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Sample records for genes tightly linked

  1. Development of molecular markers tightly linked to Pvr4 gene in pepper using next-generation sequencing.

    Science.gov (United States)

    Devran, Zübeyir; Kahveci, Erdem; Özkaynak, Ercan; Studholme, David J; Tör, Mahmut

    It is imperative to identify highly polymorphic and tightly linked markers of a known trait for molecular marker-assisted selection. Potyvirus resistance 4 (Pvr4) locus in pepper confers resistance to three pathotypes of potato virus Y and to pepper mottle virus. We describe the use of next-generation sequencing technology to generate molecular markers tightly linked to Pvr4. Initially, comparative genomics was carried out, and a syntenic region of tomato on chromosome ten was used to generate PCR-based markers and map Pvr4. Subsequently, the genomic sequence of pepper was used, and more than 5000 single-nucleotide variants (SNVs) were identified within the interval. In addition, we identified nucleotide binding site-leucine-rich repeat-type disease resistance genes within the interval. Several of these SNVs were converted to molecular markers desirable for large-scale molecular breeding programmes.

  2. The origin recognition complex interacts with a subset of metabolic genes tightly linked to origins of replication.

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    Erika Shor

    2009-12-01

    Full Text Available The origin recognition complex (ORC marks chromosomal sites as replication origins and is essential for replication initiation. In yeast, ORC also binds to DNA elements called silencers, where its primary function is to recruit silent information regulator (SIR proteins to establish transcriptional silencing. Indeed, silencers function poorly as chromosomal origins. Several genetic, molecular, and biochemical studies of HMR-E have led to a model proposing that when ORC becomes limiting in the cell (such as in the orc2-1 mutant only sites that bind ORC tightly (such as HMR-E remain fully occupied by ORC, while lower affinity sites, including many origins, lose ORC occupancy. Since HMR-E possessed a unique non-replication function, we reasoned that other tight sites might reveal novel functions for ORC on chromosomes. Therefore, we comprehensively determined ORC "affinity" genome-wide by performing an ORC ChIP-on-chip in ORC2 and orc2-1 strains. Here we describe a novel group of orc2-1-resistant ORC-interacting chromosomal sites (ORF-ORC sites that did not function as replication origins or silencers. Instead, ORF-ORC sites were comprised of protein-coding regions of highly transcribed metabolic genes. In contrast to the ORC-silencer paradigm, transcriptional activation promoted ORC association with these genes. Remarkably, ORF-ORC genes were enriched in proximity to origins of replication and, in several instances, were transcriptionally regulated by these origins. Taken together, these results suggest a surprising connection among ORC, replication origins, and cellular metabolism.

  3. Evolutionary relationship and ethnic variations of two tightly linked mutations in the gene coding for the lysosomal enzyme arylsulfatase

    Energy Technology Data Exchange (ETDEWEB)

    Ott, A.R.; Wave. J.S.; Chang, P.L. [McMaster Univ., Ontario (Canada)

    1994-09-01

    Metachromatic leukodystrophy is a neurodegenerative disease caused by deficiency of the lysosomal enzyme arylsulfatase A. However, some individuals with deficient enzyme activity appear phenotypically normal. This pseudodeficiency (PD) state is associated with two A{r_arrow}G transitions causing the loss of an N-glycosylation site in exon 6 and a polyadenylation signal at the 3{prime} end. To understand the evolutionary basis for this unusually tight linkage, we compared the occurrence of these two mutations among selected ethnic groups singly or together and their haplotype backgrounds. From 100 unrelated individuals from each of the Black, Caucasian, East Indian and Oriental populations, we found no individual carrying the polyadenylation mutation alone. However, the N-glycosylation mutation occurred independently in all the populations. RFLP analysis among random individuals revealed 7 enzyme polymorphisms (Bam II, Bgl I, Bgl II, Bsr I, Hind III, Pvu II and Taq I). Haplotype analysis among homozygous individuals and 9 multi-generation families showed that of the 7 polymorphisms, one (Bsr I) appeared indiscriminately throughout all the haplotypes studied and did not contribute to the analysis. Haplotypes established from the 6 remaining polymorphisms showed that all the alleles carrying both mutations have the same haplotype in different ethnic groups but may differ at the Bgl II and Taq I sites from those carrying only the N-glycosylation mutation. Hence, the extreme linkage disequilibrium between the two mutations associated with PD was established before the divergence of the races and the variations in frequencies are likely due to population genetic drift. Furthermore, the N-glycosylation mutation that occurs alone may appear on different haplotype backgrounds and hence is not necessarily the predecessor to the tightly-linked polyadenylation mutations in PD.

  4. Two Tightly Linked Genes at the hsa1 Locus Cause Both F1 and F2 Hybrid Sterility in Rice.

    Science.gov (United States)

    Kubo, Takahiko; Takashi, Tomonori; Ashikari, Motoyuki; Yoshimura, Atsushi; Kurata, Nori

    2016-02-01

    Molecular mechanisms of hybrid breakdown associated with sterility (F2 sterility) are poorly understood as compared with those of F1 hybrid sterility. Previously, we characterized three unlinked epistatic loci, hybrid sterility-a1 (hsa1), hsa2, and hsa3, responsible for the F2 sterility in a cross between Oryza sativa ssp. indica and japonica. In this study, we identified that the hsa1 locus contains two interacting genes, HSA1a and HSA1b, within a 30-kb region. HSA1a-j (japonica allele) encodes a highly conserved plant-specific domain of unknown function protein (DUF1618), whereas the indica allele (HSA1a-i(s)) has two deletion mutations that cause disruption of domain structure. The second gene, HSA1b-i(s), encodes an uncharacterized protein with some similarity to a nucleotide-binding protein. Homozygous introgression of indica HSA1a-i(s)-HSA1b-i(s) alleles into japonica showed female gamete abortion at an early mitotic stage. The fact that the recombinant haplotype HSA1a-j-HSA1b-i(s) caused semi-sterility in the heterozygous state with the HSA1a-i(s)-HSA1b-i(s) haplotype suggests that variation in the hsa1 locus is a possible cause of the wide-spectrum sterility barriers seen in F1 hybrids and successive generations in rice. We propose a simple genetic model to explain how a single causal mechanism can drive both F1 and F2 hybrid sterility.

  5. A highly conserved gene island of three genes on chromosome 3B of hexaploid wheat: diverse gene function and genomic structure maintained in a tightly linked block

    Directory of Open Access Journals (Sweden)

    Ma Wujun

    2010-05-01

    Full Text Available Abstract Background The complexity of the wheat genome has resulted from waves of retrotransposable element insertions. Gene deletions and disruptions generated by the fast replacement of repetitive elements in wheat have resulted in disruption of colinearity at a micro (sub-megabase level among the cereals. In view of genomic changes that are possible within a given time span, conservation of genes between species tends to imply an important functional or regional constraint that does not permit a change in genomic structure. The ctg1034 contig completed in this paper was initially studied because it was assigned to the Sr2 resistance locus region, but detailed mapping studies subsequently assigned it to the long arm of 3B and revealed its unusual features. Results BAC shotgun sequencing of the hexaploid wheat (Triticum aestivum cv. Chinese Spring genome has been used to assemble a group of 15 wheat BACs from the chromosome 3B physical map FPC contig ctg1034 into a 783,553 bp genomic sequence. This ctg1034 sequence was annotated for biological features such as genes and transposable elements. A three-gene island was identified among >80% repetitive DNA sequence. Using bioinformatics analysis there were no observable similarity in their gene functions. The ctg1034 gene island also displayed complete conservation of gene order and orientation with syntenic gene islands found in publicly available genome sequences of Brachypodium distachyon, Oryza sativa, Sorghum bicolor and Zea mays, even though the intergenic space and introns were divergent. Conclusion We propose that ctg1034 is located within the heterochromatic C-band region of deletion bin 3BL7 based on the identification of heterochromatic tandem repeats and presence of significant matches to chromodomain-containing gypsy LTR retrotransposable elements. We also speculate that this location, among other highly repetitive sequences, may account for the relative stability in gene order and

  6. A single gene controls leaf background color in caladium (Araceae) and is tightly linked to genes for leaf main vein color, spotting and rugosity

    Science.gov (United States)

    Cao, Zhe; Sui, Shunzhao; Yang, Qian; Deng, Zhanao

    2017-01-01

    Modern cultivated caladiums (Caladium×hortulanum) are grown for their long-lasting and colorful leaves. Understanding the mode of inheritance for caladium leaf characteristics is critical for plant breeders to select appropriate parents, predict progeny performance, estimate breeding population sizes needed, and increase breeding efficiencies. This study was conducted to determine the mode of inheritance of two leaf background colors (lemon and green) in caladium and to understand their relationships with four other important leaf characteristics including leaf shape, main vein color, spotting, and rugosity. Seven caladium cultivars and three breeding lines were used as parents in 19 crosses, and their progeny were phenotyped for segregation of leaf traits. Results showed that the two leaf background colors are controlled by a single nuclear locus, with two alleles, LEM and lem, which control the dominant lemon and the recessive green leaf background color, respectively. The lemon-colored cultivar ‘Miss Muffet’ and breeding lines UF-52 and UF-53 have a heterozygous genotype LEMlem. Chi-square tests showed that the leaf background color locus LEM is independent from the leaf shape locus F, but is tightly linked to three loci (S, V and RLF) controlling leaf spotting, main vein color, and rugosity in caladium. A linkage map that consists of four loci controlling major caladium leaf characteristics and extends ~15 cM was developed based on the observed recombination frequencies. This is the first report on the mode of inheritance of leaf background colors in caladium and in the Araceae family. The information gained in this study will be very useful for caladium breeding and study of the inheritance of leaf colors in other ornamental aroids, an important group of ornamental plants in the world. PMID:28101369

  7. Genetics and mapping of the R₁₁ gene conferring resistance to recently emerged rust races, tightly linked to male fertility restoration, in sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Qi, L L; Seiler, G J; Vick, B A; Gulya, T J

    2012-09-01

    Sunflower oil is one of the major sources of edible oil. As the second largest hybrid crop in the world, hybrid sunflowers are developed by using the PET1 cytoplasmic male sterility system that contributes to a 20 % yield advantage over the open-pollinated varieties. However, sunflower production in North America has recently been threatened by the evolution of new virulent pathotypes of sunflower rust caused by the fungus Puccinia helianthi Schwein. Rf ANN-1742, an 'HA 89' backcross restorer line derived from wild annual sunflower (Helianthus annuus L.), was identified as resistant to the newly emerged rust races. The aim of this study was to elucidate the inheritance of rust resistance and male fertility restoration and identify the chromosome location of the underlying genes in Rf ANN-1742. Chi-squared analysis of the segregation of rust response and male fertility in F(2) and F(3) populations revealed that both traits are controlled by single dominant genes, and that the rust resistance gene is closely linked to the restorer gene in the coupling phase. The two genes were designated as R ( 11 ) and Rf5, respectively. A set of 723 mapped SSR markers of sunflower was used to screen the polymorphism between HA 89 and the resistant plant. Bulked segregant analysis subsequently located R ( 11 ) on linkage group (LG) 13 of sunflower. Based on the SSR analyses of 192 F(2) individuals, R ( 11 ) and Rf5 both mapped to the lower end of LG13 at a genetic distance of 1.6 cM, and shared a common marker, ORS728, which was mapped 1.3 cM proximal to Rf5 and 0.3 cM distal to R ( 11 ) (Rf5/ORS728/R ( 11 )). Two additional SSRs were linked to Rf5 and R ( 11 ): ORS995 was 4.5 cM distal to Rf5 and ORS45 was 1.0 cM proximal to R ( 11 ). The advantage of such an introduced alien segment harboring two genes is its large phenotypic effect and simple inheritance, thereby facilitating their rapid deployment in sunflower breeding programs. Suppressed recombination was observed in LGs 2, 9

  8. Development and evaluation of four molecular markers tightly linked to the Potato virus Y resistance gene Rychc in diploid potato populations

    Science.gov (United States)

    In the last 15 years, Potato virus Y (PVY) has been the main pathogen causing seed potato lot rejections in North America. The most efficient and environmentally sound method of limiting incidence and spread of PVY is the use virus resistant potato cultivars. Several genes for extreme resistance to ...

  9. Molecular definition of red cell Rh haplotypes by tightly linked SphI RFLPs.

    OpenAIRE

    Huang, C. H.; Reid, M.E.; Chen, Y.; Coghlan, G.; Okubo, Y

    1996-01-01

    The Rh blood group system of human red cells contains five major antigens D, C/c, and E/e (the latter four designated "non-D") that are specified by eight gene complexes known as Rh haplotypes. In this paper, we report on the mapping of RH locus and identification of a set of SphI RFLPs that are tightly linked with the Rh structural genes. Using exon-specific probes, we have localized the SphI cleavage sites resulting in these DNA markers and derived a comprehensive map for the RH locus. It w...

  10. Identification of Molecular Genetic Markers Tightly Linked to Downy Mildew Resistant Genes in Grape%与葡萄抗霜霉病基因紧密连锁的 分子遗传标记

    Institute of Scientific and Technical Information of China (English)

    罗素兰; 贺普超; 周鹏; 郑学勤

    2001-01-01

    Bulk segregant analysis (BSA), randomly amplified polymorphic DNA(RAPD) and sequence characterized amplified region (SCAR) methods were used to tag the downy mildew-resistant genes of grape with molecular markers. Parents and their 60 individuals of an F1 progeny resulting from a cross 88-110 between 83-4-96 (Vitis quinquangularis, downy mildew-resistant) and Muscat Rose (V. vinifera, downy mildew-susceptible), three F2 progenies resulting from three crosses of self-cross and inter-cross of 88-110 F1 seedlings, as well as another interspecific F1 hybrids of 88-84 cross [Xun-3 (V. quinquangularis, downy mildew-resistant)×Ugni Blanc (V. vinifera, downy mildew-susceptible)] and the wild grapes native to China were used for the study. Among 280 Operon primers, 160 gave distinct band patterns. One RAPD marker OPO06-1500 was tightly linked to a major gene resistant to Plasmopara viticola (RPv-1). Based on Mapmaker software analysis, the map distance between RPv-1 and OPO06-1500 was 1.7cM. Marker OPO06-1500 was cloned and sequenced. According to the sequence, two specific primers were designed to amplify all plant materials. RAPD marker was converted into SCAR marker (SCO06-1500). One distinct single band only in resistant plants was amplified, whose size was the same as that of the RAPD marker. The SCAR marker’s popularity was confirmed, and it could be used for the identification of hybrid resistant to P. viticola and will be potentially useful in the development of new resistant grape cultivars.%以种间杂交组合88-110[83-4-96(毛葡萄,抗霜霉病)×粉红玫瑰(欧洲葡萄,感霜霉病)]的F1代(60个单株)及其自交或互交所得的3个F2代为试材,应用BSA、RAPD和SCAR方法研究了葡萄抗霜霉病基因的分子标记。共筛选了280个Operon引物,其中160个引物扩增出了清晰的DNA条带,发现了RAPD标记OPO06-1500与葡萄抗霜霉病主效基因(RPv-1)紧密连锁,经Mapmarker软件连锁分析,OPO06

  11. A pollen-expressed gene for a novel protein with an F-box motif that is very tightly linked to a gene for S-RNase in two species of cherry, Prunus cerasus and P. avium.

    Science.gov (United States)

    Yamane, Hisayo; Ikeda, Kazuo; Ushijima, Koichiro; Sassa, Hidenori; Tao, Ryutaro

    2003-07-01

    This study describes a novel F-box protein gene in the S-locus of sour cherry (Prunus cerasus) and sweet cherry (P. avium). The gene showed an S-haplotype-specific sequence polymorphism and the expression was specific to pollen. Genomic DNA blot analysis of eight sweet cherry cultivars with the probe for the F-box protein gene under low stringency conditions yielded RFLP bands specific to the S-haplotypes of each cultivar. We discuss the possibility of the gene for the F-box protein being a candidate for the male determinant of gametophytic self-incompatibility in PRUNUS:

  12. Molecular definition of red cell Rh haplotypes by tightly linked SphI RFLPs.

    Science.gov (United States)

    Huang, C H; Reid, M E; Chen, Y; Coghlan, G; Okubo, Y

    1996-01-01

    The Rh blood group system of human red cells contains five major antigens D, C/c, and E/e (the latter four designated "non-D") that are specified by eight gene complexes known as Rh haplotypes. In this paper, we report on the mapping of RH locus and identification of a set of SphI RFLPs that are tightly linked with the Rh structural genes. Using exon-specific probes, we have localized the SphI cleavage sites resulting in these DNA markers and derived a comprehensive map for the RH locus. It was found that the SphI fragments encompassing exons 4-7 of the Rh genes occur in four banding patterns or frameworks that correspond to the distribution and segregation of the common Rh haplotypes. This linkage disequilibrium allowed a genotype-phenotype correlation and direct determination of Rh zygosity related to the Rh-positive or Rh-negative status (D/D, D/d, and d/d). Studies on the occurrence of SphI RFLPs in a number of rare Rh variants indicated that Rh phenotypic diversity has taken place on different haplotype backgrounds and has arisen by diverse genetic mechanisms. The molecular definition of Rh haplotypes by SphI RFLP frameworks should provide a useful procedure for genetic counseling and prenatal assessment of Rh alloimmunization.

  13. NY-ESO-1 expression is tightly linked to TMPRSS2-ERG fusion in prostate cancer.

    Science.gov (United States)

    Grupp, Katharina; Ospina-Klinck, Daniel; Tsourlakis, Maria Christina; Koop, Christina; Wilczak, Waldemar; Adam, Meike; Simon, Ronald; Sauter, Guido; Izbicki, Jakob Robert; Graefen, Markus; Huland, Hartwig; Steurer, Stefan; Schlomm, Thorsten; Minner, Sarah; Quaas, Alexander

    2014-07-01

    NY-ESO-1 has been suggested as therapeutic cancer vaccine in prostate cancer. This study was undertaken to explore the relationship of NY-ESO-1 with tumor phenotype, biochemical recurrence, and molecular subgroups in hormone-naive prostate cancers. NY-ESO-1 immunohistochemistry was analyzed on a tissue microarray containing 11,152 prostate cancer samples. Results were compared to clinically follow-up data, ERG status, and deletions on PTEN, 3p13, 5q21, and 6q15. NY-ESO-1 expression was absent in benign prostate glands. In prostate cancer, NY-ESO-1 positivity was found 8.8% of our 8,761 interpretable tumors including 5.8% with weak, 2.5% with moderate, and 0.5% with strong expression. There was a threefold higher rate of NY-ESO-1 expression in ERG fusion positive tumors than in ERG negative cancers (P ESO-1 expression was associated with early biochemical recurrence (P = 0.0002) and high Gleason grade (P ESO-1 expression was also linked to PTEN (P = 0.0012) and 6q15 deletions (P = 0.0005). Our observations indicate a tight link of NY-ESO-1 expression to ERG activation and (to a lesser extent) PTEN- and 6q15-deletions in prostate cancer. The impact of these interactions on the likelihood of response to immunotherapy is unclear. The prognostic impact of NY-ESO-1 expression is little and not independent of histologic variables. © 2014 Wiley Periodicals, Inc.

  14. Powerful haplotype-based Hardy-Weinberg equilibrium tests for tightly linked loci.

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    Wei-Gao Mao

    Full Text Available Recently, there have been many case-control studies proposed to test for association between haplotypes and disease, which require the Hardy-Weinberg equilibrium (HWE assumption of haplotype frequencies. As such, haplotype inference of unphased genotypes and development of haplotype-based HWE tests are crucial prior to fine mapping. The goodness-of-fit test is a frequently-used method to test for HWE for multiple tightly-linked loci. However, its degrees of freedom dramatically increase with the increase of the number of loci, which may lack the test power. Therefore, in this paper, to improve the test power for haplotype-based HWE, we first write out two likelihood functions of the observed data based on the Niu's model (NM and inbreeding model (IM, respectively, which can cause the departure from HWE. Then, we use two expectation-maximization algorithms and one expectation-conditional-maximization algorithm to estimate the model parameters under the HWE, IM and NM models, respectively. Finally, we propose the likelihood ratio tests LRT[Formula: see text] and LRT[Formula: see text] for haplotype-based HWE under the NM and IM models, respectively. We simulate the HWE, Niu's, inbreeding and population stratification models to assess the validity and compare the performance of these two LRT tests. The simulation results show that both of the tests control the type I error rates well in testing for haplotype-based HWE. If the NM model is true, then LRT[Formula: see text] is more powerful. While, if the true model is the IM model, then LRT[Formula: see text] has better performance in power. Under the population stratification model, LRT[Formula: see text] is still more powerful. To this end, LRT[Formula: see text] is generally recommended. Application of the proposed methods to a rheumatoid arthritis data set further illustrates their utility for real data analysis.

  15. Researchers Pinpoint More Genes Linked to Vitiligo

    Science.gov (United States)

    ... 161452.html Researchers Pinpoint More Genes Linked to Vitiligo Genetic clues to this autoimmune disease could lead ... identified more genes linked to the autoimmune disease vitiligo, which causes patches of white skin and hair. ...

  16. Identification of a RAPD marker linked to a blast resistance gene in Oryza sativa L.

    Institute of Scientific and Technical Information of China (English)

    LUJun; ZHUANGJieyun; LINHongxuan; ZHENGKangle

    1994-01-01

    Marker-aided selection has received more attention in recent years. This relies on the exploitation of close linkage between molecular markers and target gene(s). We report here a randomly amplified polymorphic DNA (RAID) marker tightly linked to the blast resistance gene Pi-11(t) derived from Hongjiaozhan, which confers the resistante to race ZBI of Pyricularia oryzae Car.

  17. Sibship T2 association tests of complex diseases for tightly linked markers.

    Science.gov (United States)

    Fan, Ruzong; Knapp, Michael

    2005-06-01

    For population case-control association studies, the false-positive rates can be high due to inappropriate controls, which can occur if there is population admixture or stratification. Moreover, it is not always clear how to choose appropriate controls. Alternatively, the parents or normal sibs can be used as controls of affected sibs. For late-onset complex diseases, parental data are not usually available. One way to study late-onset disorders is to perform sib-pair or sibship analyses. This paper proposes sibship-based Hotelling's T2 test statistics for high-resolution linkage disequilibrium mapping of complex diseases. For a sample of sibships, suppose that each sibship consists of at least one affected sib and at least one normal sib. Assume that genotype data of multiple tightly linked markers/haplotypes are available for each individual in the sample. Paired Hotelling's T2 test statistics are proposed for high-resolution association studies using normal sibs as controls for affected sibs, based on two coding methods: 'haplotype/allele coding' and 'genotype coding'. The paired Hotelling's T2 tests take into account not only the correlation among the markers, but also take the correlation within each sib-pair. The validity of the proposed method is justified by rigorous mathematical and statistical proofs under the large sample theory. The non-centrality parameter approximations of the test statistics are calculated for power and sample size calculations. By carrying out power and simulation studies, it was found that the non-centrality parameter approximations of the test statistics were accurate. By power and type I error analysis, the test statistics based on the 'haplotype/allele coding' method were found to be advantageous in comparison to the test statistics based on the 'genotype coding' method. The test statistics based on multiple markers can have higher power than those based on a single marker. The test statistics can be applied not only for bi

  18. Incorporation of pentraxin 3 into hyaluronan matrices is tightly regulated and promotes matrix cross-linking.

    Science.gov (United States)

    Baranova, Natalia S; Inforzato, Antonio; Briggs, David C; Tilakaratna, Viranga; Enghild, Jan J; Thakar, Dhruv; Milner, Caroline M; Day, Anthony J; Richter, Ralf P

    2014-10-31

    Mammalian oocytes are surrounded by a highly hydrated hyaluronan (HA)-rich extracellular matrix with embedded cumulus cells, forming the cumulus cell·oocyte complex (COC) matrix. The correct assembly, stability, and mechanical properties of this matrix, which are crucial for successful ovulation, transport of the COC to the oviduct, and its fertilization, depend on the interaction between HA and specific HA-organizing proteins. Although the proteins inter-α-inhibitor (IαI), pentraxin 3 (PTX3), and TNF-stimulated gene-6 (TSG-6) have been identified as being critical for COC matrix formation, its supramolecular organization and the molecular mechanism of COC matrix stabilization remain unknown. Here we used films of end-grafted HA as a model system to investigate the molecular interactions involved in the formation and stabilization of HA matrices containing TSG-6, IαI, and PTX3. We found that PTX3 binds neither to HA alone nor to HA films containing TSG-6. This long pentraxin also failed to bind to products of the interaction between IαI, TSG-6, and HA, among which are the covalent heavy chain (HC)·HA and HC·TSG-6 complexes, despite the fact that both IαI and TSG-6 are ligands of PTX3. Interestingly, prior encounter with IαI was required for effective incorporation of PTX3 into TSG-6-loaded HA films. Moreover, we demonstrated that this ternary protein mixture made of IαI, PTX3, and TSG-6 is sufficient to promote formation of a stable (i.e. cross-linked) yet highly hydrated HA matrix. We propose that this mechanism is essential for correct assembly of the COC matrix and may also have general implications in other inflammatory processes that are associated with HA cross-linking. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. X-linked genes and mental functioning

    National Research Council Canada - National Science Library

    Skuse, David H

    2005-01-01

    ... (as indicated by the large number of X-linked mental retardation syndromes). In addition, there is evidence for relatively specific effects of X-linked genes on social-cognition and emotional regulation...

  20. Analysis of a taurine-dependent promoter in Sinorhizobium meliloti that offers tight modulation of gene expression

    National Research Council Canada - National Science Library

    Mostafavi, Mina; Lewis, Jainee Christa; Saini, Tanisha; Bustamante, Julian Albert; Gao, Ivan Thomas; Tran, Tuyet Thi; King, Sean Nicholas; Huang, Zhenzhong; Chen, Joseph C

    2014-01-01

    .... A tightly regulated promoter that enables titratable expression of a cloned gene in these different models is highly desirable, as it can facilitate observation of phenotypes that would otherwise...

  1. Prediction of heterogeneous differential genes by detecting outliers to a Gaussian tight cluster.

    Science.gov (United States)

    Yang, Zihua; Yang, Zhengrong

    2013-03-05

    Heterogeneously and differentially expressed genes (hDEG) are a common phenomenon due to bio-logical diversity. A hDEG is often observed in gene expression experiments (with two experimental conditions) where it is highly expressed in a few experimental samples, or in drug trial experiments for cancer studies with drug resistance heterogeneity among the disease group. These highly expressed samples are called outliers. Accurate detection of outliers among hDEGs is then desirable for dis- ease diagnosis and effective drug design. The standard approach for detecting hDEGs is to choose the appropriate subset of outliers to represent the experimental group. However, existing methods typically overlook hDEGs with very few outliers. We present in this paper a simple algorithm for detecting hDEGs by sequentially testing for potential outliers with respect to a tight cluster of non- outliers, among an ordered subset of the experimental samples. This avoids making any restrictive assumptions about how the outliers are distributed. We use simulated and real data to illustrate that the proposed algorithm achieves a good separation between the tight cluster of low expressions and the outliers for hDEGs. The proposed algorithm assesses each potential outlier in relation to the cluster of potential outliers without making explicit assumptions about the outlier distribution. Simulated examples and and breast cancer data sets are used to illustrate the suitability of the proposed algorithm for identifying hDEGs with small numbers of outliers.

  2. PPARγ ligand production is tightly linked to clonal expansion during initiation of adipocyte differentiation

    DEFF Research Database (Denmark)

    Hallenborg, Philip; Koefoed Petersen, Rasmus; Feddersen, Søren;

    2014-01-01

    of differentiation. Concomitant with agonist production, murine fibroblasts undergo two rounds of mitosis referred to as mitotic clonal expansion. Here we show that mouse embryonic fibroblasts deficient in either of two cell cycle inhibitors, the transcription factor p53 or its target gene encoding the cyclin...

  3. Identification of Amplified Fragment Length Polymorphism (AFLP Markers Tightly Associated with Drought Stress Gene in Male Sterile and Fertile Salvia miltiorrhiza Bunge

    Directory of Open Access Journals (Sweden)

    Hongbo Guo

    2013-03-01

    Full Text Available Consistent grain yield in drought environment has attracted wide attention due to global climate change. However, the important drought-related traits/genes in crops have been rarely reported. Many near-isogenic lines (NILs of male sterile and fertile Salvia miltiorrhiza have been obtained in our previous work through testcross and backcross in continuous field experiments conducted in 2006–2009. Both segregating sterile and fertile populations were subjected to bulked segregant analysis (BSA and amplified fragment length polymorphism (AFLP with 384 and 170 primer combinations, respectively. One out of 14 AFLP markers (E9/M3246 was identified in treated fertile population as tightly linked to the drought stress gene with a recombination frequency of 6.98% and at a distance of 7.02 cM. One of 15 other markers (E2/M5357 was identified in a treated sterile population that is closely associated with the drought stress gene. It had a recombination frequency of 4.65% and at a distance of 4.66 cM. Interestingly, the E9/M3246 fragment was found to be identical to another AFLP fragment E11/M4208 that was tightly linked to the male sterile gene of S. miltiorrhiza with 95% identity and e-value 4 × 10−93. Blastn analysis suggested that the drought stress gene sequence showed higher identity with nucleotides in Arabidopsis chromosome 1–5.

  4. Identification of Amplified Fragment Length Polymorphism (AFLP) Markers Tightly Associated with Drought Stress Gene in Male Sterile and Fertile Salvia miltiorrhiza Bunge.

    Science.gov (United States)

    Zhang, Yuejin; Guo, Lijun; Shu, Zhiming; Sun, Yiyue; Chen, Yuanyuan; Liang, Zongsuo; Guo, Hongbo

    2013-03-22

    Consistent grain yield in drought environment has attracted wide attention due to global climate change. However, the important drought-related traits/genes in crops have been rarely reported. Many near-isogenic lines (NILs) of male sterile and fertile Salvia miltiorrhiza have been obtained in our previous work through testcross and backcross in continuous field experiments conducted in 2006-2009. Both segregating sterile and fertile populations were subjected to bulked segregant analysis (BSA) and amplified fragment length polymorphism (AFLP) with 384 and 170 primer combinations, respectively. One out of 14 AFLP markers (E9/M3246) was identified in treated fertile population as tightly linked to the drought stress gene with a recombination frequency of 6.98% and at a distance of 7.02 cM. One of 15 other markers (E2/M5357) was identified in a treated sterile population that is closely associated with the drought stress gene. It had a recombination frequency of 4.65% and at a distance of 4.66 cM. Interestingly, the E9/M3246 fragment was found to be identical to another AFLP fragment E11/M4208 that was tightly linked to the male sterile gene of S. miltiorrhiza with 95% identity and e-value 4 × 10-93. Blastn analysis suggested that the drought stress gene sequence showed higher identity with nucleotides in Arabidopsis chromosome 1-5.

  5. Cross-links between ribosomal proteins of 30S subunits in 70S tight couples and in 30S subunits.

    Science.gov (United States)

    Lambert, J M; Boileau, G; Cover, J A; Traut, R R

    1983-08-01

    Ribosome 70S tight couples and 30S subunits derived from them were modified with 2-iminothiolane under conditions where about two sulfhydryl groups per protein were added to the ribosomal particles. The 70S and 30S particles were not treated with elevated concentrations of NH4Cl, in contrast to those used in earlier studies. The modified particles were oxidized to promote disulfide bond formation. Proteins were extracted from the cross-linked particles by using conditions to preclude disulfide interchange. Disulfide-linked protein complexes were fractionated on the basis of charge by electrophoresis in polyacrylamide/urea gels at pH 5.5. The proteins from sequential slices of the urea gels were analyzed by two-dimensional diagonal polyacrylamide/sodium dodecyl sulfate gel electrophoresis. Final identification of proteins in cross-linked complexes was made by radioiodination of the proteins, followed by two-dimensional polyacrylamide/urea gel electrophoresis. Attention was focused on cross-links between 30S proteins. We report the identification of 27 cross-linked dimers and 2 trimers of 30S proteins, all but one of which were found in both 70S ribosomes and free 30S subunits in similar yield. Seven of the cross-links, S3-S13, S13-S21, S14-S19, S7-S12, S9-S13, S11-S21, and S6-S18-S21, have not been reported previously when 2-iminothiolane was used. Cross-links S3-S13, S13-S21, S7-S12, S11-S21, and S6-S18-S21 are reported for the first time. The identification of the seven new cross-links is illustrated and discussed in detail. Ten of the dimers reported in the earlier studies of Sommer & Traut (1976) [Sommer, A., & Traut, R. R. (1976) J. Mol. Biol. 106, 995-1015], using 30S subunits treated with high salt concentrations, were not found in the experiments reported here.

  6. High diversity of West African bat malaria parasites and a tight link with rodent Plasmodium taxa.

    Science.gov (United States)

    Schaer, Juliane; Perkins, Susan L; Decher, Jan; Leendertz, Fabian H; Fahr, Jakob; Weber, Natalie; Matuschewski, Kai

    2013-10-22

    As the only volant mammals, bats are captivating for their high taxonomic diversity, for their vital roles in ecosystems--particularly as pollinators and insectivores--and, more recently, for their important roles in the maintenance and transmission of zoonotic viral diseases. Genome sequences have identified evidence for a striking expansion of and positive selection in gene families associated with immunity. Bats have also been known to be hosts of malaria parasites for over a century, and as hosts, they possess perhaps the most phylogenetically diverse set of hemosporidian genera and species. To provide a molecular framework for the study of these parasites, we surveyed bats in three remote areas of the Upper Guinean forest ecosystem. We detected four distinct genera of hemosporidian parasites: Plasmodium, Polychromophilus, Nycteria, and Hepatocystis. Intriguingly, the two species of Plasmodium in bats fall within the clade of rodent malaria parasites, indicative of multiple host switches across mammalian orders. We show that Nycteria species form a very distinct phylogenetic group and that Hepatocystis parasites display an unusually high diversity and prevalence in epauletted fruit bats. The diversity and high prevalence of novel lineages of chiropteran hemosporidians underscore the exceptional position of bats among all other mammalian hosts of hemosporidian parasites and support hypotheses of pathogen tolerance consistent with the exceptional immunology of bats.

  7. High diversity of West African bat malaria parasites and a tight link with rodent Plasmodium taxa

    Science.gov (United States)

    Schaer, Juliane; Perkins, Susan L.; Decher, Jan; Leendertz, Fabian H.; Fahr, Jakob; Weber, Natalie; Matuschewski, Kai

    2013-01-01

    As the only volant mammals, bats are captivating for their high taxonomic diversity, for their vital roles in ecosystems—particularly as pollinators and insectivores—and, more recently, for their important roles in the maintenance and transmission of zoonotic viral diseases. Genome sequences have identified evidence for a striking expansion of and positive selection in gene families associated with immunity. Bats have also been known to be hosts of malaria parasites for over a century, and as hosts, they possess perhaps the most phylogenetically diverse set of hemosporidian genera and species. To provide a molecular framework for the study of these parasites, we surveyed bats in three remote areas of the Upper Guinean forest ecosystem. We detected four distinct genera of hemosporidian parasites: Plasmodium, Polychromophilus, Nycteria, and Hepatocystis. Intriguingly, the two species of Plasmodium in bats fall within the clade of rodent malaria parasites, indicative of multiple host switches across mammalian orders. We show that Nycteria species form a very distinct phylogenetic group and that Hepatocystis parasites display an unusually high diversity and prevalence in epauletted fruit bats. The diversity and high prevalence of novel lineages of chiropteran hemosporidians underscore the exceptional position of bats among all other mammalian hosts of hemosporidian parasites and support hypotheses of pathogen tolerance consistent with the exceptional immunology of bats. PMID:24101466

  8. A transgenic mutant of Lactuca sativa (lettuce) with a T-DNA tightly linked to loss of downy mildew resistance.

    Science.gov (United States)

    Okubara, P A; Arroyo-Garcia, R; Shen, K A; Mazier, M; Meyers, B C; Ochoa, O E; Kim, S; Yang, C H; Michelmore, R W

    1997-11-01

    One hundred and ninety-two independent primary transformants of lettuce cv. Diana were obtained by co-cultivation with Agrobacterium tumefaciens carrying constructs containing maize Ac transposase and Ds. R2 families were screened for mutations at four genes (Dm) for resistance to downy mildew. One family, designated dm3t524, had lost resistance to an isolate of Bremia lactucae expressing the avirulence gene Avr3. Loss of resistance segregated as a single recessive allele of Dm3. The mutation was not due to a large deletion as all molecular markers flanking Dm3 were present. Loss of Dm3 activity co-segregated with a T-DNA from which Ds had excised. Genomic DNA flanking the right border of this T-DNA was isolated by inverse polymerase chain reaction. This genomic sequence was present in four to five copies in wild-type cv. Diana. One copy was missing in all eight deletion mutants of Dm3 and altered in dm3t524, indicating tight physical linkage to Dm3. Three open reading frames (ORFs) occurred in a 6.6-kb region flanking the insertion site; however, expression of these ORFs was not detected. No similarities were detected between these ORFs and resistance genes cloned from other species. Transgenic complementation with 11-to 27-kb genomic fragments of Diana spanning the insertion site failed to restore Dm3 function to two ethyl methanesulfonate (EMS)-induced mutants of Dm3 or to cv. Cobham Green, which naturally lacks Dm3 activity. Therefore, either the T-DNA inserted extremely close to, but not within, Dm3 and the mutation may have been caused by secondary movement of Ds, or Dm3 activity is encoded by a gene extending beyond the fragments used for complementation.

  9. Impairments in neurogenesis are not tightly linked to depressive behavior in a transgenic mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Daniel M Iascone

    Full Text Available Alzheimer's disease (AD, the most common cause of dementia, is also associated with depression. Although the precise mechanisms that lead to depression in AD are unknown, the impairments in adult hippocampal neurogenesis observed in AD may play a role. Adult-born neurons play a critical role in regulating both cognition and mood, and reduced hippocampal neurogenesis is associated with depression in other neurological disorders. To assess the relationship between Alzheimer's disease, neurogenesis, and depression, we studied human amyloid precursor protein (hAPP transgenic mice, a well-characterized model of AD. We report that reductions in hippocampal neurogenesis are evident early in disease progression in hAPP mice, but a mild depressive phenotype manifests only in later stages of disease. We found that hAPP mice exhibited a reduction in BrdU-positive cells in the subgranular zone of the dentate gyrus in the hippocampus, as well as a reduction in doublecortin-expressing cells, relative to nontransgenic controls at 5-7 months of age. These alterations in neurogenesis appeared to worsen with age, as the magnitude of reduction in doublecortin-expressing cells was greater in hAPP mice at 13-15 months of age. Only 13-15 month old hAPP mice exhibited depressive behavior in the tail suspension test. However, mice at both age groups exhibited deficits in spatial memory, which was observed in the Morris water maze test for hippocampus-dependent memory. These findings indicate that neurogenesis impairments are accompanied by cognitive deficits, but are not tightly linked to depressive behavior in hAPP mice.

  10. Haplotype analysis of DNA microsatellites tightly linked to the locus of Usher syndrome type I on chromosome 11q

    Energy Technology Data Exchange (ETDEWEB)

    Korostishevsky, M.; Kalinsky, H.; Seroussi, E. [Sackler Faculty of Medicine, Ramat-Aviv (Israel)] [and other

    1994-09-01

    Usher syndrome type I (USHI), an autosomal recessive disorder associated with congenital sensorineural deafness and progressive visual loss, is closely linked to the D11S533 locus. The availability of 7 other polymorphic markers within few centimorgans spanning the disease locus allowed us to identify a unique and single haplotype among all carriers of USHI gene in the Samaritan kindred. Occurrence of recombination in this small chromosomal interval is rare, hindering the detection of the mitotic recombination events needed for analysis by traditional linkage methods. Attempts to order the eight loci by linkage disequilibrium models proved to be problematic. However, our haplotype analysis implied that recombinations which had arisen in past generations may be utilized in fine mapping of the USHI gene and in resolving the conflicting linkage maps previously obtained for this region. We have developed a simple algorithm for predicting the order of the microsatellites on the basis of haplotype resemblance. The following chromosomal map in which the USHI gene is closest to D11S533 (location score of 31.0 by multipoint analysis) is suggested: D11S916, GARP, D11S527, D11S533, OMP, D11S906, D11S911, D11S937. Physical mapping efforts are currently directed to verify and to detail the map of this chromosomal region.

  11. Development of Molecular Marker Linked to Cf-10 Gene Using SSR and AFLP Method in Tomato

    Institute of Scientific and Technical Information of China (English)

    Li Ning; Jiang Jing-bin; Li Jing-fu; Xu Xiang-yang

    2012-01-01

    The leaf mould resistance gene Cf-10 on tomato confered resistant or immune to all prevalent physiological races of Cladosporium fulvum presented in three northeastern provinces of China in inoculation test. In order to better utilize Cf-10 gene in a marker-assisted selection program and to permit the pyramiding of one or several resistance genes in a cultivar, tightly linked SSR and AFLP markers were obtained by the bulked segregant analysis method. One SSR marker and three AFLP markers were identified linked to Cf-10 gene, with the distance of 9.73, 5.8, 8.5, and 10.6 cM, respectively. These markers will facilitate the selection of resistant tomato germplasm containing Cf-10 gene.

  12. MHC Genes Linked to Autoimmune Disease.

    Science.gov (United States)

    Deitiker, Philip; Atassi, M Zouhair

    2015-01-01

    Autoimmune diseases (ADs), or autoinflammatoiy diseases, are growing in complexity as diagnoses improve and many factors escalate disease risk. Considerable genetic similarity is found among ADs, and they are frequently associated with major histocompatibility complex (MHC) genes. However, a given disease may be associated with more than one human leukocyte antigen (HLA) allotype, and a given HLA may be associated with more than one AD. The associations of non-MHC genes with AD present an additional problem, and the situation is further complicated by the role that other factors, such as age, diet, therapeutic drugs, and regional influences, play in disease. This review discusses some of the genetics and biochemistry of HLA-linked AD and inflammation, covering some of the best-studied examples and summarizing indicators for class I- and II-mediated disease. However, the scope of this review limits a detailed discussion of all known ADs.

  13. Ribosomal protein L7a is encoded by a gene (Surf-3) within the tightly clustered mouse surfeit locus.

    Science.gov (United States)

    Giallongo, A; Yon, J; Fried, M

    1989-01-01

    The mouse Surfeit locus, which contains a cluster of at least four genes (Surf-1 to Surf-4), is unusual in that adjacent genes are separated by no more than 73 base pairs (bp). The heterogeneous 5' ends of Surf-1 and Surf-2 are separated by only 15 to 73 bp, the 3' ends of Surf-1 and Surf-3 are only 70 bp apart, and the 3' ends of Surf-2 and Surf-4 overlap by 133 bp. This very tight clustering suggests a cis interaction between adjacent Surfeit genes. The Surf-3 gene (which could code for a basic polypeptide of 266 amino acids) is a highly expressed member of a pseudogene-containing multigene family. By use of an anti-peptide serum (against the C-terminal nine amino acids of the putative Surf-3 protein) for immunofluorescence and immunoblotting of mouse cell components and by in vitro translation of Surf-3 cDNA hybrid-selected mRNA, the Surf-3 gene product was identified as a 32-kilodalton ribosomal protein located in the 60S ribosomal subunit. From its subunit location, gel migration, and homology with a limited rat ribosomal peptide sequence, the Surf-3 gene was shown to encode the mouse L7a ribosomal protein. The Surf-3 gene is highly conserved through evolution and was detected by nucleic acid hybridization as existing in multiple copies (multigene families) in other mammals and as one or a few copies in birds, Xenopus, Drosophila, and Schizosaccharomyces pombe. The Surf-3 C-terminal anti-peptide serum detects a 32-kilodalton protein in other mammals, birds, and Xenopus but not in Drosophila and S. pombe. The possible effect of interaction of the Surf-3 ribosomal protein gene with adjacent genes in the Surfeit locus at the transcriptional or posttranscriptional level or both levels is discussed. Images PMID:2648130

  14. Acid phosphatase-1 1, a molecular marker tightly linked to root-knot nematode resistance in tomato.

    NARCIS (Netherlands)

    Aarts, J.M.M.J.G.

    1993-01-01

    Root knot nematode resistance in tomato is a genetic trait which is determined by a single dominant gene ( Mi ) on chromosome 6 of tomato. Information about the mRNA or protein product is completely lacking, which precludes the cloning of Mi by conventional strategies based on gene expression. Howev

  15. Co-expression of six tightly clustered odorant receptor genes in the antenna of the malaria mosquito Anopheles gambiae

    Directory of Open Access Journals (Sweden)

    Tim eKarner

    2015-03-01

    Full Text Available The behavior of female malaria mosquitoes, Anopheles gambiae, especially seeking out blood hosts or selecting oviposition sites, highly depends on the detection of relevant odorants by their sense of smell. This is mediated by olfactory sensory neurons (OSNs which express distinct odorant receptor (OR types. In the genome of A. gambiae 76 genes have been annotated to encode putative odorant receptors and the majority of these AgOR genes are arranged in clusters. To assess whether clustered AgOR genes are expressed in a characteristic manner we explored the topographic expression pattern of six tightly adjoined AgOR genes in the female antenna. Whole mount fluorescence in situ hybridization experiments were performed to visualize the olfactory neurons which express a distinct AgOR type in order to determine the number and the distribution of the cells. We found that within the thirteen antennal segments about 75 cells contain mRNA for the four receptor types AgOR13, AgOR15, AgOR17 and AgOR55. Moreover, about half of these cells also transcribe mRNA for the subtypes AgOR16 and AgOR47. Subsequent RT-PCR experiments with primer pairs spanning the coding regions of adjacent AgOR genes revealed the existence of polycistronic mRNA. This result indicates that individual genes were not transcribed but mRNA was comprised of coding sequence from several genes within the studied cluster. Taken together, the data indicate a unique principle for the expression of odorant receptor genes arranged in a large cluster and suggest that the corresponding olfactory neurons are endowed with a distinct set of odorant receptor types.

  16. Gene Variant from Africa Linked to Black Obesity

    Science.gov (United States)

    ... html Gene Variant From Africa Linked to Black Obesity Study sees first biological pathway to weight gain ... identified an Africa-specific gene variant associated with obesity. The team found that about 1 percent of ...

  17. A Novel Tightly Regulated Gene Expression System for the Human Intestinal Symbiont Bacteroides thetaiotaomicron

    Directory of Open Access Journals (Sweden)

    Regis Stentz

    2016-07-01

    Full Text Available There is considerable interest in studying the function of Bacteroides species resident in the human gastrointestinal (GI-tract and the contribution they make to host health. Reverse genetics and protein expression techniques, such as those developed for well-characterised Escherichia coli cannot be applied to Bacteroides species as they and other members of the Bacteriodetes phylum have unique promoter structures. The availability of useful Bacteroides-specific genetic tools is therefore limited. Here we describe the development of an effective mannan-controlled gene expression system for Bacteroides thetaiotaomicron containing the mannan-inducible promoter–region of an α-1,2-mannosidase gene (BT_3784, a ribosomal binding site designed to modulate expression, a multiple cloning site to facilitate the cloning of genes of interest, and a transcriptional terminator. Using the Lactobacillus pepI as a reporter gene, mannan induction resulted in an increase of reporter activity in a time- and concentration-dependent manner with a wide range of activity. The endogenous BtcepA cephalosporinase gene was used to demonstrate the suitability of this novel expression system, enabling the isolation of a His-tagged version of BtCepA. We have also shown with experiments performed in mice that the system can be induced in vivo in the presence of an exogenous source of mannan. By enabling the controlled expression of endogenous and exogenous genes in B. thetaiotaomicron this novel inducer-dependent expression system will aid in defining the physiological role of individual genes and the functional analyses of their products.

  18. Regulation of male fertility by X-linked genes.

    Science.gov (United States)

    Zheng, Ke; Yang, Fang; Wang, Peijing Jeremy

    2010-01-01

    Infertility is a worldwide reproductive health problem, affecting men and women about equally. Mouse genetic studies demonstrate that more than 200 genes specifically or predominantly regulate fertility. However, few genetic causes of infertility in humans have been identified. Here, we focus on the regulation of male fertility by X-linked, germ cell-specific genes. Previous genomic studies reveal that the mammalian X chromosome is enriched for genes expressed in early spermatogenesis. Recent genetic studies in mice show that X-linked, germ cell-specific genes, such as A-kinase anchor protein 4 (Akap4), nuclear RNA export factor 2 (Nxf2), TBP-associated factor 7l (Taf7l), and testis-expressed gene 11 (Tex11), indeed play important roles in the regulation of male fertility. Moreover, we find that the Taf7l Tex11 double-mutant males exhibit much more severe defects in meiosis than either single mutant, suggesting that these 2 X-linked genes regulate male meiosis synergistically. The X-linked, germ cell-specific genes are particularly attractive in the study of male infertility in humans. Because males are hemizygous for X-linked genes, loss-of-function mutations in the single-copy X-linked genes, unlike in autosomal genes, would not be masked by a normal allele. The genetic studies of X-linked, germ cell-specific genes in mice have laid a foundation for mutational analysis of their human orthologues in infertile men.

  19. Evolution of closely linked gene pairs in vertebrate genomes

    NARCIS (Netherlands)

    Franck, E.; Hulsen, T.; Huynen, M.A.; Jong, de W.W.; Lunsen, N.H.; Madsen, O.

    2008-01-01

    The orientation of closely linked genes in mammalian genomes is not random: there are more head-to-head (h2h) gene pairs than expected. To understand the origin of this enrichment in h2h gene pairs, we have analyzed the phylogenetic distribution of gene pairs separated by less than 600 bp of interge

  20. Acid phosphatase-1.1, a molecular marker tightly linked to root-knot nematode resistance in tomato

    NARCIS (Netherlands)

    Aarts, J.M.M.J.G.

    1993-01-01

    Root knot nematode resistance in tomato is a genetic trait which is determined by a single dominant gene ( Mi ) on chromosome 6 of tomato. Information about the mRNA or protein product is completely lacking, which precludes the cloning of Mi by

  1. SCAR, RAPD and RFLP markers linked to a dominant gene (Are) conferring resistance to anthracnose in common bean.

    Science.gov (United States)

    Adam-Blondon, A F; Sévignac, M; Bannerot, H; Dron, M

    1994-08-01

    Anthracnose, caused by the fungusColletotrichum lindemuthianum, is a severe disease of common bean (Phaseolus vulgaris L.) controlled, in Europe, by a single dominant gene,Are. Four pairs of near-isogenic lines (NILs) were constructed, in which theAre gene was introgressed into different genetic backgrounds. These pairs of NILs were used to search for DNA markers linked to the resistance gene. Nine molecular markers, five RAPDs and four RFLPs, were found to discriminate between the resistant and the susceptible members of these NILs. A backcross progeny of 120 individuals was analysed to map these markers in relation to theAre locus. Five out of the nine markers were shown to be linked to theAre gene within a distance of 12.0 cM. The most tightly linked, a RAPD marker, was used to generate a pair of primers that specifically amplify this RAPD (sequence characterized amplified region, SCAR).

  2. The Aspergillus nidulans alcA promoter drives tightly regulated conditional gene expression in Aspergillus fumigatus permitting validation of essential genes in this human pathogen.

    Science.gov (United States)

    Romero, Beatriz; Turner, Geoffrey; Olivas, Israel; Laborda, Fernando; De Lucas, J Ramón

    2003-11-01

    Aspergillus fumigatus causes invasive aspergillosis, a mycosis that is usually fatal in immunocompromised patients. Functional genomics in this fungus will aid the discovery of novel antifungal drugs to treat invasive aspergillosis. However, there is still a need for appropriate molecular genetic tools to facilitate such functional studies. Here, we describe the use of a conditional gene expression system allowing the identification of novel therapeutic targets through validation of essential genes in A. fumigatus. This system is based on the capacity of the Aspergillus nidulans alcA promoter (alcA(p)) to tightly regulate gene expression in this fungus. Conditionally regulated gene expression in A. fumigatus was demonstrated by transcriptional and phenotypic analyses of strains expressing a nuclear migration gene with a terminal phenotype, the A. fumigatus nudC gene, under control of this promoter. This conditional expression system, the first one described in A. fumigatus, will also be useful for investigating the function of essential genes by altering the threonine/glucose ratio in the growth medium.

  3. Host specificity of Sporisorium reilianum is tightly linked to generation of the phytoalexin luteolinidin by Sorghum bicolor.

    Science.gov (United States)

    Zuther, Katja; Kahnt, Jörg; Utermark, Jan; Imkampe, Julia; Uhse, Simon; Schirawski, Jan

    2012-09-01

    The smut fungus Sporisorium reilianum occurs in two varieties (S. reilianum f. sp. reilianum and S. reilianum f. sp. zeae) that cause head smut disease on sorghum and maize, respectively. Prior to plant infection, compatible haploid sporidia of S. reilianum fuse to form infectious dikaryotic hyphae that penetrate the leaf surface, spread throughout the plant, and reach the inflorescences, in which spore formation occurs. To elucidate the basis of host specificity of the two S. reilianum varieties, we compared disease etiology of S. reilianum f. sp. reilianum and S. reilianum f. sp. zeae on sorghum and maize. Both varieties could penetrate and multiply in both hosts. However, red spots appeared on inoculated leaves after sorghum infection with S. reilianum f. sp. zeae. Using matrix-assisted laser desorption-ionization time of flight analysis of leaf extracts, we show that sorghum reacts with the production of the red and orange phytoalexins luteolinidin and apigeninidin upon colonization by S. reilianum f. sp. zeae but not by S. reilianum f. sp. reilianum. Using in vitro growth assays, we demonstrate that luteolinidin but not apigeninidin slows vegetative growth of both S. reilianum f. sp. zeae and S. reilianum f. sp. reilianum. However, the phytoalexin biosynthesis gene SbDFR3 is only induced in sorghum after infection with S. reilianum f. sp. zeae, as shown by quantitative real-time polymerase chain reaction. This suggests that regulation of luteolinidin biosynthesis determines infection success of S. reilianum on sorghum.

  4. Gene Linked to Excess Male Hormones in Female Infertility Disorder

    Science.gov (United States)

    ... Gene linked to excess male hormones in female infertility disorder Discovery by NIH-supported researchers may lead ... androgens, symptoms of PCOS include irregular menstrual cycles, infertility, and insulin resistance (difficulty using insulin.) The condition ...

  5. Many Early Colon Cancers Linked to Inherited Genes

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_162574.html Many Early Colon Cancers Linked to Inherited Genes One in 6 diagnosed ... inherited condition. It increases the rate of many cancers, including colon cancer, according to the U.S. National Library of ...

  6. Gene variant linked to lung cancer risk

    Science.gov (United States)

    A variation of the gene NFKB1, called rs4648127, is associated with an estimated 44 percent reduction in lung cancer risk. When this information, derived from samples obtained as part of a large NCI-sponsored prevention clinical trial, was compared with d

  7. Enhanced detection of polymorphic DNA by multiple arbitrary amplicon profiling of endonuclease-digested DNA: identification of markers tightly linked to the supernodulation locus in soybean.

    Science.gov (United States)

    Caetano-Anollés, G; Bassam, B J; Gresshoff, P M

    1993-10-01

    Multiple endonuclease digestion of template DNA or amplification products can increase significantly the detection of polymorphic DNA in fingerprints generated by multiple arbitrary amplicon profiling (MAAP). This coupling of endonuclease cleavage and amplification of arbitrary stretches of DNA, directed by short oligonucleotide primers, readily allowed distinction of closely related fungal and bacterial isolates and plant cultivars. MAAP analysis of cleaved template DNA enabled the identification of molecular markers linked to a developmental locus of soybean (Glycine max L. Merrill). Ethyl methane sulfonate (EMS)-induced supernodulating, near-isogenic lines altered in the nts locus, which controls nodule formation, could be distinguished from each other and from the parent cultivar by amplification of template pre-digested with 2-3 restriction enzymes. A total of 42 DNA polymorphisms were detected using only 19 octamer primers. In the absence of digestion, 25 primers failed to differentiate these soybean genotypes. Several polymorphic products co-segregated tightly with the nts locus in F2 families from crosses between the allelic mutants nts382 and nts1007 and the ancestral G. soja Sieb. & Succ. PI468.397. Our results suggest that EMS is capable of inducing extensive DNA alterations, probably around discrete mutational hot-spots. EMS-induced DNA polymorphisms may constitute sequence-tagged markers diagnostic of specific genomic regions.

  8. Tight turns

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    The Italian National Institute for Nuclear Physics (INFN) has successfully tested the first model of a new fast-ramping curved dipole magnet. This is great news for CERN, which sees the advance as holding potential for the future of the SPS.   The first model of a new fast-ramping curved dipole magnet being prepared for cryogenic testing at the LASA laboratory (INFN Milano, Italy). On 16 July INFN introduced an innovative dipole magnet. With a length of some 4 metres, it can produce a 4.5 Tesla magnetic field and achieve a tighter bend than ever before (the bending radius has been squeezed to a remarkable 66.7 metres). This new magnet was designed in the first instance for GSI’s SIS300 synchrotron (in Germany), which will require 60 dipoles of this type. "Achieving such a tight bend demanded a major R&D effort," stressed Pasquale Fabbricatore, the spokesman of the INFN collaboration responsible for the magnet’s development. "We had to not o...

  9. STS Gene in a Pedigree with X-linked Ichthyosis

    Institute of Scientific and Technical Information of China (English)

    LIU An; XIAO Shengxiang; TAN Shengshun; LEI Xiaobing; ZHANG Jiangan; JIAO Ting; LIU Yan

    2005-01-01

    To investigate the gene mutation in a pedigree with X-linked ichthyosis (XLI) and to explore the relationship between the mutation and its clinical manifestations, genomic DNA of affected members, the normal member of the pedigree and 50 unrelated normal members was extracted with a whole blood genomic DNA extraction kit and the DNA was used as a template for the polymerase chain reaction (PCR)-mediated amplification of exon 1 and exon 10 of the STS gene. hHb6 (human hair basic keratin) gene was used as the internal control. Our results showed that the STS gene was deleted in affected members in the pedigree with X-linked ichthyosis. The normal member of the pedigree and 50 unrelated normal members had no such deletion. The proband and his mother had products in the internal control after PCR amplification. The blank control had no product. It is concluded that deletion of the STS gene existed in this pedigree with X-linked ichthyosis, and it is responsible for the unique skin lesions of X-linked ichthyosis.

  10. Drosophila X-Linked Genes Have Lower Translation Rates than Autosomal Genes.

    Science.gov (United States)

    Zhang, Zhenguo; Presgraves, Daven C

    2016-02-01

    In Drosophila, X-linked and autosomal genes achieve comparable expression at the mRNA level. Whether comparable X-autosome gene expression is realized at the translational and, ultimately, the protein levels is, however, unknown. Previous studies suggest the possibility of higher translation rates for X-linked genes owing to stronger usage of preferred codons. In this study, we use public ribosome profiling data from Drosophila melanogaster to infer translation rates on the X chromosome versus the autosomes. We find that X-linked genes have consistently lower ribosome densities than autosomal genes in S2 cells, early embryos, eggs, and mature oocytes. Surprisingly, the lower ribosome densities of X-linked genes are not consistent with faster translation elongation but instead imply slower translation initiation. In particular, X-linked genes have sequence features known to slow translation initiation such as stronger mRNA structure near start codons and longer 5'-UTRs. Comparison to outgroup species suggests that stronger mRNA structure is an evolved feature of Drosophila X chromosomes. Finally, we find that the magnitude of the X-autosome difference in ribosome densities is smaller for genes encoding members of protein complexes, suggesting that stoichiometry constrains the evolution of translation rates. In sum, our analyses suggest that Drosophila X-linked genes have evolved lower translation rates than autosomal genes despite stronger usage of preferred codons.

  11. MiRTargetLink--miRNAs, Genes and Interaction Networks.

    Science.gov (United States)

    Hamberg, Maarten; Backes, Christina; Fehlmann, Tobias; Hart, Martin; Meder, Benjamin; Meese, Eckart; Keller, Andreas

    2016-04-14

    Information on miRNA targeting genes is growing rapidly. For high-throughput experiments, but also for targeted analyses of few genes or miRNAs, easy analysis with concise representation of results facilitates the work of life scientists. We developed miRTargetLink, a tool for automating respective analysis procedures that are frequently applied. Input of the web-based solution is either a single gene or single miRNA, but also sets of genes or miRNAs, can be entered. Validated and predicted targets are extracted from databases and an interaction network is presented. Users can select whether predicted targets, experimentally validated targets with strong or weak evidence, or combinations of those are considered. Central genes or miRNAs are highlighted and users can navigate through the network interactively. To discover the most relevant biochemical processes influenced by the target network, gene set analysis and miRNA set analysis are integrated. As a showcase for miRTargetLink, we analyze targets of five cardiac miRNAs. miRTargetLink is freely available without restrictions at www.ccb.uni-saarland.de/mirtargetlink.

  12. Ileal tight junction gene expression in glucagon-like peptide 2-treated dairy bull calves with and without coccidiosis

    Science.gov (United States)

    Intestinal gut permeability is partially regulated by the intestinotrophic hormone glucagon-like peptide 2 (GLP-2). Specifically, disease models in mice and human cell lines have implicated GLP-2 in the regulation of the tight junction milieu within the intestinal tract. Therapeutic administration o...

  13. Tight junction gene expression in gastrointestinal tract of dairy calves with coccidiosis and treated with glucagon-like peptide-2

    Science.gov (United States)

    Selective permeability of the intestinal epithelium and efficient nutrient absorption are important functions for proper growth and development of calves. Damage to the intestinal mucosa can give rise to harmful long-term health effects and reduce productivity of the mature animal. Tight junction pr...

  14. Identification of Random Amplified Polymorphic DNA Markers Linked to the Co-4 Resistance Gene to Colletotrichum lindemuthianum in Common Bean.

    Science.gov (United States)

    de Arruda, M C; Alzate-Marin, A L; Chagas, J M; Moreira, M A; de Barros, E G

    2000-07-01

    ABSTRACT New cultivars of the common bean (Phaseolus vulgaris) with durable resistance to anthracnose can be developed by pyramiding major resistance genes using marker-assisted selection. To this end, it is necessary to identify sources of resistance and molecular markers tightly linked to the resistance genes. The objectives of this work were to study the inheritance of resistance to anthracnose in the cultivar TO (carrying the Co-4 gene), to identify random amplified polymorphic DNA (RAPD) markers linked to Co-4, and to introgress this gene in the cultivar Rudá. Populations F(1), F(2), F(2:3), BC(1)s, and BC(1)r from the cross Rudá x TO were inoculated with race 65 of Colletotrichum lindemuthianum, causal agent of bean anthracnose. The phenotypic ratios (resistant/susceptible) were 3:1 in the F(2) population, 1:1 in the BC(1)s, and 1:0 in the BC(1)r, confirming that resistance to anthracnose in the cultivar TO was monogenic and dominant. Six RAPD markers linked to the Co-4 gene were identified, four in the coupling phase: OPY20(830C) (0.0 centimorgan [cM]), OPC08(900C) (9.7 cM), OPI16(850C) (14.3 cM), and OPJ01(1,380C) (18.1 cM); and two in the repulsion phase: OPB03(1,800T) (3.7 cM) and OPA18(830T) (17.4 cM). OPY20(830C) and OPB03(1,800T), used in association as a codominant pair, allowed the identification of the three genotypic classes with a high degree of confidence. Marker OPY20(830C), which is tightly linked to Co-4, is being used to assist in breeding for resistance to anthracnose.

  15. The HOX-5 and surfeit gene clusters are linked in the proximal portion of mouse chromosome 2.

    Science.gov (United States)

    Stubbs, L; Huxley, C; Hogan, B; Evans, T; Fried, M; Duboule, D; Lehrach, H

    1990-04-01

    Using an interspecies backcross, we have mapped the HOX-5 and surfeit (surf) gene clusters within the proximal portion of mouse chromosome 2. While the HOX-5 cluster of homeobox-containing genes has been localized to chromosome 2, bands C3-E1, by in situ hybridization, its more precise position relative to the genes and cloned markers of chromosome 2 was not known. Surfeit, a tight cluster of at least six highly conserved "housekeeping" genes, has not been previously mapped in mouse, but has been localized to human chromosome 9q, a region of the human genome with strong homology to proximal mouse chromosome 2. The data presented here place HOX-5 in the vicinity of the closely linked set of developmental mutations rachiterata, lethargic, and fidget and place surf close to the proto-oncogene Abl, near the centromere of chromosome 2.

  16. Reducible, dibromomaleimide-linked polymers for gene delivery.

    Science.gov (United States)

    Tan, James-Kevin Y; Choi, Jennifer L; Wei, Hua; Schellinger, Joan G; Pun, Suzie H

    2015-01-01

    Polycations have been successfully used as gene transfer vehicles both in vitro and in vivo; however, their cytotoxicity has been associated with increasing molecular weight. Polymers that can be rapidly degraded after internalization are typically better tolerated by mammalian cells compared to their non-degradable counterparts. Here, we report the use of a dibromomaleimide-alkyne (DBM-alkyne) linking agent to reversibly bridge cationic polymer segments for gene delivery and to provide site-specific functionalization by azide-alkyne cycloaddition chemistry. A panel of reducible and non-reducible, statistical copolymers of (2-dimethylamino)ethyl methacrylate (DMAEMA) and oligo(ethylene glycol)methyl ether methacrylate (OEGMA) were synthesized and evaluated. When complexed with plasmid DNA, the reducible and non-reducible polymers had comparable DNA condensation properties, sizes, and transfection efficiencies. When comparing cytotoxicity, the DBM-linked, reducible polymers were significantly less toxic than the non-reducible polymers. To demonstrate polymer functionalization by click chemistry, the DBM-linked polymers were tagged with an azide-fluorophore and were used to monitor cellular uptake. Overall, this polymer system introduces the use of a reversible linker, DBM-alkyne, to the area of gene delivery and allows for facile, orthogonal, and site-specific functionalization of gene delivery vehicles.

  17. X-linked liver glycogenosis: From patient to gene

    Energy Technology Data Exchange (ETDEWEB)

    Willems, P.J.; Hendrickx, J. [Univ. of Antwert (Belgium)

    1994-09-01

    X-linked liver glycogenosis (XLG) is the most frequent glycogen storage disorder. Studying a collection of more than 50 XLG families, we have subdivided XLG into XLG I which shows a clear deficiency of phosphorylase kinase (PHK), and XLG II in which no enzyme deficiency has yet been found. However, the clinical pictures of XLG I and XLG II with hepatormegaly and growth retardation are indistinguishable. We have localized the XLG I and the XLG II gene by linkage analysis in multiple large families to the same chromosomal region in Xp22. Multipoint linkage analysis gave lod scores of above 15 in XLG I and above 4.5 in XLG II with Xp22 markers, whereas analysis of key recombinants located both disease genes between DXS143 and DXS989. Therefore, XLG I and XLG II might be due to allelic mutations in the same gene. To clone the disease gene, we searched for PHK subunit genes and isolated genomic and cDNA clones from a liver alpha subunit gene (PHKA2). As PHKA2 could be mapped by FISH and radiation hybrids to Xp22, it is a candidate gene for XLG. To prove that PHKA2 harbours the mutations responsible for XLG I and XLG II, we studied different XLG I and XLG II patients with Southern blot analysis and genomic SSCP scanning. Several mutations (nonsense mutations, splice site mutations) were identified indicating that PHKA2 is the XLG gene.

  18. Mis-splicing of the ABCC2 gene linked with Bt toxin resistance in Helicoverpa armigera.

    Science.gov (United States)

    Xiao, Yutao; Zhang, Tao; Liu, Chenxi; Heckel, David G; Li, Xianchun; Tabashnik, Bruce E; Wu, Kongming

    2014-08-26

    Toxins from the bacterium Bacillus thuringiensis (Bt) are used widely for insect control in sprays and transgenic plants, but their efficacy is reduced when pests evolve resistance. Previous work showed that mutations in a gene encoding the transporter protein ABCC2 are linked with resistance to Bt toxins Cry1Ab, Cry1Ac or both in four species of Lepidoptera. Here we compared the ABCC2 gene of Helicoverpa armigera (HaABCC2) between susceptible strains and a laboratory-selected strain with >1,000-fold resistance to Cry1Ac relative its susceptible parent strain. We discovered a 73-base pair (bp) insertion in the cDNA of the resistant strain that generates a premature stop codon expected to yield a truncated ABCC2 protein. Sequencing of genomic DNA revealed that this insertion is an intron that is not spliced out because of a 6-bp deletion at its splicing site. Analysis of progeny from crosses revealed tight genetic linkage between HaABCC2 and resistance to Cry1Ac. These results provide the first evidence that mis-splicing of a gene encoding an ABCC2 protein confers resistance to a Bt toxin.

  19. Somatic hypermutation of immunoglobulin genes is linked to transcription initiation.

    Science.gov (United States)

    Peters, A; Storb, U

    1996-01-01

    To identify DNA sequences that target the somatic hypermutation process, the immunoglobulin gene promoter located upstream of the variable (V) region was duplicated upstream of the constant (C) region of a kappa transgene. Normally, kappa genes are somatically mutated only in the VJ region, but not in the C region. In B cell hybridomas from mice with this kappa transgene (P5'C), both the VJ region and the C region, but not the region between them, were mutated at similar frequencies, suggesting that the mutation mechanism is related to transcription. The downstream promoter was not occluded by transcripts from the upstream promoter. In fact, the levels of transcripts originating from the two promoters were similar, supporting a mutation model based on initiation of transcripts. Several "hot-spots" of somatic mutation were noted, further demonstrating that this transgene has the hallmarks of somatic mutation of endogenous immunoglobulin genes. A model linking somatic mutation to transcription-coupled DNA repair is proposed.

  20. Identification of molecular markers linked to the mildew resistance gene Pl-d in apple.

    Science.gov (United States)

    James, C M; Clarke, J B; Evans, K M

    2004-12-01

    Powdery mildew poses a serious problem for apple growers, and resistance to the disease is a major objective in breeding programmes for cultivar improvement. As selective pressure allows pathogens to overcome previously reliable resistances, there is a need for the introduction of novel resistance genes into new breeding lines. This investigation is concerned with the identification of the first set of molecular markers linked to the gene for mildew resistance, Pl-d, from the accession 'D12'. As no prior information on the map position or markers for Pl-d were available, a bulked-segregant approach was used to test 49 microsatellite primers, 176 amplified fragment length polymorphism (AFLP) primers and 80 random amplified polymorphic DNA (RAPD) primers in a progeny segregating for Pl-d resistance, 'Fiesta' (susceptible) x A871-14 ('Worcester Pearmain' x 'D12'). The segregations of the markers identified in the resistant and susceptible bulks were scored in the progeny, then the recombination fractions between Pl-d and the most tightly linked markers were calculated and a map prepared. Three AFLP, one RAPD and two microsatellite markers were identified. One AFLP was developed into a sequence-characterised amplified region marker, while the microsatellites CH03C02 and CH01D03 were flanking markers, 7 and 11 recombination units, respectively, from Pl-d. Two more distant microsatellites on the same linkage group, CH01D09 and CH01G12, confirmed the orientation of the markers on the linkage group. These microsatellites place Pl-d on the bottom of linkage group 12 in published apple maps, a region where a number of other disease resistance genes have been identified.

  1. Development of a tightly regulated and highly inducible ecdysone receptor gene switch for plants through the use of retinoid X receptor chimeras.

