. The human isolates contained two large tandem duplications, the organisations of which were confirmed by PCR. Designated vGI-17 and vGI-18 these duplications spanned 63 and 109 open reading frames, respectively. PCR screening of over 30 additional MAP isolates (3 human derived, 27 animal derived and one environmental isolate confirmed that vGI-17 and vGI-18 are common across many isolates. Quantitative real-time PCR of vGI-17 demonstrated that the proportion of cells containing the vGI-17 duplication varied between 0.01 to 15% amongst isolates with human isolates containing a higher proportion of vGI-17 compared to most animal isolates. These findings suggest these duplications are transient genomic rearrangements. We hypothesise that the over-representation of vGI-17 in human derived MAP strains may enhance their ability to infect or persist within a human host by increasing genome redundancy and conferring crude regulation of protein expression across biologically important regions.

  7. Genome Sequencing

    DEFF Research Database (Denmark)

    Sato, Shusei; Andersen, Stig Uggerhøj

    2014-01-01

    The current Lotus japonicus reference genome sequence is based on a hybrid assembly of Sanger TAC/BAC, Sanger shotgun and Illumina shotgun sequencing data generated from the Miyakojima-MG20 accession. It covers nearly all expressed L. japonicus genes and has been annotated mainly based...... on transcriptional evidence. Analysis of repetitive sequences suggests that they are underrepresented in the reference assembly, reflecting an enrichment of gene-rich regions in the current assembly. Characterization of Lotus natural variation by resequencing of L. japonicus accessions and diploid Lotus species...... is currently ongoing, facilitated by the MG20 reference sequence...

  8. The platypus genome unraveled.

    Science.gov (United States)

    O'Brien, Stephen J

    2008-06-13

    The genome of the platypus has been sequenced, assembled, and annotated by an international genomics team. Like the animal itself the platypus genome contains an amalgam of mammal, reptile, and bird-like features.

  9. Functional food ingredients against colorectal cancer. An example project integrating functional genomics, nutrition and health.

    Science.gov (United States)

    Stierum, R; Burgemeister, R; van Helvoort, A; Peijnenburg, A; Schütze, K; Seidelin, M; Vang, O; van Ommen, B

    2001-08-01

    Functional Food Ingredients Against Colorectal Cancer is one of the first European Union funded Research Projects at the cross-road of functional genomics [comprising transcriptomics, the measurement of the expression of all messengers RNA (mRNAs) and proteomics, the measurement of expression/state of all proteins], nutrition and human health. The goal of Functional Food Ingredients Against Colorectal Cancer is to develop a colon epithelial cell line-based screening assay for nutrients with presumed anti-colorectal carcinogenic properties. Genes involved in colon carcinogenesis are identified at the RNA and protein level, using a variety of methods (subtractive hybridisation, DNA microarray, proteomics) in combination with models for colorectal cancer development (human biopsies, rat model for colorectal carcinogenesis, colorectal cancer epithelial cell lines). Secondly, colorectal cancer epithelial cell lines are selected, in terms of their capacity to undergo gene/protein expression changes representing different phases in the colorectal carcinogenesis. Thirdly, these cell lines are used to determine the effects of nutrients with presumed anti-carcinogenic properties (e.g. resveratrol, flavonoids) on functional genomics-derived endpoints. Once validated against the effects of these nutrients in in vivo animal models and classical biomarkers for colorectal carcinogenesis, these cell line models combined with functional genomics represent useful tools to study colorectal carcinogenesis and screen for nutrients with anti-carcinogenic properties.

  10. Genome cartography: charting the apicomplexan genome.

    Science.gov (United States)

    Kissinger, Jessica C; DeBarry, Jeremy

    2011-08-01

    Genes reside in particular genomic contexts that can be mapped at many levels. Historically, 'genetic maps' were used primarily to locate genes. Recent technological advances in the determination of genome sequences have made the analysis and comparison of whole genomes possible and increasingly tractable. What do we see if we shift our focus from gene content (the 'inventory' of genes contained within a genome) to the composition and organization of a genome? This review examines what has been learned about the evolution of the apicomplexan genome as well as the significance and impact of genomic location on our understanding of the eukaryotic genome and parasite biology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Herbarium genomics

    DEFF Research Database (Denmark)

    Bakker, Freek T.; Lei, Di; Yu, Jiaying

    2016-01-01

    Herbarium genomics is proving promising as next-generation sequencing approaches are well suited to deal with the usually fragmented nature of archival DNA. We show that routine assembly of partial plastome sequences from herbarium specimens is feasible, from total DNA extracts and with specimens...... Angiosperm families, 73 of which were from herbarium material with ages up to 146 years old. For 84 specimens, a sufficient number of paired-end reads were generated (in total 9.4 × 1012 nucleotides), yielding successful plastome assemblies for 74 specimens. Those derived from herbarium specimens have lower...... fractions of plastome-derived reads compared with those from fresh and silica-gel-dried specimens, but total herbarium assembly lengths are only slightly shorter. Specimens from wet-tropical conditions appear to have a higher number of contigs per assembly and lower N50 values. We find no significant...

  12. National Human Genome Research Institute

    Science.gov (United States)

    ... the Director Organization Reports & Publications Español The National Human Genome Research Institute conducts genetic and genomic research, funds ... genomic literacy among physicians. Funded by the National Human Genome Research Institute (NHGRI), The Universal Genomics Instructor Handbook ...

  13. Conserved genomic organisation of Group B Sox genes in insects.

    Directory of Open Access Journals (Sweden)

    Woerfel Gertrud

    2005-05-01

    Full Text Available Abstract Background Sox domain containing genes are important metazoan transcriptional regulators implicated in a wide rage of developmental processes. The vertebrate B subgroup contains the Sox1, Sox2 and Sox3 genes that have early functions in neural development. Previous studies show that Drosophila Group B genes have been functionally conserved since they play essential roles in early neural specification and mutations in the Drosophila Dichaete and SoxN genes can be rescued with mammalian Sox genes. Despite their importance, the extent and organisation of the Group B family in Drosophila has not been fully characterised, an important step in using Drosophila to examine conserved aspects of Group B Sox gene function. Results We have used the directed cDNA sequencing along with the output from the publicly-available genome sequencing projects to examine the structure of Group B Sox domain genes in Drosophila melanogaster, Drosophila pseudoobscura, Anopheles gambiae and Apis mellifora. All of the insect genomes contain four genes encoding Group B proteins, two of which are intronless, as is the case with vertebrate group B genes. As has been previously reported and unusually for Group B genes, two of the insect group B genes, Sox21a and Sox21b, contain introns within their DNA-binding domains. We find that the highly unusual multi-exon structure of the Sox21b gene is common to the insects. In addition, we find that three of the group B Sox genes are organised in a linked cluster in the insect genomes. By in situ hybridisation we show that the pattern of expression of each of the four group B genes during embryogenesis is conserved between D. melanogaster and D. pseudoobscura. Conclusion The DNA-binding domain sequences and genomic organisation of the group B genes have been conserved over 300 My of evolution since the last common ancestor of the Hymenoptera and the Diptera. Our analysis suggests insects have two Group B1 genes, SoxN and

  14. Individual capacity for DNA repair and maintenance of genomic integrity: a fertile ground for studies in the field of assisted reproduction

    Directory of Open Access Journals (Sweden)

    Radoslava Vazharova

    2016-05-01

    Full Text Available Many factors may affect the chances for successful pregnancy, especially at a later age. Fertility evaluations including genetic analysis are recommended to couples that have not achieved pregnancy within 6–12 months of unprotected intercourse. This review discusses some of the common polymorphisms in genes coding for proteins functioning in DNA damage identification and repair and maintenance of genomic integrity that may affect the chances of success in natural conception as well as in assisted reproduction (AR. Common polymorphisms in genes coding for proteins functioning in DNA damage identification and repair and maintenance of genomic integrity may affect the chances of success in assisted reproduction as well as in natural conception. The effects of carriership of different alleles of key genes of DNA repair may have differential effects in men and women and at different ages, suggesting complex interactions with the mechanisms controlling cell and tissue aging and programmed cell death. Future studies in the field are needed in order to elucidate the genotype–phenotype relationships and to translate the knowledge about individual repair capacity and maintenance of genomic integrity to potential clinical applications. Abbreviations: aCGH: microarray-based comparative genomic hybridization; AR: assisted reproduction; ATM: ataxia-telangiectasia mutated; ATP: adenosine triphosphate; BER: base excision repair; BFE: basic fertility evaluation; DMSO: dimethyl sulfoxide; FSH: follicle-stimulating hormone; GNRHR: gonadotropin-releasing hormone receptor; HMG: high-mobility group; ICSI: intracytoplasmic sperm injection; IUI: intrauterine insemination; IVF: in vitro fertilization; LH: luteinizing hormone; LIF: leukaemia inhibitory factor; MTR: methionine synthase; MTRR: methionine synthase reductase; NGS: next-generation sequencing; NER: nucleotide excision repair; NHEJ: non-homologous end joining; PAH: polycyclic aromatic hydrocarbons; PCOS

  15. Deep Sequencing of Suppression Subtractive Hybridisation Drought and Recovery Libraries of the Non-model CropTrifolium repensL.

    Science.gov (United States)

    Bisaga, Maciej; Lowe, Matthew; Hegarty, Matthew; Abberton, Michael; Ravagnani, Adriana

    2017-01-01

    White clover is a short-lived perennial whose persistence is greatly affected by abiotic stresses, particularly drought. The aim of this work was to characterize its molecular response to water deficit and recovery following re-hydration to identify targets for the breeding of tolerant varieties. We created a white clover reference transcriptome of 16,193 contigs by deep sequencing (mean base coverage 387x) four Suppression Subtractive Hybridization (SSH) libraries (a forward and a reverse library for each treatment) constructed from young leaf tissue of white clover at the onset of the response to drought and recovery. Reads from individual libraries were then mapped to the reference transcriptome and processed comparing expression level data. The pipeline generated four robust sets of transcripts induced and repressed in the leaves of plants subjected to water deficit stress (6,937 and 3,142, respectively) and following re-hydration (6,695 and 4,897, respectively). Semi-quantitative polymerase chain reaction was used to verify the expression pattern of 16 genes. The differentially expressed transcripts were functionally annotated and mapped to biological processes and pathways. In agreement with similar studies in other crops, the majority of transcripts up-regulated in response to drought belonged to metabolic processes, such as amino acid, carbohydrate, and lipid metabolism, while transcripts involved in photosynthesis, such as components of the photosystem and the biosynthesis of photosynthetic pigments, were up-regulated during recovery. The data also highlighted the role of raffinose family oligosaccharides (RFOs) and the possible delayed response of the flavonoid pathways in the initial response of white clover to water withdrawal. The work presented in this paper is to our knowledge the first large scale molecular analysis of the white clover response to drought stress and re-hydration. The data generated provide a valuable genomic resource for marker

  16. The kangaroo genome

    Science.gov (United States)

    Wakefield, Matthew J.; Graves, Jennifer A. Marshall

    2003-01-01

    The kangaroo genome is a rich and unique resource for comparative genomics. Marsupial genetics and cytology have made significant contributions to the understanding of gene function and evolution, and increasing the availability of kangaroo DNA sequence information would provide these benefits on a genomic scale. Here we summarize the contributions from cytogenetic and genetic studies of marsupials, describe the genomic resources currently available and those being developed, and explore the benefits of a kangaroo genome project. PMID:12612602

  17. Genomics With Cloud Computing

    OpenAIRE

    Sukhamrit Kaur; Sandeep Kaur

    2015-01-01

    Abstract Genomics is study of genome which provides large amount of data for which large storage and computation power is needed. These issues are solved by cloud computing that provides various cloud platforms for genomics. These platforms provides many services to user like easy access to data easy sharing and transfer providing storage in hundreds of terabytes more computational power. Some cloud platforms are Google genomics DNAnexus and Globus genomics. Various features of cloud computin...

  18. Genome Maps, a new generation genome browser

    Science.gov (United States)

    Medina, Ignacio; Salavert, Francisco; Sanchez, Rubén; de Maria, Alejandro; Alonso, Roberto; Escobar, Pablo; Bleda, Marta; Dopazo, Joaquín

    2013-01-01

    Genome browsers have gained importance as more genomes and related genomic information become available. However, the increase of information brought about by new generation sequencing technologies is, at the same time, causing a subtle but continuous decrease in the efficiency of conventional genome browsers. Here, we present Genome Maps, a genome browser that implements an innovative model of data transfer and management. The program uses highly efficient technologies from the new HTML5 standard, such as scalable vector graphics, that optimize workloads at both server and client sides and ensure future scalability. Thus, data management and representation are entirely carried out by the browser, without the need of any Java Applet, Flash or other plug-in technology installation. Relevant biological data on genes, transcripts, exons, regulatory features, single-nucleotide polymorphisms, karyotype and so forth, are imported from web services and are available as tracks. In addition, several DAS servers are already included in Genome Maps. As a novelty, this web-based genome browser allows the local upload of huge genomic data files (e.g. VCF or BAM) that can be dynamically visualized in real time at the client side, thus facilitating the management of medical data affected by privacy restrictions. Finally, Genome Maps can easily be integrated in any web application by including only a few lines of code. Genome Maps is an open source collaborative initiative available in the GitHub repository (https://github.com/compbio-bigdata-viz/genome-maps). Genome Maps is available at: http://www.genomemaps.org. PMID:23748955

  19. Genome Maps, a new generation genome browser.

    Science.gov (United States)

    Medina, Ignacio; Salavert, Francisco; Sanchez, Rubén; de Maria, Alejandro; Alonso, Roberto; Escobar, Pablo; Bleda, Marta; Dopazo, Joaquín

    2013-07-01

    Genome browsers have gained importance as more genomes and related genomic information become available. However, the increase of information brought about by new generation sequencing technologies is, at the same time, causing a subtle but continuous decrease in the efficiency of conventional genome browsers. Here, we present Genome Maps, a genome browser that implements an innovative model of data transfer and management. The program uses highly efficient technologies from the new HTML5 standard, such as scalable vector graphics, that optimize workloads at both server and client sides and ensure future scalability. Thus, data management and representation are entirely carried out by the browser, without the need of any Java Applet, Flash or other plug-in technology installation. Relevant biological data on genes, transcripts, exons, regulatory features, single-nucleotide polymorphisms, karyotype and so forth, are imported from web services and are available as tracks. In addition, several DAS servers are already included in Genome Maps. As a novelty, this web-based genome browser allows the local upload of huge genomic data files (e.g. VCF or BAM) that can be dynamically visualized in real time at the client side, thus facilitating the management of medical data affected by privacy restrictions. Finally, Genome Maps can easily be integrated in any web application by including only a few lines of code. Genome Maps is an open source collaborative initiative available in the GitHub repository (https://github.com/compbio-bigdata-viz/genome-maps). Genome Maps is available at: http://www.genomemaps.org.

  20. Microarray karyotyping of commercial wine yeast strains reveals shared, as well as unique, genomic signatures

    Directory of Open Access Journals (Sweden)

    Levine R Paul

    2005-04-01

    Full Text Available Abstract Background Genetic differences between yeast strains used in wine-making may account for some of the variation seen in their fermentation properties and may also produce differing sensory characteristics in the final wine product itself. To investigate this, we have determined genomic differences among several Saccharomyces cerevisiae wine strains by using a "microarray karyotyping" (also known as "array-CGH" or "aCGH" technique. Results We have studied four commonly used commercial wine yeast strains, assaying three independent isolates from each strain. All four wine strains showed common differences with respect to the laboratory S. cerevisiae strain S288C, some of which may be specific to commercial wine yeasts. We observed very little intra-strain variation; i.e., the genomic karyotypes of different commercial isolates of the same strain looked very similar, although an exception to this was seen among the Montrachet isolates. A moderate amount of inter-strain genomic variation between the four wine strains was observed, mostly in the form of depletions or amplifications of single genes; these differences allowed unique identification of each strain. Many of the inter-strain differences appear to be in transporter genes, especially hexose transporters (HXT genes, metal ion sensors/transporters (CUP1, ZRT1, ENA genes, members of the major facilitator superfamily, and in genes involved in drug response (PDR3, SNQ1, QDR1, RDS1, AYT1, YAR068W. We therefore used halo assays to investigate the response of these strains to three different fungicidal drugs (cycloheximide, clotrimazole, sulfomethuron methyl. Strains with fewer copies of the CUP1 loci showed hypersensitivity to sulfomethuron methyl. Conclusion Microarray karyotyping is a useful tool for analyzing the genome structures of wine yeasts. Despite only small to moderate variations in gene copy numbers between different wine yeast strains and within different isolates of a given

  1. Genomic Encyclopedia of Fungi

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-08-10

    Genomes of fungi relevant to energy and environment are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 150 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such parts suggested by comparative genomics and functional analysis in these areas are presented here.

  2. JGI Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor V.

    2011-03-14

    Genomes of energy and environment fungi are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 50 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such 'parts' suggested by comparative genomics and functional analysis in these areas are presented here

  3. Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome.

    Directory of Open Access Journals (Sweden)

    Maribel Forero-Castro

    Full Text Available Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL is still a challenge.To characterize the presence of additional DNA copy number alterations (CNAs in children and adults with ALL by whole-genome oligonucleotide array (aCGH analysis, and to identify their associations with clinical features and outcome. Array-CGH was carried out in 265 newly diagnosed ALLs (142 children and 123 adults. The NimbleGen CGH 12x135K array (Roche was used to analyze genetic gains and losses. CNAs were analyzed with GISTIC and aCGHweb software. Clinical and biological variables were analyzed. Three of the patients showed chromothripsis (cth6, cth14q and cth15q. CNAs were associated with age, phenotype, genetic subtype and overall survival (OS. In the whole cohort of children, the losses on 14q32.33 (p = 0.019 and 15q13.2 (p = 0.04 were related to shorter OS. In the group of children without good- or poor-risk cytogenetics, the gain on 1p36.11 was a prognostic marker independently associated with shorter OS. In adults, the gains on 19q13.2 (p = 0.001 and Xp21.1 (p = 0.029, and the loss of 17p (p = 0.014 were independent markers of poor prognosis with respect to OS. In summary, CNAs are frequent in ALL and are associated with clinical parameters and survival. Genome-wide DNA copy number analysis allows the identification of genetic markers that predict clinical outcome, suggesting that detection of these genetic lesions will be useful in the management of patients newly diagnosed with ALL.

  4. Avian polymavirus in wild birds: genome analysis of isolates from Falconiformes and Psittaciformes.

    Science.gov (United States)

    Johne, R; Müller, H

    1998-01-01

    Avian polyomavirus (APV) infections have been reported to cause fatal disease in a wide range of psittacine species. Here we demonstrate APV infections in buzzards (Buteo buteo) and in a falcon (Falco tinnunculus) found dead in Germany, and in lovebirds (Agapornis pullaria) with fatal disease, wild-caught in Moçambique. APV infection in buzzards was determined by PCR amplification of parts of the viral genome followed by Southern blot hybridisation. The genomes of the isolates obtained from the falcon and one of the lovebirds proved to be very closely related to those of Budgerigar Fledgling Disease Virus (BFDV)-1, BFDV-2 and BFDV-3, isolated from budgerigar, chicken, and parakeet, respectively. A consensus sequence was delineated from the known nucleotide sequences of APV isolates. The significance of some nucleotide changes is discussed. Infectivity of all of these isolates was neutralized by antibodies directed against BFDV-1. Data presented in this investigation show that the polyomavirus isolates obtained from different avian species so far all belong to one genotype and one serotype within the proposed subgenus Avipolyomavirus of the family Papovaviridae. The designation Budgerigar Fledgling Disease Virus (BFDV) is, therefore, misleading as this virus type infects different species of birds. The name Avian Polymavirus and the abreviation APV should be adopted to all of the isolates investigated in detail at present. The possible role of birds of passage in the epidemiology in APV infections is discussed.

  5. Genomics With Cloud Computing

    Directory of Open Access Journals (Sweden)

    Sukhamrit Kaur

    2015-04-01

    Full Text Available Abstract Genomics is study of genome which provides large amount of data for which large storage and computation power is needed. These issues are solved by cloud computing that provides various cloud platforms for genomics. These platforms provides many services to user like easy access to data easy sharing and transfer providing storage in hundreds of terabytes more computational power. Some cloud platforms are Google genomics DNAnexus and Globus genomics. Various features of cloud computing to genomics are like easy access and sharing of data security of data less cost to pay for resources but still there are some demerits like large time needed to transfer data less network bandwidth.

  6. Diet and genomic stability.

    Science.gov (United States)

    Young, Graeme P

    2007-01-01

    Cancer results from a disordered and unstable genome - the degree of abnormality progresses as the process of oncogenesis proceeds. Such genomic instability appears to be subject to control by environmental factors as evidenced by the number of cancers that are either caused by specific environmental agents (lung, skin, cervix) or else regulated by a broader range of agents such as effect of diet on gastric and colorectal cancers. Dietary factors might interact in several ways with the genome to protect against cancer. An agent might interact directly with the genome and regulate expression (as a genetic or epigenetic regulator) or indirectly by influencing DNA 'repair' responses and so improve genomic stability. Research now shows that diet-genomic interactions in cancer go beyond interactions with the normal genome and involve enhancement of normal cellular responses to DNA damage such that genome stability is more effectively maintained. Activation of apoptosis may be a key to protection.

  7. Rat Genome Database (RGD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Rat Genome Database (RGD) is a collaborative effort between leading research institutions involved in rat genetic and genomic research to collect, consolidate,...

  8. High-Resolution Mapping of Genomic Imbalance and Identification of Gene Expression Profiles Associated with Differential Chemotherapy Response in Serous Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Marcus Bernardini

    2005-06-01

    Full Text Available Array comparative genomic hybridization (aCGH and microarray expression profiling were used to subclassify DNA and RNA alterations associated with differential response to chemotherapy in ovarian cancer. Two to 4 Mb interval arrays were used to map genomic imbalances in 26 sporadic serous ovarian tumors. Cytobands 1p36, iq42-44, 6p22.1-p21.2, 7q32.1-q34 9q33.3-q34.3, 11p15.2, 13q12.2-q13.1, 13q21.31, 17q11.2, 17q24.2-q25.3, 18q12.2, and 21q21.2-q21.3 were found to be statistically associated with chemotherapy response, and novel regions of loss at 15g11.2q15.1 and 17q21.32-q21.33 were identified. Gene expression profiles were obtained from a subset of these tumors and identified a group of genes whose differential expression was significantly associated with drug resistance. Within this group, five genes (GAPD, HMGB2, HSC70, GRP58, and HMGB1, previously shown to form a nuclear complex associated with resistance to DNA conformation-altering chemotherapeutic drugs in in vitro systems, may represent a novel class of genes associated with in vivo drug response in ovarian cancer patients. Although RNA expression change indicated only weak DNA copy number dependence, these data illustrate the value of molecular profiling at both the RNA and DNA levels to identify small genomic regions and gene subsets that could be associated with differential chemotherapy response in ovarian cancer.

  9. Exploiting the genome

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Koonin, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office

    1998-09-11

    In 1997, JASON conducted a DOE-sponsored study of the human genome project with special emphasis on the areas of technology, quality assurance and quality control, and informatics. The present study has two aims: first, to update the 1997 Report in light of recent developments in genome sequencing technology, and second, to consider possible roles for the DOE in the ''post-genomic" era, following acquisition of the complete human genome sequence.

  10. Genomic prediction using subsampling

    OpenAIRE

    Xavier, Alencar; Xu, Shizhong; Muir, William; Rainey, Katy Martin

    2017-01-01

    Background Genome-wide assisted selection is a critical tool for the?genetic improvement of plants and animals. Whole-genome regression models in Bayesian framework represent the main family of prediction methods. Fitting such models with a large number of observations involves a prohibitive computational burden. We propose the use of subsampling bootstrap Markov chain in genomic prediction. Such method consists of fitting whole-genome regression models by subsampling observations in each rou...

  11. Ebolavirus comparative genomics

    DEFF Research Database (Denmark)

    Jun, Se-Ran; Leuze, Michael R.; Nookaew, Intawat

    2015-01-01

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. To examine the dynamics of this genome, we compare more than 100 currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms...

  12. The prevalence of badnaviruses in West African yams (Dioscorea cayenensis-rotundata) and evidence of endogenous pararetrovirus sequences in their genomes.

    Science.gov (United States)

    Seal, Susan; Turaki, Aliyu; Muller, Emmanuelle; Kumar, P Lava; Kenyon, Lawrence; Filloux, Denis; Galzi, Serge; Lopez-Montes, Antonio; Iskra-Caruana, Marie-Line

    2014-06-24

    -positive yam samples from Burkina Faso (cv. Pilimpikou) were identified in which no viral particles were detected by either PAS-ELISA or ISEM. Southern hybridisation results using a yam badnavirus RT-RNaseH sequence (Gn155Dr) as probe, supported a lack of badnavirus particles in the cv. Pilimpikou and identified their equivalent sequences to be of plant genome origin. Probe Gn155Dr, however, hybridised to viral particles and plant genomic DNA in three D. rotundata samples from Guinea. These results represent the first data demonstrating the presence of integrated sequences of badnaviruses in yam. The implications of this for virus-indexing, breeding and multiplication of seed yams are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Comparative genomics of Lactobacillus

    Science.gov (United States)

    Kant, Ravi; Blom, Jochen; Palva, Airi; Siezen, Roland J.; de Vos, Willem M.

    2011-01-01

    Summary The genus Lactobacillus includes a diverse group of bacteria consisting of many species that are associated with fermentations of plants, meat or milk. In addition, various lactobacilli are natural inhabitants of the intestinal tract of humans and other animals. Finally, several Lactobacillus strains are marketed as probiotics as their consumption can confer a health benefit to host. Presently, 154 Lactobacillus species are known and a growing fraction of these are subject to draft genome sequencing. However, complete genome sequences are needed to provide a platform for detailed genomic comparisons. Therefore, we selected a total of 20 genomes of various Lactobacillus strains for which complete genomic sequences have been reported. These genomes had sizes varying from 1.8 to 3.3 Mb and other characteristic features, such as G+C content that ranged from 33% to 51%. The Lactobacillus pan genome was found to consist of approximately 14 000 protein‐encoding genes while all 20 genomes shared a total of 383 sets of orthologous genes that defined the Lactobacillus core genome (LCG). Based on advanced phylogeny of the proteins encoded by this LCG, we grouped the 20 strains into three main groups and defined core group genes present in all genomes of a single group, signature group genes shared in all genomes of one group but absent in all other Lactobacillus genomes, and Group‐specific ORFans present in core group genes of one group and absent in all other complete genomes. The latter are of specific value in defining the different groups of genomes. The study provides a platform for present individual comparisons as well as future analysis of new Lactobacillus genomes. PMID:21375712

  14. A genome blogger manifesto

    Directory of Open Access Journals (Sweden)

    Corpas Manuel

    2012-10-01

    Full Text Available Abstract Cheap prices for genomic testing have revolutionized consumers’ access to personal genomics. Exploration of personal genomes poses significant challenges for customers wishing to learn beyond provider customer reports. A vibrant community has spontaneously appeared blogging experiences and data as a way to learn about their personal genomes. No set of values has publicly been described to date encapsulating ideals and code of conduct for this community. Here I present a first attempt to address this vacuum based on my own personal experiences as genome blogger.

  15. Causes of genome instability

    DEFF Research Database (Denmark)

    Langie, Sabine A S; Koppen, Gudrun; Desaulniers, Daniel

    2015-01-01

    , genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other......Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus...... chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling...

  16. Rapid aneuploidy diagnosis of partial trisomy 7q (7q34→qter and partial monosomy 10q (10q26.12→qter by array comparative genomic hybridization using uncultured amniocytes

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2012-03-01

    Conclusion: aCGH is a useful tool for RAD of subtle chromosomal rearrangements in pregnancy, especially under the circumstance of a previous abnormal child with an unbalanced translocation derived from a parental subtle reciprocal translocation.

  17. Mixed infections and hybridisation in monogenean parasites.

    Science.gov (United States)

    Schelkle, Bettina; Faria, Patricia J; Johnson, Mireille B; van Oosterhout, Cock; Cable, Joanne

    2012-01-01

    Theory predicts that sexual reproduction promotes disease invasion by increasing the evolutionary potential of the parasite, whereas asexual reproduction tends to enhance establishment success and population growth rate. Gyrodactylid monogeneans are ubiquitous ectoparasites of teleost fish, and the evolutionary success of the specious Gyrodactylus genus is thought to be partly due to their use of various modes of reproduction. Gyrodactylus turnbulli is a natural parasite of the guppy (Poecilia reticulata), a small, tropical fish used as a model for behavioural, ecological and evolutionary studies. Using experimental infections and a recently developed microsatellite marker, we conclusively show that monogenean parasites reproduce sexually. Conservatively, we estimate that sexual recombination occurs and that between 3.7-10.9% of the parasites in our experimental crosses are hybrid genotypes with ancestors from different laboratory strains of G. turnbulli. We also provide evidence of hybrid vigour and/or inter-strain competition, which appeared to lead to a higher maximum parasite load in mixed infections. Finally, we demonstrate inbreeding avoidance for the first time in platyhelminths which may influence the distribution of parasites within a host and their subsequent exposure to the host's localized immune response. Combined reproductive modes and inbreeding avoidance may explain the extreme evolutionary diversification success of parasites such as Gyrodactylus, where host-parasite coevolution is punctuated by relatively frequent host switching.

  18. Mixed infections and hybridisation in monogenean parasites.

    Directory of Open Access Journals (Sweden)

    Bettina Schelkle

    Full Text Available Theory predicts that sexual reproduction promotes disease invasion by increasing the evolutionary potential of the parasite, whereas asexual reproduction tends to enhance establishment success and population growth rate. Gyrodactylid monogeneans are ubiquitous ectoparasites of teleost fish, and the evolutionary success of the specious Gyrodactylus genus is thought to be partly due to their use of various modes of reproduction. Gyrodactylus turnbulli is a natural parasite of the guppy (Poecilia reticulata, a small, tropical fish used as a model for behavioural, ecological and evolutionary studies. Using experimental infections and a recently developed microsatellite marker, we conclusively show that monogenean parasites reproduce sexually. Conservatively, we estimate that sexual recombination occurs and that between 3.7-10.9% of the parasites in our experimental crosses are hybrid genotypes with ancestors from different laboratory strains of G. turnbulli. We also provide evidence of hybrid vigour and/or inter-strain competition, which appeared to lead to a higher maximum parasite load in mixed infections. Finally, we demonstrate inbreeding avoidance for the first time in platyhelminths which may influence the distribution of parasites within a host and their subsequent exposure to the host's localized immune response. Combined reproductive modes and inbreeding avoidance may explain the extreme evolutionary diversification success of parasites such as Gyrodactylus, where host-parasite coevolution is punctuated by relatively frequent host switching.

  19. Genomic research in Eucalyptus.

    Science.gov (United States)

    Poke, Fiona S; Vaillancourt, René E; Potts, Brad M; Reid, James B

    2005-09-01

    Eucalyptus L'Hérit. is a genus comprised of more than 700 species that is of vital importance ecologically to Australia and to the forestry industry world-wide, being grown in plantations for the production of solid wood products as well as pulp for paper. With the sequencing of the genomes of Arabidopsis thaliana and Oryza sativa and the recent completion of the first tree genome sequence, Populus trichocarpa, attention has turned to the current status of genomic research in Eucalyptus. For several eucalypt species, large segregating families have been established, high-resolution genetic maps constructed and large EST databases generated. Collaborative efforts have been initiated for the integration of diverse genomic projects and will provide the framework for future research including exploiting the sequence of the entire eucalypt genome which is currently being sequenced. This review summarises the current position of genomic research in Eucalyptus and discusses the direction of future research.

  20. Bioinformatics decoding the genome

    CERN Multimedia

    CERN. Geneva; Deutsch, Sam; Michielin, Olivier; Thomas, Arthur; Descombes, Patrick

    2006-01-01

    Extracting the fundamental genomic sequence from the DNA From Genome to Sequence : Biology in the early 21st century has been radically transformed by the availability of the full genome sequences of an ever increasing number of life forms, from bacteria to major crop plants and to humans. The lecture will concentrate on the computational challenges associated with the production, storage and analysis of genome sequence data, with an emphasis on mammalian genomes. The quality and usability of genome sequences is increasingly conditioned by the careful integration of strategies for data collection and computational analysis, from the construction of maps and libraries to the assembly of raw data into sequence contigs and chromosome-sized scaffolds. Once the sequence is assembled, a major challenge is the mapping of biologically relevant information onto this sequence: promoters, introns and exons of protein-encoding genes, regulatory elements, functional RNAs, pseudogenes, transposons, etc. The methodological ...

  1. Genome packaging in viruses

    OpenAIRE

    Sun, Siyang; Rao, Venigalla B.; Rossmann, Michael G.

    2010-01-01

    Genome packaging is a fundamental process in a viral life cycle. Many viruses assemble preformed capsids into which the genomic material is subsequently packaged. These viruses use a packaging motor protein that is driven by the hydrolysis of ATP to condense the nucleic acids into a confined space. How these motor proteins package viral genomes had been poorly understood until recently, when a few X-ray crystal structures and cryo-electron microscopy structures became available. Here we discu...

  2. Fungal Genomics Program

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-03-12

    The JGI Fungal Genomics Program aims to scale up sequencing and analysis of fungal genomes to explore the diversity of fungi important for energy and the environment, and to promote functional studies on a system level. Combining new sequencing technologies and comparative genomics tools, JGI is now leading the world in fungal genome sequencing and analysis. Over 120 sequenced fungal genomes with analytical tools are available via MycoCosm (www.jgi.doe.gov/fungi), a web-portal for fungal biologists. Our model of interacting with user communities, unique among other sequencing centers, helps organize these communities, improves genome annotation and analysis work, and facilitates new larger-scale genomic projects. This resulted in 20 high-profile papers published in 2011 alone and contributing to the Genomics Encyclopedia of Fungi, which targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts). Our next grand challenges include larger scale exploration of fungal diversity (1000 fungal genomes), developing molecular tools for DOE-relevant model organisms, and analysis of complex systems and metagenomes.

