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Gene Locus (gene + locus)
Selected AbstractsExpression of individual immunoglobulin genes occurs in an unusual system consisting of multiple independent lociEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2004Donna Abstract Humoral immunity is effected through the rearrangement of immunoglobulin (Ig) genes in individual somatic cells committed to the B,lymphocyte lineage. Haplotype or allelic exclusion restricts B,lymphocytes to the expression of a single Ig receptor that can sustain further somatic modification. In most species, a specific Ig chain is encoded at a single genetic locus. However, in cartilaginous fish, hundreds of independent Ig heavy- (IgH) and Ig light-chain (IgL) gene loci are present, many of which are joined in the germ line. Ig gene transcripts have been amplified from single peripheral blood lymphocytes isolated from the clearnose skate (Raja eglanteria) using reverse-transcription PCR, and a single productive IgH transcript was detected in the majority of cells analyzed. Similarly, only a single IgL transcript was detected in over half of the individual cells. Taken together, these findings suggest that a mechanism for haplotype exclusion arose early in the evolution of antibody diversity and is independent of a single genetic locus. [source] Identification of a Chr 11 quantitative trait locus that modulates proliferation in the rostral migratory stream of the adult mouse brainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2010Anna Poon Abstract Neuron production takes place continuously in the rostral migratory stream (RMS) of the adult mammalian brain. The molecular mechanisms that regulate progenitor cell division and differentiation in the RMS remain largely unknown. Here, we surveyed the mouse genome in an unbiased manner to identify candidate gene loci that regulate proliferation in the adult RMS. We quantified neurogenesis in adult C57BL/6J and A/J mice, and 27 recombinant inbred lines derived from those parental strains. We showed that the A/J RMS had greater numbers of bromodeoxyuridine-labeled cells than that of C57BL/6J mice with similar cell cycle parameters, indicating that the differences in the number of bromodeoxyuridine-positive cells reflected the number of proliferating cells between the strains. AXB and BXA recombinant inbred strains demonstrated even greater variation in the numbers of proliferating cells. Genome-wide mapping of this trait revealed that chromosome 11 harbors a significant quantitative trait locus at 116.75 ± 0.75 Mb that affects cell proliferation in the adult RMS. The genomic regions that influence RMS proliferation did not overlap with genomic regions regulating proliferation in the adult subgranular zone of the hippocampal dentate gyrus. On the contrary, a different, suggestive locus that modulates cell proliferation in the subgranular zone was mapped to chromosome 3 at 102 ± 7 Mb. A subset of genes in the chromosome 11 quantitative trait locus region is associated with neurogenesis and cell proliferation. Our findings provide new insights into the genetic control of neural proliferation and an excellent starting point to identify genes critical to this process. [source] Root and butt rot of Todo fir (Abies sachalinensis) caused by Heterobasidion annosum s.l. in Hokkaido, JapanFOREST PATHOLOGY, Issue 3 2007S. Tokuda Summary The occurrence and symptoms of root and butt rot were examined in a 35 × 30 m plot of 68-year-old Todo fir plantation in Hokkaido, Japan. Forty-seven percent of the cut stumps were decayed and 52% of the decayed stumps showed similar decay characteristics with yellowish orange to light brown colouration and expanded pockets in the heartwood. Morphological characteristics of the pure cultures isolated from the decay were similar to the cultures isolated from basidiocarps of Heterobasidion annosum sensu lato, found on fallen logs outside of the research site. Also DNA analysis based on the combined data set of three gene loci (glyceraldehyde 3-phosphate dehydrogenase, heat shock protein 80,1 and elongation factor 1-alpha genes) showed that the isolates from the decay are included in the same clade with the Japanese H. annosum s.l. isolates. They form a subclade to H. parviporum (the European S group of H. annosum s.l.). This is the first report of molecular determination of H. annosum s.l. isolated from root and butt rot in a plantation in Japan. [source] Simultaneous localization of two linked disease susceptibility genesGENETIC EPIDEMIOLOGY, Issue 1 2005Joanna M. Biernacka Abstract For diseases with complex genetic etiology, more than one susceptibility gene may exist in a single chromosomal region. Extending the work of Liang et al. ([2001] Hum. Hered. 