    Science.gov (United States)

    Tavva, Venkata S; Dinkins, Randy D; Palli, Subba R; Collins, Glenn B

    2007-10-01

    Chemical inducible gene regulation systems provide essential tools for the precise regulation of transgene expression in plants and animals. Recent development of a two-hybrid ecdysone receptor (EcR) gene regulation system has solved some of the drawbacks that were associated with the monopartate gene switch. To further improve the versatility of the two-hybrid EcR gene switch for wide spread use in plants, chimeras between Homo sapiens retinoid X receptor (HsRXR) and insect, Locusta migratoria RXR (LmRXR) were tested in tobacco protoplasts as partners with Choristoneura fumiferana EcR (CfEcR) in inducing expression of the luciferase reporter gene. The RXR chimera 9 (CH9) along with CfEcR, in a two-hybrid format gave the best results in terms of low-background expression levels in the absence of ligand and high-induced expression levels of the reporter gene in the presence of nanomolar concentrations of the methoxyfenozide ligand. The performance of CH9 was further tested in corn and soybean protoplasts and the data obtained was compared with the other EcR switches that contained the wild-type LmRXR or HsRXR as EcR partners. In both transient expression studies and stable transformation experiments, the fold induction values obtained with the CH9 switch were several times higher than the values obtained with the other EcR switches containing LmRXR or HsRXR. The new CfEcR two-hybrid gene switch that uses the RXR CH9 as a partner in inducing reporter gene expression provides an efficient, ligand-sensitive and tightly regulated gene switch for plants.

  2. Temporal and Tight Hepatitis C Virus Gene Activation in Cultured Human Hepatoma Cells Mediated by a Cell-Permeable Cre Recombinase

    Institute of Scientific and Technical Information of China (English)

    Dong XIAO; Kang XU; Ying YUE; Zhong-Min GUO; Bing HUANG; Xin-Yan DENG; Huan TANG; Xi-Gu CHEN

    2004-01-01

    Conditional gene expression has greatly facilitated the examination of the functions of particular gene products. Using the Cre/lox P switching expression system, we plan to develop efficient conditional transgene activation of hepatitis C virus core protein (HCV-C) cDNA (nucleotide 342-914) in the transgenic mice to overcome "immune tolerance" formed during the embryonic period and "immune escape" against hepatitis virus antigen in our project. To use this system in vivo, the dormant transgenic construct, i.e.,pApoE-SCS-EGFP-HCV-C, was generated using techniques of standard molecular biology. The liverspecific human apoE promoter was here used to target expression of genes of interest (EGFP and HCV-C) to murine liver. Prior to generating the transgenic mice, the availability of Cre/lox P system and construct functionality were successfully verified by a cell-free recombination system and via checking the expression of EGFP and HCV-C in the human hepatoma cells at the mRNA and protein levels. These results suggest that the Cre/lox P system could tightly control expression of EGFP and HCV-C in vitro, which laid a solid foundation to conditionally activate expression of target gene(s) in transgenic mice by Cre-mediated site-specific recombination.

  3. A 'select and swap' strategy for the isolation of clones with tightly regulated transgenes.

    Science.gov (United States)

    Sullivan, M J; Carpenter, A J; Porter, A C

    2001-03-01

    Increasing numbers of biological problems are being addressed by genetic approaches that rely on inducible expression of transgenes. It is desirable that expression of such a transgene is tightly regulated, from close to zero expression in the 'off' state, to appreciable (at least physiological) expression in the 'on' state. Although there are many examples where tight regulation has been achieved, certain factors, including chromosomal position effects due to random integration of the transgene, often cause suboptimal inducibility and make the isolation of tightly regulated clones difficult and/or laborious. Here we describe a 'select and swap' strategy for the isolation, from a population of stable transfectants, of clones with tightly regulated transgenes. In this approach, a positively and negatively selectable, inducible marker gene is used to select for clones with optimal transgene regulation. After isolation of such clones, the marker gene is swapped with a linked gene of interest by the use of site-specific recombination. To test this strategy we introduced into human cells a plasmid with a tetracycline-inducible bacterial gpt gene linked to a promoterless luciferase gene, isolated clones with tight gpt expression and used the Cre/loxP site-specific recombination system to swap the gpt gene with the luciferase gene. We discuss ways for refining and developing the system and widening its applicability.

  4. Link-based quantitative methods to identify differentially coexpressed genes and gene Pairs

    Directory of Open Access Journals (Sweden)

    Ye Zhi-Qiang

    2011-08-01

    Full Text Available Abstract Background Differential coexpression analysis (DCEA is increasingly used for investigating the global transcriptional mechanisms underlying phenotypic changes. Current DCEA methods mostly adopt a gene connectivity-based strategy to estimate differential coexpression, which is characterized by comparing the numbers of gene neighbors in different coexpression networks. Although it simplifies the calculation, this strategy mixes up the identities of different coexpression neighbors of a gene, and fails to differentiate significant differential coexpression changes from those trivial ones. Especially, the correlation-reversal is easily missed although it probably indicates remarkable biological significance. Results We developed two link-based quantitative methods, DCp and DCe, to identify differentially coexpressed genes and gene pairs (links. Bearing the uniqueness of exploiting the quantitative coexpression change of each gene pair in the coexpression networks, both methods proved to be superior to currently popular methods in simulation studies. Re-mining of a publicly available type 2 diabetes (T2D expression dataset from the perspective of differential coexpression analysis led to additional discoveries than those from differential expression analysis. Conclusions This work pointed out the critical weakness of current popular DCEA methods, and proposed two link-based DCEA algorithms that will make contribution to the development of DCEA and help extend it to a broader spectrum.

  5. Localization of the tight junction protein gene TJP1 to human chromosome 15q13, distal to the Prader-Willi/Angelman region, and to mouse chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Mohandas, T.K. [Darthmouth-Hitchcock Medical Center, Lebanon, NH (United States); Chen, X.N.; Korenberg, J.R. [UCLA School of Medicine, Los Angeles, CA (United States)] [and others

    1995-12-10

    The gene encoding the tight junction (zonula occludens) protein, TJP1, was mapped to human chromosome 15q13 by fluorescence in situ hybridization (FISH) using a cDNA probe. The Jackson Laboratory backcross DNA panel derived from the cross (C57BL/6JEi X SPRET/Ei) F1 females X SPRET/Ei males was used to map the mouse Tjp1 to chromosome 7 near position 30 on the Chromosome Committee Map, a region with conserved homology to human chromosome 15q13. FISH studies on metaphases from patients with the Prader-Willi (PWS) or the Angelman syndrome (AS) showed that TJP1 maps close but distal to the PWS/AS chromosome region. 13 refs., 2 figs.

  6. Prime tight frames

    DEFF Research Database (Denmark)

    Lemvig, Jakob; Miller, Christopher; Okoudjou, Kasso A.

    2014-01-01

    to suggest effective analysis and synthesis computation strategies for such frames. Finally, we describe all prime frames constructed from the spectral tetris method, and, as a byproduct, we obtain a characterization of when the spectral tetris construction works for redundancies below two.......We introduce a class of finite tight frames called prime tight frames and prove some of their elementary properties. In particular, we show that any finite tight frame can be written as a union of prime tight frames. We then characterize all prime harmonic tight frames and use thischaracterization...

  7. Effect of calf starter feeding on gut microbial diversity and expression of genes involved in host immune responses and tight junctions in dairy calves during weaning transition.

    Science.gov (United States)

    Malmuthuge, Nilusha; Li, Meiju; Goonewardene, Laksiri A; Oba, Masahito; Guan, L Luo

    2013-05-01

    Calf starters are usually offered to dairy calves to facilitate the weaning process, however, the effect of solid feed consumption on gut health has not been well studied. This study aimed to investigate the effect of calf starter feeding on the gut bacterial community and mucosal immune functions in dairy calves during weaning transition. Mucosal tissue and digesta samples were collected from rumen, jejunum, ileum, cecum, and colon upon slaughtering of calves (n=8) after feeding the experimental diets [milk replacer (MR) or milk replacer + calf starter (MR+S)] for 6 wk. Expression of toll-like receptor (TLR) 10 was downregulated along the gut, whereas TLR2 in colon and TLR6 along the gut were upregulated in MR+S-fed calves compared with MR-fed calves. Ileal TLR9 and TLR10 showed higher expression compared with the other regions regardless of the diet. Peptidoglycan recognition protein 1 demonstrated a diet- and gut-regional dependent expression pattern, whereas β-defensin did not. The diet and gut region also affected the expression of tight junction-regulating genes claudin 4 and occludin. Bacterial diversity tended to be different between the 2 diets, whereas the bacterial density was different among gut regions and sample type. The present study revealed that changes in bacterial diversity, expression of genes encoding host mucosal immune responses, and barrier functions were associated with the MR+S diet, and suggests that solid feed consumption may alter gut microbiome and host mucosal functions during weaning transition.

  8. Gene expression analysis approach to establish possible links between Parkinson's disease, cancer and cardiovascular diseases.

    Science.gov (United States)

    Karim, Sajjad; Mirza, Zeenat; Kamal, Mohammad A; Abuzenadah, Adel M; Al-Qahtani, Mohammed H

    2014-01-01

    Non-communicable chronic diseases have been apparently established as threat to human health, and are currently the world's main killer. Cardiovascular diseases (CVD), cancer, diabetes and neurodegenerative diseases are collectively amounting to more than 60% of non-communicable disease burden across world. Tremendous advancements in healthcare enabled us to fight several health problems primarily infectious diseases. However, this increased longevity where in many cases an individual suffers from several such chronic diseases simultaneously, making treatment complex. Finding whether diseases can coexist in an individual by chance or there exists a possible association between them is vital. Our goal is to establish possible existing link among CVD, cancer and Parkinson's disease (PD) for better understanding of the associated molecular network. In this study, we integrated multiple dataset retrieved from the National Centre for Biotechnology Information's Gene Expression Omnibus database, and took a systems-biology approach to compare and distinguish the molecular network associated with PD, cancer and CVD. We identified 230, 308 and 1619 differentially expressed genes for CVD, cancer and PD dataset respectively using cut off p value2. We integrated these data with known pathways using Ingenuity Pathway Analysis tool and found following common pathways associated with all three diseases to be most affected; epithelial adherens junction signaling, remodelling of epithelial adherens junctions, role of BRCA1 in DNA damage response, sphingomyelin metabolism, 3- phosphoinositide biosynthesis, acute myeloid leukemia signaling, type I diabetes mellitus signaling, agrin interactions at neuromuscular junction, role of IL-17A in arthritis, and antigen presentation pathways. In conclusion, CVD, cancer and PD appear tightly associated at molecular level.

  9. Short communication: Glucagon-like peptide-2 and coccidiosis alter tight junction gene expression in the gastrointestinal tract of dairy calves.

    Science.gov (United States)

    Walker, M P; Evock-Clover, C M; Elsasser, T H; Connor, E E

    2015-05-01

    Tight junction (TJ) proteins are integral factors involved in gut barrier function, and therapy with glucagon-like peptide-2 (GLP-2) enhances gut integrity. Our aim was to assess effects of GLP-2 treatment on mRNA expression of 8 TJ complex proteins in the intestine of dairy calves not infected or infected with Eimeria bovis at 11±3d of age. Mucosal epithelium from jejunum, ileum, and cecum was collected at slaughter from Holstein bull calves assigned to 4 groups: noninfected, buffer-treated (n=5); noninfected, GLP-2 treated (n=4); E. bovis-infected, buffer-treated (n=5); and E. bovis-infected, GLP-2-treated (n=4). Infected calves were orally dosed with 100,000 to 200,000 sporulated E. bovis oocysts on d 0; GLP-2-treated calves received 50 µg of GLP-2/kg of body weight subcutaneously twice daily for 10d beginning on d 18; and buffer-treated calves received an equal injection volume of 0.01 M Na bicarbonate buffer. All calves were killed on d 28. The mRNA expression of coxsackie and adenovirus receptor (CXADR), claudins 1, 2, and 4 (CLDN1, CLDN2, and CLDN4), F11 receptor (F11R), junction adhesion molecule 2 (JAM2), occludin (OCLN), and tight junction protein ZO-1 (TJP1) was determined by real-time quantitative PCR. In jejunum and ileum, an interaction of E. bovis infection and GLP-2 treatment on gene expression was noted. In jejunum of noninfected calves, GLP-2 increased CXADR, CLDN2, OCLN, and TJP1 mRNA expression but had no effect on mRNA expression in infected calves. Treatment with GLP-2 also increased tight junction protein ZO-1 protein expression in jejunum of noninfected calves as determined by immunohistochemistry. In ileum, E. bovis decreased expression of JAM2, OCLN, and TJP1 in buffer-treated calves, and GLP-2 increased TJP1 expression in infected calves. In cecum, E. bovis infection reduced expression of CXADR, CLDN4, F11R, and OCLN, and GLP-2 therapy increased expression of CLDN4, F11R, OCLN, and TJP1. Results are consistent with studies in

  10. Cross-linked polyethylenimine–tripolyphosphate nanoparticles for gene delivery

    Directory of Open Access Journals (Sweden)

    Huang XZ

    2014-10-01

    Full Text Available Xianzhang Huang,1 Sujing Shen,2 Zhanfeng Zhang,1 Junhua Zhuang1 1Department of Laboratory Science, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 2Department of Laboratory Science, Guangdong Second Provincial Traditional Chinese Medicine Hospital, Guangzhou, People’s Republic of China Abstract: The high transfection efficiency of polyethylenimine (PEI makes it an attractive potential nonviral genetic vector for gene delivery and therapy. However, the highly positive charge of PEI leads to cytotoxicity and limits its application. To reduce the cytotoxicity of PEI, we prepared anion-enriched nanoparticles that combined PEI with tripolyphosphate (TPP. We then characterized the PEI-TPP nanoparticles in terms of size, zeta potential, and Fourier-transform infrared (FTIR spectra, and assessed their transfection efficiency, cytotoxicity, and ability to resist deoxyribonuclease (DNase I digestion. The cellular uptake of PEI-TPP with phosphorylated internal ribosome entry site–enhanced green fluorescent protein C1 or FAM (fluorouracil, Adriamycin [doxorubicin] and mitomycin-labeled small interfering ribonucleic acids (siRNAs was monitored by fluorescence microscopy and confocal laser microscopy. The efficiency of transfected delivery of plasmid deoxyribonucleic acid (DNA and siRNA in vitro was 1.11- to 4.20-fold higher with the PEI-TPP particles (7.6% cross-linked than with the PEI, at all N:P ratios (nitrogen in PEI to phosphorus in DNA tested. The cell viability of different cell lines was more than 90% at the chosen N:P ratios of PEI-TPP/DNA complexes. Moreover, PEI-TPP nanoparticles resisted digestion by DNase I for more than 2 hours. The time-dependent absorption experiment showed that 7.6% of cross-linked PEI-TPP particles were internalized by 293T cells within 1 hour. In summary, PEI-TPP nanoparticles effectively transfected cells while conferring little or no toxicity, and thus have potential application in gene

  11. Linking Genes to Cardiovascular Diseases: Gene Action and Gene-Environment Interactions.

    Science.gov (United States)

    Pasipoularides, Ares

    2015-12-01

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

  12. Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex

    Directory of Open Access Journals (Sweden)

    Jason R. Gerstner

    2016-10-01

    Full Text Available Abstract Background Why we sleep is still one of the most perplexing mysteries in biology. Strong evidence indicates that sleep is necessary for normal brain function and that sleep need is a tightly regulated process. Surprisingly, molecular mechanisms that determine sleep need are incompletely described. Moreover, very little is known about transcriptional changes that specifically accompany the accumulation and discharge of sleep need. Several studies have characterized differential gene expression changes following sleep deprivation. Much less is known, however, about changes in gene expression during the compensatory response to sleep deprivation (i.e. recovery sleep. Results In this study we present a comprehensive analysis of the effects of sleep deprivation and subsequent recovery sleep on gene expression in the mouse cortex. We used a non-traditional analytical method for normalization of genome-wide gene expression data, Removal of Unwanted Variation (RUV. RUV improves detection of differential gene expression following sleep deprivation. We also show that RUV normalization is crucial to the discovery of differentially expressed genes associated with recovery sleep. Our analysis indicates that the majority of transcripts upregulated by sleep deprivation require 6 h of recovery sleep to return to baseline levels, while the majority of downregulated transcripts return to baseline levels within 1–3 h. We also find that transcripts that change rapidly during recovery (i.e. within 3 h do so on average with a time constant that is similar to the time constant for the discharge of sleep need. Conclusions We demonstrate that proper data normalization is essential to identify changes in gene expression that are specifically linked to sleep deprivation and recovery sleep. Our results provide the first evidence that recovery sleep is comprised of two waves of transcriptional regulation that occur at different times and affect functionally

  13. Claudin-2 knockout by TALEN-mediated gene targeting in MDCK cells: claudin-2 independently determines the leaky property of tight junctions in MDCK cells.

    Directory of Open Access Journals (Sweden)

    Shinsaku Tokuda

    Full Text Available Tight junctions (TJs regulate the movements of substances through the paracellular pathway, and claudins are major determinants of TJ permeability. Claudin-2 forms high conductive cation pores in TJs. The suppression of claudin-2 expression by RNA interference in Madin-Darby canine kidney (MDCK II cells (a low-resistance strain of MDCK cells was shown to induce a three-fold increase in transepithelial electrical resistance (TER, which, however, was still lower than in high-resistance strains of MDCK cells. Because RNA interference-mediated knockdown is not complete and only reduces gene function, we considered the possibility that the remaining claudin-2 expression in the knockdown study caused the lower TER in claudin-2 knockdown cells. Therefore, we investigated the effects of claudin-2 knockout in MDCK II cells by establishing claudin-2 knockout clones using transcription activator-like effector nucleases (TALENs, a recently developed genome editing method for gene knockout. Surprisingly, claudin-2 knockout increased TER by more than 50-fold in MDCK II cells, and TER values in these cells (3000-4000 Ω·cm2 were comparable to those in the high-resistance strains of MDCK cells. Claudin-2 re-expression restored the TER of claudin-2 knockout cells dependent upon claudin-2 protein levels. In addition, we investigated the localization of claudin-1, -2, -3, -4, and -7 at TJs between control MDCK cells and their respective knockout cells using their TALENs. Claudin-2 and -7 were less efficiently localized at TJs between control and their knockout cells. Our results indicate that claudin-2 independently determines the 'leaky' property of TJs in MDCK II cells and suggest the importance of knockout analysis in cultured cells.

  14. Distinct microbial populations are tightly linked to the profile of dissolved iron in the methanic sediments of the Helgoland mud area, North Sea

    Directory of Open Access Journals (Sweden)

    Oluwatobi Emmanuel Oni

    2015-05-01

    Full Text Available Iron reduction in subseafloor sulfate-depleted and methane-rich marine sediments is currently a subject of interest in subsurface geomicrobiology. While iron reduction and microorganisms involved have been well studied in marine surface sediments, little is known about microorganisms responsible for iron reduction in deep methanic sediments. Here, we used quantitative PCR (Q-PCR-based 16S rRNA gene copy numbers and pyrosequencing-based relative abundances of bacteria and archaea to investigate covariance between distinct microbial populations and specific geochemical profiles in the top 5 m of sediment cores from the Helgoland mud area, North Sea. We found that gene copy numbers of bacteria and archaea were specifically higher around the peak of dissolved iron in the methanic zone (250-350 cm. The higher copy numbers at these depths were also reflected by the relative sequence abundances of members of the candidate division JS1, methanogenic and Methanohalobium/ANME-3 related archaea. The distribution of these populations was strongly correlated to the profile of pore-water Fe2+ while that of Desulfobacteraceae corresponded to the pore-water sulfate profile. Furthermore, specific JS1 populations also strongly co-varied with the distribution of Methanosaetaceae in the methanic zone. Our data suggest that the interplay among JS1 bacteria, methanogenic archaea and Methanohalobium/ANME-3-related archaea may be important for iron reduction and methane cycling in deep methanic sediments of the Helgoland mud area and perhaps in other methane-rich depositional environments.

  15. Molecular tagging and validation of microsatellite markers linked to the low germination stimulant gene (lgs) for Striga resistance in sorghum [Sorghum bicolor (L.) Moench].

    Science.gov (United States)

    Satish, Kanuganti; Gutema, Zenbaba; Grenier, Cécile; Rich, Patrick J; Ejeta, Gebisa

    2012-04-01

    Striga is a devastating parasitic weed in Africa and parts of Asia. Low Striga germination stimulant activity, a well-known resistance mechanism in sorghum, is controlled by a single recessive gene (lgs). Molecular markers linked to the lgs gene can accelerate development of Striga-resistant cultivars. Using a high density linkage map constructed with 367 markers (DArT and SSRs) and an in vitro assay for germination stimulant activity towards Striga asiatica in 354 recombinant inbred lines derived from SRN39 (low stimulant) × Shanqui Red (high stimulant), we precisely tagged and mapped the lgs gene on SBI-05 between two tightly linked microsatellite markers SB3344 and SB3352 at a distance of 0.5 and 1.5 cM, respectively. The fine-mapped lgs region was delimited to a 5.8 cM interval with the closest three markers SB3344, SB3346 and SB3343 positioned at 0.5, 0.7 and 0.9 cM, respectively. We validated tightly linked markers in a set of 23 diverse sorghum accessions, most of which were known to be Striga resistant, by genotyping and phenotyping for germination stimulant activity towards both S. asiatica and S. hermonthica. The markers co-segregated with Striga germination stimulant activity in 21 of the 23 tested lines. The lgs locus similarly affected germination stimulant activity for both Striga species. The identified markers would be useful in marker-assisted selection for introgressing this trait into susceptible sorghum cultivars. Examination of the sorghum genome sequence and comparative analysis with the rice genome suggests some candidate genes in the fine-mapped region (400 kb) that may affect strigolactone biosynthesis or exudation. This work should form a foundation for map-based cloning of the lgs gene and aid in elucidation of an exact mechanism for resistance based on low Striga germination stimulant activity.

  16. Inactivation of X-linked tumor suppressor genes in human cancer.

    Science.gov (United States)

    Liu, Runhua; Kain, Mandy; Wang, Lizhong

    2012-04-01

    Cancer cells silence autosomal tumor suppressor genes by Knudson's two-hit mechanism in which loss-of-function mutations and then loss of heterozygosity occur at the tumor suppressor gene loci. However, the identification of X-linked tumor suppressor genes has challenged the traditional theory of 'two-hit inactivation' in tumor suppressor genes, introducing the novel concept that a single genetic hit can cause loss of tumor suppressor function. The mechanism through which these genes are silenced in human cancer is unclear, but elucidating the details will greatly enhance our understanding of the pathogenesis of human cancer. Here, we review the identification of X-linked tumor suppressor genes and discuss the potential mechanisms of their inactivation. In addition, we also discuss how the identification of X-linked tumor suppressor genes can potentially lead to new approaches in cancer therapy.

  17. Identification of microsatellite markers (SSR linked to a new bacterial blight resistance gene xa33(t in rice cultivar ‘Ba7’

    Directory of Open Access Journals (Sweden)

    Theerayut Toojinda

    2009-05-01

    Full Text Available This study attempts to identify a new source of bacterial blight (BB resistance gene and microsatellite makers (SSR linked to it. A total number of 139 F2 progenies generated from a cross between the resistant donor ‘Ba7’and ‘Pin Kaset’ were developed and used for this study. A Thai Xoo isolate, TXO16, collected from Phitsanulok province, was used to evaluate the resistance reaction in the F2 population. The segregation ratio of resistance (R and susceptibility (S was statistically fitted to 1R:3S model indicating single recessive gene segregation. Twenty F2 individuals consisting of 10 resistant and 10 susceptible plants were chosen for DNA analysis. Sixty-two polymorphic markers covering all rice chromosomes were used to identify the location and linked markers of the resistance gene. Four SSR markers, viz. RM30, RM7243, RM5509 and RM400, located on the long arm of rice chromosome 6, could clearly discriminate between resistant and susceptible phenotypes, and 161 BC2F2:3 individuals carrying BB resistance gene were developed through MAS using these SSR markers. This population was inoculated with TXO16 to validate and confirm the location of the gene and linked markers. The segregation ratio was statistically fitted to 1R:3S model confirming a recessive nature of the gene action in this germplasm. Phenotypic-genotypic association including five additional markers suggested that RM20590 was tightly linked to this resistance gene (R2=59.12 %. The BB phenotype was controlled by a recessive gene with incomplete dominance of susceptible allele providing intermediate resistance to Xoo pathogen in heterozygotes. The location of the gene was in the vicinity of a dominant gene, Xa7, which was previously reported. However, the resistance gene identified here was different from Xa7 because of the different nature of gene action. Consequently, this gene was tentatively designated as xa33(t. The resistance gene from rice cultivar ‘Ba7’ and the

  18. RefSeq and LocusLink: NCBI gene-centered resources.

    Science.gov (United States)

    Pruitt, K D; Maglott, D R

    2001-01-01

    Thousands of genes have been painstakingly identified and characterized a few genes at a time. Many thousands more are being predicted by large scale cDNA and genomic sequencing projects, with levels of evidence ranging from supporting mRNA sequence and comparative genomics to computing ab initio models. This, coupled with the burgeoning scientific literature, makes it critical to have a comprehensive directory for genes and reference sequences for key genomes. The NCBI provides two resources, LocusLink and RefSeq, to meet these needs. LocusLink organizes information around genes to generate a central hub for accessing gene-specific information for fruit fly, human, mouse, rat and zebrafish. RefSeq provides reference sequence standards for genomes, transcripts and proteins; human, mouse and rat mRNA RefSeqs, and their corresponding proteins, are discussed here. Together, RefSeq and LocusLink provide a non-redundant view of genes and other loci to support research on genes and gene families, variation, gene expression and genome annotation. Additional information about LocusLink and RefSeq is available at http://www.ncbi.nlm.nih.gov/LocusLink/.

  19. Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiology

    Science.gov (United States)

    Spataro, Nino; Rodríguez, Juan Antonio; Navarro, Arcadi

    2017-01-01

    Abstract Do genes presenting variation that has been linked to human disease have different biological properties than genes that have never been related to disease? What is the relationship between disease and fitness? Are the evolutionary pressures that affect genes linked to Mendelian diseases the same to those acting on genes whose variation contributes to complex disorders? The answers to these questions could shed light on the architecture of human genetic disorders and may have relevant implications when designing mapping strategies in future genetic studies. Here we show that, relative to non-disease genes, human disease (HD) genes have specific evolutionary profiles and protein network properties. Additionally, our results indicate that the mutation-selection balance renders an insufficient account of the evolutionary history of some HD genes and that adaptive selection could also contribute to shape their genetic architecture. Notably, several biological features of HD genes depend on the type of pathology (complex or Mendelian) with which they are related. For example, genes harbouring both causal variants for Mendelian disorders and risk factors for complex disease traits (Complex-Mendelian genes), tend to present higher functional relevance in the protein network and higher expression levels than genes associated only with complex disorders. Moreover, risk variants in Complex-Mendelian genes tend to present higher odds ratios than those on genes associated with the same complex disorders but with no link to Mendelian diseases. Taken together, our results suggest that genetic variation at genes linked to Mendelian disorders plays an important role in driving susceptibility to complex disease. PMID:28053046

  20. Gene Essentiality Is a Quantitative Property Linked to Cellular Evolvability.

    Science.gov (United States)

    Liu, Gaowen; Yong, Mei Yun Jacy; Yurieva, Marina; Srinivasan, Kandhadayar Gopalan; Liu, Jaron; Lim, John Soon Yew; Poidinger, Michael; Wright, Graham Daniel; Zolezzi, Francesca; Choi, Hyungwon; Pavelka, Norman; Rancati, Giulia

    2015-12-03

    Gene essentiality is typically determined by assessing the viability of the corresponding mutant cells, but this definition fails to account for the ability of cells to adaptively evolve to genetic perturbations. Here, we performed a stringent screen to assess the degree to which Saccharomyces cerevisiae cells can survive the deletion of ~1,000 individual "essential" genes and found that ~9% of these genetic perturbations could in fact be overcome by adaptive evolution. Our analyses uncovered a genome-wide gradient of gene essentiality, with certain essential cellular functions being more "evolvable" than others. Ploidy changes were prevalent among the evolved mutant strains, and aneuploidy of a specific chromosome was adaptive for a class of evolvable nucleoporin mutants. These data justify a quantitative redefinition of gene essentiality that incorporates both viability and evolvability of the corresponding mutant cells and will enable selection of therapeutic targets associated with lower risk of emergence of drug resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Escape of X-linked miRNA genes from meiotic sex chromosome inactivation.

    Science.gov (United States)

    Sosa, Enrique; Flores, Luis; Yan, Wei; McCarrey, John R

    2015-11-01

    Past studies have indicated that transcription of all X-linked genes is repressed by meiotic sex chromosome inactivation (MSCI) during the meiotic phase of spermatogenesis in mammals. However, more recent studies have shown an increase in steady-state levels of certain X-linked miRNAs in pachytene spermatocytes, suggesting that either synthesis of these miRNAs increases or that degradation of these miRNAs decreases dramatically in these cells. To distinguish between these possibilities, we performed RNA-FISH to detect nascent transcripts from multiple miRNA genes in various spermatogenic cell types. Our results show definitively that Type I X-linked miRNA genes are subject to MSCI, as are all or most X-linked mRNA genes, whereas Type II and III X-linked miRNA genes escape MSCI by continuing ongoing, active transcription in primary spermatocytes. We corroborated these results by co-localization of RNA-FISH signals with both a corresponding DNA-FISH signal and an immunofluorescence signal for RNA polymerase II. We also found that X-linked miRNA genes that escape MSCI locate non-randomly to the periphery of the XY body, whereas genes that are subject to MSCI remain located within the XY body in pachytene spermatocytes, suggesting that the mechanism of escape of X-linked miRNA genes from MSCI involves their relocation to a position outside of the repressive chromatin domain associated with the XY body. The fact that Type II and III X-linked miRNA genes escape MSCI suggests an immediacy of function of the encoded miRNAs specifically required during the meiotic stages of spermatogenesis.

  2. GeneLink: a database to facilitate genetic studies of complex traits

    Directory of Open Access Journals (Sweden)

    Wolfsberg Tyra G

    2004-10-01

    Full Text Available Abstract Background In contrast to gene-mapping studies of simple Mendelian disorders, genetic analyses of complex traits are far more challenging, and high quality data management systems are often critical to the success of these projects. To minimize the difficulties inherent in complex trait studies, we have developed GeneLink, a Web-accessible, password-protected Sybase database. Results GeneLink is a powerful tool for complex trait mapping, enabling genotypic data to be easily merged with pedigree and extensive phenotypic data. Specifically designed to facilitate large-scale (multi-center genetic linkage or association studies, GeneLink securely and efficiently handles large amounts of data and provides additional features to facilitate data analysis by existing software packages and quality control. These include the ability to download chromosome-specific data files containing marker data in map order in various formats appropriate for downstream analyses (e.g., GAS and LINKAGE. Furthermore, an unlimited number of phenotypes (either qualitative or quantitative can be stored and analyzed. Finally, GeneLink generates several quality assurance reports, including genotyping success rates of specified DNA samples or success and heterozygosity rates for specified markers. Conclusions GeneLink has already proven an invaluable tool for complex trait mapping studies and is discussed primarily in the context of our large, multi-center study of hereditary prostate cancer (HPC. GeneLink is freely available at http://research.nhgri.nih.gov/genelink.

  3. A BAC-bacterial recombination method to generate physically linked multiple gene reporter DNA constructs

    Directory of Open Access Journals (Sweden)

    Gong Shiaochin

    2009-03-01

    Full Text Available Abstract Background Reporter gene mice are valuable animal models for biological research providing a gene expression readout that can contribute to cellular characterization within the context of a developmental process. With the advancement of bacterial recombination techniques to engineer reporter gene constructs from BAC genomic clones and the generation of optically distinguishable fluorescent protein reporter genes, there is an unprecedented capability to engineer more informative transgenic reporter mouse models relative to what has been traditionally available. Results We demonstrate here our first effort on the development of a three stage bacterial recombination strategy to physically link multiple genes together with their respective fluorescent protein (FP reporters in one DNA fragment. This strategy uses bacterial recombination techniques to: (1 subclone genes of interest into BAC linking vectors, (2 insert desired reporter genes into respective genes and (3 link different gene-reporters together. As proof of concept, we have generated a single DNA fragment containing the genes Trap, Dmp1, and Ibsp driving the expression of ECFP, mCherry, and Topaz FP reporter genes, respectively. Using this DNA construct, we have successfully generated transgenic reporter mice that retain two to three gene readouts. Conclusion The three stage methodology to link multiple genes with their respective fluorescent protein reporter works with reasonable efficiency. Moreover, gene linkage allows for their common chromosomal integration into a single locus. However, the testing of this multi-reporter DNA construct by transgenesis does suggest that the linkage of two different genes together, despite their large size, can still create a positional effect. We believe that gene choice, genomic DNA fragment size and the presence of endogenous insulator elements are critical variables.

  4. Daniel Link, Suturas. Imágenes, escritura, vida

    Directory of Open Access Journals (Sweden)

    Lucia Faienza

    2015-11-01

    Full Text Available Ultimo di una trilogia saggistica preceduto da Clases (2005 e Fantasmas (2009, Suturas (2015 chiude il cerchio di quella che il suo autore, Daniel Link, chiama «interrogación sobre lo viviente». Già il titolo mostra l’ambiguità da cui prende avvio la riflessione di Link e che attraversa la pluralità degli oggetti su cui si posa lo sguardo dell’autore: la ”sutura” è tanto la cucitura che unisce la vecchia cultura letteraria con le nuove culture digitali e post-letterarie, quanto la cicatrice che marca la “ferita” di questo cambio di paradigma dentro al corpo della contemporaneità.

  5. Two tobacco AP1-like gene promoters with highly specific, tightly regulated and uniquely expressed activity during floral transition, initiation and development

    Science.gov (United States)

    Biotech engineering of agronomic traits requires an array of highly specific and tightly regulated promoters in flower or other tissues. In this study, we isolated and characterized two tobacco AP1-like promoters (termed NtAP1La and NtAP1Lb1) in transgenic plants using GUS reporter and tissue-speci...

  6. Refinement of the localization of the X-linked ocular albinism gene

    Energy Technology Data Exchange (ETDEWEB)

    Bergen, A.A.B.; Zijp, P.; Schuurman, E.J.M.; Bleeker-Wagemakers, E.M.; Apkarian, P. (Netherlands Ophthalmic Research Inst., Amsterdam (Netherlands)); Ommen, G.J.B. van (Univ. of Leiden (Netherlands))

    1993-04-01

    Although physical and genetic mapping studies assigned the X-linked ocular albinism gene to Xp22.3, the exact gene order in this region is still unclear. The authors present additional genetic mapping data concerning X-linked ocular albinism that suggests the consensus order Xpter-STS-DXS237-KAL-(OA1, DXS143)- DXS85-DXS16-Xcen. 14 refs., 1 fig.

  7. FARVATX: Family-Based Rare Variant Association Test for X-Linked Genes.

    Science.gov (United States)

    Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H; Silverman, Edwin K; Park, Taesung; Won, Sungho

    2016-09-01

    Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease. Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods.

  8. X-linked hydrocephalus : A novel missense mutation in the L1CAM gene

    NARCIS (Netherlands)

    Sztriha, L; Vos, YJ; Verlind, E; Johansen, J; Berg, B

    2002-01-01

    X-linked hydrocephalus is associated with mutations in the L1 neuronal cell adhesion molecule gene. L1 protein plays a key role in neurite outgrowth, axonal guidance, and pathfinding during the development of the nervous system. A male is described with X-linked hydrocephalus who had multiple small

  9. Genes Tied to Belly Size Also Linked to Heart Disease

    Science.gov (United States)

    ... he said, that the genes that contribute to abdominal obesity also feed the development of diabetes and heart disease -- through mechanisms other than extra belly fat. Still, everyone agreed on what the findings imply: ... vulnerable to abdominal obesity, that does not mean it's destiny. It's ...

  10. Linking stochastic fluctuations in chromatin structure and gene expression.

    Directory of Open Access Journals (Sweden)

    Christopher R Brown

    Full Text Available The number of mRNA and protein molecules expressed from a single gene molecule fluctuates over time. These fluctuations have been attributed, in part, to the random transitioning of promoters between transcriptionally active and inactive states, causing transcription to occur in bursts. However, the molecular basis of transcriptional bursting remains poorly understood. By electron microscopy of single PHO5 gene molecules from yeast, we show that the "activated" promoter assumes alternative nucleosome configurations at steady state, including the maximally repressive, fully nucleosomal, and the maximally non-repressive, nucleosome-free, configuration. We demonstrate that the observed probabilities of promoter nucleosome configurations are obtained from a simple, intrinsically stochastic process of nucleosome assembly, disassembly, and position-specific sliding; and we show that gene expression and promoter nucleosome configuration can be mechanistically coupled, relating promoter nucleosome dynamics and gene expression fluctuations. Together, our findings suggest a structural basis for transcriptional bursting, and offer new insights into the mechanism of transcriptional regulation and the kinetics of promoter nucleosome transitions.

  11. X-linked genes and risk of orofacial clefts

    DEFF Research Database (Denmark)

    Jugessur, Astanand; Skare, Øivind; Lie, Rolv T

    2012-01-01

    Orofacial clefts are common birth defects of complex etiology, with an excess of males among babies with cleft lip and palate, and an excess of females among those with cleft palate only. Although genes on the X chromosome have been implicated in clefting, there has been no association analysis...

  12. Cx32 gene mutation associated with X-linked recessive Charcot-Marie-Tooth disease

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The form of Charcot-Marie-Tooth (CMT) neuropathy that maps to Xq13 is X-linked dominant, or X-linked intermediate. Heterozygous females are more mildly affected than hemizygous males. It has been known that this type of CMT is caused by mutations of connexin32 (Cx32) gene. A typical X-linked recessive Charcot-Marie-Tooth Chinese family was analyzed with single strand conformation polymorphism method. A Cx32 gene point mutation, Arg15Gln, in exon 2 was identified in all affected family members, suggesting that this mutation is responsible for the CMT incidence of this family.

  13. Genome-wide misexpression of X-linked versus autosomal genes associated with hybrid male sterility.

    Science.gov (United States)

    Lu, Xuemei; Shapiro, Joshua A; Ting, Chau-Ti; Li, Yan; Li, Chunyan; Xu, Jin; Huang, Huanwei; Cheng, Ya-Jen; Greenberg, Anthony J; Li, Shou-Hsien; Wu, Mao-Lien; Shen, Yang; Wu, Chung-I

    2010-08-01

    Postmating reproductive isolation is often manifested as hybrid male sterility, for which X-linked genes are overrepresented (the so-called large X effect). In contrast, X-linked genes are significantly under-represented among testis-expressing genes. This seeming contradiction may be germane to the X:autosome imbalance hypothesis on hybrid sterility, in which the X-linked effect is mediated mainly through the misexpression of autosomal genes. In this study, we compared gene expression in fertile and sterile males in the hybrids between two Drosophila species. These hybrid males differ only in a small region of the X chromosome containing the Ods-site homeobox (OdsH) (also known as Odysseus) locus of hybrid sterility. Of genes expressed in the testis, autosomal genes were, indeed, more likely to be misexpressed than X-linked genes under the sterilizing action of OdsH. Since this mechanism of X:autosome interaction is only associated with spermatogenesis, a connection between X:autosome imbalance and the high rate of hybrid male sterility seems plausible.

  14. Identification of Specific RAPD Markers Linked to Anthracnose Resistant Gene in Native Wild Grapes of China

    Institute of Scientific and Technical Information of China (English)

    WANG Xi-ping; WANG Yue-jin; ZHOU Peng; ZHENG Xue-qin

    2001-01-01

    Randomly amplified polymorphic DNA (RAPD) was employed to detect molecular markers linked to anthracnose ( Spheceloma ampelinum de Bary) resistant gene in the native wild grapes ( Vitis L. ) of China. RAPD marker OPJ13-300 was linked to anthracnose resistant gene using 90-3 cross F1 V. quinquangularis Rehd (shang-24) × V. vinifera (Longyan). The marker was verified in 90-3 cross F1, Chinese wild grapes and V. riparia and European grape cuitivars. This work has provided a solid basis for molecular marker-assisted selection (MAS) to disease resistance and cloning of disease resistant genes.

  15. New insights and unresolved issues regarding insertional mutagenesis in X-linked SCID gene therapy.

    Science.gov (United States)

    Pike-Overzet, Karin; van der Burg, Mirjam; Wagemaker, Gerard; van Dongen, Jacques J M; Staal, Frank J T

    2007-11-01

    The oncogenic potential of retrovirus-mediated gene therapy has been re-emphasized because four patients developed T-cell acute lymphoblastic leukemia (T-ALL)-like disease from an otherwise successful gene therapy trial for X-linked severe combined immunodeficiency (X-linked SCID). X-linked SCID, a disease caused by inactivating mutations in the IL2Rgamma gene, is part of a heterogeneous group of SCIDs characterized by the lack of T cells in conjunction with the absence of B and/or natural killer (NK) cells. Gene therapy approaches are being developed for this group of diseases. In this review we discuss the various forms of SCID in relation to normal T-cell development. In addition, we consider the possible role of LMO2 and other T-ALL oncogenes in the development of adverse effects as seen in the X-linked SCID gene therapy trial. Furthermore, we debate whether the integration near the LMO2 locus is sufficient to result in T-ALL-like proliferations or whether the gamma-retroviral viral expression of the therapeutic IL2RG gene contributes to leukemogenesis. Finally, we review some newly developed murine models that may have added value for gene therapy safety studies.

  16. Human protein kinase C lota gene (PRKC1) is closely linked to the BTK gene in Xq21.3

    Energy Technology Data Exchange (ETDEWEB)

    Mazzarella, R.; Jones, C.; Schlessinger, D. [Washington Univ. School of Medicine, St. Louis, MO (United States)] [and others

    1995-04-10

    The human X chromosome contains many disease loci, but only a small number of X-linked genes have been cloned and characterized. One approach to finding genes in genomic DNA uses partial sequencing of random cDNAs to develop {open_quotes}expressed sequence tags{close_quotes} (ESTs). Many authors have recently reported chromosomal localization of such ESTs using hybrid panels. Twenty ESTs specific for the X chromosome have been localized to defined regions with somatic cell hybrids, and 12 of them have been physically linked to markers that detect polymorphisms. One of these ESTs, EST02087, was physically linked in a 650-kb contig to the GLA ({alpha}-galactosidase) gene involved in Fabry disease. A comparison of this contig with a 7.5-Mb YAC contig indicated that this gene is also within 250 kb of the src-like protein-tyrosine kinase BTK (X-linked agammaglobulinemia protein-tyrosine kinase) gene in Xq21.3. 14 refs., 1 fig.

  17. Sex-specific silencing of X-linked genes by Xist RNA.

    Science.gov (United States)

    Gayen, Srimonta; Maclary, Emily; Hinten, Michael; Kalantry, Sundeep

    2016-01-19

    X-inactive specific transcript (Xist) long noncoding RNA (lncRNA) is thought to catalyze silencing of X-linked genes in cis during X-chromosome inactivation, which equalizes X-linked gene dosage between male and female mammals. To test the impact of Xist RNA on X-linked gene silencing, we ectopically induced endogenous Xist by ablating the antisense repressor Tsix in mice. We find that ectopic Xist RNA induction and subsequent X-linked gene silencing is sex specific in embryos and in differentiating embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs). A higher frequency of X(ΔTsix)Y male cells displayed ectopic Xist RNA coating compared with X(ΔTsix)X female cells. This increase reflected the inability of X(ΔTsix)Y cells to efficiently silence X-linked genes compared with X(ΔTsix)X cells, despite equivalent Xist RNA induction and coating. Silencing of genes on both Xs resulted in significantly reduced proliferation and increased cell death in X(ΔTsix)X female cells relative to X(ΔTsix)Y male cells. Thus, whereas Xist RNA can inactivate the X chromosome in females it may not do so in males. We further found comparable silencing in differentiating X(ΔTsix)Y and 39,X(ΔTsix) (X(ΔTsix)O) ESCs, excluding the Y chromosome and instead implicating the X-chromosome dose as the source of the sex-specific differences. Because X(ΔTsix)X female embryonic epiblast cells and EpiSCs harbor an inactivated X chromosome prior to ectopic inactivation of the active X(ΔTsix) X chromosome, we propose that the increased expression of one or more X-inactivation escapees activates Xist and, separately, helps trigger X-linked gene silencing.

  18. Application of an Efficient Gene Targeting System Linking Secondary Metabolites to their Biosynthetic Genes in Aspergillus terreus

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Chun-Jun; Knox, Benjamin P.; Sanchez, James F.; Chiang, Yi-Ming; Bruno, Kenneth S.; Wang, Clay C.

    2013-07-19

    Nonribosomal peptides (NRPs) are natural products biosynthesized by NRP synthetases. A kusA-, pyrG- mutant strain of Aspergillusterreus NIH 2624 was developed that greatly facilitated the gene targeting efficiency in this organism. Application of this tool allowed us to link four major types of NRP related secondary metabolites to their responsible genes in A. terreus. In addition, an NRP related melanin synthetase was also identified in this species.

  19. Fragile X gene instability: Anchoring AGGs and linked microsatellites

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Nan; Yang, Weihong; Dobkin, C. [Institute for Basic Research in Developmental Disabilities, Staten Island, NY (United States)] [and others

    1995-08-01

    Interspersed AGGs within the FMR1 gene CGG repeat region may anchor the sequence and prevent slippage during replication. In order to detect the AGG position variations, we developed a method employing partial MnlI restriction analysis and analyzed X chromosomes from 187 males, including 133 normal controls (17 with 20-34 and 16 with 35-52 repeats), plus 54 fragile X premutations with 56-180 repeats. Among controls, the interspersed AGG positions were highly polymorphic, with heterozygosity of 91%. Among the control samples, 1.5% had no AGG positions, 25% had one, 71% had two, and 3% had three. Among the fragile X premutation samples, 63% had no AGG, while 37% had only one AGG. Analysis of premutation samples within fragile X families showed that variation occurred only within the 3{prime} end of the region. Thus, the instability was polar. Controls with {ge}15 pure CGG repeats were associated with the longest alleles of two nearby microsatellites, FRAXAC1 with 20-21 repeats and DXS548 with 202-206 bp and with increased microsatellite heterzygosity. The association of long pure CGG regions, as with fragile X chromosomes, with the longer and more heterozygous microsatellite alleles suggests they may be related mechanistically. Further, our results do not support a recent suggestion that the frequency of fragile X alleles may be increasing. Finally, analysis of a set of nonhuman primate samples showed that long pure CGG tracks are variable in size and are located within the 3{prime} region, which suggests that polar instability within FMR1 is evolutionarily quite old. 55 refs., 3 figs., 4 tabs.

  20. NOVEL HYBRID GENE VECTOR STABILIZED BY CROSS-LINKING WITH GOLD NANOPARTICLES

    Institute of Scientific and Technical Information of China (English)

    You-xiang Wang; Ying Zhu; Jia-cong Shen

    2008-01-01

    Enhanced stability of polyplexes in physiological condition was an important prerequisite for successful systemic gene delivery. Herein novel method was reported to develop stable gene vector by nanotechnology. Thiolated polyplexes were constructed and then cross-linked with gold nanoparticles (AuNPs) by gold-thiol interactions. TEM pictures showed that AuNPs were attached to the shell of spherical polyplexes. The hybrid gene vector was stable enough in physiological condition and maintained efficient transfection, which showed great potential in gene delivery research and application.

  1. Continuous Shearlet Tight Frames

    KAUST Repository

    Grohs, Philipp

    2010-10-22

    Based on the shearlet transform we present a general construction of continuous tight frames for L2(ℝ2) from any sufficiently smooth function with anisotropic moments. This includes for example compactly supported systems, piecewise polynomial systems, or both. From our earlier results in Grohs (Technical report, KAUST, 2009) it follows that these systems enjoy the same desirable approximation properties for directional data as the previous bandlimited and very specific constructions due to Kutyniok and Labate (Trans. Am. Math. Soc. 361:2719-2754, 2009). We also show that the representation formulas we derive are in a sense optimal for the shearlet transform. © 2010 Springer Science+Business Media, LLC.

  2. Mutational landscape of the human Y chromosome-linked genes and loci in patients with hypogonadism

    Indian Academy of Sciences (India)

    Deepali Pathak; Sandeep Kumar Yadav; Leena Rawal; Sher Ali

    2015-12-01

    Sex chromosome-related anomalies engender plethora of conditions leading to male infertility. Hypogonadotropic hypogonadism (HH) is a rare but well-known cause of male infertility. Present study was conducted to ascertain possible consensus on the alterations of the Y-linked genes and loci in males representing hypogonadism (H), which in turn culminate in reproductive dysfunction. A total of nineteen 46, XY males, clinically diagnosed with H (11 representative HH adults and eight prepubertal boys suspected of having HH) were included in the study. Sequence-tagged site screening, gene sequencing, fluorescence in situ hybridization mapping (FISH), copy number and relative expression studies by real-time PCR were conducted to uncover the altered status of the Y chromosome in the patients. The result showed random microdeletions within the (73%)/ (78%) and (26%) regions. Sequencing of the gene showed nucleotide variations within and outside of the HMG box in four males (21%). FISH uncovered mosaicism for , , genes and DYZ1 arrays, structural rearrangement for (31%) and duplication of (57%) genes. Copy number variation for seven Y-linked genes (2–8 rounds of duplication), DYZ1 arrays (495–6201copies) and differential expression of , and in the patients’ blood were observed. Present work demonstrates the organizational vulnerability of several Y-linked genes in H males. These results are envisaged to be useful during routine diagnosis of H patients.

  3. X-linked intellectual disability related genes disrupted by balanced X-autosome translocations.

    Science.gov (United States)

    Moysés-Oliveira, Mariana; Guilherme, Roberta Santos; Meloni, Vera Ayres; Di Battista, Adriana; de Mello, Claudia Berlim; Bragagnolo, Silvia; Moretti-Ferreira, Danilo; Kosyakova, Nadezda; Liehr, Thomas; Carvalheira, Gianna Maria; Melaragno, Maria Isabel

    2015-12-01

    Detailed molecular characterization of chromosomal rearrangements involving X-chromosome has been a key strategy in identifying X-linked intellectual disability-causing genes. We fine-mapped the breakpoints in four women with balanced X-autosome translocations and variable phenotypes, in order to investigate the corresponding genetic contribution to intellectual disability. We addressed the impact of the gene interruptions in transcription and discussed the consequences of their functional impairment in neurodevelopment. Three patients presented with cognitive impairment, reinforcing the association between the disrupted genes (TSPAN7-MRX58, KIAA2022-MRX98, and IL1RAPL1-MRX21/34) and intellectual disability. While gene expression analysis showed absence of TSPAN7 and KIAA2022 expression in the patients, the unexpected expression of IL1RAPL1 suggested a fusion transcript ZNF611-IL1RAPL1 under the control of the ZNF611 promoter, gene disrupted at the autosomal breakpoint. The X-chromosomal breakpoint definition in the fourth patient, a woman with normal intellectual abilities, revealed disruption of the ZDHHC15 gene (MRX91). The expression assays did not detect ZDHHC15 gene expression in the patient, thus questioning its involvement in intellectual disability. Revealing the disruption of an X-linked intellectual disability-related gene in patients with balanced X-autosome translocation is a useful tool for a better characterization of critical genes in neurodevelopment. © 2015 Wiley Periodicals, Inc.

  4. Linking fungal secondary metabolites and pathways to their genes in Aspergillus

    DEFF Research Database (Denmark)

    Petersen, Lene Maj

    organisms for genetic studies and human opportunistic pathogens. The aim of this PhD study has been divided into two major topics: 1) Discovery and characterization of novel SMs from filamentous fungi 2) Linking of fungal SMs to genes and elucidation of biosynthetic pathways The first part of this study......, analytical and natural products chemistry is critical for advances in both the linking of fungal SMs to genes and unraveling the biosynthetic pathways, as well as for the discovery of novel SMs hidden in a treasury of biosynthetic potential of filamentous fungi....

  5. Rigid aromatic linking moiety in cationic lipids for enhanced gene transfection efficiency.

    Science.gov (United States)

    Wang, Bing; Zhao, Rui-Mo; Zhang, Ji; Liu, Yan-Hong; Huang, Zheng; Yu, Qing-Ying; Yu, Xiao-Qi

    2017-08-18

    Although numerous cationic lipids have been developed as non-viral gene vectors, the structure-activity relationship (SAR) of these materials remains unclear and needs further investigation. In this work, a series of lysine-derived cationic lipids containing linkages with different rigidity were designed and synthesized. SAR studies showed that lipids with rigid aromatic linkage could promote the formation of tight liposomes and enhance DNA condensation, which is essential for the gene delivery process. These lipids could give much higher transfection efficiency than those containing more flexible aliphatic linkage in various cell lines. Moreover, the rigid aromatic linkage also affords the material higher serum tolerance ability. Flow cytometry assay revealed that the target lipids have good cellular uptake, while confocal microscopy observation showed weaker endosome escape than Lipofectamine 2000. To solve such problem and further increase the transfection efficiency, some lysosomotropic reagents were used to improve the endosome escape of lipoplex. As expected, higher transfection efficiency than Lipofectamine 2000 could be obtained via this strategy. Cytotoxicity assay showed that these lipids have lower toxicity in various cell lines than Lipofectamine 2000, suggesting their potential for further application. This work demonstrates that a rigid aromatic linkage might distinctly improve the gene transfection abilities of cationic lipids and affords information to construct safe and efficient gene vector towards practical application. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Molecular patterns of X chromosome-linked color vision genes among 134 menof European ancestry

    Energy Technology Data Exchange (ETDEWEB)

    Drummond-Borg, M.; Deeb, S.S.; Motulsky, A.G. (Univ. of Washington, Seattle (USA))

    1989-02-01

    The authors used Southern blot hybridization to study X chromosome-linked color vision genes encoding the apoproteins of red and green visual pigments in 134 unselected Caucasian men. One hundred and thirteen individuals (84.3%) had a normal arrangement of their color vision pigment genes. All had one red pigment gene; the number of green pigment genes ranged from one to five with a mode of two. The frequency of molecular genotypes indicative of normal color vision (84.3%) was significantly lower than had been observed in previous studies of color vision phenotypes. Color vision defects can be due to deletions of red or green pigment genes or due to formation of hybrid genes comprising portions of both red and green pigment genes. Characteristic anomalous patterns were seen in 15 (11.2%) individuals: 7 (5.2%) had patterns characteristic of deuteranomaly, 2 (1.5%) had patterns characteristic of deuteranopia, and 6 (4.5%) had protan patterns. Previously undescribed hybrid gene patterns consisting of both green and red pigment gene fragments in addition to normal red and green genes were observed in another 6 individuals (4.5%). Thus, DNA testing detected anomalous color vision pigment genes at a higher frequency than expected from phenotypic color vision tests.

  7. Methylation of the Glucocorticoid Receptor Gene Promoter in Preschoolers: Links with Internalizing Behavior Problems

    Science.gov (United States)

    Parade, Stephanie H.; Ridout, Kathryn K.; Seifer, Ronald; Armstrong, David A.; Marsit, Carmen J.; McWilliams, Melissa A.; Tyrka, Audrey R.

    2016-01-01

    Accumulating evidence suggests that early adversity is linked to methylation of the glucocorticoid receptor (GR) gene, "NR3C1," which is a key regulator of the hypothalamic-pituitary-adrenal axis. Yet no prior work has considered the contribution of methylation of "NR3C1" to emerging behavior problems and psychopathology in…

  8. Sex Differences in Spatial Ability: The X-Linked Gene Theory.

    Science.gov (United States)

    Blatter, Patricia

    1982-01-01

    Among the many theories attempting to explain sex differences in spatial ability, one of the most highly researched is the X-linked recessive gene theory. This is a review of the major research done on that theory and shows the conflicting nature of the results. (Author)

  9. Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation

    DEFF Research Database (Denmark)

    Kalscheuer, Vera M; Freude, Kristine; Musante, Luciana

    2003-01-01

    We found mutations in the gene PQBP1 in 5 of 29 families with nonsyndromic (MRX) and syndromic (MRXS) forms of X-linked mental retardation (XLMR). Clinical features in affected males include mental retardation, microcephaly, short stature, spastic paraplegia and midline defects. PQBP1 has previou...

  10. Sex Differences in Spatial Ability: The X-Linked Gene Theory.

    Science.gov (United States)

    Blatter, Patricia

    1982-01-01

    Among the many theories attempting to explain sex differences in spatial ability, one of the most highly researched is the X-linked recessive gene theory. This is a review of the major research done on that theory and shows the conflicting nature of the results. (Author)

  11. Influence of sex and genetic variability on expression of X-linked genes in human monocytes.

    Science.gov (United States)

    Castagné, Raphaële; Zeller, Tanja; Rotival, Maxime; Szymczak, Silke; Truong, Vinh; Schillert, Arne; Trégouët, David-Alexandre; Münzel, Thomas; Ziegler, Andreas; Cambien, François; Blankenberg, Stefan; Tiret, Laurence

    2011-11-01

    In humans, the fraction of X-linked genes with higher expression in females has been estimated to be 5% from microarray studies, a proportion lower than the 25% of genes thought to escape X inactivation. We analyzed 715 X-linked transcripts in circulating monocytes from 1,467 subjects and found an excess of female-biased transcripts on the X compared to autosomes (9.4% vs 5.5%, pgenes not previously known to escape inactivation, the most significant one was EFHC2 whose 20% of variability was explained by sex. We also investigated cis expression quantitative trait loci (eQTLs) by analyzing 15,703 X-linked SNPs. The frequency and magnitude of X-linked cis eQTLs were quite similar in males and females. Few genes exhibited a stronger genetic effect in females than in males (ARSD, DCX, POLA1 and ITM2A). These genes would deserve further investigation since they may contribute to sex pathophysiological differences.

  12. The organization structure and regulatory elements of Chlamydomonas histone genes reveal features linking plant and animal genes.

    Science.gov (United States)

    Fabry, S; Müller, K; Lindauer, A; Park, P B; Cornelius, T; Schmitt, R

    1995-09-01

    The genome of the green alga Chlamydomonas reinhardtii contains approximately 15 gene clusters of the nucleosomal (or core) histone H2A, H2B, H3 and H4 genes and at least one histone H1 gene. Seven non-allelic histone gene loci were isolated from a genomic library, physically mapped, and the nucleotide sequences of three isotypes of each core histone gene species and one linked H1 gene determined. The core histone genes are organized in clusters of H2A-H2B and H3-H4 pairs, in which each gene pair shows outwardly divergent transcription from a short (< 300 bp) intercistronic region. These intercistronic regions contain typically conserved promoter elements, namely a TATA-box and the three motifs TGGCCAG-G(G/C)-CGAG, CGTTGACC and CGGTTG. Different from the genes of higher plants, but like those of animals and the related alga Volvox, the 3' untranslated regions contain no poly A signal, but a palindromic sequence (3' palindrome) essential for mRNA processing is present. One single H1 gene was found in close linkage to a H2A-H2B pair. The H1 upstream region contains the octameric promoter element GGTTGACC (also found upstream of the core histone genes) and two specific sequence motifs that are shared only with the Volvox H1 promoters. This suggests differential transcription of the H1 and the core histone genes. The H1 gene is interrupted by two introns. Unlike Volvox H3 genes, the three sequenced H3 isoforms are intron-free. Primer-directed PCR of genomic DNA demonstrated, however, that at least 8 of the about 15 H3 genes do contain one intron at a conserved position. In synchronized C. reinhardtii cells, H4 mRNA levels (representative of all core histone mRNAs) peak during cell division, suggesting strict replication-dependent gene control. The derived peptide sequences place C. reinhardtii core histones closer to plants than to animals, except that the H2A histones are more animal-like. The peptide sequence of histone H1 is closely related to the V. carteri VH1-II

  13. Visual exploration of three-dimensional gene expression using physical views and linked abstract views.

    Science.gov (United States)

    Weber, Gunther H; Rübel, Oliver; Huang, Min-Yu; DePace, Angela H; Fowlkes, Charless C; Keränen, Soile V E; Luengo Hendriks, Cris L; Hagen, Hans; Knowles, David W; Malik, Jitendra; Biggin, Mark D; Hamann, Bernd

    2009-01-01

    During animal development, complex patterns of gene expression provide positional information within the embryo. To better understand the underlying gene regulatory networks, the Berkeley Drosophila Transcription Network Project (BDTNP) has developed methods that support quantitative computational analysis of three-dimensional (3D) gene expression in early Drosophila embryos at cellular resolution. We introduce PointCloudXplore (PCX), an interactive visualization tool that supports visual exploration of relationships between different genes' expression using a combination of established visualization techniques. Two aspects of gene expression are of particular interest: 1) gene expression patterns defined by the spatial locations of cells expressing a gene and 2) relationships between the expression levels of multiple genes. PCX provides users with two corresponding classes of data views: 1) Physical Views based on the spatial relationships of cells in the embryo and 2) Abstract Views that discard spatial information and plot expression levels of multiple genes with respect to each other. Cell Selectors highlight data associated with subsets of embryo cells within a View. Using linking, these selected cells can be viewed in multiple representations. We describe PCX as a 3D gene expression visualization tool and provide examples of how it has been used by BDTNP biologists to generate new hypotheses.

  14. What can HPA axis-linked genes tell us about anxiety disorders in adolescents?

    Directory of Open Access Journals (Sweden)

    Andressa Bortoluzzi

    2015-12-01

    Full Text Available Introduction: Anxiety disorders (AD share features of both anxiety and fear linked to stress response. The hypothalamic-pituitary-adrenal (HPA axis is considered the core biological pathway of the stress system and it is known that an inappropriate response to environmental stimuli may be related to individual genetic vulnerability in HPA-linked genes. Despite the biological plausibility of a relationship between the HPA axis and AD, few studies have investigated associations between genetic polymorphisms linked to the HPA axis and this complex disorder. Objective: To investigate whether AD are associated with genetic polymorphisms in HPA-linked genes in adolescents. Methods: Our study consisted of a cross-sectional evaluation of a community sample comprising a total of 228 adolescents (131 cases of AD. We extracted DNA from saliva and genotyped polymorphisms in HPA-linked genes (FKBP5: rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916; NR3C1: rs6198; CRHR1: rs878886; and SERPINA6: rs746530 with real time polymerase chain reaction (PCR. The instruments used to diagnose and assess the severity of AD were the Schedule for Affective Disorder and Schizophrenia for School-Age Children - Present and Lifetime (K-SADS-PL and the Screen for Child and Anxiety related Emotional Disorders (SCARED. Results: We failed to detect any associations between AD and genetic polymorphisms in HPA-linked genes (p > 0.05. Conclusion: To our knowledge, this is the first study evaluating these specific polymorphisms in relation to AD in adolescents, which encourages us to design further research on the subject.

  15. IDENTIFICATION OF RAPD MARKER LINKED TO POWDERY MILDEW RESISTANCE GENE Pm 12 IN WHEAT

    Institute of Scientific and Technical Information of China (English)

    GU Feng; ZHANG Qing-li; GUO Xiao-chun; LI Tao; WANG Hong-gang

    2004-01-01

    Powdery mildew is one of the most serious diseases of wheat in China. In this paper,bulked segregant analysis (BSA) was used to search for randomly amplified polymorphic DNA (RAPD) markers linked to the Pm12 gene,which confers resistance to the powdery mildew in wheat. 200 decamer primers were screened and one RAPD marker (S1071900) was identified to be linked to Pm 12 in coupling phase, and their genetic distance is 11.98 ±4.00cM. This marker can be used for marker - assisted selection in wheat breeding for the identification or pyramiding of Pm12 with other resistance genes.Key Words: Wheat, RAPD, Powdery mildew, resistance genes.

  16. X-linked dominant chondrodysplasia punctata (CDPX2) caused by single gene mosaicism in a male.

    Science.gov (United States)

    Aughton, David J; Kelley, Richard I; Metzenberg, Aida; Pureza, Vincent; Pauli, Richard M

    2003-01-30

    X-linked dominant chondrodysplasia punctata (CDPX2; Happle syndrome) is recognized almost exclusively in females, who display mosaic and asymmetric features, presumed to arise secondary to random X-inactivation. CDPX2 results from mutation of an X-linked gene coding for sterol-delta(8)-delta(7) isomerase (emopamil binding protein). We describe a boy with clinical features of CDPX2 (including those presumed to arise usually secondary to functional mosaicism in females). Biochemical and molecular studies demonstrate that he is mosaic for a sterol-delta(8)-delta(7) isomerase gene mutation. He is the first reported example of single gene mosaicism giving rise to CDPX2 in a male. Copyright 2002 Wiley-Liss, Inc.

  17. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

    Science.gov (United States)

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

    2016-02-29

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

  18. The Vf gene for scrab resistance in apple is linked to sub-lethal genes

    NARCIS (Netherlands)

    Gao, Z.S.; Weg, van de W.E.

    2006-01-01

    V f is the most widely used resistance gene in the breeding for scab resistant apple cultivars. Distorted segregation ratios for V f -resistance have frequently been reported. Here we revealed that sub-lethal genes caused the distorted segregation. The inheritance of V f was examined in six progenie

  19. An insight into the phylogenetic history of HOX linked gene families in vertebrates

    Directory of Open Access Journals (Sweden)

    Grzeschik Karl-Heinz

    2007-11-01

    Full Text Available Abstract Background The human chromosomes 2q, 7, 12q and 17q show extensive intra-genomic homology, containing duplicate, triplicate and quadruplicate paralogous regions centered on the HOX gene clusters. The fact that two or more representatives of different gene families are linked with HOX clusters is taken as evidence that these paralogous gene sets might have arisen from a single chromosomal segment through block or whole chromosome duplication events. This would imply that the constituent genes including the HOX clusters reflect the architecture of a single ancestral block (before vertebrate origin where all of these genes were linked in a single copy. Results In the present study we have employed the currently available set of protein data for a wide variety of vertebrate and invertebrate genomes to analyze the phylogenetic history of 11 multigene families with three or more of their representatives linked to human HOX clusters. A topology comparison approach revealed four discrete co-duplicated groups: group 1 involves the genes from GLI, HH, INHB, IGFBP (cluster-1, and SLC4A families; group 2 involves ERBB, ZNFN1A, and IGFBP (cluster-2 gene families; group 3 involves the HOX clusters and the SP gene family; group 4 involves the integrin beta chain and myosine light chain families. The distinct genes within each co-duplicated group share the same evolutionary history and are duplicated in concert with each other, while the constituent genes of two different co-duplicated groups may not share their evolutionary history and may not have duplicated simultaneously. Conclusion We conclude that co-duplicated groups may themselves be remnants of ancient small-scale duplications (involving chromosomal segments or gene-clusters which occurred at different time points during chordate evolution. Whereas the recent combination of genes from distinct co-duplicated groups on different chromosomal regions (human chromosomes 2q, 7, 12q, and 17q is

  20. CRISPR/Cas9 Promotes Functional Study of Testis Specific X-Linked Gene In Vivo.

    Directory of Open Access Journals (Sweden)

    Minyan Li

    Full Text Available Mammalian spermatogenesis is a highly regulated multistage process of sperm generation. It is hard to uncover the real function of a testis specific gene in vitro since the in vitro model is not yet mature. With the development of the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9 system, we can now rapidly generate knockout mouse models of testis specific genes to study the process of spermatogenesis in vivo. SYCP3-like X-linked 2 (SLX2 is a germ cell specific component, which contains a Cor1 domain and belongs to the XLR (X-linked, lymphocyte regulated family. Previous studies suggested that SLX2 might play an important role in mouse spermatogenesis based on its subcellular localization and interacting proteins. However, the function of SLX2 in vivo is still elusive. Here, to investigate the functions of SLX2 in spermatogenesis, we disrupted the Slx2 gene by using the CRISPR/Cas9 system. Since Slx2 is a testis specific X-linked gene, we obtained knockout male mice in the first generation and accelerated the study process. Compared with wild-type mice, Slx2 knockout mice have normal testis and epididymis. Histological observation of testes sections showed that Slx2 knockout affected none of the three main stages of spermatogenesis: mitosis, meiosis and spermiogenesis. In addition, we further confirmed that disruption of Slx2 did not affect the number of spermatogonial stem cells, meiosis progression or XY body formation by immunofluorescence analysis. As spermatogenesis was normal in Slx2 knockout mice, these mice were fertile. Taken together, we showed that Slx2 itself is not an essential gene for mouse spermatogenesis and CRISPR/Cas9 technique could speed up the functional study of testis specific X-linked gene in vivo.

  1. Fat accumulation in differentiated brown adipocytes is linked with expression of Hox genes.

    Science.gov (United States)

    Singh, Smita; Rajput, Yudhishthir S; Barui, Amit K; Sharma, Rajan; Datta, Tirtha K

    2016-03-01

    Homeobox (Hox) genes are involved in body plan of embryo along the anterior-posterior axis. Presence of several Hox genes in white adipose tissue (WAT) and brown adipose tissue (BAT) is indicative of involvement of Hox genes in adipogenesis. We propose that differentiation inducing agents viz. isobutyl-methyl-xanthine (IBMX), indomethacin, dexamethasone (DEX), triiodothyronine (T3) and insulin may regulate differentiation in brown adipose tissue through Hox genes. In vitro culture of brown fat stromalvascular fraction (SVF) in presence or absence of differentiation inducing agents was used for establishing relationship between fat accumulation in differentiated adipocytes and expression of Hox genes. Relative expression of Pref1, UCP1 and Hox genes was determined in different stages of adipogenesis. Presence or absence of IBMX, indomethacin and DEX during differentiation of proliferated pre-adipocytes resulted in marked differences in expression of Hox genes and lipid accumulation. In presence of these inducing agents, lipid accumulation as well as expression of HoxA1, HoxA5, HoxC4 &HoxC8 markedly enhanced. Irrespective of presence or absence of T3, insulin down regulates HoxA10. T3 results in over expression of HoxA5, HoxC4 and HoxC8 genes, whereas insulin up regulates expression of only HoxC8. Findings suggest that accumulation of fat in differentiated adipocytes is linked with expression of Hox genes.

  2. Cell cycle networks link gene expression dysregulation, mutation, and brain maldevelopment in autistic toddlers.

    Science.gov (United States)

    Pramparo, Tiziano; Lombardo, Michael V; Campbell, Kathleen; Barnes, Cynthia Carter; Marinero, Steven; Solso, Stephanie; Young, Julia; Mayo, Maisi; Dale, Anders; Ahrens-Barbeau, Clelia; Murray, Sarah S; Lopez, Linda; Lewis, Nathan; Pierce, Karen; Courchesne, Eric

    2015-12-14

    Genetic mechanisms underlying abnormal early neural development in toddlers with Autism Spectrum Disorder (ASD) remain uncertain due to the impossibility of direct brain gene expression measurement during critical periods of early development. Recent findings from a multi-tissue study demonstrated high expression of many of the same gene networks between blood and brain tissues, in particular with cell cycle functions. We explored relationships between blood gene expression and total brain volume (TBV) in 142 ASD and control male toddlers. In control toddlers, TBV variation significantly correlated with cell cycle and protein folding gene networks, potentially impacting neuron number and synapse development. In ASD toddlers, their correlations with brain size were lost as a result of considerable changes in network organization, while cell adhesion gene networks significantly correlated with TBV variation. Cell cycle networks detected in blood are highly preserved in the human brain and are upregulated during prenatal states of development. Overall, alterations were more pronounced in bigger brains. We identified 23 candidate genes for brain maldevelopment linked to 32 genes frequently mutated in ASD. The integrated network includes genes that are dysregulated in leukocyte and/or postmortem brain tissue of ASD subjects and belong to signaling pathways regulating cell cycle G1/S and G2/M phase transition. Finally, analyses of the CHD8 subnetwork and altered transcript levels from an independent study of CHD8 suppression further confirmed the central role of genes regulating neurogenesis and cell adhesion processes in ASD brain maldevelopment.