  3. Evolutionary genomics of Entamoeba

    Science.gov (United States)

    Weedall, Gareth D.; Hall, Neil

    2011-01-01

    Entamoeba histolytica is a human pathogen that causes amoebic dysentery and leads to significant morbidity and mortality worldwide. Understanding the genome and evolution of the parasite will help explain how, when and why it causes disease. Here we review current knowledge about the evolutionary genomics of Entamoeba: how differences between the genomes of different species may help explain different phenotypes, and how variation among E. histolytica parasites reveals patterns of population structure. The imminent expansion of the amount genome data will greatly improve our knowledge of the genus and of pathogenic species within it. PMID:21288488

  4. Genomics of Clostridium tetani.

    Science.gov (United States)

    Brüggemann, Holger; Brzuszkiewicz, Elzbieta; Chapeton-Montes, Diana; Plourde, Lucile; Speck, Denis; Popoff, Michel R

    2015-05-01

    Genomic information about Clostridium tetani, the causative agent of the tetanus disease, is scarce. The genome of strain E88, a strain used in vaccine production, was sequenced about 10 years ago. One additional genome (strain 12124569) has recently been released. Here we report three new genomes of C. tetani and describe major differences among all five C. tetani genomes. They all harbor tetanus-toxin-encoding plasmids that contain highly conserved genes for TeNT (tetanus toxin), TetR (transcriptional regulator of TeNT) and ColT (collagenase), but substantially differ in other plasmid regions. The chromosomes share a large core genome that contains about 85% of all genes of a given chromosome. The non-core chromosome comprises mainly prophage-like genomic regions and genes encoding environmental interaction and defense functions (e.g. surface proteins, restriction-modification systems, toxin-antitoxin systems, CRISPR/Cas systems) and other fitness functions (e.g. transport systems, metabolic activities). This new genome information will help to assess the level of genome plasticity of the species C. tetani and provide the basis for detailed comparative studies. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  5. A genome-wide study reveals rare CNVs exclusive to extreme phenotypes of Alzheimer disease.

    Science.gov (United States)

    Rovelet-Lecrux, Anne; Legallic, Solenn; Wallon, David; Flaman, Jean-Michel; Martinaud, Olivier; Bombois, Stéphanie; Rollin-Sillaire, Adeline; Michon, Agnès; Le Ber, Isabelle; Pariente, Jérémie; Puel, Michèle; Paquet, Claire; Croisile, Bernard; Thomas-Antérion, Catherine; Vercelletto, Martine; Lévy, Richard; Frébourg, Thierry; Hannequin, Didier; Campion, Dominique

    2012-06-01

    Studying rare extreme forms of Alzheimer disease (AD) may prove to be a useful strategy in identifying new genes involved in monogenic determinism of AD. Amyloid precursor protein (APP), PSEN1, and PSEN2 mutations account for only 85% of autosomal dominant early-onset AD (ADEOAD) families. We hypothesised that rare copy number variants (CNVs) could be involved in ADEOAD families without mutations in known genes, as well as in rare sporadic young-onset AD cases. Using high-resolution array comparative genomic hybridisation, we assessed the presence of rare CNVs in 21 unrelated ADEOAD cases, having no alteration on known genes, and 12 sporadic AD cases, with an age of onset younger than 55 years. The analysis revealed the presence of 7 singleton CNVs (4 in ADEOAD and 3 in sporadic cases) absent in 1078 controls and 912 late-onset AD cases. Strikingly, 4 out of 7 rearrangements target genes (KLK6, SLC30A3, MEOX2, and FPR2) encoding proteins that are tightly related to amyloid-β peptide metabolism or signalling. Although these variants are individually rare and restricted to particular subgroups of patients, these findings support the causal role, in human pathology, of a set of genes coding for molecules suspected for a long time to modify Aβ metabolism or signalling, and for which animal or cellular models have already been developed.

  6. Computational genomics of hyperthermophiles

    NARCIS (Netherlands)

    Werken, van de H.J.G.

    2008-01-01

    With the ever increasing number of completely sequenced prokaryotic genomes and the subsequent use of functional genomics tools, e.g. DNA microarray and proteomics, computational data analysis and the integration of microbial and molecular data is inevitable. This thesis describes the computational

  7. The Lotus japonicus genome

    DEFF Research Database (Denmark)

    , carbon/nitrogen and secondary metabolism, as well as advances made in high-throughput genomic and genetic approaches. Research focusing on model plants has underpinned the recent growth in plant genomics and genetics and provided a basis for investigations of major crop species. In the legume family...

  8. Phanerochaete chrysosporium genomics

    Science.gov (United States)

    Luis F. Larrondo; Rafael Vicuna; Dan Cullen

    2005-01-01

    A high quality draft genome sequence has been generated for the lignocellulose-degrading basidiomycete Phanerochaete chrysosporium (Martinez et al. 2004). Analysis of the genome in the context of previously established genetics and physiology is presented. Transposable elements and their potential relationship to genes involved in lignin degradation are systematically...

  9. Genome-Scale Models

    DEFF Research Database (Denmark)

    Bergdahl, Basti; Sonnenschein, Nikolaus; Machado, Daniel

    2016-01-01

    An introduction to genome-scale models, how to build and use them, will be given in this chapter. Genome-scale models have become an important part of systems biology and metabolic engineering, and are increasingly used in research, both in academica and in industry, both for modeling chemical pr...

  10. Safeguarding genome integrity

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Syljuåsen, Randi G

    2012-01-01

    Mechanisms that preserve genome integrity are highly important during the normal life cycle of human cells. Loss of genome protective mechanisms can lead to the development of diseases such as cancer. Checkpoint kinases function in the cellular surveillance pathways that help cells to cope with DNA...

  11. Human genome I

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    An international conference, Human Genome I, was held Oct. 2-4, 1989 in San Diego, Calif. Selected speakers discussed: Current Status of the Genome Project; Technique Innovations; Interesting regions; Applications; and Organization - Different Views of Current and Future Science and Procedures. Posters, consisting of 119 presentations, were displayed during the sessions. 119 were indexed for inclusion to the Energy Data Base

  12. Breeding-assisted genomics.

    Science.gov (United States)

    Poland, Jesse

    2015-04-01

    The revolution of inexpensive sequencing has ushered in an unprecedented age of genomics. The promise of using this technology to accelerate plant breeding is being realized with a vision of genomics-assisted breeding that will lead to rapid genetic gain for expensive and difficult traits. The reality is now that robust phenotypic data is an increasing limiting resource to complement the current wealth of genomic information. While genomics has been hailed as the discipline to fundamentally change the scope of plant breeding, a more symbiotic relationship is likely to emerge. In the context of developing and evaluating large populations needed for functional genomics, none excel in this area more than plant breeders. While genetic studies have long relied on dedicated, well-structured populations, the resources dedicated to these populations in the context of readily available, inexpensive genotyping is making this philosophy less tractable relative to directly focusing functional genomics on material in breeding programs. Through shifting effort for basic genomic studies from dedicated structured populations, to capturing the entire scope of genetic determinants in breeding lines, we can move towards not only furthering our understanding of functional genomics in plants, but also rapidly improving crops for increased food security, availability and nutrition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Genomic innovations, transcriptional plasticity and gene loss underlying the evolution and divergence of two highly polyphagous and invasive Helicoverpa pest species.

    Science.gov (United States)

    Pearce, S L; Clarke, D F; East, P D; Elfekih, S; Gordon, K H J; Jermiin, L S; McGaughran, A; Oakeshott, J G; Papanikolaou, A; Perera, O P; Rane, R V; Richards, S; Tay, W T; Walsh, T K; Anderson, A; Anderson, C J; Asgari, S; Board, P G; Bretschneider, A; Campbell, P M; Chertemps, T; Christeller, J T; Coppin, C W; Downes, S J; Duan, G; Farnsworth, C A; Good, R T; Han, L B; Han, Y C; Hatje, K; Horne, I; Huang, Y P; Hughes, D S T; Jacquin-Joly, E; James, W; Jhangiani, S; Kollmar, M; Kuwar, S S; Li, S; Liu, N-Y; Maibeche, M T; Miller, J R; Montagne, N; Perry, T; Qu, J; Song, S V; Sutton, G G; Vogel, H; Walenz, B P; Xu, W; Zhang, H-J; Zou, Z; Batterham, P; Edwards, O R; Feyereisen, R; Gibbs, R A; Heckel, D G; McGrath, A; Robin, C; Scherer, S E; Worley, K C; Wu, Y D

    2017-07-31

    Helicoverpa armigera and Helicoverpa zea are major caterpillar pests of Old and New World agriculture, respectively. Both, particularly H. armigera, are extremely polyphagous, and H. armigera has developed resistance to many insecticides. Here we use comparative genomics, transcriptomics and resequencing to elucidate the genetic basis for their properties as pests. We find that, prior to their divergence about 1.5 Mya, the H. armigera/H. zea lineage had accumulated up to more than 100 more members of specific detoxification and digestion gene families and more than 100 extra gustatory receptor genes, compared to other lepidopterans with narrower host ranges. The two genomes remain very similar in gene content and order, but H. armigera is more polymorphic overall, and H. zea has lost several detoxification genes, as well as about 50 gustatory receptor genes. It also lacks certain genes and alleles conferring insecticide resistance found in H. armigera. Non-synonymous sites in the expanded gene families above are rapidly diverging, both between paralogues and between orthologues in the two species. Whole genome transcriptomic analyses of H. armigera larvae show widely divergent responses to different host plants, including responses among many of the duplicated detoxification and digestion genes. The extreme polyphagy of the two heliothines is associated with extensive amplification and neofunctionalisation of genes involved in host finding and use, coupled with versatile transcriptional responses on different hosts. H. armigera's invasion of the Americas in recent years means that hybridisation could generate populations that are both locally adapted and insecticide resistant.

  14. Musa sebagai Model Genom

    Directory of Open Access Journals (Sweden)

    RITA MEGIA

    2005-12-01

    Full Text Available During the meeting in Arlington, USA in 2001, the scientists grouped in PROMUSA agreed with the launching of the Global Musa Genomics Consortium. The Consortium aims to apply genomics technologies to the improvement of this important crop. These genome projects put banana as the third model species after Arabidopsis and rice that will be analyzed and sequenced. Comparing to Arabidopsis and rice, banana genome provides a unique and powerful insight into structural and in functional genomics that could not be found in those two species. This paper discussed these subjects-including the importance of banana as the fourth main food in the world, the evolution and biodiversity of this genetic resource and its parasite.

  15. Genomic Prediction in Barley

    DEFF Research Database (Denmark)

    Edriss, Vahid; Cericola, Fabio; Jensen, Jens D

    2015-01-01

    Genomic prediction uses markers (SNPs) across the whole genome to predict individual breeding values at an early growth stage potentially before large scale phenotyping. One of the applications of genomic prediction in plant breeding is to identify the best individual candidate lines to contribute...... to next generation. The main goal of this study was to see the potential of using genomic prediction in a commercial Barley breeding program. The data used in this study was from Nordic Seed company which is located in Denmark. Around 350 advanced lines were genotyped with 9K Barely chip from Illumina....... Traits used in this study were grain yield, plant height and heading date. Heading date is number days it takes after 1st June for plant to head. Heritabilities were 0.33, 0.44 and 0.48 for yield, height and heading, respectively for the average of nine plots. The GBLUP model was used for genomic...

  16. The genome editing revolution

    DEFF Research Database (Denmark)

    Stella, Stefano; Montoya, Guillermo

    2016-01-01

    -Cas system has become the main tool for genome editing in many laboratories. Currently the targeted genome editing technology has been used in many fields and may be a possible approach for human gene therapy. Furthermore, it can also be used to modifying the genomes of model organisms for studying human......In the last 10 years, we have witnessed a blooming of targeted genome editing systems and applications. The area was revolutionized by the discovery and characterization of the transcription activator-like effector proteins, which are easier to engineer to target new DNA sequences than...... sequence). This ribonucleoprotein complex protects bacteria from invading DNAs, and it was adapted to be used in genome editing. The CRISPR ribonucleic acid (RNA) molecule guides to the specific DNA site the Cas9 nuclease to cleave the DNA target. Two years and more than 1000 publications later, the CRISPR...

  17. Specific patterns of gene space organisation revealed in wheat by using the combination of barley and wheat genomic resources

    Directory of Open Access Journals (Sweden)

    Waugh Robbie

    2010-12-01

    Full Text Available Abstract Background Because of its size, allohexaploid nature and high repeat content, the wheat genome has always been perceived as too complex for efficient molecular studies. We recently constructed the first physical map of a wheat chromosome (3B. However gene mapping is still laborious in wheat because of high redundancy between the three homoeologous genomes. In contrast, in the closely related diploid species, barley, numerous gene-based markers have been developed. This study aims at combining the unique genomic resources developed in wheat and barley to decipher the organisation of gene space on wheat chromosome 3B. Results Three dimensional pools of the minimal tiling path of wheat chromosome 3B physical map were hybridised to a barley Agilent 15K expression microarray. This led to the fine mapping of 738 barley orthologous genes on wheat chromosome 3B. In addition, comparative analyses revealed that 68% of the genes identified were syntenic between the wheat chromosome 3B and barley chromosome 3 H and 59% between wheat chromosome 3B and rice chromosome 1, together with some wheat-specific rearrangements. Finally, it indicated an increasing gradient of gene density from the centromere to the telomeres positively correlated with the number of genes clustered in islands on wheat chromosome 3B. Conclusion Our study shows that novel structural genomics resources now available in wheat and barley can be combined efficiently to overcome specific problems of genetic anchoring of physical contigs in wheat and to perform high-resolution comparative analyses with rice for deciphering the organisation of the wheat gene space.

  18. Phytozome Comparative Plant Genomics Portal

    Energy Technology Data Exchange (ETDEWEB)

    Goodstein, David; Batra, Sajeev; Carlson, Joseph; Hayes, Richard; Phillips, Jeremy; Shu, Shengqiang; Schmutz, Jeremy; Rokhsar, Daniel

    2014-09-09

    The Dept. of Energy Joint Genome Institute is a genomics user facility supporting DOE mission science in the areas of Bioenergy, Carbon Cycling, and Biogeochemistry. The Plant Program at the JGI applies genomic, analytical, computational and informatics platforms and methods to: 1. Understand and accelerate the improvement (domestication) of bioenergy crops 2. Characterize and moderate plant response to climate change 3. Use comparative genomics to identify constrained elements and infer gene function 4. Build high quality genomic resource platforms of JGI Plant Flagship genomes for functional and experimental work 5. Expand functional genomic resources for Plant Flagship genomes

  19. Personal genomes, participatory genomics and the anonymity ...

    Indian Academy of Sciences (India)

    2014-12-02

    Dec 2, 2014 ... gies which have enabled miniaturization, large-scale paral- lelization and improved readout coupled with highly scala- ble data capture and analysis tools, commonly known as. 'next generation' sequencing technologies (Mardis 2008). The cost of whole genome sequencing has been expected to be as ...

  20. The Banana Genome Hub

    Science.gov (United States)

    Droc, Gaëtan; Larivière, Delphine; Guignon, Valentin; Yahiaoui, Nabila; This, Dominique; Garsmeur, Olivier; Dereeper, Alexis; Hamelin, Chantal; Argout, Xavier; Dufayard, Jean-François; Lengelle, Juliette; Baurens, Franc-Christophe; Cenci, Alberto; Pitollat, Bertrand; D’Hont, Angélique; Ruiz, Manuel; Rouard, Mathieu; Bocs, Stéphanie

    2013-01-01

    Banana is one of the world’s favorite fruits and one of the most important crops for developing countries. The banana reference genome sequence (Musa acuminata) was recently released. Given the taxonomic position of Musa, the completed genomic sequence has particular comparative value to provide fresh insights about the evolution of the monocotyledons. The study of the banana genome has been enhanced by a number of tools and resources that allows harnessing its sequence. First, we set up essential tools such as a Community Annotation System, phylogenomics resources and metabolic pathways. Then, to support post-genomic efforts, we improved banana existing systems (e.g. web front end, query builder), we integrated available Musa data into generic systems (e.g. markers and genetic maps, synteny blocks), we have made interoperable with the banana hub, other existing systems containing Musa data (e.g. transcriptomics, rice reference genome, workflow manager) and finally, we generated new results from sequence analyses (e.g. SNP and polymorphism analysis). Several uses cases illustrate how the Banana Genome Hub can be used to study gene families. Overall, with this collaborative effort, we discuss the importance of the interoperability toward data integration between existing information systems. Database URL: http://banana-genome.cirad.fr/ PMID:23707967

  1. Genomic signal processing

    CERN Document Server

    Shmulevich, Ilya

    2007-01-01

    Genomic signal processing (GSP) can be defined as the analysis, processing, and use of genomic signals to gain biological knowledge, and the translation of that knowledge into systems-based applications that can be used to diagnose and treat genetic diseases. Situated at the crossroads of engineering, biology, mathematics, statistics, and computer science, GSP requires the development of both nonlinear dynamical models that adequately represent genomic regulation, and diagnostic and therapeutic tools based on these models. This book facilitates these developments by providing rigorous mathema

  2. Genomic taxonomy of vibrios

    Directory of Open Access Journals (Sweden)

    Iida Tetsuya

    2009-10-01

    Full Text Available Abstract Background Vibrio taxonomy has been based on a polyphasic approach. In this study, we retrieve useful taxonomic information (i.e. data that can be used to distinguish different taxonomic levels, such as species and genera from 32 genome sequences of different vibrio species. We use a variety of tools to explore the taxonomic relationship between the sequenced genomes, including Multilocus Sequence Analysis (MLSA, supertrees, Average Amino Acid Identity (AAI, genomic signatures, and Genome BLAST atlases. Our aim is to analyse the usefulness of these tools for species identification in vibrios. Results We have generated four new genome sequences of three Vibrio species, i.e., V. alginolyticus 40B, V. harveyi-like 1DA3, and V. mimicus strains VM573 and VM603, and present a broad analyses of these genomes along with other sequenced Vibrio species. The genome atlas and pangenome plots provide a tantalizing image of the genomic differences that occur between closely related sister species, e.g. V. cholerae and V. mimicus. The vibrio pangenome contains around 26504 genes. The V. cholerae core genome and pangenome consist of 1520 and 6923 genes, respectively. Pangenomes might allow different strains of V. cholerae to occupy different niches. MLSA and supertree analyses resulted in a similar phylogenetic picture, with a clear distinction of four groups (Vibrio core group, V. cholerae-V. mimicus, Aliivibrio spp., and Photobacterium spp.. A Vibrio species is defined as a group of strains that share > 95% DNA identity in MLSA and supertree analysis, > 96% AAI, ≤ 10 genome signature dissimilarity, and > 61% proteome identity. Strains of the same species and species of the same genus will form monophyletic groups on the basis of MLSA and supertree. Conclusion The combination of different analytical and bioinformatics tools will enable the most accurate species identification through genomic computational analysis. This endeavour will culminate in

  3. Traditional medicine and genomics

    Directory of Open Access Journals (Sweden)

    Kalpana Joshi

    2010-01-01

    Full Text Available ′Omics′ developments in the form of genomics, proteomics and metabolomics have increased the impetus of traditional medicine research. Studies exploring the genomic, proteomic and metabolomic basis of human constitutional types based on Ayurveda and other systems of oriental medicine are becoming popular. Such studies remain important to developing better understanding of human variations and individual differences. Countries like India, Korea, China and Japan are investing in research on evidence-based traditional medicines and scientific validation of fundamental principles. This review provides an account of studies addressing relationships between traditional medicine and genomics.

  4. Traditional medicine and genomics.

    Science.gov (United States)

    Joshi, Kalpana; Ghodke, Yogita; Shintre, Pooja

    2010-01-01

    'Omics' developments in the form of genomics, proteomics and metabolomics have increased the impetus of traditional medicine research. Studies exploring the genomic, proteomic and metabolomic basis of human constitutional types based on Ayurveda and other systems of oriental medicine are becoming popular. Such studies remain important to developing better understanding of human variations and individual differences. Countries like India, Korea, China and Japan are investing in research on evidence-based traditional medicines and scientific validation of fundamental principles. This review provides an account of studies addressing relationships between traditional medicine and genomics.

  5. Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  6. What Is a Genome?

    Directory of Open Access Journals (Sweden)

    Aaron David Goldman

    2016-07-01

    Full Text Available The genome is often described as the information repository of an organism. Whether millions or billions of letters of DNA, its transmission across generations confers the principal medium for inheritance of organismal traits. Several emerging areas of research demonstrate that this definition is an oversimplification. Here, we explore ways in which a deeper understanding of genomic diversity and cell physiology is challenging the concepts of physical permanence attached to the genome as well as its role as the sole information source for an organism.

  7. Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, W. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Fortson, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Joyce, G. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Kimble, H. J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Max, C. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Prince, T. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, P. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Woodin, W. H. [The MITRE Corporation, McLean, VA (US). JASON Program Office

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  8. Genomic insights into tuberculosis.

    Science.gov (United States)

    Galagan, James E

    2014-05-01

    Prevalent since pre-history, human tuberculosis - caused by the pathogen Mycobacterium tuberculosis - remains a major source of death worldwide. Moreover, increasing drug resistance poses the threat of disease resurgence. However, the expanding application of genomic techniques is providing new avenues for combating this old foe. Whole-genome sequencing, comparative genomics and systems biology are generating new insights into the origins and ongoing evolution of M. tuberculosis, as well as the molecular basis for its pathogenicity. These have important implications for our perspective of the disease, development of new drugs and vaccines, and treatment of patients using existing therapeutics.

  9. Mouse Genome Informatics (MGI)

    Data.gov (United States)

    U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...

  10. Rice Genomics: Gene discovery

    Indian Academy of Sciences (India)

    There is a need for discovering candidate genes( a lot of them all over the genome indeed ) and the unlimited allelic variation that can productively take over rice metabolism when cellular water content falls below threshold levels.

  11. Lophotrochozoan mitochondrial genomes

    Energy Technology Data Exchange (ETDEWEB)

    Valles, Yvonne; Boore, Jeffrey L.

    2005-10-01

    Progress in both molecular techniques and phylogeneticmethods has challenged many of the interpretations of traditionaltaxonomy. One example is in the recognition of the animal superphylumLophotrochozoa (annelids, mollusks, echiurans, platyhelminthes,brachiopods, and other phyla), although the relationships within thisgroup and the inclusion of some phyla remain uncertain. While much ofthis progress in phylogenetic reconstruction has been based on comparingsingle gene sequences, we are beginning to see the potential of comparinglarge-scale features of genomes, such as the relative order of genes.Even though tremendous progress is being made on the sequencedetermination of whole nuclear genomes, the dataset of choice forgenome-level characters for many animals across a broad taxonomic rangeremains mitochondrial genomes. We review here what is known aboutmitochondrial genomes of the lophotrochozoans and discuss the promisethat this dataset will enable insight into theirrelationships.

  12. Genomic definition of species

    Energy Technology Data Exchange (ETDEWEB)

    Crkvenjakov, R.; Drmanac, R.

    1991-07-01

    The subject of this paper is the definition of species based on the assumption that genome is the fundamental level for the origin and maintenance of biological diversity. For this view to be logically consistent it is necessary to assume the existence and operation of the new law which we call genome law. For this reason the genome law is included in the explanation of species phenomenon presented here even if its precise formulation and elaboration are left for the future. The intellectual underpinnings of this definition can be traced to Goldschmidt. We wish to explore some philosophical aspects of the definition of species in terms of the genome. The point of proposing the definition on these grounds is that any real advance in evolutionary theory has to be correct in both its philosophy and its science.

  13. The rise of genomics.

    Science.gov (United States)

    Weissenbach, Jean

    2016-01-01

    A brief history of the development of genomics is provided. Complete sequencing of genomes of uni- and multicellular organisms is based on important progress in sequencing and bioinformatics. Evolution of these methods is ongoing and has triggered an explosion in data production and analysis. Initial analyses focused on the inventory of genes encoding proteins. Completeness and quality of gene prediction remains crucial. Genome analyses profoundly modified our views on evolution, biodiversity and contributed to the detection of new functions, yet to be fully elucidated, such as those fulfilled by non-coding RNAs. Genomics has become the basis for the study of biology and provides the molecular support for a bunch of large-scale studies, the omics. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  14. Annotating individual human genomes.

    Science.gov (United States)

    Torkamani, Ali; Scott-Van Zeeland, Ashley A; Topol, Eric J; Schork, Nicholas J

    2011-10-01

    Advances in DNA sequencing technologies have made it possible to rapidly, accurately and affordably sequence entire individual human genomes. As impressive as this ability seems, however, it will not likely amount to much if one cannot extract meaningful information from individual sequence data. Annotating variations within individual genomes and providing information about their biological or phenotypic impact will thus be crucially important in moving individual sequencing projects forward, especially in the context of the clinical use of sequence information. In this paper we consider the various ways in which one might annotate individual sequence variations and point out limitations in the available methods for doing so. It is arguable that, in the foreseeable future, DNA sequencing of individual genomes will become routine for clinical, research, forensic, and personal purposes. We therefore also consider directions and areas for further research in annotating genomic variants. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. ANNOTATING INDIVIDUAL HUMAN GENOMES*

    Science.gov (United States)

    Torkamani, Ali; Scott-Van Zeeland, Ashley A.; Topol, Eric J.; Schork, Nicholas J.

    2014-01-01

    Advances in DNA sequencing technologies have made it possible to rapidly, accurately and affordably sequence entire individual human genomes. As impressive as this ability seems, however, it will not likely to amount to much if one cannot extract meaningful information from individual sequence data. Annotating variations within individual genomes and providing information about their biological or phenotypic impact will thus be crucially important in moving individual sequencing projects forward, especially in the context of the clinical use of sequence information. In this paper we consider the various ways in which one might annotate individual sequence variations and point out limitations in the available methods for doing so. It is arguable that, in the foreseeable future, DNA sequencing of individual genomes will become routine for clinical, research, forensic, and personal purposes. We therefore also consider directions and areas for further research in annotating genomic variants. PMID:21839162

  16. Epidemiology & Genomics Research Program

    Science.gov (United States)

    The Epidemiology and Genomics Research Program, in the National Cancer Institute's Division of Cancer Control and Population Sciences, funds research in human populations to understand the determinants of cancer occurrence and outcomes.

  17. Genomics and fish adaptation

    Directory of Open Access Journals (Sweden)

    Agostinho Antunes

    2015-12-01

    Full Text Available The completion of the human genome sequencing in 2003 opened a new perspective into the importance of whole genome sequencing projects, and currently multiple species are having their genomes completed sequenced, from simple organisms, such as bacteria, to more complex taxa, such as mammals. This voluminous sequencing data generated across multiple organisms provides also the framework to better understand the genetic makeup of such species and related ones, allowing to explore the genetic changes underlining the evolution of diverse phenotypic traits. Here, recent results from our group retrieved from comparative evolutionary genomic analyses of varied fish species will be considered to exemplify how gene novelty and gene enhancement by positive selection might have been determinant in the success of adaptive radiations into diverse habitats and lifestyles.

  18. Beyond barcoding: a mitochondrial genomics approach to molecular phylogenetics and diagnostics of blowflies (Diptera: Calliphoridae).

    Science.gov (United States)

    Nelson, Leigh A; Lambkin, Christine L; Batterham, Philip; Wallman, James F; Dowton, Mark; Whiting, Michael F; Yeates, David K; Cameron, Stephen L

    2012-12-15

    -grouping of Luciliinae with Calliphorinae. Relationships within Chrysomya were not well resolved. Whole mt genome data, supported the previously demonstrated paraphyly of Lucilia cuprina with respect to L. sericata and allowed us to conclude that it is due to hybrid introgression prior to the last common ancestor of modern sericata populations, rather than due to recent hybridisation, nuclear pseudogenes or incomplete lineage sorting. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. The human genome project

    International Nuclear Information System (INIS)

    Worton, R.

    1996-01-01

    The Human Genome Project is a massive international research project, costing 3 to 5 billion dollars and expected to take 15 years, which will identify the all the genes in the human genome - i.e. the complete sequence of bases in human DNA. The prize will be the ability to identify genes causing or predisposing to disease, and in some cases the development of gene therapy, but this new knowledge will raise important ethical issues

  20. The Genomic Standards Consortium

    DEFF Research Database (Denmark)

    Field, Dawn; Amaral-Zettler, Linda; Cochrane, Guy

    2011-01-01

    A vast and rich body of information has grown up as a result of the world's enthusiasm for 'omics technologies. Finding ways to describe and make available this information that maximise its usefulness has become a major effort across the 'omics world. At the heart of this effort is the Genomic S...... and quantity of contextual information about our public collections of genomes, metagenomes, and marker gene sequences....

  1. Decoding the human genome

    CERN Document Server

    CERN. Geneva. Audiovisual Unit; Antonerakis, S E

    2002-01-01

    Decoding the Human genome is a very up-to-date topic, raising several questions besides purely scientific, in view of the two competing teams (public and private), the ethics of using the results, and the fact that the project went apparently faster and easier than expected. The lecture series will address the following chapters: Scientific basis and challenges. Ethical and social aspects of genomics.

  2. Human Germline Genome Editing

    OpenAIRE

    Ormond, Kelly E.; Mortlock, Douglas P.; Scholes, Derek T.; Bombard, Yvonne; Brody, Lawrence C.; Faucett, W. Andrew; Garrison, Nanibaa’ A.; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E.

    2017-01-01

    With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Gen...

  3. Molluscan Evolutionary Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Simison, W. Brian; Boore, Jeffrey L.

    2005-12-01

    In the last 20 years there have been dramatic advances in techniques of high-throughput DNA sequencing, most recently accelerated by the Human Genome Project, a program that has determined the three billion base pair code on which we are based. Now this tremendous capability is being directed at other genome targets that are being sampled across the broad range of life. This opens up opportunities as never before for evolutionary and organismal biologists to address questions of both processes and patterns of organismal change. We stand at the dawn of a new 'modern synthesis' period, paralleling that of the early 20th century when the fledgling field of genetics first identified the underlying basis for Darwin's theory. We must now unite the efforts of systematists, paleontologists, mathematicians, computer programmers, molecular biologists, developmental biologists, and others in the pursuit of discovering what genomics can teach us about the diversity of life. Genome-level sampling for mollusks to date has mostly been limited to mitochondrial genomes and it is likely that these will continue to provide the best targets for broad phylogenetic sampling in the near future. However, we are just beginning to see an inroad into complete nuclear genome sequencing, with several mollusks and other eutrochozoans having been selected for work about to begin. Here, we provide an overview of the state of molluscan mitochondrial genomics, highlight a few of the discoveries from this research, outline the promise of broadening this dataset, describe upcoming projects to sequence whole mollusk nuclear genomes, and challenge the community to prepare for making the best use of these data.

  4. Genome sequencing and molecular characterisation of Staphylococcus aureus ST772-MRSA-V, "Bengal Bay Clone".

    Science.gov (United States)

    Monecke, Stefan; Baier, Vico; Coombs, Geoffrey W; Slickers, Peter; Ziegler, Albrecht; Ehricht, Ralf

    2013-12-20

    The PVL-positive ST772-MRSA-V is an emerging community-associated (CA-) MRSA clone that has been named Bengal Bay Clone since most patients have epidemiological connections to the Indian subcontinent. It is found increasingly common in other areas of the world. One isolate of ST772-MRSA-V was sequenced using the Illumina Genome Analyzer System. After initial assembling the multiple sequence contigs were analysed using different in-house annotation scripts. Results were compared to microarray hybridisation results of clinical isolates of ST772-MRSA-V, of related strains and to another ST772-MRSA-V genome sequence. According to MLST e-burst analysis, ST772-MRSA-V belongs to Clonal Complex (CC)1, differing from ST1 only in one MLST allele (pta-22). However, there are several additional differences including agr alleles (group II rather than III), capsule type (5 rather than 8), the presence of the egc enterotoxin gene cluster and of the enterotoxin homologue ORF CM14 as well as the absence of the enterotoxin H gene seh. Enterotoxin genes sec and sel are present. ST772-MRSA-V harbours the genes encoding enterotoxin A (sea) and PVL (lukS/F-PV). Both are located on the same prophage. ST772-MRSA-V may have emerged from the same lineage as globally spread CC1 and CC5 strains. It has acquired a variety of virulence factors, and for a CA-MRSA strain it has an unusually high number of genes associated with antibiotic resistance.

  5. Human social genomics.

    Directory of Open Access Journals (Sweden)

    Steven W Cole

    2014-08-01

    Full Text Available A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural "social signal transduction" pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving.

  6. RadGenomics project

    International Nuclear Information System (INIS)

    Iwakawa, Mayumi; Imai, Takashi; Harada, Yoshinobu

    2002-01-01

    Human health is determined by a complex interplay of factors, predominantly between genetic susceptibility, environmental conditions and aging. The ultimate aim of the RadGenomics (Radiation Genomics) project is to understand the implications of heterogeneity in responses to ionizing radiation arising from genetic variation between individuals in the human population. The rapid progression of the human genome sequencing and the recent development of new technologies in molecular genetics are providing us with new opportunities to understand the genetic basis of individual differences in susceptibility to natural and/or artificial environmental factors, including radiation exposure. The RadGenomics project will inevitably lead to improved protocols for personalized radiotherapy and reductions in the potential side effects of such treatment. The project will contribute to future research into the molecular mechanisms of radiation sensitivity in humans and will stimulate the development of new high-throughput technologies for a broader application of biological and medical sciences. The staff members are specialists in a variety of fields, including genome science, radiation biology, medical science, molecular biology, and informatics, and have joined the RadGenomics project from various universities, companies, and research institutes. The project started in April 2001. (author)

  7. How the genome folds

    Science.gov (United States)

    Lieberman Aiden, Erez

    2012-02-01

    I describe Hi-C, a novel technology for probing the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. Working with collaborators at the Broad Institute and UMass Medical School, we used Hi-C to construct spatial proximity maps of the human genome at a resolution of 1Mb. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

  8. Comparative Genome Viewer

    International Nuclear Information System (INIS)

    Molineris, I.; Sales, G.

    2009-01-01

    The amount of information about genomes, both in the form of complete sequences and annotations, has been exponentially increasing in the last few years. As a result there is the need for tools providing a graphical representation of such information that should be comprehensive and intuitive. Visual representation is especially important in the comparative genomics field since it should provide a combined view of data belonging to different genomes. We believe that existing tools are limited in this respect as they focus on a single genome at a time (conservation histograms) or compress alignment representation to a single dimension. We have therefore developed a web-based tool called Comparative Genome Viewer (Cgv): it integrates a bidimensional representation of alignments between two regions, both at small and big scales, with the richness of annotations present in other genome browsers. We give access to our system through a web-based interface that provides the user with an interactive representation that can be updated in real time using the mouse to move from region to region and to zoom in on interesting details.