51:64,78), we developed a method for simultaneous localization of two susceptibility genes in one region. We derived an expression for expected allele sharing of an affected sib pair (ASP) at each point across a chromosomal segment containing two susceptibility genes. Using generalized estimating equations (GEE), we developed an algorithm that uses marker identical-by-descent (IBD) sharing in affected sib pairs to simultaneously estimate the locations of the two genes and the mean IBD sharing in ASPs at these two disease loci. Confidence intervals for gene locations can be constructed based on large sample approximations. Application of the described methods to data from a genome scan for type 1 diabetes (Mein et al. [1998] Nat. Genet. 19:297,300) yielded estimates of two putative disease gene locations on chromosome 6, approximately 20 cM apart. Properties of the estimators, including bias, precision, and confidence interval coverage, were studied by simulation for a range of genetic models. The simulations demonstrated that the proposed method can improve disease gene localization and aid in resolving large peaks when two disease genes are present in one chromosomal region. Joint localization of two disease genes improves with increased excess allele sharing at the disease gene loci, increased distance between the disease genes, and increased number of affected sib pairs in the sample. Genet. Epidemiol. © 2004 Wiley-Liss, Inc. [source] Aldehyde oxidase is coamplified with the World's most common Culex mosquito insecticide resistance-associated esterasesINSECT MOLECULAR BIOLOGY, Issue 1 2000J. Hemingway Abstract The evolution and spread of insecticide resistance is an important factor in human disease prevention and crop protection. The mosquito Culex quinquefasciatus is the main vector of the disease filariasis and a member of a species complex which is a common biting nuisance worldwide. The common insecticide resistance mechanism in this species involves germline amplification of the esterases est,21 and est,21. This amplification has arisen once and rapidly spread worldwide. Less common and more variable resistance phenotypes involve coamplification of est,3 and est,1, or individual amplification of a single est,1, different alleles of the same est, and est, gene loci. Est,21 and est,21 are on the same large fragment of amplified DNA (amplicon) 2.7 kb apart. We have now shown that this amplicon contains another full-length gene immediately 5, of est,21 which codes for a molybdenum-containing hydroxylase, with highest homology to aldehyde oxidase (AO) from other organisms. The full-length putative AO gene is not present on the est,3/est,1 or est,1 amplicons, but multiple truncated 5, ends of this gene are present around the presumed est,3/est,1 amplicon breakpoint. Polymerase chain reaction (PCR) analysis of insecticide-susceptible genomic DNA demonstrated that a different allele of the putative AO gene in its non-amplified form is immediately 5, of est,. The ,AO' gene on the est,21/est,21 amplicon is expressed and resistant insects have greater AO activity. This AO activity is sensitive to inhibition by an aldehyde-containing herbicide and pesticide. This enzyme may confer a selective advantage to these insects in the presence of insecticide, as AO in mammals is believed to be important in the detoxification process of several environmental pollutants. [source] Distinct CpG island methylation profiles and BRAF mutation status in serrated and adenomatous colorectal polypsINTERNATIONAL JOURNAL OF CANCER, Issue 11 2008Yong Ho Kim Abstract A subset of colorectal cancers with CpG island methylator phenotype-high (CIMP-H) is frequently associated with MSI and BRAF V600E mutation. Since limited data are available on different histological types of colorectal polyps, we compared the pattern and the frequency of promoter methylation, CIMP-H, MSI, KRAS and BRAF V600E mutations and the relationship among these molecular parameters and the clinicopathologic characteristics in 110 serrated polyps (48 hyperplastic polyps, 32 sessile serrated adenomas and 30 serrated adenomas) and 32 tubular adenomas using 7 commonly used tumor-associated gene loci. No significant difference in the frequency of overall methylation frequency (86% vs. 100%) and CIMP-H (39% vs. 28%) between serrated polyps and tubular adenomas was observed, but proximally located serrated polyps showed more frequent methylation at 5 of 7 loci examined, and were more likely to be CIMP-H (62% vs. 22%). MGMT methylation was more common in tubular adenomas while MLH1 and HIC1 were more frequently methylated in serrated polyps. BRAF mutation was frequently present in all types of serrated polyps (80%), but was absent in tubular adenomas and was not associated with CIMP or MSI status. These results show comparable frequencies of promoter methylation of tumor-associated genes and CIMP-H, but distinct differences in gene-specific or colonic site-specific methylation profiles occur in serrated polyps and tubular adenomas. BRAF mutation occurs independently of CIMP and MSI in all types of serrated polyps