  3. Genomic architecture of MHC-linked odorant receptor gene repertoires among 16 vertebrate species.

    Science.gov (United States)

    Santos, Pablo Sandro Carvalho; Kellermann, Thomas; Uchanska-Ziegler, Barbara; Ziegler, Andreas

    2010-09-01

    The recent sequencing and assembly of the genomes of different organisms have shown that almost all vertebrates studied in detail so far have one or more clusters of genes encoding odorant receptors (OR) in close physical linkage to the major histocompatibility complex (MHC). It has been postulated that MHC-linked OR genes could be involved in MHC-influenced mate choice, comprising both pre- as well as post-copulatory mechanisms. We have therefore carried out a systematic comparison of protein sequences of these receptors from the genomes of man, chimpanzee, gorilla, orangutan, rhesus macaque, mouse, rat, dog, cat, cow, pig, horse, elephant, opossum, frog and zebra fish (amounting to a total of 559 protein sequences) in order to identify OR families exhibiting evolutionarily conserved MHC linkage. In addition, we compared the genomic structure of this region within these 16 species, accounting for presence or absence of OR gene families, gene order, transcriptional orientation and linkage to the MHC or framework genes. The results are presented in the form of gene maps and phylogenetic analyses that reveal largely concordant repertoires of gene families, at least among tetrapods, although each of the eight taxa studied (primates, rodents, ungulates, carnivores, proboscids, marsupials, amphibians and teleosts) exhibits a typical architecture of MHC (or MHC framework loci)-linked OR genes. Furthermore, the comparison of the genomic organization of this region has implications for phylogenetic relationships between closely related taxa, especially in disputed cases such as the evolutionary history of even- and odd-toed ungulates and carnivores. Finally, the largely conserved linkage between distinct OR genes and the MHC supports the concept that particular alleles within a given haplotype function in a concerted fashion during self-/non-self-discrimination processes in reproduction.

  4. Changes in barrier health status of the gill for grass carp (Ctenopharyngodon idella) during valine deficiency: Regulation of tight junction protein transcript, antioxidant status and apoptosis-related gene expression.

    Science.gov (United States)

    Feng, Lin; Luo, Jian-Bo; Jiang, Wei-Dan; Liu, Yang; Wu, Pei; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Zhang, Yong-An; Zhou, Xiao-Qiu

    2015-08-01

    This study investigated the effects of dietary valine on tight junction protein transcription, antioxidant status and apoptosis on grass carp gills (Ctenopharyngodon idella). Fish were fed six different experimental diets containing graded levels of valine (4.3, 8.0, 10.6, 13.1, 16.7, 19.1 g/kg). The results indicated that valine deficiency decreased Claudin b, Claudin 3, Occludin and ZO-1 transcription and increased Claudin 15 expression in the fish gill (P valine deficiency and valine supplementation did not have a significant effect on Claudin c and Claudin 12 expression in grass carp gills (P > 0.05). Valine deficiency also disrupted antioxidant status in the gill by decreasing anti-superoxide radicals and hydroxyl radical capacity, glutathione contents and the activities and mRNA levels of Cu/Zn superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) (P valine deficiency induced DNA fragmentation via the up-regulation of Caspase 3, Caspase 8 and Caspase 9 expressions (P valine deficiency impaired the structural integrity of fish gill by disrupted fish antioxidant defenses and regulating the expression of tight junction protein, cytokines, antioxidant enzymes, NF-κB p65, IκBα, TOR, Nrf2, Keap1 and apoptosis-related genes in the fish gill.

  5. Meiotic drive impacts expression and evolution of x-linked genes in stalk-eyed flies.

    Science.gov (United States)

    Reinhardt, Josephine A; Brand, Cara L; Paczolt, Kimberly A; Johns, Philip M; Baker, Richard H; Wilkinson, Gerald S

    2014-01-01

    Although sex chromosome meiotic drive has been observed in a variety of species for over 50 years, the genes causing drive are only known in a few cases, and none of these cases cause distorted sex-ratios in nature. In stalk-eyed flies (Teleopsis dalmanni), driving X chromosomes are commonly found at frequencies approaching 30% in the wild, but the genetic basis of drive has remained elusive due to reduced recombination between driving and non-driving X chromosomes. Here, we used RNAseq to identify transcripts that are differentially expressed between males carrying either a driving X (XSR) or a standard X chromosome (XST), and found hundreds of these, the majority of which are X-linked. Drive-associated transcripts show increased levels of sequence divergence (dN/dS) compared to a control set, and are predominantly expressed either in testes or in the gonads of both sexes. Finally, we confirmed that XSR and XST are highly divergent by estimating sequence differentiation between the RNAseq pools. We found that X-linked transcripts were often strongly differentiated (whereas most autosomal transcripts were not), supporting the presence of a relatively large region of recombination suppression on XSR presumably caused by one or more inversions. We have identified a group of genes that are good candidates for further study into the causes and consequences of sex-chromosome drive, and demonstrated that meiotic drive has had a profound effect on sequence evolution and gene expression of X-linked genes in this species.

  6. An AFLP marker linked to the leaf rust resistanc gene LrBi16 and test of allelism with Lr14a on chromosome arm 7BL

    Institute of Scientific and Technical Information of China (English)

    Peipei; Zhang; Huixin; Zhou; Caixia; Lan; Zaifeng; Li; Daqun; Liu

    2015-01-01

    Leaf rust(LR), caused by Puccinia triticina, is one of the most widespread diseases of common wheat(Triticum aestivum L.) worldwide. The LR resistance gene Lr Bi16 has been mapped on chromosome arm 7BL in Chinese wheat cultivar Bimai 16 and was closely linked to SSR loci Xcfa2257 and Xgwm344 with genetic distances of 2.8 c M and 2.9 c M, respectively. In the present study, a total of 304 AFLP primer pairs were used to screen Bimai 16 and Thatcher and resistant and susceptible DNA bulks. The polymorphic AFLP marker P-ATT/M-CGC173 bp was used to genotype F2 and F3populations to identify markers more closely linked to Lr Bi16. Marker P-ATT/M-CGC173 bp was tightly linked to Lr Bi16 with a genetic distance of0.5 c M. As Lr Bi16 was mapped near the Lr14 a locus, 809 F2 plants from the Bimai 16/RL6013(Lr14a) cross were inoculated with the Pt pathotype FHNQ to test the allelism of Lr14 a and Lr Bi16. All of the F2 plants were resistant to FHNQ(IT between; and 2), suggesting that Lr14 a and Lr Bi16 are allelic.

  7. An AFLP marker linked to the leaf rust resistance gene LrBi16 and test of allelism with Lr14a on chromosome arm 7BL

    Directory of Open Access Journals (Sweden)

    Peipei Zhang

    2015-04-01

    Full Text Available Leaf rust (LR, caused by Puccinia triticina, is one of the most widespread diseases of common wheat (Triticum aestivum L. worldwide. The LR resistance gene LrBi16 has been mapped on chromosome arm 7BL in Chinese wheat cultivar Bimai 16 and was closely linked to SSR loci Xcfa2257 and Xgwm344 with genetic distances of 2.8 cM and 2.9 cM, respectively. In the present study, a total of 304 AFLP primer pairs were used to screen Bimai 16 and Thatcher and resistant and susceptible DNA bulks. The polymorphic AFLP marker P-ATT/M-CGC173 bp was used to genotype F2 and F3 populations to identify markers more closely linked to LrBi16. Marker P-ATT/M-CGC173 bp was tightly linked to LrBi16 with a genetic distance of 0.5 cM. As LrBi16 was mapped near the Lr14a locus, 809 F2 plants from the Bimai 16/RL6013 (Lr14a cross were inoculated with the Pt pathotype FHNQ to test the allelism of Lr14a and LrBi16. All of the F2 plants were resistant to FHNQ (IT between; and 2, suggesting that Lr14a and LrBi16 are allelic.

  8. Bioreducible cross-linked nanoshell enhances gene transfection of polycation/DNA polyplex in vivo.

    Science.gov (United States)

    Piao, Ji-Gang; Ding, Sheng-Gang; Yang, Lu; Hong, Chun-Yan; You, Ye-Zi

    2014-08-11

    In this study, we have prepared a self-cross-linking PEG-based branched polymer, which easily forms a bioreducible nanoshell around polyplexes of cationic polymer and DNA, simply via heating the polyplex dispersions in the presence of this self-cross-linking branched polymer. This nanoshell can prevent the polyplex from dissociation and aggregation in physiological fluids without inhibiting the electrostatic interactions between the polymer and DNA. Furthermore, glutathione (GSH) can act as a stimulus to open the nanoshell after it has entered the cell. The polyplexes coated with the bioreducible nanoshell show an obvious enhancement in gene transfection in vivo compared with bare polyplexes.

  9. Dosage Compensation of X-Linked Muller Element F Genes but Not X-Linked Transgenes in the Australian Sheep Blowfly.

    Science.gov (United States)

    Linger, Rebecca J; Belikoff, Esther J; Scott, Maxwell J

    2015-01-01

    In most animals that have X and Y sex chromosomes, chromosome-wide mechanisms are used to balance X-linked gene expression in males and females. In the fly Drosophila melanogaster, the dosage compensation mechanism also generally extends to X-linked transgenes. Over 70 transgenic lines of the Australian sheep blowfly Lucilia cuprina have been made as part of an effort to develop male-only strains for a genetic control program of this major pest of sheep. All lines carry a constitutively expressed fluorescent protein marker gene. In all 12 X-linked lines, female larvae show brighter fluorescence than male larvae, suggesting the marker gene is not dosage compensated. This has been confirmed by quantitative RT-PCR for selected lines. To determine if endogenous X-linked genes are dosage compensated, we isolated 8 genes that are orthologs of genes that are on the fourth chromosome in D. melanogaster. Recent evidence suggests that the D. melanogaster fourth chromosome, or Muller element F, is the ancestral X chromosome in Diptera that has reverted to an autosome in Drosophila species. We show by quantitative PCR of male and female DNA that 6 of the 8 linkage group F genes reside on the X chromosome in L. cuprina. The other two Muller element F genes were found to be autosomal in L. cuprina, whereas two Muller element B genes were found on the same region of the X chromosome as the L. cuprina orthologs of the D. melanogaster Ephrin and gawky genes. We find that the L. cuprina X chromosome genes are equally expressed in males and females (i.e., fully dosage compensated). Thus, unlike in Drosophila, it appears that the Lucilia dosage compensation system is specific for genes endogenous to the X chromosome and cannot be co-opted by recently arrived transgenes.

  10. Two tobacco AP1-like gene promoters drive highly specific, tightly regulated and unique expression patterns during floral transition, initiation and development.

    Science.gov (United States)

    Zhang, Jinjin; Yan, Guohua; Wen, Zhifeng; An, Young-Qiang; Singer, Stacy D; Liu, Zongrang

    2014-02-01

    The genetic engineering of agronomic traits requires an array of highly specific and tightly regulated promoters that drive expression in floral tissues. In this study, we isolated and characterized two tobacco APETALA1-like (AP1-like) promoters (termed NtAP1La and NtAP1Lb1) in transgenic plants using the GUS reporter system, along with tissue-specific ablation analyses. Our results demonstrated that the two promoters are active in floral inflorescences but not in vegetative apical meristems or other vegetative tissues, as reflected by strong GUS staining and DT-A-mediated ablation of apical shoot tips during reproductive but not vegetative growth. We also showed that the NtAP1Lb1 promoter was more active than NtAP1La in inflorescences, as the former yielded higher frequencies and greater phenotypic evidence of tissue ablation compared to the latter. We further revealed that both promoters were uniformly expressed in the meristems of stage 1 and 2 floral buds, but were differentially expressed in floral organs later during development. While NtAP1La was found to be active in stage 4-5 carpels, later becoming confined to ovary tissue from stage 9 onwards, NtAP1Lb1 activity was apparent in all floral organs from stages 3 to 7, becoming completely absent in all floral organs from stage 11 onward. Therefore, it seems that the two tobacco promoters have acquired similar but distinct inflorescence-, floral meristem- and floral organ-specific and development-dependent regulatory features without any leaky activity in vegetative tissues. These features are novel and have rarely been observed in other flower-specific promoters characterized to date. The potential application of these promoters for engineering sterility, increasing biomass production and modifying flower architecture, as well as their putative use in flower-specific transgene excision, will be discussed.

  11. Demystifying the secret mission of enhancers: linking distal regulatory elements to target genes.

    Science.gov (United States)

    Yao, Lijing; Berman, Benjamin P; Farnham, Peggy J

    2015-01-01

    Enhancers are short regulatory sequences bound by sequence-specific transcription factors and play a major role in the spatiotemporal specificity of gene expression patterns in development and disease. While it is now possible to identify enhancer regions genomewide in both cultured cells and primary tissues using epigenomic approaches, it has been more challenging to develop methods to understand the function of individual enhancers because enhancers are located far from the gene(s) that they regulate. However, it is essential to identify target genes of enhancers not only so that we can understand the role of enhancers in disease but also because this information will assist in the development of future therapeutic options. After reviewing models of enhancer function, we discuss recent methods for identifying target genes of enhancers. First, we describe chromatin structure-based approaches for directly mapping interactions between enhancers and promoters. Second, we describe the use of correlation-based approaches to link enhancer state with the activity of nearby promoters and/or gene expression. Third, we describe how to test the function of specific enhancers experimentally by perturbing enhancer-target relationships using high-throughput reporter assays and genome editing. Finally, we conclude by discussing as yet unanswered questions concerning how enhancers function, how target genes can be identified, and how to distinguish direct from indirect changes in gene expression mediated by individual enhancers.

  12. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy.

    Science.gov (United States)

    Bione, S; Maestrini, E; Rivella, S; Mancini, M; Regis, S; Romeo, G; Toniolo, D

    1994-12-01

    Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked recessive disorder characterized by slowly progressing contractures, wasting of skeletal muscle and cardiomyopathy. Heart block is a frequent cause of death. The disease gene has been mapped to distal Xq28. Among many genes in this region, we selected eight transcripts expressed at high levels in skeletal muscle, heart and/or brain as the best candidates for the disease. We now report, in all five patients studied, unique mutations in one of the genes, STA: these mutations result in the loss of all or part of the protein. The EDMD gene encodes a novel serine-rich protein termed emerin, which contains a 20 amino acid hydrophobic domain at the C terminus, similar to that described for many membrane proteins of the secretory pathway involved in vesicular transport.

  13. Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus

    DEFF Research Database (Denmark)

    Colombo, Carlo; Porzio, Ottavia; Liu, Ming;

    2008-01-01

    Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation...... in the Ins2 gene exhibits PNDM associated with pancreatic beta cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset...... of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM....

  14. Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria

    DEFF Research Database (Denmark)

    Zhang, Qingfeng; Siegel, T Nicolai; Martins, Rafael M

    2014-01-01

    malaria. The mechanism determining upsA activation remains unknown. Here we show that an entirely new type of gene silencing mechanism involving an exonuclease-mediated degradation of nascent RNA controls the silencing of genes linked to severe malaria. We identify a novel chromatin......-associated exoribonuclease, termed PfRNase II, that controls the silencing of upsA var genes by marking their transcription start site and intron-promoter regions leading to short-lived cryptic RNA. Parasites carrying a deficient PfRNase II gene produce full-length upsA var transcripts and intron-derived antisense long non......-coding RNA. The presence of stable upsA var transcripts overcomes monoallelic expression, resulting in the simultaneous expression of both upsA and upsC type PfEMP1 proteins on the surface of individual infected red blood cells. In addition, we observe an inverse relationship between transcript levels of Pf...

  15. A bi-ordering approach to linking gene expression with clinical annotations in gastric cancer

    Directory of Open Access Journals (Sweden)

    Leckie Christopher

    2010-09-01

    Full Text Available Abstract Background In the study of cancer genomics, gene expression microarrays, which measure thousands of genes in a single assay, provide abundant information for the investigation of interesting genes or biological pathways. However, in order to analyze the large number of noisy measurements in microarrays, effective and efficient bioinformatics techniques are needed to identify the associations between genes and relevant phenotypes. Moreover, systematic tests are needed to validate the statistical and biological significance of those discoveries. Results In this paper, we develop a robust and efficient method for exploratory analysis of microarray data, which produces a number of different orderings (rankings of both genes and samples (reflecting correlation among those genes and samples. The core algorithm is closely related to biclustering, and so we first compare its performance with several existing biclustering algorithms on two real datasets - gastric cancer and lymphoma datasets. We then show on the gastric cancer data that the sample orderings generated by our method are highly statistically significant with respect to the histological classification of samples by using the Jonckheere trend test, while the gene modules are biologically significant with respect to biological processes (from the Gene Ontology. In particular, some of the gene modules associated with biclusters are closely linked to gastric cancer tumorigenesis reported in previous literature, while others are potentially novel discoveries. Conclusion In conclusion, we have developed an effective and efficient method, Bi-Ordering Analysis, to detect informative patterns in gene expression microarrays by ranking genes and samples. In addition, a number of evaluation metrics were applied to assess both the statistical and biological significance of the resulting bi-orderings. The methodology was validated on gastric cancer and lymphoma datasets.

  16. A bi-ordering approach to linking gene expression with clinical annotations in gastric cancer.

    Science.gov (United States)

    Shi, Fan; Leckie, Christopher; MacIntyre, Geoff; Haviv, Izhak; Boussioutas, Alex; Kowalczyk, Adam

    2010-09-23

    In the study of cancer genomics, gene expression microarrays, which measure thousands of genes in a single assay, provide abundant information for the investigation of interesting genes or biological pathways. However, in order to analyze the large number of noisy measurements in microarrays, effective and efficient bioinformatics techniques are needed to identify the associations between genes and relevant phenotypes. Moreover, systematic tests are needed to validate the statistical and biological significance of those discoveries. In this paper, we develop a robust and efficient method for exploratory analysis of microarray data, which produces a number of different orderings (rankings) of both genes and samples (reflecting correlation among those genes and samples). The core algorithm is closely related to biclustering, and so we first compare its performance with several existing biclustering algorithms on two real datasets - gastric cancer and lymphoma datasets. We then show on the gastric cancer data that the sample orderings generated by our method are highly statistically significant with respect to the histological classification of samples by using the Jonckheere trend test, while the gene modules are biologically significant with respect to biological processes (from the Gene Ontology). In particular, some of the gene modules associated with biclusters are closely linked to gastric cancer tumorigenesis reported in previous literature, while others are potentially novel discoveries. In conclusion, we have developed an effective and efficient method, Bi-Ordering Analysis, to detect informative patterns in gene expression microarrays by ranking genes and samples. In addition, a number of evaluation metrics were applied to assess both the statistical and biological significance of the resulting bi-orderings. The methodology was validated on gastric cancer and lymphoma datasets.

  17. Molecular markers linked to the apple scab resistance gene Vbj derived from Malus baccata jackii.

    Science.gov (United States)

    Gygax, M; Gianfranceschi, L; Liebhard, R; Kellerhals, M; Gessler, C; Patocchi, A

    2004-11-01

    Breeding for scab-resistant apple cultivars by pyramiding several resistance genes in the same genetic background is a promising way to control apple scab caused by the fungus Venturia inaequalis. To achieve this goal, DNA markers linked to the genes of interest are required in order to select seedlings with the desired resistance allele combinations. For several apple scab resistance genes, molecular markers are already available; but until now, none existed for the apple scab resistance gene Vbj originating from the crab apple Malus baccata jackii. Using bulk segregant analysis, three RAPD markers linked to Vbj were first identified. These markers were transformed into more reliable sequence-characterised amplified region (SCAR) markers that proved to be co-dominant. In addition, three SSR markers and one SCAR were identified by comparing homologous linkage groups of existing genetic maps. Discarding plants showing genotype-phenotype incongruence (GPI plants) plants, a linkage map was calculated. Vbj mapped between the markers CH05e03 (SSR) and T6-SCAR, at 0.6 cM from CH05e03 and at 3.9 cM from T6-SCAR. Without the removal of the GPI plants, Vbj was placed 15 cM away from the closest markers. Problems and pitfalls due to GPI plants and the consequences for mapping the resistance gene accurately are discussed. Finally, the usefulness of co-dominant markers for pedigree analysis is also demonstrated.

  18. [Progress on X-linked mental retardation related gene JARID1C].

    Science.gov (United States)

    Lei, Xu; Gao, Xiao-Cai; Zhang, Fu-Chang

    2010-03-01

    JARID1C is one of the genes related to X-linked mental retardation. Its express product influences transcription and expression of the related genes in brain nervous system, and may be associated with human cognitive ability. Study on the functions of JARID1C not only helps to understand its molecular role in mental retardation and human cognitive ability, but also provides references for clinical diagnosis and prevention of mental retardation. This article reviews the progresses on JARID1C in location, isolation, physiological functions, and cognitive functions of its encoding product. The future re-search work of JARID1C is also discussed.

  19. Klinefelter syndrome comorbidities linked to increased X chromosome gene dosage and altered protein interactome activity

    DEFF Research Database (Denmark)

    Belling, Kirstine González-Izarzugaza; Russo, Francesco; Jensen, Anders Boeck

    2017-01-01

    Jak-STAT pathway, dysregulated genes important for disturbed immune system (IL4), energy balance (POMC and LEP) and erythropoietin signalling in KS. We present an extended epidemiological study that links KS comorbidities to the molecular level and identify potential causal players in the disease...... of co-expressed modules as well as central hubs and gene dosage perturbed protein complexes in a KS comorbidity network build from known disease proteins and their protein-protein interactions. The systems biology approaches together pointed to novel aspects of KS disease phenotypes including perturbed...

  20. Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Bartuma, Katarina; Dominguez-Valentin, Mev

    2014-01-01

    Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer...... ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified...... for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic...

  1. Reeling of tight fit pipe

    NARCIS (Netherlands)

    Focke, E.S.

    2007-01-01

    If it would be possible to install Tight Fit Pipe by means of reeling, it would be an attractive new option for the exploitation of offshore oil and gas fields containing corrosive hydrocarbons. Tight Fit Pipe is a mechanically bonded double walled pipe where a corrosion resistant alloy liner pipe

  2. Gene expression centroids that link with low intrinsic aerobic exercise capacity and complex disease risk

    OpenAIRE

    Kivelä, Riikka; Silvennoinen, Mika; Lehti, Maarit; Rinnankoski-Tuikka,, Rita; Purhonen, Tatja; Ketola, Tarmo; Pullinen, Katri; Vuento, Meri; Mutanen, Niina; Maureen A Sartor; Reunanen, Hilkka; Koch, Lauren G.; Britton, Steven L.; Kainulainen, Heikki

    2010-01-01

    A strong link exists between low aerobic exercise capacity and complex metabolic diseases. To probe this linkage, we utilized rat models of low and high intrinsic aerobic endurance running capacity that differ also in the risk for metabolic syndrome. We investigated in skeletal muscle gene-phenotype relationships that connect aerobic endurance capacity with metabolic disease risk factors. The study compared 12 high capacity runners (HCRs) and 12 low capacity runners (LCRs) from generation 18 ...

  3. Immunoregulatory network and cancer-associated genes: molecular links and relevance to aging

    Directory of Open Access Journals (Sweden)

    Robi Tacutu

    2011-09-01

    Full Text Available Although different aspects of cancer immunity are a subject of intensive investigation, an integrative view on the possible molecular links between immunoregulators and cancer-associated genes has not yet been fully considered. In an attempt to get more insights on the problem, we analyzed these links from a network perspective. We showed that the immunoregulators could be organized into a miRNA-regulated PPI network-the immunoregulatory network. This network has numerous links with cancer, including (i cancerassociated immunoregulators, (ii direct and indirect protein-protein interactions (through the common protein partners, and (iii common miRNAs. These links may largely determine the interactions between the host's immunity and cancer, supporting the possibility for co-expression and post-transcriptional co-regulation of immunoregulatory and cancer genes. In addition, the connection between immunoregulation and cancer may lie within the realm of cancer-predisposing conditions, such as chronic inflammation and fibroproliferative repair. A gradual, age-related deterioration of the integrity and functionality of the immunoregulaory network could contribute to impaired immunity and generation of cancer-predisposing conditions.

  4. Sex-dimorphic gene expression and ineffective dosage compensation of Z-linked genes in gastrulating chicken embryos

    Directory of Open Access Journals (Sweden)

    Mathur Sachin

    2010-01-01

    Full Text Available Abstract Background Considerable progress has been made in our understanding of sex determination and dosage compensation mechanisms in model organisms such as C. elegans, Drosophila and M. musculus. Strikingly, the mechanism involved in sex determination and dosage compensation are very different among these three model organisms. Birds present yet another situation where the heterogametic sex is the female. Sex determination is still poorly understood in birds and few key determinants have so far been identified. In contrast to most other species, dosage compensation of bird sex chromosomal genes appears rather ineffective. Results By comparing microarrays from microdissected primitive streak from single chicken embryos, we identified a large number of genes differentially expressed between male and female embryos at a very early stage (Hamburger and Hamilton stage 4, long before any sexual differentiation occurs. Most of these genes are located on the Z chromosome, which indicates that dosage compensation is ineffective in early chicken embryos. Gene ontology analyses, using an enhanced annotation tool for Affymetrix probesets of the chicken genome developed in our laboratory (called Manteia, show that among these male-biased genes found on the Z chromosome, more than 20 genes play a role in sex differentiation. Conclusions These results corroborate previous studies demonstrating the rather inefficient dosage compensation for Z chromosome in birds and show that this sexual dimorphism in gene regulation is observed long before the onset of sexual differentiation. These data also suggest a potential role of non-compensated Z-linked genes in somatic sex differentiation in birds.

  5. Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q

    Energy Technology Data Exchange (ETDEWEB)

    Bell, G.I.; Xiang, Kunsan; Newman, M.V.; Wu, Songhua; Cox, N.J. (Univ. of Chicago, IL (United States)); Wright, L.G.; Spielman, R.S. (Univ. of Pennsylvania, Philadelphia (United States)); Fajans, S.S. (Univ. of Michigan, Ann Arbor (United States))

    1991-02-15

    Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterized by an early age of onset, usually before 25 years of age, and an autosomal dominant mode of inheritance. The largest and best-studies MODY pedigree is the TW family. The majority of the diabetic subjects in this pedigree has a reduced and delayed insulin-secretory response to glucose, and it has been proposed that this abnormal response is the manifestation of the basic genetic defect that leads to diabetes. Using DNA from members of the TW family, the authors tested more than 75 DNA markers for linkage with MODY. A DNA polymorphism in the adenosine deaminase gene (ADA) on the long arm of chromosome 20 was found to cosegregate with MODY. The maximum logarithm of adds (lod score) for linkage between MODY and ADA was 5.25 at a recombination fraction of 0.00. These results indicate that the odds are {gt}178,000:1 that the gene responsible for MODY is this family is tightly linked to the ADA gene on chromosome 20q.

  6. Genetics and mapping of the R11 gene conferring resistance to recently emerged rust races, tightly linked to male fertility restoration, in sunflower (Helianthus annuus L.)

    Science.gov (United States)

    Sunflower oil is one of the major sources of edible oil. As the second largest hybrid crop in the world, hybrid sunflowers are developed by using the PET1 cytoplasmic male sterility system that contributes a 20% yield advantage over the open-pollinated varieties. However, sunflower production in Nor...

  7. Winge's sex-linked color patterns and SDL in the guppy: genes or gene complexes?

    Directory of Open Access Journals (Sweden)

    I. Valentin Petrescu-Mag

    2009-01-01

    Full Text Available In Poecilia reticulata, different phenotypes appear due to dominance, codominance, poligeny, or some demonstrated interallelic interactions. Recent(both molecular and classical investigations suggest a mechanism of expression of several different loci in a single color pattern, resulting in high numbers of possible color pattern phenotypes. The color pattern seems to be determined by complex interactions of many genes (at the same locus or not, located on the same chromosome or not, under variable environmental conditions. For example, the Maculatus color pattern is due to the presence of  both Maculatus red and Maculatus black elements. On their turn, having in view the latest definitions of  the gene, both Maculatus red and Maculatus black could have a composite nature, too. Sexdetermination in the guppy is studied since the 1920s. The deepest mechanism of sex determination is not clear yet, but classical studies of Winge early in the past century and recent molecular studies revealed a possible composite nature of the so called master sex determining gene, located at SDL of the Y chromosome.

  8. Angiotensin II type 1 receptor (A1166C) gene polymorphism in ...

    African Journals Online (AJOL)

    H. El-banawy

    2015-01-05

    Jan 5, 2015 ... Renal function and blood pressure are tightly linked. .... (SNP) of the AT1R gene was done by polymerase chain ... Visualization of the digestion products was done on 2% ..... NY: Cold Spring Harbor Laboratory Press; 2006,.

  9. Dietary phenylalanine-improved intestinal barrier health in young grass carp (Ctenopharyngodon idella) is associated with increased immune status and regulated gene expression of cytokines, tight junction proteins, antioxidant enzymes and related signalling molecules.

    Science.gov (United States)

    Feng, Lin; Li, Wen; Liu, Yang; Jiang, Wei-Dan; Kuang, Sheng-Yao; Jiang, Jun; Tang, Ling; Wu, Pei; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2015-08-01

    The present work evaluated the effects of dietary phenylalanine (Phe) on the intestinal immune response, tight junction proteins transcript abundance, and the gene expression of immune- and antioxidant-related signalling molecules in the intestine. In addition, the dietary Phe (and Phe + Tyr) requirement of young grass carp (Ctenopharyngodon idella) was also estimated. Fish were fed fish meal-casein-gelatin based diets (302.3 g crude protein kg(-1)) containing 3.4 (basal diet), 6.1, 9.1, 11.5, 14.0 and 16.8 g Phe kg(-1) with a fixed amount of 10.7 g tyrosine kg(-1) for 8 weeks. The results showed that Phe deficiency or excess Phe reduced the lysozyme and acid phosphatase activities and complement C 3 content in the intestine (P 0.05). Gene expression of interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1), target of rapamycin (TOR) and inhibitor of nuclear factor κBα (IκBα) in proximal intestine (PI), mid intestine (MI) and distal intestine (DI) increased as dietary Phe increased up to 6.1, 9.1, 11.5 and 14.0 g kg(-1), respectively (P < 0.05). However, interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α) and nuclear factor-κB p65 (NF-κB p65) mRNA levels showed opposite tendencies. In addition, the mRNA level of superoxide dismutase (SOD) was significantly lower in the intestinal tissue of the group fed a diet with Phe levels of 16.8 g kg(-1) than in those of other groups (P < 0.05). The expression of NF-E2-related factor 2 (Nrf2) gene was increased as dietary Phe increased up to 9.1 g kg(-1) (P < 0.05). In conclusion, Phe improved intestinal immune status, and regulated gene expression of cytokines, tight junction proteins, antioxidant enzymes, NF-κB p65, IκBα, TOR, and Nrf2 in the fish intestine. Based on the quadratic regression analysis of lysozyme activity at a 95% maximum, the dietary Phe requirement of young grass carp (256-629 g) was estimated to be 8.31 g kg(-1), corresponding to 2.75 g 100 g(-1) protein.

  10. Linking Advanced Visualization and MATLAB for the Analysis of 3D Gene Expression Data

    Energy Technology Data Exchange (ETDEWEB)

    Ruebel, Oliver; Keranen, Soile V.E.; Biggin, Mark; Knowles, David W.; Weber, Gunther H.; Hagen, Hans; Hamann, Bernd; Bethel, E. Wes

    2011-03-30

    Three-dimensional gene expression PointCloud data generated by the Berkeley Drosophila Transcription Network Project (BDTNP) provides quantitative information about the spatial and temporal expression of genes in early Drosophila embryos at cellular resolution. The BDTNP team visualizes and analyzes Point-Cloud data using the software application PointCloudXplore (PCX). To maximize the impact of novel, complex data sets, such as PointClouds, the data needs to be accessible to biologists and comprehensible to developers of analysis functions. We address this challenge by linking PCX and Matlab via a dedicated interface, thereby providing biologists seamless access to advanced data analysis functions and giving bioinformatics researchers the opportunity to integrate their analysis directly into the visualization application. To demonstrate the usefulness of this approach, we computationally model parts of the expression pattern of the gene even skipped using a genetic algorithm implemented in Matlab and integrated into PCX via our Matlab interface.

  11. Promotion of growth by Coenzyme Q10 is linked to gene expression in C. elegans.

    Science.gov (United States)

    Fischer, Alexandra; Niklowitz, Petra; Menke, Thomas; Döring, Frank

    2014-10-03

    Coenzyme Q (CoQ, ubiquinone) is an essential component of the respiratory chain, a cofactor of pyrimidine biosynthesis and acts as an antioxidant in extra mitochondrial membranes. More recently CoQ has been identified as a modulator of apoptosis, inflammation and gene expression. CoQ deficient Caenorhabditis elegans clk-1 mutants show several phenotypes including a delayed postembryonic growth. Using wild type and two clk-1 mutants, here we established an experimental set-up to study the consequences of endogenous CoQ deficiency or exogenous CoQ supply on gene expression and growth. We found that a deficiency of endogenous CoQ synthesis down-regulates a cluster of genes that are important for growth (i.e., RNA polymerase II, eukaryotic initiation factor) and up-regulates oxidation reactions (i.e., cytochrome P450, superoxide dismutase) and protein interactions (i.e., F-Box proteins). Exogenous CoQ supply partially restores the expression of these genes as well as the growth retardation of CoQ deficient clk-1 mutants. On the other hand exogenous CoQ supply does not alter the expression of a further sub-set of genes. These genes are involved in metabolism (i.e., succinate dehydrogenase complex), cell signalling or synthesis of lectins. Thus, our work provides a comprehensive overview of genes which can be modulated in their expression by endogenous or exogenous CoQ. As growth retardation in CoQ deficiency is linked to the gene expression profile we suggest that CoQ promotes growth via gene expression.

  12. A direct molecular link between the autism candidate gene RORa and the schizophrenia candidate MIR137

    Science.gov (United States)

    Devanna, Paolo; Vernes, Sonja C.

    2014-02-01

    Retinoic acid-related orphan receptor alpha gene (RORa) and the microRNA MIR137 have both recently been identified as novel candidate genes for neuropsychiatric disorders. RORa encodes a ligand-dependent orphan nuclear receptor that acts as a transcriptional regulator and miR-137 is a brain enriched small non-coding RNA that interacts with gene transcripts to control protein levels. Given the mounting evidence for RORa in autism spectrum disorders (ASD) and MIR137 in schizophrenia and ASD, we investigated if there was a functional biological relationship between these two genes. Herein, we demonstrate that miR-137 targets the 3'UTR of RORa in a site specific manner. We also provide further support for MIR137 as an autism candidate by showing that a large number of previously implicated autism genes are also putatively targeted by miR-137. This work supports the role of MIR137 as an ASD candidate and demonstrates a direct biological link between these previously unrelated autism candidate genes.

  13. Four linked genes participate in controlling sporulation efficiency in budding yeast.

    Directory of Open Access Journals (Sweden)

    Giora Ben-Ari

    2006-11-01

    Full Text Available Quantitative traits are conditioned by several genetic determinants. Since such genes influence many important complex traits in various organisms, the identification of quantitative trait loci (QTLs is of major interest, but still encounters serious difficulties. We detected four linked genes within one QTL, which participate in controlling sporulation efficiency in Saccharomyces cerevisiae. Following the identification of single nucleotide polymorphisms by comparing the sequences of 145 genes between the parental strains SK1 and S288c, we analyzed the segregating progeny of the cross between them. Through reciprocal hemizygosity analysis, four genes, RAS2, PMS1, SWS2, and FKH2, located in a region of 60 kilobases on Chromosome 14, were found to be associated with sporulation efficiency. Three of the four "high" sporulation alleles are derived from the "low" sporulating strain. Two of these sporulation-related genes were verified through allele replacements. For RAS2, the causative variation was suggested to be a single nucleotide difference in the upstream region of the gene. This quantitative trait nucleotide accounts for sporulation variability among a set of ten closely related winery yeast strains. Our results provide a detailed view of genetic complexity in one "QTL region" that controls a quantitative trait and reports a single nucleotide polymorphism-trait association in wild strains. Moreover, these findings have implications on QTL identification in higher eukaryotes.

  14. Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency.

    Science.gov (United States)

    De Ravin, Suk See; Wu, Xiaolin; Moir, Susan; Anaya-O'Brien, Sandra; Kwatemaa, Nana; Littel, Patricia; Theobald, Narda; Choi, Uimook; Su, Ling; Marquesen, Martha; Hilligoss, Dianne; Lee, Janet; Buckner, Clarissa M; Zarember, Kol A; O'Connor, Geraldine; McVicar, Daniel; Kuhns, Douglas; Throm, Robert E; Zhou, Sheng; Notarangelo, Luigi D; Hanson, I Celine; Cowan, Mort J; Kang, Elizabeth; Hadigan, Coleen; Meagher, Michael; Gray, John T; Sorrentino, Brian P; Malech, Harry L

    2016-04-20

    X-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations inIL2RGencoding the common chain (γc) of several interleukin receptors. Gamma-retroviral (γRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector γc transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1.

  15. Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.

    Science.gov (United States)

    Horino, Satoshi; Uchiyama, Toru; So, Takanori; Nagashima, Hiroyuki; Sun, Shu-Lan; Sato, Miki; Asao, Atsuko; Haji, Yoichi; Sasahara, Yoji; Candotti, Fabio; Tsuchiya, Shigeru; Kure, Shigeo; Sugamura, Kazuo; Ishii, Naoto

    2013-01-01

    X-linked severe combined immunodeficiency (SCID-X1) is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc) gene, and characterized by a complete defect of T and natural killer (NK) cells. Gene therapy for SCID-X1 using conventional retroviral (RV) vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV) vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO) mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1.

  16. Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.

    Directory of Open Access Journals (Sweden)

    Satoshi Horino

    Full Text Available X-linked severe combined immunodeficiency (SCID-X1 is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc gene, and characterized by a complete defect of T and natural killer (NK cells. Gene therapy for SCID-X1 using conventional retroviral (RV vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1.

  17. Gene Therapy Model of X-linked Severe Combined Immunodeficiency Using a Modified Foamy Virus Vector

    Science.gov (United States)

    Horino, Satoshi; Uchiyama, Toru; So, Takanori; Nagashima, Hiroyuki; Sun, Shu-lan; Sato, Miki; Asao, Atsuko; Haji, Yoichi; Sasahara, Yoji; Candotti, Fabio; Tsuchiya, Shigeru; Kure, Shigeo; Sugamura, Kazuo; Ishii, Naoto

    2013-01-01

    X-linked severe combined immunodeficiency (SCID-X1) is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc) gene, and characterized by a complete defect of T and natural killer (NK) cells. Gene therapy for SCID-X1 using conventional retroviral (RV) vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV) vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO) mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1. PMID:23990961

  18. Gene Expression Profiling in Hereditary, BRCA1-linked Breast Cancer: Preliminary Report

    Directory of Open Access Journals (Sweden)

    Dudaladava Volha

    2006-01-01

    Full Text Available Abstract Global analysis of gene expression by DNA microarrays is nowadays a widely used tool, especially relevant for cancer research. It helps the understanding of complex biology of cancer tissue, allows identification of novel molecular markers, reveals previously unknown molecular subtypes of cancer that differ by clinical features like drug susceptibility or general prognosis. Our aim was to compare gene expression profiles in breast cancer that develop against a background of inherited predisposing mutations versus sporadic breast cancer. In this preliminary study we analysed seven hereditary, BRCA1 mutation-linked breast cancer tissues and seven sporadic cases that were carefully matched by histopathology and ER status. Additionally, we analysed 6 samples of normal breast tissue. We found that while the difference in gene expression profiles between tumour tissue and normal breast can be easily recognized by unsupervised algorithms, the difference between those two types of tumours is more discrete. However, by supervised methods of data analysis, we were able to select a set of genes that may differentiate between hereditary and sporadic tumours. The most significant difference concerns genes that code for proteins engaged in regulation of transcription, cellular metabolism, signalling, proliferation and cell death. Microarray results for chosen genes (TOB1, SEPHS2 were validated by real-time RT-PCR.

  19. An algorithm for network-based gene prioritization that encodes knowledge both in nodes and in links.

    Directory of Open Access Journals (Sweden)

    Chad Kimmel

    Full Text Available BACKGROUND: Candidate gene prioritization aims to identify promising new genes associated with a disease or a biological process from a larger set of candidate genes. In recent years, network-based methods - which utilize a knowledge network derived from biological knowledge - have been utilized for gene prioritization. Biological knowledge can be encoded either through the network's links or nodes. Current network-based methods can only encode knowledge through links. This paper describes a new network-based method that can encode knowledge in links as well as in nodes. RESULTS: We developed a new network inference algorithm called the Knowledge Network Gene Prioritization (KNGP algorithm which can incorporate both link and node knowledge. The performance of the KNGP algorithm was evaluated on both synthetic networks and on networks incorporating biological knowledge. The results showed that the combination of link knowledge and node knowledge provided a significant benefit across 19 experimental diseases over using link knowledge alone or node knowledge alone. CONCLUSIONS: The KNGP algorithm provides an advance over current network-based algorithms, because the algorithm can encode both link and node knowledge. We hope the algorithm will aid researchers with gene prioritization.

  20. Potential translational targets revealed by linking mouse grooming behavioral phenotypes to gene expression using public databases.

    Science.gov (United States)

    Roth, Andrew; Kyzar, Evan J; Cachat, Jonathan; Stewart, Adam Michael; Green, Jeremy; Gaikwad, Siddharth; O'Leary, Timothy P; Tabakoff, Boris; Brown, Richard E; Kalueff, Allan V

    2013-01-10

    Rodent self-grooming is an important, evolutionarily conserved behavior, highly sensitive to pharmacological and genetic manipulations. Mice with aberrant grooming phenotypes are currently used to model various human disorders. Therefore, it is critical to understand the biology of grooming behavior, and to assess its translational validity to humans. The present in-silico study used publicly available gene expression and behavioral data obtained from several inbred mouse strains in the open-field, light-dark box, elevated plus- and elevated zero-maze tests. As grooming duration differed between strains, our analysis revealed several candidate genes with significant correlations between gene expression in the brain and grooming duration. The Allen Brain Atlas, STRING, GoMiner and Mouse Genome Informatics databases were used to functionally map and analyze these candidate mouse genes against their human orthologs, assessing the strain ranking of their expression and the regional distribution of expression in the mouse brain. This allowed us to identify an interconnected network of candidate genes (which have expression levels that correlate with grooming behavior), display altered patterns of expression in key brain areas related to grooming, and underlie important functions in the brain. Collectively, our results demonstrate the utility of large-scale, high-throughput data-mining and in-silico modeling for linking genomic and behavioral data, as well as their potential to identify novel neural targets for complex neurobehavioral phenotypes, including grooming.

  1. Identification of Molecular Marker Linked to Salt Tolerance Gene in Alfalfa

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The study has established the F2 offspring obtained by crossing salt-tolerant with salt-sensitive alfalfa, and appraised the salt-tolerant F2 offspring seedling was evaluated in pot culture. With the F2 segregated population, the research has obtained a molecular marker linked with salt-tolerant genes of alfalfa using the improved BSA combined with RAPD. The RAPD PCR products were excised from the agarose gel and purified using a kit, then were mixed with pMD-18T vector and sequenced. Sequencing result indicated the RAPD marker was 1 438 bp in length. Similarity researches using blast in Genbank indicated that the nucleotide sequence of the RAPD marker showed 93% and 91% similarity with mth2-6el8 gene fragment (347 bp) and mth2-33122 gene fragment (334 bp) of Medicago truncatula respectively. Medicago truncatula is a close relative of alfalfa and Mth2-6e18 is a molecular marker of the gene coding for a cysteine protease which was salt inducible in some plants. These results indicated the RAPD marker was possibly related to cysteine protease genes in alfalfa.

  2. Antiporter Gene from Hordum brevisubulatum (Trin.) Link and Its Overexpression in Transgenic Tobaccos

    Institute of Scientific and Technical Information of China (English)

    Shi-You Lü; Yu-Xiang JING; Shi-Hua SHEN; Hua-Yan ZHAO; Lan-Qing MA; Xiang-Juan ZHOU; Qing REN; Yan-Fang LI

    2005-01-01

    A vacuolar Na+/H+ antiporter cDNA gene was successfully isolated from Hordeum brevisubulatum (Trin.) Link using the rapid amplification of cDNA ends (RACE) method. The gene was named HbNHX1 and was found to consist of 1 916 bp encoding a predicted polypeptide of 540 amino acids with a conserved amiloride-binding domain. Phylogenetic tree analysis of the Na+/H+ antiporters showed that the HbNHX1gene shares 55.3%-74.8% similarity with the vacuolar-type Na+/H+ antiporters. Transgenic tobaccos that contain the HbNHX1 gene, integrated by forward insertion into the tobacco genome, were obtained via Agrobacterium tumerfaciens and characterized for the determination of the concentration of Na+ and K+ions, as well as proline, in the presence of 300 mmol/L NaCl. The T1 transgenic plants showed more tolerance to salt and drought than did wild-type plants. Our data suggest that overexpression of the HbNHX1 gene could improve the tolerance of transgenic tobaccos to salt and drought through the function of the vacuolar Na+/H+ antiporter.

  3. Yeast Ataxin-7 links histone deubiquitination with gene gating and mRNA export.

    Science.gov (United States)

    Köhler, Alwin; Schneider, Maren; Cabal, Ghislain G; Nehrbass, Ulf; Hurt, Ed

    2008-06-01

    Targeting of a gene to the nuclear pore complexes (NPCs), known as gene gating, can affect its transcriptional state. However, the mechanism underlying gene gating is poorly understood. Here, we have identified SAGA-associated Sgf73 (ref. 10), the yeast orthologue of human Ataxin-7 (ref. 11), as a regulator of histone H2B ubiquitin levels, a modification linked to both transcription initiation and elongation. Sgf73 is a key component of a minimal histone-deubiquitinating complex. Activation of the H2B deubiquitinating protease, Ubp8, is cooperative and requires complex formation with the amino-terminal zinc-finger-containing domain of Sgf73 and Sgf11-Sus1. Through a separate domain, Sgf73 mediates recruitment of the TREX-2 mRNA export factors Sac3 and Thp1 to SAGA and their stable interaction with Sus1-Cdc31. This latter step is crucial to target TREX-2 to the NPC. Loss of Sgf73 from SAGA abrogates gene gating of GAL1 and causes a GAL1 mRNA export defect. Thus, Sgf73 provides a molecular scaffold to integrate the regulation of H2B ubiquitin levels, tethering of a gene to the NPC and export of mRNA.

  4. Paroxysmal dystonic choreoathetosis: Tight linkage to chromosome 2q

    Energy Technology Data Exchange (ETDEWEB)

    Fink, J.K.; Rainier, S.; Wilkowski, J.; Jones, S.M. [Univ. of Michigan, Ann Arbor, MI (United States)] [and others

    1996-07-01

    Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that last up to several hours and occur at rest both spontaneously and following caffeine or alcohol consumption. We analyzed a Polish-American kindred with autosomal dominant PDC and identified tight linkage between the disorder and microsatellite markers on chromosome 2q (maximum two-point LOD score 4.77; recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant PDC on distal chromosome 2q. The fact that three other paroxysmal neurological disorders (periodic ataxia with myokymia and hypo- and hyperkalemic periodic paralysis) are due to mutation in ion-channel genes raises the possibility that PDC is also due to an ion-channel gene mutation. It is noteworthy that a cluster of sodium-channel genes is located on distal chromosome 2q, near the PDC locus. Identifying the PDC locus on chromosome 2q will facilitate discovery whether PDC is genetically homogeneous and whether other paroxysmal movement disorders are also genetically linked to the PDC locus. 28 refs., 2 figs., 1 tab.

  5. Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes.

    Directory of Open Access Journals (Sweden)

    Peter Hevezi

    Full Text Available Efforts to unravel the mechanisms underlying taste sensation (gustation have largely focused on rodents. Here we present the first comprehensive characterization of gene expression in primate taste buds. Our findings reveal unique new insights into the biology of taste buds. We generated a taste bud gene expression database using laser capture microdissection (LCM procured fungiform (FG and circumvallate (CV taste buds from primates. We also used LCM to collect the top and bottom portions of CV taste buds. Affymetrix genome wide arrays were used to analyze gene expression in all samples. Known taste receptors are preferentially expressed in the top portion of taste buds. Genes associated with the cell cycle and stem cells are preferentially expressed in the bottom portion of taste buds, suggesting that precursor cells are located there. Several chemokines including CXCL14 and CXCL8 are among the highest expressed genes in taste buds, indicating that immune system related processes are active in taste buds. Several genes expressed specifically in endocrine glands including growth hormone releasing hormone and its receptor are also strongly expressed in taste buds, suggesting a link between metabolism and taste. Cell type-specific expression of transcription factors and signaling molecules involved in cell fate, including KIT, reveals the taste bud as an active site of cell regeneration, differentiation, and development. IKBKAP, a gene mutated in familial dysautonomia, a disease that results in loss of taste buds, is expressed in taste cells that communicate with afferent nerve fibers via synaptic transmission. This database highlights the power of LCM coupled with transcriptional profiling to dissect the molecular composition of normal tissues, represents the most comprehensive molecular analysis of primate taste buds to date, and provides a foundation for further studies in diverse aspects of taste biology.

  6. Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster.

    Science.gov (United States)

    Deng, Xinxian; Hiatt, Joseph B; Nguyen, Di Kim; Ercan, Sevinc; Sturgill, David; Hillier, LaDeana W; Schlesinger, Felix; Davis, Carrie A; Reinke, Valerie J; Gingeras, Thomas R; Shendure, Jay; Waterston, Robert H; Oliver, Brian; Lieb, Jason D; Disteche, Christine M

    2011-10-23

    Many animal species use a chromosome-based mechanism of sex determination, which has led to the coordinate evolution of dosage-compensation systems. Dosage compensation not only corrects the imbalance in the number of X chromosomes between the sexes but also is hypothesized to correct dosage imbalance within cells that is due to monoallelic X-linked expression and biallelic autosomal expression, by upregulating X-linked genes twofold (termed 'Ohno's hypothesis'). Although this hypothesis is well supported by expression analyses of individual X-linked genes and by microarray-based transcriptome analyses, it was challenged by a recent study using RNA sequencing and proteomics. We obtained new, independent RNA-seq data, measured RNA polymerase distribution and reanalyzed published expression data in mammals, C. elegans and Drosophila. Our analyses, which take into account the skewed gene content of the X chromosome, support the hypothesis of upregulation of expressed X-linked genes to balance expression of the genome.

  7. Mutations of Bruton's tyrosine kinase gene in Brazilian patients with X-linked agammaglobulinemia.

    Science.gov (United States)

    Ramalho, V D; Oliveira Júnior, E B; Tani, S M; Roxo Júnior, P; Vilela, M M S

    2010-09-01

    Mutations in Bruton's tyrosine kinase (BTK) gene are responsible for X-linked agammaglobulinemia (XLA), which is characterized by recurrent bacterial infections, profound hypogammaglobulinemia, and decreased numbers of mature B cells in peripheral blood. We evaluated 5 male Brazilian patients, ranging from 3 to 10 years of age, from unrelated families, whose diagnosis was based on recurrent infections, markedly reduced levels of IgM, IgG and IgA, and circulating B cell numbers <2%. BTK gene analysis was carried out using PCR-SSCP followed by sequencing. We detected three novel (Ala347fsX55, I355T, and Thr324fsX24) and two previously reported mutations (Q196X and E441X). Flow cytometry revealed a reduced expression of BTK protein in patients and a mosaic pattern of BTK expression was obtained from mothers, indicating that they were XLA carriers.

  8. Mutations of Bruton's tyrosine kinase gene in Brazilian patients with X-linked agammaglobulinemia

    Directory of Open Access Journals (Sweden)

    V.D. Ramalho

    2010-09-01

    Full Text Available Mutations in Bruton's tyrosine kinase (BTK gene are responsible for X-linked agammaglobulinemia (XLA, which is characterized by recurrent bacterial infections, profound hypogammaglobulinemia, and decreased numbers of mature B cells in peripheral blood. We evaluated 5 male Brazilian patients, ranging from 3 to 10 years of age, from unrelated families, whose diagnosis was based on recurrent infections, markedly reduced levels of IgM, IgG and IgA, and circulating B cell numbers <2%. BTK gene analysis was carried out using PCR-SSCP followed by sequencing. We detected three novel (Ala347fsX55, I355T, and Thr324fsX24 and two previously reported mutations (Q196X and E441X. Flow cytometry revealed a reduced expression of BTK protein in patients and a mosaic pattern of BTK expression was obtained from mothers, indicating that they were XLA carriers.

  9. Detecting RAPD Markers Linked to Ripe Rot Resistance Genes in Chinese Wild Vitis

    Institute of Scientific and Technical Information of China (English)

    WANG Yue-jin; XU Yan; ZHANG Jian-xia; ZHOU Peng; WAN Yi-zhen

    2002-01-01

    With F1 individuals of the cross combination 88-110 of 83-4-96 ( V. quinquangularis Rehd. )× Muscat Rose ( V. vinifera L. ), the RAPD marker OPC15-1300 linked to ripe rot ( Gloeosporium fruetigenum Berk. ) resistance genes in Chinese wild Vitis was gained using bulked segregation analysis(BSA). And it was found that OPC15-1300 could be hereditary from the resistant parent (83-4-96) after the marker was tested in 50 F1 plants of the cross combination 88-110, 32 accessions of 8 Chinese wild Vitis species and 14cultivars of V. vinifera L. Also, it has provided a solid basis for molecular marker-assisted selection (MAS)and for possibly cloning disease resistance genes in the future.

  10. Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Steve P. Crampton

    2014-09-01

    Full Text Available Systemic lupus erythematosus (SLE represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease.

  11. Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

    Science.gov (United States)

    Crampton, Steve P.; Morawski, Peter A.; Bolland, Silvia

    2014-01-01

    Systemic lupus erythematosus (SLE) represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS) and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease. PMID:25147296

  12. Regulatory divergence of X-linked genes and hybrid male sterility in mice.

    Science.gov (United States)

    Oka, Ayako; Shiroishi, Toshihiko

    2014-01-01

    Postzygotic reproductive isolation is the reduction of fertility or viability in hybrids between genetically diverged populations. One example of reproductive isolation, hybrid male sterility, may be caused by genetic incompatibility between diverged genetic factors in two distinct populations. Genetic factors involved in hybrid male sterility are disproportionately located on the X chromosome. Recent studies showing the evolutionary divergence in gene regulatory networks or epigenetic effects suggest that the genetic incompatibilities occur at much broader levels than had previously been thought (e.g., incompatibility of protein-protein interactions). The latest studies suggest that evolutionary divergence of transcriptional regulation causes genetic incompatibilities in hybrid animals, and that such incompatibilities preferentially involve X-linked genes. In this review, we focus on recent progress in understanding hybrid sterility in mice, including our studies, and we discuss the evolutionary significance of regulatory divergence for speciation.

  13. Genome-wide studies highlight indirect links between human replication origins and gene regulation.

    Science.gov (United States)

    Cadoret, Jean-Charles; Meisch, Françoise; Hassan-Zadeh, Vahideh; Luyten, Isabelle; Guillet, Claire; Duret, Laurent; Quesneville, Hadi; Prioleau, Marie-Noëlle

    2008-10-14

    To get insights into the regulation of replication initiation, we systematically mapped replication origins along 1% of the human genome in HeLa cells. We identified 283 origins, 10 times more than previously known. Origin density is strongly correlated with genomic landscapes, with clusters of closely spaced origins in GC-rich regions and no origins in large GC-poor regions. Origin sequences are evolutionarily conserved, and half of them map within or near CpG islands. Most of the origins overlap transcriptional regulatory elements, providing further evidence of a connection with gene regulation. Moreover, we identify c-JUN and c-FOS as important regulators of origin selection. Half of the identified replication initiation sites do not have an open chromatin configuration, showing the absence of a direct link with gene regulation. Replication timing analyses coupled with our origin mapping suggest that a relatively strict origin-timing program regulates the replication of the human genome.

  14. Improved Selection with Newly Identified RAPD Markers Linked to Resistance Gene to Four Pathotypes of Colletotrichum lindemuthianum in Common Bean.

    Science.gov (United States)

    Alzate-Marin, A L; Menarim, H; de Carvalho, G A; de Paula, T J; de Barros, E G; Moreira, M A

    1999-04-01

    ABSTRACT Three F(2) populations derived from crosses between the resistant cultivar AB 136 and the susceptible cultivar Michelite (MiA), and one F(2) population derived from a cross between AB 136 and Mexico 222 (MeA), were used to identify markers linked to anthracnose resistance genes present in cultivar AB 136. Primer OPZ04 produced a DNA band (OPZ04(560)) linked in coupling phase to the resistance gene for pathotype 89 (8.5 +/- 0.025 cM) in one population derived from the cross MiA. In the same population, primer OPZ09 produced one band (OPZ09(950)) linked in repulsion phase (20.4 +/- 0.014 cM) to the same resistance gene. The simultaneous use of markers in coupling and in repulsion phases allowed the identification of the three genotypic classes. In the other two populations from cross MiA, OPZ04(560) was linked in coupling phase to resistance genes for pathotypes 73 (2.9 +/- 0.012 cM) and 81 (2.8 +/- 0.017 cM). In population MeA, OPZ04(560) was linked in coupling phase (7.5 +/- 0.033 cM) to resistance to pathotype 64. These data suggest that a single gene or complex locus of linked resistance genes present in cultivar AB 136 confers resistance to all four pathotypes of C. lindemuthianum.

  15. Regulation of X-linked gene expression during early mouse development by Rlim.

    Science.gov (United States)

    Wang, Feng; Shin, JongDae; Shea, Jeremy M; Yu, Jun; Bošković, Ana; Byron, Meg; Zhu, Xiaochun; Shalek, Alex K; Regev, Aviv; Lawrence, Jeanne B; Torres, Eduardo M; Zhu, Lihua J; Rando, Oliver J; Bach, Ingolf

    2016-09-19

    Mammalian X-linked gene expression is highly regulated as female cells contain two and male one X chromosome (X). To adjust the X gene dosage between genders, female mouse preimplantation embryos undergo an imprinted form of X chromosome inactivation (iXCI) that requires both Rlim (also known as Rnf12) and the long non-coding RNA Xist. Moreover, it is thought that gene expression from the single active X is upregulated to correct for bi-allelic autosomal (A) gene expression. We have combined mouse genetics with RNA-seq on single mouse embryos to investigate functions of Rlim on the temporal regulation of iXCI and Xist. Our results reveal crucial roles of Rlim for the maintenance of high Xist RNA levels, Xist clouds and X-silencing in female embryos at blastocyst stages, while initial Xist expression appears Rlim-independent. We find further that X/A upregulation is initiated in early male and female preimplantation embryos.

  16. The genomic structure of human BTK, the defective gene in X-linked agammaglobulinemia

    Energy Technology Data Exchange (ETDEWEB)

    Rohrer, J.; Parolini, O. [St. Jude Children`s Research Hospital, Memphis, TN (United States); Conley, M.E. [St. Jude Children`s Research Hospital, Memphis, TN (United States)]|[Univ. of Tennessee College of Medicine, Memphis, TN (United States); Belmont, J.W. [Baylor College of Medicine, Houston, TX (United States)

    1994-12-31

    It has recently been demonstrated that mutations in the gene for Bruton`s tyrosine kinase (BTK) are responsible for X-linked agammaglobulinemia. Southern blot analysis and sequencing of cDNA were used to document deletions, insertions, and single base pair substitutions. To facilitate analysis of BTK regulation and to permit the development of assays that could be used to screen genomic DNA for mutations in BTK, the authors determined the genomic organization of this gene. Subcloning of a cosmid and a yeast artificial chromosome showed that BTK is divided into 19 exons spanning 37 kilobases of genomic DNA. Analysis of the region 5{prime} to the first untranslated exon revealed no consensus TATAA or CAAT boxes; however, three retinoic acid binding sites were identified in this region. Comparison of the structure of BTK with that of other nonreceptor tyrosine kinases, including SRC, FES, and CSK, demonstrated a lack of conservation of exon borders. Information obtained in this study will contribute to understanding of the evolution of nonreceptor tyrosine kinases. It will also be useful in diagnostic studies, including carrier detection, and in studies directed towards gene therapy or gene replacement. 29 refs., 2 figs., 2 tabs.

  17. Microcephaly gene links Trithorax and REST/NRSF to control neural stem cell proliferation and differentiation

    Science.gov (United States)

    Yang, Yawei J.; Baltus, Andrew E.; Mathew, Rebecca S.; Murphy, Elisabeth A.; Evrony, Gilad D.; Gonzalez, Dilenny M.; Wang, Estee P.; Marshall-Walker, Christine A.; Barry, Brenda J.; Murn, Jernej; Tatarakis, Antonis; Mahajan, Muktar A.; Samuels, Herbert H.; Shi, Yang; Golden, Jeffrey A.; Mahajnah, Muhammad; Shenhav, Ruthie; Walsh, Christopher A.

    2013-01-01

    SUMMARY Microcephaly is a neurodevelopmental disorder causing significantly reduced cerebral cortex size. Many known microcephaly gene products localize to centrosomes, regulating cell fate and proliferation. Here, we identify and characterize a nuclear zinc finger protein, ZNF335/NIF-1, as a causative gene for severe microcephaly, small somatic size, and neonatal death. Znf335-null mice are embryonically lethal and conditional knockout leads to severely reduced cortical size. RNA-interference and postmortem human studies show that Znf335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation. ZNF335 is a component of a vertebrate-specific, trithorax H3K4-methylation complex, directly regulating REST/NRSF, a master regulator of neural gene expression and cell fate, as well as other essential neural-specific genes. Our results reveal ZNF335 as an essential link between H3K4 complexes and REST/NRSF, and provide the first direct genetic evidence that this pathway regulates human neurogenesis and neuronal differentiation. PMID:23178126

  18. Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus.

    Science.gov (United States)

    Colombo, Carlo; Porzio, Ottavia; Liu, Ming; Massa, Ornella; Vasta, Mario; Salardi, Silvana; Beccaria, Luciano; Monciotti, Carla; Toni, Sonia; Pedersen, Oluf; Hansen, Torben; Federici, Luca; Pesavento, Roberta; Cadario, Francesco; Federici, Giorgio; Ghirri, Paolo; Arvan, Peter; Iafusco, Dario; Barbetti, Fabrizio

    2008-06-01

    Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation in the Ins2 gene exhibits PNDM associated with pancreatic beta cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset, but rapidly declined over time. When these mutant proinsulins were expressed in HEK293 cells, we observed defects in insulin protein folding and secretion. In these experiments, expression of the mutant proinsulins was also associated with increased Grp78 protein expression and XBP1 mRNA splicing, 2 markers of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells had diminished viability compared with those expressing WT proinsulin. In conclusion, we find that mutations in the insulin gene that promote proinsulin misfolding may cause PNDM.

  19. Childhood trauma as a cause of psychosis: linking genes, psychology, and biology.

    Science.gov (United States)

    van Winkel, Ruud; van Nierop, Martine; Myin-Germeys, Inez; van Os, Jim

    2013-01-01

    Recent studies have provided robust evidence for an association between childhood trauma (CT) and psychosis. Meta-analyses have quantified the association, pointing to odds ratios in the order of around 3, and prospective studies have shown that reverse causation is unlikely to explain the association. However, more work is needed to address the possibility of a gene-environment correlation, that is, whether genetic risk for psychosis predicts exposure to CT. Nevertheless, multiple studies have convincingly shown that the association between CT and psychosis remains strong and significant when controlling for genetic risk, in agreement with a possible causal association. In addition, several studies have shown plausible psychological and neurobiological mechanisms linking adverse experiences to psychosis, including induction of social defeat and reduced self-value, sensitization of the mesolimbic dopamine system, changes in the stress and immune system, and concomitant changes in stress-related brain structures, such as the hippocampus and the amygdala, findings that should be integrated, however, in more complex models of vulnerability. It is currently unclear whether genetic vulnerability plays a role in conferring the mental consequences of adversity, and which genes are likely to be involved. The current, limited evidence points to genes that are not specifically involved in psychosis but more generally in regulating mood (serotonin transporter gene), neuroplasticity (brain-derived neurotrophic factor), and the stress-response system (FKBP5), in line with a general effect of CT on a range of mental disorders, rather than suggesting specificity for psychosis.

  20. Gene Therapy for X-Linked Severe Combined Immunodeficiency: Where Do We Stand?

    Science.gov (United States)

    Cavazzana, Marina; Six, Emmanuelle; Lagresle-Peyrou, Chantal; André-Schmutz, Isabelle; Hacein-Bey-Abina, Salima

    2016-01-01

    More than 20 years ago, X-linked severe combined immunodeficiency (SCID-X1) appeared to be the best condition to test the feasibility of hematopoietic stem cell gene therapy. The seminal SCID-X1 clinical studies, based on first-generation gammaretroviral vectors, demonstrated good long-term immune reconstitution in most treated patients despite the occurrence of vector-related leukemia in a few of them. This gene therapy has successfully enabled correction of the T cell defect. Natural killer and B cell defects were only partially restored, most likely due to the absence of a conditioning regimen. The success of these pioneering trials paved the way for the extension of gene-based treatment to many other diseases of the hematopoietic system, but the unfortunate serious adverse events led to extensive investigations to define the retrovirus integration profiles. This review puts into perspective the clinical experience of gene therapy for SCID-X1, with the development and implementation of new generations of safer vectors such as self-inactivating gammaretroviral or lentiviral vectors as well as major advances in integrome knowledge. PMID:26790362

  1. A candidate gene for X-linked Ocular Albinism (OA1)

    Energy Technology Data Exchange (ETDEWEB)

    Bassi, M.T.; Schiaffino, V.; Rugarli, E. [Baylor College of Medicine, Houston, TX (United States)

    1994-09-01

    Ocular Albinism of the Nettleship-Fall type 1 (OA1) is the most common form of ocular albinism. It is transmitted as an X-linked recessive trait with affected males showing severe reduction of visual acuity, nystagmus, strabismus, photophobia. Ophthalmologic examination reveals foveal hypoplasia, hypopigmentation of the retina and iris translucency. Microscopic examination of melanocytes suggests that the underlying defect in OA1 is an abnormality in melanosome formation. Recently we assembled a 350 kb cosmid contig spanning the entire critical region on Xp22.3, which measures approximately 110 kb. A minimum set of cosmids was used to identify transcribed sequences using both cDNA selection and exon amplification. Two putative exons recovered by exon amplification strategy were found to be highly conserved throughout evolution and, therefore, they were used as probes for the screening of fetal and adult retina cDNA libraries. This led to the isolation of clones spanning a full-length cDNA which measures 7.6 kb. Sequence analysis revealed that the predicted protein product shows homology with syntrophines and a Xenopus laevis apical protein. The gene covers approximately 170 kb of DNA and spans the entire critical region for OA1, being deleted in two patients with contiguous gene deletion including OA1 and in one patient with isolated OA1. Therefore, this new gene represents a very strong candidate for involvement in OA1 (an alternative, but unlikely possibility to be considered is that the true OA1 gene lies within an intron of the former). Northern analysis revealed very high level of expression in retina and melanoma. Unlike most Xp22.3 genes, this gene is conserved in the mouse. We are currently performing SSCP analysis and direct sequencing of exons on DNAs from approximately 60 unrelated patients with OA1 for mutation detection.

  2. DIA1R is an X-linked gene related to Deleted In Autism-1.

    Directory of Open Access Journals (Sweden)

    Azhari Aziz

    Full Text Available BACKGROUND: Autism spectrum disorders (ASDS are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1 gene. METHODOLOGY/PRINCIPAL FINDINGS: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related. While DIA1 is autosomal (chromosome 3, position 3q24, DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62% similar overall (28% identical, and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. CONCLUSIONS/SIGNIFICANCE: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation.

  3. Three novel PHEX gene mutations in four Chinese families with X-linked dominant hypophosphatemic rickets

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Qing-lin [Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Xu, Jia [Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Medical College of Soochow University, Suzhou, Jiangsu province 215000 (China); Zhang, Zeng [Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); He, Jin-wei [Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Lu, Lian-song [Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Medical College of Soochow University, Suzhou, Jiangsu province 215000 (China); Fu, Wen-zhen [Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Zhang, Zhen-lin, E-mail: zzl2002@medmail.com.cn [Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer In our study, all of the patients were of Han Chinese ethnicity, which were rarely reported. Black-Right-Pointing-Pointer We identified three novel PHEX gene mutations in four unrelated families with XLH. Black-Right-Pointing-Pointer We found that the relationship between the phenotype and genotype of the PHEX gene was not invariant. Black-Right-Pointing-Pointer We found that two PHEX gene sites, p.534 and p.731, were conserved. -- Abstract: Background: X-linked hypophosphatemia (XLH), the most common form of inherited rickets, is a dominant disorder that is characterized by renal phosphate wasting with hypophosphatemia, abnormal bone mineralization, short stature, and rachitic manifestations. The related gene with inactivating mutations associated with XLH has been identified as PHEX, which is a phosphate-regulating gene with homologies to endopeptidases on the X chromosome. In this study, a variety of PHEX mutations were identified in four Chinese families with XLH. Methods: We investigated four unrelated Chinese families who exhibited typical features of XLH by using PCR to analyze mutations that were then sequenced. The laboratory and radiological investigations were conducted simultaneously. Results: Three novel mutations were found in these four families: one frameshift mutation, c.2033dupT in exon 20, resulting in p.T679H; one nonsense mutation, c.1294A > T in exon 11, resulting in p.K432X; and one missense mutation, c.2192T > C in exon 22, resulting in p.F731S. Conclusions: We found that the PHEX gene mutations were responsible for XLH in these Chinese families. Our findings are useful for understanding the genetic basis of Chinese patients with XLH.