  9. Comparative Genomics of Cryptosporidium

    Directory of Open Access Journals (Sweden)

    Aurélien J. Mazurie

    2013-01-01

    Full Text Available Until recently, the apicomplexan parasites, Cryptosporidium hominis and C. parvum, were considered the same species. However, the two parasites, now considered distinct species, exhibit significant differences in host range, infectivity, and pathogenicity, and their sequenced genomes exhibit only 95–97% identity. The availability of the complete genome sequences of these organisms provides the potential to identify the genetic variations that are responsible for the phenotypic differences between the two parasites. We compared the genome organization and structure, gene composition, the metabolic and other pathways, and the local sequence identity between the genes of these two Cryptosporidium species. Our observations show that the phenotypic differences between C. hominis and C. parvum are not due to gross genome rearrangements, structural alterations, gene deletions or insertions, metabolic capabilities, or other obvious genomic alterations. Rather, the results indicate that these genomes exhibit a remarkable structural and compositional conservation and suggest that the phenotypic differences observed are due to subtle variations in the sequences of proteins that act at the interface between the parasite and its host.

  10. Female-to-male sex reversal associated with unique Xp21.2 deletion disrupting genomic regulatory architecture of the dosage-sensitive sex reversal region.

    Science.gov (United States)

    Dangle, Pankaj; Touzon, María Sol; Reyes-Múgica, Miguel; Witchel, Selma F; Rajkovic, Aleksandar; Schneck, Francis X; Yatsenko, Svetlana A

    2017-10-01

    The XX male disorder of sex development (DSD) is a rare condition that is most commonly associated with the presence of the SRY gene on one of the X chromosomes due to unequal crossing-over between sex chromosomes during spermatogenesis. However, in about 20% of the XX male individuals, SRY is missing, although these persons have at least some testis differentiation. The genetic basis of genital ambiguity and the mechanisms triggering testis development in such patients remain unknown. The proband with 46,XX SRY -negative testicular DSD was screened for point mutations by whole exome sequencing and CNVs using a high-resolution DSD gene-targeted and whole genome array comparative genomic hybridisation. The identified Xp21.2 genomic alteration was further characterised by direct sequencing of the breakpoint junctions and bioinformatics analysis. A unique, 80 kb microdeletion removing the regulatory sequences and the NR0B1 gene was detected by microarray analysis. This deletion disturbs the human-specific genomic architecture of the Xp21.2 dosage-sensitive sex (DSS) reversal region in the XX patient with male-appearing ambiguous genitalia and ovotestis. Duplication of the DSS region containing the MAGEB and NR0B1 genes has been implicated in testis repression and sex reversal. Identification of this microdeletion highlights the importance of genomic integrity in the regulation and interaction of sex determining genes during gonadal development. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. A feasible strategy of preimplantation genetic diagnosis for carriers with chromosomal translocation: Using blastocyst biopsy and array comparative genomic hybridization

    Directory of Open Access Journals (Sweden)

    Chu-Chun Huang

    2013-09-01

    Conclusion: Our study demonstrates an effective PGD strategy with promising outcomes. Blastocyst biopsy can retrieve more genetic material and may provide more reliable results, and aCGH offers not only detection of chromosomal translocation but also more comprehensive analysis of 24 chromosomes than traditional FISH. More cases are needed to verify our results and this strategy might be considered in general clinical practice.

  12. Genomic Prediction from Whole Genome Sequence in Livestock: The 1000 Bull Genomes Project

    DEFF Research Database (Denmark)

    Hayes, Benjamin J; MacLeod, Iona M; Daetwyler, Hans D

    Advantages of using whole genome sequence data to predict genomic estimated breeding values (GEBV) include better persistence of accuracy of GEBV across generations and more accurate GEBV across breeds. The 1000 Bull Genomes Project provides a database of whole genome sequenced key ancestor bulls...

  13. A Review on Genomics APIs

    Directory of Open Access Journals (Sweden)

    Rajeswari Swaminathan

    2016-01-01

    Full Text Available The constant improvement and falling prices of whole human genome Next Generation Sequencing (NGS has resulted in rapid adoption of genomic information at both clinics and research institutions. Considered together, the complexity of genomics data, due to its large volume and diversity along with the need for genomic data sharing, has resulted in the creation of Application Programming Interface (API for secure, modular, interoperable access to genomic data from different applications, platforms, and even organizations. The Genomics APIs are a set of special protocols that assist software developers in dealing with multiple genomic data sources for building seamless, interoperable applications leading to the advancement of both genomic and clinical research. These APIs help define a standard for retrieval of genomic data from multiple sources as well as to better package genomic information for integration with Electronic Health Records. This review covers three currently available Genomics APIs: a Google Genomics, b SMART Genomics, and c 23andMe. The functionalities, reference implementations (if available and authentication protocols of each API are reviewed. A comparative analysis of the different features across the three APIs is provided in the Discussion section. Though Genomics APIs are still under active development and have yet to reach widespread adoption, they hold the promise to make building of complicated genomics applications easier with downstream constructive effects on healthcare.

  14. The genetic landscape of infantile spasms.

    Science.gov (United States)

    Michaud, Jacques L; Lachance, Mathieu; Hamdan, Fadi F; Carmant, Lionel; Lortie, Anne; Diadori, Paola; Major, Philippe; Meijer, Inge A; Lemyre, Emmanuelle; Cossette, Patrick; Mefford, Heather C; Rouleau, Guy A; Rossignol, Elsa

    2014-09-15

    Infantile spasms (IS) is an early-onset epileptic encephalopathy of unknown etiology in ∼40% of patients. We hypothesized that unexplained IS cases represent a large collection of rare single-gene disorders. We investigated 44 children with unexplained IS using comparative genomic hybridisation arrays (aCGH) (n = 44) followed by targeted sequencing of 35 known epilepsy genes (n = 8) or whole-exome sequencing (WES) of familial trios (n = 18) to search for rare inherited or de novo mutations. aCGH analysis revealed de novo variants in 7% of patients (n = 3/44), including a distal 16p11.2 duplication, a 15q11.1q13.1 tetrasomy and a 2q21.3-q22.2 deletion. Furthermore, it identified a pathogenic maternally inherited Xp11.2 duplication. Targeted sequencing was informative for ARX (n = 1/14) and STXBP1 (n = 1/8). In contrast, sequencing of a panel of 35 known epileptic encephalopathy genes (n = 8) did not identify further mutations. Finally, WES (n = 18) was very informative, with an excess of de novo mutations identified in genes predicted to be involved in neurodevelopmental processes and/or known to be intolerant to functional variations. Several pathogenic mutations were identified, including de novo mutations in STXBP1, CASK and ALG13, as well as recessive mutations in PNPO and ADSL, together explaining 28% of cases (5/18). In addition, WES identified 1-3 de novo variants in 64% of remaining probands, pointing to several interesting candidate genes. Our results indicate that IS are genetically heterogeneous with a major contribution of de novo mutations and that WES is significantly superior to targeted re-sequencing in identifying detrimental genetic variants involved in IS. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Genomes to Proteomes

    Energy Technology Data Exchange (ETDEWEB)

    Panisko, Ellen A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Grigoriev, Igor [USDOE Joint Genome Inst., Walnut Creek, CA (United States); Daly, Don S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Webb-Robertson, Bobbie-Jo [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Baker, Scott E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2009-03-01

    Biologists are awash with genomic sequence data. In large part, this is due to the rapid acceleration in the generation of DNA sequence that occurred as public and private research institutes raced to sequence the human genome. In parallel with the large human genome effort, mostly smaller genomes of other important model organisms were sequenced. Projects following on these initial efforts have made use of technological advances and the DNA sequencing infrastructure that was built for the human and other organism genome projects. As a result, the genome sequences of many organisms are available in high quality draft form. While in many ways this is good news, there are limitations to the biological insights that can be gleaned from DNA sequences alone; genome sequences offer only a bird's eye view of the biological processes endemic to an organism or community. Fortunately, the genome sequences now being produced at such a high rate can serve as the foundation for other global experimental platforms such as proteomics. Proteomic methods offer a snapshot of the proteins present at a point in time for a given biological sample. Current global proteomics methods combine enzymatic digestion, separations, mass spectrometry and database searching for peptide identification. One key aspect of proteomics is the prediction of peptide sequences from mass spectrometry data. Global proteomic analysis uses computational matching of experimental mass spectra with predicted spectra based on databases of gene models that are often generated computationally. Thus, the quality of gene models predicted from a genome sequence is crucial in the generation of high quality peptide identifications. Once peptides are identified they can be assigned to their parent protein. Proteins identified as expressed in a given experiment are most useful when compared to other expressed proteins in a larger biological context or biochemical pathway. In this chapter we will discuss the automatic

  16. Genome Sequences of Oryza Species

    KAUST Repository

    Kumagai, Masahiko

    2018-02-14

    This chapter summarizes recent data obtained from genome sequencing, annotation projects, and studies on the genome diversity of Oryza sativa and related Oryza species. O. sativa, commonly known as Asian rice, is the first monocot species whose complete genome sequence was deciphered based on physical mapping by an international collaborative effort. This genome, along with its accurate and comprehensive annotation, has become an indispensable foundation for crop genomics and breeding. With the development of innovative sequencing technologies, genomic studies of O. sativa have dramatically increased; in particular, a large number of cultivars and wild accessions have been sequenced and compared with the reference rice genome. Since de novo genome sequencing has become cost-effective, the genome of African cultivated rice, O. glaberrima, has also been determined. Comparative genomic studies have highlighted the independent domestication processes of different rice species, but it also turned out that Asian and African rice share a common gene set that has experienced similar artificial selection. An international project aimed at constructing reference genomes and examining the genome diversity of wild Oryza species is currently underway, and the genomes of some species are publicly available. This project provides a platform for investigations such as the evolution, development, polyploidization, and improvement of crops. Studies on the genomic diversity of Oryza species, including wild species, should provide new insights to solve the problem of growing food demands in the face of rapid climatic changes.

  17. Genomics of Preterm Birth

    Science.gov (United States)

    Swaggart, Kayleigh A.; Pavlicev, Mihaela; Muglia, Louis J.

    2015-01-01

    The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms. PMID:25646385

  18. Genomics of Salmonella Species

    Science.gov (United States)

    Canals, Rocio; McClelland, Michael; Santiviago, Carlos A.; Andrews-Polymenis, Helene

    Progress in the study of Salmonella survival, colonization, and virulence has increased rapidly with the advent of complete genome sequencing and higher capacity assays for transcriptomic and proteomic analysis. Although many of these techniques have yet to be used to directly assay Salmonella growth on foods, these assays are currently in use to determine Salmonella factors necessary for growth in animal models including livestock animals and in in vitro conditions that mimic many different environments. As sequencing of the Salmonella genome and microarray analysis have revolutionized genomics and transcriptomics of salmonellae over the last decade, so are new high-throughput sequencing technologies currently accelerating the pace of our studies and allowing us to approach complex problems that were not previously experimentally tractable.

  19. Yeast genome sequencing:

    DEFF Research Database (Denmark)

    Piskur, Jure; Langkjær, Rikke Breinhold

    2004-01-01

    For decades, unicellular yeasts have been general models to help understand the eukaryotic cell and also our own biology. Recently, over a dozen yeast genomes have been sequenced, providing the basis to resolve several complex biological questions. Analysis of the novel sequence data has shown...... that the minimum number of genes from each species that need to be compared to produce a reliable phylogeny is about 20. Yeast has also become an attractive model to study speciation in eukaryotes, especially to understand molecular mechanisms behind the establishment of reproductive isolation. Comparison...... they are short and degenerate and occupy different positions. Comparative genomics helps to understand the origin of yeasts and points out crucial molecular events in yeast evolutionary history, such as whole-genome duplication and horizontal gene transfer(s). In addition, the accumulating sequence data provide...

  20. Genomics of Volvocine Algae

    Science.gov (United States)

    Umen, James G.; Olson, Bradley J.S.C.

    2015-01-01

    Volvocine algae are a group of chlorophytes that together comprise a unique model for evolutionary and developmental biology. The species Chlamydomonas reinhardtii and Volvox carteri represent extremes in morphological diversity within the Volvocine clade. Chlamydomonas is unicellular and reflects the ancestral state of the group, while Volvox is multicellular and has evolved numerous innovations including germ-soma differentiation, sexual dimorphism, and complex morphogenetic patterning. The Chlamydomonas genome sequence has shed light on several areas of eukaryotic cell biology, metabolism and evolution, while the Volvox genome sequence has enabled a comparison with Chlamydomonas that reveals some of the underlying changes that enabled its transition to multicellularity, but also underscores the subtlety of this transition. Many of the tools and resources are in place to further develop Volvocine algae as a model for evolutionary genomics. PMID:25883411

  1. Brief Guide to Genomics: DNA, Genes and Genomes

    Science.gov (United States)

    ... de genómica A Brief Guide to Genomics DNA, Genes and Genomes Deoxyribonucleic acid (DNA) is the chemical ... needed to build the entire human body. A gene traditionally refers to the unit of DNA that ...

  2. Methanococcus jannaschii genome: revisited

    Science.gov (United States)

    Kyrpides, N. C.; Olsen, G. J.; Klenk, H. P.; White, O.; Woese, C. R.

    1996-01-01

    Analysis of genomic sequences is necessarily an ongoing process. Initial gene assignments tend (wisely) to be on the conservative side (Venter, 1996). The analysis of the genome then grows in an iterative fashion as additional data and more sophisticated algorithms are brought to bear on the data. The present report is an emendation of the original gene list of Methanococcus jannaschii (Bult et al., 1996). By using a somewhat more updated database and more relaxed (and operator-intensive) pattern matching methods, we were able to add significantly to, and in a few cases amend, the gene identification table originally published by Bult et al. (1996).

  3. Comparative Genomics Reveals High Genomic Diversity in the Genus Photobacterium.

    Science.gov (United States)

    Machado, Henrique; Gram, Lone

    2017-01-01

    Vibrionaceae is a large marine bacterial family, which can constitute up to 50% of the prokaryotic population in marine waters. Photobacterium is the second largest genus in the family and we used comparative genomics on 35 strains representing 16 of the 28 species described so far, to understand the genomic diversity present in the Photobacterium genus. Such understanding is important for ecophysiology studies of the genus. We used whole genome sequences to evaluate phylogenetic relationships using several analyses (16S rRNA, MLSA, fur , amino-acid usage, ANI), which allowed us to identify two misidentified strains. Genome analyses also revealed occurrence of higher and lower GC content clades, correlating with phylogenetic clusters. Pan- and core-genome analysis revealed the conservation of 25% of the genome throughout the genus, with a large and open pan-genome. The major source of genomic diversity could be traced to the smaller chromosome and plasmids. Several of the physiological traits studied in the genus did not correlate with phylogenetic data. Since horizontal gene transfer (HGT) is often suggested as a source of genetic diversity and a potential driver of genomic evolution in bacterial species, we looked into evidence of such in Photobacterium genomes. Genomic islands were the source of genomic differences between strains of the same species. Also, we found transposase genes and CRISPR arrays that suggest multiple encounters with foreign DNA. Presence of genomic exchange traits was widespread and abundant in the genus, suggesting a role in genomic evolution. The high genetic variability and indications of genetic exchange make it difficult to elucidate genome evolutionary paths and raise the awareness of the roles of foreign DNA in the genomic evolution of environmental organisms.

  4. Illuminating the Druggable Genome (IDG)

    Data.gov (United States)

    Federal Laboratory Consortium — Results from the Human Genome Project revealed that the human genome contains 20,000 to 25,000 genes. A gene contains (encodes) the information that each cell uses...

  5. Chromatin dynamics in genome stability

    DEFF Research Database (Denmark)

    Nair, Nidhi; Shoaib, Muhammad; Sørensen, Claus Storgaard

    2017-01-01

    Genomic DNA is compacted into chromatin through packaging with histone and non-histone proteins. Importantly, DNA accessibility is dynamically regulated to ensure genome stability. This is exemplified in the response to DNA damage where chromatin relaxation near genomic lesions serves to promote ...... of chromatin structure regulation in maintaining genome integrity by multiple mechanisms including facilitating DNA repair and directly suppressing endogenous DNA damage.......Genomic DNA is compacted into chromatin through packaging with histone and non-histone proteins. Importantly, DNA accessibility is dynamically regulated to ensure genome stability. This is exemplified in the response to DNA damage where chromatin relaxation near genomic lesions serves to promote...... access of relevant enzymes to specific DNA regions for signaling and repair. Furthermore, recent data highlight genome maintenance roles of chromatin through the regulation of endogenous DNA-templated processes including transcription and replication. Here, we review research that shows the importance...

  6. The Nostoc punctiforme Genome

    Energy Technology Data Exchange (ETDEWEB)

    John C. Meeks

    2001-12-31

    Nostoc punctiforme is a filamentous cyanobacterium with extensive phenotypic characteristics and a relatively large genome, approaching 10 Mb. The phenotypic characteristics include a photoautotrophic, diazotrophic mode of growth, but N. punctiforme is also facultatively heterotrophic; its vegetative cells have multiple development alternatives, including terminal differentiation into nitrogen-fixing heterocysts and transient differentiation into spore-like akinetes or motile filaments called hormogonia; and N. punctiforme has broad symbiotic competence with fungi and terrestrial plants, including bryophytes, gymnosperms and an angiosperm. The shotgun-sequencing phase of the N. punctiforme strain ATCC 29133 genome has been completed by the Joint Genome Institute. Annotation of an 8.9 Mb database yielded 7432 open reading frames, 45% of which encode proteins with known or probable known function and 29% of which are unique to N. punctiforme. Comparative analysis of the sequence indicates a genome that is highly plastic and in a state of flux, with numerous insertion sequences and multilocus repeats, as well as genes encoding transposases and DNA modification enzymes. The sequence also reveals the presence of genes encoding putative proteins that collectively define almost all characteristics of cyanobacteria as a group. N. punctiforme has an extensive potential to sense and respond to environmental signals as reflected by the presence of more than 400 genes encoding sensor protein kinases, response regulators and other transcriptional factors. The signal transduction systems and any of the large number of unique genes may play essential roles in the cell differentiation and symbiotic interaction properties of N. punctiforme.

  7. RIKEN mouse genome encyclopedia.

    Science.gov (United States)

    Hayashizaki, Yoshihide

    2003-01-01

    We have been working to establish the comprehensive mouse full-length cDNA collection and sequence database to cover as many genes as we can, named Riken mouse genome encyclopedia. Recently we are constructing higher-level annotation (Functional ANnoTation Of Mouse cDNA; FANTOM) not only with homology search based annotation but also with expression data profile, mapping information and protein-protein database. More than 1,000,000 clones prepared from 163 tissues were end-sequenced to classify into 159,789 clusters and 60,770 representative clones were fully sequenced. As a conclusion, the 60,770 sequences contained 33,409 unique. The next generation of life science is clearly based on all of the genome information and resources. Based on our cDNA clones we developed the additional system to explore gene function. We developed cDNA microarray system to print all of these cDNA clones, protein-protein interaction screening system, protein-DNA interaction screening system and so on. The integrated database of all the information is very useful not only for analysis of gene transcriptional network and for the connection of gene to phenotype to facilitate positional candidate approach. In this talk, the prospect of the application of these genome resourced should be discussed. More information is available at the web page: http://genome.gsc.riken.go.jp/.

  8. Genomic prediction using subsampling.

    Science.gov (United States)

    Xavier, Alencar; Xu, Shizhong; Muir, William; Rainey, Katy Martin

    2017-03-24

    Genome-wide assisted selection is a critical tool for the genetic improvement of plants and animals. Whole-genome regression models in Bayesian framework represent the main family of prediction methods. Fitting such models with a large number of observations involves a prohibitive computational burden. We propose the use of subsampling bootstrap Markov chain in genomic prediction. Such method consists of fitting whole-genome regression models by subsampling observations in each round of a Markov Chain Monte Carlo. We evaluated the effect of subsampling bootstrap on prediction and computational parameters. Across datasets, we observed an optimal subsampling proportion of observations around 50% with replacement, and around 33% without replacement. Subsampling provided a substantial decrease in computation time, reducing the time to fit the model by half. On average, losses on predictive properties imposed by subsampling were negligible, usually below 1%. For each dataset, an optimal subsampling point that improves prediction properties was observed, but the improvements were also negligible. Combining subsampling with Gibbs sampling is an interesting ensemble algorithm. The investigation indicates that the subsampling bootstrap Markov chain algorithm substantially reduces computational burden associated with model fitting, and it may slightly enhance prediction properties.

  9. The Rhodobacter capsulatus genome

    Czech Academy of Sciences Publication Activity Database

    Haselkorn, R.; Lapidus, A.; Kogan, Y.; Vlček, Čestmír; Pačes, Jan; Pačes, Václav; Ulbrich, P.; Pečenková, Tamara; Rebrekov, D.; Milgram, A.; Mazur, M.; Cox, R.; Kyrpides, N.; Ivanova, N.; Kapatral, V.; Los, T.; Lykidis, A.; Mikhailova, N.; Reznik, G.; Vasieva, O.; Fonstein, M.

    2001-01-01

    Roč. 70, č. 1 (2001), s. 43-52 ISSN 0166-8595 R&D Projects: GA MŠk LN00A079 Institutional research plan: CEZ:AV0Z5052915 Keywords : genome * expression * gene Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.739, year: 2001

  10. Functional genomics of tomato

    Indian Academy of Sciences (India)

    2014-10-20

    Oct 20, 2014 ... very first challenge before scientists working on tomato functional biology is to exploit this high-quality reference sequence for tapping of the ... and exploitation of the genomic diversity present in Solanum genus, in general, and ..... associated with this tool retain its labour-intensive nature, ineffectiveness for ...

  11. Searching for genomic constraints

    International Nuclear Information System (INIS)

    Lio', P.; Ruffo, S.

    1998-01-01

    The authors have analyzed general properties of very long DNA sequences belonging to simple and complex organisms, by using different correlation methods. They have distinguished those base compositional rules that concern the entire genome which they call 'genomic constraints' from the rules that depend on the 'external natural selection' acting on single genes, i. e. protein-centered constraints. They show that G + C content, purine / pyrimidine distributions and biological complexity of the organism are the most important factors which determine base compositional rules and genome complexity. Three main facts are here reported: bacteria with high G + C content have more restrictions on base composition than those with low G + C content; at constant G + C content more complex organisms, ranging from prokaryotes to higher eukaryotes (e.g. human) display an increase of repeats 10-20 nucleotides long, which are also partly responsible for long-range correlations; work selection of length 3 to 10 is stronger in human and in bacteria for two distinct reasons. With respect to previous studies, they have also compared the genomic sequence of the archeon Methanococcus jannaschii with those of bacteria and eukaryotes: it shows sometimes an intermediate statistical behaviour

  12. Better chocolate through genomics

    Science.gov (United States)

    Theobroma cacao, the cacao or chocolate tree, is a tropical understory tree whose seeds are used to make chocolate. And like any important crop, cacao is the subject of much research. On September 15, 2010, scientists publicly released a preliminary sequence of the cacao genome--which contains all o...

  13. Genomics of human longevity

    NARCIS (Netherlands)

    Slagboom, P. E.; Beekman, M.; Passtoors, W. M.; Deelen, J.; Vaarhorst, A. A.M.; Boer, J. M.; Van Den Akker, E. B.; Van Heemst, D.; De Craen, A. J.M.; Maier, A. B.; Rozing, M.; Mooijaart, S. P.; Heijmans, B. T.; Westendorp, R. G.J.

    2011-01-01

    In animal models, single-gene mutations in genes involved in insulin/IGF and target of rapamycin signalling pathways extend lifespan to a considerable extent. The genetic, genomic and epigenetic influences on human longevity are expected to be much more complex. Strikingly however, beneficial

  14. Genome stability in Caenorhabditis elegans

    NARCIS (Netherlands)

    Haaften, G.W. van

    2006-01-01

    Genome stability is closely linked to cancer. Most, if not all tumor cells show some form of genome instability, mutations can range from single point mutations to gross chromosomal rearrangements and aneuploidy. Genome instability is believed to be the driving force behind tumorigenesis. In order

  15. GenomeGraphs: integrated genomic data visualization with R

    Directory of Open Access Journals (Sweden)

    Spellman Paul T

    2009-01-01

    Full Text Available Abstract Background Biological studies involve a growing number of distinct high-throughput experiments to characterize samples of interest. There is a lack of methods to visualize these different genomic datasets in a versatile manner. In addition, genomic data analysis requires integrated visualization of experimental data along with constantly changing genomic annotation and statistical analyses. Results We developed GenomeGraphs, as an add-on software package for the statistical programming environment R, to facilitate integrated visualization of genomic datasets. GenomeGraphs uses the biomaRt package to perform on-line annotation queries to Ensembl and translates these to gene/transcript structures in viewports of the grid graphics package. This allows genomic annotation to be plotted together with experimental data. GenomeGraphs can also be used to plot custom annotation tracks in combination with different experimental data types together in one plot using the same genomic coordinate system. Conclusion GenomeGraphs is a flexible and extensible software package which can be used to visualize a multitude of genomic datasets within the statistical programming environment R.

  16. GenomeGraphs: integrated genomic data visualization with R.

    Science.gov (United States)

    Durinck, Steffen; Bullard, James; Spellman, Paul T; Dudoit, Sandrine

    2009-01-06

    Biological studies involve a growing number of distinct high-throughput experiments to characterize samples of interest. There is a lack of methods to visualize these different genomic datasets in a versatile manner. In addition, genomic data analysis requires integrated visualization of experimental data along with constantly changing genomic annotation and statistical analyses. We developed GenomeGraphs, as an add-on software package for the statistical programming environment R, to facilitate integrated visualization of genomic datasets. GenomeGraphs uses the biomaRt package to perform on-line annotation queries to Ensembl and translates these to gene/transcript structures in viewports of the grid graphics package. This allows genomic annotation to be plotted together with experimental data. GenomeGraphs can also be used to plot custom annotation tracks in combination with different experimental data types together in one plot using the same genomic coordinate system. GenomeGraphs is a flexible and extensible software package which can be used to visualize a multitude of genomic datasets within the statistical programming environment R.

  17. Chromosomal analysis of blastocyst derived from monopronucleated ICSI zygotes: approach by double trophectoderm biopsy.

    Science.gov (United States)

    Mateo, Silvia; Vidal, Francesca; Coll, Lluc; Veiga, Anna; Boada, Montserrat

    2017-09-01

    This study aims to increase the knowledge about monopronucleated ICSI-derived blastocysts, analyzing trophectoderm biopsies by aCGH and FISH to evaluate their chromosome constitution. Fifteen monopronucleated ICSI-derived blastocysts were studied. Double trophectoderm biopsy was performed and analyzed by FISH and aCGH. The blastocysts were classified according to chromosome constitution. Disagreements between the two techniques were assessed. Results obtained after FISH and aCGH analyses showed the following: 20% (3/15) and 60% (9/15) diploid females, respectively; 26.7% (4/15) and 26.7% (4/15) diploid males, respectively; and 53.3% (8/15) and 13.3% (2/15) mosaics, respectively. No mosaic male embryos were found using FISH or aCGH. There were disagreements in 40% (6/15) of the cases due to the higher detection of mosaicism by FISH compared to aCGH. The combination of FISH and aCGH has been shown to be a suitable approach to increase the knowledge about monopronucleated ICSI-derived embryos. FISH analysis of blastocysts derived from monopronucleated ICSI zygotes enabled us to conclude that aCGH underestimates haploidy. Some diploid embryos diagnosed by aCGH are in fact mosaic. In cases where these embryos would be used for reproductive purposes, extra analysis of parental genome origin is recommended.

  18. Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute's genomic medicine portfolio.

    Science.gov (United States)

    Manolio, Teri A

    2016-10-01

    Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual's genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of "Genomic Medicine Meetings," under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and difficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI's genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so. Published by Elsevier Ireland Ltd.

  19. Genome Editing Tools in Plants

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Mohanta

    2017-12-01

    Full Text Available Genome editing tools have the potential to change the genomic architecture of a genome at precise locations, with desired accuracy. These tools have been efficiently used for trait discovery and for the generation of plants with high crop yields and resistance to biotic and abiotic stresses. Due to complex genomic architecture, it is challenging to edit all of the genes/genomes using a particular genome editing tool. Therefore, to overcome this challenging task, several genome editing tools have been developed to facilitate efficient genome editing. Some of the major genome editing tools used to edit plant genomes are: Homologous recombination (HR, zinc finger nucleases (ZFNs, transcription activator-like effector nucleases (TALENs, pentatricopeptide repeat proteins (PPRs, the CRISPR/Cas9 system, RNA interference (RNAi, cisgenesis, and intragenesis. In addition, site-directed sequence editing and oligonucleotide-directed mutagenesis have the potential to edit the genome at the single-nucleotide level. Recently, adenine base editors (ABEs have been developed to mutate A-T base pairs to G-C base pairs. ABEs use deoxyadeninedeaminase (TadA with catalytically impaired Cas9 nickase to mutate A-T base pairs to G-C base pairs.

  20. Evolution of small prokaryotic genomes

    Directory of Open Access Journals (Sweden)

    David José Martínez-Cano

    2015-01-01

    Full Text Available As revealed by genome sequencing, the biology of prokaryotes with reduced genomes is strikingly diverse. These include free-living prokaryotes with ~800 genes as well as endosymbiotic bacteria with as few as ~140 genes. Comparative genomics is revealing the evolutionary mechanisms that led to these small genomes. In the case of free-living prokaryotes, natural selection directly favored genome reduction, while in the case of endosymbiotic prokaryotes neutral processes played a more prominent role. However, new experimental data suggest that selective processes may be at operation as well for endosymbiotic prokaryotes at least during the first stages of genome reduction. Endosymbiotic prokaryotes have evolved diverse strategies for living with reduced gene sets inside a host-defined medium. These include utilization of host-encoded functions (some of them coded by genes acquired by gene transfer from the endosymbiont and/or other bacteria; metabolic complementation between co-symbionts; and forming consortiums with other bacteria within the host. Recent genome sequencing projects of intracellular mutualistic bacteria showed that previously believed universal evolutionary trends like reduced G+C content and conservation of genome synteny are not always present in highly reduced genomes. Finally, the simplified molecular machinery of some of these organisms with small genomes may be used to aid in the design of artificial minimal cells. Here we review recent genomic discoveries of the biology of prokaryotes endowed with small gene sets and discuss the evolutionary mechanisms that have been proposed to explain their peculiar nature.

  1. Toward genome-enabled mycology.

    Science.gov (United States)

    Hibbett, David S; Stajich, Jason E; Spatafora, Joseph W

    2013-01-01

    Genome-enabled mycology is a rapidly expanding field that is characterized by the pervasive use of genome-scale data and associated computational tools in all aspects of fungal biology. Genome-enabled mycology is integrative and often requires teams of researchers with diverse skills in organismal mycology, bioinformatics and molecular biology. This issue of Mycologia presents the first complete fungal genomes in the history of the journal, reflecting the ongoing transformation of mycology into a genome-enabled science. Here, we consider the prospects for genome-enabled mycology and the technical and social challenges that will need to be overcome to grow the database of complete fungal genomes and enable all fungal biologists to make use of the new data.

  2. Marine Bacterial Genomics

    DEFF Research Database (Denmark)

    Machado, Henrique

    microorganisms to be used as cell factories for production. Therefore exploitation of new microbial niches and use of different strategies is an opportunity to boost discoveries. Even though scientists have started to explore several habitats other than the terrestrial ones, the marine environment stands out...... as a hitherto under-explored niche. This thesis work uses high-throughput sequencing technologies on a collection of marine bacteria established during the Galathea 3 expedition, with the purpose of unraveling new biodiversity and new bioactivities. Several tools were used for genomic analysis in order...... to better understand the potential harbored in marine bacteria. The work presented makes use of whole genome sequencing of marine bacteria to prove that the genetic repertoire for secondary metabolite production harbored in these bacteria is far larger than anticipated; to identify and develop a new...

  3. Genomic dairy cattle breeding

    DEFF Research Database (Denmark)

    Mark, Thomas; Sandøe, Peter

    2010-01-01

    , unfavourable genetic trends for metabolic, reproductive, claw and leg diseases indicate that these attempts have been insufficient. Today, novel genome-wide sequencing techniques are revolutionising dairy cattle breeding; these enable genetic changes to occur at least twice as rapidly as previously. While......, a number of potential risks are discussed, including detrimental genetic trends for non-measured welfare traits, the increased chance of spreading unfavourable mutations, reduced sharing of information arising from concerns over patents, and an increased monopoly within dairy cattle breeding that may make...... negative effects on animal welfare and to invest in breeding for increased animal welfare. Researchers are encouraged to further investigate the long-term effects of various breeding schemes that rely on genomic breeding values....

  4. Precision genome editing

    DEFF Research Database (Denmark)

    Steentoft, Catharina; Bennett, Eric P; Schjoldager, Katrine Ter-Borch Gram

    2014-01-01

    of glycobiology, primarily due to their low efficiencies, with resultant failure to impose substantial phenotypic consequences upon the final glycosylation products. Here, we review novel nuclease-based precision genome editing techniques enabling efficient and stable gene editing, including gene disruption......Precise and stable gene editing in mammalian cell lines has until recently been hampered by the lack of efficient targeting methods. While different gene silencing strategies have had tremendous impact on many biological fields, they have generally not been applied with wide success in the field...... by introducing single or double-stranded breaks at a defined genomic sequence. We here compare and contrast the different techniques and summarize their current applications, highlighting cases from the field of glycobiology as well as pointing to future opportunities. The emerging potential of precision gene...