and may serve as a marker of serrated pathway of colorectal carcinogenesis. © 2008 Wiley-Liss, Inc. [source] Analysis of chimerism during the early period after allogeneic peripheral stem cell transplantationINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2001B. Gleissner As there are few reports on early evaluation of chimerism, we assessed fluorescence short tandem repeats (STR) by polymerase chain reaction (PCR) assays to analyse donor and recipient characteristics at early time points after peripheral stem cell transplantation (PBSCT). Peripheral blood of 13 patients was analysed in 1- to 2-day intervals starting from the day of PBSCT. Donor and recipient allelic patterns were determined by a commercially available multiplex STR assay that simultaneously evaluates four or five gene loci. Mixed chimerism appeared in all patients during days 1,9 after transplantation and preceded haematologic engraftment for 3,12 days. Even patients without myeloablative conditioning therapy (n=4) revealed donor allelic patterns within 1,5 days. Nine patients changed during the following days to a complete donor allelic pattern and had an uncomplicated post-transplant disease course. Four patients did not consistently retain complete donor chimerism; two of them relapsed within the next 3 months, one died from septicemia within 7 days, and the fourth, transplanted for aplastic anaemia, is still in complete remission. Overall, STR analysis using a simple and comparatively cheap multiplex system permits the detection of chimerism very early after transplantation and may provide relevant information that correlates with the clinical follow-up. [source] Myogenic regulatory factors Myf5 and Mrf4 of fish: current status and perspectiveJOURNAL OF FISH BIOLOGY, Issue 8 2008Y. H. Chen Recent advances in the understanding of fish myogenic regulatory factors (MRF) are described in this review. Specifically, two of the MRFs are discussed, Myf5 and Mrf4, which are encoded by a highly linked gene loci (mrf4 and myf5) that is conserved among vertebrates. Experiments related to the expression patterns, biological functions and regulatory network of mrf4 and myf5 are highlighted, and examples of gene organizations and protein features among known vertebrate species are outlined. Furthermore, the complicated regulatory mechanisms of myf5 are discussed using zebrafish Danio rerio as a model. Multiple regulatory elements that control the specific expression of zebrafish myf5 are elucidated, including enhancer, silencer, proximal and distal elements, the interaction between proximal regulatory cassette ,82/,62 and its cognate binding transcription factors, and a plausible post-transcriptional regulatory mechanism. This review article highlights a fundamental molecular mechanism of mrf4 and myf5 during fish muscle development. [source] Comparative analysis of the within-population genetic structure in wild cherry (Prunus avium L.) at the self-incompatibility locus and nuclear microsatellitesMOLECULAR ECOLOGY, Issue 11 2006SILVIO SCHUELER Abstract Gametophytic self-incompatibility (SI) systems in plants exhibit high polymorphism at the SI controlling S -locus because individuals with rare alleles have a higher probability to successfully pollinate other plants than individuals with more frequent alleles. This process, referred to as frequency-dependent selection, is expected to shape number, frequency distribution, and spatial distribution of self-incompatibility alleles in natural populations. We investigated the genetic diversity and the spatial genetic structure within a Prunus avium population at two contrasting gene loci: nuclear microsatellites and the S -locus. The S -locus revealed a higher diversity (15 alleles) than the eight microsatellites (4,12 alleles). Although the frequency distribution of S -alleles differed significantly from the expected equal distribution, the S -locus showed a higher evenness than the microsatellites (Shannon's evenness index for the S -locus: E = 0.91; for the microsatellites: E = 0.48,0.83). Also, highly significant deviations from neutrality were found for the S -locus whereas only minor deviations were found for two of eight microsatellites. A comparison of the frequency distribution of S -alleles in three age-cohorts revealed no significant differences, suggesting that different levels of selection acting on the S -locus or on S- linked sites might also affect the distribution and dynamics of S -alleles. Autocorrelation analysis revealed a weak but significant spatial genetic structure for the multilocus average of the microsatellites and for the S -locus, but could not ascertain differences in the extent of spatial genetic structure between these locus types. An indirect estimate of gene dispersal, which was obtained to explain this spatial genetic pattern, indicated high levels of gene dispersal within our population (,g = 106 m). This high gene dispersal, which