  4. Efficacy of Gene Therapy for X-Linked Severe Combined Immunodeficiency

    Science.gov (United States)

    Hacein-Bey-Abina, Salima; Hauer, Julia; Lim, Annick; Picard, Capucine; Wang, Gary P.; Berry, Charles C.; Martinache, Chantal; Rieux-Laucat, Frédéric; Latour, Sylvain; Belohradsky, Bernd H.; Leiva, Lily; Sorensen, Ricardo; Debré, Marianne; Casanova, Jean Laurent; Blanche, Stephane; Durandy, Anne; Bushman, Frederic D.; Fischer, Alain; Cavazzana-Calvo, Marina

    2010-01-01

    BACKGROUND The outcomes of gene therapy to correct congenital immunodeficiencies are unknown. We reviewed long-term outcomes after gene therapy in nine patients with X-linked severe combined immunodeficiency (SCID-X1), which is characterized by the absence of the cytokine receptor common γ chain. METHODS The nine patients, who lacked an HLA-identical donor, underwent ex vivo retrovirus-mediated transfer of γ chain to autologous CD34+ bone marrow cells between 1999 and 2002. We assessed clinical events and immune function on long-term follow-up. RESULTS Eight patients were alive after a median follow-up period of 9 years (range, 8 to 11). Gene therapy was initially successful at correcting immune dysfunction in eight of the nine patients. However, acute leukemia developed in four patients, and one died. Transduced T cells were detected for up to 10.7 years after gene therapy. Seven patients, including the three survivors of leukemia, had sustained immune reconstitution; three patients required immunoglobulin-replacement therapy. Sustained thymopoiesis was established by the persistent presence of naive T cells, even after chemotherapy in three patients. The T-cell–receptor repertoire was diverse in all patients. Transduced B cells were not detected. Correction of the immunodeficiency improved the patients’ health. CONCLUSIONS After nearly 10 years of follow-up, gene therapy was shown to have corrected the immunodeficiency associated with SCID-X1. Gene therapy may be an option for patients who do not have an HLA-identical donor for hematopoietic stem-cell transplantation and for whom the risks are deemed acceptable. This treatment is associated with a risk of acute leukemia. (Funded by INSERM and others.) PMID:20660403

  5. IDENTIFYING GENES CONTROLLING FERULATE CROSS-LINKING FORMATION IN GRASS CELL WALLS

    Energy Technology Data Exchange (ETDEWEB)

    de O Buanafina, Marcia Maria

    2013-10-16

    DESCRIPTION/ABSTRACT This proposal focuses on cell wall feruloylation and our long term goal is to identify and isolate novel genes controlling feruloylation and to characterize the phenotype of mutants in this pathway, with a spotlight on cell wall properties. Currently, the genes underlying AX feruloylation have not been identified and the isolation of such genes could be of great importance in manipulating ferulates accretion to the wall. Mutation of the feruloyl transferase gene(s) should lead to less ferulates secreted to the cell wall and reduced ferulate cross-linking. Our current research is based on the hypothesis that controlling the level of total feruloylation will have a direct impact on the level of cross-linking and in turn impact biomass utility for forage and biofuel production. Our results/accomplishments for this project so far include: 1. Mutagenised Brachypodium population. We have developed EMS mutagenized populations of model grass species Brachypodium distachyon. EMS populations have been developed from over 28,000 mutagenized seeds generating 5,184 M2 families. A total of 20,793 plants have been screened and 1,233 were originally selected. 2. Selected Brachypodium mutants: Potential mutants on their levels of cell wall ferulates and cell wall AX ? have been selected from 708 M2 families. A total of 303 back-crosses to no-mutagenized parental stock have been done, followed by selfing selected genotypes in order to confirm heritability of traits and to remove extraneous mutations generated by EMS mutagenesis. We are currently growing 12 F5 and F6 populations in order to assess CW composition. If low level of ferulates are confirmed in the candidate lines selected the mutation could be altered in different in one or several kinds of genes such as genes encoding an AX feruloyl transferase; genes encoding the arabinosyl transferase; genes encoding the synthesis of the xylan backbone; genes encoding enzymes of the monolignol pathway affecting FA

  6. Conjugative plasmids: Vessels of the communal gene pool

    DEFF Research Database (Denmark)

    Norman, Anders; Hansen, Lars H.; Sørensen, Søren Johannes

    2009-01-01

    Comparative whole-genome analyses have demonstrated that horizontal gene transfer (HGT) provides a significant contribution to prokaryotic genome innovation. The evolution of specific prokaryotes is therefore tightly linked to the environment in which they live and the communal pool of genes avai...... mechanistic framework for obtaining adaptability and functional diversity that alleviates the need for large genomes of specialized ‘private genes'....

  7. A new resource for characterizing X-linked genes in Drosophila melanogaster: systematic coverage and subdivision of the X chromosome with nested, Y-linked duplications.

    Science.gov (United States)

    Cook, R Kimberley; Deal, Megan E; Deal, Jennifer A; Garton, Russell D; Brown, C Adam; Ward, Megan E; Andrade, Rachel S; Spana, Eric P; Kaufman, Thomas C; Cook, Kevin R

    2010-12-01

    Interchromosomal duplications are especially important for the study of X-linked genes. Males inheriting a mutation in a vital X-linked gene cannot survive unless there is a wild-type copy of the gene duplicated elsewhere in the genome. Rescuing the lethality of an X-linked mutation with a duplication allows the mutation to be used experimentally in complementation tests and other genetic crosses and it maps the mutated gene to a defined chromosomal region. Duplications can also be used to screen for dosage-dependent enhancers and suppressors of mutant phenotypes as a way to identify genes involved in the same biological process. We describe an ongoing project in Drosophila melanogaster to generate comprehensive coverage and extensive breakpoint subdivision of the X chromosome with megabase-scale X segments borne on Y chromosomes. The in vivo method involves the creation of X inversions on attached-XY chromosomes by FLP-FRT site-specific recombination technology followed by irradiation to induce large internal X deletions. The resulting chromosomes consist of the X tip, a medial X segment placed near the tip by an inversion, and a full Y. A nested set of medial duplicated segments is derived from each inversion precursor. We have constructed a set of inversions on attached-XY chromosomes that enable us to isolate nested duplicated segments from all X regions. To date, our screens have provided a minimum of 78% X coverage with duplication breakpoints spaced a median of nine genes apart. These duplication chromosomes will be valuable resources for rescuing and mapping X-linked mutations and identifying dosage-dependent modifiers of mutant phenotypes.

  8. Efficiency of Iepsilon promoter-directed switch recombination in GFP expression-based switch constructs works synergistically with other promoter and/or enhancer elements but is not tightly linked to the strength of transcription.

    Science.gov (United States)

    Zhang, Ke; Zhang, Ling; Yamada, Takechiyo; Vu, Michael; Lee, Anna; Saxon, Andrew

    2002-02-01

    One key unresolved issue in immunoglobulin class switch recombination (CSR) is how the accessibility of the switch region for CSR is controlled. To better understand the nature of accessibility control for human Ig CSR, we developed a novel inducible switch recombination assay based on expression of green fluorescence protein (GFP) from switch constructs undergoing substrate switch recombination (SSR). Efficient SSR depends on the cytokine-inducible Iepsilon promoter and co-stimulation with IL-4+anti-CD40. Characterization of SSR reveals that both S-S deletional recombination and S-S inversion occur. We show that the IL-4-inducible Iepsilon promoter (pIepsilon) selectively determines the efficiency of the accessibility for SSR. However, the pIepsilon-induced transcription, by itself,is not sufficient to direct efficient SSR. For efficient SSR, both pIepsilon-driven transcriptional activity and an additional promoter/enhancer-derived activity are required. The efficiency of SSR is not tightly correlated with the strength of the combined transcriptional activity. Our results suggest that the mechanism(s) underlying the transcriptional activity, e.g. DNA modification is important for controlling the accessibility for efficient switch recombination.

  9. Development of Random Amplified Polymorphism DNA Markers Linked to Powdery Mildew Resistance Gene in Melon

    Directory of Open Access Journals (Sweden)

    Budi Setiadi Daryono

    2015-11-01

    Full Text Available A random amplified polymorphic DNA (RAPD marker linked to powdery mildew resistance gene (Pm-I in melon PI 371795 was reported. However, the RAPD marker has problem in scoring. To detect powdery mildew resistance gene (Pm-I in melon accurately, the RAPD marker was cloned and sequenced to design sequence characterized amplified region (SCAR markers. SCAPMAR5 marker derived from pUBC411 primer yielded a single DNA band at 1061 bp. Segregation of SCAPMAR5 marker in bulk of F2 plants demonstrated that the marker was co-segregated with RAPD marker from which the SCAR marker was originated. Moreover, results of SCAR analysis in diverse melons showed SCAPMAR5 primers obtained a single 1061 bp linked to Pm-I in resistant melon PI 371795 and PMAR5. On the other hand, SCAPMAR5 failed to detect Pm-I in susceptible melons. Results of this study revealed that SCAR analysis not only confirmed melons that had been clearly scored for resistance to Pm-I evaluated by RAPD markers, but also clarified the ambiguous resistance results obtained by the RAPD markers.   Key words: Cucumis melo L., Pm-I, RAPD, SCAPMAR5

  10. Identification of molecular markers linked to rice bacterial blight resistance genes from Oryza meyeriana

    Directory of Open Access Journals (Sweden)

    Jing WANG,Chen CHENG,Yanru ZHOU,Yong YANG,Qiong MEI,Junmin LI,Ye CHENG,Chengqi YAN,Jianping CHEN

    2015-09-01

    Full Text Available Y73 is a progeny of asymmetric somatic hybridization between Oryza sativa cv. Dalixiang and the wild rice species Oryza meyeriana. Inoculation with a range of strains of Xanthomonas oryzae pv. oryzae showed that Y73 had inherited a high level of resistance to rice bacterial blight (BB from its wild parent. An F2 population of 7125 individuals was constructed from the cross between Y73 and a BB-susceptible cultivar IR24. After testing 615 SSR and STS markers covering the 12 rice chromosomes, 186 markers were selected that showed polymorphism between Y73 and IR24. Molecular markers linked to the BB resistance genes in Y73 were scanned using the F2 population and the polymorphic markers. The SSR marker RM128 on chromosome 1, the STS marker R03D159 on chromosome 3 and the STS marker R05D104 on chromosome 5 were found to be linked to the rice BB resistance genes in Y73.

  11. Carbamate-linked cationic lipids with different hydrocarbon chains for gene delivery.

    Science.gov (United States)

    Shi, Jia; Yu, Shijun; Zhu, Jie; Zhi, Defu; Zhao, Yinan; Cui, Shaohui; Zhang, Shubiao

    2016-05-01

    A series of carbamate-linked cationic lipids containing saturated or unsaturated hydrocarbon chains and quaternary ammonium head were designed and synthesized. After recrystallization, carbamate-linked cationic lipids with high purity (over 95%) were obtained. The structures of these lipids were proved by IR spectrum, HR-ESI-MS, HPLC, (1)H NMR and (13)C NMR. The liposomes were prepared by using these cationic lipids and neutral lipid DOPE. Particle size and zeta-potential were studied to show that they were suitable for gene transfection. The DNA-bonding ability of C12:0, C14:0 and C18:1 cationic liposomes was much better than others. The results of transfection showed that hydrophobic chains of these lipids have great effects on their transfection activity. The lipids bearing C12:0, C14:0 saturated chains or C18:1 unsaturated chain showed relatively higher transfection efficiency and lower cytotoxicity. So these cationic lipids could be used as non-viral gene carriers for further studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Arrested rearrangement of TCR V[beta] genes in thymocytes from children with x-linked severe combined immunodeficiency disease

    Energy Technology Data Exchange (ETDEWEB)

    Sleasman, J.W.; Harville, T.O.; White, G.B.; Barrett, D.J. (Univ. of Florida College of Medicine, Gainsville, FL (United States)); George, J.F. (Univ. of Alabama, Birmingham, AL (United States)); Goodenow, M.M. (Univ. of Florida College of Medicine, Gainsville, FL (United States) Univ. of Alabama, Birmingham, AL (United States))

    1994-07-01

    Human X-linked severe combined immunodeficiency disease (SCID) is an immunodeficiency disorder in which T cell development is arrested in the thymic cortex. B lymphocytes in children with X-linked SCID seem to differentiate normally. X-linked SCID is associated with a mutation in the gene that encodes the IL-2R [gamma]-chain. Because TCR-[beta] gene recombination is a pivotal initial event in T lymphocyte onteogeny within the thymus, the authors hypothesized that a failure to express normal IL-2R[gamma] could lead to impaired TCR-[beta] gene recombination in early thymic development. PCR was used to determine the status of TCR-[beta] gene-segment rearrangements in thymic DNA that had been obtained from children with X-linked SCID. The initial step in TCR-[beta] gene rearrangement, that of D[beta] to J[beta] recombination, was readily detected in all thymus samples from children with X-linked SCID; in contrast, V[beta] to DJ[beta] gene rearrangements were undetectable in the same samples. Both D[beta] to J[beta] and V[beta] to DJ[beta] TCR genes were rearranged in the thymic tissues obtained from immunologically normal children. The authors conclude that TCR[beta]-chain gene rearrangement is arrested in children with X-linked SCID. The results suggest a causative relationship between the failure of TCR [beta]-chain gene arrangements to proceed beyond DJ[beta] rearrangements and the production of a nonfunctional IL-2R [gamma]-chain. 45 refs., 3 figs.

  13. Overexpression of X-linked genes in T cells from women with lupus.

    Science.gov (United States)

    Hewagama, Anura; Gorelik, Gabriela; Patel, Dipak; Liyanarachchi, Punsisi; McCune, W Joseph; Somers, Emily; Gonzalez-Rivera, Tania; Strickland, Faith; Richardson, Bruce

    2013-03-01

    Women develop lupus more frequently than men and the reason remains incompletely understood. Evidence that men with Klinefelter's Syndrome (XXY) develop lupus at approximately the same rate as women suggests that a second X chromosome contributes. However, since the second X is normally inactivated, how it predisposes to lupus is unclear. DNA methylation contributes to the silencing of one X chromosome in women, and CD4+ T cell DNA demethylation contributes to the development of lupus-like autoimmunity. This suggests that demethylation of genes on the inactive X may predispose women to lupus, and this hypothesis is supported by a report that CD40LG, an immune gene encoded on the X chromosome, demethylates and is overexpressed in T cells from women but not men with lupus. Overexpression of other immune genes on the inactive X may also predispose women to this disease. We therefore compared mRNA and miRNA expression profiles in experimentally demethylated T cells from women and men as well as in T cells from women and men with lupus. T cells from healthy men and women were treated with the DNA methyltransferase inhibitor 5-azacytidine, then X-linked mRNAs were surveyed with oligonucleotide arrays, and X-linked miRNA's surveyed with PCR arrays. CD40LG, CXCR3, OGT, miR-98, let-7f-2*, miR 188-3p, miR-421 and miR-503 were among the genes overexpressed in women relative to men. MiRNA target prediction analyses identified CBL, which downregulates T cell receptor signaling and is decreased in lupus T cells, as a gene targeted by miR-188-3p and miR-98. Transfection with miR-98 and miR-188-3p suppressed CBL expression. The same mRNA and miRNA transcripts were also demethylated and overexpressed in CD4+ T cells from women relative to men with active lupus. Together these results further support a role for X chromosome demethylation in the female predisposition to lupus.

  14. Cross-linked Polyethylenimine as Potential DNA Vector for Gene Delivery with High Efficiency and Low Cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Wei DONG; Guang-Hui JIN; Shu-Feng LI; Qi-Ming SUN; Ding-Yuan MA; Zi-Chun HUA

    2006-01-01

    Polyethylenimine (PEI) has been known as an efficient gene carrier with the highest cationic charge potential. High transfection efficiency of PEI, along with its cytotoxicity, strongly depends on its molecular weight. To enhance its gene delivery efficiency and minimize cytotoxicity, we have synthesized small cross-linked PEI with biodegradable linkages and evaluated their transfection efficiencies in vitro. In this study, branched PEI with a molecular weight of 800 Da was cross-linked by small diacrylate [ 1,4-butanediol diacrylate or ethyleneglycol dimethacrylate (EGDMA)] for 2-6 h. The efficiencies of the cross-linked PEI in in vitro transfection of plasmid DNA containing enhanced green fluorescent protein (EGFP) reporter gene were assessed in melanoma B 16F10 cell line and other cell lines. Flow cytometry was used to quantify the cellular entry efficiency of plasmid and the transgene expression level. The cytotoxicities of the cross-linked PEI in these cells were evaluated by MTT assay. EGDMA-PEI 800-4h, a typical cross-linked PEI reported here, mediated a more efficient expression of reporter gene than the commercially available 25-kDa branched PEI control, and resulted in a 9-fold increase in gene delivery in B16F10 cells and a 16-fold increase in 293T cells, while no cytotoxicity was found at the optimized condition for gene delivery. Furthermore, the transfection activity of polyplexes was preserved in the presence of serum proteins.

  15. Gene expression centroids that link with low intrinsic aerobic exercise capacity and complex disease risk.

    Science.gov (United States)

    Kivelä, Riikka; Silvennoinen, Mika; Lehti, Maarit; Rinnankoski-Tuikka, Rita; Purhonen, Tatja; Ketola, Tarmo; Pullinen, Katri; Vuento, Meri; Mutanen, Niina; Sartor, Maureen A; Reunanen, Hilkka; Koch, Lauren G; Britton, Steven L; Kainulainen, Heikki

    2010-11-01

    A strong link exists between low aerobic exercise capacity and complex metabolic diseases. To probe this linkage, we utilized rat models of low and high intrinsic aerobic endurance running capacity that differ also in the risk for metabolic syndrome. We investigated in skeletal muscle gene-phenotype relationships that connect aerobic endurance capacity with metabolic disease risk factors. The study compared 12 high capacity runners (HCRs) and 12 low capacity runners (LCRs) from generation 18 of selection that differed by 615% for maximal treadmill endurance running capacity. On average, LCRs were heavier and had increased blood glucose, insulin, and triglycerides compared with HCRs. HCRs were higher for resting metabolic rate, voluntary activity, serum high density lipoproteins, muscle capillarity, and mitochondrial area. Bioinformatic analysis of skeletal muscle gene expression data revealed that many genes up-regulated in HCRs were related to oxidative energy metabolism. Seven mean mRNA expression centroids, including oxidative phosphorylation and fatty acid metabolism, correlated significantly with several exercise capacity and disease risk phenotypes. These expression-phenotype correlations, together with diminished skeletal muscle capillarity and mitochondrial area in LCR rats, support the general hypothesis that an inherited intrinsic aerobic capacity can underlie disease risks.

  16. Gene Therapy Studies in a Canine Model of X-Linked Severe Combined Immunodeficiency

    Science.gov (United States)

    De Ravin, Suk See; Malech, Harry L.; Sorrentino, Brian P.; Burtner, Christopher; Kiem, Hans-Peter

    2015-01-01

    Abstract Since the occurrence of T cell leukemias in the original human γ-retroviral gene therapy trials for X-linked severe combined immunodeficiency (XSCID), considerable effort has been devoted to developing safer vectors. This review summarizes gene therapy studies performed in a canine model of XSCID to evaluate the efficacy of γ-retroviral, lentiviral, and foamy viral vectors for treating XSCID and a novel method of vector delivery. These studies demonstrate that durable T cell reconstitution and thymopoiesis with no evidence of any serious adverse events and, in contrast to the human XSCID patients, sustained marking in myeloid cells and B cells with reconstitution of normal humoral immune function can be achieved for up to 5 years without any pretreatment conditioning. The presence of sustained levels of gene-marked T cells, B cells, and more importantly myeloid cells for almost 5 years is highly suggestive of transduction of either multipotent hematopoietic stem cells or very primitive committed progenitors. PMID:25603151

  17. The pkI gene encoding pyruvate kinase I links to the luxZ gene which enhances bioluminescence of the lux operon from Photobacterium leiognathi.

    Science.gov (United States)

    Lin, J W; Lu, H C; Chen, H Y; Weng, S F

    1997-10-09

    Partial 3'-end nucleotide sequence of the pkI gene (GenBank accession No. AF019143) from Photobacterium leiognathi ATCC 25521 has been determined, and the encoded pyruvate kinase I is deduced. Pyruvate kinase I is the key enzyme of glycolysis, which converts phosphoenol pyruvate to pyruvate. Alignment and comparison of pyruvate kinase Is from P. leiognathi, E. coli and Salmonella typhimurium show that they are homologous. Nucleotide sequence reveals that the pkI gene is linked to the luxZ gene that enhances bioluminescence of the lux operon from P. leiognathi. The gene order of the pkI and luxZ genes is-pk1-ter-->-R&R"-luxZ-ter"-->, whereas ter is transcriptional terminator for the pkI and related genes, and R&R" is the regulatory region and ter" is transcriptional terminator for the luxZ gene. It clearly elicits that the pkI gene and luxZ gene are divided to two operons. Functional analysis confirms that the potential hairpin loop omega T is the transcriptional terminator for the pkI and related genes. It infers that the pkI and related genes are simply linked to the luxZ gene in P. leiognathi genome.

  18. Historical divergence and gene flow: coalescent analyses of mitochondrial, autosomal and sex-linked loci in Passerina buntings.

    Science.gov (United States)

    Carling, Matthew D; Lovette, Irby J; Brumfield, Robb T

    2010-06-01

    Quantifying the role of gene flow during the divergence of closely related species is crucial to understanding the process of speciation. We collected DNA sequence data from 20 loci (one mitochondrial, 13 autosomal, and six sex-linked) for population samples of Lazuli Buntings (Passerina amoena) and Indigo Buntings (Passerina cyanea) (Aves: Cardinalidae) to test explicitly between a strict allopatric speciation model and a model in which divergence occurred despite postdivergence gene flow. Likelihood ratio tests of coalescent-based population genetic parameter estimates indicated a strong signal of postdivergence gene flow and a strict allopatric speciation model was rejected. Analyses of partitioned datasets (mitochondrial, autosomal, and sex-linked) suggest the overall gene flow patterns are driven primarily by autosomal gene flow, as there is no evidence of mitochondrial gene flow and we were unable to reject an allopatric speciation model for the sex-linked data. This pattern is consistent with either a parapatric divergence model or repeated periods of allopatry with gene flow occurring via secondary contact. These results are consistent with the low fitness of female avian hybrids under Haldane's rule and demonstrate that sex-linked loci likely are important in the initial generation of reproductive isolation, not just its maintenance.

  19. An X-linked homologue of the autosomal inprinted gene ZNF127 escapes X inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Longstreet, M.; Nicholls, R.D.; Willard, H.F. [Case Western Reserve Univ., Cleveland, OH (United States)] [and others

    1994-09-01

    The ZNF127 gene has been shown to be subject to parental imprinting in both humans and the mouse and maps to within the Prader-Willi/Angelman Syndrome critical region on chromosome 15. We have cloned two X-linked related loci, one of which, ZNFXp is a transcribed gene while the other, ZNFXq, is an untranscribed pseudogene. ZNFXp is 83.6% identical to ZNFXq and 65.4% identical to ZNF127 over 1.4 kb of open reading frame they share in common, Like ZNF127, the predicted protein sequence of ZNFXp contains a C{sub 3}HC{sub 4} zinc finger domain and C{sub 3}H zinc finger-like motifs. Whereas ZNF127 has three C{sub 3}H motifs, ZNFXp has four. A strong CpG island is located within 1 kb 5{prime} of the predicted amino terminus of ZNFXp. Expression of ZNFXp has been detected from mouse/human somatic cell hybrids containing either an active (n=2) or an inactive (n=4) chromosome, and thus escapes X inactivation. Probes made from the 3{prime} UTR of ZNFXp detect a number of related loci in both human and murine DNA, none of which is the ZNF127 locus on chromosome 15. None of the detectable murine bands shows dosage differences between males and females as would be expected for X-linked loci. This raises the possibility that ZNFXp inserted into the human X chromosome after its divergence from a common ancestor with the murine X. We have mapped ZNFXp to Xp11.4 by Southern blotting and PCR of hybrid DNAs and by fluorescence in situ hybridization (FISH). ZNFXq maps within the X Inactivation Center (XIC) region on Xq13.2, approximately 300 kb distal to the XIST gene. We find it intriguing, and perhaps significant, that two members of this gene family are subject to epigenetic regulation -- one autosomal imprinting, and the other escape from X inactivation. These results could imply an evolutionary and mechanistic relationship between these two processes.

  20. Hunting for Novel X-Linked Breast Cancer Suppressor Genes in Mouse and Human

    Science.gov (United States)

    2007-03-01

    B Fig. 5-2 CEPX RP11-344O14 (FOXP3) 353K22 344014 573N21 Fig. 5-3 C C a n c e r N o r m a l N CRepressor ZF LZ FKH E1 E2 E5E3 E4 E6 E7 E8 E9 E10...is an X-linked breast cancer suppressor gene and an important regulator of the HER-2/ErbB2 oncogene . 15. SUBJECT TERMS No subject terms provided 16...of this oncogene in breast cancer. One potential mechanism by which Foxp3 represses Her-2/ErbB2 is to inhibit the promoter activity. Analysis of the

  1. X-linked gene transcription patterns in female and male in vivo, in vitro and cloned porcine individual blastocysts.

    Directory of Open Access Journals (Sweden)

    Chi-Hun Park

    Full Text Available To determine the presence of sexual dimorphic transcription and how in vitro culture environments influence X-linked gene transcription patterns in preimplantation embryos, we analyzed mRNA expression levels in in vivo-derived, in vitro-fertilized (IVF, and cloned porcine blastocysts. Our results clearly show that sex-biased expression occurred between female and male in vivo blastocysts in X-linked genes. The expression levels of XIST, G6PD, HPRT1, PGK1, and BEX1 were significantly higher in female than in male blastocysts, but ZXDA displayed higher levels in male than in female blastocysts. Although we found aberrant expression patterns for several genes in IVF and cloned blastocysts, similar sex-biased expression patterns (on average were observed between the sexes. The transcript levels of BEX1 and XIST were upregulated and PGK1 was downregulated in both IVF and cloned blastocysts compared with in vivo counterparts. Moreover, a remarkable degree of expression heterogeneity was observed among individual cloned embryos (the level of heterogeneity was similar in both sexes but only a small proportion of female IVF embryos exhibited variability, indicating that this phenomenon may be primarily caused by faulty reprogramming by the somatic cell nuclear transfer (SCNT process rather than in vitro conditions. Aberrant expression patterns in cloned embryos of both sexes were not ameliorated by treatment with Scriptaid as a potent HDACi, although the blastocyst rate increased remarkably after this treatment. Taken together, these results indicate that female and male porcine blastocysts produced in vivo and in vitro transcriptional sexual dimorphisms in the selected X-linked genes and compensation of X-linked gene dosage may not occur at the blastocyst stage. Moreover, altered X-linked gene expression frequently occurred in porcine IVF and cloned embryos, indicating that X-linked gene regulation is susceptible to in vitro culture and the SCNT process

  2. Male X-linked genes in Drosophila melanogaster are compensated independently of the Male-Specific Lethal complex.

    Science.gov (United States)

    Philip, Philge; Stenberg, Per

    2013-10-26

    In organisms where the two sexes have unequal numbers of X-chromosomes, the expression of X-linked genes needs to be balanced not only between the two sexes, but also between X and the autosomes. In Drosophila melanogaster, the Male-Specific Lethal (MSL) complex is believed to produce a 2-fold increase in expression of genes on the male X, thus restoring this balance. Here we show that almost all the genes on the male X are effectively compensated. However, many genes are compensated without any significant recruitment of the MSL-complex. These genes are very weakly, if at all, affected by mutations or RNAi against MSL-complex components. In addition, even the genes that are strongly bound by MSL rely on mechanisms other than the MSL-complex for proper compensation. We find that long, non-ubiquitously expressed genes tend to rely less on the MSL-complex for their compensation and genes that in addition are far from High Affinity Sites tend to not bind the complex at all or very weakly. We conclude that most of the compensation of X-linked genes is produced by an MSL-independent mechanism. Similar to the case of the MSL-mediated compensation we do not yet know the mechanism behind the MSL-independent compensation that appears to act preferentially on long genes. Even if we observe similarities, it remains to be seen if the mechanism is related to the buffering that is observed in autosomal aneuploidies.

  3. Dosage compensation on the active X chromosome minimizes transcriptional noise of X-linked genes in mammals.

    Science.gov (United States)

    Yin, Shanye; Wang, Ping; Deng, Wenjun; Zheng, Hancheng; Hu, Landian; Hurst, Laurence D; Kong, Xiangyin

    2009-01-01

    Theory predicts that haploid-expressed genes should have noisier expression than comparable diploid-expressed ones with the same expression level. However, in mammals there are several classes of gene that are monoallelically expressed, including X-linked genes, imprinted genes and some other autosomal genes. Does it follow that the evolution of X chromosomes in eukaryotes comes at the cost of increased transcriptional noise in the heterogametic sex? Moreover, is escaping X-inactivation in mammalian females associated with an increase in transcriptional variation? To address these questions, we analyze gene expression variation between replicate samples of diverse mammalian cell lines in steady-state using microarray data. We observe that transcriptional variation of X-linked genes is no different to that of autosomal genes both before and after control for transcript abundance. By contrast, autosomal genes subject to allelic exclusion do have unusually high noise levels even allowing for their low transcript abundance. The prior theory we suggest was insufficient, at least as regards X-chromosomes, as it failed to appreciate the regulatory complexity of gene expression, not least the effects of genomic neighborhood. These results suggest that high noise is not a necessary consequence of haploid expression and emphasize the primacy of expression level as a determinant of noise. The latter has consequences for understanding the etiology of haplo-insufficiency and the evolution of gene expression levels. Given the coupling between expression level and noise on the X-chromosome, we suggest that part of the selective advantage of dosage compensation is noise abatement of X-linked genes.

  4. Sequence diversity patterns suggesting balancing selection in partially sex-linked genes of the plant Silene latifolia are not generated by demographic history or gene flow.

    Science.gov (United States)

    Guirao-Rico, Sara; Sánchez-Gracia, Alejandro; Charlesworth, Deborah

    2017-03-01

    DNA sequence diversity in genes in the partially sex-linked pseudoautosomal region (PAR) of the sex chromosomes of the plant Silene latifolia is higher than expected from within-species diversity of other genes. This could be the footprint of sexually antagonistic (SA) alleles that are maintained by balancing selection in a PAR gene (or genes) and affect polymorphism in linked genome regions. SA selection is predicted to occur during sex chromosome evolution, but it is important to test whether the unexpectedly high sequence polymorphism could be explained without it, purely by the combined effects of partial linkage with the sex-determining region and the population's demographic history, including possible introgression from Silene dioica. To test this, we applied approximate Bayesian computation-based model choice to autosomal sequence diversity data, to find the most plausible scenario for the recent history of S. latifolia and then to estimate the posterior density of the most relevant parameters. We then used these densities to simulate variation to be expected at PAR genes. We conclude that an excess of variants at high frequencies at PAR genes should arise in S. latifolia populations only for genes with strong associations with fully sex-linked genes, which requires closer linkage with the fully sex-linked region than that estimated for the PAR genes where apparent deviations from neutrality were observed. These results support the need to invoke selection to explain the S. latifolia PAR gene diversity, and encourage further work to test the possibility of balancing selection due to sexual antagonism. © 2016 John Wiley & Sons Ltd.

  5. Pigmentation genes link Parkinson's disease to melanoma, opening a window on both etiologies.

    Science.gov (United States)

    Herrero Hernández, Elena

    2009-03-01

    Melanomas occur more frequently among subjects with Parkinson's disease (PD) and a biological explanation for this epidemiological observation is lacking. It is also well-known that pigmentation genes play an important role in the development of melanomas. It is therefore suggested that the link between both diseases resides in genes that regulate pigmentation. Among these, those involved in the synthesis of dopamine and related compounds as melanin appear to be the most plausible candidates. Whilst it is known that individuals with fair phototypes have an increased risk for melanoma, this hypothesis suggests that the same applies to Parkinson's disease. It is therefore postulated that the accurate analysis of the phototype could be used to identify subjects at higher risk for both diseases, possibly allowing preventative interventions (photoprotective, nutritional, occupational) and prediction of risk in childhood. Another possible implication of this hypothesis is that therapeutic strategies targeting melanogenesis could maintain or perhaps restore the physiological concentrations of neuromelanin in the substantia nigra and achieve protection against neuronal loss in subjects at risk of developing PD.

  6. X chromosome array-CGH for the identification of novel X-linked mental retardation genes.

    Science.gov (United States)

    Bauters, Marijke; Van Esch, Hilde; Marynen, Peter; Froyen, Guy

    2005-01-01

    Array-CGH technology for the detection of submicroscopic copy number changes in the genome has recently been developed for the identification of novel disease-associated genes. It has been estimated that submicroscopic genomic deletions or duplications will be present in 5-7% of patients with idiopathic mental retardation (MR). Since 30% more males than females are diagnosed with MR, we have developed a full coverage X chromosome array-CGH with a theoretical resolution of 82 kb, for the detection of copy number alterations in patients with suspected X-linked mental retardation (XLMR). First, we have validated the genomic location of X-derived clones through male versus female hybridisations. Next, we validated our array for efficient and reproducible detection of known alterations in XLMR patients. In all cases, we were able to detect the deletions and duplications in males as well as females. Due to the high resolution of our X-array, the boundaries of the genomic aberrations could clearly be identified making genotype-phenotype studies more reliable. Here, we describe the production and validation of a full coverage X-array-CGH, which will allow for fast and easy screening of submicroscopic copy number alterations in XLMR patients with the aim to identify novel MR genes or mechanisms involved in a deranged cognitive development.

  7. A survey of disease connections for CD4+ T cell master genes and their directly linked genes.

    Science.gov (United States)

    Li, Wentian; Espinal-Enríquez, Jesús; Simpfendorfer, Kim R; Hernández-Lemus, Enrique

    2015-12-01

    Genome-wide association studies and other genetic analyses have identified a large number of genes and variants implicating a variety of disease etiological mechanisms. It is imperative for the study of human diseases to put these genetic findings into a coherent functional context. Here we use system biology tools to examine disease connections of five master genes for CD4+ T cell subtypes (TBX21, GATA3, RORC, BCL6, and FOXP3). We compiled a list of genes functionally interacting (protein-protein interaction, or by acting in the same pathway) with the master genes, then we surveyed the disease connections, either by experimental evidence or by genetic association. Embryonic lethal genes (also known as essential genes) are over-represented in master genes and their interacting genes (55% versus 40% in other genes). Transcription factors are significantly enriched among genes interacting with the master genes (63% versus 10% in other genes). Predicted haploinsufficiency is a feature of most these genes. Disease-connected genes are enriched in this list of genes: 42% of these genes have a disease connection according to Online Mendelian Inheritance in Man (OMIM) (versus 23% in other genes), and 74% are associated with some diseases or phenotype in a Genome Wide Association Study (GWAS) (versus 43% in other genes). Seemingly, not all of the diseases connected to genes surveyed were immune related, which may indicate pleiotropic functions of the master regulator genes and associated genes.

  8. Linkage analysis and physical mapping near the gene for x-linked agammaglobulinemia at Xq22

    Energy Technology Data Exchange (ETDEWEB)

    Parolini, O.; Lassiter, G.L.; Henry, M.J.; Conley, M.E. (Univ. of Tennessee College of Medicine, Memphis (United States) St. Jude Children' s Research Hospital, Memphis, TN (United States)); Hejtmancik, J.F. (National Inst. of Health, Bethesda, MD (United States)); Allen, R.C.; Belmont, J.W. (Baylor College of Medicine, Houston, TX (United States)); Barker, D.F. (Univ. of Utah, Salt Lake City (United States))

    1993-02-01

    The gene for x-linked agammaglobulinemia (XLA) has been mapped to Xq22. No recombinations have been reported between the gene and the prob p212 at DXS178; however, this probe is informative in only 30-40% of women and the reported flanking markers, DXS3 and DXS94, and 10-15 cM apart. To identify additional probes that might be useful in genetic counseling, we examined 11 polymorphisms that have been mapped to the Xq21.3-q22 region in 13 families with XLA. In addition, pulsed-field gel electrophoresis and yeast artificial chromosomes (YACs) were used to further characterize the segman of DNA within which the gene for SLA must lie. The results demonstrated that DXS366 and DXS442, which share a 430-kb pulsed-field fragment, could replace DXS3 as proximal flanking markers. Probes at DXS178 and DXS265 identified the same 145-kb pulsed-field fragment, and both loci were contained within a 200-kb YAC identified with the probe p212. A highly polymorphic CA repeat (DCS178CA) was isolated from one end of this YAC and used in linkage analysis. Probes at DXS101 and DXS328 shared several pulsed-field fragments, the smallest of which was 250 kb. No recombinations were seen between XLA and the DXS178-DXS265-DXS178CA complex, DXS101, DXS328, DXS87, or the gene for proteolipid protein (PLP). Key crossovers, when combined with the linkage data from families with Alport syndrome, suggested the following order of loci: cen-DXS3-DXS366-DXS442-(PLP, DXS101, DXS328, DXS178-DXS265-DXS178CA complex, XL)-(DXS87, DXS94)-DXS327-(DXS350, DXS362)-tel. Our studies also limit the segment of DNA within which the XLA gene must lie to the 3- to 4-cM distance between DCS442 and DXS94 and they identify and orient polymorphisms that can be used in genetic counseling not only for XLA but also for Pelizaeus-Merzbacher disease (PLP deficiency), Alport syndrome (COL4A5 deficiency), and Fabry disease ([alpha]-galactosidase A difficiency). 31 refs., 5 figs., 2 tabs.

  9. Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

    Directory of Open Access Journals (Sweden)

    Rico Rueedi

    2014-02-01

    Full Text Available Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8 and independent associations between single nucleotide polymorphisms (SNP and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44 and lysine (rs8101881, P = 1.2×10(-33, respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.

  10. Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links

    Science.gov (United States)

    Nicholls, Andrew W.; Salek, Reza M.; Marques-Vidal, Pedro; Morya, Edgard; Sameshima, Koichi; Montoliu, Ivan; Da Silva, Laeticia; Collino, Sebastiano; Martin, François-Pierre; Rezzi, Serge; Steinbeck, Christoph; Waterworth, Dawn M.; Waeber, Gérard; Vollenweider, Peter; Beckmann, Jacques S.; Le Coutre, Johannes; Mooser, Vincent; Bergmann, Sven; Genick, Ulrich K.; Kutalik, Zoltán

    2014-01-01

    Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on 1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10−8) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10−44) and lysine (rs8101881, P = 1.2×10−33), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers. PMID:24586186

  11. Role of the X-linked gene GPR174 in autoimmune Addison's disease.

    Science.gov (United States)

    Napier, C; Mitchell, A L; Gan, E; Wilson, I; Pearce, S H S

    2015-01-01

    Autoimmune endocrinopathies demonstrate a profound gender bias, but the reasons for this remain obscure. The 1000 genes on the X chromosome are likely to be implicated in this inherent susceptibility; various theories, including skewed X chromosome inactivation and fetal microchimerism, have been proposed. GPR174 is an Xq21 putative purinergic receptor that is widely expressed in lymphoid tissues. A single-nucleotide polymorphism, rs3827440, encoding Ser162Pro, has recently been associated with Graves' disease in Chinese and Polish populations, suggesting a role of this X chromosome gene in autoimmune disease. We investigated the role of rs3827440 in a UK cohort of patients with autoimmune Addison's disease (AAD). Samples from 286 AAD cases and 288 healthy controls were genotyped using TaqMan single-nucleotide polymorphism genotyping assays (C_25954273_10) on the Applied Biosystems 7900HT Fast real-time PCR system. Using a dominant (present/absent) model, the serine-encoding T allele of rs3827440 was present in 189 of 286 AAD patients (66%) compared with 132 of 288 unaffected controls (46%) [P = .010, odds ratio 1.80 (5%-95% confidence interval 1.22-2.67)]. An allele dosage model found a significant excess of the T allele in AAD patients compared with controls [P = .03, odds ratio 1.34 (5%-95% confidence interval 1.07-1.67)]. We have demonstrated a significant association of this X chromosome-encoded immunoreceptor with AAD for the first time. This X-linked gene could have a more generalized role in autoimmunity pathogenesis: G protein-coupled receptors are promising drugable targets, and further work to elucidate the functional role of GPR174 is now warranted.

  12. Using SNP genetic markers to elucidate the linkage of the Co-34/Phg-3 anthracnose and angular leaf spot resistance gene cluster with the Ur-14 resistance gene

    Science.gov (United States)

    The Ouro Negro common bean cultivar contains the Co-34/Phg-3 gene cluster that confers resistance to the anthracnose (ANT) and angular leaf spot (ALS) pathogens. These genes are tightly linked on chromosome 4. Ouro Negro also has the Ur-14 rust resistance gene, reportedly in the vicinity of Co- 34; ...

  13. Direct estimation of the recombination frequency between the RB1 gene and two closely linked microsatellites using sperm typing.

    Science.gov (United States)

    Girardet, A; Lien, S; Leeflang, E P; Beaufrère, L; Tuffery, S; Munier, F; Arnheim, N; Claustres, M; Pellestor, F

    1999-01-01

    In this study, single sperm typing has been used for high-resolution recombination analysis between the retinoblastoma gene and two closely linked extragenic microsatellites (D13S284 and D13S1307). The analysis of 1198 single sperm from three donors allowed the determination of recombination fractions between RB1.20 and D13S284 and RB1.20 and D13S1307 of 0.022 and 0.033, respectively. These results show that RB1 gene and the two microsatellites are closely linked, which validates their potential use in indirect genetic diagnosis of retinoblastoma.

  14. Copy number gain of VCX, X-linked multi-copy gene, leads to cell proliferation and apoptosis during spermatogenesis

    Science.gov (United States)

    Ji, Juan; Qin, Yufeng; Wang, Rong; Huang, Zhenyao; Zhang, Yan; Zhou, Ran; Song, Ling; Ling, Xiufeng; Hu, Zhibin; Miao, Dengshun; Shen, Hongbing; Xia, Yankai; Wang, Xinru; Lu, Chuncheng

    2016-01-01

    Male factor infertility affects one-sixth of couples worldwide, and non-obstructive azoospermia (NOA) is one of the most severe forms. In recent years there has been increasing evidence to implicate the participation of X chromosome in the process of spermatogenesis. To uncover the roles of X-linked multi-copy genes in spermatogenesis, we performed systematic analysis of X-linked gene copy number variations (CNVs) and Y chromosome haplogrouping in 447 idiopathic NOA patients and 485 healthy controls. Interestingly, the frequency of individuals with abnormal level copy of Variable charge, X-linked (VCX) was significantly different between cases and controls after multiple test correction (p = 5.10 × 10−5). To discriminate the effect of gain/loss copies in these genes, we analyzed the frequency of X-linked multi-copy genes in subjects among subdivided groups. Our results demonstrated that individuals with increased copy numbers of Nuclear RNA export factor 2 (NXF2) (p = 9.21 × 10−8) and VCX (p = 1.97 × 10−4) conferred the risk of NOA. In vitro analysis demonstrated that increasing copy number of VCX could upregulate the gene expression and regulate cell proliferation and apoptosis. Our study establishes a robust association between the VCX CNVs and NOA risk. PMID:27705943

  15. Copy number gain of VCX, X-linked multi-copy gene, leads to cell proliferation and apoptosis during spermatogenesis.

    Science.gov (United States)

    Ji, Juan; Qin, Yufeng; Wang, Rong; Huang, Zhenyao; Zhang, Yan; Zhou, Ran; Song, Ling; Ling, Xiufeng; Hu, Zhibin; Miao, Dengshun; Shen, Hongbing; Xia, Yankai; Wang, Xinru; Lu, Chuncheng

    2016-11-29

    Male factor infertility affects one-sixth of couples worldwide, and non-obstructive azoospermia (NOA) is one of the most severe forms. In recent years there has been increasing evidence to implicate the participation of X chromosome in the process of spermatogenesis. To uncover the roles of X-linked multi-copy genes in spermatogenesis, we performed systematic analysis of X-linked gene copy number variations (CNVs) and Y chromosome haplogrouping in 447 idiopathic NOA patients and 485 healthy controls. Interestingly, the frequency of individuals with abnormal level copy of Variable charge, X-linked (VCX) was significantly different between cases and controls after multiple test correction (p = 5.10 × 10-5). To discriminate the effect of gain/loss copies in these genes, we analyzed the frequency of X-linked multi-copy genes in subjects among subdivided groups. Our results demonstrated that individuals with increased copy numbers of Nuclear RNA export factor 2 (NXF2) (p = 9.21 × 10-8) and VCX (p = 1.97 × 10-4) conferred the risk of NOA. In vitro analysis demonstrated that increasing copy number of VCX could upregulate the gene expression and regulate cell proliferation and apoptosis. Our study establishes a robust association between the VCX CNVs and NOA risk.

  16. Identification of Co-Segregating RAPD Marker Linked to Powdery Mildew Resistance Gene Pm 18 in Wheat

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qing-li; GU Feng; LI Tao; GAO Ju-rong; WANG Hong-gang

    2004-01-01

    The Pm18 gene of wheat confers resistance to the powdery mildew which is oneof the most serious diseases in many regions of the world. In this study, bulked segregant analysis (BSA) was used to develop randomly amplified polymorphic DNA (RAPD) markers linked to Pml8 gene. Three hundred and twenty decamer primers were screened and one of them was identified as RAPD marker (S411600) linked to Pml8. Using the F2 mapping population from the cross Pml8 × Chancellor, the marker S411600 was shown to co-segregate with the gene Pml8. This marker can be conveniently used for marker-assisted selection in wheat breeding programs for the identification or pyramiding of Pml8 with other resistance genes.

  17. Mutational analysis of Btk, the defective gene in X-linked agammaglobulinemia

    Energy Technology Data Exchange (ETDEWEB)

    Conley, M.E.; Fitch-Hilgenberg, M.E.; Rohrer, J. [St. Jude Children`s Research Hospital, Memphis, TN (United States)

    1994-09-01

    Recent studies have shown that X-linked agammaglobulinemia (XLA), a disorder of B cell development, is due to mutations in an scr-like cytoplasmic tyrosine kinase, Btk. Thus far, mutations in this gene have been identified by sequencing of cDNA. To permit the detection of mutations in genomic DNA, we determined the structure of Btk and identified 19 exons in 37 kb of DNA. PCR primers were designed to amplify each exon with its splice sites. Two overlapping PCR products were employed for exons longer than 230 base pairs. Single strand conformation polymorphism (SSCP) analysis was used to screen genomic DNA from 30 unrelated families presumed to carry a mutation in Btk. It was possible to amplify DNA in every reaction from every patient. None of the DNA samples demonstrated more than one aberrant SSCP pattern. Twenty three mutations were detected in 25 families. Seven point mutations resulting in amino acid substitutions were seen. An additional 7 base pair substitutions gave rise to premature stop codons. Two splice defects were noted. Small insertions or deletions, all resulting in frameshifts and premature stop codons were seen in eight patients. One patient had an A to G transition in the ATG start codon. Two mutations, both at CpG dinucleotides, were seen in more than one family. Haplotype analysis, using CA repeats closely linked to Btk, demonstrated that the mutations in these families arose independently. We conclude from these studies that the mutations in Btk in patients with XLA are highly variable. Large deletions are uncommon, although small 1 to 4 bp insertions or deletions constitute as many as one third of the mutations. Further analysis of patients with amino acid substitutions will permit structure/function correlations.

  18. IDENTIFYING GENES CONTROLLING FERULATE CROSS-LINKING FORMATION IN GRASS CELL WALLS

    Energy Technology Data Exchange (ETDEWEB)

    de O Buanafina, Marcia Maria

    2013-10-16

    DESCRIPTION/ABSTRACT This proposal focuses on cell wall feruloylation and our long term goal is to identify and isolate novel genes controlling feruloylation and to characterize the phenotype of mutants in this pathway, with a spotlight on cell wall properties. Currently, the genes underlying AX feruloylation have not been identified and the isolation of such genes could be of great importance in manipulating ferulates accretion to the wall. Mutation of the feruloyl transferase gene(s) should lead to less ferulates secreted to the cell wall and reduced ferulate cross-linking. Our current research is based on the hypothesis that controlling the level of total feruloylation will have a direct impact on the level of cross-linking and in turn impact biomass utility for forage and biofuel production. Our results/accomplishments for this project so far include: 1. Mutagenised Brachypodium population. We have developed EMS mutagenized populations of model grass species Brachypodium distachyon. EMS populations have been developed from over 28,000 mutagenized seeds generating 5,184 M2 families. A total of 20,793 plants have been screened and 1,233 were originally selected. 2. Selected Brachypodium mutants: Potential mutants on their levels of cell wall ferulates and cell wall AX ? have been selected from 708 M2 families. A total of 303 back-crosses to no-mutagenized parental stock have been done, followed by selfing selected genotypes in order to confirm heritability of traits and to remove extraneous mutations generated by EMS mutagenesis. We are currently growing 12 F5 and F6 populations in order to assess CW composition. If low level of ferulates are confirmed in the candidate lines selected the mutation could be altered in different in one or several kinds of genes such as genes encoding an AX feruloyl transferase; genes encoding the arabinosyl transferase; genes encoding the synthesis of the xylan backbone; genes encoding enzymes of the monolignol pathway affecting FA

  19. U3 snoRNA genes are multi-copy and frequently linked to U5 snRNA genes in Euglena gracilis§

    Directory of Open Access Journals (Sweden)

    Charette J Michael

    2009-11-01

    Full Text Available Abstract Background U3 snoRNA is a box C/D small nucleolar RNA (snoRNA involved in the processing events that liberate 18S rRNA from the ribosomal RNA precursor (pre-rRNA. Although U3 snoRNA is present in all eukaryotic organisms, most investigations of it have focused on fungi (particularly yeasts, animals and plants. Relatively little is known about U3 snoRNA and its gene(s in the phylogenetically broad assemblage of protists (mostly unicellular eukaryotes. In the euglenozoon Euglena gracilis, a distant relative of the kinetoplastid protozoa, Southern analysis had previously revealed at least 13 bands hybridizing with U3 snoRNA, suggesting the existence of multiple copies of U3 snoRNA genes. Results Through screening of a λ genomic library and PCR amplification, we recovered 14 U3 snoRNA gene variants, defined by sequence heterogeneities that are mostly located in the U3 3'-stem-loop domain. We identified three different genomic arrangements of Euglena U3 snoRNA genes: i stand-alone, ii linked to tRNAArg genes, and iii linked to a U5 snRNA gene. In arrangement ii, the U3 snoRNA gene is positioned upstream of two identical tRNAArg genes that are convergently transcribed relative to the U3 gene. This scenario is reminiscent of a U3 snoRNA-tRNA gene linkage previously described in trypanosomatids. We document here twelve different U3 snoRNA-U5 snRNA gene arrangements in Euglena; in each case, the U3 gene is linked to a downstream and convergently oriented U5 gene, with the intergenic region differing in length and sequence among the variants. Conclusion The multiple U3 snoRNA-U5 snRNA gene linkages, which cluster into distinct families based on sequence similarities within the intergenic spacer, presumably arose by genome, chromosome, and/or locus duplications. We discuss possible reasons for the existence of the unusually large number of U3 snoRNA genes in the Euglena genome. Variability in the signal intensities of the multiple Southern

  20. Genetic link between Asians and native Americans: evidence from HLA genes and haplotypes.

    Science.gov (United States)

    Tokunaga, K; Ohashi, J; Bannai, M; Juji, T

    2001-09-01

    We have been studying polymorphisms of HLA class I and II genes in East Asians including Buryat in Siberia, Mongolian, Han Chinese, Man Chinese, Korean Chinese, South Korean, and Taiwan indigenous populations in collaboration with many Asian scientists. Regional populations in Japan, Hondo-Japanese, Ryukyuan, and Ainu, were also studied. HLA-A, -B, and -DRB1 gene frequencies were subjected to the correspondence analysis and calculation of DA distances. The correspondence analysis demonstrated several major clusters of human populations in the world. "Mongoloid" populations were highly diversified, in which several clusters such as Northeast Asians, Southeast Asians, Oceanians, and Native Americans were observed. Interestingly, an indigenous population in North Japan, Ainu, was placed relatively close to Native Americans in the correspondence analysis. Distribution of particular HLA-A, -B, -DRB1 alleles and haplotypes was also analyzed in relation to migration and dispersal routes of ancestral populations. A number of alleles and haplotypes showed characteristic patterns of regional distribution. For example, B39-HR5-DQ7 (B*3901-DRB1*1406-DQB1*0301) was shared by Ainu and Native Americans. A24-Cw8-B48 was commonly observed in Taiwan indigenous populations, Maori in New Zealand, Orochon in Northeast China, Inuit, and Tlingit. These findings further support the genetic link between East Asians and Native Americans. We have proposed that various ancestral populations in East Asia, marked by different HLA haplotypes, had migrated and dispersed through multiple routes. Moreover, relatively small genetic distances and the sharing of several HLA haplotypes between Ainu and Native Americans suggest that these populations are descendants of some Upper Paleolithic populations of East Asia.

  1. Novel X-linked genes revealed by quantitative polymerase chain reaction in the green anole, Anolis carolinensis.

    Science.gov (United States)

    Rovatsos, Michail; Altmanová, Marie; Pokorná, Martina Johnson; Kratochvíl, Lukáš

    2014-08-28

    The green anole, Anolis carolinensis (ACA), is the model reptile for a vast array of biological disciplines. It was the first nonavian reptile to have its genome fully sequenced. During the genome project, the XX/XY system of sex chromosomes homologous to chicken chromosome 15 (GGA15) was revealed, and 106 X-linked genes were identified. We selected 38 genes located on eight scaffolds in ACA and having orthologs located on GGA15, then tested their linkage to ACA X chromosome by using comparative quantitative fluorescent real-time polymerase chain reaction applied to male and female genomic DNA. All tested genes appeared to be X-specific and not present on the Y chromosome. Assuming that all genes located on these scaffolds should be localized to the ACA X chromosome, we more than doubled the number of known X-linked genes in ACA, from 106 to 250. While demonstrating that the gene content of chromosome X in ACA and GGA15 is largely conserved, we nevertheless showed that numerous interchromosomal rearrangements had occurred since the splitting of the chicken and anole evolutionary lineages. The presence of many ACA X-specific genes localized to distinct contigs indicates that the ACA Y chromosome should be highly degenerated, having lost a large amount of its original gene content during evolution. The identification of novel genes linked to the X chromosome and absent on the Y chromosome in the model lizard species contributes to ongoing research as to the evolution of sex determination in reptiles and provides important information for future comparative and functional genomics.

  2. Mutation pattern in the Bruton's tyrosine kinase gene in 26 unrelated patients with X-linked agammaglobulinemia

    DEFF Research Database (Denmark)

    Vorechovský, I; Luo, L; Hertz, Jens Michael

    1997-01-01

    Mutation pattern was characterized in the Bruton's tyrosine kinase gene (BTK) in 26 patients with X-linked agammaglobulinemia, the first described immunoglobulin deficiency, and was related to BTK expression. A total of 24 different mutations were identified. Most BTK mutations were found to resu...

  3. A conceptual model linking functional gene expression and reductive dechlorination rates of chlorinated ethenes in clay rich groundwater sediment

    DEFF Research Database (Denmark)

    Bælum, Jacob; Chambon, Julie Claire Claudia; Scheutz, Charlotte

    2013-01-01

    We used current knowledge of cellular processes involved in reductive dechlorination to develop a conceptual model to describe the regulatory system of dechlorination at the cell level; the model links bacterial growth and substrate consumption to the abundance of messenger RNA of functional gene...

  4. The apoptosis linked gene ALG-2 is dysregulated in tumors of various origin and contributes to cancer cell viability

    DEFF Research Database (Denmark)

    la Cour, Jonas; Høj, Berit Rahbek; Mollerup, Jens

    2008-01-01

    The apoptosis linked gene-2 (ALG-2), discovered as a proapoptotic calcium binding protein, has recently been found upregulated in lung cancer tissue indicating that this protein may play a role in the pathology of cancer cells and/or may be a tumor marker. Using immunohistochemistry on tissue mic...

  5. Serotonin transporter gene-linked polymorphism affects detection of facial expressions.

    Directory of Open Access Journals (Sweden)

    Ai Koizumi

    Full Text Available Previous studies have demonstrated that the serotonin transporter gene-linked polymorphic region (5-HTTLPR affects the recognition of facial expressions and attention to them. However, the relationship between 5-HTTLPR and the perceptual detection of others' facial expressions, the process which takes place prior to emotional labeling (i.e., recognition, is not clear. To examine whether the perceptual detection of emotional facial expressions is influenced by the allelic variation (short/long of 5-HTTLPR, happy and sad facial expressions were presented at weak and mid intensities (25% and 50%. Ninety-eight participants, genotyped for 5-HTTLPR, judged whether emotion in images of faces was present. Participants with short alleles showed higher sensitivity (d' to happy than to sad expressions, while participants with long allele(s showed no such positivity advantage. This effect of 5-HTTLPR was found at different facial expression intensities among males and females. The results suggest that at the perceptual stage, a short allele enhances the processing of positive facial expressions rather than that of negative facial expressions.

  6. Linking genes to communities and ecosystems: Daphnia as an ecogenomic model

    Science.gov (United States)

    Miner, Brooks E.; De Meester, Luc; Pfrender, Michael E.; Lampert, Winfried; Hairston, Nelson G.

    2012-01-01

    How do genetic variation and evolutionary change in critical species affect the composition and functioning of populations, communities and ecosystems? Illuminating the links in the causal chain from genes up to ecosystems is a particularly exciting prospect now that the feedbacks between ecological and evolutionary changes are known to be bidirectional. Yet to fully explore phenomena that span multiple levels of the biological hierarchy requires model organisms and systems that feature a comprehensive triad of strong ecological interactions in nature, experimental tractability in diverse contexts and accessibility to modern genomic tools. The water flea Daphnia satisfies these criteria, and genomic approaches capitalizing on the pivotal role Daphnia plays in the functioning of pelagic freshwater food webs will enable investigations of eco-evolutionary dynamics in unprecedented detail. Because its ecology is profoundly influenced by both genetic polymorphism and phenotypic plasticity, Daphnia represents a model system with tremendous potential for developing a mechanistic understanding of the relationship between traits at the genetic, organismal and population levels, and consequences for community and ecosystem dynamics. Here, we highlight the combination of traits and ecological interactions that make Daphnia a definitive model system, focusing on the additional power and capabilities enabled by recent molecular and genomic advances. PMID:22298849

  7. Genes Linked to Production of Secondary Metabolites in Talaromyces atroroseus Revealed Using CRISPR-Cas9

    Science.gov (United States)

    Nielsen, Maria Lund; Isbrandt, Thomas; Rasmussen, Kasper Bøwig; Thrane, Ulf; Hoof, Jakob Blæsbjerg; Larsen, Thomas Ostenfeld; Mortensen, Uffe Hasbro

    2017-01-01

    The full potential of fungal secondary metabolism has until recently been impeded by the lack of universal genetic tools for most species. However, the emergence of several CRISPR-Cas9-based genome editing systems adapted for several genera of filamentous fungi have now opened the doors for future efforts in discovery of novel natural products and elucidation and engineering of their biosynthetic pathways in fungi where no genetic tools are in place. So far, most studies have focused on demonstrating the performance of CRISPR-Cas9 in various fungal model species, and recently we presented a versatile CRISPR-Cas9 system that can be successfully applied in several diverse Aspergillus species. Here we take it one step further and show that our system can be used also in a phylogenetically distinct and largely unexplored species from the genus of Talaromyces. Specifically, we exploit CRISPR-Cas9-based genome editing to identify a new gene in T. atroroseus responsible for production of polyketide-nonribosomal peptide hybrid products, hence, linking fungal secondary metabolites to their genetic origin in a species where no genetic engineering has previously been performed. PMID:28056079

  8. Genes Linked to Production of Secondary Metabolites in Talaromyces atroroseus Revealed Using CRISPR-Cas9.

    Science.gov (United States)

    Nielsen, Maria Lund; Isbrandt, Thomas; Rasmussen, Kasper Bøwig; Thrane, Ulf; Hoof, Jakob Blæsbjerg; Larsen, Thomas Ostenfeld; Mortensen, Uffe Hasbro

    2017-01-01

    The full potential of fungal secondary metabolism has until recently been impeded by the lack of universal genetic tools for most species. However, the emergence of several CRISPR-Cas9-based genome editing systems adapted for several genera of filamentous fungi have now opened the doors for future efforts in discovery of novel natural products and elucidation and engineering of their biosynthetic pathways in fungi where no genetic tools are in place. So far, most studies have focused on demonstrating the performance of CRISPR-Cas9 in various fungal model species, and recently we presented a versatile CRISPR-Cas9 system that can be successfully applied in several diverse Aspergillus species. Here we take it one step further and show that our system can be used also in a phylogenetically distinct and largely unexplored species from the genus of Talaromyces. Specifically, we exploit CRISPR-Cas9-based genome editing to identify a new gene in T. atroroseus responsible for production of polyketide-nonribosomal peptide hybrid products, hence, linking fungal secondary metabolites to their genetic origin in a species where no genetic engineering has previously been performed.

  9. Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton.

    Science.gov (United States)

    Qin, Juan; Li, Dengwen; Zhou, Yunqiang; Xie, Songbo; Du, Xin; Hao, Ziwei; Liu, Ruming; Liu, Xinqi; Liu, Min; Zhou, Jun

    2017-01-10

    Breast cancer is the most prevalent cancer in women. Although it begins as local disease, breast cancer frequently metastasizes to the lymph nodes and distant organs. Therefore, novel therapeutic targets are needed for the management of this disease. Apoptosis-linked gene 2 (ALG-2) is a calcium-binding protein crucial for diverse physiological processes and has recently been implicated in cancer development. However, it remains unclear whether this protein is involved in the pathogenesis of breast cancer. Here, we demonstrate that the expression of ALG-2 is significantly upregulated in breast cancer tissues and is correlated with clinicopathological characteristics indicative of tumor malignancy. Our data further show that ALG-2 stimulates breast cancer growth and metastasis in mice. ALG-2 also promotes breast cancer cell proliferation, survival, and motility in vitro. Mechanistic data reveal that ALG-2 disrupts the localization of centrosome proteins, resulting in spindle multipolarity and chromosome missegregation. In addition, ALG-2 drives the polarization and migration of breast cancer cells by facilitating the rearrangement of microtubules and microfilaments. These findings reveal a critical role for ALG-2 in the pathogenesis of breast cancer and have important implications for its diagnosis and therapy.

  10. Methylation state of the EDA gene promoter in Chinese X-linked hypohidrotic ectodermal dysplasia carriers.

    Directory of Open Access Journals (Sweden)

    Wei Yin

    Full Text Available INTRODUCTION: Hypodontia, hypohidrosis, sparse hair and characteristic faces are the main characters of X-linked hypohidrotic ectodermal dysplasia (XLHED which is caused by genetic ectodysplasin A (EDA deficiency. Heterozygous female carriers tend to have mild to moderate XLHED phenotype, even though 30% of them present no obvious symptom. METHODS: A large Chinese XLHED family was reported and the entire coding region and exon-intron boundaries of EDA gene were sequenced. To elucidate the mechanism for carriers' tempered phenotype, we analyzed the methylation level on four sites of the promoter of EDA by the pyrosequencing system. RESULTS: A known frameshift mutation (c.573-574 insT was found in this pedigree. Combined with the pedigrees we reported before, 120 samples comprised of 23 carrier females from 11 families and 97 healthy females were analyzed for the methylation state of EDA promoter. Within 95% confidence interval (CI, 18 (78.26% carriers were hypermethylated at these 4 sites. CONCLUSION: Chinese XLHED carriers often have a hypermethylated EDA promoter.

  11. Bruton's tyrosine kinase gene mutations in Turkish patients with X-linked agammaglobulinemia from a single center: Novel mutations in βTK gene

    NARCIS (Netherlands)

    Ç. Aydoǧmuş (Çiǧdem); Y. Camcioǧlu (Yildiz); M. van der Burg (Mirjam); H. Çokuǧraş (H.); N. Akçakaya (Necla); J.J.M. van Dongen (Jacques)

    2013-01-01

    textabstractObjective: X-linked agammaglobulinemia (XLA) is caused by a mutation in the Bruton's tyrosine kinase gene and is characterized by a delay in the maturation and differentiation of B lymphocytes. Patients with XLA have either absent or very low levels of circulating mature B cells (<1%), p

  12. Bruton's tyrosine kinase gene mutations in Turkish patients with X-linked agammaglobulinemia from a single center: Novel mutations in βTK gene

    NARCIS (Netherlands)

    Ç. Aydoǧmuş (Çiǧdem); Y. Camcioǧlu (Yildiz); M. van der Burg (Mirjam); H. Çokuǧraş (H.); N. Akçakaya (Necla); J.J.M. van Dongen (Jacques)

    2013-01-01

    textabstractObjective: X-linked agammaglobulinemia (XLA) is caused by a mutation in the Bruton's tyrosine kinase gene and is characterized by a delay in the maturation and differentiation of B lymphocytes. Patients with XLA have either absent or very low levels of circulating mature B cells (<1%),

  13. An Important Member of Tight Junctions: Claudins

    Directory of Open Access Journals (Sweden)

    Ozlem Demirpence

    2016-01-01

    Full Text Available The tight junction (TJs, the most apically located of the intercellular junctional complexes, inhibits solute and water flow through the paracellular space, termed the %u201Cbarrier%u201D function. TJs participate in signal transduction mechanisms that regulate epithelial cell proliferation, gene expression, differentiation and morphogenesis. The claudin family of transmembrane proteins localized to the TJ. Loss of expression of Claudin causes of suppression TJs function. Recent studies have shown that altered levels of the different claudins may be related to invasion and progression of carcinoma cells in several primary neoplasms. A better knowledge of the mechanisms underlying carcinogenesis will likely result in the development of novel approaches for the diagnosis and therapy.

  14. Weakly tight functions and their decomposition

    Directory of Open Access Journals (Sweden)

    Mona Khare

    2005-01-01

    Full Text Available The present paper deals with the study of a weakly tight function and its relation to tight functions. We obtain a Jordan-decomposition-type theorem for a locally bounded weakly tight real-valued function defined on a sublattice of IX, followed by the notion of a total variation.

  15. Expectation-maximization algorithm for determining natural selection of Y-linked genes through two-sex branching processes.

    Science.gov (United States)

    González, M; Gutiérrez, C; Martínez, R

    2012-09-01

    A two-dimensional bisexual branching process has recently been presented for the analysis of the generation-to-generation evolution of the number of carriers of a Y-linked gene. In this model, preference of females for males with a specific genetic characteristic is assumed to be determined by an allele of the gene. It has been shown that the behavior of this kind of Y-linked gene is strongly related to the reproduction law of each genotype. In practice, the corresponding offspring distributions are usually unknown, and it is necessary to develop their estimation theory in order to determine the natural selection of the gene. Here we deal with the estimation problem for the offspring distribution of each genotype of a Y-linked gene when the only observable data are each generation's total numbers of males of each genotype and of females. We set out the problem in a non parametric framework and obtain the maximum likelihood estimators of the offspring distributions using an expectation-maximization algorithm. From these estimators, we also derive the estimators for the reproduction mean of each genotype and forecast the distribution of the future population sizes. Finally, we check the accuracy of the algorithm by means of a simulation study.

  16. Testosterone regulates tight junction proteins and influences prostatic autoimmune responses.

    Science.gov (United States)

    Meng, Jing; Mostaghel, Elahe A; Vakar-Lopez, Funda; Montgomery, Bruce; True, Larry; Nelson, Peter S

    2011-06-01

    Testosterone and inflammation have been linked to the development of common age-associated diseases affecting the prostate gland including prostate cancer, prostatitis, and benign prostatic hypertrophy. We hypothesized that testosterone regulates components of prostate tight junctions which serve as a barrier to inflammation, thus providing a connection between age- and treatment-associated testosterone declines and prostatic pathology. We examined the expression and distribution of tight junction proteins in prostate biospecimens from mouse models and a clinical study of chemical castration, using transcript profiling, immunohistochemistry, and electron microscopy. We determined that low serum testosterone is associated with reduced transcript and protein levels of Claudin 4 and Claudin 8, resulting in defective tight junction ultrastructure in benign prostate glands. Expression of Claudin 4 and Claudin 8 was negatively correlated with the mononuclear inflammatory infiltrate caused by testosterone deprivation. Testosterone suppression also induced an autoimmune humoral response directed toward prostatic proteins. Testosterone supplementation in castrate mice resulted in re-expression of tight junction components in prostate epithelium and significantly reduced prostate inflammatory cell numbers. These data demonstrate that tight junction architecture in the prostate is related to changes in serum testosterone levels, and identify an androgen-regulated mechanism that potentially contributes to the development of prostate inflammation and consequent pathology.

  17. H4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation.

    Science.gov (United States)

    Vielle, Anne; Lang, Jackie; Dong, Yan; Ercan, Sevinc; Kotwaliwale, Chitra; Rechtsteiner, Andreas; Appert, Alex; Chen, Q Brent; Dose, Andrea; Egelhofer, Thea; Kimura, Hiroshi; Stempor, Przemyslaw; Dernburg, Abby; Lieb, Jason D; Strome, Susan; Ahringer, Julie

    2012-09-01

    The Caenorhabditis elegans dosage compensation complex (DCC) equalizes X-chromosome gene dosage between XO males and XX hermaphrodites by two-fold repression of X-linked gene expression in hermaphrodites. The DCC localizes to the X chromosomes in hermaphrodites but not in males, and some subunits form a complex homologous to condensin. The mechanism by which the DCC downregulates gene expression remains unclear. Here we show that the DCC controls the methylation state of lysine 20 of histone H4, leading to higher H4K20me1 and lower H4K20me3 levels on the X chromosomes of XX hermaphrodites relative to autosomes. We identify the PR-SET7 ortholog SET-1 and the Suv4-20 ortholog SET-4 as the major histone methyltransferases for monomethylation and di/trimethylation of H4K20, respectively, and provide evidence that X-chromosome enrichment of H4K20me1 involves inhibition of SET-4 activity on the X. RNAi knockdown of set-1 results in synthetic lethality with dosage compensation mutants and upregulation of X-linked gene expression, supporting a model whereby H4K20me1 functions with the condensin-like C. elegans DCC to repress transcription of X-linked genes. H4K20me1 is important for mitotic chromosome condensation in mammals, suggesting that increased H4K20me1 on the X may restrict access of the transcription machinery to X-linked genes via chromatin compaction.

  18. Sex-linked pheromone receptor genes of the European corn borer, Ostrinia nubilalis, are in tandem arrays.

    Directory of Open Access Journals (Sweden)

    Yuji Yasukochi

    Full Text Available BACKGROUND: Tuning of the olfactory system of male moths to conspecific female sex pheromones is crucial for correct species recognition; however, little is known about the genetic changes that drive speciation in this system. Moths of the genus Ostrinia are good models to elucidate this question, since significant differences in pheromone blends are observed within and among species. Odorant receptors (ORs play a critical role in recognition of female sex pheromones; eight types of OR genes expressed in male antennae were previously reported in Ostrinia moths. METHODOLOGY/PRINCIPAL FINDINGS: We screened an O. nubilalis bacterial artificial chromosome (BAC library by PCR, and constructed three contigs from isolated clones containing the reported OR genes. Fluorescence in situ hybridization (FISH analysis using these clones as probes demonstrated that the largest contig, which contained eight OR genes, was located on the Z chromosome; two others harboring two and one OR genes were found on two autosomes. Sequence determination of BAC clones revealed the Z-linked OR genes were closely related and tandemly arrayed; moreover, four of them shared 181-bp direct repeats spanning exon 7 and intron 7. CONCLUSIONS/SIGNIFICANCE: This is the first report of tandemly arrayed sex pheromone receptor genes in Lepidoptera. The localization of an OR gene cluster on the Z chromosome agrees with previous findings for a Z-linked locus responsible for O. nubilalis male behavioral response to sex pheromone. The 181-bp direct repeats might enhance gene duplications by unequal crossovers. An autosomal locus responsible for male response to sex pheromone in Heliothis virescens and H. subflexa was recently reported to contain at least four OR genes. Taken together, these findings support the hypothesis that generation of additional copies of OR genes can increase the potential for male moths to acquire altered specificity for pheromone components, and accordingly

  19. Enriching regulatory networks by bootstrap learning using optimised GO-based gene similarity and gene links mined from PubMed abstracts

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Ronald C.; Sanfilippo, Antonio P.; McDermott, Jason E.; Baddeley, Robert L.; Riensche, Roderick M.; Jensen, Russell S.; Verhagen, Marc; Pustejovsky, James

    2011-02-18

    Transcriptional regulatory networks are being determined using “reverse engineering” methods that infer connections based on correlations in gene state. Corroboration of such networks through independent means such as evidence from the biomedical literature is desirable. Here, we explore a novel approach, a bootstrapping version of our previous Cross-Ontological Analytic method (XOA) that can be used for semi-automated annotation and verification of inferred regulatory connections, as well as for discovery of additional functional relationships between the genes. First, we use our annotation and network expansion method on a biological network learned entirely from the literature. We show how new relevant links between genes can be iteratively derived using a gene similarity measure based on the Gene Ontology that is optimized on the input network at each iteration. Second, we apply our method to annotation, verification, and expansion of a set of regulatory connections found by the Context Likelihood of Relatedness algorithm.