  5. Genomic research perspectives in Kazakhstan

    Directory of Open Access Journals (Sweden)

    Ainur Akilzhanova

    2014-01-01

    Full Text Available Introduction: Technological advancements rapidly propel the field of genome research. Advances in genetics and genomics such as the sequence of the human genome, the human haplotype map, open access databases, cheaper genotyping and chemical genomics, have transformed basic and translational biomedical research. Several projects in the field of genomic and personalized medicine have been conducted at the Center for Life Sciences in Nazarbayev University. The prioritized areas of research include: genomics of multifactorial diseases, cancer genomics, bioinformatics, genetics of infectious diseases and population genomics. At present, DNA-based risk assessment for common complex diseases, application of molecular signatures for cancer diagnosis and prognosis, genome-guided therapy, and dose selection of therapeutic drugs are the important issues in personalized medicine. Results: To further develop genomic and biomedical projects at Center for Life Sciences, the development of bioinformatics research and infrastructure and the establishment of new collaborations in the field are essential. Widespread use of genetic tools will allow the identification of diseases before the onset of clinical symptoms, the individualization of drug treatment, and could induce individual behavioral changes on the basis of calculated disease risk. However, many challenges remain for the successful translation of genomic knowledge and technologies into health advances, such as medicines and diagnostics. It is important to integrate research and education in the fields of genomics, personalized medicine, and bioinformatics, which will be possible with opening of the new Medical Faculty at Nazarbayev University. People in practice and training need to be educated about the key concepts of genomics and engaged so they can effectively apply their knowledge in a matter that will bring the era of genomic medicine to patient care. This requires the development of well

  6. Genomics Portals: integrative web-platform for mining genomics data.

    Science.gov (United States)

    Shinde, Kaustubh; Phatak, Mukta; Johannes, Freudenberg M; Chen, Jing; Li, Qian; Vineet, Joshi K; Hu, Zhen; Ghosh, Krishnendu; Meller, Jaroslaw; Medvedovic, Mario

    2010-01-13

    A large amount of experimental data generated by modern high-throughput technologies is available through various public repositories. Our knowledge about molecular interaction networks, functional biological pathways and transcriptional regulatory modules is rapidly expanding, and is being organized in lists of functionally related genes. Jointly, these two sources of information hold a tremendous potential for gaining new insights into functioning of living systems. Genomics Portals platform integrates access to an extensive knowledge base and a large database of human, mouse, and rat genomics data with basic analytical visualization tools. It provides the context for analyzing and interpreting new experimental data and the tool for effective mining of a large number of publicly available genomics datasets stored in the back-end databases. The uniqueness of this platform lies in the volume and the diversity of genomics data that can be accessed and analyzed (gene expression, ChIP-chip, ChIP-seq, epigenomics, computationally predicted binding sites, etc), and the integration with an extensive knowledge base that can be used in such analysis. The integrated access to primary genomics data, functional knowledge and analytical tools makes Genomics Portals platform a unique tool for interpreting results of new genomics experiments and for mining the vast amount of data stored in the Genomics Portals backend databases. Genomics Portals can be accessed and used freely at http://GenomicsPortals.org.

  7. eGenomics: Cataloguing Our Complete Genome Collection III

    Directory of Open Access Journals (Sweden)

    Dawn Field

    2007-01-01

    Full Text Available This meeting report summarizes the proceedings of the “eGenomics: Cataloguing our Complete Genome Collection III” workshop held September 11–13, 2006, at the National Institute for Environmental eScience (NIEeS, Cambridge, United Kingdom. This 3rd workshop of the Genomic Standards Consortium was divided into two parts. The first half of the three-day workshop was dedicated to reviewing the genomic diversity of our current and future genome and metagenome collection, and exploring linkages to a series of existing projects through formal presentations. The second half was dedicated to strategic discussions. Outcomes of the workshop include a revised “Minimum Information about a Genome Sequence” (MIGS specification (v1.1, consensus on a variety of features to be added to the Genome Catalogue (GCat, agreement by several researchers to adopt MIGS for imminent genome publications, and an agreement by the EBI and NCBI to input their genome collections into GCat for the purpose of quantifying the amount of optional data already available (e.g., for geographic location coordinates and working towards a single, global list of all public genomes and metagenomes.

  8. Genomics Portals: integrative web-platform for mining genomics data

    Science.gov (United States)

    2010-01-01

    Background A large amount of experimental data generated by modern high-throughput technologies is available through various public repositories. Our knowledge about molecular interaction networks, functional biological pathways and transcriptional regulatory modules is rapidly expanding, and is being organized in lists of functionally related genes. Jointly, these two sources of information hold a tremendous potential for gaining new insights into functioning of living systems. Results Genomics Portals platform integrates access to an extensive knowledge base and a large database of human, mouse, and rat genomics data with basic analytical visualization tools. It provides the context for analyzing and interpreting new experimental data and the tool for effective mining of a large number of publicly available genomics datasets stored in the back-end databases. The uniqueness of this platform lies in the volume and the diversity of genomics data that can be accessed and analyzed (gene expression, ChIP-chip, ChIP-seq, epigenomics, computationally predicted binding sites, etc), and the integration with an extensive knowledge base that can be used in such analysis. Conclusion The integrated access to primary genomics data, functional knowledge and analytical tools makes Genomics Portals platform a unique tool for interpreting results of new genomics experiments and for mining the vast amount of data stored in the Genomics Portals backend databases. Genomics Portals can be accessed and used freely at http://GenomicsPortals.org. PMID:20070909

  9. The Genome Atlas Resource

    DEFF Research Database (Denmark)

    Azam Qureshi, Matloob; Rotenberg, Eva; Stærfeldt, Hans Henrik

    2010-01-01

    with scripts and algorithms developed in a variety of programming languages at the Centre for Biological Sequence Analysis in order to create a three-tier software application for genome analysis. The results are made available via a web interface developed in Java, PHP and Perl CGI. User......-configurable and dynamic views of Chromosomal maps are made possible through an updated GeneWiz browser (version 0.94) which uses Java to allow rapid zooming in and out of the atlases....

  10. Malaria Genome Sequencing Project

    Science.gov (United States)

    2004-01-01

    proteins in plastid segregation mutants of Toxoplasma gandii. L. Biot. Parasito . Today 11, 1-4 (1995). Chem. 276, 28436-28442 (2001). 11. Su, X. et al... parasito - gene mapping studies have shown that regions of gene synteny exist phorous vacuole membrane29 . between species of rodent malaria9 and between...Carucci, D. J. Rodent models of malaria in the genomics era. Trends Parasito , 18, selection of karyotype mutants and non-gametocyte producer mutants

  11. National Plant Genome Initiative

    Science.gov (United States)

    2004-01-01

    from the soil allow the development of new strategies for fortification of plant foods with nutrients beneficial to human and animal health ( iron and... calcium , for example) and might suggest new approaches for using plants to clean up soils with unsafe levels of heavy metal pollutants such as...involved in uptake of iron , a key nutrient for human health, thus validating the approach. Based upon past studies of genomic and EST sequences, it was

  12. Human Germline Genome Editing.

    Science.gov (United States)

    Ormond, Kelly E; Mortlock, Douglas P; Scholes, Derek T; Bombard, Yvonne; Brody, Lawrence C; Faucett, W Andrew; Garrison, Nanibaa' A; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E

    2017-08-03

    With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy. (2) Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research. (3) Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  13. Genomic technologies in neonatology

    Directory of Open Access Journals (Sweden)

    L. N. Chernova

    2017-01-01

    Full Text Available In recent years, there has been a tremendous trend toward personalized medicine. Advances in the field forced clinicians, including neonatologists, to take a fresh look at prevention, tactics of management and therapy of various diseases. In the center of attention of foreign, and increasingly Russian, researchers and doctors, there are individual genomic data that allow not only to assess the risks of some form of pathology, but also to successfully apply personalized strategies of prediction, prevention and targeted treatment. This article provides a brief review of the latest achievements of genomic technologies in newborns, examines the problems and potential applications of genomics in promoting the concept of personalized medicine in neonatology. The increasing amount of personalized data simply impossible to analyze only by the human mind. In this connection, the need of computers and bioinformatics is obvious. The article reveals the role of translational bioinformatics in the analysis and integration of the results of the accumulated fundamental research into complete clinical decisions. The latest advances in neonatal translational bioinformatics such as clinical decision support systems are considered. It helps to monitor vital parameters of newborns influencing the course of a particular disease, to calculate the increased risks of the development of various pathologies and to select the drugs.

  14. Genomic Alterations in Primary Gastric Adenocarcinomas Correlate with Clinicopathological Characteristics and Survival

    Directory of Open Access Journals (Sweden)

    Marjan M. Weiss

    2004-01-01

    Full Text Available Background & aims: Pathogenesis of gastric cancer is driven by an accumulation of genetic changes that to a large extent occur at the chromosomal level. In order to investigate the patterns of chromosomal aberrations in gastric carcinomas, we performed genome‐wide microarray based comparative genomic hybridisation (microarray CGH. With this recently developed technique chromosomal aberrations can be studied with high resolution and sensitivity. Methods: Array CGH was applied to a series of 35 gastric adenocarcinomas using a genome‐wide scanning array with 2275 BAC and P1 clones spotted in triplicate. Each clone contains at least one STS for linkage to the sequence of the human genome. These arrays provide an average resolution of 1.4 Mb across the genome. DNA copy number changes were correlated with clinicopathological tumour characteristics as well as survival. Results: All thirty‐five cancers showed chromosomal aberrations and 16 of the 35 tumours showed one or more amplifications. The most frequent aberrations are gains of 8q24.2, 8q24.1, 20q13.12, 20q13.2, 7p11.2, 1q32.3, 8p23.1–p23.3, losses of 5q14.1, 18q22.1, 19p13.12–p13.3, 9p21.3–p24.3, 17p13.1–p13.3, 13q31.1, 16q22.1, 21q21.3, and amplifications of 7q21–q22, and 12q14.1–q21.1. These aberrations were correlated to clinicopathological characteristics and survival. Gain of 1q32.3 was significantly correlated with lymph node status (p=0.007. Tumours with loss of 18q22.1, as well as tumours with amplifications were associated with poor survival (p=0.02, both. Conclusions: Microarray CGH has revealed several chromosomal regions that have not been described before in gastric cancer at this frequency and resolution, such as amplification of at 7q21–q22 and 12q14.1–q21.1, as well gains at 1q32.3, 7p11.2, and losses at 13q13.1. Interestingly, gain of 1q32.3 and loss of 18q22.1 are associated with a bad prognosis indicating that these regions could harbour gene(s that may

  15. Prenatal diagnosis of a distal 3p deletion associated with fetoplacental chromosomal discrepancy and confined placental mosaicism detected by array comparative genomic hybridization

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2013-06-01

    Conclusion: Fetal tissue and amniocytes offer more reliable resources for aCGH characterization of prenatally detected aneuploidy compared with placental tissues. A molecular cytogenetic evaluation of prenatally detected aneuploidy using placental tissue should raise concerns of confined placental mosaicism and fetoplacental chromosomal discrepancy.

  16. Rapid aneuploidy diagnosis by multiplex ligation-dependent probe amplification and array comparative genomic hybridization in pregnancy with major congenital malformations

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2011-03-01

    Conclusions: Prenatal diagnosis of major congenital malformations should alert one to the possibility of chromosomal abnormalities. Multiplex ligation-dependent probe amplification and aCGH have the advantage of rapid aneuploidy diagnosis of common aneuploidies in cases with major congenital malformations.

  17. Array-Comparative Genomic Hybridization Analysis in Fetuses with Major Congenital Malformations Reveals that 24% of Cases Have Pathogenic Deletions/Duplications.

    Science.gov (United States)

    Di Gregorio, Eleonora; Gai, Giorgia; Botta, Giovanni; Calcia, Alessandro; Pappi, Patrizia; Talarico, Flavia; Savin, Elisa; Ribotta, Marisa; Zonta, Andrea; Mancini, Cecilia; Giorgio, Elisa; Cavalieri, Simona; Restagno, Gabriella; Ferrero, Giovanni B; Viora, Elsa; Pasini, Barbara; Grosso, Enrico; Brusco, Alfredo; Brussino, Alessandro

    2015-01-01

    Karyotyping and aCGH are routinely used to identify genetic determinants of major congenital malformations (MCMs) in fetal deaths or terminations of pregnancy after prenatal diagnosis. Pathogenic rearrangements are found with a variable rate of 9-39% for aCGH. We collected 33 fetuses, 9 with a single MCM and 24 with MCMs involving 2-4 organ systems. aCGH revealed copy number variants in 14 out of 33 cases (42%). Eight were classified as pathogenic which account for a detection rate of 24% (8/33) considering fetuses with 1 or more MCMs and 33% (8/24) taking into account fetuses with multiple malformations only. Three of the pathogenic variants were known microdeletion syndromes (22q11.21 deletion, central chromosome 22q11.21 deletion, and TAR syndrome) and 5 were large rearrangements, adding up to >11 Mb per subject and comprising strong phenotype-related genes. One of those was a de novo complex rearrangement, and the remaining 4 duplications and 2 deletions were 130-900 kb in size, containing 1-7 genes, and were classified as variants of unknown clinical significance. Our study confirms aCGH as a powerful technique to ascertain the genetic etiology of fetal major congenital malformations. © 2015 S. Karger AG, Basel.

  18. Nutritional genomics: an approach to the genome-environment interaction

    OpenAIRE

    Xacur-Garcia, F.; Castillo-Quan, J. I.; Hernandez-Escalante, V. M.; Laviada-Molina, H.

    2008-01-01

    Nutritional genomics forms part of the genomic sciences and addresses the interaction between genes and the human diet, its influence on metabolism and subsequent susceptibility to develop common diseases. It encompasses both nutrigenomics, which explores the effects of nutrients on the genome, proteome and metabolome; and nutrigenetics, that explores the effects of genetic variations on the diet/disease interaction. A number of mechanisms drive the gene/diet interaction: elements in the diet...

  19. Genomic Data Commons and Genomic Cloud Pilots - Google Hangout

    Science.gov (United States)

    Join us for a live, moderated discussion about two NCI efforts to expand access to cancer genomics data: the Genomic Data Commons and Genomic Cloud Pilots. NCI subject matters experts will include Louis M. Staudt, M.D., Ph.D., Director Center for Cancer Genomics, Warren Kibbe, Ph.D., Director, NCI Center for Biomedical Informatics and Information Technology, and moderated by Anthony Kerlavage, Ph.D., Chief, Cancer Informatics Branch, Center for Biomedical Informatics and Information Technology. We welcome your questions before and during the Hangout on Twitter using the hashtag #AskNCI.

  20. Invariants of DNA genomic signals

    Science.gov (United States)

    Cristea, Paul Dan A.

    2005-02-01

    For large scale analysis purposes, the conversion of genomic sequences into digital signals opens the possibility to use powerful signal processing methods for handling genomic information. The study of complex genomic signals reveals large scale features, maintained over the scale of whole chromosomes, that would be difficult to find by using only the symbolic representation. Based on genomic signal methods and on statistical techniques, the paper defines parameters of DNA sequences which are invariant to transformations induced by SNPs, splicing or crossover. Re-orienting concatenated coding regions in the same direction, regularities shared by the genomic material in all exons are revealed, pointing towards the hypothesis of a regular ancestral structure from which the current chromosome structures have evolved. This property is not found in non-nuclear genomic material, e.g., plasmids.

  1. Comparative Genomics in Homo sapiens.

    Science.gov (United States)

    Oti, Martin; Sammeth, Michael

    2018-01-01

    Genomes can be compared at different levels of divergence, either between species or within species. Within species genomes can be compared between different subpopulations, such as human subpopulations from different continents. Investigating the genomic differences between different human subpopulations is important when studying complex diseases that are affected by many genetic variants, as the variants involved can differ between populations. The 1000 Genomes Project collected genome-scale variation data for 2504 human individuals from 26 different populations, enabling a systematic comparison of variation between human subpopulations. In this chapter, we present step-by-step a basic protocol for the identification of population-specific variants employing the 1000 Genomes data. These variants are subsequently further investigated for those that affect the proteome or RNA splice sites, to investigate potentially biologically relevant differences between the populations.

  2. Genomic selection in plant breeding.

    Science.gov (United States)

    Newell, Mark A; Jannink, Jean-Luc

    2014-01-01

    Genomic selection (GS) is a method to predict the genetic value of selection candidates based on the genomic estimated breeding value (GEBV) predicted from high-density markers positioned throughout the genome. Unlike marker-assisted selection, the GEBV is based on all markers including both minor and major marker effects. Thus, the GEBV may capture more of the genetic variation for the particular trait under selection.

  3. Advances in editing microalgae genomes

    OpenAIRE

    Daboussi, Fayza

    2017-01-01

    There have been significant advances in microalgal genomics over the last decade. Nevertheless, there are still insufficient tools for the manipulation of microalgae genomes and the development of microalgae as industrial biofactories. Several research groups have recently contributed to progress by demonstrating that particular nucleases can be used for targeted and stable modifications of the genomes of some microalgae species. The nucleases include Meganucleases, Zinc Finger nucleases, TAL...

  4. Genomic profile of antibiotic resistant, classical ctxB positive Vibrio cholerae O1 biotype El Tor isolated in 2003 and 2005 from Puri, India: A retrospective study

    Directory of Open Access Journals (Sweden)

    T Bhotra

    2016-01-01

    Full Text Available Objectives: To examine eight strains of Vibrio cholerae O1 isolated in 2003 and 2005 from Puri, India, for antibiotic susceptibility, presence of virulence and regulatory genes, cholera toxin (CT production, CTX arrangement and genomic profiles. Materials and Methods: Bacterial strains were tested for antibiotic susceptibility using disc diffusion assay. Polymerase chain reaction determined the presence of antibiotic resistance, virulence and regulatory genes. To determine the type of cholera toxin subunit B (ctxB, nucleotide sequencing was performed. Southern hybridisation determined the number and arrangement of CTXΦ. Ribotyping and pulsed-field gel electrophoresis (PFGE were used to determine the genomic profile of isolates. Results: All the eight strains, except one strain, showed resistant to nalidixic acid, sulphamethoxazole, streptomycin and trimethoprim and possessed the sullI, strB, dfrA1 and int SXT genes. All the strains carried the toxin-co-regulated pilus pathogenicity island, the CTX genetic element, the repeat in toxin and produced CT. Restriction fragment length polymorphism (RFLP analysis showed that V. cholerae O1 possess a single copy of the CTX element flanked by tandemly arranged RS element. Nucleotide sequencing of the ctxB gene showed the presence of classical ctxB. RFLP analysis of conserved rRNA gene showed two ribotype patterns. PFGE analysis also showed at least three PFGE patterns, irrespective of year of isolations, indicating the genomic relatedness among them. Conclusion: Overall, these data suggest that classical ctxB-positive V. cholerae O1 El Tor strains that appeared in 2003 continue to cause infection in 2005 in Puri, India, and belong to identical ribotype(s and/or pulsotype(s. There is need to continuous monitor the emergence of variant of El Tor because it will improve our understanding of the evolution of new clones of variant of V. cholerae.

  5. Genomic profile of antibiotic resistant, classicalctxBpositiveVibrio choleraeO1 biotype El Tor isolated in 2003 and 2005 from Puri, India: A retrospective study.

    Science.gov (United States)

    Bhotra, T; Das, M M; Pal, B B; Singh, D V

    2016-01-01

    To examine eight strains of Vibrio cholerae O1 isolated in 2003 and 2005 from Puri, India, for antibiotic susceptibility, presence of virulence and regulatory genes, cholera toxin (CT) production, CTX arrangement and genomic profiles. Bacterial strains were tested for antibiotic susceptibility using disc diffusion assay. Polymerase chain reaction determined the presence of antibiotic resistance, virulence and regulatory genes. To determine the type of cholera toxin subunit B (ctxB), nucleotide sequencing was performed. Southern hybridisation determined the number and arrangement of CTXΦ. Ribotyping and pulsed-field gel electrophoresis (PFGE) were used to determine the genomic profile of isolates. All the eight strains, except one strain, showed resistant to nalidixic acid, sulphamethoxazole, streptomycin and trimethoprim and possessed the sullI, strB, dfrA1 and int SXT genes. All the strains carried the toxin-co-regulated pilus pathogenicity island, the CTX genetic element, the repeat in toxin and produced CT. Restriction fragment length polymorphism (RFLP) analysis showed that V. cholerae O1 possess a single copy of the CTX element flanked by tandemly arranged RS element. Nucleotide sequencing of the ctxB gene showed the presence of classical ctxB. RFLP analysis of conserved rRNA gene showed two ribotype patterns. PFGE analysis also showed at least three PFGE patterns, irrespective of year of isolations, indicating the genomic relatedness among them. Overall, these data suggest that classical ctxB-positive V. cholerae O1 El Tor strains that appeared in 2003 continue to cause infection in 2005 in Puri, India, and belong to identical ribotype(s) and/or pulsotype(s). There is need to continuous monitor the emergence of variant of El Tor because it will improve our understanding of the evolution of new clones of variant of V. cholerae.

  6. Comparative RNA genomics

    DEFF Research Database (Denmark)

    Backofen, Rolf; Gorodkin, Jan; Hofacker, Ivo L.

    2018-01-01

    small RNAs is their reliance of conserved secondary structures. Large scale sequencing projects, on the other hand, have profoundly changed our understanding of eukaryotic genomes. Pervasively transcribed, they give rise to a plethora of large and evolutionarily extremely flexible noncoding RNAs...... that exert a vastly diverse array of molecule functions. In this chapter we provide a—necessarily incomplete—overview of the current state of comparative analysis of noncoding RNAs, emphasizing computational approaches as a means to gain a global picture of the modern RNA world....

  7. Genomic rearrangements and diseases

    OpenAIRE

    Loviglio, M. N.

    2016-01-01

    Copy number variations (CNVs) are major contributors of genomic imbalances disorders. On the short arm of chromosome 16, CNVs of the distal 220 kb BP2-BP3 region show mirror effect on BMI and head size, and association with autism and schizophrenia, as previously reported for the proximal 600 kb BP4-BP5 deletion and duplication. These two CNVs-prone regions at 16p11.2 are also reciprocally engaged in complex chromatin looping, successfully confirmed by 4C-seq, FISH, Hi-C and concomitant...

  8. Genomic taxonomy of vibrios

    DEFF Research Database (Denmark)

    Thompson, Cristiane C.; Vicente, Ana Carolina P.; Souza, Rangel C.

    2009-01-01

    BACKGROUND: Vibrio taxonomy has been based on a polyphasic approach. In this study, we retrieve useful taxonomic information (i.e. data that can be used to distinguish different taxonomic levels, such as species and genera) from 32 genome sequences of different vibrio species. We use a variety...... > 95% DNA identity in MLSA and supertree analysis, > 96% AAI, 61% proteome identity. Strains of the same species and species of the same genus will form monophyletic groups on the basis of MLSA and supertree. CONCLUSION: The combination of different......-based server. This novel approach to microbial systematics will result in a tremendous advance concerning biodiversity discovery, description, and understanding....

  9. Genomic effects of glucocorticoids.

    Science.gov (United States)

    Grbesa, Ivana; Hakim, Ofir

    2017-05-01

    Glucocorticoids and their receptor (GR) have been an important area of research because of their pleiotropic physiological functions and extensive use in the clinic. In addition, the association between GR and glucocorticoids, which is highly specific, leads to rapid nuclear translocation where GR associates with chromatin to regulate gene transcription. This simplified model system has been instrumental for studying the complexity of transcription regulation processes occurring at chromatin. In this review we discuss our current understanding of GR action that has been enhanced by recent developments in genome wide measurements of chromatin accessibility, histone marks, chromatin remodeling and 3D chromatin structure in various cell types responding to glucocorticoids.

  10. Genomic Feature Models

    DEFF Research Database (Denmark)

    Sørensen, Peter; Edwards, Stefan McKinnon; Rohde, Palle Duun

    -additive genetic mechanisms. These modeling approaches have proven to be highly useful to determine population genetic parameters as well as prediction of genetic risk or value. We present a series of statistical modelling approaches that use prior biological information for evaluating the collective action......Whole-genome sequences and multiple trait phenotypes from large numbers of individuals will soon be available in many populations. Well established statistical modeling approaches enable the genetic analyses of complex trait phenotypes while accounting for a variety of additive and non...

  11. Organizational heterogeneity of vertebrate genomes.

    Directory of Open Access Journals (Sweden)

    Svetlana Frenkel

    Full Text Available Genomes of higher eukaryotes are mosaics of segments with various structural, functional, and evolutionary properties. The availability of whole-genome sequences allows the investigation of their structure as "texts" using different statistical and computational methods. One such method, referred to as Compositional Spectra (CS analysis, is based on scoring the occurrences of fixed-length oligonucleotides (k-mers in the target DNA sequence. CS analysis allows generating species- or region-specific characteristics of the genome, regardless of their length and the presence of coding DNA. In this study, we consider the heterogeneity of vertebrate genomes as a joint effect of regional variation in sequence organization superimposed on the differences in nucleotide composition. We estimated compositional and organizational heterogeneity of genome and chromosome sequences separately and found that both heterogeneity types vary widely among genomes as well as among chromosomes in all investigated taxonomic groups. The high correspondence of heterogeneity scores obtained on three genome fractions, coding, repetitive, and the remaining part of the noncoding DNA (the genome dark matter--GDM allows the assumption that CS-heterogeneity may have functional relevance to genome regulation. Of special interest for such interpretation is the fact that natural GDM sequences display the highest deviation from the corresponding reshuffled sequences.

  12. Genome Trees from Conservation Profiles.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available The concept of the genome tree depends on the potential evolutionary significance in the clustering of species according to similarities in the gene content of their genomes. In this respect, genome trees have often been identified with species trees. With the rapid expansion of genome sequence data it becomes of increasing importance to develop accurate methods for grasping global trends for the phylogenetic signals that mutually link the various genomes. We therefore derive here the methodological concept of genome trees based on protein conservation profiles in multiple species. The basic idea in this derivation is that the multi-component "presence-absence" protein conservation profiles permit tracking of common evolutionary histories of genes across multiple genomes. We show that a significant reduction in informational redundancy is achieved by considering only the subset of distinct conservation profiles. Beyond these basic ideas, we point out various pitfalls and limitations associated with the data handling, paving the way for further improvements. As an illustration for the methods, we analyze a genome tree based on the above principles, along with a series of other trees derived from the same data and based on pair-wise comparisons (ancestral duplication-conservation and shared orthologs. In all trees we observe a sharp discrimination between the three primary domains of life: Bacteria, Archaea, and Eukarya. The new genome tree, based on conservation profiles, displays a significant correspondence with classically recognized taxonomical groupings, along with a series of departures from such conventional clusterings.

  13. Genome engineering in Vibrio cholerae

    DEFF Research Database (Denmark)

    Val, Marie-Eve; Skovgaard, Ole; Ducos-Galand, Magaly

    2012-01-01

    Although bacteria with multipartite genomes are prevalent, our knowledge of the mechanisms maintaining their genome is very limited, and much remains to be learned about the structural and functional interrelationships of multiple chromosomes. Owing to its bi-chromosomal genome architecture and its....... This difficulty was surmounted using a unique and powerful strategy based on massive rearrangement of prokaryotic genomes. We developed a site-specific recombination-based engineering tool, which allows targeted, oriented, and reciprocal DNA exchanges. Using this genetic tool, we obtained a panel of V. cholerae...

  14. A REVIEW ON GENOME EDITING

    OpenAIRE

    Akshay Patil, Latesh Patil, H. P. Suryawanshi, S. P. Pawar

    2017-01-01

    The Present Review report contains the information about Genome Editing. In this report genome editing is illustrated at the basic level for better understanding. It contains History of Genome Editing from 1800 to Current day i.e. from concept of DNA till current time. Genome editing is an technique to make every human smarter not our choice, by customizing next generation the way we want it to be like to be look and also the intellectual capacity. In this Concept, the viral Immunity is used ...

  15. Childhood apraxia of speech without intellectual deficit in a patient with cri du chat syndrome.

    Science.gov (United States)

    Marignier, Stéphanie; Lesca, Gaetan; Marguin, Jessica; Bussy, Gérald; Sanlaville, Damien; des Portes, Vincent

    2012-06-01

    We report an 11-year-old girl for whom the diagnosis of cri du chat syndrome (CdCS) was made during a genetic investigation of childhood apraxia of speech. The patient presented with the classic chromosome 5 short arm deletion found in CdCS. The microdeletion, characterised using aCGH (array Comparative Genomic Hybridisation), was 12.85 Mb, overlapping the 5p15.2 and 5p15.3 critical regions. CdCS is typically associated with severe mental retardation while this patient had normal intellectual performance, confirmed by normal results from categorisation tasks. This mild phenotype was assessed using a comprehensive cognitive battery. Language evaluation showed normal receptive vocabulary scores, in contrast with obvious oro-facial dyspraxia. Disabled fine motor skills were confirmed as well as weak visuo-spatial reasoning abilities. In conclusion, fine cognitive assessment may be worthwhile for patients with CdCS since good intellectual functioning may be masked by severe speech and gestural dyspraxia, thus requiring specific teaching and rehabilitation strategies. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  16. Genome Writing: Current Progress and Related Applications

    Directory of Open Access Journals (Sweden)

    Yueqiang Wang

    2018-02-01

    Full Text Available The ultimate goal of synthetic biology is to build customized cells or organisms to meet specific industrial or medical needs. The most important part of the customized cell is a synthetic genome. Advanced genomic writing technologies are required to build such an artificial genome. Recently, the partially-completed synthetic yeast genome project represents a milestone in this field. In this mini review, we briefly introduce the techniques for de novo genome synthesis and genome editing. Furthermore, we summarize recent research progresses and highlight several applications in the synthetic genome field. Finally, we discuss current challenges and future prospects. Keywords: Synthetic biology, Genome writing, Genome editing, Bioethics, Biosafety

  17. Comparative genomics of Lactobacillus and other LAB

    DEFF Research Database (Denmark)

    Wassenaar, Trudy M.; Lukjancenko, Oksana

    2014-01-01

    The genomes of 66 LABs, belonging to five different genera, were compared for genome size and gene content. The analyzed genomes included 37 Lactobacillus genomes of 17 species, six Lactococcus lactis genomes, four Leuconostoc genomes of three species, six Streptococcus genomes of two species...... that of the others, with the two Streptococcus species having the shortest genomes. The widest distribution in genome content was observed for Lactobacillus. The number of tRNA and rRNA gene copies varied considerably, with exceptional high numbers observed for Lb. delbrueckii, while these numbers were relatively...

  18. Whole genome analysis of a Vietnamese trio

    Indian Academy of Sciences (India)

    2015-02-04

    Feb 4, 2015 ... 2008), Korean genome (Ahn et al. 2009), Japanese genome. (Fujimoto et al. 2010), Pakistani genome (Azim et al. 2013),. Turkish genome (Dogan et al. 2014) and Russian genome. (Skryabin et al. 2009). Being the 14th largest country by population in the world,. Vietnam has about 90 million people of 54 ...

  19. Genome Update: alignment of bacterial chromosomes

    DEFF Research Database (Denmark)

    Ussery, David; Jensen, Mette; Poulsen, Tine Rugh

    2004-01-01

    There are four new microbial genomes listed in this month's Genome Update, three belonging to Gram-positive bacteria and one belonging to an archaeon that lives at pH 0; all of these genomes are listed in Table 1⇓. The method of genome comparison this month is that of genome alignment and, as an ...

  20. The prevalence of the HPV 16 genome, integrated viral status and p53 genotype in cervical cancer population of north-eastern Hungary, the correlation with the established markers of tumour progression.

    Science.gov (United States)

    Hernádi, Zoltán; Sápy, Tamás; Krasznai, Zoárd T

    2004-03-15

    To evaluate the prevalence of the HPV 16 integrated status and the p53 genotype in cervical cancer in north-eastern Hungary and their correlation with the established prognostic factors. Parallel with the routine histological examination, Southern blot hybridisation and multiplex PCRs were used to detect type/physical state of HPV DNA in primary tumours and in regional lymph nodes combined with p53 genotyping of 83 patients. 46.9% (39/83) prevalence rate of HPV 16 genome was found. The frequency of viral integration (76.9% in primary tumours and 95.2% in regional lymph nodes) and that of the p53Arg homozygous genotype (64.1%) proved to be higher than reported from other parts of the world. The HPV 16 integration and the p53 genotype, failed to correlate with the FIGO stage and lymphatic spread. The prevalence of the integrated status of the HPV 16 genome combined with homozygous p53Arg genotype is relatively high in Hungary. These factors however failed to show a strong correlation with the established markers of tumour progression.

  1. Genomics and cardiovascular disease.

    Science.gov (United States)

    Frazier, Lorraine; Johnson, Rolanda L; Sparks, Elizabeth

    2005-01-01

    To describe genetic knowledge and discovery in the area of cardiovascular disease (CVD) and to discuss how these new advances will influence the clinical care of affected people. A selective review of the literature is presented on the disease mechanism of both the Mendelian and multifactorial genetic cardiovascular conditions. A case study approach is used to illustrate how the genetic paradigm affects the healthcare experience of a family affected with familial hypertrophic cardiomyopathy. The current state of CVD treatment remains complex. An understanding of genomic concepts and a genome-based approach is necessary to determine: (a) the risk of CVD susceptibility beyond traditional risk factors; (b) early detection of illness; (c) response to treatment; and (d) molecular taxonomy of the disease. The results of genetic research, education, and teaching will lead to a new understanding of genes and pathways, resulting in powerful new therapeutic approaches to CVD. The challenge is to translate genetic discoveries into clinical practice that ultimately leads to preventing CVD and reducing mortality.

  2. ENCODE whole-genome data in the UCSC Genome Browser

    Science.gov (United States)

    Rosenbloom, Kate R.; Dreszer, Timothy R.; Pheasant, Michael; Barber, Galt P.; Meyer, Laurence R.; Pohl, Andy; Raney, Brian J.; Wang, Ting; Hinrichs, Angie S.; Zweig, Ann S.; Fujita, Pauline A.; Learned, Katrina; Rhead, Brooke; Smith, Kayla E.; Kuhn, Robert M.; Karolchik, Donna; Haussler, David; Kent, W. James

    2010-01-01

    The Encyclopedia of DNA Elements (ENCODE) project is an international consortium of investigators funded to analyze the human genome with the goal of producing a comprehensive catalog of functional elements. The ENCODE Data Coordination Center at The University of California, Santa Cruz (UCSC) is the primary repository for experimental results generated by ENCODE investigators. These results are captured in the UCSC Genome Bioinformatics database and download server for visualization and data mining via the UCSC Genome Browser and companion tools (Rhead et al. The UCSC Genome Browser Database: update 2010, in this issue). The ENCODE web portal at UCSC (http://encodeproject.org or http://genome.ucsc.edu/ENCODE) provides information about the ENCODE data and convenient links for access. PMID:19920125

  3. A Taste of Algal Genomes from the Joint Genome Institute

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Alan; Grigoriev, Igor

    2012-06-17

    Algae play profound roles in aquatic food chains and the carbon cycle, can impose health and economic costs through toxic blooms, provide models for the study of symbiosis, photosynthesis, and eukaryotic evolution, and are candidate sources for bio-fuels; all of these research areas are part of the mission of DOE's Joint Genome Institute (JGI). To date JGI has sequenced, assembled, annotated, and released to the public the genomes of 18 species and strains of algae, sampling almost all of the major clades of photosynthetic eukaryotes. With more algal genomes currently undergoing analysis, JGI continues its commitment to driving forward basic and applied algal science. Among these ongoing projects are the pan-genome of the dominant coccolithophore Emiliania huxleyi, the interrelationships between the 4 genomes in the nucleomorph-containing Bigelowiella natans and Guillardia theta, and the search for symbiosis genes of lichens.