may be partly due to the self-incompatibility system itself, aids the effective gene flow of the microsatellites, thereby decreasing the contrast between the neutral microsatellites and the S -locus. [source] Statistical power when testing for genetic differentiationMOLECULAR ECOLOGY, Issue 10 2001N. Ryman Abstract A variety of statistical procedures are commonly employed when testing for genetic differentiation. In a typical situation two or more samples of individuals have been genotyped at several gene loci by molecular or biochemical means, and in a first step a statistical test for allele frequency homogeneity is performed at each locus separately, using, e.g. the contingency chi-square test, Fisher's exact test, or some modification thereof. In a second step the results from the separate tests are combined for evaluation of the joint null hypothesis that there is no allele frequency difference at any locus, corresponding to the important case where the samples would be regarded as drawn from the same statistical and, hence, biological population. Presently, there are two conceptually different strategies in use for testing the joint null hypothesis of no difference at any locus. One approach is based on the summation of chi-square statistics over loci. Another method is employed by investigators applying the Bonferroni technique (adjusting the P -value required for rejection to account for the elevated alpha errors when performing multiple tests simultaneously) to test if the heterogeneity observed at any particular locus can be regarded significant when considered separately. Under this approach the joint null hypothesis is rejected if one or more of the component single locus tests is considered significant under the Bonferroni criterion. We used computer simulations to evaluate the statistical power and realized alpha errors of these strategies when evaluating the joint hypothesis after scoring multiple loci. We find that the ,extended' Bonferroni approach generally is associated with low statistical power and should not be applied in the current setting. Further, and contrary to what might be expected, we find that ,exact' tests typically behave poorly when combined in existing procedures for joint hypothesis testing. Thus, while exact tests are generally to be preferred over approximate ones when testing each particular locus, approximate tests such as the traditional chi-square seem preferable when addressing the joint hypothesis. [source] Data protection in biomaterial banks for Parkinson's disease research: The model of GEPARD (Gene bank Parkinson's Disease Germany)MOVEMENT DISORDERS, Issue 5 2007Karla Eggert MD Abstract Parkinson's disease (PD) is the second most common neurodegenerative disease. Although 10 gene loci have been identified to cause a Parkinsonian syndrome, these loci account only for a minority of PD patients. Large, systematic research programs are required to collect, store, and analyze DNA samples and clinical information to support further discovery of additional genetic components of PD or other movement disorders. Such programs facilitate research into the relationship between genotype and phenotype. The German Competence Network on Parkinson's disease (CNP) initiated the Gene Bank Parkinson's Disease Germany (GEPARD), providing an administrative and scientific infrastructure for the storage of DNA and clinical data that are electronically accessible and protective of patient rights. In this article, we offer guidance on how to establish a framework for a clinical genetic data and DNA bank, and describe GEPARD as a model that may be useful to other local, national, and international research groups developing similar programs. © 2006 Movement Disorder Society [source] Familial fibronectin glomerulopathy: analysis of chromosome 1q32 and uteroglobin gene loci in a large New Zealand familyNEPHROLOGY, Issue 5 2001Robert Walker SUMMARY: Recently, a newly recognized familial glomerulopathy with predominant fibronectin deposits has been reported. This is the first report of a family with this condition in Australasia and spans two generations over a 30-year period, with the histologically confirmed glomerulopathy present in the father and five out of eight siblings. The clinical presentations have ranged from asymptomatic proteinuria, pregnancy-associated proteinuria and the nephrotic syndrome to hypertension and proteinuria with progressive renal failure. The time-course from presentation to renal failure was over a 20 years. Histology demonstrated global and diffuse thickening of capillary loops, but no cellular proliferation. Immunofluorescence demonstrated granular positivity for IgM in the capillary loops only. Electron microscopy demonstrated massive electron-dense subendothelial granular deposits with occasional small fibrils and unremarkable epithelial cell foot processes. Immunohistochemical staining was strongly positive for