  20. Thermal Hydraulic Performance of Tight Lattice Bundle

    Science.gov (United States)

    Yamamoto, Yasushi; Akiba, Miyuki; Morooka, Shinichi; Shirakawa, Kenetsu; Abe, Nobuaki

    Recently, the reduced moderation spectrum BWR has been studied. The fast neutron spectrum is obtained through triangular tight lattice fuel. However, there are few thermal hydraulic test data and thermal hydraulic correlation applicable to critical power prediction in such a tight lattice bundle. This study aims to enhance the database of the thermal hydraulic performance of the tight lattice bundle whose rod gap is about 1mm. Therefore, thermal hydraulic performance measurement tests of tight lattice bundles for the critical power, the pressure drop and the counter current flow limiting were performed. Moreover, the correlations to evaluate the thermal-hydraulic performance of the tight lattice bundle were developed.

  1. Network inference analysis identifies an APRR2-like gene linked to pigment accumulation in tomato and pepper fruits.

    Science.gov (United States)

    Pan, Yu; Bradley, Glyn; Pyke, Kevin; Ball, Graham; Lu, Chungui; Fray, Rupert; Marshall, Alexandra; Jayasuta, Subhalai; Baxter, Charles; van Wijk, Rik; Boyden, Laurie; Cade, Rebecca; Chapman, Natalie H; Fraser, Paul D; Hodgman, Charlie; Seymour, Graham B

    2013-03-01

    Carotenoids represent some of the most important secondary metabolites in the human diet, and tomato (Solanum lycopersicum) is a rich source of these health-promoting compounds. In this work, a novel and fruit-related regulator of pigment accumulation in tomato has been identified by artificial neural network inference analysis and its function validated in transgenic plants. A tomato fruit gene regulatory network was generated using artificial neural network inference analysis and transcription factor gene expression profiles derived from fruits sampled at various points during development and ripening. One of the transcription factor gene expression profiles with a sequence related to an Arabidopsis (Arabidopsis thaliana) ARABIDOPSIS PSEUDO RESPONSE REGULATOR2-LIKE gene (APRR2-Like) was up-regulated at the breaker stage in wild-type tomato fruits and, when overexpressed in transgenic lines, increased plastid number, area, and pigment content, enhancing the levels of chlorophyll in immature unripe fruits and carotenoids in red ripe fruits. Analysis of the transcriptome of transgenic lines overexpressing the tomato APPR2-Like gene revealed up-regulation of several ripening-related genes in the overexpression lines, providing a link between the expression of this tomato gene and the ripening process. A putative ortholog of the tomato APPR2-Like gene in sweet pepper (Capsicum annuum) was associated with pigment accumulation in fruit tissues. We conclude that the function of this gene is conserved across taxa and that it encodes a protein that has an important role in ripening.

  2. Speciation in Passerina buntings: introgression patterns of sex-linked loci identify a candidate gene region for reproductive isolation.

    Science.gov (United States)

    Carling, Matthew D; Brumfield, Robb T

    2009-03-01

    Sex-chromosomes are thought to play an important role in speciation, but few studies of non-model organisms have investigated the relative influence of multiple sex-linked markers on reproductive isolation. We collected 222 individuals along a geographical transect spanning the hybrid zone between Passerina amoena and P. cyanea (Aves: Cardinalidae). Using maximum-likelihood cline fitting methods, we estimated locus-specific introgression rates for 10 z-linked markers. Although the cline width estimates ranged from 2.8 to 584 km, eight of 10 loci had cline widths between 224 and 271 km. We also used coalescent-based estimates of locus-specific divergence times between P. amoena and P. cyanea to test a recently proposed hypothesis of an inverse relationship between divergence time and cline width but did not find a significant association. The narrow width (2.8 km) of the cline estimated from the VLDLR9 locus indicates strong selection retarding introgression of alleles at this locus across the hybrid zone. Interestingly, a mutation in the very low density lipoprotein receptor (VLDLR) gene, in which VLDLR9 is an intron, is known to reduce the egg-laying ability of some chickens, suggesting a possible link between this gene region and reproductive isolation between P. amoena and P. cyanea. These results underscore the importance of sampling multiple loci to investigate introgression patterns across a chromosome or genome and support previous findings of the importance of sex-linked genes in speciation.

  3. Medial prefrontal cortex: genes linked to bipolar disorder and schizophrenia have altered expression in the highly social maternal phenotype.

    Science.gov (United States)

    Eisinger, Brian E; Driessen, Terri M; Zhao, Changjiu; Gammie, Stephen C

    2014-01-01

    The transition to motherhood involves CNS changes that modify sociability and affective state. However, these changes also put females at risk for post-partum depression and psychosis, which impairs parenting abilities and adversely affects children. Thus, changes in expression and interactions in a core subset of genes may be critical for emergence of a healthy maternal phenotype, but inappropriate changes of the same genes could put women at risk for post-partum disorders. This study evaluated microarray gene expression changes in medial prefrontal cortex (mPFC), a region implicated in both maternal behavior and psychiatric disorders. Post-partum mice were compared to virgin controls housed with females and isolated for identical durations. Using the Modular Single-set Enrichment Test (MSET), we found that the genetic landscape of maternal mPFC bears statistical similarity to gene databases associated with schizophrenia (5 of 5 sets) and bipolar disorder (BPD, 3 of 3 sets). In contrast to previous studies of maternal lateral septum (LS) and medial preoptic area (MPOA), enrichment of autism and depression-linked genes was not significant (2 of 9 sets, 0 of 4 sets). Among genes linked to multiple disorders were fatty acid binding protein 7 (Fabp7), glutamate metabotropic receptor 3 (Grm3), platelet derived growth factor, beta polypeptide (Pdgfrb), and nuclear receptor subfamily 1, group D, member 1 (Nr1d1). RT-qPCR confirmed these gene changes as well as FMS-like tyrosine kinase 1 (Flt1) and proenkephalin (Penk). Systems-level methods revealed involvement of developmental gene networks in establishing the maternal phenotype and indirectly suggested a role for numerous microRNAs and transcription factors in mediating expression changes. Together, this study suggests that a subset of genes involved in shaping the healthy maternal brain may also be dysregulated in mental health disorders and put females at risk for post-partum psychosis with aspects of schizophrenia

  4. Medial prefrontal cortex: genes linked to bipolar disorder and schizophrenia have altered expression in the highly social maternal phenotype

    Directory of Open Access Journals (Sweden)

    Brian E Eisinger

    2014-04-01

    Full Text Available The transition to motherhood involves CNS changes that modify sociability and affective state. However, these changes also put females at risk for postpartum depression and psychosis, which impairs parenting abilities and adversely affects children. Thus, changes in expression and interactions in a core subset of genes may be critical for emergence of a healthy maternal phenotype, but inappropriate changes of the same genes could put women at risk for postpartum disorders. This study evaluated microarray gene expression changes in medial prefrontal cortex (mPFC, a region implicated in both maternal behavior and psychiatric disorders. Postpartum mice were compared to virgin controls housed with females and isolated for identical durations. Using the Modular Single-set Enrichment Test (MSET, we found that the genetic landscape of maternal mPFC bears statistical similarity to gene databases associated with schizophrenia (5 of 5 sets and bipolar disorder (BPD, 3 of 3 sets. In contrast to previous studies of maternal lateral septum and medial preoptic area, enrichment of autism and depression-linked genes was not significant (2 of 9 sets, 0 of 4 sets. Among genes linked to multiple disorders were fatty acid binding protein 7 (Fabp7, glutamate metabotropic receptor 3 (Grm3, platelet derived growth factor, beta polypeptide (Pdgfrb, and nuclear receptor subfamily 1, group D, member 1 (Nr1d1. RT-qPCR confirmed these gene changes as well as FMS-like tyrosine kinase 1 (Flt1 and proenkephalin (Penk. Systems-level methods revealed involvement of developmental gene networks in establishing the maternal phenotype and indirectly suggested a role for numerous microRNAs and transcription factors in mediating expression changes. Together, this study suggests that a subset of genes involved in shaping the healthy maternal brain may also be dysregulated in mental health disorders and put females at risk for postpartum psychosis with aspects of schizophrenia and BPD.

  5. Variation in the X-linked EFHC2 gene is associated with social cognitive abilities in males.

    Science.gov (United States)

    Startin, Carla M; Fiorentini, Chiara; de Haan, Michelle; Skuse, David H

    2015-01-01

    Females outperform males on many social cognitive tasks. X-linked genes may contribute to this sex difference. Males possess one X chromosome, while females possess two X chromosomes. Functional variations in X-linked genes are therefore likely to impact more on males than females. Previous studies of X-monosomic women with Turner syndrome suggest a genetic association with facial fear recognition abilities at Xp11.3, specifically at a single nucleotide polymorphism (SNP rs7055196) within the EFHC2 gene. Based on a strong hypothesis, we investigated an association between variation at SNP rs7055196 and facial fear recognition and theory of mind abilities in males. As predicted, males possessing the G allele had significantly poorer facial fear detection accuracy and theory of mind abilities than males possessing the A allele (with SNP variant accounting for up to 4.6% of variance). Variation in the X-linked EFHC2 gene at SNP rs7055196 is therefore associated with social cognitive abilities in males.

  6. Why tight-binding theory?

    Science.gov (United States)

    Harrison, Walter A.

    2002-12-01

    In the context of computational physics other methods are more accurate, but tight-binding theory allows very direct physical interpretation and is simple enough to allow much more realistic treatments beyond the local density approximation. We address several important questions of this last category: How does the gap enhancement from Coulomb correlations vary from material to material? Should the enhanced gap be used for calculating the dielectric constant? For calculating the effective mass in k-dot-p theory? How valid is the scissors approximation? How does one line up bands at an interface? How should we match the envelope function at interfaces in effective-mass theory? Why can the resulting quantum-well states seem to violate the uncertainty principle? How should f-shell electrons be treated when they are intermediate between band-like and core-like? The answers to all of these questions are given and discussed.

  7. Diagnosing the tight building syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, S.A.

    1987-12-01

    Formaldehyde is but one of many chemicals capable of causing the tight building syndrome or environmentally induced illness (EI). The spectrum of symptoms it may induce includes attacks of headache, flushing, laryngitis, dizziness, nausea, extreme weakness, arthralgia, unwarranted depression, dysphonia, exhaustion, inability to think clearly, arrhythmia or muscle spasms. The nonspecificity of such symptoms can baffle physicians from many specialties. Presented herein is a simple office method for demonstrating that formaldehyde is among the etiologic agents triggering these symptoms. The very symptoms that patients complain of can be provoked within minutes, and subsequently abolished, with an intradermal injection of the appropriate strength of formaldehyde. This injection aids in convincing the patient of the cause of the symptoms so he can initiate measure to bring his disease under control.

  8. Invasive tightly coupled processor arrays

    CERN Document Server

    LARI, VAHID

    2016-01-01

    This book introduces new massively parallel computer (MPSoC) architectures called invasive tightly coupled processor arrays. It proposes strategies, architecture designs, and programming interfaces for invasive TCPAs that allow invading and subsequently executing loop programs with strict requirements or guarantees of non-functional execution qualities such as performance, power consumption, and reliability. For the first time, such a configurable processor array architecture consisting of locally interconnected VLIW processing elements can be claimed by programs, either in full or in part, using the principle of invasive computing. Invasive TCPAs provide unprecedented energy efficiency for the parallel execution of nested loop programs by avoiding any global memory access such as GPUs and may even support loops with complex dependencies such as loop-carried dependencies that are not amenable to parallel execution on GPUs. For this purpose, the book proposes different invasion strategies for claiming a desire...

  9. Fingerprinting with Equiangular Tight Frames

    CERN Document Server

    Mixon, Dustin G; Kiyavash, Negar; Fickus, Matthew

    2011-01-01

    Digital fingerprinting is a framework for marking media files, such as images, music, or movies, with user-specific signatures to deter illegal distribution. Multiple users can collude to produce a forgery that can potentially overcome a fingerprinting system. This paper proposes an equiangular tight frame fingerprint design which is robust to such collusion attacks. We motivate this design by considering digital fingerprinting in terms of compressed sensing. The attack is modeled as linear averaging of multiple marked copies before adding a Gaussian noise vector. The content owner can then determine guilt by exploiting correlation between each user's fingerprint and the forged copy. The worst-case error probability of this detection scheme is analyzed and bounded. Simulation results demonstrate the average-case performance is similar to the performance of orthogonal and simplex fingerprint designs, while accommodating several times as many users.

  10. The effect of hitch-hiking on genes linked to a balanced polymorphism in a subdivided population

    DEFF Research Database (Denmark)

    Schierup, M H; Charlesworth, D; Vekemans, X

    2000-01-01

    The effect of multi-allelic balancing selection on nucleotide diversity at linked neutral sites was investigated by simulations of subdivided populations. The motivation is to understand the behaviour of self-recognition systems such as the MHC and plant self-incompatibility. For neutral sites, t...... to detect balancing selection by its effects on linked variation, using tests such as Tajima's D, is reduced when genes in a subdivided population are sampled from the total population, rather than within demes. Udgivelsesdato: 2000-Aug...

  11. Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency

    Directory of Open Access Journals (Sweden)

    B.E. Strauss

    2007-05-01

    Full Text Available A successful gene therapy clinical trial that also encountered serious adverse effects has sparked extensive study and debate about the future directions for retrovirus-mediated interventions. Treatment of X-linked severe combined immunodeficiency with an oncoretrovirus harboring a normal copy of the gc gene was applied in two clinical trials, essentially curing 13 of 16 infants, restoring a normal immune system without the need for additional immune-related therapies. Approximately 3 years after their gene therapy, tragically, 3 of these children, all from the same trial, developed leukemia as a result of this experimental treatment. The current understanding of the mechanism behind this leukemogenesis involves three critical and cooperating factors, i.e., viral integration, oncogene activation, and the function of the therapeutic gene. In this review, we will explore the causes of this unwanted event and some of the possibilities for reducing the risk of its reoccurrence.

  12. A novel BTK gene mutation creates a de-novo splice site in an X-linked agammaglobulinemia patient.

    Science.gov (United States)

    Chear, Chai Teng; Ripen, Adiratna Mat; Mohamed, Sharifah Adlena Syed; Dhaliwal, Jasbir Singh

    2015-04-15

    Bruton's tyrosine kinase (BTK), encoded by the BTK gene, is a cytoplasmic protein critical in B cell development. Mutations in the BTK gene cause X-linked agammaglobulinemia (XLA), a primary immunodeficiency with characteristically low or absent B cells and antibodies. This report describes a five year-old boy who presented with otitis externa, arthritis, reduced immunoglobulins and no B cells. Flow cytometry showed undetectable monocyte BTK expression. Sequencing revealed a novel mutation at exon 13 of the BTK gene which created a de novo splice site with a proximal 5 nucleotide loss resulting in a truncated BTK protein. The patient still suffered from ear infection despite intravenous immunoglobulin replacement therapy. In this study, mosaicism was seen only in the mother's genomic DNA. These results suggest that a combination of flow cytometry and BTK gene analysis is important for XLA diagnosis and carrier screening.

  13. The relationship between three X-linked genes and the risk for hypertension among northeastern Han Chinese.

    Science.gov (United States)

    Li, Jinxin; Feng, Min; Wang, Yanli; Li, Yaodong; Zhang, Yanyi; Li, Lei; Xiong, Jian; Lu, Changzhu; Wang, Bin; Cheng, Zuheng; Tang, Baopeng; Niu, Wenquan

    2015-12-01

    Incidences of hypertension are increasing and this condition is more common in men than in women. We selected six well-characterized polymorphisms from three X-linked genes (ACE2, AGTR2, apelin) aiming to investigate their interactive association with hypertension among northeastern Han Chinese. This was a case-control study involving 1009 hypertensive patients and 756 normotensive controls. All polymorphisms except rs3761581 in the apelin gene satisfied the Hardy-Weinberg equilibrium in females. The genotype and allele distributions of rs1403543 in the AGTR2 gene and rs56204867 in the apelin gene differed significantly between patients and controls for both genders, even after the Bonferroni correction (Pgenes by themselves may play an independent leading role in determining susceptibility to hypertension in both genders. © The Author(s) 2014.

  14. A young Drosophila duplicate gene plays essential roles in spermatogenesis by regulating several Y-linked male fertility genes.

    Directory of Open Access Journals (Sweden)

    Yun Ding

    Full Text Available Gene duplication is supposed to be the major source for genetic innovations. However, how a new duplicate gene acquires functions by integrating into a pathway and results in adaptively important phenotypes has remained largely unknown. Here, we investigated the biological roles and the underlying molecular mechanism of the young kep1 gene family in the Drosophila melanogaster species subgroup to understand the origin and evolution of new genes with new functions. Sequence and expression analysis demonstrates that one of the new duplicates, nsr (novel spermatogenesis regulator, exhibits positive selection signals and novel subcellular localization pattern. Targeted mutagenesis and whole-transcriptome sequencing analysis provide evidence that nsr is required for male reproduction associated with sperm individualization, coiling, and structural integrity of the sperm axoneme via regulation of several Y chromosome fertility genes post-transcriptionally. The absence of nsr-like expression pattern and the presence of the corresponding cis-regulatory elements of the parental gene kep1 in the pre-duplication species Drosophila yakuba indicate that kep1 might not be ancestrally required for male functions and that nsr possibly has experienced the neofunctionalization process, facilitated by changes of trans-regulatory repertories. These findings not only present a comprehensive picture about the evolution of a new duplicate gene but also show that recently originated duplicate genes can acquire multiple biological roles and establish novel functional pathways by regulating essential genes.

  15. Derivation of consensus inactivation status for X-linked genes from genome-wide studies.

    Science.gov (United States)

    Balaton, Bradley P; Cotton, Allison M; Brown, Carolyn J

    2015-01-01

    X chromosome inactivation is the epigenetic silencing of the majority of the genes on one of the X chromosomes in XX therian mammals. In humans, approximately 15 % of genes consistently escape from this inactivation and another 15 % of genes vary between individuals or tissues in whether they are subject to, or escape from, inactivation. Multiple studies have provided inactivation status calls for a large subset of the genes on the X chromosome; however, these studies vary in which genes they were able to make calls for and in some cases which call they give a specific gene. This analysis aggregated three published studies that have examined X chromosome inactivation status of genes across the X chromosome, generating consensus calls and identifying discordancies. The impact of expression level and chromosomal location on X chromosome inactivation status was also assessed. Overall, we assigned a consensus XCI status 639 genes, including 78 % of protein-coding genes expressed outside of the testes, with a lower frequency for non-coding RNA and testis-specific genes. Study-specific discordancies suggest that there may be instability of XCI during cell culture and also highlight study-specific variations in call type. We observe an enrichment of discordant genes at boundaries between genes subject to and escaping from inactivation. This study has compiled a comprehensive list of X-chromosome inactivation statuses for genes and also discovered some biases which will help guide future studies examining X-chromosome inactivation.

  16. Affected kindred analysis of human X chromosome exomes to identify novel X-linked intellectual disability genes.

    Directory of Open Access Journals (Sweden)

    Tejasvi S Niranjan

    Full Text Available X-linked Intellectual Disability (XLID is a group of genetically heterogeneous disorders caused by mutations in genes on the X chromosome. Deleterious mutations in ~10% of X chromosome genes are implicated in causing XLID disorders in ~50% of known and suspected XLID families. The remaining XLID genes are expected to be rare and even private to individual families. To systematically identify these XLID genes, we sequenced the X chromosome exome (X-exome in 56 well-established XLID families (a single affected male from 30 families and two affected males from 26 families using an Agilent SureSelect X-exome kit and the Illumina HiSeq 2000 platform. To enrich for disease-causing mutations, we first utilized variant filters based on dbSNP, the male-restricted portions of the 1000 Genomes Project, or the Exome Variant Server datasets. However, these databases present limitations as automatic filters for enrichment of XLID genes. We therefore developed and optimized a strategy that uses a cohort of affected male kindred pairs and an additional small cohort of affected unrelated males to enrich for potentially pathological variants and to remove neutral variants. This strategy, which we refer to as Affected Kindred/Cross-Cohort Analysis, achieves a substantial enrichment for potentially pathological variants in known XLID genes compared to variant filters from public reference databases, and it has identified novel XLID candidate genes. We conclude that Affected Kindred/Cross-Cohort Analysis can effectively enrich for disease-causing genes in rare, Mendelian disorders, and that public reference databases can be used effectively, but cautiously, as automatic filters for X-linked disorders.

  17. Affected kindred analysis of human X chromosome exomes to identify novel X-linked intellectual disability genes.

    Science.gov (United States)

    Niranjan, Tejasvi S; Skinner, Cindy; May, Melanie; Turner, Tychele; Rose, Rebecca; Stevenson, Roger; Schwartz, Charles E; Wang, Tao

    2015-01-01

    X-linked Intellectual Disability (XLID) is a group of genetically heterogeneous disorders caused by mutations in genes on the X chromosome. Deleterious mutations in ~10% of X chromosome genes are implicated in causing XLID disorders in ~50% of known and suspected XLID families. The remaining XLID genes are expected to be rare and even private to individual families. To systematically identify these XLID genes, we sequenced the X chromosome exome (X-exome) in 56 well-established XLID families (a single affected male from 30 families and two affected males from 26 families) using an Agilent SureSelect X-exome kit and the Illumina HiSeq 2000 platform. To enrich for disease-causing mutations, we first utilized variant filters based on dbSNP, the male-restricted portions of the 1000 Genomes Project, or the Exome Variant Server datasets. However, these databases present limitations as automatic filters for enrichment of XLID genes. We therefore developed and optimized a strategy that uses a cohort of affected male kindred pairs and an additional small cohort of affected unrelated males to enrich for potentially pathological variants and to remove neutral variants. This strategy, which we refer to as Affected Kindred/Cross-Cohort Analysis, achieves a substantial enrichment for potentially pathological variants in known XLID genes compared to variant filters from public reference databases, and it has identified novel XLID candidate genes. We conclude that Affected Kindred/Cross-Cohort Analysis can effectively enrich for disease-causing genes in rare, Mendelian disorders, and that public reference databases can be used effectively, but cautiously, as automatic filters for X-linked disorders.

  18. Functional analysis of seven genes linked to body mass index and adiposity by genome-wide association studies: a review.

    Science.gov (United States)

    Speakman, John R

    2013-01-01

    Genome-wide association studies (GWAS) have identified a total of about 40 single nucleotide polymorphisms (SNPs) that show significant linkage to body mass index, a widely utilised surrogate measure of adiposity. However, only 8 of these associations have been confirmed by follow-up GWAS using more sophisticated measures of adiposity (computed tomography). Among these 8, there is a SNP close to the gene FTO which has been the subject of considerable work to diagnose its function. The remaining 7 SNPs are adjacent to, or within, the genes NEGR1, TMEM18, ETV5, FLJ35779, LINGO2, SH2B1 and GIPR, most of which are less well studied than FTO, particularly in the context of obesity. This article reviews the available data on the functions of these genes, including information gleaned from studies in humans and animal models. At present, we have virtually no information on the putative mechanism associating the genes FLJ35779 and LINGO2 to obesity. All of these genes are expressed in the brain, and for 2 of them (SH2B1 and GIPR), a direct link to the appetite regulation system is known. SH2B1 is an enhancer of intracellular signalling in the JAK-STAT pathway, and GIPR is the receptor for an appetite-linked hormone (GIP) produced by the alimentary tract. NEGR1, ETV5 and SH2B1 all have suggested roles in neurite outgrowth, and hence SNPs adjacent to these genes may affect development of the energy balance circuitry. Although the genes have central patterns of gene expression, implying a central neuronal connection to energy balance, for at least 4 of them (NEGR1, TMEM18, SH2B1 and GIPR), there are also significant peripheral functions related to adipose tissue biology. These functions may contribute to their effects on the obese phenotype. © 2013 S. Karger AG, Basel.

  19. Familial idiopathic gonadotropin deficiency not linked to gene for gonadotropin-releasing hormone (GnRH) in Brazilian kindred

    Energy Technology Data Exchange (ETDEWEB)

    Faraco, J.; Francke, U.; Toledo, S. [Stanford Univ. School of Medicine, CA (United States)

    1994-09-01

    Familial idiopathic gonadotropin deficiency (FIGD) is an autosomal recessive disorder which results in failure to develop secondary sexual characteristics. The origin is a hypothalamic defect resulting in insufficient secretion of gonadotropin-releasing hormone GnRH (also called LHRH, luteinizing hormone releasing hormone) and follicle-stimuating hormone (FSH). FIGD has been determined to be a separate entity from Kallmann syndrome which presents with hypogonadism as well as anosmia. The FIGD phenotype appears to be analogous to the phenotype of the hpg (hypogonadal) mouse. Because the hpg phenotype is the result of a structurally abnormal GnRH gene, we have studied the GnRH gene in individuals from a previously reported Brazilian FIGD family. An informative dimorphic marker in the signal peptide sequence of the GnRH gene allowed assessment of linkage between the disease gene and the GnRH locus in this pedigree. We have concluded that the GnRH locus is not linked to the disease-causing mutation in these hypogonadal individuals. Recent evidence suggests that neuropeptide Y (NPY) may play a role in the initiation of puberty. We hypothesize that mutations in NPY may result in failure to secrete GnRH. We have characterized three diallelic frequent-cutter restriction fragment length polymorphisms within the human NPY locus, and are currently using these markers to determine if the NPY gene is linked to, and possibly the site of the disease mutation in this kindred.

  20. Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD

    Directory of Open Access Journals (Sweden)

    Rogaeva Ekaterina

    2006-12-01

    Full Text Available Abstract Background A new locus for amyotrophic lateral sclerosis – frontotemporal dementia (ALS-FTD has recently been ascribed to chromosome 9p. Methods We identified chromosome 9p segregating haplotypes within two families with ALS-FTD (F476 and F2 and undertook mutational screening of candidate genes within this locus. Results Candidate gene sequencing at this locus revealed the presence of a disease segregating stop mutation (Q342X in the intraflagellar transport 74 (IFT74 gene in family 476 (F476, but no mutation was detected within IFT74 in family 2 (F2. While neither family was sufficiently informative to definitively implicate or exclude IFT74 mutations as a cause of chromosome 9-linked ALS-FTD, the nature of the mutation observed within F476 (predicted to truncate the protein by 258 amino acids led us to sequence the open reading frame of this gene in a large number of ALS and FTD cases (n = 420. An additional sequence variant (G58D was found in a case of sporadic semantic dementia. I55L sequence variants were found in three other unrelated affected individuals, but this was also found in a single individual among 800 Human Diversity Gene Panel samples. Conclusion Confirmation of the pathogenicity of IFT74 sequence variants will require screening of other chromosome 9p-linked families.

  1. Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa.

    Science.gov (United States)

    Beltran, William A; Cideciyan, Artur V; Lewin, Alfred S; Iwabe, Simone; Khanna, Hemant; Sumaroka, Alexander; Chiodo, Vince A; Fajardo, Diego S; Román, Alejandro J; Deng, Wen-Tao; Swider, Malgorzata; Alemán, Tomas S; Boye, Sanford L; Genini, Sem; Swaroop, Anand; Hauswirth, William W; Jacobson, Samuel G; Aguirre, Gustavo D

    2012-02-07

    Hereditary retinal blindness is caused by mutations in genes expressed in photoreceptors or retinal pigment epithelium. Gene therapy in mouse and dog models of a primary retinal pigment epithelium disease has already been translated to human clinical trials with encouraging results. Treatment for common primary photoreceptor blindness, however, has not yet moved from proof of concept to the clinic. We evaluated gene augmentation therapy in two blinding canine photoreceptor diseases that model the common X-linked form of retinitis pigmentosa caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, which encodes a photoreceptor ciliary protein, and provide evidence that the therapy is effective. After subretinal injections of adeno-associated virus-2/5-vectored human RPGR with human IRBP or GRK1 promoters, in vivo imaging showed preserved photoreceptor nuclei and inner/outer segments that were limited to treated areas. Both rod and cone photoreceptor function were greater in treated (three of four) than in control eyes. Histopathology indicated normal photoreceptor structure and reversal of opsin mislocalization in treated areas expressing human RPGR protein in rods and cones. Postreceptoral remodeling was also corrected: there was reversal of bipolar cell dendrite retraction evident with bipolar cell markers and preservation of outer plexiform layer thickness. Efficacy of gene therapy in these large animal models of X-linked retinitis pigmentosa provides a path for translation to human treatment.

  2. Organization of a resistance gene cluster linked to rhizomania resistance in sugar beet

    Science.gov (United States)

    Genetic resistance to rhizomania has been in use for over 40 years. Characterization of the molecular basis for susceptibility and resistance has proved challenging. Nucleotide-binding leucine-rich-repeat-containing (NB-LRR) genes have been implicated in numerous gene-for-gene resistance interaction...

  3. Genomewide association analysis for awn length linked to the seed shattering gene qSH1 in rice

    Indian Academy of Sciences (India)

    RISPER AUMA MAGWA; HU ZHAO; WEN YAO; WEIBO XIE; LIN YANG; YONGZHONG XING; XUFENG BAI

    2016-09-01

    Awn is one of the most important domesticated traits in rice (Oryza sativa). Understanding the genetic basis of awn length is important for grain harvest and production, because long awn length is disadvantageous for both grain harvest and milling. We investigated the awn length of 529 rice cultivars and performed a Genomewide association studies (GWAS) in the indica andjaponica subpopulations, and the whole population. In total, we found 17 loci associated with awn length. Of these loci, seven were linked to previously reported quantitative trait loci, and one was linked to the awn gene An-1 . Nine novel loci were repeatedly identified in different environments. One of the nine associations was identified in both the whole and japonica populations. Special interest was the detection of the most significant association SNP, sf0136352825, which was less than 95 kb from the seed shattering gene qSH1. These results may provide potentially favourable haplotypes for molecular breeding in rice.

  4. AFLP Marker Linked to Turnip Mosaic Virus Susceptible Gene in Chinese Cabbage (Brassica rapa L.ssp.pekinensis)

    Institute of Scientific and Technical Information of China (English)

    HAN He-ping; SUN Ri-fei; ZHANG Shu-jiang; LI Fei; ZHANG Shi-fan; NIU Xin-ke

    2004-01-01

    Turnip mosaic virus (TuMV) which has several strains causes the most important virusdisease in Chinese cabbage in terms of crop damage. In China, Chinese cabbage is infectedby a mixture of strains, breeding of cultivar for the TuMV resistance has become themajor aim. Screening the molecular marker linked to the TuMV-resistance gene formolecular assisted selection is the major method to improve the breeding efficiency. Inthis study, we used AFLP technique and the method of bulked segregant analysis(BSA) tostudy the progeny of Brp0058 x Brp0108, and identified two DNA molecular marker linked toTurnip mosaic virus-resistance gene with a recombination frequency 7.5 cM and 8.4 cM.

  5. Y-linked variation for autosomal immune gene regulation has the potential to shape sexually dimorphic immunity.

    Science.gov (United States)

    Kutch, Ian C; Fedorka, Kenneth M

    2015-12-01

    Sexually dimorphic phenotypes arise from the differential expression of male and female shared genes throughout the genome. Unfortunately, the underlying molecular mechanisms by which dimorphic regulation manifests and evolves are unclear. Recent work suggests that Y-chromosomes may play an important role, given that Drosophila melanogaster Ys were shown to influence the regulation of hundreds of X and autosomal genes. For Y-linked regulatory variation (YRV) to facilitate sexually dimorphic evolution, however, it must exist within populations (where selection operates) and influence male fitness. These criteria have seldom been investigated, leaving the potential for dimorphic evolution via YRV unclear. Interestingly, male and female D. melanogaster differ in immune gene regulation. Furthermore, immune gene regulation appears to be influenced by the Y-chromosome, suggesting it may contribute to dimorphic immune evolution. We address this possibility by introgressing Y-chromosomes from a single wild population into an isogenic background (to create Y-lines) and assessing immune gene regulation and bacterial defence. We found that Y-line males differed in their immune gene regulation and their ability to defend against Serratia marcescens. Moreover, gene expression and bacterial defence were positively genetically correlated. These data indicate that the Y-chromosome has the potential to shape the evolution of sexually dimorphic immunity in this system.

  6. Extended-spectrum β-lactamases, carbapenemases and the mcr-1 gene: is there a historical link?

    Science.gov (United States)

    Rhouma, Mohamed; Letellier, Ann

    2017-03-01

    The plasmid mediated mcr-1 gene encoding for Enterobacteriaceae colistin resistance has been recently identified across five continents. The objective of the present study was to trace historical events concerning the discovery and emergence of the mcr-1 gene along with ESBL and carbapenemase genes since several studies have reported identifying mcr-1 genes among Extended-Spectrum β-Lactamases (ESBL) and/or carbapenemase producing Escherichia coli. A retrospective study reported the identification of the mcr-1 gene in E. coli strains isolated in the 1980s, and this seems to correspond to the first identification of ESBL enzymes. The first discovery of the New Delhi metallo-beta-lactamase-1 (NDM-1) in 2009 was associated with a significant increase in mcr-1 gene prevalence in E. coli strains obtained from food producing animals. We noticed that a historical link has existed between mcr-1, ESBL and carbapenemase genes since the 1980s, and we believe that the re-evaluation of colistin use in livestock needs an overall approach that includes not only colistin use reduction but also the reduction of all antibiotic use. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  7. Identification of an AFLP marker linked to the stripe rust resistance gene Yr1O in wheat

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AFLP analysis of near-isogenic lines of the stripe rust resistance gene Yr10 was carried out with 6 Pst Ⅰprimers and 10 Taq Ⅰ -primers with the donor parent of Yr10 gene as the check. A total of about 4200 distinguishable bands were amplified, of which 5 were stable. The genetic linkage of the 5 polymorphic DNA fragments with the target gene were tested preliminarily on a segregating F2 population derived from a cross between the gene donor parent "Moro" and susceptible cultivar "Mingxian 169". The DNA fragment PT0502 was found closely linked to the Yr10 gene and cloned and sequenced. Based on the sequence specific primers for PCR were designed and synthesized. Genetic linkage analysis with 195 segregating F2 plants indicated that the genetic distance was 05 cM between the main product SC200 fragment produced by PCR with the primers and the Yr10 gene. The primers can be used to detect the Yr10 gene quickly, effectively and exactly.``

  8. X-Linked Candidate Genes for a Ciliopathy-Like Disorder.

    Science.gov (United States)

    Pavey, Ashleigh R; Vilboux, Thierry; Babcock, Holly E; Ahronovich, Margot; Solomon, Benjamin D

    2016-04-01

    The ability to interrogate the genome via chromosomal microarray and sequencing-based technologies has accelerated the ability to rapidly and accurately define etiologies as well as new candidate genes related to genetic conditions. We describe a male patient with a lethal presentation of a multiple congenital anomaly syndrome that appeared consistent with a ciliopathy phenotype. The patient was found to have a novel maternally inherited 1.9-Mb X chromosome deletion including 4 known genes. Presently, the biological functions of these genes are not well delineated. However, at least one of these genes may be a promising candidate gene for this pattern of anomalies based on the function of related genes and information from publicly available copy number variant databases of control and affected individuals. These genes would bear further scrutiny in larger cohorts of patients with similar phenotypes.

  9. An AFLP marker linked to the Pm-1 gene that confers resistance to Podosphaera xanthii race 1 in Cucumis melo

    Directory of Open Access Journals (Sweden)

    Ana Paula Matoso Teixeira

    2008-01-01

    Full Text Available Brazil produced 330,000 metric tons of melons in 2005, principally in the Northeast region where one of the most important melon pathogens is the powdery mildew fungus Podosphaera xanthii. The disease is controlled mainly by incorporating single dominant resistance genes into commercial hybrids. We report on linkage analysis of the Pm-1 resistance gene, introgressed from the AF125Pm-1 Cantalupensis Charentais-type breeding line into the yellow-fleshed melon (Group Inodorus breeding line AF426-S by backcrossing to produce the resistant line AF426-R, and the amplified fragment length polymorphism (AFLP marker M75/H35_155 reported to be polymorphic between AF426-S and AF426-R. Segregation analysis of M75/H35_155 using a backcross population of 143 plants derived from [AF426-R x AF426-S] x AF426-S and screened for resistance to P. xanthii race 1 produced a recombination frequency of 4.9%, indicating close linkage between M75/H35_155 and Pm-1. Using the same segregating population, the M75/H35_155 marker had previously been reported to be distantly linked to Prv¹, a gene conferring resistance to papaya ringspot virus-type W. Since M75/H35_155 is linked to Prv¹ at a distance of 40.9 cM it is possible that Pm-1 and Prv¹ are also linked.

  10. X-linked genes and risk of orofacial clefts: evidence from two population-based studies in Scandinavia.

    Directory of Open Access Journals (Sweden)

    Astanand Jugessur

    Full Text Available BACKGROUND: Orofacial clefts are common birth defects of complex etiology, with an excess of males among babies with cleft lip and palate, and an excess of females among those with cleft palate only. Although genes on the X chromosome have been implicated in clefting, there has been no association analysis of X-linked markers. METHODOLOGY/PRINCIPAL FINDINGS: We added new functionalities in the HAPLIN statistical software to enable association analysis of X-linked markers and an exploration of various causal scenarios relevant to orofacial clefts. Genotypes for 48 SNPs in 18 candidate genes on the X chromosome were analyzed in two population-based samples from Scandinavia (562 Norwegian and 235 Danish case-parent triads. For haplotype analysis, we used a sliding-window approach and assessed isolated cleft lip with or without cleft palate (iCL/P separately from isolated cleft palate only (iCPO. We tested three statistical models in HAPLIN, allowing for: i the same relative risk in males and females, ii sex-specific relative risks, and iii X-inactivation in females. We found weak but consistent associations with the oral-facial-digital syndrome 1 (OFD1 gene (formerly known as CXORF5 in the Danish iCL/P samples across all models, but not in the Norwegian iCL/P samples. In sex-specific analyses, the association with OFD1 was in male cases only. No analyses showed associations with iCPO in either the Norwegian or the Danish sample. CONCLUSIONS: The association of OFD1 with iCL/P is plausible given the biological relevance of this gene. However, the lack of replication in the Norwegian samples highlights the need to verify these preliminary findings in other large datasets. More generally, the novel analytic methods presented here are widely applicable to investigations of the role of X-linked genes in complex traits.

  11. X-linked genes and risk of orofacial clefts: evidence from two population-based studies in Scandinavia.

    Science.gov (United States)

    Jugessur, Astanand; Skare, Øivind; Lie, Rolv T; Wilcox, Allen J; Christensen, Kaare; Christiansen, Lene; Nguyen, Truc Trung; Murray, Jeffrey C; Gjessing, Håkon K

    2012-01-01

    Orofacial clefts are common birth defects of complex etiology, with an excess of males among babies with cleft lip and palate, and an excess of females among those with cleft palate only. Although genes on the X chromosome have been implicated in clefting, there has been no association analysis of X-linked markers. We added new functionalities in the HAPLIN statistical software to enable association analysis of X-linked markers and an exploration of various causal scenarios relevant to orofacial clefts. Genotypes for 48 SNPs in 18 candidate genes on the X chromosome were analyzed in two population-based samples from Scandinavia (562 Norwegian and 235 Danish case-parent triads). For haplotype analysis, we used a sliding-window approach and assessed isolated cleft lip with or without cleft palate (iCL/P) separately from isolated cleft palate only (iCPO). We tested three statistical models in HAPLIN, allowing for: i) the same relative risk in males and females, ii) sex-specific relative risks, and iii) X-inactivation in females. We found weak but consistent associations with the oral-facial-digital syndrome 1 (OFD1) gene (formerly known as CXORF5) in the Danish iCL/P samples across all models, but not in the Norwegian iCL/P samples. In sex-specific analyses, the association with OFD1 was in male cases only. No analyses showed associations with iCPO in either the Norwegian or the Danish sample. The association of OFD1 with iCL/P is plausible given the biological relevance of this gene. However, the lack of replication in the Norwegian samples highlights the need to verify these preliminary findings in other large datasets. More generally, the novel analytic methods presented here are widely applicable to investigations of the role of X-linked genes in complex traits.

  12. X-linked familial exudative vitreoretinopathy caused by an arginine to leucine substitution in exon 3 of the Norrie gene

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, K.; Perry, Y.M.; Ferrell, R.E. [Univ. of Pittsburg, PA (United States)] [and others

    1994-09-01

    Familial exudative vitreoretinopathy (FEVR) is a disorder characterized by abnormal vascularization of the peripheral retina affecting both the retina and the vitreous body. This is a bilateral disorder and leads to a clinical phenotype resembling retinopathy of prematurity, but affected individuals experience a normal gestational period, and they do not have a history of oxygen therapy. Manifestations of the disorder may include retinal folds, retinal traction, sub- or intraretinal exudates, and in severe cases enophthalmos or phthisis ultimately leading to blindness. Autosomal dominant and X-linked patterns of segregation have been reported. We studied a large three-generation family in which FEVR segregated as an X-linked recessive trait. The Norrie gene was examined because of a prior report of mutation in this gene in a small X-linked FEVR family. Exons 1-3 of the Norrie gene were amplified and screened for mutations by single stranded conformational analysis. A variant conformer of exon 3 was observed in an affected male and in combination with the normal conformer in an obligate carrier female. Sequence analysis revealed a G{r_arrow}T transversion destroying an MspI restriction site. The mutation was present in all affected males, and all obligate carrier females were heterozygous for the mutation. The mutation was not present in unaffected males or in 108 randomly selected normal females. The G{r_arrow}T mutation leads to the substitution of a hydrophobic leucine residue for the positively charged arginine normally present at position 121 of the Norrie gene product. This study confirms that mutation in the Norrie gene can lead to the FEVR phenotype and the existence of allelic heterogeneity.

  13. Tight Junctions in Salivary Epithelium

    Directory of Open Access Journals (Sweden)

    Olga J. Baker

    2010-01-01

    Full Text Available Epithelial cell tight junctions (TJs consist of a narrow belt-like structure in the apical region of the lateral plasma membrane that circumferentially binds each cell to its neighbor. TJs are found in tissues that are involved in polarized secretions, absorption functions, and maintaining barriers between blood and interstitial fluids. The morphology, permeability, and ion selectivity of TJ vary among different types of tissues and species. TJs are very dynamic structures that assemble, grow, reorganize, and disassemble during physiological or pathological events. Several studies have indicated the active role of TJ in intestinal, renal, and airway epithelial function; however, the functional significance of TJ in salivary gland epithelium is poorly understood. Interactions between different combinations of the TJ family (each with their own unique regulatory proteins define tissue specificity and functions during physiopathological processes; however, these interaction patterns have not been studied in salivary glands. The purpose of this review is to analyze some of the current data regarding the regulatory components of the TJ that could potentially affect cellular functions of the salivary epithelium.

  14. Stem loop sequences specific to transposable element IS605 are found linked to lipoprotein genes in Borrelia plasmids.

    Directory of Open Access Journals (Sweden)

    Nicholas Delihas

    Full Text Available BACKGROUND: Plasmids of Borrelia species are dynamic structures that contain a large number of repetitive genes, gene fragments, and gene fusions. In addition, the transposable element IS605/200 family, as well as degenerate forms of this IS element, are prevalent. In Helicobacter pylori, flanking regions of the IS605 transposase gene contain sequences that fold into identical small stem loops. These function in transposition at the single-stranded DNA level. METHODOLOGY/PRINCIPAL FINDINGS: In work reported here, bioinformatics techniques were used to scan Borrelia plasmid genomes for IS605 transposable element specific stem loop sequences. Two variant stem loop motifs are found in the left and right flanking regions of the transposase gene. Both motifs appear to have dispersed in plasmid genomes and are found "free-standing" and phylogenetically conserved without the associated IS605 transposase gene or the adjacent flanking sequence. Importantly, IS605 specific stem loop sequences are also found at the 3' ends of lipoprotein genes (PFam12 and PFam60, however the left and right sequences appear to develop their own evolutionary patterns. The lipoprotein gene-linked left stem loop sequences maintain the IS605 stem loop motif in orthologs but only at the RNA level. These show mutations whereby variants fold into phylogenetically conserved RNA-type stem loops that contain the wobble non-Watson-Crick G-U base-pairing. The right flanking sequence is associated with the family lipoprotein-1 genes. A comparison of homologs shows that the IS605 stem loop motif rapidly dissipates, but a more elaborate secondary structure appears to develop in its place. CONCLUSIONS/SIGNIFICANCE: Stem loop sequences specific to the transposable element IS605 are present in plasmid regions devoid of a transposase gene and significantly, are found linked to lipoprotein genes in Borrelia plasmids. These sequences are evolutionarily conserved and/or structurally developed in

  15. Detection of bacterial blight resistant gene xa5 using linked marker ...

    African Journals Online (AJOL)

    USER

    2010-06-14

    Jun 14, 2010 ... Key words: Rice, xa5, bacterial blight, linked marker. INTRODUCTION ... be the only reliable method to control the disease. Investigations ... DNA extraction. Total genomic DNA was extracted using young leaves at seedling.

  16. The sex-linked fidget mutation abolishes Brn4/Pou3f4 gene expression in the embryonic inner ear.

    Science.gov (United States)

    Phippard, D; Boyd, Y; Reed, V; Fisher, G; Masson, W K; Evans, E P; Saunders, J C; Crenshaw, E B

    2000-01-01

    We have demonstrated that the phenotype of the mouse mutant sex-linked fidget ( slf ) is caused by developmental malformations of the inner ear that result in hearing loss and vestibular dysfunction. Recently, pilot mapping experiments suggested that the mouse Brn4 / Pou3f4 gene co-segregated with the slf locus on the mouse X chromosome. These mapping data, in conjunction with the observation that the vertical head-shaking phenotype of slf mutants is identical to that observed in mice with a targeted deletion of the Brn4 gene, suggested that slf is a mutant allele of the Brn4 gene. In this paper, we have identified the nature of the slf mutation, and demonstrated that it is an X chromosomal inversion with one breakpoint close to Brn4. This inversion selectively eliminates the expression of the Brn4 gene in the developing inner ear, but not the neural tube. Finally, these results demonstrate that the slf mutation is a good mouse model for the most prevalent form of X-linked congenital deafness in man, which is associated with mutations in the human Brn4 ortholog, POU3F4.

  17. Linking Genes and Brain Development of Honeybee Workers: A Whole-Transcriptome Approach

    Science.gov (United States)

    Vleurinck, Christina; Raub, Stephan; Sturgill, David; Oliver, Brian; Beye, Martin

    2016-01-01

    Honeybees live in complex societies whose capabilities far exceed those of the sum of their single members. This social synergism is achieved mainly by the worker bees, which form a female caste. The worker bees display diverse collaborative behaviors and engage in different behavioral tasks, which are controlled by the central nervous system (CNS). The development of the worker brain is determined by the female sex and the worker caste determination signal. Here, we report on genes that are controlled by sex or by caste during differentiation of the worker’s pupal brain. We sequenced and compared transcriptomes from the pupal brains of honeybee workers, queens and drones. We detected 333 genes that are differently expressed and 519 genes that are differentially spliced between the sexes, and 1760 genes that are differentially expressed and 692 genes that are differentially spliced between castes. We further found that 403 genes are differentially regulated by both the sex and caste signals, providing evidence of the integration of both signals through differential gene regulation. In this gene set, we found that the molecular processes of restructuring the cell shape and cell-to-cell signaling are overrepresented. Our approach identified candidate genes that may be involved in brain differentiation that ensures the various social worker behaviors. PMID:27490820

  18. The somatic hypermutation activity of a follicular lymphoma links to large insertions and deletions of immunoglobulin genes.

    Science.gov (United States)

    Wu, H Y; Kaartinen, M

    1995-07-01

    A biopsy specimen from a patient with follicular lymphoma was divided into two fragments. DNA was extracted from one fragment and a 1.2 kb region of the functional heavy chain (IgH) gene was amplified, cloned and sequenced (eight clones). From the other fragment a cell line (HF-1) was started. The IgH gene region was amplified from the cell line, and sequenced without cloning. The nine sequences obtained could be arranged into a genealogical tree where the individual sequences differed from the deduced ancestor by 16-29 single nucleotide changes, some also by an insertion and/or a deletion. It is apparent that the sequence alterations were caused by somatic mutations during the growth of the lymphoma. The comparison of the sequences with two published (allelic) germline sequences of the human JH region showed approximately 20% non-homology. The differences included five additional multinucleotide insertion/deletion changes, the longest of them a 101-nucleotide insertion. Two long insertions were homologous to the adjacent germline sequences. We propose that most of the changes observed, including long deletions and insertions, represent or are linked to somatic hypermutation events of the Ig gene type. Although in a few cases large deletions and insertions (> 2 bp) have been found in mutated immunoglobulin genes, our results, for the first time, firmly link these deletions/insertions to somatic hypermutations; their frequency was found to be 2.2% of the observed mutational events in the non-translated gene regions. HF-1 is the first follicular lymphoma line successfully established from a lymphoma known to have hypermutated its Ig genes during the malignant growth. It is a candidate cell line to be studied for its ability to generate mutations of B cell type in cell cultures.

  19. Genes for and molecular markers linked with resistance to Phytophthora fragariae in strawberry

    NARCIS (Netherlands)

    Weg, van de W.E.; Henken, B.; Haymes, K.M.; den Nijs, A.P.M.

    1998-01-01

    A gene-for-gene model is presented which explains interactions between cultivars of strawberry and races of Phytophthora fragariae var. fragariae, the causal agent of red core (red stele) root rot. The model allows the constitution of a universal differential set of strawberry genotypes and the char

  20. Misregulation of Gene Expression and Sterility in Interspecies Hybrids: Causal Links and Alternative Hypotheses.

    Science.gov (United States)

    Civetta, Alberto

    2016-05-01

    Understanding the origin of species is of interest to biologist in general and evolutionary biologist in particular. Hybrid male sterility (HMS) has been a focus in studies of speciation because sterility imposes a barrier to free gene flow between organisms, thus effectively isolating them as distinct species. In this review, I focus on the role of differential gene expression in HMS and speciation. Microarray and qPCR assays have established associations between misregulation of gene expression and sterility in hybrids between closely related species. These studies originally proposed disrupted expression of spermatogenesis genes as a causative of sterility. Alternatively, rapid genetic divergence of regulatory elements, particularly as they relate to the male sex (fast-male evolution), can drive the misregulation of sperm developmental genes in the absence of sterility. The use of fertile hybrids (both backcross and F1 progeny) as controls has lent support to this alternative explanation. Differences in gene expression between fertile and sterile hybrids can also be influenced by a pattern of faster evolution of the sex chromosome (fast-X evolution) than autosomes. In particular, it would be desirable to establish whether known X-chromosome sterility factors can act as trans-regulatory drivers of genome-wide patterns of misregulation. Genome-wide expression studies coupled with assays of proxies of sterility in F1 and BC progeny have identified candidate HMS genes but functional assays, and a better phenotypic characterization of sterility phenotypes, are needed to rigorously test how these genes might contribute to HMS.

  1. Development of co-dominant SCAR markers linked to resistant gene against the Fusarium oxysporum f. sp. radicis-lycopersici.

    Science.gov (United States)

    Mutlu, Nedim; Demirelli, Aylin; Ilbi, Hülya; Ikten, Cengiz

    2015-09-01

    We developed highly reliable co-dominant SCAR markers linked to the Frl gene. FORL testing is difficult. The marker is expected to be quickly adapted for MAS by tomato breeders. Fusarium oxysporum f. sp. radicis-lycopersici causes Fusarium crown and root rot (FCR), an economically important soil-borne disease of tomato. The resistance against FCR is conferred by a single dominant gene (Frl) located on chromosome 9. The aim of this study was to develop molecular markers linked to the Frl gene for use in marker-assisted breeding (MAS) programs. The FCR-resistant 'Fla. 7781' and susceptible 'B560' lines were crossed, and F1 was both selfed and backcrossed to 'B560' to generate segregating F2 and BC1 populations. The two conserved set II (COSII) markers were found linked to the Frl gene, one co-segregated with FCR resistance in both F2 and BC1 populations and the other was 8.5 cM away. Both COSII markers were converted into co-dominant SCAR markers. SCARFrl marker produced a 950 and a 1000 bp fragments for resistant and susceptible alleles, respectively. The linkage of SCARFrl marker was confirmed in BC2F3 populations developed by backcrossing the resistant 'Fla. 7781' to five different susceptible lines. The SCARFrl marker has been in use in the tomato breeding programs in BATEM, Antalya, Turkey, since 2012 and has proved highly reliable. The SCARFrl marker is expected to aid in the development of FCR-resistant lines via marker-assisted selection (MAS).

  2. MAF45, a highly polymorphic marker for the pseudoautosomal region of the sheep genome, is not linked to the FecXI (Inverdale) gene.

    Science.gov (United States)

    Swarbrick, P A; Schmack, A E; Crawford, A M

    1992-07-01

    A highly polymorphic dinucleotide repeat, or microsatellite, that shows partial sex-linked inheritance in sheep has been isolated from the sheep genome. Our data indicate that the locus is in the pseudoautosomal region approximately 13 cm from the boundary with the sex-linked regions. The locus, designated MAF45, has 12 alleles with a PIC of 0.84. The same primers amplify a single polymorphic locus in cattle and goats. This locus was not linked to the Inverdale gene, an X-linked gene that increases the ovulation rate in sheep.

  3. Regulation of Gene Function: A Comparison of X-Linked Enzyme Activity Levels in Normal and Intersexual Triploids of DROSOPHILA MELANOGASTER

    Science.gov (United States)

    Lucchesi, John C.; Rawls, John M.

    1973-01-01

    We have measured gene function in normal and male-like intersexual triploids of Drosophila melanogaster by assaying crude extracts of whole flies or thoraces for levels of an X-linked (6-phosphogluconate dehydrogenase) and an autosomal (NADP-dependent isocitrate dehydrogenase) enzyme activity. Our observations lead us to conclude that each dose of the X-linked gene is more active in the cells of these intersexes than it is in normal triploid or diploid female cells. These results indicate that a level of activity intermediate between the normal male and female levels is possible for X-linked genes. PMID:4144727

  4. IL-2R{gamma} gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease

    Energy Technology Data Exchange (ETDEWEB)

    Henthorn, P.S.; Fimiani, V.M.; Patterson, D.F. [Univ. of Pennsylvania School of Veterinary Medicine, Philadelphia, PA (United States)] [and others

    1994-09-01

    X-linked severe combined immunodeficiency (SCID) is characterized by profound defects in cellular and humoral immunity and, in humans, is associated with mutations in the gene for the {gamma} chain of the IL-2 receptor (IL-2R{gamma}). We have examined this gene in a colony of dogs established from a single X-linked SCID carrier female. Affected dogs have a 4-bp deletion in the first exon of the IL-2R{gamma} gene, which precludes the production of a functional protein, demonstrating that the canine disease is a true homologue of human X-linked SCID. 37 refs., 3 figs.

  5. Intraneural GJB1 gene delivery improves nerve pathology in a model of X-linked Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Sargiannidou, Irene; Kagiava, Alexia; Bashiardes, Stavros; Richter, Jan; Christodoulou, Christina; Scherer, Steven S; Kleopa, Kleopas A

    2015-08-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is a common inherited neuropathy caused by mutations in the GJB1 gene encoding the gap junction protein connexin32 (Cx32). Clinical studies and disease models indicate that neuropathy mainly results from Schwann cell autonomous, loss-of-function mechanisms; therefore, CMT1X may be treatable by gene replacement. A lentiviral vector LV.Mpz-GJB1 carrying the GJB1 gene under the Schwann cell-specific myelin protein zero (Mpz) promoter was generated and delivered into the mouse sciatic nerve by a single injection immediately distal to the sciatic notch. Enhanced green fluorescent protein (EGFP) reporter gene expression was quantified and Cx32 expression was examined on a Cx32 knockout (KO) background. A gene therapy trial was performed in a Cx32 KO model of CMT1X. EGFP was expressed throughout the length of the sciatic nerve in up to 50% of Schwann cells starting 2 weeks after injection and remaining stable for up to 16 weeks. Following LV.Mpz-GJB1 injection into Cx32 KO nerves, we detected Cx32 expression and correct localization in non-compact myelin areas where gap junctions are normally formed. Gene therapy trial by intraneural injection in groups of 2-month-old Cx32 KO mice, before demyelination onset, significantly reduced the ratio of abnormally myelinated fibers (p = 0.00148) and secondary inflammation (p = 0.0178) at 6 months of age compared to mock-treated animals. Gene delivery using a lentiviral vector leads to efficient gene expression specifically in Schwann cells. Restoration of Cx32 expression ameliorates nerve pathology in a disease model and provides a promising approach for future treatments of CMT1X and other inherited neuropathies. © 2015 American Neurological Association.

  6. X chromosome-linked Kallmann syndrome: clinical heterogeneity in three siblings carrying an intragenic deletion of the KAL-1 gene.

    Science.gov (United States)

    Massin, Nathalie; Pêcheux, Christophe; Eloit, Corinne; Bensimon, Jean-Louis; Galey, Julie; Kuttenn, Frédérique; Hardelin, Jean-Pierre; Dodé, Catherine; Touraine, Philippe

    2003-05-01

    Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia. The gene underlying the X chromosome-linked form of the disease, KAL-1, consists of 14 coding exons. It encodes a glycoprotein, anosmin-1, which is involved in the embryonic migration of GnRH-synthesizing neurons and the differentiation of the olfactory bulbs. We describe herein the clinical heterogeneity in three affected brothers who carry a large deletion (exons 3-13) in KAL-1. All three had a history of hypogonadotropic hypogonadism with delayed puberty. Although brain magnetic resonance imaging showed hypoplastic olfactory bulbs in the three siblings, variable degrees of anosmia/hyposmia were shown by olfactometry. In addition, these brothers had different phenotypic anomalies, i.e. unilateral renal aplasia (siblings B and C), high-arched palate (sibling A), brachymetacarpia (sibling A), mirror movements (siblings A and B), and abnormal eye movements (sibling C). Last but not least, sibling A suffered from a severe congenital hearing impairment, a feature that had been reported in KS but had not yet been ascribed unambiguously to the X-linked form of the disease. The variable phenotype, both qualitatively and quantitatively, in this family further emphasizes the role of putative modifier genes, and/or epigenetic factors, in the expressivity of the X-linked KS.

  7. A multilevel pan-cancer map links gene mutations tocancer hallmarks

    Institute of Scientific and Technical Information of China (English)

    TheoAKnijnenburg; TychoBismeijer; LodewykFAWessels; IlyaShmulevich

    2015-01-01

    Background:A central challenge in cancer research is to create models that bridge the gap between the molecular level on which interventions can be designed and the cellular and tissue levels on which the disease phenotypes are manifested. This study was undertaken to construct such a model from functional annotations and explore its use when integrated with large-scale cancer genomics data. Methods:We created a map that connects genes to cancer hallmarks via signaling pathways. We projected gene mutation and focal copy number data from various cancer types onto this map. We performed statistical analyses to uncover mutually exclusive and co-occurring oncogenic aberrations within this topology. Results:Our analysis showed that although the genetic ifngerprint of tumor types could be very different, there were less variations at the level of hallmarks, consistent with the idea that different genetic alterations have similar functional outcomes. Additionally, we showed how the multilevel map could help to clarify the role of infrequently mutated genes, and we demonstrated that mutually exclusive gene mutations were more prevalent in pathways, whereas many co-occurring gene mutations were associated with hallmark characteristics. Conclusions:Overlaying this map with gene mutation and focal copy number data from various cancer types makes it possible to investigate the similarities and differences between tumor samples systematically at the levels of not only genes but also pathways and hallmarks.

  8. Imprinted Genes and the Environment: Links to the Toxic Metals Arsenic, Cadmium and Lead

    Directory of Open Access Journals (Sweden)

    Lisa Smeester

    2014-06-01

    Full Text Available Imprinted genes defy rules of Mendelian genetics with their expression tied to the parent from whom each allele was inherited. They are known to play a role in various diseases/disorders including fetal growth disruption, lower birth weight, obesity, and cancer. There is increasing interest in understanding their influence on environmentally-induced disease. The environment can be thought of broadly as including chemicals present in air, water and soil, as well as food. According to the Agency for Toxic Substances and Disease Registry (ATSDR, some of the highest ranking environmental chemicals of concern include metals/metalloids such as arsenic, cadmium, lead and mercury. The complex relationships between toxic metal exposure, imprinted gene regulation/expression and health outcomes are understudied. Herein we examine trends in imprinted gene biology, including an assessment of the imprinted genes and their known functional roles in the cell, particularly as they relate to toxic metals exposure and disease. The data highlight that many of the imprinted genes have known associations to developmental diseases and are enriched for their role in the TP53 and AhR pathways. Assessment of the promoter regions of the imprinted genes resulted in the identification of an enrichment of binding sites for two transcription factor families, namely the zinc finger family II and PLAG transcription factors. Taken together these data contribute insight into the complex relationships between toxic metals in the environment and imprinted gene biology.

  9. Prioritizing genes for X-linked diseases using population exome data.

    Science.gov (United States)

    Ge, Xiaoyan; Kwok, Pui-Yan; Shieh, Joseph T C

    2015-02-01

    Many new disease genes can be identified through high-throughput sequencing. Yet, variant interpretation for the large amounts of genomic data remains a challenge given variation of uncertain significance and genes that lack disease annotation. As clinically significant disease genes may be subject to negative selection, we developed a prediction method that measures paucity of non-synonymous variation in the human population to infer gene-based pathogenicity. Integrating human exome data of over 6000 individuals from the NHLBI Exome Sequencing Project, we tested the utility of the prediction method based on the ratio of non-synonymous to synonymous substitution rates (dN/dS) on X-chromosome genes. A low dN/dS ratio characterized genes associated with childhood disease and outcome. Furthermore, we identify new candidates for diseases with early mortality and demonstrate intragenic localized patterns of variants that suggest pathogenic hotspots. Our results suggest that intrahuman substitution analysis is a valuable tool to help prioritize novel disease genes in sequence interpretation.

  10. Uncultivated microbial eukaryotic diversity: a method to link ssu rRNA gene sequences with morphology.

    Directory of Open Access Journals (Sweden)

    Marissa B Hirst

    Full Text Available Protists have traditionally been identified by cultivation and classified taxonomically based on their cellular morphologies and behavior. In the past decade, however, many novel protist taxa have been identified using cultivation independent ssu rRNA sequence surveys. New rRNA "phylotypes" from uncultivated eukaryotes have no connection to the wealth of prior morphological descriptions of protists. To link phylogenetically informative sequences with taxonomically informative morphological descriptions, we demonstrate several methods for combining whole cell rRNA-targeted fluorescent in situ hybridization (FISH with cytoskeletal or organellar immunostaining. Either eukaryote or ciliate-specific ssu rRNA probes were combined with an anti-α-tubulin antibody or phalloidin, a common actin stain, to define cytoskeletal features of uncultivated protists in several environmental samples. The eukaryote ssu rRNA probe was also combined with Mitotracker® or a hydrogenosomal-specific anti-Hsp70 antibody to localize mitochondria and hydrogenosomes, respectively, in uncultivated protists from different environments. Using rRNA probes in combination with immunostaining, we linked ssu rRNA phylotypes with microtubule structure to describe flagellate and ciliate morphology in three diverse environments, and linked Naegleria spp. to their amoeboid morphology using actin staining in hay infusion samples. We also linked uncultivated ciliates to morphologically similar Colpoda-like ciliates using tubulin immunostaining with a ciliate-specific rRNA probe. Combining rRNA-targeted FISH with cytoskeletal immunostaining or stains targeting specific organelles provides a fast, efficient, high throughput method for linking genetic sequences with morphological features in uncultivated protists. When linked to phylotype, morphological descriptions of protists can both complement and vet the increasing number of sequences from uncultivated protists, including those of

  11. Inheritance of Resistance to SMV3 and Identification of RAPD Marker Linked to the Resistant Gene in Soybean

    Institute of Scientific and Technical Information of China (English)

    ZHENG Cui-ming; CHANG Ru-zhen; QIU Li-juan

    2002-01-01

    One SMV resistant soybean line (95-5383) was crossed with four susceptible soybean varieties/line ( HB1, Tiefeng21, Amsoy, Williams) and one resistant introduced line PI486355. Their F1 and F2individuals were identified for SMV resistance by inoculation with SMV3. The results showed that in the four crosses of resistant × susceptible, F1 were susceptible and the ratio of F2 populations was 1 resistant : 3susceptible (mosaic and necrosis), indicating that 95-5383 carries one recessive gene that confer resistance to SMV3. There is segregation of susceptibility in F2 progenies from the cross of 95-5383 × PI486355, indicating that the SMV3 resistant gene in 95-5383 is located at different locus from PI486355. By bulked segregating analysis (BSA) in F2 populations of 95-5383 × HB1, one codominant RAPD marker OPN11980/1070 closely linked to SMV3 resistance gene amplified with RAPD primer OPN11 was identified. The DNA fragment OPN11980 was amplified in resistant parent 95-5383 and resistant bulk, and OPN111070 was amplified in susceptible parent HB1 and susceptible bulk. OPN11980/1070 was amplified in F1. Identification of the markers in F2 plants showed that the codominant marker OPN11980/1070 is closely linked to the SMV resistance locus in95-5383, with genetic distance of 2.1cM.

  12. A novel splicing site mutation of the GPR143 gene in a Chinese X-linked ocular albinism pedigree.

    Science.gov (United States)

    Cai, C Y; Zhu, H; Shi, W; Su, L; Shi, O; Cai, C Q; Ling, C; Li, W D

    2013-11-18

    Ocular albinism is an X-linked inherited disease characterized by hypopigmentation of the iris and nystagmus. To identify a new disease-causing mutation of ocular albinism, we collected a Han Chinese pedigree with 7 male congenital nystagmus patients over 3 generations. Slit-lamp photography and optical coherence tomography were performed for the proband. Genomic DNA was extracted from a whole blood sample from the proband using the high-salt method. Polymerase chain reaction (PCR) sequencing was carried out for GPR143 and FRMD7 genes. The three-dimensional structures of the wild-type and mutant GPR143 proteins were determined using SWISS-MODEL. The transmission of the disease in the pedigree clearly followed an X-linked pattern. The proband had significant iris and fundus hypopigmentation. Optical coherence tomography showed severe foveal hypoplasias in both eyes of the proband. A novel splicing site (G/C) mutation was found on the boundary of the 6th intron and the 7th exon of the GPR143 gene, resulting in a 9-amino-acid deletion (codons 257-265) in the 6th transmembrane domain of the GPR143 protein. In conclusion, a novel splicing site mutation of the GPR143 gene was found in a Han Chinese congenital ocular albinism pedigree.

  13. Enzymatic repair of selected cross-linked homoduplex molecules enhances nuclear gene rescue from Pompeii and Herculaneum remains.

    Science.gov (United States)

    Di Bernardo, Giovanni; Del Gaudio, Stefania; Cammarota, Marcella; Galderisi, Umberto; Cascino, Antonino; Cipollaro, Marilena

    2002-02-15

    Ancient DNA (aDNA) samples extracted from the bone remains of six equids buried by the Vesuvius eruption in 79 AD were investigated to test pre-amplification and enzymatic repair procedures designed to enhance the rescue of nuclear genes. The extracts, which proved all positive for Equidae mtDNA amplification, proved positive only four times out of 18 when tested for single-copy Equidae nuclear genes (epsilon globin, p53 and gamma interferon). Pre-amplification did not change the number of retrieved aDNA sequences but 10 times out of 14 enzymatic repair restored the amplifiability of the genes analysed, proving that repair increases the rate of successful rescue from 22 to alpha(lambda)mu(omicron)sigma(tau) 80%. These findings support the hypothesis that some of these cross-linked aDNA molecules, which are not completely separated when DNA is extracted under denaturing conditions, become homoduplex substrates for Pol I and/or T4 ligase action upon renaturation. aDNA authenticity is proved by the homology of the nucleotide sequences of loci tested to the corresponding modern Equidae sequences. Data also indicate that cross-linked homoduplex molecules selected by denaturation of the extract are repaired without any chimera formation. The general features of aDNA amplification with and without denaturation and enzymatic repair are discussed.

  14. DNA Isn't Destiny: Healthy Living Can Overcome Genes Linked to Heart Disease

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_161999.html DNA Isn't Destiny: Healthy Living Can Overcome Genes ... unhealthy lifestyle choices. "For heart attack at least, DNA is not destiny," Kathiresan said. "You have control ...

  15. Identification of the gene-regulatory landscape in skeletal development and potential links to skeletal regeneration

    Directory of Open Access Journals (Sweden)

    Hironori Hojo

    2017-06-01

    Full Text Available A class of gene-regulatory elements called enhancers are the main mediators controlling quantitative, temporal and spatial gene expressions. In the course of evolution, the enhancer landscape of higher organisms such as mammals has become quite complex, exerting biological functions precisely and coordinately. In mammalian skeletal development, the master transcription factors Sox9, Runx2 and Sp7/Osterix function primarily through enhancers on the genome to achieve specification and differentiation of skeletal cells. Recently developed genome-scale analyses have shed light on multiple layers of gene regulations, uncovering not only the primary mode of actions of these transcription factors on skeletal enhancers, but also the relation of the epigenetic landscape to three-dimensional chromatin architecture. Here, we review findings on the emerging framework of gene-regulatory networks involved in skeletal development. We further discuss the power of genome-scale analyses to provide new insights into genetic diseases and regenerative medicine in skeletal tissues.

  16. A gene for nonsyndromic X-linked mental retardation (MRX77) maps to Xq12-Xq21.33.

    Science.gov (United States)

    Sismani, Carolina; Syrrou, Maria; Christodoulou, Kyproula; Hamel, Ben; Chelly, Jamel; Yntema, Helger G; van Bokhoven, Hans; Tzoufi, Meropi; Georgiou, Ioannis; Patsalis, Philippos C

    2003-09-15

    Nonsyndromic X-linked mental retardation (MRX) is a highly heterogeneous condition in which mental retardation appears to be the only consistent manifestation. According to the most recent data, 77 MRX families with a lod score of >2 have been mapped and eight genes have been cloned. We hereby report on a linkage analysis performed on a Greek family with apparently nonsyndromic MRX. The affected males have moderate to severe mental retardation, severe speech problems, and aggressive behavior. Two-point linkage analysis with 26 polymorphic markers spanning the entire X chromosome was carried out. We could assign the causative gene to a 27 Mb interval in Xq12-Xq21.33. The maximum LOD score was found for markers DXS1225, DXS8114, and DXS990 at 2.36, 2.06, 2.06, respectively at theta = 0.00. Recombination was observed for DXS983 at the proximal side and DXS6799 at the distal side. Nineteen other MRX families have been described with a partial overlapping disease gene interval in proximal Xq. No mutations were found in the MRX77 family for three known or candidate MRX genes, from this region OPHN1, RSK4, and ATR-X. These data indicate that the Xq12-Xq21.33 interval contains at least one additional MRX gene.