  4. Genomic selection: genome-wide prediction in plant improvement.

    Science.gov (United States)

    Desta, Zeratsion Abera; Ortiz, Rodomiro

    2014-09-01

    Association analysis is used to measure relations between markers and quantitative trait loci (QTL). Their estimation ignores genes with small effects that trigger underpinning quantitative traits. By contrast, genome-wide selection estimates marker effects across the whole genome on the target population based on a prediction model developed in the training population (TP). Whole-genome prediction models estimate all marker effects in all loci and capture small QTL effects. Here, we review several genomic selection (GS) models with respect to both the prediction accuracy and genetic gain from selection. Phenotypic selection or marker-assisted breeding protocols can be replaced by selection, based on whole-genome predictions in which phenotyping updates the model to build up the prediction accuracy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Parasite Genome Projects and the Trypanosoma cruzi Genome Initiative

    Directory of Open Access Journals (Sweden)

    Wim Degrave

    1997-11-01

    Full Text Available Since the start of the human genome project, a great number of genome projects on other "model" organism have been initiated, some of them already completed. Several initiatives have also been started on parasite genomes, mainly through support from WHO/TDR, involving North-South and South-South collaborations, and great hopes are vested in that these initiatives will lead to new tools for disease control and prevention, as well as to the establishment of genomic research technology in developing countries. The Trypanosoma cruzi genome project, using the clone CL-Brener as starting point, has made considerable progress through the concerted action of more than 20 laboratories, most of them in the South. A brief overview of the current state of the project is given

  6. Genome update: the 1000th genome - a cautionary tale

    DEFF Research Database (Denmark)

    Lagesen, Karin; Ussery, David; Wassenaar, Gertrude Maria

    2010-01-01

    There are now more than 1000 sequenced prokaryotic genomes deposited in public databases and available for analysis. Currently, although the sequence databases GenBank, DNA Database of Japan and EMBL are synchronized continually, there are slight differences in content at the genomes level...... for a variety of logistical reasons, including differences in format and loading errors, such as those caused by file transfer protocol interruptions. This means that the 1000th genome will be different in the various databases. Some of the data on the highly accessed web pages are inaccurate, leading to false......, of the 1000 genomes available, not a single protein is conserved across all genomes. Excluding the members of the Archaea, only a total of four genes are conserved in all bacteria: two protein genes and two RNA genes....

  7. Genome graphs and the evolution of genome inference

    Science.gov (United States)

    Paten, Benedict; Novak, Adam M.; Eizenga, Jordan M.; Garrison, Erik

    2017-01-01

    The human reference genome is part of the foundation of modern human biology and a monumental scientific achievement. However, because it excludes a great deal of common human variation, it introduces a pervasive reference bias into the field of human genomics. To reduce this bias, it makes sense to draw on representative collections of human genomes, brought together into reference cohorts. There are a number of techniques to represent and organize data gleaned from these cohorts, many using ideas implicitly or explicitly borrowed from graph-based models. Here, we survey various projects underway to build and apply these graph-based structures—which we collectively refer to as genome graphs—and discuss the improvements in read mapping, variant calling, and haplotype determination that genome graphs are expected to produce. PMID:28360232

  8. Theory of microbial genome evolution

    Science.gov (United States)

    Koonin, Eugene

    Bacteria and archaea have small genomes tightly packed with protein-coding genes. This compactness is commonly perceived as evidence of adaptive genome streamlining caused by strong purifying selection in large microbial populations. In such populations, even the small cost incurred by nonfunctional DNA because of extra energy and time expenditure is thought to be sufficient for this extra genetic material to be eliminated by selection. However, contrary to the predictions of this model, there exists a consistent, positive correlation between the strength of selection at the protein sequence level, measured as the ratio of nonsynonymous to synonymous substitution rates, and microbial genome size. By fitting the genome size distributions in multiple groups of prokaryotes to predictions of mathematical models of population evolution, we show that only models in which acquisition of additional genes is, on average, slightly beneficial yield a good fit to genomic data. Thus, the number of genes in prokaryotic genomes seems to reflect the equilibrium between the benefit of additional genes that diminishes as the genome grows and deletion bias. New genes acquired by microbial genomes, on average, appear to be adaptive. Evolution of bacterial and archaeal genomes involves extensive horizontal gene transfer and gene loss. Many microbes have open pangenomes, where each newly sequenced genome contains more than 10% `ORFans', genes without detectable homologues in other species. A simple, steady-state evolutionary model reveals two sharply distinct classes of microbial genes, one of which (ORFans) is characterized by effectively instantaneous gene replacement, whereas the other consists of genes with finite, distributed replacement rates. These findings imply a conservative estimate of at least a billion distinct genes in the prokaryotic genomic universe.

  9. OryzaGenome: Genome Diversity Database of Wild Oryza Species

    KAUST Repository

    Ohyanagi, Hajime

    2015-11-18

    The species in the genus Oryza, encompassing nine genome types and 23 species, are a rich genetic resource and may have applications in deeper genomic analyses aiming to understand the evolution of plant genomes. With the advancement of next-generation sequencing (NGS) technology, a flood of Oryza species reference genomes and genomic variation information has become available in recent years. This genomic information, combined with the comprehensive phenotypic information that we are accumulating in our Oryzabase, can serve as an excellent genotype-phenotype association resource for analyzing rice functional and structural evolution, and the associated diversity of the Oryza genus. Here we integrate our previous and future phenotypic/habitat information and newly determined genotype information into a united repository, named OryzaGenome, providing the variant information with hyperlinks to Oryzabase. The current version of OryzaGenome includes genotype information of 446 O. rufipogon accessions derived by imputation and of 17 accessions derived by imputation-free deep sequencing. Two variant viewers are implemented: SNP Viewer as a conventional genome browser interface and Variant Table as a textbased browser for precise inspection of each variant one by one. Portable VCF (variant call format) file or tabdelimited file download is also available. Following these SNP (single nucleotide polymorphism) data, reference pseudomolecules/ scaffolds/contigs and genome-wide variation information for almost all of the closely and distantly related wild Oryza species from the NIG Wild Rice Collection will be available in future releases. All of the resources can be accessed through http://viewer.shigen.info/oryzagenome/.

  10. Cri-du-Chat syndrome diagnosed in a 21-year-old woman by means of comparative genomic hybridization

    Directory of Open Access Journals (Sweden)

    Wilmar Saldarriaga

    2017-07-01

    The following is the case report of a 21-year-old female patient with severe mental retardation and trichotillomania, who does not control sphincters and does not bathe or eat by herself. Her communication is based only on sounds and dysmorphic facies. The G-band karyotype reported is 46, XX. a-CGH shows 18.583Mb interstitial microdeletion in 5p15.33p14.3, including the cri-du-chat critical region. In children or adults with unexplained mental retardation and normal karyotype results (like this case, an a-CGH should be performed to make an etiological diagnosis, establish the prognosis, order additional medical tests and specific treatments, and offer appropriate genetic counseling.

  11. Fueling Future with Algal Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor

    2012-07-05

    Algae constitute a major component of fundamental eukaryotic diversity, play profound roles in the carbon cycle, and are prominent candidates for biofuel production. The US Department of Energy Joint Genome Institute (JGI) is leading the world in algal genome sequencing (http://jgi.doe.gov/Algae) and contributes of the algal genome projects worldwide (GOLD database, 2012). The sequenced algal genomes offer catalogs of genes, networks, and pathways. The sequenced first of its kind genomes of a haptophyte E.huxleyii, chlorarachniophyte B.natans, and cryptophyte G.theta fill the gaps in the eukaryotic tree of life and carry unique genes and pathways as well as molecular fossils of secondary endosymbiosis. Natural adaptation to conditions critical for industrial production is encoded in algal genomes, for example, growth of A.anophagefferens at very high cell densities during the harmful algae blooms or a global distribution across diverse environments of E.huxleyii, able to live on sparse nutrients due to its expanded pan-genome. Communications and signaling pathways can be derived from simple symbiotic systems like lichens or complex marine algae metagenomes. Collectively these datasets derived from algal genomics contribute to building a comprehensive parts list essential for algal biofuel development.

  12. Comparative genomic hybridization: practical guidelines.

    NARCIS (Netherlands)

    Jeuken, J.W.M.; Sprenger, S.H.; Wesseling, P.

    2002-01-01

    Comparative genomic hybridization (CGH) is a technique used to identify copy number changes throughout a genome. Until now, hundreds of CGH studies have been published reporting chromosomal imbalances in a large variety of human neoplasms. Additionally, technical improvements of specific steps in a

  13. Cocoa/Cotton Comparative Genomics

    Science.gov (United States)

    With genome sequence from two members of the Malvaceae family recently made available, we are exploring syntenic relationships, gene content, and evolutionary trajectories between the cacao and cotton genomes. An assembly of cacao (Theobroma cacao) using Illumina and 454 sequence technology yielded ...

  14. Future Health Applications of Genomics

    Science.gov (United States)

    McBride, Colleen M.; Bowen, Deborah; Brody, Lawrence C.; Condit, Celeste M.; Croyle, Robert T.; Gwinn, Marta; Khoury, Muin J.; Koehly, Laura M.; Korf, Bruce R.; Marteau, Theresa M.; McLeroy, Kenneth; Patrick, Kevin; Valente, Thomas W.

    2014-01-01

    Despite the quickening momentum of genomic discovery, the communication, behavioral, and social sciences research needed for translating this discovery into public health applications has lagged behind. The National Human Genome Research Institute held a 2-day workshop in October 2008 convening an interdisciplinary group of scientists to recommend forward-looking priorities for translational research. This research agenda would be designed to redress the top three risk factors (tobacco use, poor diet, and physical inactivity) that contribute to the four major chronic diseases (heart disease, type 2 diabetes, lung disease, and many cancers) and account for half of all deaths worldwide. Three priority research areas were identified: (1) improving the public’s genetic literacy in order to enhance consumer skills; (2) gauging whether genomic information improves risk communication and adoption of healthier behaviors more than current approaches; and (3) exploring whether genomic discovery in concert with emerging technologies can elucidate new behavioral intervention targets. Important crosscutting themes also were identified, including the need to: (1) anticipate directions of genomic discovery; (2) take an agnostic scientific perspective in framing research questions asking whether genomic discovery adds value to other health promotion efforts; and (3) consider multiple levels of influence and systems that contribute to important public health problems. The priorities and themes offer a framework for a variety of stakeholders, including those who develop priorities for research funding, interdisciplinary teams engaged in genomics research, and policymakers grappling with how to use the products born of genomics research to address public health challenges. PMID:20409503

  15. Genome editing in cardiovascular diseases.

    Science.gov (United States)

    Strong, Alanna; Musunuru, Kiran

    2017-01-01

    Genome-editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) systems, have emerged as an invaluable technology to achieve somatic and germline genomic manipulation in cells and model organisms for multiple applications, including the creation of knockout alleles, introducing desired mutations into genomic DNA, and inserting novel transgenes. Genome editing is being rapidly adopted into all fields of biomedical research, including the cardiovascular field, where it has facilitated a greater understanding of lipid metabolism, electrophysiology, cardiomyopathies, and other cardiovascular disorders, has helped to create a wider variety of cellular and animal models, and has opened the door to a new class of therapies. In this Review, we discuss the applications of genome-editing technology throughout cardiovascular disease research and the prospect of in vivo genome-editing therapies in the future. We also describe some of the existing limitations of genome-editing tools that will need to be addressed if cardiovascular genome editing is to achieve its full scientific and therapeutic potential.

  16. The promise of insect genomics

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, Cornelis J P; Cazzamali, Giuseppe; Williamson, Michael

    2007-01-01

    Insects are the largest animal group in the world and are ecologically and economically extremely important. This importance of insects is reflected by the existence of currently 24 insect genome projects. Our perspective discusses the state-of-the-art of these genome projects and the impacts...

  17. Comparative Genomics of the Cucurbitaceae

    Science.gov (United States)

    The genome size for watermelon, melon, cucumber, and pumpkin is 425, 454, 367, and 502 Mbp, respectively, and considered medium size as compared with most other crops. Whole-genome duplication is common in angiosperm plants. Research has revealed a paleohexaploidy (') event in the common ancestor of...

  18. Bioinformatics of genomic association mapping

    NARCIS (Netherlands)

    Vaez Barzani, Ahmad

    2015-01-01

    In this thesis we present an overview of bioinformatics-based approaches for genomic association mapping, with emphasis on human quantitative traits and their contribution to complex diseases. We aim to provide a comprehensive walk-through of the classic steps of genomic association mapping

  19. International genomic evaluation methods for dairy cattle

    Science.gov (United States)

    Background Genomic evaluations are rapidly replacing traditional evaluation systems used for dairy cattle selection. Economies of scale in genomics promote cooperation across country borders. Genomic information can be transferred across countries using simple conversion equations, by modifying mult...

  20. Open chromatin in plant genomes.

    Science.gov (United States)

    Zhang, Wenli; Zhang, Tao; Wu, Yufeng; Jiang, Jiming

    2014-01-01

    Sensitivity to DNase I digestion is an indicator of the accessibility and configuration of chromatin in eukaryotic genomes. Open chromatin exhibits high sensitivity to DNase I cleavage. DNase I hypersensitive sites (DHSs) in eukaryotic genomes can be identified through DNase I treatment followed by sequencing (DNase-seq). DHSs are most frequently associated with various cis-regulatory DNA elements, including promoters, enhancers, and silencers in both animal and plant genomes. Genome-wide identification of DHSs provides an efficient method to interpret previously un-annotated regulatory DNA sequences. In this review, we provide an overview of the historical perspective of DHS research in eukaryotes. We summarize the main achievements of DHS research in model animal species and review the recent progress of DHS research in plants. We finally discuss possible future directions of using DHS as a tool in plant genomics research. © 2014 S. Karger AG, Basel.

  1. [Trends of angiosperm genome evolution].

    Science.gov (United States)

    Sheremet'ev, S N; Gamaleĭ, Iu V; Slemnev, N N

    2011-01-01

    Direction of evolutionary variability of parameters of genome size and structurally functional activity of plants on life forms groups and angiosperms taxa are analyzed. It is shown that, in the Cretaceous-Cenozoic, their nuclear genome tended to increase. Functional genome efficiency (intensity of functions per 1 pg of DNA) decreased from as much as possible high at trees and lianas of rain and monsoonal forests of the Paleogene to minimum at shrubs, perennial and annual grasses of meadow-steppe vegetation which had appeared in the neogene. Important for the vegetation environmental changes in temperature, humidity and CO2 concentration in an adverse direction are discussed as the cause of evolutionary genome size growth and decrease in its functional efficiency. Price for phylogenetic adaptogenesis of angiosperms to the step Cenozoic climate cooling was 4-fold and more genome growth.

  2. Allele coding in genomic evaluation

    DEFF Research Database (Denmark)

    Standen, Ismo; Christensen, Ole Fredslund

    2011-01-01

    Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker...... effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous...... this centered allele coding. This study considered effects of different allele coding methods on inference. Both marker-based and equivalent models were considered, and restricted maximum likelihood and Bayesian methods were used in inference. \\paragraph*{Results:} Theoretical derivations showed that parameter...

  3. Pathophysiology of MDS: genomic aberrations.

    Science.gov (United States)

    Ichikawa, Motoshi

    2016-01-01

    Myelodysplastic syndromes (MDS) are characterized by clonal proliferation of hematopoietic stem/progenitor cells and their apoptosis, and show a propensity to progress to acute myelogenous leukemia (AML). Although MDS are recognized as neoplastic diseases caused by genomic aberrations of hematopoietic cells, the details of the genetic abnormalities underlying disease development have not as yet been fully elucidated due to difficulties in analyzing chromosomal abnormalities. Recent advances in comprehensive analyses of disease genomes including whole-genome sequencing technologies have revealed the genomic abnormalities in MDS. Surprisingly, gene mutations were found in approximately 80-90% of cases with MDS, and the novel mutations discovered with these technologies included previously unknown, MDS-specific, mutations such as those of the genes in the RNA-splicing machinery. It is anticipated that these recent studies will shed new light on the pathophysiology of MDS due to genomic aberrations.

  4. Genomic methods take the plunge

    DEFF Research Database (Denmark)

    Cammen, Kristina M.; Andrews, Kimberly R.; Carroll, Emma L.

    2016-01-01

    The dramatic increase in the application of genomic techniques to non-model organisms (NMOs) over the past decade has yielded numerous valuable contributions to evolutionary biology and ecology, many of which would not have been possible with traditional genetic markers. We review this recent...... progression with a particular focus on genomic studies of marine mammals, a group of taxa that represent key macroevolutionary transitions from terrestrial to marine environments and for which available genomic resources have recently undergone notable rapid growth. Genomic studies of NMOs utilize...... an expanding range of approaches, including whole genome sequencing, restriction site-associated DNA sequencing, array-based sequencing of single nucleotide polymorphisms and target sequence probes (e.g., exomes), and transcriptome sequencing. These approaches generate different types and quantities of data...

  5. [Preface for genome editing special issue].

    Science.gov (United States)

    Gu, Feng; Gao, Caixia

    2017-10-25

    Genome editing technology, as an innovative biotechnology, has been widely used for editing the genome from model organisms, animals, plants and microbes. CRISPR/Cas9-based genome editing technology shows its great value and potential in the dissection of functional genomics, improved breeding and genetic disease treatment. In the present special issue, the principle and application of genome editing techniques has been summarized. The advantages and disadvantages of the current genome editing technology and future prospects would also be highlighted.

  6. Privacy in the Genomic Era

    Science.gov (United States)

    NAVEED, MUHAMMAD; AYDAY, ERMAN; CLAYTON, ELLEN W.; FELLAY, JACQUES; GUNTER, CARL A.; HUBAUX, JEAN-PIERRE; MALIN, BRADLEY A.; WANG, XIAOFENG

    2015-01-01

    Genome sequencing technology has advanced at a rapid pace and it is now possible to generate highly-detailed genotypes inexpensively. The collection and analysis of such data has the potential to support various applications, including personalized medical services. While the benefits of the genomics revolution are trumpeted by the biomedical community, the increased availability of such data has major implications for personal privacy; notably because the genome has certain essential features, which include (but are not limited to) (i) an association with traits and certain diseases, (ii) identification capability (e.g., forensics), and (iii) revelation of family relationships. Moreover, direct-to-consumer DNA testing increases the likelihood that genome data will be made available in less regulated environments, such as the Internet and for-profit companies. The problem of genome data privacy thus resides at the crossroads of computer science, medicine, and public policy. While the computer scientists have addressed data privacy for various data types, there has been less attention dedicated to genomic data. Thus, the goal of this paper is to provide a systematization of knowledge for the computer science community. In doing so, we address some of the (sometimes erroneous) beliefs of this field and we report on a survey we conducted about genome data privacy with biomedical specialists. Then, after characterizing the genome privacy problem, we review the state-of-the-art regarding privacy attacks on genomic data and strategies for mitigating such attacks, as well as contextualizing these attacks from the perspective of medicine and public policy. This paper concludes with an enumeration of the challenges for genome data privacy and presents a framework to systematize the analysis of threats and the design of countermeasures as the field moves forward. PMID:26640318

  7. Privacy in the Genomic Era.

    Science.gov (United States)

    Naveed, Muhammad; Ayday, Erman; Clayton, Ellen W; Fellay, Jacques; Gunter, Carl A; Hubaux, Jean-Pierre; Malin, Bradley A; Wang, Xiaofeng

    2015-09-01

    Genome sequencing technology has advanced at a rapid pace and it is now possible to generate highly-detailed genotypes inexpensively. The collection and analysis of such data has the potential to support various applications, including personalized medical services. While the benefits of the genomics revolution are trumpeted by the biomedical community, the increased availability of such data has major implications for personal privacy; notably because the genome has certain essential features, which include (but are not limited to) (i) an association with traits and certain diseases, (ii) identification capability (e.g., forensics), and (iii) revelation of family relationships. Moreover, direct-to-consumer DNA testing increases the likelihood that genome data will be made available in less regulated environments, such as the Internet and for-profit companies. The problem of genome data privacy thus resides at the crossroads of computer science, medicine, and public policy. While the computer scientists have addressed data privacy for various data types, there has been less attention dedicated to genomic data. Thus, the goal of this paper is to provide a systematization of knowledge for the computer science community. In doing so, we address some of the (sometimes erroneous) beliefs of this field and we report on a survey we conducted about genome data privacy with biomedical specialists. Then, after characterizing the genome privacy problem, we review the state-of-the-art regarding privacy attacks on genomic data and strategies for mitigating such attacks, as well as contextualizing these attacks from the perspective of medicine and public policy. This paper concludes with an enumeration of the challenges for genome data privacy and presents a framework to systematize the analysis of threats and the design of countermeasures as the field moves forward.

  8. The South Asian genome.

    Directory of Open Access Journals (Sweden)

    John C Chambers

    Full Text Available The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.

  9. Inheritance of the yeast mitochondrial genome

    DEFF Research Database (Denmark)

    Piskur, Jure

    1994-01-01

    Mitochondrion, extrachromosomal genetics, intergenic sequences, genome size, mitochondrial DNA, petite mutation, yeast......Mitochondrion, extrachromosomal genetics, intergenic sequences, genome size, mitochondrial DNA, petite mutation, yeast...

  10. Plantagora: modeling whole genome sequencing and assembly of plant genomes.

    Directory of Open Access Journals (Sweden)

    Roger Barthelson

    Full Text Available BACKGROUND: Genomics studies are being revolutionized by the next generation sequencing technologies, which have made whole genome sequencing much more accessible to the average researcher. Whole genome sequencing with the new technologies is a developing art that, despite the large volumes of data that can be produced, may still fail to provide a clear and thorough map of a genome. The Plantagora project was conceived to address specifically the gap between having the technical tools for genome sequencing and knowing precisely the best way to use them. METHODOLOGY/PRINCIPAL FINDINGS: For Plantagora, a platform was created for generating simulated reads from several different plant genomes of different sizes. The resulting read files mimicked either 454 or Illumina reads, with varying paired end spacing. Thousands of datasets of reads were created, most derived from our primary model genome, rice chromosome one. All reads were assembled with different software assemblers, including Newbler, Abyss, and SOAPdenovo, and the resulting assemblies were evaluated by an extensive battery of metrics chosen for these studies. The metrics included both statistics of the assembly sequences and fidelity-related measures derived by alignment of the assemblies to the original genome source for the reads. The results were presented in a website, which includes a data graphing tool, all created to help the user compare rapidly the feasibility and effectiveness of different sequencing and assembly strategies prior to testing an approach in the lab. Some of our own conclusions regarding the different strategies were also recorded on the website. CONCLUSIONS/SIGNIFICANCE: Plantagora provides a substantial body of information for comparing different approaches to sequencing a plant genome, and some conclusions regarding some of the specific approaches. Plantagora also provides a platform of metrics and tools for studying the process of sequencing and assembly

  11. The Perennial Ryegrass GenomeZipper – Targeted Use of Genome Resources for Comparative Grass Genomics

    DEFF Research Database (Denmark)

    Pfeiffer, Matthias; Martis, Mihaela; Asp, Torben

    2013-01-01

    Whole-genome sequences established for model and major crop species constitute a key resource for advanced genomic research. For outbreeding forage and turf grass species like ryegrasses (Lolium spp.), such resources have yet to be developed. Here, we present a model of the perennial ryegrass (Lo...

  12. Comparative Genomics Reveals High Genomic Diversity in the Genus Photobacterium

    DEFF Research Database (Denmark)

    Machado, Henrique; Gram, Lone

    2017-01-01

    Vibrionaceae is a large marine bacterial family, which can constitute up to 50% of the prokaryotic population in marine waters. Photobacterium is the second largest genus in the family and we used comparative genomics on 35 strains representing 16 of the 28 species described so far, to understand...... the genomic diversity present in the Photobacterium genus. Such understanding is important for ecophysiology studies of the genus. We used whole genome sequences to evaluate phylogenetic relationships using several analyses (16S rRNA, MLSA, fur, amino-acid usage, ANI), which allowed us to identify two...

  13. Comparative genomics reveals insights into avian genome evolution and adaptation

    DEFF Research Database (Denmark)

    Zhang, Guojie; Li, Cai; Li, Qiye

    2014-01-01

    Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size...... this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits....

  14. Components of Adenovirus Genome Packaging

    Science.gov (United States)

    Ahi, Yadvinder S.; Mittal, Suresh K.

    2016-01-01

    Adenoviruses (AdVs) are icosahedral viruses with double-stranded DNA (dsDNA) genomes. Genome packaging in AdV is thought to be similar to that seen in dsDNA containing icosahedral bacteriophages and herpesviruses. Specific recognition of the AdV genome is mediated by a packaging domain located close to the left end of the viral genome and is mediated by the viral packaging machinery. Our understanding of the role of various components of the viral packaging machinery in AdV genome packaging has greatly advanced in recent years. Characterization of empty capsids assembled in the absence of one or more components involved in packaging, identification of the unique vertex, and demonstration of the role of IVa2, the putative packaging ATPase, in genome packaging have provided compelling evidence that AdVs follow a sequential assembly pathway. This review provides a detailed discussion on the functions of the various viral and cellular factors involved in AdV genome packaging. We conclude by briefly discussing the roles of the empty capsids, assembly intermediates, scaffolding proteins, portal vertex and DNA encapsidating enzymes in AdV assembly and packaging. PMID:27721809

  15. The genome of Eucalyptus grandis

    Energy Technology Data Exchange (ETDEWEB)

    Myburg, Alexander A.; Grattapaglia, Dario; Tuskan, Gerald A.; Hellsten, Uffe; Hayes, Richard D.; Grimwood, Jane; Jenkins, Jerry; Lindquist, Erika; Tice, Hope; Bauer, Diane; Goodstein, David M.; Dubchak, Inna; Poliakov, Alexandre; Mizrachi, Eshchar; Kullan, Anand R. K.; Hussey, Steven G.; Pinard, Desre; van der Merwe, Karen; Singh, Pooja; van Jaarsveld, Ida; Silva-Junior, Orzenil B.; Togawa, Roberto C.; Pappas, Marilia R.; Faria, Danielle A.; Sansaloni, Carolina P.; Petroli, Cesar D.; Yang, Xiaohan; Ranjan, Priya; Tschaplinski, Timothy J.; Ye, Chu-Yu; Li, Ting; Sterck, Lieven; Vanneste, Kevin; Murat, Florent; Soler, Marçal; Clemente, Hélène San; Saidi, Naijib; Cassan-Wang, Hua; Dunand, Christophe; Hefer, Charles A.; Bornberg-Bauer, Erich; Kersting, Anna R.; Vining, Kelly; Amarasinghe, Vindhya; Ranik, Martin; Naithani, Sushma; Elser, Justin; Boyd, Alexander E.; Liston, Aaron; Spatafora, Joseph W.; Dharmwardhana, Palitha; Raja, Rajani; Sullivan, Christopher; Romanel, Elisson; Alves-Ferreira, Marcio; Külheim, Carsten; Foley, William; Carocha, Victor; Paiva, Jorge; Kudrna, David; Brommonschenkel, Sergio H.; Pasquali, Giancarlo; Byrne, Margaret; Rigault, Philippe; Tibbits, Josquin; Spokevicius, Antanas; Jones, Rebecca C.; Steane, Dorothy A.; Vaillancourt, René E.; Potts, Brad M.; Joubert, Fourie; Barry, Kerrie; Pappas, Georgios J.; Strauss, Steven H.; Jaiswal, Pankaj; Grima-Pettenati, Jacqueline; Salse, Jérôme; Van de Peer, Yves; Rokhsar, Daniel S.; Schmutz, Jeremy

    2014-06-11

    Eucalypts are the world s most widely planted hardwood trees. Their broad adaptability, rich species diversity, fast growth and superior multipurpose wood, have made them a global renewable resource of fiber and energy that mitigates human pressures on natural forests. We sequenced and assembled >94% of the 640 Mbp genome of Eucalyptus grandis into its 11 chromosomes. A set of 36,376 protein coding genes were predicted revealing that 34% occur in tandem duplications, the largest proportion found thus far in any plant genome. Eucalypts also show the highest diversity of genes for plant specialized metabolism that act as chemical defence against biotic agents and provide unique pharmaceutical oils. Resequencing of a set of inbred tree genomes revealed regions of strongly conserved heterozygosity, likely hotspots of inbreeding depression. The resequenced genome of the sister species E. globulus underscored the high inter-specific genome colinearity despite substantial genome size variation in the genus. The genome of E. grandis is the first reference for the early diverging Rosid order Myrtales and is placed here basal to the Eurosids. This resource expands knowledge on the unique biology of large woody perennials and provides a powerful tool to accelerate comparative biology, breeding and biotechnology.

  16. Functional genomics of intracellular bacteria.

    Science.gov (United States)

    de Barsy, Marie; Greub, Gilbert

    2013-07-01

    During the genomic era, a large amount of whole-genome sequences accumulated, which identified many hypothetical proteins of unknown function. Rapidly, functional genomics, which is the research domain that assign a function to a given gene product, has thus been developed. Functional genomics of intracellular pathogenic bacteria exhibit specific peculiarities due to the fastidious growth of most of these intracellular micro-organisms, due to the close interaction with the host cell, due to the risk of contamination of experiments with host cell proteins and, for some strict intracellular bacteria such as Chlamydia, due to the absence of simple genetic system to manipulate the bacterial genome. To identify virulence factors of intracellular pathogenic bacteria, functional genomics often rely on bioinformatic analyses compared with model organisms such as Escherichia coli and Bacillus subtilis. The use of heterologous expression is another common approach. Given the intracellular lifestyle and the many effectors that are used by the intracellular bacteria to corrupt host cell functions, functional genomics is also often targeting the identification of new effectors such as those of the T4SS of Brucella and Legionella.

  17. [Genome editing of industrial microorganism].

    Science.gov (United States)

    Zhu, Linjiang; Li, Qi

    2015-03-01

    Genome editing is defined as highly-effective and precise modification of cellular genome in a large scale. In recent years, such genome-editing methods have been rapidly developed in the field of industrial strain improvement. The quickly-updating methods thoroughly change the old mode of inefficient genetic modification, which is "one modification, one selection marker, and one target site". Highly-effective modification mode in genome editing have been developed including simultaneous modification of multiplex genes, highly-effective insertion, replacement, and deletion of target genes in the genome scale, cut-paste of a large DNA fragment. These new tools for microbial genome editing will certainly be applied widely, and increase the efficiency of industrial strain improvement, and promote the revolution of traditional fermentation industry and rapid development of novel industrial biotechnology like production of biofuel and biomaterial. The technological principle of these genome-editing methods and their applications were summarized in this review, which can benefit engineering and construction of industrial microorganism.

  18. Recurring genomic breaks in independent lineages support genomic fragility

    Directory of Open Access Journals (Sweden)

    Hannenhalli Sridhar

    2006-11-01

    Full Text Available Abstract Background Recent findings indicate that evolutionary breaks in the genome are not randomly distributed, and that certain regions, so-called fragile regions, are predisposed to breakages. Previous approaches to the study of genomic fragility have examined the distribution of breaks, as well as the coincidence of breaks with segmental duplications and repeats, within a single species. In contrast, we investigate whether this regional fragility is an inherent genomic characteristic and is thus conserved over multiple independent lineages. Results We do this by quantifying the extent to which certain genomic regions are disrupted repeatedly in independent lineages. Our investigation, based on Human, Chimp, Mouse, Rat, Dog and Chicken, suggests that the propensity of a chromosomal region to break is significantly correlated among independent lineages, even when covariates are considered. Furthermore, the fragile regions are enriched for segmental duplications. Conclusion Based on a novel methodology, our work provides additional support for the existence of fragile regions.

  19. Genome Modeling System: A Knowledge Management Platform for Genomics.

    Directory of Open Access Journals (Sweden)

    Malachi Griffith

    2015-07-01

    Full Text Available In this work, we present the Genome Modeling System (GMS, an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395 and matched lymphoblastoid line (HCC1395BL. These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms.

  20. The bonobo genome compared with the chimpanzee and human genomes

    Science.gov (United States)

    Prüfer, Kay; Munch, Kasper; Hellmann, Ines; Akagi, Keiko; Miller, Jason R.; Walenz, Brian; Koren, Sergey; Sutton, Granger; Kodira, Chinnappa; Winer, Roger; Knight, James R.; Mullikin, James C.; Meader, Stephen J.; Ponting, Chris P.; Lunter, Gerton; Higashino, Saneyuki; Hobolth, Asger; Dutheil, Julien; Karakoç, Emre; Alkan, Can; Sajjadian, Saba; Catacchio, Claudia Rita; Ventura, Mario; Marques-Bonet, Tomas; Eichler, Evan E.; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Junhold, Jörg; Patterson, Nick; Siebauer, Michael; Good, Jeffrey M.; Fischer, Anne; Ptak, Susan E.; Lachmann, Michael; Symer, David E.; Mailund, Thomas; Schierup, Mikkel H.; Andrés, Aida M.; Kelso, Janet; Pääbo, Svante

    2012-01-01

    Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours1–4, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other. PMID:22722832

  1. Implementing Genome-Driven Oncology

    Science.gov (United States)

    Hyman, David M.; Taylor, Barry S.; Baselga, José

    2017-01-01

    Early successes in identifying and targeting individual oncogenic drivers, together with the increasing feasibility of sequencing tumor genomes, have brought forth the promise of genome-driven oncology care. As we expand the breadth and depth of genomic analyses, the biological and clinical complexity of its implementation will be unparalleled. Challenges include target credentialing and validation, implementing drug combinations, clinical trial designs, targeting tumor heterogeneity, and deploying technologies beyond DNA sequencing, among others. We review how contemporary approaches are tackling these challenges and will ultimately serve as an engine for biological discovery and increase our insight into cancer and its treatment. PMID:28187282

  2. Human genome. 1993 Program report

    Energy Technology Data Exchange (ETDEWEB)

    1994-03-01

    The purpose of this report is to update the Human Genome 1991-92 Program Report and provide new information on the DOE genome program to researchers, program managers, other government agencies, and the interested public. This FY 1993 supplement includes abstracts of 60 new or renewed projects and listings of 112 continuing and 28 completed projects. These two reports, taken together, present the most complete published view of the DOE Human Genome Program through FY 1993. Research is progressing rapidly toward 15-year goals of mapping and sequencing the DNA of each of the 24 different human chromosomes.