fibronectin and negative for type I or type IV collagen and transforming growth factor , in all biopsies. Genetic studies of familial fibronectin glomerulopathy have recently highlighted two genetic loci. Firstly, a large five-generation pedigree has been described with linkage of fibronectin glomerulopathy to chromosome 1q32. Secondly, fibronectin glomerulopathy has been reported in uteroglobin gene knockout mice. In our studies, DNA sequence analysis of the uteroglobin gene showed that it was normal in all family members, and a DNA polymorphism in the uteroglobin gene did not co-segregate with the disease. In addition, DNA microsatellite markers at the 1q32 locus did not co-segregate with the disease in our family. We presume that the underlying abnormality involves as yet undefined glomerular extracellular matrix regulation and is inherited as an autosomal dominant condition. These data favour genetic heterogeneity for the aetiology of fibronectin glomerulopathy. [source] Role of candidate genes in the responses to long-term overfeeding: review of findingsOBESITY REVIEWS, Issue 1 2004O. Ukkola Summary An overfeeding experiment conducted with 12 pairs of young male identical twins revealed that genetic factors were likely to play an important role in the response to caloric affluence. Significant intrapair resemblance was observed for the overfeeding-induced changes in body weight, fat mass, abdominal fat, fasting insulin, fasting cholesterol and triglycerides. In an attempt to define the molecular basis of these genotype,energy balance interaction effects, a panel of candidate genes has been investigated. Among the most significant findings, an adipsin polymorphism was associated with increases in body weight, total fat mass and subcutaneous fat in response to overfeeding. In addition, the beta2 adrenergic receptor gene Gln27Glu polymorphism showed a strong association with the gains in body weight and subcutaneous fat. Only a few markers were related to abdominal fat changes and, among them, the adipsin Hinc II polymorphism was associated with both computed tomography (CT)-measured abdominal visceral and total fat. The changes in insulin parameters brought about by long-term overfeeding were influenced most consistently by leptin receptor (LEPR) Gln223Arg and insulin-like growth factor-II Apa I polymorphisms. The LEPR Gln223Arg variant was also associated with the changes in plasma total triglycerides and high-density lipoprotein cholesterol concentrations. Further research with larger sample sizes should make it possible to identify the specific contributions of DNA sequence variations at multiple candidate gene loci in the complex response to chronic positive energy balance. [source] Novel recombinant congenic mouse strain developing arthritis with enthesopathyPATHOLOGY INTERNATIONAL, Issue 7 2008Shiro Mori Based on the hypothesis that the complex pathological and immunological manifestations of rheumatoid arthritis (RA) and the related diseases are under the control of multiple gene loci with allelic polymorphism, a recombinant congenic mouse strain was prepared between an MRL/Mp- lpr/lpr (MRL/lpr) strain, which develops arthritis resembling RA, and a non-arthritic strain C3H/HeJ- lpr/lpr (C3H/lpr). In MRL/lpr × (MRL/lpr × C3H/lpr) F1 mice, the mice developing severe arthritis were selected based on joint swelling to further continue intercrosses, and then an McH- lpr/lpr -RA1 (McH/lpr-RA1) strain was established and its histopathological phenotypes of joints and autoimmune traits were analyzed. Arthritis in McH/lpr-RA1 mice developed at a higher incidence by 20 weeks of age, compared with that in the MRL/lpr mice, who had severe synovitis (ankle, 60.3%; knee, 65.1%), and also fibrous and fibrocartilaginous lesions of articular ligamenta resembling enthesopathy (ankle, 79.4%; knee, 38.1%), resulting in ankylosis. The lymphoproliferative disorder was less, and serum levels of IgG and IgG autoantibodies including anti-dsDNA and rheumatoid factor were lower than those of both MRL/lpr and C3H/lpr strains. McH/lpr-RA1 mice may provide a new insight into the study of RA regarding the common genomic spectrum of seronegative RA and enthesopathy. [source] Development of yellow-seeded Brassica napus of double low qualityPLANT BREEDING, Issue 6 2001M. H. Rahman Abstract Two yellow-seeded white-petalled Brassica napus F7 inbred lines, developed from interspecific crosses, containing 26,28% emcic acid and more than 40 ,mol glucosinolates (GLS)/g seed were crossed with two black/dark brown seeded B. napus varieties of double low quality and 287 doubled haploid (DH) lines were produced. The segregation in the DH lines indicated that three to four gene loci are involved in the determination of seed colour, and yellow seeds are formed when all alleles in all loci are in the homozygous recessive state. A dominant gene governed white petal colour and is linked with an erucic acid allele