  17. MRG-1, an autosome-associated protein, silences X-linked genes and protects germline immortality in Caenorhabditis elegans.

    Science.gov (United States)

    Takasaki, Teruaki; Liu, Zheng; Habara, Yasuaki; Nishiwaki, Kiyoji; Nakayama, Jun-Ichi; Inoue, Kunio; Sakamoto, Hiroshi; Strome, Susan

    2007-02-01

    MRG15, a mammalian protein related to the mortality factor MORF4, is required for cell proliferation and embryo survival. Our genetic analysis has revealed that the Caenorhabditis elegans ortholog MRG-1 serves similar roles. Maternal MRG-1 promotes embryo survival and is required for proliferation and immortality of the primordial germ cells (PGCs). As expected of a chromodomain protein, MRG-1 associates with chromatin. Unexpectedly, it is concentrated on the autosomes and not detectable on the X chromosomes. This association is not dependent on the autosome-enriched protein MES-4. Focusing on possible roles of MRG-1 in regulating gene expression, we determined that MRG-1 is required to maintain repression in the maternal germ line of transgenes on extrachromosomal arrays, and of several X-linked genes previously shown to depend on MES-4 for repression. MRG-1 is not required for PGCs to acquire transcriptional competence or for the turn-on of expression of several PGC-expressed genes (pgl-1, glh-1, glh-4 and nos-1). By contrast to this result in PGCs, MRG-1 is required for ectopic expression of those germline genes in somatic cells lacking the NuRD complex component MEP-1. We discuss how an autosome-enriched protein might repress genes on the X chromosome, promote PGC proliferation and survival, and influence the germ versus soma distinction.

  18. Upregulation of skeletal muscle inflammatory genes links inflammation with insulin resistance in women with the metabolic syndrome.

    Science.gov (United States)

    Poelkens, Fleur; Lammers, Gerwen; Pardoel, Elisabeth M; Tack, Cees J; Hopman, Maria T E

    2013-10-01

    The metabolic syndrome, a combination of interrelated metabolic risk factors, is associated with insulin resistance and promotes the development of cardiovascular diseases and type 2 diabetes mellitus. There is a close link between inflammation and metabolic disease, but the responsible mechanisms remain elusive. The aim of this study was to identify differentially expressed genes in insulin-resistant skeletal muscle tissue of women with the metabolic syndrome compared with healthy control women. Women with the metabolic syndrome (n = 19) and healthy control women (n = 20) were extensively phenotyped, insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp, and a skeletal muscle biopsy was obtained. Gene expression levels were compared between the two groups by microarrays. The upregulated genes in skeletal muscle of the women with the metabolic syndrome were primarily enriched for inflammatory response-associated genes. The three most significantly upregulated of this group, interleukin 6 receptor (IL6R), histone deacetylase 9 (HDAC9) and CD97 molecule (CD97), were significantly correlated with insulin resistance. Taken together, these findings suggest an important role for a number of inflammatory-related genes in the development of skeletal muscle insulin resistance.

  19. Transcriptional profiling of peripheral lymphoid tissue reveals genes and networks linked to SSBP/1 scrapie pathology in sheep.

    Science.gov (United States)

    Gossner, Anton; Roupaka, Sofia; Foster, Jim; Hunter, Nora; Hopkins, John

    2011-12-15

    Transmissible spongiform encephalopathies (TSEs) are slow and progressive neurodegenerative diseases of humans and animals. The major target organ for all TSEs is the brain but some TSE agents are associated with prior accumulation within the peripheral lymphoid system. Many studies have examined the effects of scrapie infection on the expression of central nervous system (CNS) genes, but this study examines the progression of scrapie pathology in the peripheral lymphoid system and how scrapie infection affects the transcriptome of the lymph nodes and spleen. Infection of sheep with SSBP/1 scrapie resulted in PrP(Sc) deposition in the draining prescapular lymph node (PSLN) by 25 days post infection (dpi) in VRQ/VRQ genotype sheep and 75 dpi in tonsils and spleen. Progression of PrP(Sc) deposition in VRQ/ARR animals was 25 dpi later in the PSLN and 250 dpi later in spleen. Microarray analysis of 75 dpi tissues from VRQ/VRQ sheep identified 52 genes in PSLN and 37 genes in spleen cells that showed significant difference (P ≤ 0.05) between scrapie-infected and mock-infected animals. Transcriptional pathway analysis highlighted immunological disease, cell death and neurological disease as the biological pathways associated with scrapie pathogenesis in the peripheral lymphoid system. PrP(Sc) accumulation of lymphoid tissue resulted in the repression of genes linked to inflammation and oxidative stress, and the up-regulation of genes related to apoptosis.

  20. SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease.

    Science.gov (United States)

    Rivat, Christine; Booth, Claire; Alonso-Ferrero, Maria; Blundell, Michael; Sebire, Neil J; Thrasher, Adrian J; Gaspar, H Bobby

    2013-02-14

    X-linked lymphoproliferative disease (XLP1) arises from mutations in the gene encoding SLAM-associated protein (SAP) and leads to abnormalities of NKT-cell development, NK-cell cytotoxicity, and T-dependent humoral function. Curative treatment is limited to allogeneic hematopoietic stem cell (HSC) transplantation. We tested whether HSC gene therapy could correct the multilineage defects seen in SAP(-/-) mice. SAP(-/-) murine HSCs were transduced with lentiviral vectors containing either SAP or reporter gene before transplantation into irradiated recipients. NKT-cell development was significantly higher and NK-cell cytotoxicity restored to wild-type levels in mice receiving the SAP vector in comparison to control mice. Baseline immunoglobulin levels were significantly increased and T-dependent humoral responses to NP-CGG, including germinal center formation, were restored in SAP-transduced mice.We demonstrate for the first time that HSC gene transfer corrects the cellular and humoral defects in SAP(-/-) mice providing proof of concept for gene therapy in XLP1.

  1. Missing Links in Genes to Traits: Toward Teaching for an Integrated Framework of Genetics

    Science.gov (United States)

    Pavlova, Iglika V.; Kreher, Scott A.

    2013-01-01

    Genetics, one of the most influential fields, underlies all of biology and produces discoveries that are in the news daily. However, many students leave introductory biology and genetics courses lacking a coherent framework of knowledge to use in their daily lives. We identify substantial "missing links" in the teaching of foundational…

  2. Missing Links in Genes to Traits: Toward Teaching for an Integrated Framework of Genetics

    Science.gov (United States)

    Pavlova, Iglika V.; Kreher, Scott A.

    2013-01-01

    Genetics, one of the most influential fields, underlies all of biology and produces discoveries that are in the news daily. However, many students leave introductory biology and genetics courses lacking a coherent framework of knowledge to use in their daily lives. We identify substantial "missing links" in the teaching of foundational…

  3. Type 1 Diabetes Candidate Genes Linked to Pancreatic Islet Cell Inflammation and Beta-Cell Apoptosis

    Science.gov (United States)

    Størling, Joachim; Pociot, Flemming

    2017-01-01

    Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established. A significant part of the genes located in the T1D susceptibility loci are expressed in human islets and β cells and mounting evidence suggests that some of these genes modulate the β-cell response to the immune system and viral infection and regulate apoptotic β-cell death. Here, we discuss the current status of T1D susceptibility loci and candidate genes with focus on pancreatic islet cell inflammation and β-cell apoptosis. PMID:28212332

  4. Type 1 Diabetes Candidate Genes Linked to Pancreatic Islet Cell Inflammation and Beta-Cell Apoptosis.

    Science.gov (United States)

    Størling, Joachim; Pociot, Flemming

    2017-02-16

    Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established. A significant part of the genes located in the T1D susceptibility loci are expressed in human islets and β cells and mounting evidence suggests that some of these genes modulate the β-cell response to the immune system and viral infection and regulate apoptotic β-cell death. Here, we discuss the current status of T1D susceptibility loci and candidate genes with focus on pancreatic islet cell inflammation and β-cell apoptosis.

  5. Regulation of Aggression by Obesity-Linked Genes TfAP-2 and Twz Through Octopamine Signaling in Drosophila

    Science.gov (United States)

    Williams, Michael J.; Goergen, Philip; Rajendran, Jayasimman; Klockars, Anica; Kasagiannis, Anna; Fredriksson, Robert; Schiöth, Helgi B.

    2014-01-01

    In Drosophila, the monoamine octopamine, through mechanisms that are not completely understood, regulates both aggression and mating behavior. Interestingly, our study demonstrates that the Drosophila obesity-linked homologs Transcription factor AP-2 (TfAP-2; TFAP2B in humans) and Tiwaz (Twz; KCTD15 in humans) interact to modify male behavior by controlling the expression of Tyramine β-hydroxylase and Vesicular monanime transporter, genes necessary for octopamine production and secretion. Furthermore, we reveal that octopamine in turn regulates aggression through the Drosophila cholecystokinin satiation hormone homolog Drosulfakinin (Dsk). Finally, we establish that TfAP-2 is expressed in octopaminergic neurons known to control aggressive behavior and that TfAP-2 requires functional Twz for its activity. We conclude that genetically manipulating the obesity-linked homologs TfAP-2 and Twz is sufficient to affect octopamine signaling, which in turn modulates Drosophila male behavior through the regulation of the satiation hormone Dsk. PMID:24142897

  6. Linking the serotonin transporter gene, family environments, hippocampal volume and depression onset: A prospective imaging gene × environment analysis.

    Science.gov (United States)

    Little, Keriann; Olsson, Craig A; Youssef, George J; Whittle, Sarah; Simmons, Julian G; Yücel, Murat; Sheeber, Lisa B; Foley, Debra L; Allen, Nicholas B

    2015-11-01

    A single imaging gene-environment (IGxE) framework that is able to simultaneously model genetic, neurobiological, and environmental influences on psychopathology outcomes is needed to improve understanding of how complex interrelationships between allelic variation, differences in neuroanatomy or neuroactivity, and environmental experience affect risk for psychiatric disorder. In a longitudinal study of adolescent development we demonstrate the utility of such an IGxE framework by testing whether variation in parental behavior at age 12 altered the strength of an imaging genetics pathway, involving an indirect association between allelic variation in the serotonin transporter gene to variation in hippocampal volume and consequent onset of major depressive disorder by age 18. Results were consistent with the presence of an indirect effect of the serotonin transporter S-allele on depression onset via smaller left and right hippocampal volumes that was significant only in family environments involving either higher levels of parental aggression or lower levels of positive parenting. The previously reported finding of S-allele carriers' increased risk of depression in adverse environments may, therefore, be partly because of the effects of these environments on a neurobiological pathway from the serotonin transporter gene to depression onset that proceeds through variation in hippocampal volume.

  7. Male dominance linked to size and age, but not to 'good genes' in brown trout (Salmo trutta

    Directory of Open Access Journals (Sweden)

    Evanno Guillaume

    2007-11-01

    Full Text Available Abstract Background Males that are successful in intra-sexual competition are often assumed to be of superior quality. In the mating system of most salmonid species, intensive dominance fights are common and the winners monopolise most mates and sire most offspring. We drew a random sample of mature male brown trout (Salmo trutta from two wild populations and determined their dominance hierarchy or traits linked to dominance. The fish were then stripped and their sperm was used for in vitro fertilisations in two full-factorial breeding designs. We recorded embryo viability until hatching in both experiments, and juvenile survival during 20 months after release into a natural streamlet in the second experiment. Since offspring of brown trout get only genes from their fathers, we used offspring survival as a quality measure to test (i whether males differ in their genetic quality, and if so, (ii whether dominance or traits linked to dominance reveal 'good genes'. Results We found significant additive genetic variance on embryo survival, i.e. males differed in their genetic quality. Older, heavier and larger males were more successful in intra-sexual selection. However, neither dominance nor dominance indicators like body length, weight or age were significantly linked to genetic quality measured as embryo or juvenile survival. Conclusion We found no evidence that females can improve their offspring's genetic viability by mating with large and dominant males. If there still were advantages of mating with dominant males, they may be linked to non-genetic benefits or to genetic advantages that are context dependent and therefore possibly not revealed under our experimental conditions – even if we found significant additive genetic variation for embryo viability under such conditions.

  8. Closely linked H2B genes in the marine copepod, Tigriopus californicus indicate a recent gene duplication or gene conversion event.

    Science.gov (United States)

    Brown, D; Cook, A; Wagner, M; Wells, D

    1992-01-01

    Two nonallelic histone gene clusters were characterized in the marine copepod, Tigriopus californicus. The DNA sequence of one of the clusters reveals six genes in the contiguous arrangement of H2B, H1, H3, H4, H2B and H2A. The order of genes within the second cluster is H3, H4, H2B and H2A. There is no evidence for the presence of an H1 gene in this cluster. Comparison of the three copepod H2B genes reveals a high degree of similarity between the 5' upstream regions and between the amino terminal halves of the two H2B genes found within the same cluster. From these data we infer that gene duplication and/or gene conversion events occurred within this cluster in the recent past.

  9. Shared molecular and functional frameworks among five complex human disorders: a comparative study on interactomes linked to susceptibility genes.

    Directory of Open Access Journals (Sweden)

    Ramesh Menon

    Full Text Available BACKGROUND: Genome-wide association studies (gwas are invaluable in revealing the common variants predisposing to complex human diseases. Yet, until now, the large volumes of data generated from such analyses have not been explored extensively enough to identify the molecular and functional framework hosting the susceptibility genes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the relationships among five neurodegenerative and/or autoimmune complex human diseases (Parkinson's disease--Park, Alzheimer's disease--Alz, multiple sclerosis--MS, rheumatoid arthritis--RA and Type 1 diabetes--T1D by characterising the interactomes linked to their gwas-genes. An initial study on the MS interactome indicated that several genes predisposing to the other autoimmune or neurodegenerative disorders may come into contact with it, suggesting that susceptibility to distinct diseases may converge towards common molecular and biological networks. In order to test this hypothesis, we performed pathway enrichment analyses on each disease interactome independently. Several issues related to immune function and growth factor signalling pathways appeared in all autoimmune diseases, and, surprisingly, in Alzheimer's disease. Furthermore, the paired analyses of disease interactomes revealed significant molecular and functional relatedness among autoimmune diseases, and, unexpectedly, between T1D and Alz. CONCLUSIONS/SIGNIFICANCE: The systems biology approach highlighted several known pathogenic processes, indicating that changes in these functions might be driven or sustained by the framework linked to genetic susceptibility. Moreover, the comparative analyses among the five genetic interactomes revealed unexpected genetic relationships, which await further biological validation. Overall, this study outlines the potential of systems biology to uncover links between genetics and pathogenesis of complex human disorders.

  10. Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression.

    Directory of Open Access Journals (Sweden)

    Adolfo Sequeira

    Full Text Available BACKGROUND: Most studies investigating the neurobiology of depression and suicide have focused on the serotonergic system. While it seems clear that serotonergic alterations play a role in the pathogenesis of these major public health problems, dysfunction in additional neurotransmitter systems and other molecular alterations may also be implicated. Microarray expression studies are excellent screening tools to generate hypotheses about additional molecular processes that may be at play. In this study we investigated brain regions that are known to be implicated in the neurobiology of suicide and major depression are likely to represent valid global molecular alterations. METHODOLOGY/PRINCIPAL FINDINGS: We performed gene expression analysis using the HG-U133AB chipset in 17 cortical and subcortical brain regions from suicides with and without major depression and controls. Total mRNA for microarray analysis was obtained from 663 brain samples isolated from 39 male subjects, including 26 suicide cases and 13 controls diagnosed by means of psychological autopsies. Independent brain samples from 34 subjects and animal studies were used to control for the potential confounding effects of comorbidity with alcohol. Using a Gene Ontology analysis as our starting point, we identified molecular pathways that may be involved in depression and suicide, and performed follow-up analyses on these possible targets. Methodology included gene expression measures from microarrays, Gene Score Resampling for global ontological profiling, and semi-quantitative RT-PCR. We observed the highest number of suicide specific alterations in prefrontal cortical areas and hippocampus. Our results revealed alterations of synaptic neurotransmission and intracellular signaling. Among these, Glutamatergic (GLU and GABAergic related genes were globally altered. Semi-quantitative RT-PCR results investigating expression of GLU and GABA receptor subunit genes were consistent with

  11. Serodiagnosis of cutaneous leishmaniasis: assessment of an enzyme-linked immunosorbent assay using a peptide sequence from gene B protein

    DEFF Research Database (Denmark)

    Jensen, A T; Gaafar, A; Ismail, A

    1996-01-01

    An enzyme-linked immunosorbent assay (ELISA) using a 28 amino acid sequence of the repetitive element of gene B protein (GBP) from Leishmania major was developed for serodiagnosis of cutaneous leishmaniasis (CL). The assay was compared to ELISAs using crude amastigote and promastigote antigens from...... clinical history (GBPP ELISA; P = 0.038; amastigote ELISA; P = 0.004; and promastigote ELISA; P = 0.017). In the former group, the sensitivities of the five ELISAs were 100% (GBPP), 87% (amastigote), 93% (promastigote), 67% (L. donovani), and 53% (L. major), respectively....

  12. Combination of adenovirus and cross-linked low molecular weight PEI improves efficiency of gene transduction

    Energy Technology Data Exchange (ETDEWEB)

    Han Jianfeng; Zhao Dong; Zhong Zhirong; Zhang Zhirong; Gong Tao; Sun Xun, E-mail: xunsun22@gmail.com [Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 610041 (China)

    2010-03-12

    Recombinant adenovirus (Ad)-mediated gene therapy is an exciting novel strategy in cancer treatment. However, poor infection efficiency with coxsackievirus and adenovirus receptor (CAR) down-regulated cancer cell lines is one of the major challenges for its practical and extensive application. As an alternative method of viral gene delivery, a non-viral carrier using cationic materials could compensate for the limitation of adenovirus. In our study, adenovectors were complexed with a new synthetic polymer PEI-DEG-bis-NPC (PDN) based on polyethylenimine (PEI), and then the properties of the vehicle were characterized by measurement of size distribution, zeta potential and transmission electron microscopy (TEM). Enhancement of gene transduction by Ad/PDN complexes was observed in both CAR-overexpressing cell lines (A549) and CAR-lacking cell lines (MDCK, CHO, LLC), as a result of facilitating binding and cell uptake of adenoviral particles by the cationic component. Ad/PDN complexes also promoted the inhibition of tumor growth in vivo and prolonged the survival time of tumor-bearing mice. These data suggest that a combination of viral and non-viral gene delivery methods may offer a new approach to successful cancer gene therapy.

  13. Stability analysis of a model gene network links aging, stress resistance, and negligible senescence.

    Science.gov (United States)

    Kogan, Valeria; Molodtsov, Ivan; Menshikov, Leonid I; Shmookler Reis, Robert J; Fedichev, Peter

    2015-08-28

    Several animal species are considered to exhibit what is called negligible senescence, i.e. they do not show signs of functional decline or any increase of mortality with age. Recent studies in naked mole rat and long-lived sea urchins showed that these species do not alter their gene-expression profiles with age as much as other organisms do. This is consistent with exceptional endurance of naked mole rat tissues to various genotoxic stresses. We conjectured, therefore, that the lifelong transcriptional stability of an organism may be a key determinant of longevity. We analyzed the stability of a simple genetic-network model and found that under most common circumstances, such a gene network is inherently unstable. Over a time it undergoes an exponential accumulation of gene-regulation deviations leading to death. However, should the repair systems be sufficiently effective, the gene network can stabilize so that gene damage remains constrained along with mortality of the organism. We investigate the relationship between stress-resistance and aging and suggest that the unstable regime may provide a mathematical basis for the Gompertz "law" of aging in many species. At the same time, this model accounts for the apparently age-independent mortality observed in some exceptionally long-lived animals.

  14. Correlation between connexin 32 gene mutations and clinical phenotype in X-linked dominant Charcot-Marie-Tooth neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Ionasescu, V.; Ionasescu, R.; Searby, C. [Univ. of Iowa Hospitals and Clinics, Iowa City, IA (United States)

    1996-06-14

    We studied the relationship between the genotype and clinical phenotype in 27 families with dominant X-linked Charcot-Marie-Tooth (CMTX1) neuropathy. Twenty-two families showed mutations in the coding region of the connexin32 (cx32) gene. The mutations include four nonsense mutations, eight missense mutations, two medium size deletions, and one insertion. Most missense mutations showed a mild clinical phenotype (five out of eight), whereas all nonsense mutations, the larger of the two deletions, and the insertion that produced frameshifts showed severe phenotypes. Five CMTX1 families with mild clinical phenotype showed no point mutations of the cx32 gene coding region. Three of these families showed positive genetic linkage with the markers of the Xq13.1 region. The genetic linkage of the remaining two families could not be evaluated because of their small size. 25 refs., 1 fig., 1 tab.

  15. A novel Bruton's tyrosine kinase gene (BTK) invariant splice site mutation in a Malaysian family with X-linked agammaglobulinemia.

    Science.gov (United States)

    Chear, Chai Teng; Gill, Harvindar Kaur; Ramly, Nazatul Haslina; Dhaliwal, Jasbir Singh; Bujang, Noraini; Ripen, Adiratna Mat; Mohamad, Saharuddin Bin

    2013-12-01

    X-linked agammaglobulinemia (XLA) is a rare genetic disorder caused by mutations in the Bruton's tyrosine kinase (BTK) gene. These mutations cause defects in early B cell development. A patient with no circulating B cells and low serum immunoglobulin isotypes was studied as were his mother and sister. Monocyte BTK protein expression was evaluated by flow cytometry. The mutation was determined using PCR and followed by sequencing. Flow cytometry showed the patient lacked BTK protein expression in his monocytes while the mother and sister had 62% and 40% of the monocytes showing BTK protein expressions respectively. The patient had a novel base substitution in the first nucleotide of intron 9 in the BTK gene, and the mutation was IVS9+1Gagammaglobulinemia and may be used for subsequent genetic counseling, carrier detection and prenatal diagnosis.

  16. Amelogenin signal peptide mutation: Correlation between mutations in the amelogenin gene (AMGX) and manifestations of X-linked amelogenesis imperfecta

    Energy Technology Data Exchange (ETDEWEB)

    Lagerstroem-Fermer, M.; Nilsson, M.; Pettersson, U. [Univ. of Uppsala (Sweden)] [and others

    1995-03-01

    Formation of tooth enamel is a poorly understood biological process. In this study the authors describe a 9-bp deletion in exon 2 of the amelogenin gene (AMGX) causing X-linked hypoplastic amelogenesis imperfecta, a disease characterized by defective enamel. The mutation results in the loss of 3 amino acids and exchange of 1 in the signal peptide of the amelogenin protein. This deletion in the signal peptide probably interferes with translocation of the amelogenin protein during synthesis, resulting in the thin enamel observed in affected members of the family. The authors compare this mutation to a previously reported mutation in the amelogenin gene that causes a different disease phenotype. The study illustrates that molecular analysis can help explain the various manifestations of a tooth disorder and thereby provide insights into the mechanisms of tooth enamel formation. 16 refs., 2 figs., 1 tab.

  17. Elevated urinary albumin excretion is not linked to the angiotensin I-converting enzyme gene polymorphism in clinically healthy subjects

    DEFF Research Database (Denmark)

    Clausen, P; Jensen, J S; Borch-Johnsen, K

    2000-01-01

    aged 40-65 years with elevated UAE in a dipstick negative urinary sample (n = 27) from The Copenhagen City Heart Study. Neither the ACE genotype distribution (p = 0.12) nor the D and I allele frequencies (p = 0.69) differed significantly between subjects with elevated UAE and a matched normoalbuminuric......An elevated urinary albumin excretion (UAE) in non-diabetic subjects without renal or cardiovascular disease has been shown to be predictive of ischaemic heart disease. An insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene has been identified and the D allele...... control group (n = 46). Elevated UAE in clinically healthy subjects is not linked to the ACE gene polymorphism....

  18. Link between confusional migraine, hemiplegic migraine and episodic ataxia type 2: hypothesis, family genealogy, gene typing and classification.

    Science.gov (United States)

    Cleves, C; Parikh, S; Rothner, A D; Tepper, S J

    2010-06-01

    An association between hemiplegic migraine (HM) and episodic ataxia type 2 (EA2) has been described; both disorders are linked to mutations in the CACNA1A gene. Although confusion occurs in 21% of patients with HM, we found only one case in the literature of confusional episodes associated with ataxia without hemiplegia. These findings raise the possibility of confusional episodes being part of both the HM and EA2 phenotype. However, a patient with episodic ataxia, confusional spells and CACNA1A gene mutations has not been identified. We describe four individuals, spanning three generations of a family, with episodic ataxia without hemiplegia and confusion, in association with a CACNA1A mutation. We follow with a description of the relationship between the CACNA1A mutations and the three syndromes, suggesting a potential need for a new classification in which the conditions can be subsumed.

  19. Novel form of a single X-linked visual pigment gene in a unique dichromatic color-vision defect.

    Science.gov (United States)

    Hayashi, Takaaki; Kubo, Akiko; Takeuchi, Tomokazu; Gekka, Tamaki; Goto-Omoto, Satoshi; Kitahara, Kenji

    2006-01-01

    In normal trichromats, the long- (L) and middle-wavelength-sensitive (M) pigment genes are arranged in a head-to-tandem array on the X chromosome. Two amino acids at positions 277 and 285, encoded by exon 5 of the L and M genes, respectively, are essential for the spectral difference between L and M pigments whose spectral peaks are at approximately 560 and 530 nm. Intragenic or intergenic unequal crossing-over commonly occurs between the highly homologous L and M genes, resulting in red-green color vision deficiencies. The dichromacy is usually associated with a single L gene for deuteranopia or a single 5' L-M 3' hybrid gene with M-gene exon 5 for protanopia. We clinically diagnosed a total of 88 male dichromats using a Nagel model I anomaloscope, which included one unclassified subject in addition to 31 protanopes and 56 deuteranopes. The objective of this study was to characterize the phenotype of the subject and to determine the genotype of his X-linked pigment genes. The subject accepted not only any red-green mixture but also an extended yellow-scale range at each matching point (i.e. 20 to 32 scale units at the green primary and 3.5 to 6 scale units at the red primary). The slopes of regression lines were in the range of -0.34 to -0.23, while the mean slopes for the protanopes and deuteranopes were -0.38 and -0.01, respectively. Spectral sensitivity tests showed that the subject's curve was shifted between the protanope and deuteranope curves. Molecular analysis revealed a novel form of a single pigment gene with a unique arrangement of exon 5 (Y277 from the L gene and A285 from the M gene). The predicted lambdamax (541 to 546 nm) of the unique pigment was closer to the M than to the L pigment. Our outcome suggests that intragenic unequal crossing-over may have occurred between amino acid positions 279 and 283.

  20. Methylation-sensitive linking libraries enhance gene-enriched sequencing of complex genomes and map DNA methylation domains

    Directory of Open Access Journals (Sweden)

    Bharti Arvind K

    2008-12-01

    Full Text Available Abstract Background Many plant genomes are resistant to whole-genome assembly due to an abundance of repetitive sequence, leading to the development of gene-rich sequencing techniques. Two such techniques are hypomethylated partial restriction (HMPR and methylation spanning linker libraries (MSLL. These libraries differ from other gene-rich datasets in having larger insert sizes, and the MSLL clones are designed to provide reads localized to "epigenetic boundaries" where methylation begins or ends. Results A large-scale study in maize generated 40,299 HMPR sequences and 80,723 MSLL sequences, including MSLL clones exceeding 100 kb. The paired end reads of MSLL and HMPR clones were shown to be effective in linking existing gene-rich sequences into scaffolds. In addition, it was shown that the MSLL clones can be used for anchoring these scaffolds to a BAC-based physical map. The MSLL end reads effectively identified epigenetic boundaries, as indicated by their preferential alignment to regions upstream and downstream from annotated genes. The ability to precisely map long stretches of fully methylated DNA sequence is a unique outcome of MSLL analysis, and was also shown to provide evidence for errors in gene identification. MSLL clones were observed to be significantly more repeat-rich in their interiors than in their end reads, confirming the correlation between methylation and retroelement content. Both MSLL and HMPR reads were found to be substantially gene-enriched, with the SalI MSLL libraries being the most highly enriched (31% align to an EST contig, while the HMPR clones exhibited exceptional depletion of repetitive DNA (to ~11%. These two techniques were compared with other gene-enrichment methods, and shown to be complementary. Conclusion MSLL technology provides an unparalleled approach for mapping the epigenetic status of repetitive blocks and for identifying sequences mis-identified as genes. Although the types and natures of

  1. Gene conversion in the rice genome

    DEFF Research Database (Denmark)

    Xu, Shuqing; Clark, Terry; Zheng, Hongkun;

    2008-01-01

    BACKGROUND: Gene conversion causes a non-reciprocal transfer of genetic information between similar sequences. Gene conversion can both homogenize genes and recruit point mutations thereby shaping the evolution of multigene families. In the rice genome, the large number of duplicated genes...... is not tightly linked to natural selection in the rice genome. To assess the contribution of segmental duplication on gene conversion statistics, we determined locations of conversion partners with respect to inter-chromosomal segment duplication. The number of conversions associated with segmentation is less...

  2. Novel mutations in the connexin 32 gene associated with X-linked Charcot-Marie-Tooth disease

    Energy Technology Data Exchange (ETDEWEB)

    Tan, C.; Ainsworth, P. [Victoria Hospital, Ontario (Canada)]|[Childrens Hospital of Western Ontario (Canada)

    1994-09-01

    Charcot-Marie-Tooth disease is a pathologically and genetically hetergenous group of disorders that cause a progressive neuropathy, defined pathologically by degeneration of the myelin (CMT 1) of the axon (CMT 2) of the peripheral nerves. An X-linked type of the demyelinating form of this disorder (CMT X) has recently been linked to mutations in the connexin 32 (Cx32) gene, which codes for a 284 amino acid gap junction protein found in myelinated peripheral nerve. To date some 7 different mutations in this gene have been identified as being responsible for CMT X. The majority of these predict nonconservative amino acid substitutions, while one is a frameshift mutation which predicts a premature stop at codon 21. We report the results of molecular studies on three further local CMT X kindreds. The Cx32 gene was amplified by PCR in three overlapping fragments 300-450 bp in length using leukocyte-derived DNA as template. These were either sequenced directly using a deaza dGTP sequencing protocol, or were cloned and sequenced using a TA vector. In two of the kindreds the affected members carried a point mutation which was predicted to effect a non-conservative amino acid change within the first transmembrane domain. Both of these mutations caused a restriction site alteration (the loss of an Nla III and the creation of a Pvu II, respectively), and the former mutation was observed to segregate with the clinicial phenotype in affected family members. Affected members of the third kindred, which was a very large multigenerational family that had been extensively studied previously, were shown to carry a point mutation predicted to cause a premature truncation of the Cx32 gene product in the intracellular carboxy terminus. This mutation obliterated an Rsa I site which allowed a rapid screen of several other family members.

  3. Identification of a RAPD marker linked to the Co-6 anthracnose resistant gene in common bean cultivar AB 136

    Directory of Open Access Journals (Sweden)

    Alzate-Marin Ana Lilia

    2000-01-01

    Full Text Available The pathogenic variability of the fungus Colletotrichum lindemuthianum represents an obstacle for the creation of resistant common bean (Phaseolus vulgaris L. varieties. Gene pyramiding is an alternative strategy for the development of varieties with durable resistance. RAPD markers have been proposed as a means to facilitate pyramiding of resistance genes without the need for multiple inoculations of the pathogens. The main aims of this work were to define the inheritance pattern of resistance present in common bean cultivar AB 136 in segregating populations derived from crosses with cultivar Rudá (susceptible to most C. lindemuthianum races and to identify RAPD markers linked to anthracnose resistance. The two progenitors, populations F1 and F2, F2:3 families and backcross-derived plants were inoculated with race 89 of C. lindemuthianum under environmentally controlled greenhouse conditions. The results indicate that a single dominant gene, Co-6, controls common bean resistance to this race, giving a segregation ratio between resistant and susceptible plants of 3:1 in the F2, 1:0 in the backcrosses to AB 136 and 1:1 in the backcross to Rudá. The segregation ratio of F2:3 families derived from F2 resistant plants was 1:2 (homozygous to heterozygous resistant. Molecular marker analyses in the F2 population identified a DNA band of approximately 940 base pairs (OPAZ20(940, linked in coupling phase at 7.1 cM of the Co-6 gene. This marker is being used in our backcross breeding program to develop Rudá-derived common bean cultivars resistant to anthracnose and adapted to central Brazil.

  4. Functional coupling analysis suggests link between the obesity gene FTO and the BDNF-NTRK2 signaling pathway

    Directory of Open Access Journals (Sweden)

    Rask-Andersen Mathias

    2011-11-01

    Full Text Available Abstract Background The Fat mass and obesity gene (FTO has been identified through genome wide association studies as an important genetic factor contributing to a higher body mass index (BMI. However, the molecular context in which this effect is mediated has yet to be determined. We investigated the potential molecular network for FTO by analyzing co-expression and protein-protein interaction databases, Coxpresdb and IntAct, as well as the functional coupling predicting multi-source database, FunCoup. Hypothalamic expression of FTO-linked genes defined with this bioinformatics approach was subsequently studied using quantitative real time-PCR in mouse feeding models known to affect FTO expression. Results We identified several candidate genes for functional coupling to FTO through database studies and selected nine for further study in animal models. We observed hypothalamic expression of Profilin 2 (Pfn2, cAMP-dependent protein kinase catalytic subunit beta (Prkacb, Brain derived neurotrophic factor (Bdnf, neurotrophic tyrosine kinase, receptor, type 2 (Ntrk2, Signal transducer and activator of transcription 3 (Stat3, and Btbd12 to be co-regulated in concert with Fto. Pfn2 and Prkacb have previously not been linked to feeding regulation. Conclusions Gene expression studies validate several candidates generated through database studies of possible FTO-interactors. We speculate about a wider functional role for FTO in the context of current and recent findings, such as in extracellular ligand-induced neuronal plasticity via NTRK2/BDNF, possibly via interaction with the transcription factor CCAAT/enhancer binding protein β (C/EBPβ.

  5. Hybridisation-based resequencing of 17 X-linked intellectual disability genes in 135 patients reveals novel mutations in ATRX, SLC6A8 and PQBP1

    NARCIS (Netherlands)

    Jensen, L.R.; Chen, W.; Moser, B.; Lipkowitz, B.; Schroeder, C.; Musante, L.; Tzschach, A.; Kalscheuer, V.M.M.; Meloni, I.; Raynaud, M.; Esch, H. van; Chelly, J.; Brouwer, A.P. de; Hackett, A.; Haar, S. van der; Henn, W.; Gecz, J.; Riess, O.; Bonin, M.; Reinhardt, R.; Ropers, H.H.; Kuss, A.W.

    2011-01-01

    X-linked intellectual disability (XLID), also known as X-linked mental retardation, is a highly genetically heterogeneous condition for which mutations in >90 different genes have been identified. In this study, we used a custom-made sequencing array based on the Affymetrix 50k platform for mutation

  6. Hormonal interactions and gene regulation can link monoecy and environmental plasticity to the evolution of dioecy in plants.

    Science.gov (United States)

    Golenberg, Edward M; West, Nicholas W

    2013-06-01

    Most models for dioecy in flowering plants assume that dioecy arises directly from hermaphroditism through a series of independent feminizing and masculinizing mutations that become chromosomally linked. However, dioecy appears to evolve most frequently through monoecious grades. The major genetic models do not explain the evolution of unisexual flowers in monoecious and submonoecious populations, nor do they account for environmentally induced sexual plasticity. In this review, we explore the roles of environmental stress and hormones on sex determination, and propose a model that can explain the evolution of dioecy through monoecy, and the mechanisms of environmental sex determination. Environmental stresses elicit hormones that allow plants to mediate the negative effects of the stresses. Many of these same hormones are involved in the regulation of floral developmental genes. Recent studies have elucidated the mechanisms whereby these hormones interact and can act as switchpoints in regulatory pathways. Consequently, differential concentrations of plant hormones can regulate whole developmental pathways, providing a mechanism for differential development within isogenic individuals such as seen in monoecious plants. Sex-determining genes in such systems will evolve to generate clusters of coexpressed suites. Coexpression rather than coinheritance of gender-specific genes will define the sexual developmental fate. Therefore, selection for gender type will drive evolution of the regulatory sequences of such genes rather than their synteny. Subsequent mutations to hyper- or hyposensitive alleles within the hormone response pathway can result in segregating dioecious populations. Simultaneously, such developmental systems will remain sensitive to external stimuli that modify hormone responses.

  7. A novel AVPR2 gene mutation of X-linked congenital nephrogenic diabetes insipidus in an Asian pedigree.

    Science.gov (United States)

    Guo, Wei-Hong; Li, Qiang; Wei, Hong-Yan; Lu, Hong-Yan; Qu, Hui-Qi; Zhu, Mei

    2016-10-01

    Polyuria and polydipsia are the characteristics of congenital nephrogenic diabetes insipidus (CNDI). Approximately 90% of all patients with CNDI have X-linked hereditary disease, which is due to a mutation of the arginine vasopressin receptor 2 ( AVPR2) gene. This case report describes a 54-year-old male with polyuria and polydipsia and several male members of his pedigree who had the same symptoms. The proband was diagnosed with diabetes insipidus using a water-deprivation and arginine vasopressin stimulation test. Genomic DNA from the patient and his family members was extracted and the AVPR2 gene was sequenced. A novel missense mutation of a cytosine to guanine transition at position 972 (c.972C > G) was found, which resulted in the substitution of isoleucine for methionine at amino acid position 324 (p.I324M) in the seventh transmembrane domain of the protein. The proband's mother and daughter were heterozygous for this mutation. The novel mutation of the AVPR2 gene further broadens the phenotypic spectrum of the AVPR2 gene.

  8. Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse

    Directory of Open Access Journals (Sweden)

    Rabeah A. Al-Temaimi

    2016-04-01

    Full Text Available Colorectal cancer (CRC is one of the leading causes of cancer mortality. Metastasis remains the primary cause of CRC death. Predicting the possibility of metastatic relapse in early-stage CRC is of paramount importance to target therapy for patients who really need it and spare those with low-potential of metastasis. Ninety-six stage II CRC cases were stratified using high-resolution array comparative genomic hybridization (aCGH data based on a predictive survival algorithm and supervised clustering. All genes included within the resultant copy number aberrations were each interrogated independently at mRNA level using CRC expression datasets available from public repositories, which included 1820 colon cancers, and 167 normal colon tissues. Reduced mRNA expression driven by copy number losses and increased expression driven by copy number gains revealed 42 altered transcripts (29 reduced and 13 increased transcripts associated with metastatic relapse, short disease-free or overall survival, and/or epithelial to mesenchymal transition (EMT. Resultant genes were classified based on gene ontology (GO, which identified four functional enrichment groups involved in growth regulation, genomic integrity, metabolism, and signal transduction pathways. The identified 42 genes may be useful for predicting metastatic relapse in stage II CRC. Further studies are necessary to validate these findings.

  9. Genomewide analysis of phospholipid signaling genes in Phytophthora spp.: novelties and a missing link

    NARCIS (Netherlands)

    Meijer, H.J.G.; Govers, F.

    2006-01-01

    Phospholipids are cellular membrane components in eukaryotic cells that execute many important roles in signaling. Genes encoding enzymes required for phosphollipid signaling and metabolism have been characterized in several organisms, but only a few have been described for oomycetes. In this study,

  10. Connexin32 gene mutations in X-linked dominant Charcot-Marie-Tooth disease (CMTX1)

    NARCIS (Netherlands)

    Janssen, EAM; Kemp, S; Hensels, GW; Sie, OG; deDieSmulders, CEM; Hoogendijk, JE; deVisser, M; Bolhuis, PA

    Single-strand conformational polymorphisms (SSCP) of the connexin32 gene were analyzed in 121 patients possibly affected by Charcot-Marie-Tooth (CMT) disease. The 121 patients were selected from 443 possible CMT/HNPP (hereditary neuropathy with liability to pressure palsies) patients based on

  11. Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse.

    Science.gov (United States)

    Al-Temaimi, Rabeah A; Tan, Tuan Zea; Marafie, Makia J; Thiery, Jean Paul; Quirke, Philip; Al-Mulla, Fahd

    2016-04-28

    Colorectal cancer (CRC) is one of the leading causes of cancer mortality. Metastasis remains the primary cause of CRC death. Predicting the possibility of metastatic relapse in early-stage CRC is of paramount importance to target therapy for patients who really need it and spare those with low-potential of metastasis. Ninety-six stage II CRC cases were stratified using high-resolution array comparative genomic hybridization (aCGH) data based on a predictive survival algorithm and supervised clustering. All genes included within the resultant copy number aberrations were each interrogated independently at mRNA level using CRC expression datasets available from public repositories, which included 1820 colon cancers, and 167 normal colon tissues. Reduced mRNA expression driven by copy number losses and increased expression driven by copy number gains revealed 42 altered transcripts (29 reduced and 13 increased transcripts) associated with metastatic relapse, short disease-free or overall survival, and/or epithelial to mesenchymal transition (EMT). Resultant genes were classified based on gene ontology (GO), which identified four functional enrichment groups involved in growth regulation, genomic integrity, metabolism, and signal transduction pathways. The identified 42 genes may be useful for predicting metastatic relapse in stage II CRC. Further studies are necessary to validate these findings.

  12. Connexin32 gene mutations in X-linked dominant Charcot-Marie-Tooth disease (CMTX1)

    NARCIS (Netherlands)

    Janssen, EAM; Kemp, S; Hensels, GW; Sie, OG; deDieSmulders, CEM; Hoogendijk, JE; deVisser, M; Bolhuis, PA

    1997-01-01

    Single-strand conformational polymorphisms (SSCP) of the connexin32 gene were analyzed in 121 patients possibly affected by Charcot-Marie-Tooth (CMT) disease. The 121 patients were selected from 443 possible CMT/HNPP (hereditary neuropathy with liability to pressure palsies) patients based on geneti

  13. Connexin32 gene mutations in X-linked dominant Charcot-Marie-Tooth disease (CMTX1)

    NARCIS (Netherlands)

    Janssen, EAM; Kemp, S; Hensels, GW; Sie, OG; deDieSmulders, CEM; Hoogendijk, JE; deVisser, M; Bolhuis, PA

    1997-01-01

    Single-strand conformational polymorphisms (SSCP) of the connexin32 gene were analyzed in 121 patients possibly affected by Charcot-Marie-Tooth (CMT) disease. The 121 patients were selected from 443 possible CMT/HNPP (hereditary neuropathy with liability to pressure palsies) patients based on geneti

  14. Surfactant Protein-D-Encoding Gene Variant Polymorphisms Are Linked to Respiratory Outcome in Premature Infants

    DEFF Research Database (Denmark)

    Sorensen, Grith Lykke; Dahl, Marianne; Tan, Qihua

    2014-01-01

    OBJECTIVE: Associations between the genetic variation within or downstream of the surfactant protein-D-encoding gene (SFTPD), which encodes the collectin surfactant protein-D (SP-D) and may lead to respiratory distress syndrome or bronchopulmonary dysplasia, recently were reported. Our aim was to...

  15. Linking gene, brain, and behavior: DRD4, frontal asymmetry, and temperament.

    Science.gov (United States)

    Schmidt, Louis A; Fox, Nathan A; Perez-Edgar, Koraly; Hamer, Dean H

    2009-07-01

    Gene-environment interactions involving exogenous environmental factors are known to shape behavior and personality development. Although gene-environment interactions involving endogenous environmental factors are hypothesized to play an equally important role, this conceptual approach has not been empirically applied in the study of early-developing temperament in humans. Here we report evidence for a gene-endoenvironment (i.e., resting frontal brain electroencephalogram, EEG, asymmetry) interaction in predicting child temperament. The dopamine D4 receptor (DRD4) gene (long allele vs. short allele) moderated the relation between resting frontal EEG asymmetry (left vs. right) at 9 months and temperament at 48 months. Children who exhibited left frontal EEG asymmetry at 9 months and who possessed the DRD4 long allele were significantly more soothable at 48 months than other children. Among children with right frontal EEG asymmetry at 9 months, those with the DRD4 long allele had significantly more difficulties focusing and sustaining attention at 48 months than those with the DRD4 short allele. Resting frontal EEG asymmetry did not influence temperament in the absence of the DRD4 long allele. We discuss how the interaction of genetic and endoenvironmental factors may confer risk and protection for different behavioral styles in children.

  16. Characterization of the NADH-linked acetylacetoin reductase/2,3-butanediol dehydrogenase gene from Bacillus cereus YUF-4.

    Science.gov (United States)

    Hosaka, T; Ui, S; Ohtsuki, T; Mimura, A; Ohkuma, M; Kudo, T

    2001-01-01

    A 1.4-kbp DNA fragment, including the NADH-linked acetylacetoin reductase/2,3-butanediol dehydrogenase (AACRII/BDH) gene from the chromosomal DNA of Bacillus cereus YUF-4, was cloned in Escherichia coli DH5alpha after its insertion into pUC119, and the resulting plasmid was named pAACRII119. The AACRII/BDH gene had an open reading frame consisting of 1047 bp encoding 349 amino acids. The enzyme exhibited not only AACR activity, but also BDH activity. However, the gene was not located in a 2,3-butanediol (BD) operon, as is the case in the BDH gene of Klebsiella pneumoniae and that of K. terrigena. In addition, there was no BD-cycle-related enzyme gene in the region surrounding the AACRII/BDH gene. The AACR and BDH activities in E. coli DH5alpha/pAACRII119 were 200-fold higher than those in the original B. cereus YUF-4. The characteristics of the AACRII/BDH from E. coli DH 5alpha/pAACRII119 are similar to those of the AACRII/BDH from B. cereus YUF-4. The AACRII/BDH was considered to belong to the NAD(P)- and zinc-dependent long-chain alcohol dehydrogenase (group I ADH) family on the basis of the following distinctive characteristics: it possessed 14 strictly conserved residues of microbial group I ADH and consisted of about 350 amino acids. The enzymatic and genetic characteristics of AACRII/BDH were completely different from those of BDHs belonging to the short-chain dehydrogenase/reductase family. These findings indicated that the AACRII/BDH could be considered a new type of BDH.

  17. Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

    Science.gov (United States)

    Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

    2017-07-12

    Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate 7, 41% vs 17%; P = 2 × 10(-4) ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017. © 2017 American Cancer Society. © 2017 American Cancer Society.

  18. Mid-gestational gene expression profile in placenta and link to pregnancy complications.

    Directory of Open Access Journals (Sweden)

    Liis Uusküla

    Full Text Available Despite the importance of placenta in mediating rapid physiological changes in pregnancy, data on temporal dynamics of placental gene expression are limited. We completed the first transcriptome profiling of human placental gene expression dynamics (GeneChips, Affymetrix®; ~47,000 transcripts from early to mid-gestation (n = 10; gestational weeks 5-18 and report 154 genes with significant transcriptional changes (ANOVA, FDR P<0.1. TaqMan RT-qPCR analysis (n = 43; gestational weeks 5-41 confirmed a significant (ANOVA and t-test, FDR P<0.05 mid-gestational peak of placental gene expression for BMP5, CCNG2, CDH11, FST, GATM, GPR183, ITGBL1, PLAGL1, SLC16A10 and STC1, followed by sharp decrease in mRNA levels at term (t-test, FDR P<0.05. We hypothesized that normal course of late pregnancy may be affected when genes characteristic to mid-gestation placenta remain highly expressed until term, and analyzed their expression in term placentas from normal and complicated pregnancies [preeclampsia (PE, n = 12; gestational diabetes mellitus (GDM, n = 12; small- and large-for-gestational-age newborns (SGA, LGA, n = 12+12]. STC1 (stanniocalcin 1 exhibited increased mRNA levels in all studied complications, with the most significant effect in PE- and SGA-groups (t-test, FDR P<0.05. In post-partum maternal plasma, the highest STC1 hormone levels (ELISA, n = 129 were found in women who had developed PE and delivered a SGA newborn (median 731 vs 418 pg/ml in controls; ANCOVA, P = 0.00048. Significantly higher expression (t-test, FDR P<0.05 of CCNG2 and LYPD6 accompanied with enhanced immunostaining of the protein was detected in placental sections of PE and GDM cases (n = 15. Our study demonstrates the importance of temporal dynamics of placental transcriptional regulation across three trimesters of gestation. Interestingly, many genes with high expression in mid-gestation placenta have also been implicated in adult complex disease, promoting the discussion on

  19. Development and mapping of SSR markers linked to resistance-gene homologue clusters in common bean

    Institute of Scientific and Technical Information of China (English)

    Luz; Nayibe; Garzon; Matthew; Wohlgemuth; Blair

    2014-01-01

    Common bean is an important but often a disease-susceptible legume crop of temperate,subtropical and tropical regions worldwide. The crop is affected by bacterial, fungal and viral pathogens. The strategy of resistance-gene homologue(RGH) cloning has proven to be an efficient tool for identifying markers and R(resistance) genes associated with resistances to diseases. Microsatellite or SSR markers can be identified by physical association with RGH clones on large-insert DNA clones such as bacterial artificial chromosomes(BACs). Our objectives in this work were to identify RGH-SSR in a BAC library from the Andean genotype G19833 and to test and map any polymorphic markers to identify associations with known positions of disease resistance genes. We developed a set of specific probes designed for clades of common bean RGH genes and then identified positive BAC clones and developed microsatellites from BACs having SSR loci in their end sequences. A total of 629 new RGH-SSRs were identified and named BMr(bean microsatellite RGH-associated markers). A subset of these markers was screened for detecting polymorphism in the genetic mapping population DOR364 × G19833. A genetic map was constructed with a total of 264 markers,among which were 80 RGH loci anchored to single-copy RFLP and SSR markers. Clusters of RGH-SSRs were observed on most of the linkage groups of common bean and in positions associated with R-genes and QTL. The use of these new markers to select for disease resistance is discussed.

  20. Development and validation of high-throughput single nucleotide polymorphisms for wheat streak mosaic virus resistance gene Wsm2

    Science.gov (United States)

    Wheat streak mosaic virus (WSMV) can cause significant yield loss in wheat (Triticum aestivum L.) in the Great Plains of North America. A recently identified WSMV resistance gene, Wsm2, was mapped to chromosome 3BS in germplasm line ‘CO960293–2’. Effective genetic markers tightly linked to the gene ...

  1. The PML gene is linked to a megabase-scale insertion/deletion restriction fragment length polymorphism

    Energy Technology Data Exchange (ETDEWEB)

    Goy, A.; Xiao, Y.H.; Passalaris, T. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States)] [and others

    1995-03-20

    The PML gene located on chromosome band 15q22 is involved with the RAR{alpha} locus (17q21) in a balanced reciprocal translocation uniquely observed in acute promyelocytic leukemia. Physical mapping studies by pulsed-field gel electrophoresis revealed that the PML gene is flanked by two CpG islands that are separated by a variable distance in normal individuals. Several lines of evidence demonstrate that this is the consequence of a large insertion/deletion polymorphism linked to the PML locus: (1) overlapping fragments obtained with a variety of rare-cutting restriction enzymes demonstrated the same variability in distance between the flanking CpG islands; (2) mapping with restriction enzymes insensitive to CpG methylation confirmed that the findings were not a consequence of variable methylation of CpG dinucleotides; (3) the polymorphism followed a Mendelian inheritance pattern. This polymorphism is localized 3{prime} to the PML locus. There are five common alleles, described on the basis of BssHII fragments, ranging from 220 to 350 kb with increments of approximately 30 kb between alleles. Both heterozygous (61%) and homozygous (391%) patterns were observed in normal individuals. Mega-base-scale insertion/deletion restriction fragment length polymorphisms are very rare and have been described initially in the context of multigene families. Such structures have been also reported as likely regions of genetic instability. High-resolution restriction mapping of this particular structure linked to the PML locus is underway. 47 refs., 4 figs., 1 tab.

  2. Two mutational hotspots in the interleukin-2 receptor {gamma} chain gene causing human X-linked severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Pepper, A.E.; Puck, J.M. [National Institutes of Health, Bethesda, MD (United States); Buckley, R.H. [and others

    1995-09-01

    Human severe combined immunodeficiency (SCID), a syndrome of profoundly impaired cellular and humoral immunity, is most commonly caused by mutations in the X-linked gene for interleukin-2 (IL-2) receptor {gamma} chain (IL2RG). For mutational analysis of IL2RG in males with SCID, SSCP screening was followed by DNA sequencing. Of 40 IL2RG mutations found in unrelated SCID patients, 6 were point mutations at the CpG dinucleotide at cDNA 690-691, encoding amino acid R226. This residue lies in the extracellular domain of the protein in a region not previously recognized to be significantly conserved in the cytokine receptor gene family, 11 amino acids upstream from the highly conserved WSXWS motif. Three additional instances of mutation at another CpG dinucleotide at cDNA 879 produced a premature termination signal in the intracellular domain of IL2RG, resulting in loss of the SH2-homologous intracellular domain known to be essential for signaling from the IL-2 receptor complex. Mutations at these two hotspots constitute >20% of the X-linked SCID mutations found by our group and a similar proportion of all reported IL2RG mutations. 41 refs., 5 figs., 1 tab.

  3. Lifting scheme of symmetric tight wavelets frames

    Institute of Scientific and Technical Information of China (English)

    ZHUANG BoJin; YUAN WeiTao; PENG LiZhong

    2008-01-01

    This paper proposes a method to realize the lifting scheme of tight frame wavelet filters. As for 4-channel tight frame wavelet filter, the tight frame transforms' ma-trix is 2×4, but the lifting scheme transforms' matrix must be 4×4. And in the case of 3-channel tight frame wavelet filter, the transforms' matrix is 2×3, but the lifting scheme transforms' matrix must be 3×3. In order to solve this problem, we intro-duce two concepts: transferred polyphase matrix for 4-channel filters and trans-ferred unitary matrix for 3-channel filters. The transferred polyphase matrix is sym-metric/antisymmetric. Thus, we use this advantage to realize the lifting scheme.

  4. Trees, Tight-Spans and Point Configuration

    CERN Document Server

    Herrmann, Sven

    2011-01-01

    Tight-spans of metrics were first introduced by Isbell in 1964 and rediscovered and studied by others, most notably by Dress who gave them this name. Subsequently, it was found that tight-spans could be defined for more general maps, such as directed metrics and distances, and more recently for diversities. In this paper, we show that all of these tight-spans can be defined in terms of point configurations. This provides a useful way in which to study these objects in a unified and systematic way. We also show that by using point configurations we can recover results concerning one-dimensional tight-spans for all of the maps we consider, as well as extend these and other results to more general maps such as symmetric and unsymmetric maps.

  5. Expansion of Frames to Tight Frames

    Institute of Scientific and Technical Information of China (English)

    Deng Feng LI; Wen Chang SUN

    2009-01-01

    We show that every Bessel sequence (and therefore every frame) in a separable Hilbert space can be expanded to a tight frame by adding some elements. The proof is based on a recent generalization of the frame concept, the g-frame, which illustrates that g-frames could be useful in the study of frame theory. As an application, we prove that any Gabor frame can be expanded to a tight frame by adding one window function.

  6. Behavioral Resilience In the Post-Genomic Era: Emerging Models Linking Genes With Environment

    Directory of Open Access Journals (Sweden)

    Richard eRende

    2012-03-01

    Full Text Available One of the most important deliverables of the post-genomic era has been a new and nuanced appreciation of how the environment shapes – and holds potential to alter – the expression of susceptibility genes for behavioral dimensions and disorders. This paper will consider three themes that have emerged from cutting-edge research studies that utilize newer molecular genetic approaches as well as tried-and-true genetic epidemiological methodologies, with particular reference to evolving perspectives on resilience and plasticity. These themes are: 1 evidence for replicable and robust shared environmental effects on a number of clinically relevant behaviors in childhood and adolescence; 2 evolving research on gene-environment interaction; and 3 a newer focus on differential susceptibility and plasticity. The net sum of these themes is that consideration of genetic effects on behavioral dimensions and disorders needs to be connected to thinking about the role of environment as a potent source for promoting resilience and change.

  7. 125 INCOMPLETE COMPENSATORY UP-REGULATION OF X-LINKED GENES IN BOVINE GERMLINE, EARLY EMBRYOS, AND SOMATIC TISSUES.

    Science.gov (United States)

    Duan, J; Jue, N K; Jiang, Z; O'Neill, R; Wolf, E; Blomberg, L A; Dong, H; Zheng, X; Chen, J; Tian, X

    2016-01-01

    The maintenance of a proper gene dosage is essential in cellular networks. To resolve the dosage imbalance between eutherian females (XX) and male (XY), X chromosome inactivation (XCI) occurs in females, while X-chromosome dosage compensation up-regulates the active X to balance its expression with that of autosome pairs [Ohno's hypothesis; Ohno 1967 Sex Chromosomes and Sex-linked Genes (Springer-Verlag), p. 99]. These phenomena have been well studied in humans and mice, despite many controversies over the existence of such up-regulation. Using RNA sequencing data, we determined X chromosome dosage compensation in the bovine by analysing the global expression profiles of germ cells, embryos, and somatic tissues. Eight bovine RNA-seq data sets were obtained in from the Gene Expression Omnibus, covering bovine immature/mature oocytes (GSE59186 and GSE52415), pre-implantation conceptuses (GSE59186, GSE52415, and GSE56513), extra-embryonic tissues (PRJNA229443), and male/female somatic tissues (GSE74076, GSE63509, PRJEB6377, and GSE65125). The RNAseq data were trimmed and non-uniquely (paralogs included) mapped to the bovine reference genome assembly UMD3.1.1 using Hisat2 (version 2.0.5) aligner. The mRNA level of each gene, estimated by transformed transcripts per kilobase million was quantified by IsoEM (version 1.1.5). These RNA-seq data sets represented 4 chromosome scenarios in cells: XXXX:AAAA (diploid immature oocyte with DNA duplication), XX:AA (haploid mature oocyte with DNA duplication), XX:AA and X:AA (gradual changed X status in bovine pre-implantation conceptuses), and X:AA (extra-embryonic tissues and somatic cells in female with one active X or XY male) were analysed for dosage compensation. A total of 959 X-linked genes and 20,316 autosome genes were used to calculate the relative X to autosomal gene (A) expression (RXE): log2 (X expression) - log2 (A expression). The following dosage determinations were made: RXE values ≥ 0: complete dosage

  8. Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

    Directory of Open Access Journals (Sweden)

    Atique M Ahmed

    2014-08-01

    Full Text Available Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all. Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94% and 134 (92% patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen

  9. Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

    Science.gov (United States)

    Ahmed, Atique M; Pinheiro, Miguel M; Divis, Paul C; Siner, Angela; Zainudin, Ramlah; Wong, Ing Tien; Lu, Chan Woon; Singh-Khaira, Sarina K; Millar, Scott B; Lynch, Sean; Willmann, Matthias; Singh, Balbir; Krishna, Sanjeev; Cox-Singh, Janet

    2014-08-01

    Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human

  10. Prenatal sex determination in suspicious cases of X-linked recessive diseases by the amelogenin gene

    Directory of Open Access Journals (Sweden)

    Amir Abbas Rahimi

    2014-02-01

    Conclusion: Sex detection of fetus before delivery in the first trimester of pregnancy, will prevent babies with abnormalities being born. It can also be used in detection of recessive sex related diseases in In Vitro Fertilization cases for sex detection and to transfer female fetus to the mother. Our optimized molecular detection system was designed on the basis of amelogenin gene, which can determine the sex in blood, chorionic villi, and single cell in vitro fertilization with high sensitivity and specificity.

  11. Expression of novel genes linked to the androgen-induced, proliferative shutoff in prostate cancer cells.

    Science.gov (United States)

    Geck, P; Szelei, J; Jimenez, J; Lin, T M; Sonnenschein, C; Soto, A M

    1997-01-01

    Androgens control cell numbers in the prostate through three separate pathways: (a) inhibition of cell death, (b) induction of cell proliferation (Step-1) and (c) inhibition of cell proliferation (Step-2, proliferative shutoff). The mechanisms underlying these phenomena are incompletely understood. The human prostate carcinoma LNCaP variants express these pathways as follows: LNCaP-FGC express both steps, LNCaP-LNO expresses Step-2, LNCaP-TAC expresses Step-1, and LNCaP-TJA cells express neither step. These cells facilitated the search for mediators of the androgen-induced proliferative shutoff pathway. Androgen exposure for 24 h or longer induced an irreversible proliferative shutoff in LNCaP-FGC cells. The Wang and Brown approach for identifying differentially expressed mRNAs was used to search for mediators of Step-2. Ten unique inserts were identified and from those ten, three genes were further studied. The basal expression of these genes in shutoff-negative variants was not affected by androgen exposure. They were induced by androgens in shutoff-positive LNCaP variants and the androgen receptor-transfected, shutoff-positive, MCF7-AR1 cells. These genes were induced only in the range of androgen concentrations that elicited the shutoff response. Time course analysis showed that their induction precedes the commitment point by 12-18 h. In addition, they were expressed in the normal prostate during proliferative shutoff. These features suggest that the candidate genes have a role in the regulation cascade for proliferative shutoff.

  12. Chloroplast two-component systems: evolution of the link between photosynthesis and gene expression

    OpenAIRE

    Puthiyaveetil, Sujith; Allen, John F.

    2009-01-01

    Two-component signal transduction, consisting of sensor kinases and response regulators, is the predominant signalling mechanism in bacteria. This signalling system originated in prokaryotes and has spread throughout the eukaryotic domain of life through endosymbiotic, lateral gene transfer from the bacterial ancestors and early evolutionary precursors of eukaryotic, cytoplasmic, bioenergetic organelles—chloroplasts and mitochondria. Until recently, it was thought that two-component systems i...

  13. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

    Science.gov (United States)

    Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

    2016-05-01

    Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine.

  14. Construction of an integrated gene regulatory network link to stress-related immune system in cattle.

    Science.gov (United States)

    Behdani, Elham; Bakhtiarizadeh, Mohammad Reza

    2017-08-20

    The immune system is an important biological system that is negatively impacted by stress. This study constructed an integrated regulatory network to enhance our understanding of the regulatory gene network used in the stress-related immune system. Module inference was used to construct modules of co-expressed genes with bovine leukocyte RNA-Seq data. Transcription factors (TFs) were then assigned to these modules using Lemon-Tree algorithms. In addition, the TFs assigned to each module were confirmed using the promoter analysis and protein-protein interactions data. Therefore, our integrated method identified three TFs which include one TF that is previously known to be involved in immune response (MYBL2) and two TFs (E2F8 and FOXS1) that had not been recognized previously and were identified for the first time in this study as novel regulatory candidates in immune response. This study provides valuable insights on the regulatory programs of genes involved in the stress-related immune system.

  15. RAB39B gene mutations are not linked to familial Parkinson’s disease in China

    Science.gov (United States)

    Kang, Ji-feng; Luo, Yang; Tang, Bei-sha; Wan, Chang-min; Yang, Yang; Li, Kai; Liu, Zhen-hua; Sun, Qi-ying; Xu, Qian; Yan, Xin-xiang; Guo, Ji-feng

    2016-01-01

    Recently, RAB39B mutations were reported to be a causative factor in patients with Parkinson’s disease (PD). To validate the role of RAB39B in familial PD, a total of 195 subjects consisting of 108 PD families with autosomal-dominant (AD) inheritance and 87 PD families with autosomal-recessive (AR) inheritance in the Chinese Han population from mainland China were included in this study. We did not identify any variants in the coding region or the exon-intron boundaries of the gene by Sanger sequencing method in the DNA samples of 180 patients (100 with AD and 80 with AR). Furthermore, we did not find any variants in the RAB39B gene when Whole-exome sequencing (WES) was applied to DNA samples from 15 patients (8 with AD and 7 with AR) for further genetic analysis. Additionally, when quantitative real-time PCR was used to exclude large rearrangement variants in these patients, we found no dosage mutations in RAB39B gene. Our results suggest that RAB39B mutation is very rare in familial PD and may not be a major cause of familial PD in the Chinese Han Population. PMID:27694831

  16. A Pathologic Link between Wilms Tumor Suppressor Gene, WT1, and IFI16

    Directory of Open Access Journals (Sweden)

    Marianne K-H. Kim

    2008-01-01

    Full Text Available The Wilms tumor gene (WT1 is mutated or deleted in patients with heredofamilial syndromes associated with the development of Wilms tumors, but is infrequently mutated in sporadic Wilms tumors. By comparing the microarray profiles of syndromic versus sporadic Wilms tumors and WT1-inducible Saos-2 osteosarcoma cells, we identified interferon-inducible protein 16 (IFI16, a transcriptional modulator, as a differentially expressed gene and a candidate WT1 target gene. WT1 induction in Saos-2 osteosarcoma cells led to strong induction of IFI16 expression and its promoter activity was responsive to the WT1 protein. Immunohistochemical analysis showed that IFI16 and WT1 colocalized in WT1-replete Wilms tumors, but not in normal human midgestation fetal kidneys, suggesting that the ability of WT1 to regulate IFI16 in tumors represented an aberrant pathologic relationship. In addition, endogenous IFI16 and WT1 interacted in vivo in two Wilms tumor cell lines. Furthermore, IFI16 augmented the transcriptional activity of WT1 on both synthetic and physiological promoters. Strikingly, short hairpin RNA (shRNA-mediated knockdown of either IFI16 or WT1 led to decreased growth of Wilms tumor cells. These data suggest that IFI16 and WT1, in certain cellular context including sporadic Wilms tumors, may support cell survival.

  17. Functionalized layered double hydroxide nanoparticles conjugated with disulfide-linked polycation brushes for advanced gene delivery.

    Science.gov (United States)

    Hu, H; Xiu, K M; Xu, S L; Yang, W T; Xu, F J

    2013-06-19

    Layered double hydroxides (LDHs) have aroused great attention as potential nanosized drug delivery carriers, but independent inorganic LDH wrapped with DNA shows very low transfection efficiency. To manipulate and control the surface properties of LDH nanoparticles is of crucial importance in the designing of LDH-based drug carriers. In this work, surface-initiated atom transfer radical polymerization (ATRP) of 2-(dimethylamino)ethyl methacrylate (DMAEMA) is employed to tailor the functionality of LDH surfaces in a well-controlled manner and produce a series of well-defined novel gene delivery vectors (termed as LDH-PDs), where a flexible three-step method was first developed to introduce the ATRP initiation sites containing disulfide bonds onto LDH surfaces. In comparison the pristine LDH particles, the resultant LDH-PDs exhibited better ability to condense plasmid DNA (pDNA) and much higher levels to delivery genes in different cell lines including COS7 and HepG2 cell lines. Moreover, the LDH-PDs also could largely enhance cellular uptake. This present study demonstrates that functionalization of bioinorganic LDH with flexible polycation brushes is an effective means to produce new LDH-based gene delivery systems.

  18. Early Phenylpropanoid Biosynthetic Steps in Cannabis sativa: Link between Genes and Metabolites

    Directory of Open Access Journals (Sweden)

    Immacolata Coraggio

    2013-06-01

    Full Text Available Phenylalanine ammonia-lyase (PAL, Cinnamic acid 4-hydroxylase (C4H and 4-Coumarate: CoA ligase (4CL catalyze the first three steps of the general phenylpropanoid pathway whereas chalcone synthase (CHS catalyzes the first specific step towards flavonoids production. This class of specialized metabolites has a wide range of biological functions in plant development and defence and a broad spectrum of therapeutic activities for human health. In this study, we report the isolation of hemp PAL and 4CL cDNA and genomic clones. Through in silico analysis of their deduced amino acid sequences, more than an 80% identity with homologues genes of other plants was shown and phylogenetic relationships were highlighted. Quantitative expression analysis of the four above mentioned genes, PAL and 4CL enzymatic activities, lignin content and NMR metabolite fingerprinting in different Cannabis sativa tissues were evaluated. Furthermore, the use of different substrates to assay PAL and 4CL enzymatic activities indicated that different isoforms were active in different tissues. The diversity in secondary metabolites content observed in leaves (mainly flavonoids and roots (mainly lignin was discussed in relation to gene expression and enzymatic activities data.

  19. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders

    Directory of Open Access Journals (Sweden)

    Qingying Meng

    2016-05-01

    Full Text Available Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient–host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control and hippocampus (cognitive processing from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine.

  20. A PRACTICAL APPROACH TO THE DETECTION OF ANDROGEN RECEPTOR GENE-MUTATIONS AND PEDIGREE ANALYSIS IN FAMILIES WITH X-LINKED ANDROGEN INSENSITIVITY

    NARCIS (Netherlands)

    RISSTALPERS, C; HOOGENBOEZEM, T; SLEDDENS, HFBM; VERLEUNMOOIJMAN, MCT; DEGENHART, HJ; DROP, SLS; HALLEY, DJJ; Oosterwijk, Jan; HODGINS, MB; TRAPMAN, J; BRINKMANN, AO

    1994-01-01

    Androgen insensitivity syndrome (AIS) is an X-linked disorder in which defects in the androgen receptor gene have prevented the normal development of both internal and external male structures in 46,XY individuals. This survey reports the analysis of 11 AIS subjects. The androgen receptor gene of th

  1. Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

    DEFF Research Database (Denmark)

    Basse, Astrid L.; Dixen, Karen; Yadav, Rachita;

    2015-01-01

    NR1H3, MYC, KLF4, ESR1, RELA and BCL6, which were linked to the overall changes in gene expression during the adipose tissue remodeling. Finally, the perirenal adipose tissue expressed both brown and brite/beige adipocyte marker genes at birth, the expression of which changed substantially over time...

  2. Gene-Environment Interplay in the Link of Friends' and Nonfriends' Behaviors with Children's Social Reticence in a Competitive Situation

    Science.gov (United States)

    Guimond, Fanny-Alexandra; Brendgen, Mara; Vitaro, Frank; Forget-Dubois, Nadine; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2014-01-01

    This study used a genetically informed design to assess the effects of friends' and nonfriends' reticent and dominant behaviors on children's observed social reticence in a competitive situation. Potential gene-environment correlations (rGE) and gene-environment interactions (GxE) in the link between (a) friends' and…

  3. X-linked mental retardation: a comprehensive molecular screen of 47 candidate genes from a 7.4 Mb interval in Xp11.

    NARCIS (Netherlands)

    Jensen, L.R.; Lenzner, S.; Moser, B.; Freude, K.; Tzschach, A.; Wei, C.; Fryns, J.P.; Chelly, J.; Turner, G.; Moraine, C.; Hamel, B.C.J.; Ropers, H.H.; Kuss, A.W.

    2007-01-01

    About 30% of the mutations causing nonsyndromic X-linked mental retardation (MRX) are thought to be located in Xp11 and in the pericentromeric region, with a particular clustering of gene defects in a 7.4 Mb interval flanked by the genes ELK1 and ALAS2. To search for these mutations, 47 brain-expres

  4. [A simple method to correct genetic distance between linked genes and a correction of calculating data in tetrad analysis in Neurospora crassa].