  3. Capturing prokaryotic dark matter genomes.

    Science.gov (United States)

    Gasc, Cyrielle; Ribière, Céline; Parisot, Nicolas; Beugnot, Réjane; Defois, Clémence; Petit-Biderre, Corinne; Boucher, Delphine; Peyretaillade, Eric; Peyret, Pierre

    2015-12-01

    Prokaryotes are the most diverse and abundant cellular life forms on Earth. Most of them, identified by indirect molecular approaches, belong to microbial dark matter. The advent of metagenomic and single-cell genomic approaches has highlighted the metabolic capabilities of numerous members of this dark matter through genome reconstruction. Thus, linking functions back to the species has revolutionized our understanding of how ecosystem function is sustained by the microbial world. This review will present discoveries acquired through the illumination of prokaryotic dark matter genomes by these innovative approaches. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  4. Applied Genomics of Foodborne Pathogens

    DEFF Research Database (Denmark)

    This book provides a timely and thorough snapshot into the emerging and fast evolving area of applied genomics of foodborne pathogens. Driven by the drastic advance of whole genome shot gun sequencing (WGS) technologies, genomics applications are becoming increasingly valuable and even essential...... in studying, surveying and controlling foodborne microbial pathogens. The vast opportunities brought by this trend are often at odds with the lack of bioinformatics know-how among food safety and public health professionals, since such expertise is not part of a typical food microbiology curriculum and skill...

  5. Radiation Induced Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F.

    2011-03-01

    Radiation induced genomic instability can be observed in the progeny of irradiated cells multiple generations after irradiation of parental cells. The phenotype is well established both in vivo (Morgan 2003) and in vitro (Morgan 2003), and may be critical in radiation carcinogenesis (Little 2000, Huang et al. 2003). Instability can be induced by both the deposition of energy in irradiated cells as well as by signals transmitted by irradiated (targeted) cells to non-irradiated (non-targeted) cells (Kadhim et al. 1992, Lorimore et al. 1998). Thus both targeted and non-targeted cells can pass on the legacy of radiation to their progeny. However the radiation induced events and cellular processes that respond to both targeted and non-targeted radiation effects that lead to the unstable phenotype remain elusive. The cell system we have used to study radiation induced genomic instability utilizes human hamster GM10115 cells. These cells have a single copy of human chromosome 4 in a background of hamster chromosomes. Instability is evaluated in the clonal progeny of irradiated cells and a clone is considered unstable if it contains three or more metaphase sub-populations involving unique rearrangements of the human chromosome (Marder and Morgan 1993). Many of these unstable clones have been maintained in culture for many years and have been extensively characterized. As initially described by Clutton et al., (Clutton et al. 1996) many of our unstable clones exhibit persistently elevated levels of reactive oxygen species (Limoli et al. 2003), which appear to be due dysfunctional mitochondria (Kim et al. 2006, Kim et al. 2006). Interestingly, but perhaps not surprisingly, our unstable clones do not demonstrate a “mutator phenotype” (Limoli et al. 1997), but they do continue to rearrange their genomes for many years. The limiting factor with this system is the target – the human chromosome. While some clones demonstrate amplification of this chromosome and thus lend

  6. Identification of genomic sites for CRISPR/Cas9-based genome editing in the Vitis vinifera genome

    Science.gov (United States)

    CRISPR/Cas9 has been recently demonstrated as an effective and popular genome editing tool for modifying genomes of human, animals, microorganisms, and plants. Success of such genome editing is highly dependent on the availability of suitable target sites in the genomes to be edited. Many specific t...

  7. Challenges in Whole-Genome Annotation of Pyrosequenced Eukaryotic Genomes

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Alan; Grigoriev, Igor

    2009-04-17

    Pyrosequencing technologies such as 454/Roche and Solexa/Illumina vastly lower the cost of nucleotide sequencing compared to the traditional Sanger method, and thus promise to greatly expand the number of sequenced eukaryotic genomes. However, the new technologies also bring new challenges such as shorter reads and new kinds and higher rates of sequencing errors, which complicate genome assembly and gene prediction. At JGI we are deploying 454 technology for the sequencing and assembly of ever-larger eukaryotic genomes. Here we describe our first whole-genome annotation of a purely 454-sequenced fungal genome that is larger than a yeast (>30 Mbp). The pezizomycotine (filamentous ascomycote) Aspergillus carbonarius belongs to the Aspergillus section Nigri species complex, members of which are significant as platforms for bioenergy and bioindustrial technology, as members of soil microbial communities and players in the global carbon cycle, and as agricultural toxigens. Application of a modified version of the standard JGI Annotation Pipeline has so far predicted ~;;10k genes. ~;;12percent of these preliminary annotations suffer a potential frameshift error, which is somewhat higher than the ~;;9percent rate in the Sanger-sequenced and conventionally assembled and annotated genome of fellow Aspergillus section Nigri member A. niger. Also,>90percent of A. niger genes have potential homologs in the A. carbonarius preliminary annotation. Weconclude, and with further annotation and comparative analysis expect to confirm, that 454 sequencing strategies provide a promising substrate for annotation of modestly sized eukaryotic genomes. We will also present results of annotation of a number of other pyrosequenced fungal genomes of bioenergy interest.

  8. The Global Cancer Genomics Consortium: interfacing genomics and cancer medicine.

    Science.gov (United States)

    2012-08-01

    The Global Cancer Genomics Consortium (GCGC) is an international collaborative platform that amalgamates cancer biologists, cutting-edge genomics, and high-throughput expertise with medical oncologists and surgical oncologists; they address the most important translational questions that are central to cancer research and treatment. The annual GCGC symposium was held at the Advanced Centre for Treatment Research and Education in Cancer, Mumbai, India, from November 9 to 11, 2011. The symposium showcased international next-generation sequencing efforts that explore cancer-specific transcriptomic changes, single-nucleotide polymorphism, and copy number variations in various types of cancers, as well as the structural genomics approach to develop new therapeutic targets and chemical probes. From the spectrum of studies presented at the symposium, it is evident that the translation of emerging cancer genomics knowledge into clinical applications can only be achieved through the integration of multidisciplinary expertise. In summary, the GCGC symposium provided practical knowledge on structural and cancer genomics approaches, as well as an exclusive platform for focused cancer genomics endeavors. ©2012 AACR.

  9. Do echinoderm genomes measure up?

    Science.gov (United States)

    Cameron, R Andrew; Kudtarkar, Parul; Gordon, Susan M; Worley, Kim C; Gibbs, Richard A

    2015-08-01

    Echinoderm genome sequences are a corpus of useful information about a clade of animals that serve as research models in fields ranging from marine ecology to cell and developmental biology. Genomic information from echinoids has contributed to insights into the gene interactions that drive the developmental process at the molecular level. Such insights often rely heavily on genomic information and the kinds of questions that can be asked thus depend on the quality of the sequence information. Here we describe the history of echinoderm genomic sequence assembly and present details about the quality of the data obtained. All of the sequence information discussed here is posted on the echinoderm information web system, Echinobase.org. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Gene finding in novel genomes

    Directory of Open Access Journals (Sweden)

    Korf Ian

    2004-05-01

    Full Text Available Abstract Background Computational gene prediction continues to be an important problem, especially for genomes with little experimental data. Results I introduce the SNAP gene finder which has been designed to be easily adaptable to a variety of genomes. In novel genomes without an appropriate gene finder, I demonstrate that employing a foreign gene finder can produce highly inaccurate results, and that the most compatible parameters may not come from the nearest phylogenetic neighbor. I find that foreign gene finders are more usefully employed to bootstrap parameter estimation and that the resulting parameters can be highly accurate. Conclusion Since gene prediction is sensitive to species-specific parameters, every genome needs a dedicated gene finder.

  11. Genome engineering in human cells.

    Science.gov (United States)

    Song, Minjung; Kim, Young-Hoon; Kim, Jin-Soo; Kim, Hyongbum

    2014-01-01

    Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

  12. Genomic Resources for Cancer Epidemiology

    Science.gov (United States)

    This page provides links to research resources, complied by the Epidemiology and Genomics Research Program, that may be of interest to genetic epidemiologists conducting cancer research, but is not exhaustive.

  13. Nuclear species-diagnostic SNP markers mined from 454 amplicon sequencing reveal admixture genomic structure of modern citrus varieties.

    Directory of Open Access Journals (Sweden)

    Franck Curk

    Full Text Available Most cultivated Citrus species originated from interspecific hybridisation between four ancestral taxa (C. reticulata, C. maxima, C. medica, and C. micrantha with limited further interspecific recombination due to vegetative propagation. This evolution resulted in admixture genomes with frequent interspecific heterozygosity. Moreover, a major part of the phenotypic diversity of edible citrus results from the initial differentiation between these taxa. Deciphering the phylogenomic structure of citrus germplasm is therefore essential for an efficient utilization of citrus biodiversity in breeding schemes. The objective of this work was to develop a set of species-diagnostic single nucleotide polymorphism (SNP markers for the four Citrus ancestral taxa covering the nine chromosomes, and to use these markers to infer the phylogenomic structure of secondary species and modern cultivars. Species-diagnostic SNPs were mined from 454 amplicon sequencing of 57 gene fragments from 26 genotypes of the four basic taxa. Of the 1,053 SNPs mined from 28,507 kb sequence, 273 were found to be highly diagnostic for a single basic taxon. Species-diagnostic SNP markers (105 were used to analyse the admixture structure of varieties and rootstocks. This revealed C. maxima introgressions in most of the old and in all recent selections of mandarins, and suggested that C. reticulata × C. maxima reticulation and introgression processes were important in edible mandarin domestication. The large range of phylogenomic constitutions between C. reticulata and C. maxima revealed in mandarins, tangelos, tangors, sweet oranges, sour oranges, grapefruits, and orangelos is favourable for genetic association studies based on phylogenomic structures of the germplasm. Inferred admixture structures were in agreement with previous hypotheses regarding the origin of several secondary species and also revealed the probable origin of several acid citrus varieties. The developed species

  14. Genomic activation of the EGFR and HER2-neu genes in a significant proportion of invasive epithelial ovarian cancers

    Directory of Open Access Journals (Sweden)

    Ghislain Vanessa

    2008-01-01

    Full Text Available Abstract Background The status of the EGFR and HER2-neu genes has not been fully defined in ovarian cancer. An integrated analysis of both genes could help define the proportion of patients that would potentially benefit from targeted therapies. Methods We determined the tumour mutation status of the entire tyrosine kinase (TK domain of the EGFR and HER2-neu genes in a cohort of 52 patients with invasive epithelial ovarian cancer as well as the gene copy number and protein expression of both genes in 31 of these patients by DGGE and direct sequecing, immunohistochemistry and Fluorescent in Situ Hybridisation (FISH. Results The EGFR was expressed in 59% of the cases, with a 2+/3+ staining intensity in 38%. HER2-neu expression was found in 35%, with a 2/3+ staining in 18%. No mutations were found in exons 18–24 of the TK domains of EGFR and HER2-neu. High polysomy of the EGFR gene was observed in 13% of the invasive epthelial cancers and amplification of the HER2-neu gene was found in 10% and correlated with a high expression level by immunohistochemistry. Mutations within the tyrosine kinase domain were not found in the entire TK domain of both genes, but have been found in very rare cases by others. Conclusion Genomic alteration of the HER2-neu and EGFR genes is frequent (25% in ovarian cancer. EGFR/HER2-neu targeted therapies should be investigated prospectively and specifically in that subset of patients.

  15. 2004 Structural, Function and Evolutionary Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Douglas L. Brutlag Nancy Ryan Gray

    2005-03-23

    This Gordon conference will cover the areas of structural, functional and evolutionary genomics. It will take a systematic approach to genomics, examining the evolution of proteins, protein functional sites, protein-protein interactions, regulatory networks, and metabolic networks. Emphasis will be placed on what we can learn from comparative genomics and entire genomes and proteomes.

  16. Utilizing linkage disequilibrium information from Indian Genome ...

    Indian Academy of Sciences (India)

    Utilizing linkage disequilibrium information from Indian Genome. Variation Database for mapping mutations: SCA12 case study. SAMIRA BAHL1, IKHLAK AHMED2, THE INDIAN GENOME VARIATION CONSORTIUM3 and MITALI MUKERJI1. 1Functional Genomics Unit, Institute of Genomics and Integrative Biology (CSIR), ...

  17. Genomic Aspects of Research Involving Polyploid Plants

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaohan [ORNL; Ye, Chuyu [ORNL; Tschaplinski, Timothy J [ORNL; Wullschleger, Stan D [ORNL; Tuskan, Gerald A [ORNL

    2011-01-01

    Almost all extant plant species have spontaneously doubled their genomes at least once in their evolutionary histories, resulting in polyploidy which provided a rich genomic resource for evolutionary processes. Moreover, superior polyploid clones have been created during the process of crop domestication. Polyploid plants generated by evolutionary processes and/or crop domestication have been the intentional or serendipitous focus of research dealing with the dynamics and consequences of genome evolution. One of the new trends in genomics research is to create synthetic polyploid plants which provide materials for studying the initial genomic changes/responses immediately after polyploid formation. Polyploid plants are also used in functional genomics research to study gene expression in a complex genomic background. In this review, we summarize the recent progress in genomics research involving ancient, young, and synthetic polyploid plants, with a focus on genome size evolution, genomics diversity, genomic rearrangement, genetic and epigenetic changes in duplicated genes, gene discovery, and comparative genomics. Implications on plant sciences including evolution, functional genomics, and plant breeding are presented. It is anticipated that polyploids will be a regular subject of genomics research in the foreseeable future as the rapid advances in DNA sequencing technology create unprecedented opportunities for discovering and monitoring genomic and transcriptomic changes in polyploid plants. The fast accumulation of knowledge on polyploid formation, maintenance, and divergence at whole-genome and subgenome levels will not only help plant biologists understand how plants have evolved and diversified, but also assist plant breeders in designing new strategies for crop improvement.

  18. Whole genome analysis of a Vietnamese trio

    Indian Academy of Sciences (India)

    2015-02-04

    Feb 4, 2015 ... The Ti/Tv ratios are 2.063, 2.064 and 2.063 in the child, father and mother genomes, respectively. The number of detected SNPs in each genome is comparable to those re- ported in other individual genome-wide studies such as. 3,132,608 SNPs in the first Japanese individual genome. (Fujimoto et al.

  19. Genomic instability and radiation effects

    International Nuclear Information System (INIS)

    Christian Streffer

    2007-01-01

    Complete text of publication follows. Cancer, genetic mutations and developmental abnormalities are apparently associated with an increased genomic instability. Such phenomena have been frequently shown in human cancer cells in vitro and in situ. It is also well-known that individuals with a genetic predisposition for cancer proneness, such as ataxia telangiectesia, Fanconi anaemia etc. demonstrate a general high genomic instability e.g. in peripheral lymphocytes before a cancer has developed. Analogous data have been found in mice which develop a specific congenital malformation which has a genetic background. Under these aspects it is of high interest that ionising radiation can increase the genomic instability of mammalian cells after exposures in vitro an in vivo. This phenomenon is expressed 20 to 40 cell cycles after the exposure e.g. by de novo chromosomal aberrations. Such effects have been observed with high and low LET radiation, high LET radiation is more efficient. With low LET radiation a good dose response is observed in the dose range 0.2 to 2.0 Gy, Recently it has been reported that senescence and genomic instability was induced in human fibroblasts after 1 mGy carbon ions (1 in 18 cells are hit), apparently bystander effects also occurred under these conditions. The instability has been shown with DNA damage, chromosomal aberrations, gene mutation and cell death. It is also transferred to the next generation of mice with respect to gene mutations, chromosomal aberrations and congenital malformations. Several mechanisms have been discussed. The involvement of telomeres has gained interest. Genomic instability seems to be induced by a general lesion to the whole genome. The transmission of one chromosome from an irradiated cell to an non-irradiated cell leads to genomic instability in the untreated cells. Genomic instability increases mutation rates in the affected cells in general. As radiation late effects (cancer, gene mutations and congenital

  20. IS4 family goes genomic

    Directory of Open Access Journals (Sweden)

    Mahillon Jacques

    2008-01-01

    Full Text Available Abstract Background Insertion sequences (ISs are small, mobile DNA entities able to expand in prokaryotic genomes and trigger important rearrangements. To understand their role in evolution, accurate IS taxonomy is essential. The IS4 family is composed of ~70 elements and, like some other families, displays extremely elevated levels of internal divergence impeding its classification. The increasing availability of complete genome sequences provides a valuable source for the discovery of additional IS4 elements. In this study, this genomic database was used to update the structural and functional definition of the IS4 family. Results A total of 227 IS4-related sequences were collected among more than 500 sequenced bacterial and archaeal genomes, representing more than a three fold increase of the initial inventory. A clear division into seven coherent subgroups was discovered as well as three emerging families, which displayed distinct structural and functional properties. The IS4 family was sporadically present in 17 % of analyzed genomes, with most of them displaying single or a small number of IS4 elements. Significant expansions were detected only in some pathogens as well as among certain extremophiles, suggesting the probable involvement of some elements in bacterial and archaeal adaptation and/or evolution. Finally, it should be noted that some IS4 subgroups and two emerging families occurred preferentially in specific phyla or exclusively inside a specific genus. Conclusion The present taxonomic update of IS4 and emerging families will facilitate the classification of future elements as they arise from ongoing genome sequencing. Their narrow genomic impact and the existence of both IS-poor and IS-rich thriving prokaryotes suggested that these families, and probably ISs in general, are occasionally used as a tool for genome flexibility and evolution, rather than just representing self sustaining DNA entities.

  1. GOBASE: an organelle genome database

    OpenAIRE

    O?Brien, Emmet A.; Zhang, Yue; Wang, Eric; Marie, Veronique; Badejoko, Wole; Lang, B. Franz; Burger, Gertraud

    2008-01-01

    The organelle genome database GOBASE, now in its 21st release (June 2008), contains all published mitochondrion-encoded sequences (?913 000) and chloroplast-encoded sequences (?250 000) from a wide range of eukaryotic taxa. For all sequences, information on related genes, exons, introns, gene products and taxonomy is available, as well as selected genome maps and RNA secondary structures. Recent major enhancements to database functionality include: (i) addition of an interface for RNA editing...

  2. Functional genomics of probiotic Lactobacilli.

    Science.gov (United States)

    Klaenhammer, Todd R; Altermann, Eric; Pfeiler, Erika; Buck, Brock Logan; Goh, Yong-Jun; O'Flaherty, Sarah; Barrangou, Rodolphe; Duong, Tri

    2008-09-01

    Lactic acid bacteria (LAB) have been used in fermentation processes for millennia. Recent applications such as the use of living cultures as probiotics have significantly increased industrial interest. Related bacterial strains can differ significantly in their genotype and phenotype, and features from one bacterial strain or species cannot necessarily be applied to a related one. These strain or family-specific differences often represent unique and applicable traits. Since 2002, the complete genomes of 13 probiotic LABs have been published. The presentation will discuss these genomes and highlight probiotic traits that are predicted, or functionally linked to genetic content. We have conducted a comparative genomic analysis of 4 completely sequenced Lactobacillus strains versus 25 lactic acid bacterial genomes present in the public database at the time of analysis. Using Differential Blast Analysis, each genome is compared with 3 other Lactobacillus and 25 other LAB genomes. Differential Blast Analysis highlighted strain-specific genes that were not represented in any other LAB used in this analysis and also identified group-specific genes shared within lactobacilli. Lactobacillus-specific genes include mucus-binding proteins involved in cell-adhesion and several transport systems for carbohydrates and amino acids. Comparative genomic analysis has identified gene targets in Lactobacillus acidophilus for functional analysis, including adhesion to mucin and intestinal epithelial cells, acid tolerance, bile tolerance, and quorum sensing. Whole genome transcriptional profiling of L. acidophilus, and isogenic mutants thereof, has revealed the impact of varying conditions (pH, bile, carbohydrates) and food matrices on the expression of genes important to probiotic-linked mechanisms.

  3. Population Genomics of Paramecium Species.

    Science.gov (United States)

    Johri, Parul; Krenek, Sascha; Marinov, Georgi K; Doak, Thomas G; Berendonk, Thomas U; Lynch, Michael

    2017-05-01

    Population-genomic analyses are essential to understanding factors shaping genomic variation and lineage-specific sequence constraints. The dearth of such analyses for unicellular eukaryotes prompted us to assess genomic variation in Paramecium, one of the most well-studied ciliate genera. The Paramecium aurelia complex consists of ∼15 morphologically indistinguishable species that diverged subsequent to two rounds of whole-genome duplications (WGDs, as long as 320 MYA) and possess extremely streamlined genomes. We examine patterns of both nuclear and mitochondrial polymorphism, by sequencing whole genomes of 10-13 worldwide isolates of each of three species belonging to the P. aurelia complex: P. tetraurelia, P. biaurelia, P. sexaurelia, as well as two outgroup species that do not share the WGDs: P. caudatum and P. multimicronucleatum. An apparent absence of global geographic population structure suggests continuous or recent dispersal of Paramecium over long distances. Intergenic regions are highly constrained relative to coding sequences, especially in P. caudatum and P. multimicronucleatum that have shorter intergenic distances. Sequence diversity and divergence are reduced up to ∼100-150 bp both upstream and downstream of genes, suggesting strong constraints imposed by the presence of densely packed regulatory modules. In addition, comparison of sequence variation at non-synonymous and synonymous sites suggests similar recent selective pressures on paralogs within and orthologs across the deeply diverging species. This study presents the first genome-wide population-genomic analysis in ciliates and provides a valuable resource for future studies in evolutionary and functional genetics in Paramecium. © The Author 2017. 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.

  4. Genome Exploitation and Bioinformatics Tools

    Science.gov (United States)

    de Jong, Anne; van Heel, Auke J.; Kuipers, Oscar P.

    Bioinformatic tools can greatly improve the efficiency of bacteriocin screening efforts by limiting the amount of strains. Different classes of bacteriocins can be detected in genomes by looking at different features. Finding small bacteriocins can be especially challenging due to low homology and because small open reading frames (ORFs) are often omitted from annotations. In this chapter, several bioinformatic tools/strategies to identify bacteriocins in genomes are discussed.

  5. Plague in the genomic area.

    Science.gov (United States)

    Drancourt, M

    2012-03-01

    With plague being not only a subject of interest for historians, but still a disease of public health concern in several countries, mainly in Africa, there were hopes that analyses of the Yersinia pestis genomes would put an end to this deadly epidemic pathogen. Genomics revealed that Y. pestis isolates evolved from Yersinia pseudotuberculosis in Central Asia some millennia ago, after the acquisition of two Y. pestis-specific plasmids balanced genomic reduction parallel with the expansion of insertion sequences, illustrating the modern concept that, except for the acquisition of plasmid-borne toxin-encoding genes, the increased virulence of Y. pestis resulted from gene loss rather than gene acquisition. The telluric persistence of Y. pestis reminds us of this close relationship, and matters in terms of plague epidemiology. Whereas biotype Orientalis isolates spread worldwide, the Antiqua and Medievalis isolates showed more limited expansion. In addition to animal ectoparasites, human ectoparasites such as the body louse may have participated in this expansion and in devastating historical epidemics. The recent analysis of a Black Death genome indicated that it was more closely related to the Orientalis branch than to the Medievalis branch. Modern Y. pestis isolates grossly exhibit the same gene content, but still undergo micro-evolution in geographically limited areas by differing in the genome architecture, owing to inversions near insertion sequences and the stabilization of the YpfPhi prophage in Orientalis biotype isolates. Genomics have provided several new molecular tools for the genotyping and phylogeographical tracing of isolates and description of plague foci. However, genomics and post-genomics approaches have not yet provided new tools for the prevention, diagnosis and management of plague patients and the plague epidemics still raging in some sub-Saharan countries. © 2012 The Author. Clinical Microbiology and Infection © 2012 European Society of

  6. A review of the evolution of viviparity in squamate reptiles: the past, present and future role of molecular biology and genomics.

    Science.gov (United States)

    Murphy, Bridget F; Thompson, Michael B

    2011-07-01

    Squamate reptiles (lizards and snakes) offer a unique model system for testing hypotheses about the evolutionary transition from oviparity (egg-laying) to viviparity (live-bearing) in amniote vertebrates. The evolution of squamate viviparity has occurred remarkably frequently (>108 times) and has resulted in major changes in reproductive physiology. Such frequent changes in reproductive strategy pose two questions: (1) what are the molecular mechanisms responsible for the evolution of squamate viviparity? (2) Are these molecular mechanisms the same for separate origins of viviparity? Molecular approaches, such as RT-PCR, in situ hybridisation, Western blotting and immunofluorescence, have been invaluable for identifying genes and proteins that are involved in squamate placental development, materno-foetal immunotolerance, placental transport, placental angiogenesis, hormone synthesis and hormone receptor expression. However, the candidate-gene or -protein approach that has been used until now does not allow for de novo gene/protein discovery; results to date suggest that the reproductive physiologies of mammals and squamate reptiles are very similar, but this conclusion may simply be due to a limited capacity to study the subset of genes and proteins that are unique to reptiles. Progress has also been slowed by the lack of appropriate molecular and genomic resources for squamate reptiles. The advent of next-generation sequencing provides a relatively inexpensive way to conduct rapid high-throughput sequencing of genomes and transcriptomes. We discuss the potential use of next-generation sequencing technologies to analyse differences in gene expression between oviparous and viviparous squamates, provide important sequence information for reptiles, and generate testable hypotheses for the evolution of viviparity.

  7. A comparative study of genome-wide SNP, CGH microarray and protein expression analysis to explore genotypic and phenotypic mechanisms of acquired antiestrogen resistance in breast cancer.

    Science.gov (United States)

    Johnson, Neil; Speirs, Valerie; Curtin, Nicola J; Hall, Andrew G

    2008-09-01

    Allelic imbalance is a common feature of many malignancies. We have measured allelic imbalance in genomic DNA from the breast cancer cell lines T47D, MDA-MB-231, two antiestrogen sensitive (MCF7N and MCF7L) and two resistant MCF7 cell lines (MMU2 and LCC9) using single nucleotide polymorphism (SNP) oligonucleotide microarrays. DNA from MCF7(L) and MMU2 cells was also analysed by comparative genome hybridisation (CGH) to compare with SNP microarray data. Proteins previously determined to be involved in disease progression were quantified by Western blot and compared to array data. The SNP and CGH array both detected cytogenetic abnormalities commonly found in breast cancer: amplification of chromosomes 11q13-14.1, 17q and 20q containing cyclin D1, BCAS1 and 3 (Breast Cancer Amplified Sequence) and AIB1 (Amplified in Breast cancer) genes; losses at 6q, 9p and X chromosomes, which included ERalpha (Estrogen Receptor alpha) and p16 ( INK4A ) genes. However the SNP chip array data additionally identified regions of loss of heterozygosity (LOH) followed by duplication of the remaining allele-uniparental disomy (UPD). Good concordance between SNP arrays and CGH analyses was observed, however there was poor correlation between gene copy number and protein levels between the cell lines. There were reductions in ERalpha, cyclin D1 and p27 protein levels whilst p21 protein levels were elevated in antiestrogen resistant MCF7 cell lines. Although protein levels varied there was no difference in gene copy number. This study shows SNP and CGH array analysis are powerful tools for analysis of allelic imbalance in breast cancer. However, the antiestrogen resistant phenotype was likely to be due to changes in gene expression and protein degradation rather than in altered gene copy number.

  8. The fishes of Genome 10K

    KAUST Repository

    Bernardi, Giacomo

    2012-09-01

    The Genome 10K project aims to sequence the genomes of 10,000 vertebrates, representing approximately one genome for each vertebrate genus. Since fishes (cartilaginous fishes, ray-finned fishes and lobe-finned fishes) represent more than 50% of extant vertebrates, it is planned to target 4,000 fish genomes. At present, nearly 60 fish genomes are being sequenced at various public funded labs, and under a Genome 10K and BGI pilot project. An additional 100 fishes have been identified for sequencing in the next phase of Genome 10K project. © 2012 Elsevier B.V.

  9. Packaging the fly genome: domains and dynamics.

    Science.gov (United States)

    White, Rob

    2012-09-01

    Two independent genomic approaches have recently converged to provide insight into the domain organization of the Drosophila genome. Genome-wide mapping of chromosomal proteins and histone modifications has generated detailed maps of the Drosophila chromatin landscape and has led to the identification of a number of different chromatin states and their distribution in domains across the genome. A remarkably similar domain organization is derived from whole genome mapping of chromatin interactions that reveals the segmentation of the genome into structural domains. This review focuses on our current understanding of this domain architecture which provides a foundation for our understanding of the link between chromatin organization and the dynamic activity of the genome.

  10. Mutational Dynamics of Aroid Chloroplast Genomes

    Science.gov (United States)

    Ahmed, Ibrar; Biggs, Patrick J.; Matthews, Peter J.; Collins, Lesley J.; Hendy, Michael D.; Lockhart, Peter J.

    2012-01-01

    A characteristic feature of eukaryote and prokaryote genomes is the co-occurrence of nucleotide substitution and insertion/deletion (indel) mutations. Although similar observations have also been made for chloroplast DNA, genome-wide associations have not been reported. We determined the chloroplast genome sequences for two morphotypes of taro (Colocasia esculenta; family Araceae) and compared these with four publicly available aroid chloroplast genomes. Here, we report the extent of genome-wide association between direct and inverted repeats, indels, and substitutions in these aroid chloroplast genomes. We suggest that alternative but not mutually exclusive hypotheses explain the mutational dynamics of chloroplast genome evolution. PMID:23204304

  11. Rat Genome and Model Resources.

    Science.gov (United States)

    Shimoyama, Mary; Smith, Jennifer R; Bryda, Elizabeth; Kuramoto, Takashi; Saba, Laura; Dwinell, Melinda

    2017-07-01

    Rats remain a major model for studying disease mechanisms and discovery, validation, and testing of new compounds to improve human health. The rat's value continues to grow as indicated by the more than 1.4 million publications (second to human) at PubMed documenting important discoveries using this model. Advanced sequencing technologies, genome modification techniques, and the development of embryonic stem cell protocols ensure the rat remains an important mammalian model for disease studies. The 2004 release of the reference genome has been followed by the production of complete genomes for more than two dozen individual strains utilizing NextGen sequencing technologies; their analyses have identified over 80 million variants. This explosion in genomic data has been accompanied by the ability to selectively edit the rat genome, leading to hundreds of new strains through multiple technologies. A number of resources have been developed to provide investigators with access to precision rat models, comprehensive datasets, and sophisticated software tools necessary for their research. Those profiled here include the Rat Genome Database, PhenoGen, Gene Editing Rat Resource Center, Rat Resource and Research Center, and the National BioResource Project for the Rat in Japan. © The Author 2017. Published by Oxford University Press.

  12. Evolutionary genomics of environmental pollution.

    Science.gov (United States)

    Whitehead, Andrew

    2014-01-01

    Chemical toxins have been a persistent source of evolutionary challenges throughout the history of life, and deep within the genomic storehouse of evolutionary history lay ancient adaptations to diverse chemical poisons. However, the rate of change of contemporary environments mediated by human-introduced pollutants is rapidly screening this storehouse and severely testing the adaptive potential of many species. In this chapter, we briefly review the deep history of evolutionary adaptation to environmental toxins, and then proceed to describe the attributes of stressors and populations that may facilitate contemporary adaptation to pollutants introduced by humans. We highlight that phenotypes derived to enable persistence in polluted habitats may be multi-dimensional, requiring global genome-scale tools and approaches to uncover their mechanistic basis, and include examples of recent progress in the field. The modern tools of genomics offer promise for discovering how pollutants interact with genomes on physiological timescales, and also for discovering what genomic attributes of populations may enable resistance to pollutants over evolutionary timescales. Through integration of these sophisticated genomics tools and approaches with an understanding of the deep historical forces that shaped current populations, a more mature understanding of the mechanistic basis of contemporary ecological-evolutionary dynamics should emerge.

  13. The dynamic genome of Hydra.

    Science.gov (United States)

    Chapman, Jarrod A; Kirkness, Ewen F; Simakov, Oleg; Hampson, Steven E; Mitros, Therese; Weinmaier, Thomas; Rattei, Thomas; Balasubramanian, Prakash G; Borman, Jon; Busam, Dana; Disbennett, Kathryn; Pfannkoch, Cynthia; Sumin, Nadezhda; Sutton, Granger G; Viswanathan, Lakshmi Devi; Walenz, Brian; Goodstein, David M; Hellsten, Uffe; Kawashima, Takeshi; Prochnik, Simon E; Putnam, Nicholas H; Shu, Shengquiang; Blumberg, Bruce; Dana, Catherine E; Gee, Lydia; Kibler, Dennis F; Law, Lee; Lindgens, Dirk; Martinez, Daniel E; Peng, Jisong; Wigge, Philip A; Bertulat, Bianca; Guder, Corina; Nakamura, Yukio; Ozbek, Suat; Watanabe, Hiroshi; Khalturin, Konstantin; Hemmrich, Georg; Franke, André; Augustin, René; Fraune, Sebastian; Hayakawa, Eisuke; Hayakawa, Shiho; Hirose, Mamiko; Hwang, Jung Shan; Ikeo, Kazuho; Nishimiya-Fujisawa, Chiemi; Ogura, Atshushi; Takahashi, Toshio; Steinmetz, Patrick R H; Zhang, Xiaoming; Aufschnaiter, Roland; Eder, Marie-Kristin; Gorny, Anne-Kathrin; Salvenmoser, Willi; Heimberg, Alysha M; Wheeler, Benjamin M; Peterson, Kevin J; Böttger, Angelika; Tischler, Patrick; Wolf, Alexander; Gojobori, Takashi; Remington, Karin A; Strausberg, Robert L; Venter, J Craig; Technau, Ulrich; Hobmayer, Bert; Bosch, Thomas C G; Holstein, Thomas W; Fujisawa, Toshitaka; Bode, Hans R; David, Charles N; Rokhsar, Daniel S; Steele, Robert E

    2010-03-25

    The freshwater cnidarian Hydra was first described in 1702 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals. Today, Hydra is an important model for studies of axial patterning, stem cell biology and regeneration. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann-Mangold organizer, pluripotency genes and the neuromuscular junction.