that, in the homozygous condition, produces 26,28% erucic acid. Four gene loci are involved in the control of total GLS content where low GLS was due to the presence of recessive alleles in the homozygous condition in all loci. From the DH breeding population a yellow-seeded, yellow-petalled, zero erucic acid line was obtained. This line was further crossed with conventional B. napus varieties of double low quality and, following pedigree selection, a yellow seeded B. napus of double low quality was obtained. The yellow seeds had higher oil plus protein content and lower fibre content than black seeds. A reduction of the concentration of chromogenic substances was found in the transparent seed coat of the yellow-seeded B. napus. [source] Mapping of quantitative trait loci affecting behaviour in swineANIMAL GENETICS, Issue 4 2009G. Reiner Summary Behavioural indices in vertebrates are under genetic control at least to some extent. In spite of significant behavioural problems in farm animals, information on the genetic background of behaviour is sparse. The aim of this study was to map QTL for behavioural indices in swine under healthy conditions and after infection with Sarcocystis miescheriana, as behaviour can be significantly influenced by disease. This well-described parasite model subsequently leads to acute (day 14 p.i.), subclinical (day 28 p.i.) and chronic disease (day 42 p.i.), allowing the study and comparison of the behaviour of pigs under four different states of health or disease. The study was based on a well-described Pietrain/Meishan F2 family that has recently allowed the detection of QTL for disease resistance. We have mapped six genome-wide significant and 24 chromosome-wide significant QTL for six behavioural indices in swine. Six of these QTL (i.e. 20% of total QTL) showed effects on behavioural traits of the healthy pigs (day 0). Some of them (QTL on SSC11 and 18) lost influence on behavioural activities during disease, while the effects of others (QTL on SSC5, SSC8) partly remained during the whole experiment, although with different effects on the distinct behavioural indices. The disease model has been of high relevance to detect effects of gene loci on behavioural indices. Considering the importance of segregating alleles and environmental conditions that allow the identification of the phenotype, we conclude that there are indeed QTL with interesting effects on behavioural indices in swine. [source] The effects of polymorphisms in the DGAT1, leptin and growth hormone receptor gene loci on body energy, blood metabolic and reproductive traits of Holstein cowsANIMAL GENETICS, Issue 1 2009G. Oikonomou Summary The objective of this study was to examine the impact of polymorphisms in the acyl-CoA:diacylglycerol acyltransferase (DGAT1), leptin and growth hormone receptor genes on body energy (body condition score, total body energy content and cumulative effective energy balance) and blood metabolic traits (levels of ,-hydroxybutyrate, glucose and non-esterified fatty acids), measured once before the first calving and then repeatedly throughout first lactation in 497 Holstein cows. The influence of the same polymorphisms on cow reproductive performance and health during the first and second lactations was also assessed. Several reproductive traits were considered including interval, conception and insemination traits, as well as incidence of metritis and reproductive problems. Genotyping was performed using PCR-RFLP (DGAT1, leptin) or allele-specific PCR (growth hormone receptor). For each locus, the effect of allele substitution on body energy and blood metabolic traits was estimated using random regression models. The same effect on reproductive traits was assessed with single-trait mixed linear models. Significant (P < 0.05) effects on specific reproductive traits were observed. DGAT1 and growth hormone receptor alleles responsible for significant increases in milk production were found to have an adverse effect on reproduction, while the leptin allele responsible for significant increase in milk production was linked to marginally increased metritis frequency. Furthermore, the three studied loci were also found to significantly (P < 0.05) affect certain body energy and blood metabolic traits. Several associations are published for the first time, but these should be confirmed by other investigators before the polymorphisms are used in gene-assisted selection. [source] Location analysis of DNA-bound proteins at the whole-genome level: untangling transcriptional regulatory networksBIOESSAYS, Issue 6 2001Béatrice Nal In this post-sequencing era, geneticists can focus on functional genomics on a much larger scale than ever before. One goal is the discovery and elucidation of the intricate genetic networks that co-ordinate transcriptional activation in different regulatory circuitries. High-throughput gene expression measurement using DNA arrays has thus become routine strategy. This approach, however, does not directly identify gene loci that belong to the same regulatory group; e.g., those that are bound by a common (set of) transcription factor(s). Working in yeast, two groups have recently published an elegant method that could circumvent this problem, by combining chromatin immunoprecipitation and DNA microarrays.