    Science.gov (United States)

    Li, You-Yong; Zhao, Yuan-Zeng

    2003-05-01

    The present paper is dealing with a simple method to correct the distance of linked genes in tetrad analysis in Neurospora crassa. It is suggested that the data of 4-thread double crossing over should be added in two single crossing over respectively in centromere maping when calculating crossover value of the two genes locating across the centromere.

  5. Implications of the genetic epidemiology of globin haplotypes linked to the sickle cell gene in southern Iran.

    Science.gov (United States)

    Rahimi, Zohreh; Merat, Ahmad; Gerard, Nathalie; Krishnamoorthy, Rajagopal; Nagel, Ronald L

    2006-12-01

    To determine the origin of sickle cell mutation in different ethnic groups living in southern Iran, we studied the haplotype background of the betaS and betaA genes in subjects from the provinces of Fars, Khuzestan, Bushehr, Hormozgan, and Kerman and from the islands of Khark and Qeshm. beta-globin gene cluster haplotypes were determined using the PCR-RFLP technique. Detection of -alpha 3.7 deletion and beta-thalassemia mutations were defined by PCR and reverse dot blot techniques, respectively. The framework of the beta-globin gene was determined using denaturing gradient gel electrophoresis. We found that the betaS mutation in southern Iran is associated with multiple mutational events. Most of the patients were from two ethnic groups: Farsi speakers (presumably Persian in origin) from Fars province and patients of Arab origin from Khuzestan province. In both ethnic groups the Arab-Indian haplotype was the most prevalent. The frequencies of the Arab-Indian and African haplotypes in sickle cell anemia patients from the provinces of Fars and Khuzestan were similar. Among betaA chromosomes the Bantu A2 haplotype was the most prevalent. The decrease in alpha-globin production in SS patients and AS individuals appeared to be related to the reduction in mean cell volume and mean cell hemoglobin. The Arab-Indian haplotype gene flow into this region of Iran can be traced to the Sassanian Empire. It is likely that the influx of betaS genes linked to the Benin and Bantu haplotypes, of African origin, must have occurred during the Arab slave trade.

  6. Double-hairpin molecular-beacon-based amplification detection for gene diagnosis linked to cancer.

    Science.gov (United States)

    Xu, Huo; Zhang, Rongbo; Li, Feng; Zhou, Yingying; Peng, Ting; Wang, Xuedong; Shen, Zhifa

    2016-09-01

    A powerful double-hairpin molecular beacon (DHMB) was developed for cancer-related KRAS gene detection based on the one-to-two stoichiometry. During target DNA detection, DHMB can execute signal transduction even if no any exogenous element is involved. Unlike the conventional molecular beacon based on the one-to-one interaction, one target DNA not only hybridizes with one DHMB and opens its hairpin but also promotes the interaction between two DHMBs, causing the separation of two fluorophores from quenchers. This leads to an enhanced fluorescence signal. As a result, the target KRAS gene is able to be detected within a wide dynamic range from 0.05 to 200 nM with the detection limit of 50 pM, indicating a dramatic improvement compared with traditional molecular beacons. Moreover, the point mutations existing in target DNAs can be easily screened. The potential application for target species in real samples was indicated by the analysis of PCR amplicons of DNAs from the DNA extracted from SW620 cell. Besides becoming a promising candidate probe for molecular biology research and clinical diagnosis of genetic diseases, the DHMB is expected to provide a significant insight into the design of DNA probe-based homogenous sensing systems. Graphical Abstract A powerful double-hairpin molecular beacon (DHMB) was developed for cancer-related gene KRAS detection based on the one-to-two stoichiometry. Without the help of any exogenous probe, the point mutation is easily screened, and the target DNA can be quantified down to 50 pM, indicating a dramatic improvement compared with traditional molecular beacons.

  7. Identification of Molecular Markers Linked to TuMV Resistant Gene in Cabbage

    Institute of Scientific and Technical Information of China (English)

    GAO Jinping; WANG Chao; LIU Ying

    2008-01-01

    A total of 144 F2 individuals were obtained from the crossing between 1047 (susceptible) and A21 (resistant).Two RAPD markers were screened out in 200 random primers using BSA(Bulked Segregant Analysis). Two RAPD markers, designated as AG13/2000 and U16/660,were 7.7 cM and 8.38 cM apart from the TuMV resistant gene,respectively. The two RAPD fragments were converted to SCAR markers.SCAR markers were confined in germplasm.

  8. Transcriptional Regulation of Chemokine Genes: A Link to Pancreatic Islet Inflammation?

    Directory of Open Access Journals (Sweden)

    Susan J. Burke

    2015-05-01

    Full Text Available Enhanced expression of chemotactic cytokines (aka chemokines within pancreatic islets likely contributes to islet inflammation by regulating the recruitment and activation of various leukocyte populations, including macrophages, neutrophils, and T-lymphocytes. Because of the powerful actions of these chemokines, precise transcriptional control is required. In this review, we highlight what is known about the signals and mechanisms that govern the transcription of genes encoding specific chemokine proteins in pancreatic islet β-cells, which include contributions from the NF-κB and STAT1 pathways. We further discuss increased chemokine expression in pancreatic islets during autoimmune-mediated and obesity-related development of diabetes.

  9. MHC-dependent mate choice is linked to a trace-amine-associated receptor gene in a mammal.

    Science.gov (United States)

    Santos, Pablo S C; Courtiol, Alexandre; Heidel, Andrew J; Höner, Oliver P; Heckmann, Ilja; Nagy, Martina; Mayer, Frieder; Platzer, Matthias; Voigt, Christian C; Sommer, Simone

    2016-12-12

    Major histocompatibility complex (MHC) genes play a pivotal role in vertebrate self/nonself recognition, parasite resistance and life history decisions. In evolutionary terms, the MHC's exceptional diversity is likely maintained by sexual and pathogen-driven selection. Even though MHC-dependent mating preferences have been confirmed for many species, the sensory and genetic mechanisms underlying mate recognition remain cryptic. Since olfaction is crucial for social communication in vertebrates, variation in chemosensory receptor genes could explain MHC-dependent mating patterns. Here, we investigated whether female mate choice is based on MHC alleles and linked to variation in chemosensory trace amine-associated receptors (TAARs) in the greater sac-winged bat (Saccopteryx bilineata). We sequenced several MHC and TAAR genes and related their variation to mating and paternity data. We found strong evidence for MHC class I-dependent female choice for genetically diverse and dissimilar males. We also detected a significant interaction between mate choice and the female TAAR3 genotype, with TAAR3-heterozygous females being more likely to choose MHC-diverse males. These results suggest that TAARs and olfactory cues may be key mediators in mammalian MHC-dependent mate choice. Our study may help identify the ligands involved in the chemical communication between potential mates.

  10. A quantitative real-time PCR method using an X-linked gene for sex typing in pigs.

    Science.gov (United States)

    Ballester, Maria; Castelló, Anna; Ramayo-Caldas, Yuliaxis; Folch, Josep M

    2013-06-01

    At present, a wide range of molecular sex-typing protocols in wild and domestic animals are available. In pigs, most of these methods are based on PCR amplification of X-Y homologous genes followed by gel electrophoresis which is time-consuming and in some cases expensive. In this paper, we describe, for the first time, a SYBR green-based quantitative real-time PCR (qPCR) assay using an X-linked gene, the glycoprotein M6B, for genetic sexing of pigs. Taking into account the differences in the glycoprotein M6B gene copy number between genders, we determine the correct sex of 54 pig samples from either diaphragm or hair follicle from different breeds using the 2(-ΔΔCT) method for relative quantification. Our qPCR assay represents a quick, inexpensive, and reliable tool for sex determination in pigs. This new protocol could be easily adapted to other species in which the sex determination was required.

  11. Genome wide association mapping in Arabidopsis thaliana identifies novel genes involved in linking allyl glucosinolate to altered biomass and defense

    Directory of Open Access Journals (Sweden)

    Marta Francisco

    2016-07-01

    Full Text Available A key limitation in modern biology is the ability to rapidly identify genes underlying newly identified complex phenotypes. Genome wide association studies (GWAS have become an increasingly important approach for dissecting natural variation by associating phenotypes with genotypes at a genome wide level. Recent work is showing that the Arabidopsis thaliana defense metabolite, allyl glucosinolate (GSL, may provide direct feedback regulation, linking defense metabolism outputs to the growth and defense responses of the plant. However, there is still a need to identify genes that underlie this process. To start developing a deeper understanding of the mechanism(s that modulate the ability of exogenous allyl GSL to alter growth and defense, we measured changes in plant biomass and defense metabolites in a collection of natural 96 A. thaliana accessions fed with 50 µM of allyl GSL. Exogenous allyl GSL was introduced exclusively to the roots and the compound transported to the leaf leading to a wide range of heritable effects upon plant biomass and endogenous GSL accumulation. Using natural variation we conducted GWAS to identify a number of new genes which potentially control allyl responses in various plant processes. This is one of the first instances in which this approach has been successfully utilized to begin dissecting a novel phenotype to the underlying molecular/polygenic basis.

  12. Epigenetic changes in the hypothalamic pro-opiomelanocortin gene: a mechanism linking maternal undernutrition to obesity in the offspring?

    Science.gov (United States)

    Stevens, Adam; Begum, Ghazala; White, Anne

    2011-06-11

    Maternal undernutrition is associated with programming of obesity in offspring. While previous evidence has linked programming to the hypothalamic, pituitary, and adrenal (HPA) axis it could also affect the hypothalamic neuropeptides which regulate food intake and energy balance. Alpha melanocyte stimulating hormone (αMSH), a key regulator of these neuronal pathways, is derived from pro-opiomelanocortin (POMC) which is therefore a prime target for the programming of obesity. Several models of maternal undernutrition have identified changes in POMC in hypothalami from foetuses or offspring at various ages. These models have also shown that the offspring go on to develop obesity and/or glucose intolerance. It is our hypothesis that programming leads to epigenetic changes in hypothalamic neuropeptide genes. Therefore when there is subsequent increased food availability, the epigenetic changes could cause dysfunctional transcriptional regulation of energy balance. We present evidence of epigenetic changes in the POMC gene promoter in foetal hypothalami after peri-conceptional undernutrition. In this model there are also epigenetic changes in the hypothalamic glucocorticoid receptor with consequent up-regulation of the receptor which could lead to alterations in the regulation of POMC and neuropeptide Y (NPY) in the hypothalamus. Thus maternal undernutrition could cause epigenetic changes in the POMC and glucocorticoid receptor genes, in the foetal hypothalamus, which may predispose the offspring to altered regulation of food intake, energy expenditure and glucose homeostasis, later in life. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  13. Potential technical solutions to recover tight oil: Literature and simulation study of tight oil development

    OpenAIRE

    Zhang, Kai

    2014-01-01

    Over past decades, technology innovation drove unconventional resourcesbecome conventional. Incorporating the technologies applied in shale gasdevelopment, exploiting tight oil comes into stage recently. Advanced technology such as long horizontal wells combined with massivelyhydraulic fracturing was established as necessity to exploit tight oil reserve, however,primary recovery remains as low as 5.0-10.0% of original oil in place in tight oilreservoir with these technologies applied.[1] ...

  14. Mechanistic links between cellular trade-offs, gene expression, and growth.

    Science.gov (United States)

    Weiße, Andrea Y; Oyarzún, Diego A; Danos, Vincent; Swain, Peter S

    2015-03-01

    Intracellular processes rarely work in isolation but continually interact with the rest of the cell. In microbes, for example, we now know that gene expression across the whole genome typically changes with growth rate. The mechanisms driving such global regulation, however, are not well understood. Here we consider three trade-offs that, because of limitations in levels of cellular energy, free ribosomes, and proteins, are faced by all living cells and we construct a mechanistic model that comprises these trade-offs. Our model couples gene expression with growth rate and growth rate with a growing population of cells. We show that the model recovers Monod's law for the growth of microbes and two other empirical relationships connecting growth rate to the mass fraction of ribosomes. Further, we can explain growth-related effects in dosage compensation by paralogs and predict host-circuit interactions in synthetic biology. Simulating competitions between strains, we find that the regulation of metabolic pathways may have evolved not to match expression of enzymes to levels of extracellular substrates in changing environments but rather to balance a trade-off between exploiting one type of nutrient over another. Although coarse-grained, the trade-offs that the model embodies are fundamental, and, as such, our modeling framework has potentially wide application, including in both biotechnology and medicine.

  15. Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Rajan, Thangavelu Soundara; Scionti, Domenico; Diomede, Francesca; Grassi, Gianpaolo; Pollastro, Federica; Piattelli, Adriano; Cocco, Lucio; Bramanti, Placido; Mazzon, Emanuela; Trubiani, Oriana

    2017-04-01

    Research in recent years has extensively investigated the therapeutic efficacy of mesenchymal stromal cells in regenerative medicine for many neurodegenerative diseases at preclinical and clinical stages. However, the success rate of stem cell therapy remains less at translational phase. Lack of relevant animal models that potentially simulate the molecular etiology of human pathological symptoms might be a reason behind such poor clinical outcomes associated with stem cell therapy. Apparently, self-renewal and differentiation ability of mesenchymal stem cells may help to study the early developmental signaling pathways connected with the diseases, such as Alzheimer's disease, Amyotrophic lateral sclerosis (ALS), etc., at in vitro level. Cannabidiol, a non-psychotrophic cannabinoid, has been demonstrated as a potent anti-inflammatory and neuroprotective agent in neurological preclinical models. In the present study, we investigated the modulatory role of cannabidiol on genes associated with ALS using human gingiva-derived mesenchymal stromal cells (hGMSCs) as an in vitro model system. Next generation transcriptomic sequencing analysis demonstrated considerable modifications in the expression of genes connected with ALS pathology, oxidative stress, mitochondrial dysfunction, and excitotoxicity in hGMSCs treated with cannabidiol. Our results suggest the efficacy of cannabidiol to delineate the unknown molecular pathways, which may underlie ALS pathology at an early stage using hGMSCs as a compelling in vitro system. J. Cell. Biochem. 118: 819-828, 2017. © 2016 Wiley Periodicals, Inc.

  16. Quantitative trait loci linked to PRNP gene controlling health and production traits in INRA 401 sheep

    Directory of Open Access Journals (Sweden)

    Brunel Jean-Claude

    2007-07-01

    Full Text Available Abstract In this study, the potential association of PrP genotypes with health and productive traits was investigated. Data were recorded on animals of the INRA 401 breed from the Bourges-La Sapinière INRA experimental farm. The population consisted of 30 rams and 852 ewes, which produced 1310 lambs. The animals were categorized into three PrP genotype classes: ARR homozygous, ARR heterozygous, and animals without any ARR allele. Two analyses differing in the approach considered were carried out. Firstly, the potential association of the PrP genotype with disease (Salmonella resistance and production (wool and carcass traits was studied. The data used included 1042, 1043 and 1013 genotyped animals for the Salmonella resistance, wool and carcass traits, respectively. The different traits were analyzed using an animal model, where the PrP genotype effect was included as a fixed effect. Association analyses do not indicate any evidence of an effect of PrP genotypes on traits studied in this breed. Secondly, a quantitative trait loci (QTL detection approach using the PRNP gene as a marker was applied on ovine chromosome 13. Interval mapping was used. Evidence for one QTL affecting mean fiber diameter was found at 25 cM from the PRNP gene. However, a linkage between PRNP and this QTL does not imply unfavorable linkage disequilibrium for PRNP selection purposes.

  17. Association between 5-hydroxytryptamine transporter gene-linked polymorphic region and smoking behavior in Chinese males

    Institute of Scientific and Technical Information of China (English)

    CHU Shui-lian; XIAO Dan; WANG Chen; JING Hang

    2009-01-01

    Background Tobacco use is the major risk factor for numerous health problems. However, only 5% of smokers can successfully quit without therapy owing to the highly addictive properties of nicotine. The serotoninergic system may be involved in smoking behavior because nicotine increases brain serotonin secretion, nicotine withdrawal decreases serotonin levels, and a selective serotonin reuptake inhibitor antagonizes the response to nicotine withdrawal. Serotonin transporter (5-HTT) is the most important protein, as it adjusts the serotonin concentration in the synaptic cleft. There is a polymorphism in the upstream regulatory region of the 5-HTT gene, named 5-hydroxytryptamine transporter gene-Iinked poyymorphic region (5-HTTLPR). Compared with the L allele, the S allele of the polymorphism is associated with decreased transcription efficiency of the 5-HTT gene. In this study, we investigated the relationship between this gene polymorphism and smoking behavior in Chinese males.Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find 5-HTTLPR gene polymorphisms in 144 smokers and 135 age-matched healthy non-smokers. A questionnaire was completed in all recruited subjects.Results The proportion of L/L (15.3% vs 5.2%) and S/L (50.0% vs 33.3%) genotypes was significantly higher in the smokers than that in the non-smokers (χ2=21.9; P <0.01). The odds ratio (OR) adjusted by age, education, effects of family members and friends who smoke, and alcohol intake was 2.9 (95%CI 1.78-4.80). In smokers, the number of cigarettes/day (L/L vs S/L vs S/S: 28+12 vs 20±8 vs 16±6, χ2=18.5, P <0.01), smoking index (L/L vs S/L vs S/S.. 561±446vs 393±341 vs 237+901, χ2=12.5, P <0.01) and score on the Fagerstrom test for nicotine dependence (FTND) (L/L vs S/L vs S/S. 7.8±1.6 vs 6.2±9.5 vs 3.5±9.1, χ2=48.3, P <0.01) were significantly higher in smokers with an L/L or S/L genotype than that in the smokers with the S/S genotype

  18. Androgen-Dependent Sertoli Cell Tight Junction Remodeling Is Mediated by Multiple Tight Junction Components

    National Research Council Canada - National Science Library

    Chakraborty, Papia; William Buaas, F; Sharma, Manju; Smith, Benjamin E; Greenlee, Anne R; Eacker, Stephen M; Braun, Robert E

    2014-01-01

    Sertoli cell tight junctions (SCTJs) of the seminiferous epithelium create a specialized microenvironment in the testis to aid differentiation of spermatocytes and spermatids from spermatogonial stem cells...

  19. Bending the Rules of Transcriptional Repression: Tightly Looped DNA Directly Represses T7 RNA Polymerase

    OpenAIRE

    Lionberger, Troy A.; Meyhöfer, Edgar

    2010-01-01

    From supercoiled DNA to the tight loops of DNA formed by some gene repressors, DNA in cells is often highly bent. Despite evidence that transcription by RNA polymerase (RNAP) is affected in systems where DNA is deformed significantly, the mechanistic details underlying the relationship between polymerase function and mechanically stressed DNA remain unclear. Seeking to gain additional insight into the regulatory consequences of highly bent DNA, we hypothesize that tightly looping DNA is alone...

  20. Transcriptional heterogeneity in the lactase gene within cell-type is linked to the epigenome

    Science.gov (United States)

    Oh, Edward; Jeremian, Richie; Oh, Gabriel; Groot, Daniel; Susic, Miki; Lee, KwangHo; Foy, Kelly; Laird, Peter W.; Petronis, Arturas; Labrie, Viviane

    2017-01-01

    Transcriptional variation in histologically- and genetically- identical cells is a widespread phenomenon in tissues, yet the processes conferring this heterogeneity are not well understood. To identify contributing factors, we analyzed epigenetic profiles associated with the in vivo transcriptional gradient of the mouse lactase gene (Lct), which occurs in enterocytes along the proximal-to-distal axis of the small intestine. We found that epigenetic signatures at enhancer and promoter elements aligns with transcriptional variation of Lct in enterocytes. Age and phenotype-specific environmental cues (lactose exposure after weaning) induced changes to epigenetic modifications and CTCF binding at select regulatory elements, which corresponded to the alterations in the intestinal Lct mRNA gradient. Thus, epigenetic modifications in combination with CTCF binding at regulatory elements account for the transcriptional gradient in Lct in cells of the same type. Epigenetic divergence within enterocytes may contribute to the functional specialization of intestinal subregions. PMID:28139744

  1. Microgravity-Induced Transcriptome Adaptation in Mouse Paraspinal longissimus dorsi Muscle Highlights Insulin Resistance-Linked Genes

    Directory of Open Access Journals (Sweden)

    Guido Gambara

    2017-05-01

    Full Text Available Microgravity as well as chronic muscle disuse are two causes of low back pain originated at least in part from paraspinal muscle deconditioning. At present no study investigated the complexity of the molecular changes in human or mouse paraspinal muscles exposed to microgravity. The aim of this study was to evaluate longissimus dorsi adaptation to microgravity at both morphological and global gene expression level. C57BL/N6 male mice were flown aboard the BION-M1 biosatellite for 30 days (BF or housed in a replicate flight habitat on ground (BG. Myofiber cross sectional area and myosin heavy chain subtype patterns were respectively not or slightly altered in longissimus dorsi of BF mice. Global gene expression analysis identified 89 transcripts differentially regulated in longissimus dorsi of BF vs. BG mice. Microgravity-induced gene expression changes of lipocalin 2 (Lcn2, sestrin 1(Sesn1, phosphatidylinositol 3-kinase, regulatory subunit polypeptide 1 (p85 alpha (Pik3r1, v-maf musculoaponeurotic fibrosarcoma oncogene family protein B (Mafb, protein kinase C delta (Prkcd, Muscle Atrophy F-box (MAFbx/Atrogin-1/Fbxo32, and Muscle RING Finger 1 (MuRF-1 were further validated by real time qPCR analysis. In conclusion, our study highlighted the regulation of transcripts mainly linked to insulin sensitivity and metabolism in longissimus dorsi following 30 days of microgravity exposure. The apparent absence of robust signs of back muscle atrophy in space-flown mice, despite the overexpression of Atrogin-1 and MuRF-1, opens new questions on the possible role of microgravity-sensitive genes in the regulation of peripheral insulin resistance following unloading and its consequences on paraspinal skeletal muscle physiology.

  2. Molecular characterization of RAPD and SCAR marker linked to the frog-eye leaf spot resistance gene in soybean

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Two fragments SCS3620 and SCS3580 of the co-dominant marker OPS03620&580 that were linked to the resistance gene of soybean frog-eye leaf spot have been completely sequenced.A significant insertion of 30 bp is the main reason of the polymorphism between the two fragments.The results of Southern hybridization indicate that SCS3620 derives from a single- or low-copy sequence and can be used as an RFLP probe.A co-dominant SCAR marker SCS3620&580 has been developed based on the sequences.The segregation of SCS3620&580 is similar to that of RAPD marker OPS03620&580.Significant polymorphism has been shown between resistant and susceptible genotypes when 62 soybean genotypes were surveyed for the SCAR marker.Therefore,the marker can be used in the resistance breeding of soybean frog-eye leaf spot by marker-assisted selection.

  3. Dextran-graft-linear poly(ethylene imine)s for gene delivery: importance of the linking strategy.

    Science.gov (United States)

    Ochrimenko, Sofia; Vollrath, Antje; Tauhardt, Lutz; Kempe, Kristian; Schubert, Stephanie; Schubert, Ulrich S; Fischer, Dagmar

    2014-11-26

    Low molar mass linear poly(ethylene imine)s (lPEI) were grafted onto dextran via different synthesis routes aiming at the elucidation of structure-property relationships of dextran-graft-linear poly(ethylene imine) (dex-g-lPEI) conjugates for gene delivery applications. Beside the molar mass of well-defined lPEIs and the linker unit, also the amount of lPEI in the polymeric vectors was varied. The synthesized dextran modifications were characterized regarding their chemical structure and showed enhanced complexation and stabilization of DNA against enzymatic degradation. The transfection efficiency of dex-g-lPEIs was increased compared to unmodified lPEI and revealed a dependency of the used linking strategy. All complexes of DNA and dex-g-lPEIs were found to be nontoxic, but the synthesis route showed a strong influence on the aggregation of red blood cells. In conclusion, the linking strategy of lPEI to dextran has a significant impact on the physicochemical characteristics of DNA/polymer complexes, the biocompatibility as well as the transfection efficiency. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Inheritance Analysis and Identification of SSR Markers Linked to Late Blight Resistant Gene in Tomato

    Institute of Scientific and Technical Information of China (English)

    ZHU Hai-shan; WU Tao; ZHANG Zhen-xian

    2006-01-01

    Late blight caused by Phytophthora infestans is the most serious disease of tomato production in China. Studies on the genetics of resistance and identification of molecular markers are very useful for breeding late blight resistant varieties.The objective of this paper was to study the inheritance of late blight resistance and identify simple sequence repeat (SSR)markers associated with resistance allele in tomato (Lycopersicon esculentum Mill). The results came from an F2 progeny of 241 plants derived from a cross between 5# inbred line that is susceptible to late blight and a resistant accession CLN2037E. The late blight responses of F2 plants were tested by artificially inoculation of detached-leaflets in plate and natural infection assayed under greenhouse conditions. Both methods showed that the resistance is dominant and inherited as monogenic trait. Genetic mapping and linkage analysis showed that the late blight resistance gene Ph-ROL was located on chromosome 9 with a genetic distance of 5.7 cM to the SSR marker TOM236.

  5. Functional enhancers at the gene-poor 8q24 cancer-linked locus.

    Directory of Open Access Journals (Sweden)

    Li Jia

    2009-08-01

    Full Text Available Multiple discrete regions at 8q24 were recently shown to contain alleles that predispose to many cancers including prostate, breast, and colon. These regions are far from any annotated gene and their biological activities have been unknown. Here we profiled a 5-megabase chromatin segment encompassing all the risk regions for RNA expression, histone modifications, and locations occupied by RNA polymerase II and androgen receptor (AR. This led to the identification of several transcriptional enhancers, which were verified using reporter assays. Two enhancers in one risk region were occupied by AR and responded to androgen treatment; one contained a single nucleotide polymorphism (rs11986220 that resides within a FoxA1 binding site, with the prostate cancer risk allele facilitating both stronger FoxA1 binding and stronger androgen responsiveness. The study reported here exemplifies an approach that may be applied to any risk-associated allele in non-protein coding regions as it emerges from genome-wide association studies to better understand the genetic predisposition of complex diseases.

  6. A new autosomal dominant eye and lung syndrome linked to mutations in TIMP3 gene

    Science.gov (United States)

    Meunier, Isabelle; Bocquet, Béatrice; Labesse, Gilles; Zeitz, Christina; Defoort-Dhellemmes, Sabine; Lacroux, Annie; Mauget-Faysse, Martine; Drumare, Isabelle; Gamez, Anne-Sophie; Mathieu, Cyril; Marquette, Virginie; Sagot, Lola; Dhaenens, Claire-Marie; Arndt, Carl; Carroll, Patrick; Remy-Jardin, Martine; Cohen, Salomon Yves; Sahel, José-Alain; Puech, Bernard; Audo, Isabelle; Mrejen, Sarah; Hamel, Christian P.

    2016-01-01

    To revisit the autosomal dominant Sorsby fundus dystrophy (SFD) as a syndromic condition including late-onset pulmonary disease. We report clinical and imaging data of ten affected individuals from 2 unrelated families with SFD and carrying heterozygous TIMP3 mutations (c.572A > G, p.Y191C, exon 5, in family 1 and c.113C > G, p.S38C, exon 1, in family 2). In family 1, all SFD patients older than 50 (two generations) had also a severe emphysema, despite no history of smoking or asthma. In the preceding generation, the mother died of pulmonary emphysema and she was blind after the age of 50. Her two great-grandsons (<20 years), had abnormal Bruch Membrane thickness, a sign of eye disease. In family 2, eye and lung diseases were also associated in two generations, both occurred later, and lung disease was moderate (bronchiectasis). This is the first report of a syndromic SFD in line with the mouse model uncovering the role of TIMP3 in human lung morphogenesis and functions. The TIMP3 gene should be screened in familial pulmonary diseases with bronchiectasis, associated with a medical history of visual loss. In addition, SFD patients should be advised to avoid tobacco consumption, to practice sports, and to undergo regular pulmonary examinations. PMID:27601084

  7. A paradigm linking herpesvirus immediate-early gene expression apoptosis and myalgic encephalomyelitis chronic fatigue syndrome

    Directory of Open Access Journals (Sweden)

    A Martin Lerner

    2011-02-01

    Full Text Available A Martin Lerner1, Safedin Beqaj21Department of Medicine, William Beaumont Hospital, Royal Oak, MI, USA; 2DCL Medical Laboratories, Indianapolis, IN, USAAbstract: There is no accepted science to relate herpesviruses (Epstein–Barr virus [EBV], human cytomegalovirus [HCMV], and human herpesvirus 6 [HHV6] as causes of myalgic encephalomyelitis (ME/chronic fatigue syndrome (CFS. ME/CFS patients have elevated serum immunoglobulin (IgG serum antibody titers to EBV, HCMV, and HHV6, but there is no herpesvirus DNA-emia, herpesvirus antigenemia, or uniformly elevated IgM serum antibody titers to the complete virions. We propose that herpesvirus EBV, HCMV, and HHV6 immediate-early gene expression in ME/CFS patients leads to host cell dysregulation and host cell apoptosis without lytic herpesvirus replication. Specific antiviral nucleosides, which alleviate ME/CFS, namely valacyclovir for EBV ME/CFS and valganciclovir for HCMV/HHV6 ME/CFS, inhibit herpesvirus DNA polymerases and/or thymidine kinase functions, thus inhibiting lytic virus replication. New host cell recruitment thus ceases. In the absence of new herpesvirus, nonpermissive herpesvirus replication stops, and ME/CFS recovery ensues.Keywords: ME/CFS, Epstein–Barr virus (EBV, human cytomegalovirus (HCMV, HHV6, abortive replication

  8. Structural variation around prolactin gene linked to quantitative traits in an elite Holstein sire family.

    Science.gov (United States)

    Cowan, C M; Dentine, M R; Ax, R L; Schuler, L A

    1990-05-01

    Digestion of genomic DNA with the restriction endonuclease Avail disclosed a probable insertion deletion of approximately 200 base pairs (bp) near the prolactin gene. Two alleles were apparent as three distinct hybridization patterns. These alleles were statistically associated with quantitative trait loci among sons of one elite Holstein sire family. The favorable genotype was correlated with the presence of a 1.15-kb hybridization band inherited from the sire when genomic DNA was probed with a full-length cDNA for prolactin. Pedigree estimates of genetic merit among genotypes were similar, differing by only 19.3 kg for milk in ancestor merit. Comparisons of genetic estimates for quantitative yield traits in offspring of this heterozygous sire showed significant (Pcheese yield dollars, and protein dollars. The estimated differences between homozygous genotypes for USDA Transmitting Abilities of PDM, PD$, Cheese Yield $ and Protein $ were 282.93 kg, $74.35, $48.58 and $53.67, respectively. However, the estimated breeding values from progeny ranged over 900 kg in transmitting ability for milk. Frequency of the favorable marker allele was estimated to be 0.231 in the elite cow population used as dams of sons. These results demonstrate the potential of molecular biological techniques to discriminate between individuals within a family and to predict breeding values for selection schemes.

  9. Horizontal gene transfers link a human MRSA pathogen to contagious bovine mastitis bacteria.

    Directory of Open Access Journals (Sweden)

    Thomas Brody

    Full Text Available BACKGROUND: Acquisition of virulence factors and antibiotic resistance by many clinically important bacteria can be traced to horizontal gene transfer (HGT between related or evolutionarily distant microflora. Comparative genomic analysis has become an important tool for identifying HGT DNA in emerging pathogens. We have adapted the multi-genome alignment tool EvoPrinter to facilitate discovery of HGT DNA sequences within bacterial genomes and within their mobile genetic elements. PRINCIPAL FINDINGS: EvoPrinter analysis of 13 different Staphylococcus aureus genomes revealed that one of the human isolates, the hospital epidemic methicillin-resistant MRSA252 strain, uniquely shares multiple putative HGT DNA sequences with different causative agents of bovine mastitis that are not found in the other human S. aureus isolates. MRSA252 shares over 14 different DNA sequence blocks with the bovine mastitis ET3 S. aureus strain RF122, and many of the HGT DNAs encode virulence factors. EvoPrinter analysis of the MRSA252 chromosome also uncovered virulence-factor encoding HGT events with the genome of Listeria monocytogenes and a Staphylococcus saprophyticus associated plasmid. Both bacteria are also causal agents of contagious bovine mastitis. CONCLUSIONS: EvoPrinter analysis reveals that the human MRSA252 strain uniquely shares multiple DNA sequence blocks with different causative agents of bovine mastitis, suggesting that HGT events may be occurring between these pathogens. These findings have important implications with regard to animal husbandry practices that inadvertently enhance the contact of human and livestock bacterial pathogens.

  10. Well testing of tight gas reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Jahanbani, A.; Aguilera, R. [Calgary Univ., AB (Canada)

    2008-07-01

    This paper discussed methods of evaluating tight gas sand reservoirs. Conventional well testing is not used in tight gas reservoirs due to their low permeability. Tight gas well testing techniques include pressure-dependent permeability testing; the estimation of pseudo--time at the average pressure of the region of influence; and supercharge effect testing. Pre-frac test analysis techniques were also discussed. Pressure-transient test designs were reviewed along with instantaneous source response methods for calculating influence functions. Impulse-fracture tests were discussed, as well as perforation inflow diagnostic testing. Perforation inflow tests provided reasonable estimates of reservoir parameters. Methods of determining pressure-dependent permeability data were discussed. After closure analysis (ACA) was used to analyze formation permeability. It was concluded that ACA can be coupled with pre-closure analysis to optimize fracture stimulation plans. The 22 refs., 17 figs.

  11. Topological games and productively countably tight spaces

    OpenAIRE

    2013-01-01

    The two main results of this work are the following: if a space $X$ is such that player II has a winning strategy in the game $\\gone(\\Omega_x, \\Omega_x)$ for every $x \\in X$, then $X$ is productively countably tight. On the other hand, if a space is productively countably tight, then $\\sone(\\Omega_x, \\Omega_x)$ holds for every $x \\in X$. With these results, several other results follow, using some characterizations made by Uspenskii and Scheepers.

  12. Classifying tight Weyl-Heisenberg frames

    DEFF Research Database (Denmark)

    Cazsazza, P.; Janssen, A. J. E. M.; Christensen, Ole

    1999-01-01

    A Weyl-Heisenberg frame for L^2(R) is a frame consisting of translates and modulates of a fixed function. In this paper we give necessary and sufficient conditions for this family to form a tight WH-frame. This allows us to write down explicitly all functions g for which all translates and modula......A Weyl-Heisenberg frame for L^2(R) is a frame consisting of translates and modulates of a fixed function. In this paper we give necessary and sufficient conditions for this family to form a tight WH-frame. This allows us to write down explicitly all functions g for which all translates...

  13. Brain white matter structure and COMT gene are linked to second-language learning in adults.

    Science.gov (United States)

    Mamiya, Ping C; Richards, Todd L; Coe, Bradley P; Eichler, Evan E; Kuhl, Patricia K

    2016-06-28

    Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects' grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype.

  14. A Variation in the Cerebroside Sulfotransferase Gene Is Linked to Exercise-Modified Insulin Resistance and to Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    A. Roeske-Nielsen

    2009-01-01

    Full Text Available Aims. The glycosphingolipid β-galactosylceramide-3-O-sulfate (sulfatide is present in the secretory granules of the insulin producing β-cells and may act as a molecular chaperone of insulin. The final step in sulfatide synthesis is performed by cerebroside sulfotransferase (CST (EC 2.8.2.11. The aim of this study was to investigate whether two single nucleotide polymorphisms (SNP, rs2267161 located in an exon or rs42929 located in an intron, in the gene encoding CST are linked to type 2 diabetes (T2D. Methods. As a population survey, 265 male and female patients suffering from T2D and 291 gender matched controls were examined. Results. A higher proportion of T2D patients were heterozygous at SNP rs2267161 with both T (methionine and C (valine alleles present (49.8% versus 41.3%, P=.04. The calculated odd risk for T2D was 1.47 (1.01–2.15, P=.047. Among female controls, the homozygous CC individuals displayed lower insulin resistance measured by HOMA-IR (P=.05 than the C/T or TT persons; this was particularly prevalent in individuals who exercise (P=.03. Conclusion. Heterozygosity at SNP rs2267161 in the gene encoding the CST enzyme confers increased risk of T2D. Females with the CC allele showed lower insulin resistance.

  15. "Screening of the Bruton Tyrosine Kinase (BTK Gene Mutations in 13 Iranian Patients with Presumed X-Linked Agammaglobulinemia "

    Directory of Open Access Journals (Sweden)

    "Asghar Aghamohammadi

    2004-12-01

    Full Text Available X-linked agammaglobulinemia (XLA is an immunodeficiency caused by mutations in the Bruton tyrosine kinase (Btk gene. In order to identify the mutations in Btk gene in Iranian patients with antibody deficiency, 13 male patients with an XLA phenotype from 11 unrelated families were enrolled as the subjects of investigation for Btk mutation analysis using PCR-SSCP followed by sequencing. Five different mutations were identified in 5 patients from 5 unrelated families. Three mutations had been reported previously including TTTG deletion in intron 15 (4 bps upstream of exon 16 boundary, nonsense point mutation (1896G>A that resulted in a premature stop codon (W588X in kinase domain, and nucleotide alteration in invariant splice donor site of exon12 (IVS12+1G>A. While 2 novel missense mutations (2084A>G, 1783T>C were identified leading to amino acid changes (I651T, Y551H. The results of this study further support the notion that molecular genetic testing represents an important tool for definitive and early diagnosis of XLA and may allow accurate carrier detection and prenatal diagnosis.

  16. A novel mutation of gap junction protein β 1 gene in X-linked Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Chen, Sheng Dong; Li, Zheng Xi; Guan, Yang Tai; Zhou, Xia Jun; Jiang, Jian Ming; Hao, Yong

    2011-06-01

    In this study we report a novel mutation in the gap junction protein beta 1 (GJB1) gene of a Chinese X-linked Charcot-Marie-Tooth disease (CMTX1) family, which has specific electrophysiological characteristics. Twenty members in the family were studied by clinical neurological examination and GJB1 gene mutation analysis, and 3 patients were studied electrophysiologically. The proband and his mother also underwent sural nerve biopsy. All patients have the CMT phenotype, except for 2 asymptomatic carriers. Electrophysiological examinations showed non-uniform slowing of motor conduction velocities and partial motor conduction blocks and temporal dispersion. Sural nerve biopsy confirmed a predominantly demyelinating neuropathy, and an Asn2Lys mutation in the amino-terminal domain was found in 9 members of this family, but not in 25 normal controls in the family. This family represents a novel mutation in the GJB1 form of CMTX1. The mutation in the amino-terminus has an impact on the electrophysiological characteristics of the disease. Copyright © 2011 Wiley Periodicals, Inc.

  17. A variation in the cerebroside sulfotransferase gene is linked to exercise-modified insulin resistance and to type 2 diabetes

    DEFF Research Database (Denmark)

    Roeske-Nielsen, A.; Buschard, K.; Manson, J.E.

    2009-01-01

    .11). The aim of this study was to investigate whether two single nucleotide polymorphisms (SNP), rs2267161 located in an exon or rs42929 located in an intron, in the gene encoding CST are linked to type 2 diabetes (T2D). METHODS: As a population survey, 265 male and female patients suffering from T2D and 291......, the homozygous CC individuals displayed lower insulin resistance measured by HOMA-IR (P = .05) than the C/T or TT persons; this was particularly prevalent in individuals who exercise (P = .03). CONCLUSION: Heterozygosity at SNP rs2267161 in the gene encoding the CST enzyme confers increased risk of T2D. Females......AIMS: The glycosphingolipid beta-galactosylceramide-3-O-sulfate (sulfatide) is present in the secretory granules of the insulin producing beta-cells and may act as a molecular chaperone of insulin. The final step in sulfatide synthesis is performed by cerebroside sulfotransferase (CST) (EC 2.8.2...

  18. Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Duggirala, R.; Stern, M.P.; Reinhart, L.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1996-09-01

    Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low-income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and {approximately}73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is {approximately}15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans. 66 refs., 3 figs., 4 tabs.

  19. Identification of Three Novel Mutations in the FRMD7 Gene for X-linked Idiopathic Congenital Nystagmus

    Science.gov (United States)

    Zhang, Xiao; Ge, Xianglian; Yu, Ying; Zhang, Yilan; Wu, Yaming; Luan, Yin; Sun, Ji; Qu, Jia; Jin, Zi-Bing; Gu, Feng

    2014-01-01

    Idiopathic congenital nystagmus (ICN) consists of involuntary and periodic ocular motility, often with seriously reduced visual acuity. To identify the genetic defects associated with X-linked ICN, we performed PCR-based DNA direct sequencing of two candidate genes, FRMD7 and GPR143, in four families. Mutation analysis led to identification of three novel mutations, p.S260R, p.Q487X, and p.V549Y fsX554, in FRMD7 in three of the recruited families. Results from structural modeling indicated that the p.S260R may potentially disrupt FRMD7 function through loss of a phosphorylation site and/or interference with protein-protein interactions. Both p.Q487X, and p.V549Y fsX554 mutations were predicted to generate nonfunctional truncated proteins. Using a capture next generation sequencing method, we excluded CASK as the responsible gene for the remaining family. Combining sequence analysis and structural modeling, we report three novel mutations in FRMD7 in three independent families with XLICN, and provide molecular insights for future XLICN diagnosis and treatment.

  20. Organizational and functional status of the Y-linked genes and loci in the infertile patients having normal spermiogram.

    Directory of Open Access Journals (Sweden)

    Anju Kumari

    Full Text Available Male fertility is an orchestrated interplay of loci on the Y chromosome with a number of genes from across the other chromosomes. In this context, micro-deletions in the Y chromosome have been correlated with spermatogenic failure often leading to infertility. However, causes of infertility in the patients with the normal spermiogram have remained unclear and therefore pose another level of challenge. In the present study, we analyzed 64 STSs, studied different Y-linked genes and loci and conducted single nucleotide variant (SNV analyses in 31 infertile males with normal spermiogram along with 67 normal fertile males (NFMs to gain an insight into the organization of their Y chromosome. Further, employing quantitative real-time PCR (qPCR, we studied copy number variation of DYZ1 arrays and three genes and mutational status of SRY by direct sequence analyses. STS analyses of the AZFa, b and c regions in these patients showed known and new mutations. Further, copies of DAZ and BPY2 in the patients were found to be affected (p < 0.001 compared to those in NFMs. All the patients had normal copy number of the SRY however its sequence analysis (in silico showed mutations in eight patients. In four of these eight patients, SRY mutations resulted into truncated proteins. Similarly, DYZ1 analysis showed micro-deletions and it's much reduced copy number (p < 0.001 as compared to those in NFMs. Present study in males with unexplained infertility revealed deletions similar to those observed in oligospermic and azoospermic patients. Thus, there are some common but still unknown factors underlying infertility in these patients irrespective of their spermatogenic status. This work is envisaged to augment DNA diagnosis, proving beneficial in the context of in vitro fertilization (IVF and genetic counselling.

  1. Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium.

    Science.gov (United States)

    de Brouwer, Arjan P M; Yntema, Helger G; Kleefstra, Tjitske; Lugtenberg, Dorien; Oudakker, Astrid R; de Vries, Bert B A; van Bokhoven, Hans; Van Esch, Hilde; Frints, Suzanne G M; Froyen, Guy; Fryns, Jean-Pierre; Raynaud, Martine; Moizard, Marie-Pierre; Ronce, Nathalie; Bensalem, Anissa; Moraine, Claude; Poirier, Karine; Castelnau, Laetitia; Saillour, Yoann; Bienvenu, Thierry; Beldjord, Chérif; des Portes, Vincent; Chelly, Jamel; Turner, Gillian; Fullston, Tod; Gecz, Jozef; Kuss, Andreas W; Tzschach, Andreas; Jensen, Lars Riff; Lenzner, Steffen; Kalscheuer, Vera M; Ropers, Hans-Hilger; Hamel, Ben C J

    2007-02-01

    The EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes. For 42% of the families with obligate female carriers, the mental retardation phenotype could be explained by a mutation. There was no difference between families with (lod score >2) or without (lod score <2) significant linkage to the X chromosome. For families with two to five affected brothers (brother pair=BP families) only 17% of the MR could be explained. This is significantly lower (P=0.0067) than in families with obligate carrier females and indicates that the MR in about 40% (17/42) of the BP families is due to a single genetic defect on the X chromosome. The mutation frequency of XLMR genes in BP families is lower than can be expected on basis of the male to female ratio of patients with MR or observed recurrence risks. This might be explained by genetic risk factors on the X chromosome, resulting in a more complex etiology in a substantial portion of XLMR patients. The EuroMRX effort is the first attempt to unravel the molecular basis of cognitive dysfunction by large-scale approaches in a large patient cohort. Our results show that it is now possible to identify 42% of the genetic defects in non-syndromic and syndromic XLMR families with obligate female carriers.

  2. A rearrangement of the Z chromosome topology influences the sex-linked gene display in the European corn borer, Ostrinia nubilalis.

    Science.gov (United States)

    Kroemer, Jeremy A; Coates, Brad S; Nusawardani, Tyasning; Rider, S Dean; Fraser, Lisa M; Hellmich, Richard L

    2011-07-01

    Males are homogametic (ZZ) and females are heterogametic (WZ) with respect to the sex chromosomes in many species of butterflies and moths (insect order Lepidoptera). Genes on the Z chromosome influence traits involved in larval development, environmental adaptation, and reproductive isolation. To facilitate the investigation of these traits across Lepidoptera, we developed 43 degenerate primer pairs to PCR amplify orthologs of 43 Bombyx mori Z chromosome-linked genes. Of the 34 orthologs that amplified by PCR in Ostrinia nubilalis, 6 co-segregated with the Z chromosome anchor markers kettin (ket) and lactate dehydrogenase (ldh), and produced a consensus genetic linkage map of ~89 cM in combination with 5 AFLP markers. The O. nubilalis and B. mori Z chromosomes are comparatively co-linear, although potential gene inversions alter terminal gene orders and a translocation event disrupted synteny at one chromosome end. Compared to B. mori orthologs, O. nubilalis Z chromosome-linked genes showed conservation of tissue-specific and growth-stage-specific expression, although some genes exhibited species-specific expression across developmental stages or tissues. The O. nubilalis Z chromosome linkage map provides new tools for isolating quantitative trait loci (QTL) involved in sex-linked traits that drive speciation and it exposes genome rearrangements as a possible mechanism for differential gene regulation in Lepidoptera.

  3. Isolation and characterization of multiple F-box genes linked to the S9- and S10-RNase in apple (Malus × domestica Borkh.).

    Science.gov (United States)

    Okada, Kazuma; Moriya, Shigeki; Haji, Takashi; Abe, Kazuyuki

    2013-06-01

    Using 11 consensus primer pairs designed from S-linked F-box genes of apple and Japanese pear, 10 new F-box genes (MdFBX21 to 30) were isolated from the apple cultivar 'Spartan' (S(9)S(10)). MdFBX21 to 23 and MdFBX24 to 30 were completely linked to the S(9) -RNase and S(10-)RNase, respectively, and showed pollen-specific expression and S-haplotype-specific polymorphisms. Therefore, these 10 F-box genes are good candidates for the pollen determinant of self-incompatibility in apple. Phylogenetic analysis and comparison of deduced amino acid sequences of MdFBX21 to 30 with those of 25 S-linked F-box genes previously isolated from apple showed that a deduced amino acid identity of greater than 88.0 % can be used as the tentative criterion to classify F-box genes into one type. Using this criterion, 31 of 35 F-box genes of apple were classified into 11 types (SFBB1-11). All types included F-box genes derived from S(3-) and S(9-)haplotypes, and seven types included F-box genes derived from S(3-), S(9-), and S(10-)haplotypes. Moreover, comparison of nucleotide sequences of S-RNases and multiple F-box genes among S(3-), S(9-), and S(10-)haplotypes suggested that F-box genes within each type showed high nucleotide identity regardless of the identity of the S-RNase. The large number of F-box genes as candidates for the pollen determinant and the high degree of conservation within each type are consistent with the collaborative non-self-recognition model reported for Petunia. These findings support that the collaborative non-self-recognition system also exists in apple.

  4. Tight Focusing of Partially Coherent Vortex Beams

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar Singh

    2012-01-01

    Full Text Available Tight focusing of partially polarized vortex beams has been studied. Compact form of the coherence matrix has been derived for polarized vortex beams. Effects of topological charge and polarization distribution of the incident beam on intensity distribution, degree of polarization, and coherence have been investigated.

  5. Tight adversary bounds for composite functions

    NARCIS (Netherlands)

    Hoyer, P.; Spalek, R.

    2005-01-01

    The quantum adversary method is a very versatile method for proving lower bounds on quantum algorithms. It has many equivalent formulations, yields tight bounds for many computational problems, and has natural connections to classical lower bounds. One of its formulations is in terms of the spectral

  6. A Tight Bound for the Lamplighter Problem

    OpenAIRE

    Ganapathy, Murali K.; Tetali, Prasad

    2006-01-01

    We settle an open problem, raised by Y. Peres and D. Revelle, concerning the $L^2$ mixing time of the random walk on the lamplighter graph. We also provide general bounds relating the entropy decay of a Markov chain to the separation distance of the chain, and show that the lamplighter graphs once again provide examples of tightness of our results.

  7. Expression of 5 S rRNA genes linked to 35 S rDNA in plants, their epigenetic modification and regulatory element divergence

    Directory of Open Access Journals (Sweden)

    Garcia Sònia

    2012-06-01

    Full Text Available Abstract Background In plants, the 5 S rRNA genes usually occur as separate tandems (S-type arrangement or, less commonly, linked to 35 S rDNA units (L-type. The activity of linked genes remains unknown so far. We studied the homogeneity and expression of 5 S genes in several species from family Asteraceae known to contain linked 35 S-5 S units. Additionally, their methylation status was determined using bisulfite sequencing. Fluorescence in situ hybridization was applied to reveal the sub-nuclear positions of rDNA arrays. Results We found that homogenization of L-type units went to completion in most (4/6 but not all species. Two species contained major L-type and minor S-type units (termed Ls-type. The linked genes dominate 5 S rDNA expression while the separate tandems do not seem to be expressed. Members of tribe Anthemideae evolved functional variants of the polymerase III promoter in which a residing C-box element differs from the canonical angiosperm motif by as much as 30%. On this basis, a more relaxed consensus sequence of a plant C-box: (5’-RGSWTGGGTG-3’ is proposed. The 5 S paralogs display heavy DNA methylation similarly as to their unlinked counterparts. FISH revealed the close association of 35 S-5 S arrays with nucleolar periphery indicating that transcription of 5 S genes may occur in this territory. Conclusions We show that the unusual linked arrangement of 5 S genes, occurring in several plant species, is fully compatible with their expression and functionality. This extraordinary 5 S gene dynamics is manifested at different levels, such as variation in intrachromosomal positions, unit structure, epigenetic modification and considerable divergence of regulatory motifs.

  8. Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population

    OpenAIRE

    2014-01-01

    Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Oc...

  9. Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population

    OpenAIRE

    2013-01-01

    Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Oc...

  10. An Objective Measure of Noseband Tightness and Its Measurement Using a Novel Digital Tightness Gauge

    Science.gov (United States)

    Casey, Vincent

    2017-01-01

    Noseband tightness is difficult to assess in horses participating in equestrian sports such as dressage, show jumping and three-day-eventing. There is growing concern that nosebands are commonly tightened to such an extent as to restrict normal equine behaviour and possibly cause injury. In the absence of a clear agreed definition of noseband tightness, a simple model of the equine nose-noseband interface environment was developed in order to guide further studies in this area. The normal force component of the noseband tensile force was identified as the key contributor to sub-noseband tissue compression. The model was used to inform the design of a digital tightness gauge which could reliably measure the normal force component of the noseband tensile force. A digital tightness gauge was developed to measure this parameter under nosebands fitted to bridled horses. Results are presented for field tests using two prototype designs. Prototype version three was used in field trial 1 (n = 15, frontal nasal plane sub-noseband site). Results of this trial were used to develop an ergonomically designed prototype, version 4, which was tested in a second field trial (n = 12, frontal nasal plane and lateral sub-noseband site). Nosebands were set to three tightness settings in each trial as judged by a single rater using an International Society for Equitation Science (ISES) taper gauge. Normal forces in the range 7–95 N were recorded at the frontal nasal plane while a lower range 1–28 N was found at the lateral site for the taper gauge range used in the trials. The digital tightness gauge was found to be simple to use, reliable, and safe and its use did not agitate the animals in any discernable way. A simple six point tightness scale is suggested to aid regulation implementation and the control of noseband tightness using normal force measurement as the objective tightness discriminant. PMID:28045955

  11. Relevant Genes Linked to Virulence Are Required for Salmonella Typhimurium to Survive Intracellularly in the Social Amoeba Dictyostelium discoideum.

    Science.gov (United States)

    Riquelme, Sebastián; Varas, Macarena; Valenzuela, Camila; Velozo, Paula; Chahin, Nicolás; Aguilera, Paulina; Sabag, Andrea; Labra, Bayron; Álvarez, Sergio A; Chávez, Francisco P; Santiviago, Carlos A

    2016-01-01

    The social amoeba Dictyostelium discoideum has proven to be a useful model for studying relevant aspects of the host-pathogen interaction. In this work, D. discoideum was used as a model to study the ability of Salmonella Typhimurium to survive in amoebae and to evaluate the contribution of selected genes in this process. To do this, we performed infection assays using axenic cultures of D. discoideum co-cultured with wild-type S. Typhimurium and/or defined mutant strains. Our results confirmed that wild-type S. Typhimurium is able to survive intracellularly in D. discoideum. In contrast, mutants ΔaroA and ΔwaaL are defective in intracellular survival in this amoeba. Next, we included in our study a group of mutants in genes directly linked to Salmonella virulence. Of note, mutants ΔinvA, ΔssaD, ΔclpV, and ΔphoPQ also showed an impaired ability to survive intracellularly in D. discoideum. This indicates that S. Typhimurium requires a functional biosynthetic pathway of aromatic compounds, a lipopolysaccharide containing a complete O-antigen, the type III secretion systems (T3SS) encoded in SPI-1 and SPI-2, the type VI secretion system (T6SS) encoded in SPI-6 and PhoP/PhoQ two-component system to survive in D. discoideum. To our knowledge, this is the first report on the requirement of O-antigen and T6SS in the survival of Salmonella within amoebae. In addition, mutants ΔinvA and ΔssaD were internalized in higher numbers than the wild-type strain during competitive infections, suggesting that S. Typhimurium requires the T3SS encoded in SPI-1 and SPI-2 to evade phagocytosis by D. discoideum. Altogether, these results indicate that S. Typhimurium exploits a common set of genes and molecular mechanisms to survive within amoeba and animal host cells. The use of D. discoideum as a model for host-pathogen interactions will allow us to discover the gene repertoire used by Salmonella to survive inside the amoeba and to study the cellular processes that are affected

  12. Ancestral Y-linked genes were maintained by translocation to the X and Y chromosomes fused to an autosomal pair in the Okinawa spiny rat Tokudaia muenninki.

    Science.gov (United States)

    Murata, Chie; Kuroki, Yoko; Imoto, Issei; Kuroiwa, Asato

    2016-09-01

    Two species of the genus Tokudaia lack the Y chromosome and SRY, but several Y-linked genes have been rescued by translocation or transposition to other chromosomes. Tokudaia muenninki is the only species in the genus that maintains the Y owing to sex chromosome-autosome fusions. According to previous studies, many SRY pseudocopies and other Y-linked genes have evolved by excess duplication in this species. Using RNA-seq and RT-PCR, we found that ZFY, EIF2S3Y, TSPY, UTY, DDX3Y, USP9Y, and RBMY, but not UBA1Y, had high deduced amino acid sequence similarity and similar expression patterns with other rodents, suggesting that these genes were functional. Based on FISH and quantitative real-time PCR, all of the genes except for UTY and DDX3Y were amplified on the X and Y chromosomes with approximately 10-66 copies in the male genome. In a comparative analysis of the 372.4-kb BAC sequence and Y-linked gene transcripts from T. muenninki with the mouse Y genomic sequence, we observed that multiple-copy genes in the ancestral Y genome were nonfunctional, indicating that the gene functions were assumed by amplified copies. We also found a LTR sequence at the distal end of a SRY duplication unit, suggesting that unequal sister chromatid exchange mediated by retrotransposable elements could have been involved in SRY amplification. Our results revealed that the Y-linked genes were rescued from degeneration via translocations to other sex chromosomal regions and amplification events in T. muenninki.

  13. Dosage compensation of X-chromosome inactivation center-linked genes in porcine preimplantation embryos: Non-chromosome-wide initiation of X-chromosome inactivation in blastocysts.

    Science.gov (United States)

    Hwang, Jae Yeon; Oh, Jong-Nam; Park, Chi-Hun; Lee, Dong-Kyung; Lee, Chang-Kyu

    2015-11-01

    X-chromosome inactivation (XCI) is an epigenetic mechanism that occurs in the eutherian embryo development to equalize the dosage of X-linked genes between males and females. This event is regulated by various factors, and the genes located in the X-chromosome inactivation center (XIC), which is known to be an evolutionary conserved region, are associated with XCI; however, a number of studies regarding this epigenetic event and genomic region are primarily performed in mouse models despite its species-specific features. Thus, in this study, the porcine XIC was identified, and we analyzed the expression of XIC-linked genes in porcine preimplantation embryos. Comparative sequence analysis revealed that the porcine XIC is synteny with that of human and the non-coding RNAs were less conserved compared with the protein coding genes in the XIC. Among the XIC-linked genes, the expression levels of CHIC1 and RLIM were decreased from morula to blastocyst development and their dosage was compensated between the male and female blastocysts. Additionally, the CpG sites of CHIC1 were approximately 50% methylated in parthenote blastocysts. Contrary to these genes, XIST and LOC102165544, an uncharacterized non-coding gene, showed dramatically increased expression levels after the morula stage and preferential female expression in blastocysts. Imprinted XIST expression was not observed, and their CpG sites were hypo-methylated in parthenogenic blastocysts. These results demonstrate that the porcine XIC consists of an evolutionary conserved structure with fewer sequences conserved non-coding RNAs. In addition, a few XIC-linked genes would likely achieve dosage compensation, but XCI would not be completed in porcine blastocysts.

  14. Arginine vasotocin, isotocin and nonapeptide receptor gene expression link to social status and aggression in sex-dependent patterns.

    Science.gov (United States)

    Lema, S C; Sanders, K E; Walti, K A

    2015-02-01

    Nonapeptide hormones of the vasopressin/oxytocin family regulate social behaviours. In mammals and birds, variation in behaviour also is linked to expression patterns of the V1a-type receptor and the oxytocin/mesotocin receptor in the brain. Genome duplications, however, expand the diversity of nonapeptide receptors in actinopterygian fishes, and two distinct V1a-type receptors (v1a1 and v1a2) for vasotocin, as well as at least two V2-type receptors (v2a and v2b), have been identified in these taxa. The present study investigates how aggression connected to social status relates to the abundance patterns of gene transcripts encoding four vasotocin receptors, an isotocin receptor (itr), pro-vasotocin (proVT) and pro-isotocin (proIT) in the brain of the pupfish Cyprinodon nevadensis amargosae. Sexually-mature pupfish were maintained in mixed-sex social groups and assessed for individual variation in aggressive behaviours. Males in these groups behaved more aggressively than females, and larger fish exhibited higher aggression relative to smaller fish of the same sex. Hypothalamic proVT transcript abundance was elevated in dominant males compared to subordinate males, and correlated positively with individual variation in aggression in both social classes. Transcripts encoding vasotocin receptor v1a1 were at higher levels in the telencephalon and hypothalamus of socially subordinate males than dominant males. Dominant males exhibited elevated hypothalamic v1a2 receptor transcript abundance relative to subordinate males and females, and telencephalic v1a2 mRNA abundance in dominant males was also associated positively with individual aggressiveness. Transcripts in the telencephalon encoding itr were elevated in females relative to males, and both telencephalic proIT and hypothalamic itr transcript abundance varied with female social status. Taken together, these data link hypothalamic proVT expression to aggression and implicate forebrain expression of the V1a

  15. Regulatory region with putA gene of proline dehydrogenase that links to the lum and the lux operons in Photobacterium leiognathi.

    Science.gov (United States)

    Lin, J W; Yu, K Y; Chen, H Y; Weng, S F

    1996-02-27

    Nucleotide sequence of regulatory region (R & R) with putA gene (EMBL Accession No. U39227) from Photobacterium leiognathi PL741 has been determined, and the putA gene encoded amino acid sequence of proline dehydrogenase is deduced. Alignment and comparison of proline dehydrogenase of P. leiognathi with the proline dehydrogenase domain in the PutA protein of Escherichia coli and Salmonella typhimurium show that they are homologous. Nucleotide sequence reveals that regulatory region with the putA gene is linked to the lum and lux operons in genome; the gene order is (R & R: regulatory region; ter:transcriptional terminator), whereas the R & R is the regulatory region for the lum and the lux operons, ter is the transcriptional terminator for the lum operon, and R & R(I) apparently is the regulatory region for the putA and related genes. Nucleotide sequence analysis illustrates the specific inverted repeat (SIR), cAMP-CRP consensus sequence, canonical -10/-35 promoter, putative operator and Shine-Dalgarno (SD) sequence on the regulatory region R & R(I) for the putA and related genes; it suggests that the putA and related genes are simply linked to the lum and the lux operons in genome, the regulatory region R & R(I) is independent for the putA and related genes.

  16. Molecular genetics of X chromosome-linked color vision among populations of African and Japanese ancestry: High frequency of a shortened red pigment gene among Afro-Americans

    Energy Technology Data Exchange (ETDEWEB)

    Joergensen, A.L.; Deeb, S.S.; Motulsky, A.G. (Univ. of Washington, Seattle (USA))

    1990-09-01

    Red-green color vision in humans is mediated by the X chromosome-linked highly homologous red and green pigment genes. Color vision defects are caused by deletions and fusions involving these genes. However, the authors found the frequency of molecular abnormalities among Caucasians to be twice as high as that of phenotypic color vision defects. Among Japanese the frequency of phenotypic and molecular color vision defects was similar. Among Afro-Americans, molecular defects were at least five times more frequent than phenotypic color vision defects. In addition, 35% of Afro-Americans, 2% of Japanese, and <1% of Caucasians had a shortened red pigment gene not associated with phenotpyic color vision defects. This gene lacked 1.9 kilobases in its first intron and had the identical size as the green pigment gene from which it presumably originated by gene conversion in an ancestral African population. This gene and the closely linked glucose-6-phosphate dehydrogenase A{sup +} variant were in linkage equilibrium. A model for the evolutionary origin of the color vision pigment genes in higher primates is portrayed.

  17. Gene-environment interplay in the link of friends' and nonfriends' behaviors with children's social reticence in a competitive situation.

    Science.gov (United States)

    Guimond, Fanny-Alexandra; Brendgen, Mara; Vitaro, Frank; Forget-Dubois, Nadine; Dionne, Ginette; Tremblay, Richard E; Boivin, Michel

    2014-03-01

    This study used a genetically informed design to assess the effects of friends' and nonfriends' reticent and dominant behaviors on children's observed social reticence in a competitive situation. Potential gene-environment correlations (rGE) and gene-environment interactions (GxE) in the link between (a) friends' and nonfriends' behaviors and (b) children's social reticence were examined. The sample comprised 466 twin children (i.e., the target children), each of whom was assessed in kindergarten together with a same-sex friend and two nonfriend classmates of either sex. Multilevel regression analyses revealed that children with a genetic disposition for social reticence showed more reticent behavior in the competitive situation and were more likely to affiliate with reticent friends (i.e., rGE). Moreover, a higher level of children's reticent behavior was predicted by their friends' higher social reticence (particularly for girls) and their friends' higher social dominance, independently of children's genetic disposition. Children's social reticence was also predicted by their nonfriends' behaviors. Specifically, children were less reticent when male nonfriends showed high levels of social reticence in the competitive situation, and this was particularly true for children with a genetic disposition for social reticence (i.e., GxE). Moreover, children genetically vulnerable for social reticence seemed to foster dominant behavior in their female nonfriend peers (i.e., rGE). In turn, male nonfriends seemed to be more dominant as soon as the target children were reticent, even if the target children did not have a stable genetic disposition for this behavior.

  18. Monocytes of patients with amyotrophic lateral sclerosis linked to gene mutations display altered TDP-43 subcellular distribution.

    Science.gov (United States)

    De Marco, G; Lomartire, A; Calvo, A; Risso, A; De Luca, E; Mostert, M; Mandrioli, J; Caponnetto, C; Borghero, G; Manera, U; Canosa, A; Moglia, C; Restagno, G; Fini, N; Tarella, C; Giordana, M T; Rinaudo, M T; Chiò, A

    2017-02-01

    Cytoplasmic accumulation of the nuclear protein transactive response DNA-binding protein 43 (TDP-43) is an early determinant of motor neuron degeneration in most amyotrophic lateral sclerosis (ALS) cases. We previously disclosed this accumulation in circulating lymphomonocytes (CLM) of ALS patients with mutant TARDBP, the TDP-43-coding gene, as well as of a healthy individual carrying the parental TARDBP mutation. Here, we investigate TDP-43 subcellular localization in CLM and in the constituent cells, lymphocytes and monocytes, of patients with various ALS-linked mutant genes. TDP-43 subcellular localization was analysed with western immunoblotting and immunocytofluorescence in CLM of healthy controls (n = 10), patients with mutant TARDBP (n = 4, 1 homozygous), valosin-containing protein (VCP; n = 2), fused in sarcoma/translocated in liposarcoma (FUS; n = 2), Cu/Zn superoxide dismutase 1 (SOD1; n = 6), chromosome 9 open reading frame 72 (C9ORF72; n = 4), without mutations (n = 5) and neurologically unaffected subjects with mutant TARDBP (n = 2). TDP-43 cytoplasmic accumulation was found (P TDP-43 subcellular localization described for motor neurons of corresponding groups. Accumulation also characterized CLM of the healthy individuals with mutant TARDBP and of some patients with mutant SOD1 or C9ORF72. In 5 patients, belonging to categories described to carry TDP-43 mislocalization in motor neurons (3 C9ORF72, 1 TARDBP and 1 without mutations), TDP-43 cytoplasmic accumulation was not detected in CLM or in lymphocytes but was in monocytes. In ALS forms characterized by TDP-43 mislocalization in motor neurons, monocytes display this alteration, even when not manifest in CLM. Monocytes may be used to support diagnosis, as well as to identify subjects at risk, of ALS and to develop/monitor targeted treatments. © 2016 British Neuropathological Society.

  19. The X-files of inflammation: cellular mosaicism of X-linked polymorphic genes and the female advantage in the host response to injury and infection.

    Science.gov (United States)

    Spolarics, Zoltán

    2007-06-01

    Females as compared with males display better general health status, longevity, and improved clinical course after injury and infection. It is generally believed that the female advantage is associated with the effects of sex hormones. This review argues that the sex benefit of females during the host response is associated with polymorphism of X-linked genes and cellular mosaicism for X-linked parental alleles. Cells from females carry both parental X chromosomes (maternal, Xm; or paternal, Xp), whereas males carry only one (Xm). Because of dosage compensation and random X inactivation, half of the cells from females express either Xm or Xp. Therefore, females are cellular mosaics for their X-linked polymorphic genes. This cellular mosaicism in females represents a more adaptive and balanced cellular machinery that is advantageous during the innate immune response. Several genes encoding key metabolic and regulatory proteins reside on the X chromosome, including members of the apoptotic cascade, hormone homeostasis, glucose metabolic enzymes, superoxide-producing machinery, and the toll-like receptor/nuclear factor kappaB/c-Jun N-terminal kinase signaling pathway. Polymorphic forms of these X-linked proteins are likely to manifest in phenotypic differences in the mosaic cell populations in females and may contribute to sex-related differences in the host response to injury and infection. The unique inheritance pattern of X-linked polymorphisms and their potential confounding effects in clinical trials are also discussed; furthermore, we present potential biomarkers for studying mosaic cell populations of innate immunity.

  20. Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q

    Energy Technology Data Exchange (ETDEWEB)

    Fink, J.K.; Wu, C.T.B.; Jones, S.M.

    1994-09-01

    Familial spastic paraplegia (FSP) (MIM No.18260) constitutes a clinically and genetically diverse group of disorders that share the primary feature of progressive, severe, lower extremity spasticity. FSP is classified according to the mode of inheritance and whether progressive spasticity occurs in isolation ({open_quotes}uncomplicated FSP{close_quotes}) or with other neurologic abnormalities ({open_quotes}complicated FSP{close_quotes}), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, or deafness. Recently, autosomal dominant, uncomplicated FSP was shown to be genetically heterogeneous and tightly linked to a group of microsatellite markers on chromosome 14q in one large kindred. We examined 126 members of a non-consanguineous North American kindred of Irish descent. FSP was diagnosed in 31 living subjects who developed insidiously progressive gait disturbance between ages 12 and 35 years. Using genetic linkage analysis to microsatellite DNA polymorphisms, we showed that the FSP locus on chromosome 14q was exluded from linkage with the disorder in our family. Subsequently, we searched for genetic linkage between the disorder and microsatellite DNA polymorphisms spanning approximately 50% of the genome. We observed significantly positive, two-point maximum lod scores (Z) for markers on chromosome 15q: D15S128 (Z=9.70, {theta}=0.05), D15S165 (Z=3.30, {theta}=0.10), and UT511 (Z=3.86, {theta}=0.10). Our data clearly establishes that one locus for autosomal dominant, uncomplicated FSP is mapped to the pericentric region of chromosome 15q. Identifying genes responsible for chromosome 15q-linked and chromosome 14q-linked FSP will greatly advance our understanding of this condition and hopefully other inherited and degenerative brain and spinal cord disorders that are also characterized by axonal degeneration.

  1. Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly.

    NARCIS (Netherlands)

    Giannandrea, M.; Bianchi, V.; Mignogna, M.L.; Sirri, A.; Carrabino, S.; D'Elia, E.; Vecellio, M.; Russo, S.; Cogliati, F.; Larizza, L.; Ropers, H.H.; Tzschach, A.; Kalscheuer, V.M.M.; Oehl-Jaschkowitz, B.; Skinner, C.; Schwartz, C.E.; Gecz, J.; Esch, H. van; Raynaud, M.; Chelly, J.; Brouwer, A.P.M. de; Toniolo, D.; D'Adamo, P.

    2010-01-01

    Human Mental Retardation (MR) is a common and highly heterogeneous pediatric disorder affecting around 3% of the general population; at least 215 X-linked MR (XLMR) conditions have been described, and mutations have been identified in 83 different genes, encoding proteins with a variety of function,

  2. 8-Methoxypsoralen DNA interstrand cross-linking of the ribosomal RNA genes in Tetrahymena thermophila. Distribution, repair and effect on rRNA synthesis

    DEFF Research Database (Denmark)

    Fengquin, X; Nielsen, Henrik; Zhen, W;

    1993-01-01

    between three domains (terminal spacer, transcribed region and central spacer) as defined by restriction enzyme analysis (BamHI and ClaI). It is furthermore shown that a dosage resulting in approximately one cross-link per rDNA molecule (21 kbp, two genes) is sufficient to block RNA synthesis. Finally...

  3. Fine mapping of the chromosome 5B region carrying closely linked rust resistance genes Yr47 and Lr52 in wheat

    Science.gov (United States)

    The widely effective and linked rust resistance genes Yr47 and Lr52 were previously mapped in the short arm of chromosome 5B in two F3 populations (Aus28183/Aus27229 and Aus28187/Aus27229). The Aus28183/Aus27229 F3 population was advanced to generate an F6 recombinant inbred line (RIL) population t...