  14. Human genomics: implications for health.

    Science.gov (United States)

    Wasi, P

    1997-01-01

    Human genome research which tries to map and sequence all the 3 billion nucleotides in the entire DNA is progressing rapidly. Completion of the human genome sequencing is expected before the year 2005. Human genes, totalling 50,000-100,000, will be identified, allowing the complete set of proteins--'the proteome' to be known. This together with genomic research in other species will lead to complete understanding of life at the molecular level and also its evolutionary history of 3,500 million years. Genomics will bring about a revolution in biology and health, because it is equivalent to having a 'Biological Periodic Table' which is a foundation for understanding life, health, disease and for deriving of new tools for diagnosis, treatment, prognosis and prevention. Human genomics will give rise to Predictive--Preventive Medicine and Precision Medicine. It will have profound social implications. Preparation for the future is needed for societies to cope with and make proper use of the tremendous changes to be brought about by genomics.

  15. A Genome-Wide Perspective on Metabolism

    DEFF Research Database (Denmark)

    Rauch, Alexander; Mandrup, Susanne

    2015-01-01

    number of technologies that can be used to obtain genome-wide insight into how genomes are reprogrammed during development and in response to specific external signals. By applying such technologies, we have begun to reveal the cross-talk between metabolism and the genome, i.e., how genomes...... are reprogrammed in response to metabolites, and how the regulation of metabolic networks is coordinated at the genomic level....

  16. HGVA: the Human Genome Variation Archive

    OpenAIRE

    Lopez, Javier; Coll, Jacobo; Haimel, Matthias; Kandasamy, Swaathi; Tarraga, Joaquin; Furio-Tari, Pedro; Bari, Wasim; Bleda, Marta; Rueda, Antonio; Gr?f, Stefan; Rendon, Augusto; Dopazo, Joaquin; Medina, Ignacio

    2017-01-01

    Abstract High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic...

  17. Detection of recurrent 4p16.3 microdeletion with 2p25.3 microduplication by multiplex ligation-dependent probe amplification and array comparative genomic hybridization in a fetus from a family with Wolf–Hirschhorn syndrome

    Directory of Open Access Journals (Sweden)

    Wen-Xu Yang

    2016-02-01

    Conclusion: The combined use of MLPA and aCGH is an effective way to diagnose recurrent WHS. Although WHS is typically caused by a de novo deletion, prenatal diagnosis and genetic counseling are necessary in the next pregnancy in families that have suffered such cases.

  18. Genomics of ankylosing spondylitis.

    Science.gov (United States)

    Thomas, Gethin P; Brown, Matthew A

    2010-09-01

    Ankylosing spondylitis (AS) is the prototypic and most prevalent and debilitating spondyloarthropathy, a group of arthritides where the spine and pelvis are specifically targeted. Unlike many other forms of arthritis in which joint damage is mediated through tissue destruction, in AS uncontrolled bone formation occurs, frequently resulting in joint fusion and consequently significant disability. It is estimated that there are 2.4 million spondyloarthritis sufferers in the U.S., twice as many as rheumatoid arthritis. The pathogenesis of AS is very poorly understood and both genetics and gene expression profiling approaches have been utilized to elucidate the underlying mechanisms and pathways that drive the disease. Using powerful genome-wide association study approaches a number of candidate genes have been found to be associated with AS. However, although such approaches can identify genes that can contribute to the disease process, they do not inform us of the actual changes in gene/cell activity at any point in the disease process. Expression profiling allows us to take a "snapshot" of cellular activity and what gene activity changes are underlying those changes. A number of expression profiling studies have been undertaken in AS, looking at both circulating cells and tissues from affected joints. The results to date have been somewhat disappointing with little consensus on gene activity changes due to the low power of the studies undertaken. Some more recent better powered studies have identified diagnostic expression profiles that do point to a possible role for expression profiling in early AS diagnosis. Future studies will require collaborative approaches to target specific disease stages and sites with larger numbers of samples.

  19. A dictionary based informational genome analysis

    Directory of Open Access Journals (Sweden)

    Castellini Alberto

    2012-09-01

    Full Text Available Abstract Background In the post-genomic era several methods of computational genomics are emerging to understand how the whole information is structured within genomes. Literature of last five years accounts for several alignment-free methods, arisen as alternative metrics for dissimilarity of biological sequences. Among the others, recent approaches are based on empirical frequencies of DNA k-mers in whole genomes. Results Any set of words (factors occurring in a genome provides a genomic dictionary. About sixty genomes were analyzed by means of informational indexes based on genomic dictionaries, where a systemic view replaces a local sequence analysis. A software prototype applying a methodology here outlined carried out some computations on genomic data. We computed informational indexes, built the genomic dictionaries with different sizes, along with frequency distributions. The software performed three main tasks: computation of informational indexes, storage of these in a database, index analysis and visualization. The validation was done by investigating genomes of various organisms. A systematic analysis of genomic repeats of several lengths, which is of vivid interest in biology (for example to compute excessively represented functional sequences, such as promoters, was discussed, and suggested a method to define synthetic genetic networks. Conclusions We introduced a methodology based on dictionaries, and an efficient motif-finding software application for comparative genomics. This approach could be extended along many investigation lines, namely exported in other contexts of computational genomics, as a basis for discrimination of genomic pathologies.

  20. The Genomic Code: Genome Evolution and Potential Applications

    KAUST Repository

    Bernardi, Giorgio

    2016-01-25

    The genome of metazoans is organized according to a genomic code which comprises three laws: 1) Compositional correlations hold between contiguous coding and non-coding sequences, as well as among the three codon positions of protein-coding genes; these correlations are the consequence of the fact that the genomes under consideration consist of fairly homogeneous, long (≥200Kb) sequences, the isochores; 2) Although isochores are defined on the basis of purely compositional properties, GC levels of isochores are correlated with all tested structural and functional properties of the genome; 3) GC levels of isochores are correlated with chromosome architecture from interphase to metaphase; in the case of interphase the correlation concerns isochores and the three-dimensional “topological associated domains” (TADs); in the case of mitotic chromosomes, the correlation concerns isochores and chromosomal bands. Finally, the genomic code is the fourth and last pillar of molecular biology, the first three pillars being 1) the double helix structure of DNA; 2) the regulation of gene expression in prokaryotes; and 3) the genetic code.

  1. Genome sequencing and population genomics in non-model organisms.

    Science.gov (United States)

    Ellegren, Hans

    2014-01-01

    High-throughput sequencing technologies are revolutionizing the life sciences. The past 12 months have seen a burst of genome sequences from non-model organisms, in each case representing a fundamental source of data of significant importance to biological research. This has bearing on several aspects of evolutionary biology, and we are now beginning to see patterns emerging from these studies. These include significant heterogeneity in the rate of recombination that affects adaptive evolution and base composition, the role of population size in adaptive evolution, and the importance of expansion of gene families in lineage-specific adaptation. Moreover, resequencing of population samples (population genomics) has enabled the identification of the genetic basis of critical phenotypes and cast light on the landscape of genomic divergence during speciation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Human Genome Education Program

    Energy Technology Data Exchange (ETDEWEB)

    Richard Myers; Lane Conn

    2000-05-01

    The funds from the DOE Human Genome Program, for the project period 2/1/96 through 1/31/98, have provided major support for the curriculum development and field testing efforts for two high school level instructional units: Unit 1, ''Exploring Genetic Conditions: Genes, Culture and Choices''; and Unit 2, ''DNA Snapshots: Peaking at Your DNA''. In the original proposal, they requested DOE support for the partial salary and benefits of a Field Test Coordinator position to: (1) complete the field testing and revision of two high school curriculum units, and (2) initiate the education of teachers using these units. During the project period of this two-year DOE grant, a part-time Field-Test Coordinator was hired (Ms. Geraldine Horsma) and significant progress has been made in both of the original proposal objectives. Field testing for Unit 1 has occurred in over 12 schools (local and non-local sites with diverse student populations). Field testing for Unit 2 has occurred in over 15 schools (local and non-local sites) and will continue in 12-15 schools during the 96-97 school year. For both curricula, field-test sites and site teachers were selected for their interest in genetics education and in hands-on science education. Many of the site teachers had no previous experience with HGEP or the unit under development. Both of these first-year biology curriculum units, which contain genetics, biotechnology, societal, ethical and cultural issues related to HGP, are being implemented in many local and non-local schools (SF Bay Area, Southern California, Nebraska, Hawaii, and Texas) and in programs for teachers. These units will reach over 10,000 students in the SF Bay Area and continues to receive support from local corporate and private philanthropic organizations. Although HGEP unit development is nearing completion for both units, data is still being gathered and analyzed on unit effectiveness and student learning. The final field

  3. Allele coding in genomic evaluation

    Directory of Open Access Journals (Sweden)

    Christensen Ole F

    2011-06-01

    Full Text Available Abstract Background Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call this centered allele coding. This study considered effects of different allele coding methods on inference. Both marker-based and equivalent models were considered, and restricted maximum likelihood and Bayesian methods were used in inference. Results Theoretical derivations showed that parameter estimates and estimated marker effects in marker-based models are the same irrespective of the allele coding, provided that the model has a fixed general mean. For the equivalent models, the same results hold, even though different allele coding methods lead to different genomic relationship matrices. Calculated genomic breeding values are independent of allele coding when the estimate of the general mean is included into the values. Reliabilities of estimated genomic breeding values calculated using elements of the inverse of the coefficient matrix depend on the allele coding because different allele coding methods imply different models. Finally, allele coding affects the mixing of Markov chain Monte Carlo algorithms, with the centered coding being

  4. Genomic selection in maritime pine.

    Science.gov (United States)

    Isik, Fikret; Bartholomé, Jérôme; Farjat, Alfredo; Chancerel, Emilie; Raffin, Annie; Sanchez, Leopoldo; Plomion, Christophe; Bouffier, Laurent

    2016-01-01

    A two-generation maritime pine (Pinus pinaster Ait.) breeding population (n=661) was genotyped using 2500 SNP markers. The extent of linkage disequilibrium and utility of genomic selection for growth and stem straightness improvement were investigated. The overall intra-chromosomal linkage disequilibrium was r(2)=0.01. Linkage disequilibrium corrected for genomic relationships derived from markers was smaller (rV(2)=0.006). Genomic BLUP, Bayesian ridge regression and Bayesian LASSO regression statistical models were used to obtain genomic estimated breeding values. Two validation methods (random sampling 50% of the population and 10% of the progeny generation as validation sets) were used with 100 replications. The average predictive ability across statistical models and validation methods was about 0.49 for stem sweep, and 0.47 and 0.43 for total height and tree diameter, respectively. The sensitivity analysis suggested that prior densities (variance explained by markers) had little or no discernible effect on posterior means (residual variance) in Bayesian prediction models. Sampling from the progeny generation for model validation increased the predictive ability of markers for tree diameter and stem sweep but not for total height. The results are promising despite low linkage disequilibrium and low marker coverage of the genome (∼1.39 markers/cM). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. The genome of Chenopodium quinoa

    KAUST Repository

    Jarvis, David Erwin

    2017-02-08

    Chenopodium quinoa (quinoa) is a highly nutritious grain identified as an important crop to improve world food security. Unfortunately, few resources are available to facilitate its genetic improvement. Here we report the assembly of a high-quality, chromosome-scale reference genome sequence for quinoa, which was produced using single-molecule real-time sequencing in combination with optical, chromosome-contact and genetic maps. We also report the sequencing of two diploids from the ancestral gene pools of quinoa, which enables the identification of sub-genomes in quinoa, and reduced-coverage genome sequences for 22 other samples of the allotetraploid goosefoot complex. The genome sequence facilitated the identification of the transcription factor likely to control the production of anti-nutritional triterpenoid saponins found in quinoa seeds, including a mutation that appears to cause alternative splicing and a premature stop codon in sweet quinoa strains. These genomic resources are an important first step towards the genetic improvement of quinoa.

  6. Genomic disorders on chromosome 22.

    Science.gov (United States)

    Yu, Shihui; Graf, William D; Shprintzen, Robert J

    2012-12-01

    Chromosome 22, the first human chromosome to be completely sequenced, is prone to genomic alterations. Copy-number variants (CNVs) are common because of an enrichment of low-copy repeat sequences that precipitate a high frequency of nonallelic homologous misalignments and unequal recombination during meiosis. Among these is one of the most common multiple anomaly syndromes in humans and the most common microdeletion syndrome, velocardiofacial syndrome (VCFS), also known as 22q11.2 deletion syndrome and DiGeorge syndrome. This review will focus on the recent literature dealing with both the molecular and clinical aspects of chromosome 22 genomic variations. Although the literature covering this area is expansive, the majority is descriptive or analytical of the problems presented by these genomic disorders, and there is little evidence of translational research including treatment outcomes. With the increased use of microarray analysis in both research and clinical practice, variations in CNVs are becoming elucidated. Genomic analysis continues to characterize genes and gene effect. Research on the COMT gene continues to yield interesting findings, including a possible sex-mediated effect because of its regulatory role with estrogen. There is a small amount of treatment outcome data relevant to neuropsychiatric disorders in VCFS, but based on small samples and short-term follow-up. Although hundreds of studies in the past year have focused on genomic disorders of chromosome 22, little progress has been made in the implementation of translational research, even for more common disorders including VCFS.

  7. The genome of Chenopodium quinoa.

    Science.gov (United States)

    Jarvis, David E; Ho, Yung Shwen; Lightfoot, Damien J; Schmöckel, Sandra M; Li, Bo; Borm, Theo J A; Ohyanagi, Hajime; Mineta, Katsuhiko; Michell, Craig T; Saber, Noha; Kharbatia, Najeh M; Rupper, Ryan R; Sharp, Aaron R; Dally, Nadine; Boughton, Berin A; Woo, Yong H; Gao, Ge; Schijlen, Elio G W M; Guo, Xiujie; Momin, Afaque A; Negrão, Sónia; Al-Babili, Salim; Gehring, Christoph; Roessner, Ute; Jung, Christian; Murphy, Kevin; Arold, Stefan T; Gojobori, Takashi; Linden, C Gerard van der; van Loo, Eibertus N; Jellen, Eric N; Maughan, Peter J; Tester, Mark

    2017-02-16

    Chenopodium quinoa (quinoa) is a highly nutritious grain identified as an important crop to improve world food security. Unfortunately, few resources are available to facilitate its genetic improvement. Here we report the assembly of a high-quality, chromosome-scale reference genome sequence for quinoa, which was produced using single-molecule real-time sequencing in combination with optical, chromosome-contact and genetic maps. We also report the sequencing of two diploids from the ancestral gene pools of quinoa, which enables the identification of sub-genomes in quinoa, and reduced-coverage genome sequences for 22 other samples of the allotetraploid goosefoot complex. The genome sequence facilitated the identification of the transcription factor likely to control the production of anti-nutritional triterpenoid saponins found in quinoa seeds, including a mutation that appears to cause alternative splicing and a premature stop codon in sweet quinoa strains. These genomic resources are an important first step towards the genetic improvement of quinoa.

  8. Manipulating duckweed through genome duplication.

    Science.gov (United States)

    Vunsh, R; Heinig, U; Malitsky, S; Aharoni, A; Avidov, A; Lerner, A; Edelman, M

    2015-01-01

    Significant inter- and intraspecific genetic variation exists in duckweed, thus the potential for genome plasticity and manipulation is high. Polyploidy is recognised as a major mechanism of adaptation and speciation in plants. We produced several genome-duplicated lines of Landoltia punctata (Spirodela oligorrhiza) from both whole plants and regenerating explants using a colchicine-based cocktail. These lines stably maintained an enlarged frond and root morphology. DNA ploidy levels determined by florescence-activated cell sorting indicated genome duplication. Line A4 was analysed after 75 biomass doublings. Frond area, fresh and dry weights, rhizoid number and length were significantly increased versus wild type, while the growth rate was unchanged. This resulted in accumulation of biomass 17-20% faster in the A4 plants. We sought to determine if specific differences in gene products are found in the genome duplicated lines. Non-targeted ultra performance LC-quadrupole time of flight mass spectrometry was employed to compare some of the lines and the wild type to seek identification of up-regulated metabolites. We putatively identified differential metabolites in Line A65 as caffeoyl hexoses. The combination of directed genome duplication and metabolic profiling might offer a path for producing stable gene expression, leading to altered production of secondary metabolites. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

  9. Genomic composition factors affect codon usage in porcine genome

    DEFF Research Database (Denmark)

    Khobondo, J O; Okeno, Tobias O; Kahi, A K

    2015-01-01

    The objective of the study was to determine the codon usage bias in the porcine genome and decipher its determinants. To investigate the underlying mechanisms of codon bias, the coding sequence (CDS) from the swine reference sequence (ssc10.2) was extracted using Biomart. An in house built Perl...... script was used to derive various genomic traits and codon indices. Analysis was done using R statistical package, and correlations and multivariate regressions were performed. We report the existence of codon usage bias that might suggest existence of weak translational selection. The codon bias...

  10. Prenatal diagnosis and array comparative genomic hybridization characterization of interstitial deletions of 8q23.3–q24.11 and 8q24.13 associated with Langer-Giedion syndrome, Cornelia de Lange syndrome and haploinsufficiency of TRPS1, RAD21 and EXT1

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2015-10-01

    Conclusion: In the present case, the conventional cytogenetic analysis of cultured amniocytes revealed del(8(q23.3q24.13, whereas aCGH analysis of cultured amniocytes showed the deletions of 8q23.3–q24.11 and 8q24.13 with the presence of the segment 8q24.12. Therefore, aCGH provides the advantage of better understanding of the nature of interstitial deletion and genotype–phenotype correlation in this case.

  11. A physical map of the human genome

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, J.D.; Marra, M.; Hillier, L.; Waterston, R.H.; Chinwalla, A.; Wallis, J.; Sekhon, M.; Wylie, K.; Mardis, E.R.; Wilson, R.K.; Fulton, R.; Kucaba, T.A.; Wagner-McPherson, C.; Barbazuk, W.B.; Gregory, S.G.; Humphray, S.J.; French, L.; Evans, R.S.; Bethel, G.; Whittaker, A.; Holden, J.L.; McCann, O.T.; Dunham, A.; Soderlund, C.; Scott, C.E.; Bentley, D.R.; Schuler, G.; Chen, H.-C.; Jang, W.; Green, E.D.; Idol, J.R.; Maduro, V.V. Braden; Montgomery, K.T.; Lee, E.; Miller, A.; Emerling, S.; Kucherlapati; Gibbs, R.; Scherer, S.; Gorrell, J.H.; Sodergren, E.; Clerc-Blankenburg, K.; Tabor, P.; Naylor, S.; Garcia, D.; de Jong, P.J.; Catanese, J.J.; Nowak, N.; Osoegawa, K.; Qin, S.; Rowen, L.; Madan, A.; Dors, M.; Hood, L.; Trask, B.; Friedman, C.; Massa, H.; Cheung, V.G.; Kirsch, I.R.; Reid, T.; Yonescu, R.; Weissenbach, J.; Bruls, T.; Heilig, R.; Branscomb, E.; Olsen, A.; Doggett, N.; Cheng, J.F.; Hawkins, T.; Myers, R.M.; Shang, J.; Ramirez, L.; Schmutz, J.; Velasquez, O.; Dixon, K.; Stone, N.E.; Cox, D.R.; Haussler, D.; Kent, W.J.; Furey, T.; Rogic, S.; Kennedy, S.; Jones, S.; Rosenthal, A.; Wen, G.; Schilhabel, M.; Gloeckner, G.; Nyakatura, G.; Siebert, R.; Schlegelberger, B.; Korenberg, J.; Chen, X.N.; Fujiyama, A.; Hattori, M.; Toyoda, A.; Yada, T.; Park, H.S.; Sakaki, Y.; Shimizu, N.; Asakawa, S.; Kawasaki, K.; Sasaki, T.; Shintani, A.; Shimizu, A.; Shibuya, K.; Kudoh, J.; Minoshima, S.; Ramser, J.; Seranski, P.; Hoff, C.; Poustka, A.; Reinhardt, R.; Lehrach, H.

    2001-01-01

    The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

  12. Enhancer Identification through Comparative Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Bristow, James; Pennacchio, Len A.

    2006-10-01

    With the availability of genomic sequence from numerousvertebrates, a paradigm shift has occurred in the identification ofdistant-acting gene regulatory elements. In contrast to traditionalgene-centric studies in which investigators randomly scanned genomicfragments that flank genes of interest in functional assays, the modernapproach begins electronically with publicly available comparativesequence datasets that provide investigators with prioritized lists ofputative functional sequences based on their evolutionary conservation.However, although a large number of tools and resources are nowavailable, application of comparative genomic approaches remains far fromtrivial. In particular, it requires users to dynamically consider thespecies and methods for comparison depending on the specific biologicalquestion under investigation. While there is currently no single generalrule to this end, it is clear that when applied appropriately,comparative genomic approaches exponentially increase our power ingenerating biological hypotheses for subsequent experimentaltesting.

  13. Explosives, Genomics, and the Environment

    Directory of Open Access Journals (Sweden)

    Kieran C. O’Doherty

    2013-03-01

    Full Text Available RDX is an explosive that is also a neurotoxin and implicated in adverse health outcomes. Because of its widespread use in military and civilian operations, there is growing concern about potential environmental and health implications. One promising method of bioremediation involves genomic studies of soil microbes. These health concerns and technological issues intersect with social and political dimensions raising questions about public responses to genomic technologies and the degree of environmental accounting expected from the military. In cases of novel technologies entering into contested social spaces, public engagement can be useful to inform broader policy debates. Building on previous work, in this article, we outline the rationale, methods, and results of a public deliberation on these issues. To our knowledge, this is the first study of its kind on the issues of RDX pollution and microbial genomics, and thus provides an important baseline on public sentiment on these issues.

  14. The genome of Theobroma cacao.

    Science.gov (United States)

    Argout, Xavier; Salse, Jerome; Aury, Jean-Marc; Guiltinan, Mark J; Droc, Gaetan; Gouzy, Jerome; Allegre, Mathilde; Chaparro, Cristian; Legavre, Thierry; Maximova, Siela N; Abrouk, Michael; Murat, Florent; Fouet, Olivier; Poulain, Julie; Ruiz, Manuel; Roguet, Yolande; Rodier-Goud, Maguy; Barbosa-Neto, Jose Fernandes; Sabot, Francois; Kudrna, Dave; Ammiraju, Jetty Siva S; Schuster, Stephan C; Carlson, John E; Sallet, Erika; Schiex, Thomas; Dievart, Anne; Kramer, Melissa; Gelley, Laura; Shi, Zi; Bérard, Aurélie; Viot, Christopher; Boccara, Michel; Risterucci, Ange Marie; Guignon, Valentin; Sabau, Xavier; Axtell, Michael J; Ma, Zhaorong; Zhang, Yufan; Brown, Spencer; Bourge, Mickael; Golser, Wolfgang; Song, Xiang; Clement, Didier; Rivallan, Ronan; Tahi, Mathias; Akaza, Joseph Moroh; Pitollat, Bertrand; Gramacho, Karina; D'Hont, Angélique; Brunel, Dominique; Infante, Diogenes; Kebe, Ismael; Costet, Pierre; Wing, Rod; McCombie, W Richard; Guiderdoni, Emmanuel; Quetier, Francis; Panaud, Olivier; Wincker, Patrick; Bocs, Stephanie; Lanaud, Claire

    2011-02-01

    We sequenced and assembled the draft genome of Theobroma cacao, an economically important tropical-fruit tree crop that is the source of chocolate. This assembly corresponds to 76% of the estimated genome size and contains almost all previously described genes, with 82% of these genes anchored on the 10 T. cacao chromosomes. Analysis of this sequence information highlighted specific expansion of some gene families during evolution, for example, flavonoid-related genes. It also provides a major source of candidate genes for T. cacao improvement. Based on the inferred paleohistory of the T. cacao genome, we propose an evolutionary scenario whereby the ten T. cacao chromosomes were shaped from an ancestor through eleven chromosome fusions.

  15. Genomics, medicine and public health

    Directory of Open Access Journals (Sweden)

    Alexander M. Trbovich

    2006-12-01

    Full Text Available Public health genomics unifies the scientific disciplines of genetics and public health. Public health genomics aims to facilitate the transfer of newly acquired knowledge in genetic and molecular biology into classical medicine, to evaluate the currently available genetic tests, and to educate both the medical community and the general population about advancements in molecular and cell biology of medical interest. Due to various factors, the application of new genetic discoveries in classical medicine and the evaluation of the current genetic clinical tests occur at relatively slow paste. The challenge of public health genomics is to create the most effective modus for coexistence of new molecular and cell biology discoveries and classical medical techniques in applied medicine. The ultimate goal is to accomplish a truly individualized medical therapy.

  16. Genomic imprinting in farm animals.

    Science.gov (United States)

    Tian, Xiuchun Cindy

    2014-02-01

    The mouse is the first species in which genomic imprinting was studied. Imprinting research in farm species has lagged behind owing to a lack of sequencing and genetic background information, as well as long generation intervals and high costs in tissue collection. Since the creation of Dolly, the first cloned mammal from an adult sheep, studies on genomic imprinting in domestic species have accelerated because animals from cloning and other assisted reproductive technologies exhibit phenotypes of imprinting disruptions. Although this review focuses on new developments in farm animals, most of the imprinting mechanism information was derived from the mouse.

  17. Genomic Signals of Reoriented ORFs

    Directory of Open Access Journals (Sweden)

    Paul Dan Cristea

    2004-01-01

    Full Text Available Complex representation of nucleotides is used to convert DNA sequences into complex digital genomic signals. The analysis of the cumulated phase and unwrapped phase of DNA genomic signals reveals large-scale features of eukaryote and prokaryote chromosomes that result from statistical regularities of base and base-pair distributions along DNA strands. By reorienting the chromosome coding regions, a “hidden” linear variation of the cumulated phase has been revealed, along with the conspicuous almost linear variation of the unwrapped phase. A model of chromosome longitudinal structure is inferred on these bases.

  18. Easyfig: a genome comparison visualizer.

    Science.gov (United States)

    Sullivan, Mitchell J; Petty, Nicola K; Beatson, Scott A

    2011-04-01

    Easyfig is a Python application for creating linear comparison figures of multiple genomic loci with an easy-to-use graphical user interface. BLAST comparisons between multiple genomic regions, ranging from single genes to whole prokaryote chromosomes, can be generated, visualized and interactively coloured, enabling a rapid transition between analysis and the preparation of publication quality figures. Easyfig is freely available (under a GPL license) for download (for Mac OS X, Unix and Microsoft Windows) from the SourceForge web site: http://easyfig.sourceforge.net/.

  19. Fungal genomics beyond Saccharomyces cerevisiae?

    DEFF Research Database (Denmark)

    Hofmann, Gerald; Mcintyre, Mhairi; Nielsen, Jens

    2003-01-01

    Fungi are used extensively in both fundamental research and industrial applications. Saccharomyces cerevisiae has been the model organism for fungal research for many years, particularly in functional genomics. However, considering the diversity within the fungal kingdom, it is obvious...... that the application of the existing methods of genome, transcriptome, proteome and metabolome analysis to other fungi has enormous potential, especially for the production of food and food ingredients. The developments in the past year demonstrate that we have only just started to exploit this potential....

  20. Genome editing comes of age.

    Science.gov (United States)

    Kim, Jin-Soo

    2016-09-01

    Genome editing harnesses programmable nucleases to cut and paste genetic information in a targeted manner in living cells and organisms. Here, I review the development of programmable nucleases, including zinc finger nucleases (ZFNs), TAL (transcription-activator-like) effector nucleases (TALENs) and CRISPR (cluster of regularly interspaced palindromic repeats)-Cas9 (CRISPR-associated protein 9) RNA-guided endonucleases (RGENs). I specifically highlight the key advances that set the foundation for the rapid and widespread implementation of CRISPR-Cas9 genome editing approaches that has revolutionized the field.

  1. Genomic composition factors affect codon usage in porcine genome ...

    African Journals Online (AJOL)

    The objective of the study was to determine the codon usage bias in the porcine genome and decipher its determinants. To investigate the underlying mechanisms of codon bias, the coding sequence (CDS) from the swine reference sequence (ssc10.2) was extracted using Biomart. An in house built Perl script was used to ...

  2. [Nutritional genomics: an approach to the genome-environment interaction].

    Science.gov (United States)

    Xacur-García, Fiona; Castillo-Quan, Jorge I; Hernández-Escalante, Víctor M; Laviada-Molina, Hugo

    2008-11-01

    Nutritional genomics forms part of the genomic sciences and addresses the interaction between genes and the human diet, its influence on metabolism and subsequent susceptibility to develop common diseases. It encompasses both nutrigenomics, which explores the effects of nutrients on the genome, proteome and metabolome; and nutrigenetics, that explores the effects of genetic variations on the diet/disease interaction. A number of mechanisms drive the gene/diet interaction: elements in the diet can act as links for transcription factor receptors and after intermediary concentrations, thereby modifying chromatin and impacting genetic regulation; affect signal pathways, regulating phosphorylation of tyrosine in receptors; decrease signaling through the inositol pathway; and act through epigenetic mechanisms, silencing DNA fragments by methylation of cytosine. The signals generated by polyunsaturated fatty acids are so powerful that they can even bypass insulin mediated lipogenesis, stimulated by carbohydrates. Some fatty acids modify the expression of genes that participate in fatty acid transport by lipoproteins. Nutritional genomics has myriad possible therapeutic and preventive applications: in patients with enzymatic deficiencies; in those with a genetic predisposition to complex diseases such as dyslipidemia, diabetes and cancer; in those that already suffer these diseases; in those with altered mood or memory; during the aging process; in pregnant women; and as a preventive measure in the healthy population.

  3. Genomic composition factors affect codon usage in porcine genome

    African Journals Online (AJOL)

    j.khobondo

    2015-01-28

    Jan 28, 2015 ... expression of target genes in vivo or in vitro and improve the accuracy of gene prediction from genomic sequences thus maximizing ... These biological breakthroughs revealed the importance of studying the degeneracy of ... diversity, gene expression and evolution, and adaptation to micro environment.

  4. Enhancing the genome editing toolbox: genome wide CRISPR arrayed libraries.

    Science.gov (United States)

    Metzakopian, Emmanouil; Strong, Alex; Iyer, Vivek; Hodgkins, Alex; Tzelepis, Konstantinos; Antunes, Liliana; Friedrich, Mathias J; Kang, Qiaohua; Davidson, Teresa; Lamberth, Jacob; Hoffmann, Christina; Davis, Gregory D; Vassiliou, George S; Skarnes, William C; Bradley, Allan

    2017-05-22

    CRISPR-Cas9 technology has accelerated biological research becoming routine for many laboratories. It is rapidly replacing conventional gene editing techniques and has high utility for both genome-wide and gene-focussed applications. Here we present the first individually cloned CRISPR-Cas9 genome wide arrayed sgRNA libraries covering 17,166 human and 20,430 mouse genes at a complexity of 34,332 sgRNAs for human and 40,860 sgRNAs for the mouse genome. For flexibility in generating stable cell lines the sgRNAs have been cloned in a lentivirus backbone containing PiggyBac transposase recognition elements together with fluorescent and drug selection markers. Over 95% of tested sgRNA induced specific DNA cleavage as measured by CEL-1 assays. Furthermore, sgRNA targeting GPI anchor protein pathway genes induced loss of function mutations in human and mouse cell lines measured by FLAER labelling. These arrayed libraries offer the prospect for performing screens on individual genes, combinations as well as larger gene sets. They also facilitate rapid deconvolution of signals from genome-wide screens. This set of vectors provide an organized comprehensive gene editing toolbox of considerable scientific value.

  5. The Phaeodactylum genome reveals the evolutionary history of diatom genomes

    Czech Academy of Sciences Publication Activity Database

    Bowler, Ch.; Allen, A. E.; Badger, J. H.; Grimwood, J.; Jabbari, K.; Kuo, A.; Maheswari, U.; Martens, C.; Maumus, F.; Otillar, R. P.; Rayko, E.; Salamov, A.; Vandepoele, K.; Beszteri, B.; Gruber, A.; Heijde, M.; Katinka, M.; Mock, T.; Valentin, K.; Verret, F.; Berges, J. A.; Brownlee, C.; Cadoret, J.-P.; Chiovitti, A.; Choi, Ch. J.; Coesel, S.; De Martino, A.; Detter, J. Ch.; Durkin, C.; Falciatore, A.; Fournet, J.; Haruta, M.; Huysman, M. J. J.; Jenkins, B. D.; Jiroutová, Kateřina; Jorgensen, R. E.; Joubert, Y.; Kaplan, A.; Kröger, N.; Kroth, P. G.; La Roche, J.; Lindquist, E.; Lommer, M.; Martin–Jézéquel, V.; Lopez, P. J.; Lucas, S.; Mangogna, M.; McGinnis, K.; Medlin, L. K.; Montsant, A.; Oudot–Le Secq, M.-P.; Napoli, C.; Oborník, Miroslav; Schnitzler Parker, M.; Petit, J.-L.; Porcel, B. M.; Poulsen, N.; Robison, M.; Rychlewski, L.; Rynearson, T. A.; Schmutz, J.; Shapiro, H.; Siaut, M.; Stanley, M.; Sussman, M. R.; Taylor, A. R.; Vardi, A.; von Dassow, P.; Vyverman, W.; Willis, A.; Wyrwicz, L. S.; Rokhsar, D. S.; Weissenbach, J.; Armbrust, E. V.; Green, B. R.; Van de Peer, Y.; Grigoriev, I. V.

    2008-01-01

    Roč. 456, 13-11-2008 (2008), s. 239-244 ISSN 0028-0836 Institutional research plan: CEZ:AV0Z60220518 Keywords : Phaeodactylum * genome * evolution * diatom Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 31.434, year: 2008

  6. Genome surfing as driver of microbial genomic diversity

    Science.gov (United States)

    Historical changes in population size, such as those caused by demographic range expansions, can produce nonadaptive changes in genomic diversity through mechanisms such as gene surfing. We propose that demographic range expansion of a microbial population capable of horizontal gene exchange can res...

  7. An Exploration into Fern Genome Space.

    Science.gov (United States)

    Wolf, Paul G; Sessa, Emily B; Marchant, Daniel Blaine; Li, Fay-Wei; Rothfels, Carl J; Sigel, Erin M; Gitzendanner, Matthew A; Visger, Clayton J; Banks, Jo Ann; Soltis, Douglas E; Soltis, Pamela S; Pryer, Kathleen M; Der, Joshua P

    2015-08-26

    Ferns are one of the few remaining major clades of land plants for which a complete genome sequence is lacking. Knowledge of genome space in ferns will enable broad-scale comparative analyses of land plant genes and genomes, provide insights into genome evolution across green plants, and shed light on genetic and genomic features that characterize ferns, such as their high chromosome numbers and large genome sizes. As part of an initial exploration into fern genome space, we used a whole genome shotgun sequencing approach to obtain low-density coverage (∼0.4X to 2X) for six fern species from the Polypodiales (Ceratopteris, Pteridium, Polypodium, Cystopteris), Cyatheales (Plagiogyria), and Gleicheniales (Dipteris). We explore these data to characterize the proportion of the nuclear genome represented by repetitive sequences (including DNA transposons, retrotransposons, ribosomal DNA, and simple repeats) and protein-coding genes, and to extract chloroplast and mitochondrial genome sequences. Such initial sweeps of fern genomes can provide information useful for selecting a promising candidate fern species for whole genome sequencing. We also describe variation of genomic traits across our sample and highlight some differences and similarities in repeat structure between ferns and seed plants. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  8. Genome Size Dynamics and Evolution in Monocots

    Directory of Open Access Journals (Sweden)

    Ilia J. Leitch

    2010-01-01

    Full Text Available Monocot genomic diversity includes striking variation at many levels. This paper compares various genomic characters (e.g., range of chromosome numbers and ploidy levels, occurrence of endopolyploidy, GC content, chromosome packaging and organization, genome size between monocots and the remaining angiosperms to discern just how distinctive monocot genomes are. One of the most notable features of monocots is their wide range and diversity of genome sizes, including the species with the largest genome so far reported in plants. This genomic character is analysed in greater detail, within a phylogenetic context. By surveying available genome size and chromosome data it is apparent that different monocot orders follow distinctive modes of genome size and chromosome evolution. Further insights into genome size-evolution and dynamics were obtained using statistical modelling approaches to reconstruct the ancestral genome size at key nodes across the monocot phylogenetic tree. Such approaches reveal that while the ancestral genome size of all monocots was small (1C=1.9 pg, there have been several major increases and decreases during monocot evolution. In addition, notable increases in the rates of genome size-evolution were found in Asparagales and Poales compared with other monocot lineages.

  9. Challenges to genome sequence dissection in sweetpotato

    Science.gov (United States)

    Isobe, Sachiko; Shirasawa, Kenta; Hirakawa, Hideki

    2017-01-01

    The development of next generation sequencing (NGS) technologies has enabled the determination of whole genome sequences in many non-model plant species. However, genome sequencing in sweetpotato (Ipomoea batatas (L.) Lam) is still difficult because of the hexaploid genome structure. Previous studies suggested that a diploid wild relative, I. trifida (H.B.K.) Don., is the most possible ancestor of sweetpotato. Therefore, the genetic and genomic features of I. trifida have been studied as a potential reference for sweetpotato. Meanwhile, several research groups have begun the challenging task of directly sequencing the sweetpotato genome. In this manuscript, we review the recent results and activities of large-scale genome and transcriptome analysis related to genome sequence dissection in sweetpotato under the sections as follows: I. trifida genome and transcript sequencing, genome sequences of I. nil (Japanese morning glory), transcript sequences in sweetpotato, chloroplast sequences, transposable elements and transfer DNA. The recent international activities of de novo whole genome sequencing in sweetpotato are also described. The large-scale publically available genome and transcript sequence resources and the international genome sequencing streams are expected to promote the genome sequence dissection in sweetpotato. PMID:28465666

  10. Burkholderia pseudomallei genome plasticity associated with genomic island variation

    Directory of Open Access Journals (Sweden)

    Currie Bart J

    2008-04-01

    Full Text Available Abstract Background Burkholderia pseudomallei is a soil-dwelling saprophyte and the cause of melioidosis. Horizontal gene transfer contributes to the genetic diversity of this pathogen and may be an important determinant of virulence potential. The genome contains genomic island (GI regions that encode a broad array of functions. Although there is some evidence for the variable distribution of genomic islands in B. pseudomallei isolates, little is known about the extent of variation between related strains or their association with disease or environmental survival. Results Five islands from B. pseudomallei strain K96243 were chosen as representatives of different types of genomic islands present in this strain, and their presence investigated in other B. pseudomallei. In silico analysis of 10 B. pseudomallei genome sequences provided evidence for the variable presence of these regions, together with micro-evolutionary changes that generate GI diversity. The diversity of GIs in 186 isolates from NE Thailand (83 environmental and 103 clinical isolates was investigated using multiplex PCR screening. The proportion of all isolates positive by PCR ranged from 12% for a prophage-like island (GI 9, to 76% for a metabolic island (GI 16. The presence of each of the five GIs did not differ between environmental and disease-associated isolates (p > 0.05 for all five islands. The cumulative number of GIs per isolate for the 186 isolates ranged from 0 to 5 (median 2, IQR 1 to 3. The distribution of cumulative GI number did not differ between environmental and disease-associated isolates (p = 0.27. The presence of GIs was defined for the three largest clones in this collection (each defined as a single sequence type, ST, by multilocus sequence typing; these were ST 70 (n = 15 isolates, ST 54 (n = 11, and ST 167 (n = 9. The rapid loss and/or acquisition of gene islands was observed within individual clones. Comparisons were drawn between isolates obtained

  11. Hybridisation between cherry tomato (small fry) and Petomech for ...

    African Journals Online (AJOL)

    The objective of this study was to determin the heritability of shortened fruit maturation (SFM) period in a hybrid from a cross between cherry (Small fry) tomato and Petomech. A field experiment was carried out at the Crops Research Institute (CRI), Kwadaso. A cross was made between Petomech and Small fry.

  12. Exciton Hybridisation in Organic-Inorganic Semiconductor Microcavities

    National Research Council Canada - National Science Library

    Lidzey, David

    2002-01-01

    ... that could be either a laser or a very efficient LED. The report describes fabrication of new types of microcavity containing organic semiconductors, including strongly-coupled microcavities based on two metallic mirrors...

  13. hybridisation between cherry tomato (small fry) and petomech for ...

    African Journals Online (AJOL)

    ACSS

    Scientific Industrial Research (CSIR)-Crops. Research Institute, Kwadaso, Kumasi in Ghana. The research field area of ... fresh by weighing pericarp tissues including external, internal and transverse parts, excluding seeds, using a weighing scale. Twenty-three fruits were collected from each of the genotypes, representing ...

  14. Biofilm biodiversity presented by fluorescent in situ hybridisation

    Directory of Open Access Journals (Sweden)

    Wolf Mirela

    2017-01-01

    Full Text Available Numerous microorganisms may be present in the water distribution system. This is associated with the imperfection of purification processes, or secondary water pollution. Not only it results in the deterioration of water quality parameters, but it also increases threat of epidemiological problems. The water that is biologically unstable creates ideal conditions for colonization of the microorganisms to the inner surface of pipelines which may form biofilm. The key issue, enabling prevention and control of the impact of the development of biofilms, is to assess the biodiversity of microbiocenosis. In order to obtain comprehensive characteristics of microorganisms communities on a particular substrate, it is necessary to combine several techniques. Further analysis using molecular biology methods are usually after traditional methods of assessing the microbiological quality of water. Standard methods do not reflect the actual species composition, because they are targeted at the bacteria that can be isolated and cultured in the laboratory. Conventional methods are capable of detecting less than 10% of the organisms in the sample. In order to study the biodiversity of organisms inhabiting a biofilm (apart from the conventional methods analyses of the diversity of nucleic acids should be used. The first method could be the polymerase chain reaction (PCR and denaturing gradient gel electrophoresis (DGGE. Another way may be fluorescence in situ hybridization, which allows to detect determined DNA sequence using specially labeled oligonucleotide probes. Visualization of the material is performed using a fluorescence microscope. The main purpose of this article is to present rapid and precise identification groups of microorganisms in their natural habitat in biofilm using fluorescent in situ hybridization method (FISH . FISH method can be successfully used to visualize these microorganisms, which show difficulties in culturing, as well as to provide knowledge on the phylogenetic structure in different habitats. FISH technique allows the quantitative description of environmental samples.

  15. Interspecific hybridisation of Lathyrus sativus (Guaya) with wild ...

    African Journals Online (AJOL)

    Except for the reciprocal crosses of L. sativus and L. pseudo-cicera, others failed to develop viable seeds. In several of the interspecific hybrids, pod development was observed but embryos aborted during early stages of development. Embryo culture was attempted to rescue these immature embryos. The response of the ...

  16. Inferred hybridisation, sympatry and movements of Chorister Robin ...

    African Journals Online (AJOL)

    Chat C. natalensis have previously only been recorded from the Eastern Cape province, South Africa. We extend the occurrence of inferred hybrids with ringed and photographed examples from KwaZulu-Natal and Limpopo provinces.

  17. Detection of human papillomavirus DNA with in situ hybridisation in ...

    African Journals Online (AJOL)

    HPV-16, 18 and 33, have been implicated in squamous cell carcinogenesis because of their ability to immortalise human. Department of Medical Virology, University of Stelienbosch,. Tygerberg, W. Cape. Estrelita Janse Van Rensburg, M.MED. (VIROL). Department of Oral Pathology and Oral Biology, Medical University.

  18. Advancing Eucalyptus Genomics: Cytogenomics Reveals Conservation of Eucalyptus Genomes

    Science.gov (United States)

    Ribeiro, Teresa; Barrela, Ricardo M.; Bergès, Hélène; Marques, Cristina; Loureiro, João; Morais-Cecílio, Leonor; Paiva, Jorge A. P.

    2016-01-01

    The genus Eucalyptus encloses several species with high ecological and economic value, being the subgenus Symphyomyrtus one of the most important. Species such as E. grandis and E. globulus are well characterized at the molecular level but knowledge regarding genome and chromosome organization is very scarce. Here we characterized and compared the karyotypes of three economically important species, E. grandis, E. globulus, and E. calmadulensis, and three with ecological relevance, E. pulverulenta, E. cornuta, and E. occidentalis, through an integrative approach including genome size estimation, fluorochrome banding, rDNA FISH, and BAC landing comprising genes involved in lignin biosynthesis. All karyotypes show a high degree of conservation with pericentromeric 35S and 5S rDNA loci in the first and third pairs, respectively. GC-rich heterochromatin was restricted to the 35S rDNA locus while the AT-rich heterochromatin pattern was species-specific. The slight differences in karyotype formulas and distribution of AT-rich heterochromatin, along with genome sizes estimations, support the idea of Eucalyptus genome evolution by local expansions of heterochromatin clusters. The unusual co-localization of both rDNA with AT-rich heterochromatin was attributed mainly to the presence of silent transposable elements in those loci. The cinnamoyl CoA reductase gene (CCR1) previously assessed to linkage group 10 (LG10) was clearly localized distally at the long arm of chromosome 9 establishing an unexpected correlation between the cytogenetic chromosome 9 and the LG10. Our work is novel and contributes to the understanding of Eucalyptus genome organization which is essential to develop successful advanced breeding strategies for this genus. PMID:27148332

  19. Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute’s genomic medicine portfolio

    Science.gov (United States)

    Manolio, Teri A.

    2016-01-01

    Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual’s genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of “Genomic Medicine Meetings,” under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and diffficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI’s genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so. PMID:27612677

  20. Genome size variation in the genus Avena.

    Science.gov (United States)

    Yan, Honghai; Martin, Sara L; Bekele, Wubishet A; Latta, Robert G; Diederichsen, Axel; Peng, Yuanying; Tinker, Nicholas A

    2016-03-01

    Genome size is an indicator of evolutionary distance and a metric for genome characterization. Here, we report accurate estimates of genome size in 99 accessions from 26 species of Avena. We demonstrate that the average genome size of C genome diploid species (2C = 10.26 pg) is 15% larger than that of A genome species (2C = 8.95 pg), and that this difference likely accounts for a progression of size among tetraploid species, where AB Avena have experienced genome downsizing in relation to their diploid progenitors. Genome size measurements could provide additional quality control for species identification in germplasm collections, especially in cases where diploid and polyploid species have similar morphology.

  1. Strategies and tools for whole genome alignments

    Energy Technology Data Exchange (ETDEWEB)

    Couronne, Olivier; Poliakov, Alexander; Bray, Nicolas; Ishkhanov,Tigran; Ryaboy, Dmitriy; Rubin, Edward; Pachter, Lior; Dubchak, Inna

    2002-11-25

    The availability of the assembled mouse genome makespossible, for the first time, an alignment and comparison of two largevertebrate genomes. We have investigated different strategies ofalignment for the subsequent analysis of conservation of genomes that areeffective for different quality assemblies. These strategies were appliedto the comparison of the working draft of the human genome with the MouseGenome Sequencing Consortium assembly, as well as other intermediatemouse assemblies. Our methods are fast and the resulting alignmentsexhibit a high degree of sensitivity, covering more than 90 percent ofknown coding exons in the human genome. We have obtained such coveragewhile preserving specificity. With a view towards the end user, we havedeveloped a suite of tools and websites for automatically aligning, andsubsequently browsing and working with whole genome comparisons. Wedescribe the use of these tools to identify conserved non-coding regionsbetween the human and mouse genomes, some of which have not beenidentified by other methods.

  2. V-GAP: Viral genome assembly pipeline

    KAUST Repository

    Nakamura, Yoji

    2015-10-22

    Next-generation sequencing technologies have allowed the rapid determination of the complete genomes of many organisms. Although shotgun sequences from large genome organisms are still difficult to reconstruct perfect contigs each of which represents a full chromosome, those from small genomes have been assembled successfully into a very small number of contigs. In this study, we show that shotgun reads from phage genomes can be reconstructed into a single contig by controlling the number of read sequences used in de novo assembly. We have developed a pipeline to assemble small viral genomes with good reliability using a resampling method from shotgun data. This pipeline, named V-GAP (Viral Genome Assembly Pipeline), will contribute to the rapid genome typing of viruses, which are highly divergent, and thus will meet the increasing need for viral genome comparisons in metagenomic studies.

  3. Gramene database: navigating plant comparative genomics resources

    Science.gov (United States)

    Gramene (http://www.gramene.org) is an online, open source, curated resource for plant comparative genomics and pathway analysis designed to support researchers working in plant genomics, breeding, evolutionary biology, system biology, and metabolic engineering. It exploits phylogenetic relationship...

  4. India, Genomic diversity & Disease susceptibility

    Indian Academy of Sciences (India)

    Table of contents. India, Genomic diversity & Disease susceptibility · India, a paradise for Genetic Studies · Involved in earlier stages of Immune response protecting us from Diseases, Responsible for kidney and other transplant rejections Inherited from our parents · PowerPoint Presentation · Slide 5 · Slide 6 · Slide 7.

  5. The genome of a songbird

    Science.gov (United States)

    Warren, Wesley C.; Clayton, David F.; Ellegren, Hans; Arnold, Arthur P.; Hillier, LaDeana W.; Künstner, Axel; Searle, Steve; White, Simon; Vilella, Albert J.; Fairley, Susan; Heger, Andreas; Kong, Lesheng; Ponting, Chris P.; Jarvis, Erich D.; Mello, Claudio V.; Minx, Pat; Lovell, Peter; Velho, Tarciso A. F.; Ferris, Margaret; Balakrishnan, Christopher N.; Sinha, Saurabh; Blatti, Charles; London, Sarah E.; Li, Yun; Lin, Ya-Chi; George, Julia; Sweedler, Jonathan; Southey, Bruce; Gunaratne, Preethi; Watson, Michael; Nam, Kiwoong; Backström, Niclas; Smeds, Linnea; Nabholz, Benoit; Itoh, Yuichiro; Whitney, Osceola; Pfenning, Andreas R.; Howard, Jason; Völker, Martin; Skinner, Bejamin M.; Griffin, Darren K.; Ye, Liang; McLaren, William M.; Flicek, Paul; Quesada, Victor; Velasco, Gloria; Lopez-Otin, Carlos; Puente, Xose S.; Olender, Tsviya; Lancet, Doron; Smit, Arian F. A.; Hubley, Robert; Konkel, Miriam K.; Walker, Jerilyn A.; Batzer, Mark A.; Gu, Wanjun; Pollock, David D.; Chen, Lin; Cheng, Ze; Eichler, Evan E.; Stapley, Jessica; Slate, Jon; Ekblom, Robert; Birkhead, Tim; Burke, Terry; Burt, David; Scharff, Constance; Adam, Iris; Richard, Hugues; Sultan, Marc; Soldatov, Alexey; Lehrach, Hans; Edwards, Scott V.; Yang, Shiaw-Pyng; Li, XiaoChing; Graves, Tina; Fulton, Lucinda; Nelson, Joanne; Chinwalla, Asif; Hou, Shunfeng; Mardis, Elaine R.; Wilson, Richard K.

    2010-01-01

    The zebra finch is an important model organism in several fields1,2 with unique relevance to human neuroscience3,4. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken5—the only bird with a sequenced genome until now6. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes7. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour. PMID:20360741

  6. Genome position and gene amplification

    Czech Academy of Sciences Publication Activity Database

    Jirsová, Pavla; Snijders, A.M.; Kwek, S.; Roydasgupta, R.; Fridlyand, J.; Tokuyasu, T.; Pinkel, D.; Albertson, D. G.

    2007-01-01

    Roč. 8, č. 6 (2007), r120 ISSN 1474-760X Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : gene amplification * array comparative genomic hybridization * oncogene Subject RIV: BO - Biophysics Impact factor: 6.589, year: 2007

  7. Fungal genome resources at NCBI

    Science.gov (United States)

    Robbertse, B.; Tatusova, T.

    2011-01-01

    The National Center for Biotechnology Information (NCBI) is well known for the nucleotide sequence archive, GenBank and sequence analysis tool BLAST. However, NCBI integrates many types of biomolecular data from variety of sources and makes it available to the scientific community as interactive web resources as well as organized releases of bulk data. These tools are available to explore and compare fungal genomes. Searching all databases with Fungi [organism] at http://www.ncbi.nlm.nih.gov/ is the quickest way to find resources of interest with fungal entries. Some tools though are resources specific and can be indirectly accessed from a particular database in the Entrez system. These include graphical viewers and comparative analysis tools such as TaxPlot, TaxMap and UniGene DDD (found via UniGene Homepage). Gene and BioProject pages also serve as portals to external data such as community annotation websites, BioGrid and UniProt. There are many different ways of accessing genomic data at NCBI. Depending on the focus and goal of research projects or the level of interest, a user would select a particular route for accessing genomic databases and resources. This review article describes methods of accessing fungal genome data and provides examples that illustrate the use of analysis tools. PMID:22737589

  8. Scalable Computing for Evolutionary Genomics

    NARCIS (Netherlands)

    Prins, J.C.P.; Belhachemi, D.; Möller, S.; Smant, G.

    2012-01-01

    Genomic data analysis in evolutionary biology is becoming so computationally intensive that analysis of multiple hypotheses and scenarios takes too long on a single desktop computer. In this chapter, we discuss techniques for scaling computations through parallelization of calculations, after giving

  9. Ecological Genomics of Marine Picocyanobacteria†

    Science.gov (United States)

    Scanlan, D. J.; Ostrowski, M.; Mazard, S.; Dufresne, A.; Garczarek, L.; Hess, W. R.; Post, A. F.; Hagemann, M.; Paulsen, I.; Partensky, F.

    2009-01-01

    Summary: Marine picocyanobacteria of the genera Prochlorococcus and Synechococcus numerically dominate the picophytoplankton of the world ocean, making a key contribution to global primary production. Prochlorococcus was isolated around 20 years ago and is probably the most abundant photosynthetic organism on Earth. The genus comprises specific ecotypes which are phylogenetically distinct and differ markedly in their photophysiology, allowing growth over a broad range of light and nutrient conditions within the 45°N to 40°S latitudinal belt that they occupy. Synechococcus and Prochlorococcus are closely related, together forming a discrete picophytoplankton clade, but are distinguishable by their possession of dissimilar light-harvesting apparatuses and differences in cell size and elemental composition. Synechococcus strains have a ubiquitous oceanic distribution compared to that of Prochlorococcus strains and are characterized by phylogenetically discrete lineages with a wide range of pigmentation. In this review, we put our current knowledge of marine picocyanobacterial genomics into an environmental context and present previously unpublished genomic information arising from extensive genomic comparisons in order to provide insights into the adaptations of these marine microbes to their environment and how they are reflected at the genomic level. PMID:19487728

  10. Biclustering Sparse Binary Genomic Data

    NARCIS (Netherlands)

    Van Uitert, M.; Meuleman, W.; Wessels, L.F.A.

    2008-01-01

    Genomic datasets often consist of large, binary, sparse data matrices. In such a dataset, one is often interested in finding contiguous blocks that (mostly) contain ones. This is a biclustering problem, and while many algorithms have been proposed to deal with gene expression data, only two

  11. Genomic Heritability: What Is It?

    DEFF Research Database (Denmark)

    de los Campos, Gustavo; Sorensen, Daniel; Gianola, Daniel

    2015-01-01

    Whole-genome regression methods are being increasingly used for the analysis and prediction of complex traits and diseases. In human genetics, these methods are commonly used for inferences about genetic parameters, such as the amount of genetic variance among individuals or the proportion of phe...

  12. Bioinformatica ten behoeve van genomics

    NARCIS (Netherlands)

    Pennings JLA; Hoebee B; TOX

    2007-01-01

    Sinds enkele jaren wordt op het RIVM genomicsonderzoek uitgevoerd. Genomics omvat grootschalig onderzoek naar het erfelijk materiaal (DNA) van organismen. Dit onderzoek levert inzicht op in de manier waarop erfelijke eigenschappen zich vertalen naar het functioneren van een cel, en uiteindelijk

  13. Nutritional genomics and personalized diet

    African Journals Online (AJOL)

    Nagwa E.A. Gaboon

    Nutritional genomics. Abstract Nutritional genetics is considered as the combination of nutrigenomics and nutrigenetics. Nutrigenomics is establishing the .... on the knowledge of nutritional requirements, nutritional status, and genotype (i.e., person- alized nutrition) can be used to prevent, mitigate, or cure chronic disease. 3.

  14. The genome of Chenopodium quinoa

    NARCIS (Netherlands)

    Jarvis, D.E.; Shwen Ho, Yung; Lightfoot, Damien J.; Schmöckel, Sandra M.; Li, Bo; Borm, T.J.A.; Ohyanagi, Hajime; Mineta, Katsuhiko; Mitchell, Craig T.; Saber, Noha; Kharbatia, Najeh M.; Rupper, Ryan R.; Sharp, Aaron R.; Dally, Nadine; Boughton, Berin A.; Woo, Yong H.; Gao, Ge; Schijlen, E.G.W.M.; Guo, Xiujie; Momin, Afaque A.; Negräo, Sónia; Al-Babili, Salim; Gehring, Christoph; Roessner, Ute; Jung, Christian; Murphy, Kevin; Arold, Stefan T.; Gojobori, Takashi; Linden, van der C.G.; Loo, van E.N.; Jellen, Eric N.; Maughan, Peter J.; Tester, Mark

    2017-01-01

    Chenopodium quinoa (quinoa) is a highly nutritious grain identified as an important crop to improve world food security. Unfortunately, few resources are available to facilitate its genetic improvement. Here we report the assembly of a high-quality, chromosome-scale reference genome sequence for

  15. Searching and Indexing Genomic Databases via Kernelization

    Directory of Open Access Journals (Sweden)

    Travis eGagie

    2015-02-01

    Full Text Available The rapid advance of DNA sequencing technologies has yielded databases of thousands of genomes. To search and index these databases effectively, it is important that we take advantage of the similarity between those genomes. Several authors have recently suggested searching or indexing only one reference genome and the parts of the other genomes where they differ. In this paper we survey the twenty-year history of this idea and discuss its relation to kernelization in parameterized complexity.

  16. Searching and Indexing Genomic Databases via Kernelization.

    Science.gov (United States)

    Gagie, Travis; Puglisi, Simon J

    2015-01-01

    The rapid advance of DNA sequencing technologies has yielded databases of thousands of genomes. To search and index these databases effectively, it is important that we take advantage of the similarity between those genomes. Several authors have recently suggested searching or indexing only one reference genome and the parts of the other genomes where they differ. In this paper, we survey the 20-year history of this idea and discuss its relation to kernelization in parameterized complexity.

  17. Genomics-assisted breeding in fruit trees

    OpenAIRE

    Iwata, Hiroyoshi; Minamikawa, Mai F.; Kajiya-Kanegae, Hiromi; Ishimori, Motoyuki; Hayashi, Takeshi

    2016-01-01

    Recent advancements in genomic analysis technologies have opened up new avenues to promote the efficiency of plant breeding. Novel genomics-based approaches for plant breeding and genetics research, such as genome-wide association studies (GWAS) and genomic selection (GS), are useful, especially in fruit tree breeding. The breeding of fruit trees is hindered by their long generation time, large plant size, long juvenile phase, and the necessity to wait for the physiological maturity of the pl...

  18. GRAbB : Selective Assembly of Genomic Regions, a New Niche for Genomic Research

    NARCIS (Netherlands)

    Brankovics, Balázs; Zhang, Hao; van Diepeningen, Anne D; van der Lee, Theo A J; Waalwijk, Cees; de Hoog, G Sybren

    GRAbB (Genomic Region Assembly by Baiting) is a new program that is dedicated to assemble specific genomic regions from NGS data. This approach is especially useful when dealing with multi copy regions, such as mitochondrial genome and the rDNA repeat region, parts of the genome that are often

  19. Genomic Organization of Leishmania Species

    Directory of Open Access Journals (Sweden)

    B Kazemi

    2011-09-01

    Full Text Available Leishmania is a protozoan parasite belonging to the family Trypanosomatidae, which is found among 88 different countries. The parasite lives as an amastigote in vertebrate macro­phages and as a promastigote in the digestive tract of sand fly. It can be cultured in the laboratory us­ing appropriate culture media. Although the sexual cycle of Leishmania has not been observed during the promastigote and amastigote stages, it has been reported by some researchers. Leishma­nia has eukaryotic cell organization. Cell culture is convenient and cost effective, and because posttranslational modifications are common processes in the cultured cells, the cells are used as hosts for preparing eukaryotic recombinant proteins for research. Several transcripts of rDNA in the Leishmania genome are suitable regions for conducting gene transfer. Old World Leishmania spp. has 36 chromosomes, while New World Leishmania spp. has 34 or 35 chromo­somes. The genomic organization and parasitic characteristics have been investigated. Leishmania spp. has a unique genomic organization among eukaryotes; the genes do not have introns, and the chromosomes are smaller with larger numbers of genes confined to a smaller space within the nucleus. Leishmania spp. genes are organized on one or both DNA strands and are transcribed as polycistronic (prokaryotic-like transcripts from undefined promoters. Regulation of gene expres­sion in the members of Trypanosomatidae differs from that in other eukaryotes. The trans-splic­ing phenomenon is a necessary step for mRNA processing in lower eukaryotes and is observed in Leishmania spp. Another particular feature of RNA editing in Leishmania spp. is that mitochon­drial genes encoding respiratory enzymes are edited and transcribed. This review will discuss the chromosomal and mitochondrial (kinetoplast genomes of Leishmania spp. as well as the phenome­non of RNA editing in the kinetoplast genome.

  20. International network of cancer genome projects

    NARCIS (Netherlands)

    Hudson, Thomas J.; Anderson, Warwick; Aretz, Axel; Barker, Anna D.; Bell, Cindy; Bernabé, Rosa R.; Bhan, M. K.; Calvo, Fabien; Eerola, Iiro; Gerhard, Daniela S.; Guttmacher, Alan; Guyer, Mark; Hemsley, Fiona M.; Jennings, Jennifer L.; Kerr, David; Klatt, Peter; Kolar, Patrik; Kusuda, Jun; Lane, David P.; Laplace, Frank; Lu, Youyong; Nettekoven, Gerd; Ozenberger, Brad; Peterson, Jane; Rao, T. S.; Remacle, Jacques; Schafer, Alan J.; Shibata, Tatsuhiro; Stratton, Michael R.; Vockley, Joseph G.; Watanabe, Koichi; Yang, Huanming; Yuen, Matthew M. F.; Knoppers, Bartha M.; Bobrow, Martin; Cambon-Thomsen, Anne; Dressler, Lynn G.; Dyke, Stephanie O. M.; Joly, Yann; Kato, Kazuto; Kennedy, Karen L.; Nicolás, Pilar; Parker, Michael J.; Rial-Sebbag, Emmanuelle; Romeo-Casabona, Carlos M.; Shaw, Kenna M.; Wallace, Susan; Wiesner, Georgia L.; Zeps, Nikolajs; Lichter, Peter; Biankin, Andrew V.; Chabannon, Christian; Chin, Lynda; Clément, Bruno; de Alava, Enrique; Degos, Françoise; Ferguson, Martin L.; Geary, Peter; Hayes, D. Neil; Johns, Amber L.; Kasprzyk, Arek; Nakagawa, Hidewaki; Penny, Robert; Piris, Miguel A.; Sarin, Rajiv; Scarpa, Aldo; van de Vijver, Marc; Futreal, P. Andrew; Aburatani, Hiroyuki; Bayés, Mónica; Bowtell, David D. L.; Campbell, Peter J.; Estivill, Xavier; Grimmond, Sean M.; Gut, Ivo; Hirst, Martin; López-Otín, Carlos; Majumder, Partha; Marra, Marco; McPherson, John D.; Ning, Zemin; Puente, Xose S.; Ruan, Yijun; Stunnenberg, Hendrik G.; Swerdlow, Harold; Velculescu, Victor E.; Wilson, Richard K.; Xue, Hong H.; Yang, Liu; Spellman, Paul T.; Bader, Gary D.; Boutros, Paul C.; Flicek, Paul; Getz, Gad; Guigó, Roderic; Guo, Guangwu; Haussler, David; Heath, Simon; Hubbard, Tim J.; Jiang, Tao; Jones, Steven M.; Li, Qibin; López-Bigas, Nuria; Luo, Ruibang; Muthuswamy, Lakshmi; Ouellette, B. F. Francis; Pearson, John V.; Quesada, Victor; Raphael, Benjamin J.; Sander, Chris; Speed, Terence P.; Stein, Lincoln D.; Stuart, Joshua M.; Teague, Jon W.; Totoki, Yasushi; Tsunoda, Tatsuhiko; Valencia, Alfonso; Wheeler, David A.; Wu, Honglong; Zhao, Shancen; Zhou, Guangyu; Lathrop, Mark; Thomas, Gilles; Yoshida, Teruhiko; Axton, Myles; Gunter, Chris; Miller, Linda J.; Zhang, Junjun; Haider, Syed A.; Wang, Jianxin; Yung, Christina K.; Cross, Anthony; Liang, Yong; Gnaneshan, Saravanamuttu; Guberman, Jonathan; Hsu, Jack; Chalmers, Don R. C.; Hasel, Karl W.; Kaan, Terry S. H.; Lowrance, William W.; Masui, Tohru; Rodriguez, Laura Lyman; Vergely, Catherine; Cloonan, Nicole; Defazio, Anna; Eshleman, James R.; Etemadmoghadam, Dariush; Gardiner, Brooke A.; Kench, James G.; Sutherland, Robert L.; Tempero, Margaret A.; Waddell, Nicola J.; Wilson, Peter J.; Gallinger, Steve; Tsao, Ming-Sound; Shaw, Patricia A.; Petersen, Gloria M.; Mukhopadhyay, Debabrata; DePinho, Ronald A.; Thayer, Sarah; Shazand, Kamran; Beck, Timothy; Sam, Michelle; Timms, Lee; Ballin, Vanessa; Ji, Jiafu; Zhang, Xiuqing; Chen, Feng; Hu, Xueda; Yang, Qi; Tian, Geng; Zhang, Lianhai; Xing, Xiaofang; Li, Xianghong; Zhu, Zhenggang; Yu, Yingyan; Yu, Jun; Tost, Jörg; Brennan, Paul; Holcatova, Ivana; Zaridze, David; Brazma, Alvis; Egevad, Lars; Prokhortchouk, Egor; Banks, Rosamonde Elizabeth; Uhlén, Mathias; Viksna, Juris; Ponten, Fredrik; Skryabin, Konstantin; Birney, Ewan; Borg, Ake; Børresen-Dale, Anne-Lise; Caldas, Carlos; Foekens, John A.; Martin, Sancha; Reis-Filho, Jorge S.; Richardson, Andrea L.; Sotiriou, Christos; van't Veer, Laura; Birnbaum, Daniel; Blanche, Hélène; Boucher, Pascal; Boyault, Sandrine; Masson-Jacquemier, Jocelyne D.; Pauporté, Iris; Pivot, Xavier; Vincent-Salomon, Anne; Tabone, Eric; Theillet, Charles; Treilleux, Isabelle; Bioulac-Sage, Paulette; Decaens, Thomas; Franco, Dominique; Gut, Marta; Samuel, Didier; Zucman-Rossi, Jessica; Eils, Roland; Brors, Benedikt; Korbel, Jan O.; Korshunov, Andrey; Landgraf, Pablo; Lehrach, Hans; Pfister, Stefan; Radlwimmer, Bernhard; Reifenberger, Guido; Taylor, Michael D.; von Kalle, Christof; Majumder, Partha P.; Pederzoli, Paolo; Lawlor, Rita T.; Delledonne, Massimo; Bardelli, Alberto; Gress, Thomas; Klimstra, David; Zamboni, Giuseppe; Nakamura, Yusuke; Miyano, Satoru; Fujimoto, Akihiro; Campo, Elias; de Sanjosé, Silvia; Montserrat, Emili; González-Díaz, Marcos; Jares, Pedro; Himmelbaue, Heinz; Bea, Silvia; Aparicio, Samuel; Easton, Douglas F.; Collins, Francis S.; Compton, Carolyn C.; Lander, Eric S.; Burke, Wylie; Green, Anthony R.; Hamilton, Stanley R.; Kallioniemi, Olli P.; Ley, Timothy J.; Liu, Edison T.; Wainwright, Brandon J.

    2010-01-01

    The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the