  4. Linking Gene Expression in the Intestine to Production of Gametes Through the Phosphate Transporter PITR-1 in Caenorhabditis elegans

    Science.gov (United States)

    Balklava, Zita; Rathnakumar, Navin D.; Vashist, Shilpa; Schweinsberg, Peter J.; Grant, Barth D.

    2016-01-01

    Inorganic phosphate is an essential mineral for both prokaryotic and eukaryotic cell metabolism and structure. Its uptake into the cell is mediated by membrane-bound transporters and coupled to Na+ transport. Mammalian sodium-dependent Pi cotransporters have been grouped into three families NaPi-I, NaPi-II, and NaPi-III. Despite being discovered more than two decades ago, very little is known about requirements for NaPi-III transporters in vivo, in the context of intact animal models. Here we find that impaired function of the Caenorhabditis elegans NaPi-III transporter, pitr-1, results in decreased brood size and dramatically increased expression of vitellogenin by the worm intestine. Unexpectedly, we found that the effects of pitr-1 mutation on vitellogenin expression in the intestine could only be rescued by expression of pitr-1 in the germline, and not by expression of pitr-1 in the intestine itself. Our results indicate the existence of a signal from the germline that regulates gene expression in the intestine, perhaps linking nutrient export from the intestine to production of gametes by the germline. PMID:27449055

  5. Tight-binding treatment of conjugated polymers

    DEFF Research Database (Denmark)

    Lynge, Thomas Bastholm

    This PhD thesis concerns conjugated polymers which constitute a constantly growing research area. Today, among other things, conjugated polymers play a role in plastic based solar cells, photodetectors and light emitting diodes, and even today such plastic-based components constitute an alternative...... of tomorrow. This thesis specifically treats the three conjugated polymers trans-polyacetylene (tPA), poly(para-phenylene) (PPP) and poly(para-phe\\-nylene vinylene) (PPV). The present results, which are derived within the tight-binding model, are divided into two parts. In one part, analytic results...... are derived for the optical properties of the polymers expressed in terms of the optical susceptibility both in the presence and in the absence of a static electric field. In the other part, the cumputationally efficient Density Functional-based Tight-Binding (DFTB) model is applied to the description...

  6. Evolution of linked avirulence effectors in Leptosphaeria maculans is affected by genomic environment and exposure to resistance genes in host plants.

    Directory of Open Access Journals (Sweden)

    Angela P Van de Wouw

    Full Text Available Brassica napus (canola cultivars and isolates of the blackleg fungus, Leptosphaeria maculans interact in a 'gene for gene' manner whereby plant resistance (R genes are complementary to pathogen avirulence (Avr genes. Avirulence genes encode proteins that belong to a class of pathogen molecules known as effectors, which includes small secreted proteins that play a role in disease. In Australia in 2003 canola cultivars with the Rlm1 resistance gene suffered a breakdown of disease resistance, resulting in severe yield losses. This was associated with a large increase in the frequency of virulence alleles of the complementary avirulence gene, AvrLm1, in fungal populations. Surprisingly, the frequency of virulence alleles of AvrLm6 (complementary to Rlm6 also increased dramatically, even though the cultivars did not contain Rlm6. In the L. maculans genome, AvrLm1 and AvrLm6 are linked along with five other genes in a region interspersed with transposable elements that have been degenerated by Repeat-Induced Point (RIP mutations. Analyses of 295 Australian isolates showed deletions, RIP mutations and/or non-RIP derived amino acid substitutions in the predicted proteins encoded by these seven genes. The degree of RIP mutations within single copy sequences in this region was proportional to their proximity to the degenerated transposable elements. The RIP alleles were monophyletic and were present only in isolates collected after resistance conferred by Rlm1 broke down, whereas deletion alleles belonged to several polyphyletic lineages and were present before and after the resistance breakdown. Thus, genomic environment and exposure to resistance genes in B. napus has affected the evolution of these linked avirulence genes in L. maculans.

  7. New slow-rusting leaf rust and stripe rust resistance genes Lr67 and Yr46 in wheat are pleiotropic or closely linked.

    Science.gov (United States)

    Herrera-Foessel, Sybil A; Lagudah, Evans S; Huerta-Espino, Julio; Hayden, Matthew J; Bariana, Harbans S; Singh, Davinder; Singh, Ravi P

    2011-01-01

    The common wheat genotype 'RL6077' was believed to carry the gene Lr34/Yr18 that confers slow-rusting adult plant resistance (APR) to leaf rust and stripe rust but located to a different chromosome through inter-chromosomal reciprocal translocation. However, haplotyping using the cloned Lr34/Yr18 diagnostic marker and the complete sequencing of the gene indicated Lr34/Yr18 is absent in RL6077. We crossed RL6077 with the susceptible parent 'Avocet' and developed F(3), F(4) and F(6) populations from photoperiod-insensitive F(3) lines that were segregating for resistance to leaf rust and stripe rust. The populations were characterized for leaf rust resistance at two Mexican sites, Cd. Obregon during the 2008-2009 and 2009-2010 crop seasons, and El Batan during 2009, and for stripe rust resistance at Toluca, a third Mexican site, during 2009. The F(3) population was also evaluated for stripe rust resistance at Cobbitty, Australia, during 2009. Most lines had correlated responses to leaf rust and stripe rust, indicating that either the same gene, or closely linked genes, confers resistance to both diseases. Molecular mapping using microsatellites led to the identification of five markers (Xgwm165, Xgwm192, Xcfd71, Xbarc98 and Xcfd23) on chromosome 4DL that are associated with this gene(s), with the closest markers being located at 0.4 cM. In a parallel study in Canada using a Thatcher × RL6077 F(3) population, the same leaf rust resistance gene was designated as Lr67 and mapped to the same chromosomal region. The pleiotropic, or closely linked, gene derived from RL6077 that conferred stripe rust resistance in this study was designated as Yr46. The slow-rusting gene(s) Lr67/Yr46 can be utilized in combination with other slow-rusting genes to develop high levels of durable APR to leaf rust and stripe rust in wheat.

  8. Comparative analysis of the ATRX promoter and 5' regulatory region reveals conserved regulatory elements which are linked to roles in neurodevelopment, alpha-globin regulation and testicular function

    OpenAIRE

    Tang, Paisu; Frankenberg, Stephen; Argentaro, Anthony; Graves, Jennifer M; Familari, Mary

    2011-01-01

    Background ATRX is a tightly-regulated multifunctional protein with crucial roles in mammalian development. Mutations in the ATRX gene cause ATR-X syndrome, an X-linked recessive developmental disorder resulting in severe mental retardation and mild alpha-thalassemia with facial, skeletal and genital abnormalities. Although ubiquitously expressed the clinical features of the syndrome indicate that ATRX is not likely to be a global regulator of gene expression but involved in regulating specif...

  9. Characterization of novel isoforms and evaluation of SNF2L/SMARCA1 as a candidate gene for X-linked mental retardation in 12 families linked to Xq25-26

    Directory of Open Access Journals (Sweden)

    Lavigne Paul

    2008-02-01

    Full Text Available Abstract Background Mutations in genes whose products modify chromatin structure have been recognized as a cause of X-linked mental retardation (XLMR. These genes encode proteins that regulate DNA methylation (MeCP2, modify histones (RSK2 and JARID1C, and remodel nucleosomes through ATP hydrolysis (ATRX. Thus, genes encoding other chromatin modifying proteins should also be considered as disease candidate genes. In this work, we have characterized the SNF2L gene, encoding an ATP-dependent chromatin remodeling protein of the ISWI family, and sequenced the gene in patients from 12 XLMR families linked to Xq25-26. Methods We used an in silico and RT-PCR approach to fully characterize specific SNF2L isoforms. Mutation screening was performed in 12 patients from individual families with syndromic or non-syndromic XLMR. We sequenced each of the 25 exons encompassing the entire coding region, complete 5' and 3' untranslated regions, and consensus splice-sites. Results The SNF2L gene spans 77 kb and is encoded by 25 exons that undergo alternate splicing to generate several distinct transcripts. Specific isoforms are generated through the alternate use of exons 1 and 13, and by the use of alternate donor splice sites within exon 24. Alternate splicing within exon 24 removes a NLS sequence and alters the subcellular distribution of the SNF2L protein. We identified 3 single nucleotide polymorphisms but no mutations in our 12 patients. Conclusion Our results demonstrate that there are numerous splice variants of SNF2L that are expressed in multiple cell types and which alter subcellular localization and function. SNF2L mutations are not a cause of XLMR in our cohort of patients, although we cannot exclude the possibility that regulatory mutations might exist. Nonetheless, SNF2L remains a candidate for XLMR localized to Xq25-26, including the Shashi XLMR syndrome.

  10. Deoxynivalenol impairs hepatic and intestinal gene expression of selected oxidative stress, tight junction and inflammation proteins in broiler chickens, but addition of an adsorbing agent shifts the effects to the distal parts of the small intestine.

    Science.gov (United States)

    Osselaere, Ann; Santos, Regiane; Hautekiet, Veerle; De Backer, Patrick; Chiers, Koen; Ducatelle, Richard; Croubels, Siska

    2013-01-01

    Broiler chickens are rather resistant to deoxynivalenol and thus, clinical signs are rarely seen. However, effects of subclinical concentrations of deoxynivalenol on both the intestine and the liver are less frequently studied at the molecular level. During our study, we investigated the effects of three weeks of feeding deoxynivalenol on the gut wall morphology, intestinal barrier function and inflammation in broiler chickens. In addition, oxidative stress was evaluated in both the liver and intestine. Besides, the effect of a clay-based mycotoxin adsorbing agent on these different aspects was also studied. Our results show that feeding deoxynivalenol affects the gut wall morphology both in duodenum and jejenum of broiler chickens. A qRT-PCR analysis revealed that deoxynivalenol acts in a very specific way on the intestinal barrier, since only an up-regulation in mRNA expression of claudin 5 in jejunum was observed, while no effects were seen on claudin 1, zona occludens 1 and 2. Addition of an adsorbing agent resulted in an up-regulation of all the investigated genes coding for the intestinal barrier in the ileum. Up-regulation of Toll-like receptor 4 and two markers of oxidative stress (heme-oxigenase or HMOX and xanthine oxidoreductase or XOR) were mainly seen in the jejunum and to a lesser extent in the ileum in response to deoxynivalenol, while in combination with an adsorbing agent main effect was seen in the ileum. These results suggest that an adsorbing agent may lead to higher concentrations of deoxynivalenol in the more distal parts of the small intestine. In the liver, XOR was up-regulated due to DON exposure. HMOX and HIF-1α (hypoxia-inducible factor 1α) were down-regulated due to feeding DON but also due to feeding the adsorbing agent alone or in combination with DON.

  11. The Immature Fiber Mutant Phenotype of Cotton (Gossypium hirsutum Is Linked to a 22-bp Frame-Shift Deletion in a Mitochondria Targeted Pentatricopeptide Repeat Gene

    Directory of Open Access Journals (Sweden)

    Gregory N. Thyssen

    2016-06-01

    Full Text Available Cotton seed trichomes are the most important source of natural fibers globally. The major fiber thickness properties influence the price of the raw material, and the quality of the finished product. The recessive immature fiber (im gene reduces the degree of fiber cell wall thickening by a process that was previously shown to involve mitochondrial function in allotetraploid Gossypium hirsutum. Here, we present the fine genetic mapping of the im locus, gene expression analysis of annotated proteins near the locus, and association analysis of the linked markers. Mapping-by-sequencing identified a 22-bp deletion in a pentatricopeptide repeat (PPR gene that is completely linked to the immature fiber phenotype in 2837 F2 plants, and is absent from all 163 cultivated varieties tested, although other closely linked marker polymorphisms are prevalent in the diversity panel. This frame-shift mutation results in a transcript with two long open reading frames: one containing the N-terminal transit peptide that targets mitochondria, the other containing only the RNA-binding PPR domains, suggesting that a functional PPR protein cannot be targeted to mitochondria in the im mutant. Taken together, these results suggest that PPR gene Gh_A03G0489 is involved in the cotton fiber wall thickening process, and is a promising candidate gene at the im locus. Our findings expand our understanding of the molecular mechanisms that modulate cotton fiber fineness and maturity, and may facilitate the development of cotton varieties with superior fiber attributes.

  12. Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling.

    Science.gov (United States)

    Basse, Astrid L; Dixen, Karen; Yadav, Rachita; Tygesen, Malin P; Qvortrup, Klaus; Kristiansen, Karsten; Quistorff, Bjørn; Gupta, Ramneek; Wang, Jun; Hansen, Jacob B

    2015-03-19

    Large mammals are capable of thermoregulation shortly after birth due to the presence of brown adipose tissue (BAT). The majority of BAT disappears after birth and is replaced by white adipose tissue (WAT). We analyzed the postnatal transformation of adipose in sheep with a time course study of the perirenal adipose depot. We observed changes in tissue morphology, gene expression and metabolism within the first two weeks of postnatal life consistent with the expected transition from BAT to WAT. The transformation was characterized by massively decreased mitochondrial abundance and down-regulation of gene expression related to mitochondrial function and oxidative phosphorylation. Global gene expression profiling demonstrated that the time points grouped into three phases: a brown adipose phase, a transition phase and a white adipose phase. Between the brown adipose and the transition phase 170 genes were differentially expressed, and 717 genes were differentially expressed between the transition and the white adipose phase. Thirty-eight genes were shared among the two sets of differentially expressed genes. We identified a number of regulated transcription factors, including NR1H3, MYC, KLF4, ESR1, RELA and BCL6, which were linked to the overall changes in gene expression during the adipose tissue remodeling. Finally, the perirenal adipose tissue expressed both brown and brite/beige adipocyte marker genes at birth, the expression of which changed substantially over time. Using global gene expression profiling of the postnatal BAT to WAT transformation in sheep, we provide novel insight into adipose tissue plasticity in a large mammal, including identification of novel transcriptional components linked to adipose tissue remodeling. Moreover, our data set provides a useful resource for further studies in adipose tissue plasticity.

  13. The role of tight junctions in mammary gland function.

    Science.gov (United States)

    Stelwagen, Kerst; Singh, Kuljeet

    2014-03-01

    Tight junctions (TJ) are cellular structures that facilitate cell-cell communication and are important in maintaining the three-dimensional structure of epithelia. It is only during the last two decades that the molecular make-up of TJ is becoming unravelled, with two major transmembrane-spanning structural protein families, called occludin and claudins, being the true constituents of the TJ. These TJ proteins are linked via specific scaffolding proteins to the cell's cytoskeleton. In the mammary gland TJ between adjacent secretory epithelial cells are formed during lactogenesis and are instrumental in establishing and maintaining milk synthesis and secretion, whereas TJ integrity is compromised during mammary involution and also as result of mastitis and periods of mammary inflamation (including mastitis). They prevent the paracellular transport of ions and small molecules between the blood and milk compartments. Formation of intact TJ at the start of lactation is important for the establishment of the lactation. Conversely, loss of TJ integrity has been linked to reduced milk secretion and mammary function and increased paracellular transport of blood components into the milk and vice versa. In addition to acting as a paracellular barrier, the TJ is increasingly linked to playing an active role in intracellular signalling. This review focusses on the role of TJ in mammary function of the normal, non-malignant mammary gland, predominantly in ruminants, the major dairy producing species.

  14. Tight junction disruption: Helicobacter pylori and dysregulation of the gastric mucosal barrier.

    Science.gov (United States)

    Caron, Tyler J; Scott, Kathleen E; Fox, James G; Hagen, Susan J

    2015-10-28

    Long-term chronic infection with Helicobacter pylori (H. pylori) is a risk factor for gastric cancer development. In the multi-step process that leads to gastric cancer, tight junction dysfunction is thought to occur and serve as a risk factor by permitting the permeation of luminal contents across an otherwise tight mucosa. Mechanisms that regulate tight junction function and structure in the normal stomach, or dysfunction in the infected stomach, however, are largely unknown. Although conventional tight junction components are expressed in gastric epithelial cells, claudins regulate paracellular permeability and are likely the target of inflammation or H. pylori itself. There are 27 different claudin molecules, each with unique properties that render the mucosa an intact barrier that is permselective in a way that is consistent with cell physiology. Understanding the architecture of tight junctions in the normal stomach and then changes that occur during infection is important but challenging, because most of the reports that catalog claudin expression in gastric cancer pathogenesis are contradictory. Furthermore, the role of H. pylori virulence factors, such as cytotoxin-associated gene A and vacoulating cytotoxin, in regulating tight junction dysfunction during infection is inconsistent in different gastric cell lines and in vivo, likely because non-gastric epithelial cell cultures were initially used to unravel the details of their effects on the stomach. Hampering further study, as well, is the relative lack of cultured cell models that have tight junction claudins that are consistent with native tissues. This summary will review the current state of knowledge about gastric tight junctions, normally and in H. pylori infection, and make predictions about the consequences of claudin reorganization during H. pylori infection.

  15. Ambiguity of human gene symbols in LocusLink and MEDLINE: creating an inventory and a disambiguation test collection

    NARCIS (Netherlands)

    M. Weeber (Marc); R.J.A. Schijvenaars (Bob); E.M. van Mulligen (Erik); B. Mons (Barend); R. Jelier (Rob); C.C. van der Eijk (Christiaan); J.A. Kors (Jan)

    2003-01-01

    textabstractGenes are discovered almost on a daily basis and new names have to be found. Although there are guidelines for gene nomenclature, the naming process is highly creative. Human genes are often named with a gene symbol and a longer, more descriptive term; the short form is

  16. Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q

    Energy Technology Data Exchange (ETDEWEB)

    Fink, J.K.; Wu, C.B.; Jones, S.M.; Lesicki, A.; Reinglass, T. [Univ. of Michigan, Ann Arbor, MI (United States); Sharp, G.B.; Lange, B.M. [Arkansas Children`s Hospital, Little Rock, AR (United States); Varvil, T.; Otterud, B.; Leppert, M. [Univ. of Utah, Salt Lake City, UT (United States)

    1995-01-01

    Autosomal dominant, uncomplicated familial spastic paraplegia (FSP) is a genetically heterogeneous disorder characterized by insidiously progressive lower-extremity spasticity. Recently, a locus on chromosome 14q was shown to be tightly linked with the disorder in one of three families. We performed linkage analysis in a kindred with autosomal dominant uncomplicated FSP. After excluding the chromosome 14q locus, we observed tight linkage of the disorder to a group of markers on chromosome 15q (maximum two-point lod score 9.70; {theta} = .05). Our results clearly establish the existence of a locus for autosomal dominant FSP in the centromeric region of chromosome 15q. Comparing clinical and genetic features in FSP families linked to chromosome 14q with those linked to chromosome 15q may provide insight into the pathophysiology of this disorder. 34 refs., 1 fig., 1 tab.

  17. X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: Evidence from segregation analysis for dependence on X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Xiangdong Bu; Rotter, J.I. (Cedars-Sinai Medical Center, Los Angeles, CA (United States) Univ. of California, Los Angeles (United States))

    1991-09-15

    Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, the authors show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, they have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11{plus minus}0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.l08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome-linked locus.

  18. Identification and glycerol-induced correction of misfolding mutations in the X-linked mental retardation gene CASK.

    Directory of Open Access Journals (Sweden)

    Leslie E W LaConte

    Full Text Available The overwhelming amount of available genomic sequence variation information demands a streamlined approach to examine known pathogenic mutations of any given protein. Here we seek to outline a strategy to easily classify pathogenic missense mutations that cause protein misfolding and are thus good candidates for chaperone-based therapeutic strategies, using previously identified mutations in the gene CASK. We applied a battery of bioinformatics algorithms designed to predict potential impact on protein structure to five pathogenic missense mutations in the protein CASK that have been shown to underlie pathologies ranging from X-linked mental retardation to autism spectrum disorder. A successful classification of the mutations as damaging was not consistently achieved despite the known pathogenicity. In addition to the bioinformatics analyses, we performed molecular modeling and phylogenetic comparisons. Finally, we developed a simple high-throughput imaging assay to measure the misfolding propensity of the CASK mutants in situ. Our data suggests that a phylogenetic analysis may be a robust method for predicting structurally damaging mutations in CASK. Mutations in two evolutionarily invariant residues (Y728C and W919R exhibited a strong propensity to misfold and form visible aggregates in the cytosolic milieu. The remaining mutations (R28L, Y268H, and P396S showed no evidence of aggregation and maintained their interactions with known CASK binding partners liprin-α3 Mint-1, and Veli, indicating an intact structure. Intriguingly, the protein aggregation caused by the Y728C and W919R mutations was reversed by treating the cells with a chemical chaperone (glycerol, providing a possible therapeutic strategy for treating structural mutations in CASK in the future.

  19. The homeobox gene mirror links EGF signalling to embryonic dorso-ventral axis formation through notch activation.

    Science.gov (United States)

    Jordan, K C; Clegg, N J; Blasi, J A; Morimoto, A M; Sen, J; Stein, D; McNeill, H; Deng, W M; Tworoger, M; Ruohola-Baker, H

    2000-04-01

    Recent studies in vertebrates and Drosophila melanogaster have revealed that Fringe-mediated activation of the Notch pathway has a role in patterning cell layers during organogenesis. In these processes, a homeobox-containing transcription factor is responsible for spatially regulating fringe (fng) expression and thus directing activation of the Notch pathway along the fng expression border. Here we show that this may be a general mechanism for patterning epithelial cell layers. At three stages in Drosophila oogenesis, mirror (mirr) and fng have complementary expression patterns in the follicle-cell epithelial layer, and at all three stages loss of mirr enlarges, and ectopic expression of mirr restricts, fng expression, with consequences for follicle-cell patterning. These morphological changes are similar to those caused by Notch mutations. Ectopic expression of mirr in the posterior follicle cells induces a stripe of rhomboid (rho) expression and represses pipe (pip), a gene with a role in the establishment of the dorsal-ventral axis, at a distance. Ectopic Notch activation has a similar long-range effect on pip. Our results suggest that Mirror and Notch induce secretion of diffusible morphogens and we have identified TGF-beta (encoded by dpp) as such a molecule in germarium. We also found that mirr expression in dorsal follicle cells is induced by the EGF-receptor (EGFR) pathway and that mirr then represses pip expression in all but the ventral follicle cells, connecting EGFR activation in the dorsal follicle cells to repression of pip in the dorsal and lateral follicle cells. Our results suggest that the differentiation of ventral follicle cells is not a direct consequence of germline signalling, but depends on long-range signals from dorsal follicle cells, and provide a link between early and late events in Drosophila embryonic dorsal-ventral axis formation.

  20. Comparisons of Maize pericarp color1 Alleles Reveal Paralogous Gene Recombination and an Organ-Specific Enhancer Region

    National Research Council Canada - National Science Library

    Feng Zhang; Thomas Peterson

    2005-01-01

    ... (for red pericarp/white cob) alleles, P1-rw1077 and P1-rw751::Ac. Structural analysis of P1-rw1077 indicated that this allele was generated by recombination between p1 and the tightly linked paralogous gene, p2...

  1. Atom laser dynamics in a tight waveguide

    Energy Technology Data Exchange (ETDEWEB)

    Campo, A del; Lizuain, I; Muga, J G [Departamento de Quimica-Fisica, UPV-EHU, Apartado. 644, Bilbao (Spain); Pons, M [Departamento de Fisica Aplicada I, E.U.I.T. de Minas y Obras Publicas, UPV-EHU, 48901 Barakaldo (Spain); Moshinsky, M [Instituto de Fisica, Universidad Nacional Autonoma de Mexico, Apartado Postal 20-364, 01000 Mexico D.F. (Mexico)], E-mail: adolfo.delcampo@ehu.es

    2008-02-15

    We study the transient dynamics that arise during the formation of an atom laser beam in a tight waveguide. The time dependent density profile develops a series of wiggles which are related to the diffraction in time phenomenon. The apodization of matter waves, which relies on the use of smooth aperture functions, allows to suppress such oscillations in a time interval, after which there is a revival of the diffraction in time. The revival time scale is directly related to the inverse of the harmonic trap frequency for the atom reservoir.

  2. Inward Leakage in Tight-Fitting PAPRs

    Directory of Open Access Journals (Sweden)

    Frank C. Koh

    2011-01-01

    Full Text Available A combination of local flow measurement techniques and fog flow visualization was used to determine the inward leakage for two tight-fitting powered air-purifying respirators (PAPRs, the 3M Breathe-Easy PAPR and the SE 400 breathing demand PAPR. The PAPRs were mounted on a breathing machine head form, and flows were measured from the blower and into the breathing machine. Both respirators leaked a little at the beginning of inhalation, probably through their exhalation valves. In both cases, the leakage was not enough for fog to appear at the mouth of the head form.

  3. TIGHT-BINDING DESCRIPTION OF TICx

    Directory of Open Access Journals (Sweden)

    V.I.Ivashchenko

    2004-01-01

    Full Text Available A parametrized non-orthogonal tight-binding (TB method combined with the coherent-potential-approximation is applied to the study of the electronic structure of disordered off-stoichiometric TiCx, the lattice relaxation and the electronic spectra of the TiC (001 surface, the local relaxation and energetic states of TiC structures with one or two vacancies in both the non-metal and metal sublattices. The calculated results are in good agreement with available experimental and theoretical data. The importance of the overlap matrix elements of the TB Hamiltonian in describing the electronic structure of this class of compounds is emphasized.

  4. Transferable Tight-Binding Potential for Hydrocarbons

    CERN Document Server

    Wang, Y; Wang, Yang

    1994-01-01

    A transferable tight-binding potential has been constructed for heteroatomic systems containing carbon and hydrogen. The electronic degree of freedom is treated explicitly in this potential using a small set of transferable parameters which has been fitted to small hydrocarbons and radicals. Transferability to other higher hydrocarbons were tested by comparison with ab initio calculations and experimental data. The potential can correctly reproduce changes in the electronic configuration as a function of the local bonding geometry around each carbon atom. This type of potential is well suited for computer simulations of covalently bonded systems in both gas-phase and condensed-phase systems.

  5. Tight Reference Frame–Independent Quantum Teleportation

    Directory of Open Access Journals (Sweden)

    Dominic Verdon

    2017-01-01

    Full Text Available We give a tight scheme for teleporting a quantum state between two parties whose reference frames are misaligned by an action of a finite symmetry group. Unlike previously proposed schemes, ours requires no additional tokens or data to be passed between the participants; the same amount of classical information is transferred as for ordinary quantum teleportation, and the Hilbert space of the entangled resource is of the same size. In the terminology of Peres and Scudo, our protocol relies on classical communication of unspeakable information.

  6. A Poincar\\'e-Birkhoff theorem for tight Reeb flows on $S^3$

    CERN Document Server

    Hryniewicz, Umberto; Salomão, Pedro A S

    2011-01-01

    We consider Reeb flows on the tight 3-sphere admitting a pair of closed orbits forming a Hopf link. If the rotation numbers of the transverse linearized dynamics at these orbits fail to satisfy a certain resonance condition then there exist infinitely many periodic trajectories distinguished by their linking numbers with the components of the link. This result admits a natural comparison to the Poincar\\'e-Birkhoff theorem on area-preserving annulus homeomorphisms. An analogous theorem holds on SO(3) and applies to geodesic flows of Finsler metrics on $S^2$.

  7. Hyperexpression of the X chromosome in both sexes results in extensive female bias of X-linked genes in the flour beetle.

    Science.gov (United States)

    Prince, Eldon G; Kirkland, Donna; Demuth, Jeffery P

    2010-07-12

    A genome's ability to produce two separate sexually dimorphic phenotypes is an intriguing biological mystery. Microarray-based studies of a handful of model systems suggest that much of the mystery can be explained by sex-biased gene expression evolved in response to sexually antagonistic selection. We present the first whole-genome study of sex-biased expression in the red flour beetle, Tribolium castaneum. Tribolium is a model for the largest eukaryotic order, Coleoptera, and we show that in whole-body adults, approximately 20% of the transcriptome is differentially regulated between the sexes. Among T. castaneum, Drosophila melanogaster, and Anopheles gambiae, we identify 416 1:1:1 orthologs with conserved sex-biased expression. Overrepresented functional categories among sex-biased genes are primarily those involved in gamete production and development. The genomic distribution of sex-biased genes in T. castaneum is distinctly nonrandom, with the strongest deficit of male-biased genes on the X chromosome (9 of 793) of any species studied to date. Tribolium also shows a significant enrichment of X-linked female-biased genes (408 of 793). Our analyses suggest that the extensive female bias of Tribolium X chromosome gene expression is due to hyperexpression of X-linked genes in both males and females. We propose that the overexpression of X chromosomes in females is an evolutionary side effect of the need to dosage compensate in males and that mechanisms to reduce female X chromosome gene expression to autosomal levels are sufficient but imperfect.

  8. Tight junction-associated MARVEL proteins marveld3, tricellulin, and occludin have distinct but overlapping functions.

    Science.gov (United States)

    Raleigh, David R; Marchiando, Amanda M; Zhang, Yong; Shen, Le; Sasaki, Hiroyuki; Wang, Yingmin; Long, Manyuan; Turner, Jerrold R

    2010-04-01

    In vitro studies have demonstrated that occludin and tricellulin are important for tight junction barrier function, but in vivo data suggest that loss of these proteins can be overcome. The presence of a heretofore unknown, yet related, protein could explain these observations. Here, we report marvelD3, a novel tight junction protein that, like occludin and tricellulin, contains a conserved four-transmembrane MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain. Phylogenetic tree reconstruction; analysis of RNA and protein tissue distribution; immunofluorescent and electron microscopic examination of subcellular localization; characterization of intracellular trafficking, protein interactions, dynamic behavior, and siRNA knockdown effects; and description of remodeling after in vivo immune activation show that marvelD3, occludin, and tricellulin have distinct but overlapping functions at the tight junction. Although marvelD3 is able to partially compensate for occludin or tricellulin loss, it cannot fully restore function. We conclude that marvelD3, occludin, and tricellulin define the tight junction-associated MARVEL protein family. The data further suggest that these proteins are best considered as a group with both redundant and unique contributions to epithelial function and tight junction regulation.

  9. Bioabsorbable thread for tight tying of bones.

    Science.gov (United States)

    Hattori, K; Tomita, N; Tamai, S; Ikada, Y

    2000-01-01

    The purpose of this research was to develop a bioabsorbable thread for tight fixation of fractured bones and to examine its mechanical performance in an in-vitro simulation study. The thread is a blend of bioabsorbable poly(L-lactic acid); (PLLA) and poly(epsilon-caprolactone); (PCL) fibers and can be tightly connected by fusion welding of the PCL fibers. The tying strength of the PLLA-PCL blend thread was 39.7 N, which was comparable to that of stainless steel wire. A testing machine was fabricated to measure the fatigue strength of the tying by simulating bone fixation. The results showed that metal wires always failed because of breakage within 25,000 loading cycles, whereas the blend threads did not fail until 50,000 loading cycles. The looseness of tying for simulated bone fixation by the blend thread was within 1mm even after 50 000 loading cycles. In-vivo testing using rats revealed that the blend thread did not cause any severe inflammatory reaction.

  10. Mutational analysis of the biglycan gene excludes it as a candidate for x-linked dominant chondrodysplasia punctata, dyskeratosis congenita, and incontinentia pigmenti

    Energy Technology Data Exchange (ETDEWEB)

    Das, S.; Metzenberg, A.; Gitschier, J. (Univ. of California, San Francisco, CA (United States)); Pai, G.S. (Medical Univ. of South Carolina, Charleston, SC (United States))

    1994-05-01

    Biglycan is a small proteoglycan expressed mainly in cells of connective tissue, including chondrocytes, ostocytes, epithelial cells, and endothelial cells. The biglycan cDNA is 1,685 bp long. The biglycan gene was amplified in six segments by using nested PCR. Primers were synthesized to amplify exons 2-8 of the biglycan gene. Exon 1 was not amplified, as it consists entirely of 5[prime] untranslated sequence. Each exon was separately amplified, except for exons 5-7, which, because of their small size, were amplified in two segments and were subjected to SSCP analysis. Results indicate the presence of two different haplotypes for exon 2 and three different haplotypes for exon 4. Further SSCP analysis of control samples from nine females and one male confirmed that the exon 2 and exon 4 haplotypes consist of polymorphisms, rather than of mutations that specifically affect this patient population. Our results support recently described work that proposes that the biglycan gene may not be involved in X-linked dominant chondrodysplasia punctata. The absence of mutations in the biglycan gene in X-linked dominant chondrodysplasia punctata, dyskeratosis congenita, and incontinentia pigmenti suggest it is highly unlikely that mutations in this gene are responsible for any of these disorders.

  11. Older Age Results in Differential Gene Expression after Mild Traumatic Brain Injury and is Linked to Imaging Differences at Acute Follow-up

    Directory of Open Access Journals (Sweden)

    Young-Eun Cho

    2016-07-01

    Full Text Available Older age consistently relates to a lesser ability to fully recover from a traumatic brain injury (TBI; however, there is limited data to explicate the nature of age-related risks. This study was undertaken to determine the relationship of age on gene-activity following a TBI, and how this biomarker relates to changes in neuroimaging findings. A younger group (between the ages of 19-35 years, and an older group (between the ages of 60-89 years were compared on global gene-activity within 48 hours following a TBI, and then at follow-up within 1-week. At each time-point gene-expression profiles, and imaging findings from magnetic resonance imaging (MRI and computed tomography (CT were obtained and compared. The younger group was found to have greater gene expression of inflammatory regulatory genes at 48 hours and 1 week in genes such as basic leucine zipper transcription factor 2 (BACH2, leucine rich repeat neuronal 3 (LRRN3 and lymphoid enhancer-binding factor 1 (LEF1 compared to the older group. In the older group, there was increased activity in genes within S100 family, including calcium binding protein P (S100P and S100 calcium binding protein A8 (S100A8, which previous studies have linked to poor recovery from TBI. The older group also had reduced activity of the noggin (NOG gene, which is a member of the transforming growth factor-β (TGF-β superfamily and is linked to neuro-recovery and neuro-regeneration compared to the younger group. We link these gene-expression findings that were validated to neuroimaging, reporting that in the older group with a MRI finding of TBI related damage, there was a lesser likelihood to then have a negative MRI finding at follow-up compared to the younger group. Together, these data indicate that age impacts gene activity following a TBI, and suggests that this differential activity related to immune regulation and neuro-recovery contributes to a lesser likelihood of neuronal recovery in older patients as

  12. Role of the complex upstream region of the GDH2 gene in nitrogen regulation of the NAD-linked glutamate dehydrogenase in Saccharomyces cerevisiae.

    OpenAIRE

    Miller, S. M; Magasanik, B

    1991-01-01

    We analyzed the upstream region of the GDH2 gene, which encodes the NAD-linked glutamate dehydrogenase in Saccharomyces cerevisiae, for elements important for the regulation of the gene by the nitrogen source. The levels of this enzyme are high in cells grown with glutamate as the sole source of nitrogen and low in cells grown with glutamine or ammonium. We found that this regulation occurs at the level of transcription and that a total of six sites are required to cause a CYC1-lacZ fusion to...

  13. Systematic identification of core transcription factors mediating dysregulated links bridging inflammatory bowel diseases and colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Yun Xiao

    Full Text Available Accumulating evidence shows a tight link between inflammation and cancer. However, comprehensive identification of pivotal transcription factors (i.e., core TFs mediating the dysregulated links remains challenging, mainly due to a lack of samples that can effectively reflect the connections between inflammation and tumorigenesis. Here, we constructed a series of TF-mediated regulatory networks from a large compendium of expression profiling of normal colonic tissues, inflammatory bowel diseases (IBDs and colorectal cancer (CRC, which contains 1201 samples in total, and then proposed a network-based approach to characterize potential links bridging inflammation and cancer. For this purpose, we computed significantly dysregulated relationships between inflammation and their linked cancer networks, and then 24 core TFs with their dysregulated genes were identified. Collectively, our approach provides us with quite important insight into inflammation-associated tumorigenesis in colorectal cancer, which could also be applied to identify functionally dysregulated relationships mediating the links between other different disease phenotypes.

  14. Variation in the Genetic Repertoire of Viruses Infecting Micromonas pusilla Reflects Horizontal Gene Transfer and Links to Their Environmental Distribution

    Science.gov (United States)

    Finke, Jan F.; Winget, Danielle M.; Chan, Amy M.; Suttle, Curtis A.

    2017-01-01

    Prasinophytes, a group of eukaryotic phytoplankton, has a global distribution and is infected by large double-stranded DNA viruses (prasinoviruses) in the family Phycodnaviridae. This study examines the genetic repertoire, phylogeny, and environmental distribution of phycodnaviruses infecting Micromonas pusilla, other prasinophytes and chlorophytes. Based on comparisons among the genomes of viruses infecting M. pusilla and other phycodnaviruses, as well as the genome from a host isolate of M. pusilla, viruses infecting M. pusilla (MpVs) share a limited set of core genes, but vary strongly in their flexible pan-genome that includes numerous metabolic genes, such as those associated with amino acid synthesis and sugar manipulation. Surprisingly, few of these presumably host-derived genes are shared with M. pusilla, but rather have their closest non-viral homologue in bacteria and other eukaryotes, indicating horizontal gene transfer. A comparative analysis of full-length DNA polymerase (DNApol) genes from prasinoviruses with their overall gene content, demonstrated that the phylogeny of DNApol gene fragments reflects the gene content of the viruses; hence, environmental DNApol gene sequences from prasinoviruses can be used to infer their overall genetic repertoire. Thus, the distribution of virus ecotypes across environmental samples based on DNApol sequences implies substantial underlying differences in gene content that reflect local environmental conditions. Moreover, the high diversity observed in the genetic repertoire of prasinoviruses has been driven by horizontal gene transfer throughout their evolutionary history, resulting in a broad suite of functional capabilities and a high diversity of prasinovirus ecotypes. PMID:28534829

  15. A novel putative enterococcal pathogenicity island linked to the esp virulence gene of Enterococcus faecium and associated with epidemicity.

    Science.gov (United States)

    Leavis, Helen; Top, Janetta; Shankar, Nathan; Borgen, Katrine; Bonten, Marc; van Embden, Jan; Willems, Rob J L

    2004-02-01

    Enterococcus faecalis harbors a virulence-associated surface protein encoded by the esp gene. This gene has been shown to be part of a 150-kb putative pathogenicity island. A gene similar to esp has recently been found in Enterococcus faecium isolates recovered from hospitalized patients. In the present study we analyzed the polymorphism in the esp gene of E. faecium, and we investigated the association of esp with neighboring chromosomal genes. The esp gene showed considerable sequence heterogeneity in the regions encoding the nonrepeat N- and C-terminal domains of the Esp protein as well as differences in the number of repeats. DNA sequencing of chromosomal regions flanking the esp gene of E. faecium revealed seven open reading frames, representing putative genes implicated in virulence, regulation of transcription, and antibiotic resistance. These flanking regions were invariably associated with the presence or absence of the esp gene in E. faecium, indicating that esp in E. faecium is part of a distinct genetic element. Because of the presence of virulence genes in this gene cluster, the lower G+C content relative to that of the genome, and the presence of esp in E. faecium isolates associated with nosocomial outbreaks and clinically documented infections, we conclude that this genetic element constitutes a putative pathogenicity island, the first one described in E. faecium. Except for the presence of esp and araC, this pathogenicity island is completely different from the esp-containing pathogenicity island previously disclosed in E. faecalis.

  16. Analysis of Differentially Expressed Genes and Signaling Pathways Related to Intramuscular Fat Deposition in Skeletal Muscle of Sex-Linked Dwarf Chickens

    Directory of Open Access Journals (Sweden)

    Yaqiong Ye

    2014-01-01

    Full Text Available Intramuscular fat (IMF plays an important role in meat quality. However, the molecular mechanisms underlying IMF deposition in skeletal muscle have not been addressed for the sex-linked dwarf (SLD chicken. In this study, potential candidate genes and signaling pathways related to IMF deposition in chicken leg muscle tissue were characterized using gene expression profiling of both 7-week-old SLD and normal chickens. A total of 173 differentially expressed genes (DEGs were identified between the two breeds. Subsequently, 6 DEGs related to lipid metabolism or muscle development were verified in each breed based on gene ontology (GO analysis. In addition, KEGG pathway analysis of DEGs indicated that some of them (GHR, SOCS3, and IGF2BP3 participate in adipocytokine and insulin signaling pathways. To investigate the role of the above signaling pathways in IMF deposition, the gene expression of pathway factors and other downstream genes were measured by using qRT-PCR and Western blot analyses. Collectively, the results identified potential candidate genes related to IMF deposition and suggested that IMF deposition in skeletal muscle of SLD chicken is regulated partially by pathways of adipocytokine and insulin and other downstream signaling pathways (TGF-β/SMAD3 and Wnt/catenin-β pathway.

  17. Ex Vivo γ-Retroviral Gene Therapy of Dogs with X-linked Severe Combined Immunodeficiency and the Development of a Thymic T Cell Lymphoma

    Science.gov (United States)

    Kennedy, Douglas R.; Hartnett, Brian J.; Kennedy, Jeffrey S.; Vernau, William; Moore, Peter F.; O’Malley, Thomas; Burkly, Linda C.; Henthorn, Paula S.; Felsburg, Peter J.

    2011-01-01

    We have previously shown that in vivo γ-retroviral gene therapy of dogs with X-linked severe combined immunodeficiency (XSCID) results in sustained T cell reconstitution and sustained marking in myeloid and B cells for up to 4 years with no evidence of any serious adverse effects. The purpose of this study was to determine whether ex vivo γ-retroviral gene therapy of XSCID dogs results in a similar outcome. Eight of 12 XSCID dogs treated with an average of dose of 5.8 × 106 transduced CD34+ cells/kg successfully engrafted producing normal numbers of gene-corrected CD45RA+ (naïve) T cells. However, this was followed by a steady decrease in CD45RA+ T cells, T cell diversity, and thymic output as measured by T cell receptor excision circles (TRECs) resulting in a T cell lymphopenia. None of the dogs survived past 11 months post treatment. At necropsy, few gene-corrected thymocytes were observed correlating with the TREC levels and one of the dogs was diagnosed with a thymic T cell lymphoma that was attributed to the gene therapy. This study highlights the outcome differences between the ex vivo and in vivo approach to γ-retroviral gene therapy and is the first to document a serious adverse event following gene therapy in a canine model of a human genetic disease. PMID:21536334

  18. A bioinformatics tool for linking gene expression profiling results with public databases of microRNA target predictions

    Science.gov (United States)

    Creighton, Chad J.; Nagaraja, Ankur K.; Hanash, Samir M.; Matzuk, Martin M.; Gunaratne, Preethi H.

    2008-01-01

    MicroRNAs are short (∼22 nucleotides) noncoding RNAs that regulate the stability and translation of mRNA targets. A number of computational algorithms have been developed to help predict which microRNAs are likely to regulate which genes. Gene expression profiling of biological systems where microRNAs might be active can yield hundreds of differentially expressed genes. The commonly used public microRNA target prediction databases facilitate gene-by-gene searches. However, integration of microRNA–mRNA target predictions with gene expression data on a large scale using these databases is currently cumbersome and time consuming for many researchers. We have developed a desktop software application which, for a given target prediction database, retrieves all microRNA:mRNA functional pairs represented by an experimentally derived set of genes. Furthermore, for each microRNA, the software computes an enrichment statistic for overrepresentation of predicted targets within the gene set, which could help to implicate roles for specific microRNAs and microRNA-regulated genes in the system under study. Currently, the software supports searching of results from PicTar, TargetScan, and miRanda algorithms. In addition, the software can accept any user-defined set of gene-to-class associations for searching, which can include the results of other target prediction algorithms, as well as gene annotation or gene-to-pathway associations. A search (using our software) of genes transcriptionally regulated in vitro by estrogen in breast cancer uncovered numerous targeting associations for specific microRNAs—above what could be observed in randomly generated gene lists—suggesting a role for microRNAs in mediating the estrogen response. The software and Excel VBA source code are freely available at http://sigterms.sourceforge.net. PMID:18812437

  19. A bioinformatics tool for linking gene expression profiling results with public databases of microRNA target predictions.

    Science.gov (United States)

    Creighton, Chad J; Nagaraja, Ankur K; Hanash, Samir M; Matzuk, Martin M; Gunaratne, Preethi H

    2008-11-01

    MicroRNAs are short (approximately 22 nucleotides) noncoding RNAs that regulate the stability and translation of mRNA targets. A number of computational algorithms have been developed to help predict which microRNAs are likely to regulate which genes. Gene expression profiling of biological systems where microRNAs might be active can yield hundreds of differentially expressed genes. The commonly used public microRNA target prediction databases facilitate gene-by-gene searches. However, integration of microRNA-mRNA target predictions with gene expression data on a large scale using these databases is currently cumbersome and time consuming for many researchers. We have developed a desktop software application which, for a given target prediction database, retrieves all microRNA:mRNA functional pairs represented by an experimentally derived set of genes. Furthermore, for each microRNA, the software computes an enrichment statistic for overrepresentation of predicted targets within the gene set, which could help to implicate roles for specific microRNAs and microRNA-regulated genes in the system under study. Currently, the software supports searching of results from PicTar, TargetScan, and miRanda algorithms. In addition, the software can accept any user-defined set of gene-to-class associations for searching, which can include the results of other target prediction algorithms, as well as gene annotation or gene-to-pathway associations. A search (using our software) of genes transcriptionally regulated in vitro by estrogen in breast cancer uncovered numerous targeting associations for specific microRNAs-above what could be observed in randomly generated gene lists-suggesting a role for microRNAs in mediating the estrogen response. The software and Excel VBA source code are freely available at http://sigterms.sourceforge.net.

  20. Computational modeling with forward and reverse engineering links signaling network and genomic regulatory responses: NF-κB signaling-induced gene expression responses in inflammation

    Directory of Open Access Journals (Sweden)

    Peng Chien

    2010-06-01

    Full Text Available Abstract Background Signal transduction is the major mechanism through which cells transmit external stimuli to evoke intracellular biochemical responses. Diverse cellular stimuli create a wide variety of transcription factor activities through signal transduction pathways, resulting in different gene expression patterns. Understanding the relationship between external stimuli and the corresponding cellular responses, as well as the subsequent effects on downstream genes, is a major challenge in systems biology. Thus, a systematic approach is needed to integrate experimental data and theoretical hypotheses to identify the physiological consequences of environmental stimuli. Results We proposed a systematic approach that combines forward and reverse engineering to link the signal transduction cascade with the gene responses. To demonstrate the feasibility of our strategy, we focused on linking the NF-κB signaling pathway with the inflammatory gene regulatory responses because NF-κB has long been recognized to play a crucial role in inflammation. We first utilized forward engineering (Hybrid Functional Petri Nets to construct the NF-κB signaling pathway and reverse engineering (Network Components Analysis to build a gene regulatory network (GRN. Then, we demonstrated that the corresponding IKK profiles can be identified in the GRN and are consistent with the experimental validation of the IKK kinase assay. We found that the time-lapse gene expression of several cytokines and chemokines (TNF-α, IL-1, IL-6, CXCL1, CXCL2 and CCL3 is concordant with the NF-κB activity profile, and these genes have stronger influence strength within the GRN. Such regulatory effects have highlighted the crucial roles of NF-κB signaling in the acute inflammatory response and enhance our understanding of the systemic inflammatory response syndrome. Conclusion We successfully identified and distinguished the corresponding signaling profiles among three microarray

  1. Naturally fractured tight gas reservoir detection optimization

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-11-30

    The work plan for October 1, 1997 to September 30, 1998 consisted of investigation of a number of topical areas. These topical areas were reported in four quarterly status reports, which were submitted to DOE earlier. These topical areas are reviewed in this volume. The topical areas covered during the year were: (1) Development of preliminary tests of a production method for determining areas of natural fracturing. Advanced Resources has demonstrated that such a relationship exists in the southern Piceance basin tight gas play. Natural fracture clusters are genetically related to stress concentrations (also called stress perturbations) associated with local deformation such a faulting. The mechanical explanation of this phenomenon is that deformation generally initiates at regions where the local stress field is elevated beyond the regional. (2) Regional structural and geologic analysis of the Greater Green River Basin (GGRB). Application of techniques developed and demonstrated during earlier phases of the project for sweet-spot delineation were demonstrated in a relatively new and underexplored play: tight gas from continuous-typeUpper Cretaceous reservoirs of the Greater Green River Basin (GGRB). The effort included data acquisition/processing, base map generation, geophysical and remote sensing analysis and the integration of these data and analyses. (3) Examination of the Table Rock field area in the northern Washakie Basin of the Greater Green River Basin. This effort was performed in support of Union Pacific Resources- and DOE-planned horizontal drilling efforts. The effort comprised acquisition of necessary seismic data and depth-conversion, mapping of major fault geometry, and analysis of displacement vectors, and the development of the natural fracture prediction. (4) Greater Green River Basin Partitioning. Building on fundamental fracture characterization work and prior work performed under this contract, namely structural analysis using satellite and

  2. The Cost Implications of Less Tight Versus Tight Control of Hypertension in Pregnancy (CHIPS Trial)

    Science.gov (United States)

    Ahmed, Rashid J.; Gafni, Amiram; Hu, Zheng Jing; Pullenayegum, Eleanor; von Dadelszen, Peter; Rey, Evelyne; Ross, Susan; Asztalos, Elizabeth; Murphy, Kellie E.; Menzies, Jennifer; Sanchez, J. Johanna; Ganzevoort, Wessel; Helewa, Michael; Lee, Shoo K.; Lee, Terry; Logan, Alexander G.; Moutquin, Jean-Marie; Singer, Joel; Thornton, Jim G.; Welch, Ross; Magee, Laura A.

    2016-01-01

    The CHIPS randomized controlled trial (Control of Hypertension in Pregnancy Study) found no difference in the primary perinatal or secondary maternal outcomes between planned “less tight” (target diastolic 100 mm Hg) and “tight” (target diastolic 85 mm Hg) blood pressure management strategies among women with chronic or gestational hypertension. This study examined which of these management strategies is more or less costly from a third-party payer perspective. A total of 981 women with singleton pregnancies and nonsevere, nonproteinuric chronic or gestational hypertension were randomized at 14 to 33 weeks to less tight or tight control. Resources used were collected from 94 centers in 15 countries and costed as if the trial took place in each of 3 Canadian provinces as a cost-sensitivity analysis. Eleven hospital ward and 24 health service costs were obtained from a similar trial and provincial government health insurance schedules of medical benefits. The mean total cost per woman–infant dyad was higher in less tight versus tight control, but the difference in mean total cost (DM) was not statistically significant in any province: Ontario ($30 191.62 versus $24 469.06; DM $5723, 95% confidence interval, −$296 to $12 272; P=0.0725); British Columbia ($30 593.69 versus $24 776.51; DM $5817; 95% confidence interval, −$385 to $12 349; P=0.0725); or Alberta ($31 510.72 versus $25 510.49; DM $6000.23; 95% confidence interval, −$154 to $12 781; P=0.0637). Tight control may benefit women without increasing risk to neonates (as shown in the main CHIPS trial), without additional (and possibly lower) cost to the healthcare system. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01192412. PMID:27550914

  3. Naturally fractured tight gas reservoir detection optimization

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-06-01

    Building upon the partitioning of the Greater Green River Basin (GGRB) that was conducted last quarter, the goal of the work this quarter has been to conclude evaluation of the Stratos well and the prototypical Green River Deep partition, and perform the fill resource evaluation of the Upper Cretaceous tight gas play, with the goal of defining target areas of enhanced natural fracturing. The work plan for the quarter of November 1-December 31, 1998 comprised four tasks: (1) Evaluation of the Green River Deep partition and the Stratos well and examination of potential opportunity for expanding the use of E and P technology to low permeability, naturally fractured gas reservoirs, (2) Gas field studies, and (3) Resource analysis of the balance of the partitions.

  4. On the Countable Tightness of Product Spaces

    Institute of Scientific and Technical Information of China (English)

    Chuan LIU; Shou LIN

    2005-01-01

    In this paper, we discuss the countable tightness of products of spaces which are quotient simages of locally separable metric spaces, or k-spaces with a star-countable k-network. The main result is that the following conditions are equivalent: (1) b = ω1; (2) t(Sω× Sω1 ) >ω; (3) For any pair (X, Y),which are k-spaces with a point-countable k-network consisting of cosmic subspaces, t(X × Y) ≤ωif and only if one of X, Y is first countable or both X, Y are locally cosmic spaces. Many results on the k-space property of products of spaces with certain k-networks could be deduced from the above theorem.

  5. Analysis of the CAG repeat region of the androgen receptor gene in a kindred with X-linked spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Belsham, D D; Yee, W C; Greenberg, C R; Wrogemann, K

    1992-10-01

    Herein we describe a family with X-linked spinal and bulbar muscular atrophy (SBMA or Kennedy's disease), an adult onset neuromuscular disease characterized by slow progression, predominant proximal and bulbar muscle weakness. One frequent association is the appearance of gynecomastia. This disorder was previously shown to be linked to the locus DXYS1 on the proximal long arm of the X chromosome. Recently, a report implicated a mutation at the N-terminus of the androgen receptor gene involving amplification of CAG repeats as the cause of X-linked SBMA. We studied this region of the androgen receptor in a kindred clinically suspected but not confirmed of having X-linked SBMA by the polymerase chain reaction (PCR) followed by Southern analysis and DNA sequencing. The mutated allele was found to have an increased number of 51 CAG repeats confirming the clinical diagnosis of SBMA. Normal individuals revealed 23 repeat numbers within the normal range, while another unrelated X-linked SBMA patient had an enlarged CAG repeat region. The carrier or disease status could be established or confirmed in 12 individuals of this family on the basis of detecting normal and disease alleles reflected by the number of CAG repeats.

  6. Modularity of Plant Metabolic Gene Clusters: A Trio of Linked Genes That Are Collectively Required for Acylation of Triterpenes in Oat[W][OA

    Science.gov (United States)

    Mugford, Sam T.; Louveau, Thomas; Melton, Rachel; Qi, Xiaoquan; Bakht, Saleha; Hill, Lionel; Tsurushima, Tetsu; Honkanen, Suvi; Rosser, Susan J.; Lomonossoff, George P.; Osbourn, Anne

    2013-01-01

    Operon-like gene clusters are an emerging phenomenon in the field of plant natural products. The genes encoding some of the best-characterized plant secondary metabolite biosynthetic pathways are scattered across plant genomes. However, an increasing number of gene clusters encoding the synthesis of diverse natural products have recently been reported in plant genomes. These clusters have arisen through the neo-functionalization and relocation of existing genes within the genome, and not by horizontal gene transfer from microbes. The reasons for clustering are not yet clear, although this form of gene organization is likely to facilitate co-inheritance and co-regulation. Oats (Avena spp) synthesize antimicrobial triterpenoids (avenacins) that provide protection against disease. The synthesis of these compounds is encoded by a gene cluster. Here we show that a module of three adjacent genes within the wider biosynthetic gene cluster is required for avenacin acylation. Through the characterization of these genes and their encoded proteins we present a model of the subcellular organization of triterpenoid biosynthesis. PMID:23532069

  7. 酒酒球菌抗酒精基因RAPD标记的研究%RAPD specific molecular markers linked to alcohol resistance gene in Oenococcus oeni

    Institute of Scientific and Technical Information of China (English)

    王坐京; 李西柱; 周利国; 刘树文

    2009-01-01

    以抗酒精酒酒球菌和酒精敏性酒酒球菌为材料,提取基因组DNA构建抗性与敏性基因池,对RAPD-PCR反应体系进行优化,利用RAPD分子标记技术对45条随机引物进行筛选.结果引物S90在750bp附近扩增出了差异条带,且重复性好,这表明S90750是与酒酒球菌抗酒精基因相连锁的RAPD标记.%The study was carried out using the alcohol resistance Oenococcus oeni and the alcohol sensitive O.oeni as the material. After extracting Genomic DNA to construction resistance and the sensitive gene pools and optimizing the RAPD-PCR conditions, RAPD molecular marker technology was applied to screen in 45 random primers which were used to amplify the two types of gene pools. Only primer S90 was identified to be linked to the resistant gene nearby 750 bp, and the repeatability was good. Therefore, the RAPD markers S90750 are linked to the alcohol resistance gene in O.oeni.

  8. Mapping of a gene (MRXS9) for X-linked mental retardation, microcephaly, and variably short stature to Xq12-q21.31.

    Science.gov (United States)

    Shrimpton, A E; Daly, K M; Hoo, J J

    1999-05-28

    Three boys from two families were identified as having a syndrome of X-linked mental retardation (XLMR) with microcephaly and short stature, clinically resembling Renpenning syndrome but with normal size of testicles in affected men. When the effort to map the gene for the above condition was initiated, it was realized that the two families were actually related to each other. Over 50 polymorphic markers of known locations along the X chromosome were scored in this family in a study to map the disease gene. Nine affected and four unaffected males were genotyped to produce a maximum LOD score of 4.42 at zero recombination with markers in proximal Xq. The results indicate that the gene responsible for this disorder is located in the cytogenetic Xq12 to Xq21.31 interval of the X chromosome within a section of chromosome of about 17 cM between the AR and DXS1217 loci over some 25 mb. Since the gene for the X-linked mental retardation from the original Saskatchewan family described by Renpenning [Renpenning et al., 1962: Can Med Assoc J 87:954-956; Fox and Gerrard, 1980: Am J Med Genet 7:491-495] was recently mapped to a different nonoverlapping region [Stevenson et al., 1998: Am J Hum Genet 62:1092-1101] this would appear to be a separate disorder.

  9. Characterization of RAPD Markers, and the RFLP Marker Linked to Powdery Mildew Resistance Gene Derived from Different Accessions of H. villosa

    Institute of Scientific and Technical Information of China (English)

    LI Hui; CHEN Xiao; SHI Ai-nong; KONG Fan-jing; S Leath; J P Murphy; JIA Xu

    2005-01-01

    The analysis was carried out on performance of the resistance gene from Haynaldia villosa accession of the former Soviet Union to different isolates of Bluemerie graminis. Polymorphisms were revealed between 6D/6V substitution line Pm930640and its pedigree parents using five RAPD markers of OPAN031700, OPAI017oo, OPAL03750, OPAD07480 and OPAG1558oscreened out from 120 random 10-mers primers. Three RAPD markers of OPAN03, OPAI01 and OPAL03 were linked with the resistance gene by analysis of F2 population of Chancellor×Pm930640. Analysis of 29 wheat lines including part of lines conferring the known genes from Pm1 to Pm20 respectively, lines conferring resistance gene from two H. villosaaccessions and the related wheat parents, were analyzed and the results showed that these markers not only linked to thegene resistant to powdery mildew from H. villosa, but also detected different genetic backgrounds. OPAL03750 can beused as the marker to distinguish the different resistant lines from two H. villosa accessions because it was only observedin the materials from H. villosa of the former Soviet Union. RFLP analysis also showed the polymorphisms between twoH. villosa accessions and their derived resistant lines.

  10. X-linked Alport syndrome: an SSCP-based mutation survey over all 51 exons of the COL4A5 gene.

    Science.gov (United States)

    Renieri, A.; Bruttini, M.; Galli, L.; Zanelli, P.; Neri, T.; Rossetti, S.; Turco, A.; Heiskari, N.; Zhou, J.; Gusmano, R.; Massella, L.; Banfi, G.; Scolari, F.; Sessa, A.; Rizzoni, G.; Tryggvason, K.; Pignatti, P. F.; Savi, M.; Ballabio, A.; De Marchi, M.

    1996-01-01

    The COL4A5 gene encodes the alpha5 (type IV) collagen chain and is defective in X-linked Alport syndrome (AS). Here, we report the first systematic analysis of all 51 exons of COL4A5 gene in a series of 201 Italian AS patients. We have previously reported nine major rearrangements, as well as 18 small mutations identified in the same patient series by SSCP analysis of several exons. After systematic analysis of all 51 exons of COL4A5, we have now identified 30 different mutations: 10 glycine substitutions in the triple helical domain of the protein, 9 frameshift mutations, 4 in-frame deletions, 1 start codon, 1 nonsense, and 5 splice-site mutations. These mutations were either unique or found in two unrelated families, thus excluding the presence of a common mutation in the coding part of the gene. Overall, mutations were detected in only 45% of individuals with a certain or likely diagnosis of X-linked AS. This finding suggests that mutations in noncoding segments of COL4A5 account for a high number of X-linked AS cases. An alternative hypothesis is the presence of locus heterogeneity, even within the X-linked form of the disease. A genotype/phenotype comparison enabled us to better substantiate a significant correlation between the degree of predicted disruption of the alpha5 chain and the severity of phenotype in affected male individuals. Our study has significant implications in the diagnosis and follow-up of AS patients. PMID:8651296

  11. Linking intronic polymorphism on the CHD1-Z gene with fitness correlates in Black-tailed Godwits Limosa l. limosa

    NARCIS (Netherlands)

    Schroeder, Julia; Kentie, Rosemarie; van der Velde, Marco; Both, Christiaan; Haddrath, Oliver; Baker, Allan J.; Piersma, Theunis; Hooijmeijer, Jos C.E.W.

    2010-01-01

    We show that variation in an intronic length polymorphism in the CHD1-Z gene in Black-tailed Godwits Limosa l. limosa is associated with fitness correlates. This is the second example of the CHDZ-1 gene being correlated with fitness, a previous study having established that Moorhens Gallinula chloro

  12. Positional Cloning in Xp22 : towards the isolation of the gene involved in X-linked retinoschisis

    NARCIS (Netherlands)

    Vosse, Esther van de

    1998-01-01

    The study was aimed at the positional cloning of disease genes in Xp22.1-p22.2. To this end a YAC contig covering this region was constructed. To identify candidate genes for the diseases localised in this region exon trapping was applied. Several novel transcripts were isolated from the region, of

  13. A point mutation in the gene for asparagine-linked glycosylation 10B (Alg10b) causes nonsyndromic hearing impairment in mice (Mus musculus).

    Science.gov (United States)

    Probst, Frank J; Corrigan, Rebecca R; Del Gaudio, Daniela; Salinger, Andrew P; Lorenzo, Isabel; Gao, Simon S; Chiu, Ilene; Xia, Anping; Oghalai, John S; Justice, Monica J

    2013-01-01

    The study of mouse hearing impairment mutants has led to the identification of a number of human hearing impairment genes and has greatly furthered our understanding of the physiology of hearing. The novel mouse mutant neurological/sensory 5 (nse5) demonstrates a significantly reduced or absent startle response to sound and is therefore a potential murine model of human hearing impairment. Genetic analysis of 500 intercross progeny localized the mutant locus to a 524 kilobase (kb) interval on mouse chromosome 15. A missense mutation in a highly-conserved amino acid was found in the asparagine-linked glycosylation 10B gene (Alg10b), which is within the critical interval for the nse5 mutation. A 20.4 kb transgene containing a wildtype copy of the Alg10b gene rescued the mutant phenotype in nse5/nse5 homozygous animals, confirming that the mutation in Alg10b is responsible for the nse5/nse5 mutant phenotype. Homozygous nse5/nse5 mutants had abnormal auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and cochlear microphonics (CMs). Endocochlear potentials (EPs), on the other hand, were normal. ABRs and DPOAEs also confirmed the rescue of the mutant nse5/nse5 phenotype by the wildtype Alg10b transgene. These results suggested a defect in the outer hair cells of mutant animals, which was confirmed by histologic analysis. This is the first report of mutation in a gene involved in the asparagine (N)-linked glycosylation pathway causing nonsyndromic hearing impairment, and it suggests that the hearing apparatus, and the outer hair cells in particular, are exquisitely sensitive to perturbations of the N-linked glycosylation pathway.

  14. A point mutation in the gene for asparagine-linked glycosylation 10B (Alg10b causes nonsyndromic hearing impairment in mice (Mus musculus.

    Directory of Open Access Journals (Sweden)

    Frank J Probst

    Full Text Available The study of mouse hearing impairment mutants has led to the identification of a number of human hearing impairment genes and has greatly furthered our understanding of the physiology of hearing. The novel mouse mutant neurological/sensory 5 (nse5 demonstrates a significantly reduced or absent startle response to sound and is therefore a potential murine model of human hearing impairment. Genetic analysis of 500 intercross progeny localized the mutant locus to a 524 kilobase (kb interval on mouse chromosome 15. A missense mutation in a highly-conserved amino acid was found in the asparagine-linked glycosylation 10B gene (Alg10b, which is within the critical interval for the nse5 mutation. A 20.4 kb transgene containing a wildtype copy of the Alg10b gene rescued the mutant phenotype in nse5/nse5 homozygous animals, confirming that the mutation in Alg10b is responsible for the nse5/nse5 mutant phenotype. Homozygous nse5/nse5 mutants had abnormal auditory brainstem responses (ABRs, distortion product otoacoustic emissions (DPOAEs, and cochlear microphonics (CMs. Endocochlear potentials (EPs, on the other hand, were normal. ABRs and DPOAEs also confirmed the rescue of the mutant nse5/nse5 phenotype by the wildtype Alg10b transgene. These results suggested a defect in the outer hair cells of mutant animals, which was confirmed by histologic analysis. This is the first report of mutation in a gene involved in the asparagine (N-linked glycosylation pathway causing nonsyndromic hearing impairment, and it suggests that the hearing apparatus, and the outer hair cells in particular, are exquisitely sensitive to perturbations of the N-linked glycosylation pathway.

  15. Late blight resistance gene from Solanum ruiz-ceballosii is located on potato chromosome X and linked to violet flower colour

    Directory of Open Access Journals (Sweden)

    Śliwka Jadwiga

    2012-02-01

    Full Text Available Abstract Background Phytophthora infestans (Mont. de Bary, the causal organism of late blight, is economically the most important pathogen of potato and resistance against it has been one of the primary goals of potato breeding. Some potentially durable, broad-spectrum resistance genes against this disease have been described recently. However, to obtain durable resistance in potato cultivars more genes are needed to be identified to realize strategies such as gene pyramiding or use of genotype mixtures based on diverse genes. Results A major resistance gene, Rpi-rzc1, against P. infestans originating from Solanum ruiz-ceballosii was mapped to potato chromosome X using Diversity Array Technology (DArT and sequence-specific PCR markers. The gene provided high level of resistance in both detached leaflet and tuber slice tests. It was linked, at a distance of 3.4 cM, to violet flower colour most likely controlled by the previously described F locus. The marker-trait association with the closest marker, violet flower colour, explained 87.1% and 85.7% of variance, respectively, for mean detached leaflet and tuber slice resistance. A genetic linkage map that consisted of 1,603 DArT markers and 48 reference sequence-specific PCR markers of known chromosomal localization with a total map length of 1204.8 cM was constructed. Conclusions The Rpi-rzc1 gene described here can be used for breeding potatoes resistant to P. infestans and the breeding process can be expedited using the molecular markers and the phenotypic marker, violet flower colour, identified in this study. Knowledge of the chromosomal localization of Rpi-rzc1 can be useful for design of gene pyramids. The genetic linkage map constructed in this study contained 1,149 newly mapped DArT markers and will be a valuable resource for future mapping projects using this technology in the Solanum genus.

  16. An X-linked body color gene of the frog Rana rugosa and its application to the molecular analysis of gonadal sex differentiation.

    Science.gov (United States)

    Miura, I; Kitamoto, H; Koizumi, Y; Ogata, M; Sasaki, K

    2011-01-01

    We identified a sex-linked, recessive body color gene, presently designated w (whitish-yellow), in the frog Rana rugosa from the Iwakuni population in Western Japan. This is the first time a sex-linked body color gene was found in amphibians so far. In this population of R. rugosa, males are the heterogametic sex, but the sex chromosomes are still homomorphic. When heterozygous males (Ww), which were produced by crossing a whitish-yellow female (ww) found in the field and a wild-type male (WW) of the same population, were backcrossed to the homozygous whitish-yellow female (ww), the resultant male offspring were all wild-type, whereas the females were all whitish-yellow. This result definitely indicates that w is recessive and X-linked, and its wild-type allele W is located on the Y chromosome. Using this strain (X(w)X(w) female and X(w)Y(W) male), we found that expression of Dmrt1 and Rspo1, which are involved in testicular and ovarian differentiation in vertebrates, was higher in males and females, respectively, prior to the onset of the sexually dimorphic expression of Cyp17 and Cyp19, which are involved in biosynthesis of sex steroids and are critical markers of gonadal sex differentiation.

  17. Intra-individual conflicts between autosomal and X-linked altruistic genes: evolutionary perspectives of sex-specific grandmothering.

    Science.gov (United States)

    Seki, Motohide

    2012-07-07

    Alloparental care by females toward their grandoffspring can evolve by kin selection. Previous theoretical studies predicted that selection favors autosomal and X-chromosomal genes, causing altruism toward maternal grandoffspring and paternal granddaughters, respectively, and two corresponding types of biased grandparental investment are suggested by empirical studies on human populations. Using discrete-time two-locus-two-allele models, I examined a possible conflict between the autosomal and the X-chromosomal altruistic genes over the carrier female's time and resources. This conflict is expected to occur when each grandmother has access to only maternal or paternal grandchildren as a result of her residence situation. The conditions under which each or both kinds of altruistic genes evolve (against non-altruistic genes) mainly represent the conflicting relationship between the autosomal and X-chromosomal altruistic genes. In addition, depending on the settings, the models exhibit bistable or periodic behaviors, and one type of gene can be considered parasitic in the latter behavior. On the whole, the results suggest that the X-chromosomal altruistic genes rather than the autosomal ones exhibit more difficulty increasing or fixing with this kind of conflict.

  18. Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family

    Directory of Open Access Journals (Sweden)

    Balda Maria S

    2009-12-01

    Full Text Available Abstract Background Tight junctions are an intercellular adhesion complex of epithelial and endothelial cells, and form a paracellular barrier that restricts the diffusion of solutes on the basis of size and charge. Tight junctions are formed by multiprotein complexes containing cytosolic and transmembrane proteins. How these components work together to form functional tight junctions is still not well understood and will require a complete understanding of the molecular composition of the junction. Results Here we identify a new transmembrane component of tight junctions: MarvelD3, a four-span transmembrane protein. Its predicted transmembrane helices form a Marvel (MAL and related proteins for vesicle traffic and membrane link domain, a structural motif originally discovered in proteins involved in membrane apposition and fusion events, such as the tight junction proteins occludin and tricellulin. In mammals, MarvelD3 is expressed as two alternatively spliced isoforms. Both isoforms exhibit a broad tissue distribution and are expressed by different types of epithelial as well as endothelial cells. MarvelD3 co-localises with occludin at tight junctions in intestinal and corneal epithelial cells. RNA interference experiments in Caco-2 cells indicate that normal MarvelD3 expression is not required for the formation of functional tight junctions but depletion results in monolayers with increased transepithelial electrical resistance. Conclusions Our data indicate that MarvelD3 is a third member of the tight junction-associated occludin family of transmembrane proteins. Similar to occludin, normal expression of MarvelD3 is not essential for the formation of functional tight junctions. However, MarvelD3 functions as a determinant of epithelial paracellular permeability properties.

  19. Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol

    Energy Technology Data Exchange (ETDEWEB)

    Akane, Hirotoshi [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Saito, Fumiyo [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Shiraki, Ayako [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Takeyoshi, Masahiro; Imatanaka, Nobuya [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Itahashi, Megu [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Murakami, Tomoaki [Laboratory of Veterinary Toxicology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

    2014-09-01

    We previously found that the 28-day oral toxicity study of glycidol at 200 mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cere