(1,2) The method is likely to provide a powerful tool for the dissection of global regulatory networks in eukaryotic cells. BioEssays 23:473,476, 2001. © 2001 John Wiley & Sons, Inc. [source] Unravelling evolutionary lineages among South African velvet worms (Onychophora: Peripatopsis) provides evidence for widespread cryptic speciationBIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 1 2009SAVEL R. DANIELS The endemic South African velvet worm genus Peripatopsis currently contains eight recognized species described from variable morphological characters and the current taxonomy is unsatisfactory. In an attempt to investigate evolutionary relationships within Peripatopsis, we collected 137 individuals from 34 sample localities for six of the eight species. Sequence data derived from two partial mitochondrial (mt)DNA gene loci (COI and 12S rRNA), as well as partial sequence data from the ribosomal nuclear 18S rDNA locus in combination with gross morphological characters and scanning electron microscopy (SEM), was used to examine evolutionary relationships. Phylogenetic relationships were investigated using minimum evolution (ME) and Bayesian inferences (BI). Additionally, we also undertook a maximum likelihood (ML) analyses on the combined DNA sequence data set. The combined DNA evidence topologies derived from the ME, BI, and ML was highly congruent and was characterized by the presence of multiple lineages within recognized taxa. Peripatopsis clavigera, Peripatopsis moseleyi, and Peripatopsis sedgwicki each comprised two evolutionary lineages; Peripatopsis capensis comprised three; and Peripatopsis balfouri comprised six operational taxonomic units respectively. Genealogical exclusivity at both mtDNA and nuclear DNA among the geographically coherent groups coupled with pronounced sequence divergence suggested a two-fold increase in the number of species within Peripatopsis. Previously used gross morphological characters (such as the number of leg pairs and colour) were either highly variable within operational taxonomic units, or were invariant, suggesting that alternative morphological characters are necessary for species discrimination. SEM results revealed potentially useful diagnostic characters that can discriminate between at least discriminate some of the newly-identified lineages. © 2009 The Linnean Society of London, Biological Journal of the Linnean Society 2009, 97, 200,216. [source] Multiple origins of symbioses between ascomycetes and bryophytes suggested by a five-gene phylogenyCLADISTICS, Issue 3 2010Soili Stenroos Numerous species of microscopic fungi inhabit mosses and hepatics. They are severely overlooked and their identity and nutritional strategies are mostly unknown. Most of these bryosymbiotic fungi belong to the Ascomycota. Their fruit-bodies are extremely small, often reduced and simply structured, which is why they cannot be reliably identified and classified by their morphological and anatomical characters. A phylogenetic hypothesis of bryosymbiotic ascomycetes is presented. New sequences of 78 samples, including 61 bryosymbionts, were produced, the total amount of terminals being 206. Of these, 202 are Ascomycetes. Sequences from the following five gene loci were used: rDNA SSU, rDNA LSU, RPB2, mitochondrial rDNA SSU, and rDNA 5.8S. The program TNT was used for tree search and support value estimation. We show that bryosymbiotic fungi occur in numerous lineages, one of which represents a newly discovered lineage among the Ascomycota and exhibits a tripartite association with cyanobacteria and sphagna. A new genus Trizodia is proposed for this basal clade. Our results demonstrate that even highly specialized life strategies can be adopted multiple times during evolution, and that in many cases bryosymbionts appear to have evolved from saprobic ancestors. ,© The Willi Hennig Society 2009. [source] The chemotaxis defect of Shwachman-Diamond Syndrome leukocytesCYTOSKELETON, Issue 3 2004Vesna Stepanovic Abstract Shwachman-Diamond Syndrome (SDS) is a rare autosomal recessive, multisystem disorder presenting in childhood with intermittent neutropenia and pancreatic insufficiency. It is characterized by recurrent infections independent of neutropenia, suggesting a functional neutrophil defect. While mutations at a single gene locus (SBDS) appear to be responsible for SDS in a majority of patients, the function of that gene and a specific defect in SDS neutrophil behavior have not been elucidated. Therefore, employing 2D and 3D computer-assisted motion analysis systems, we have analyzed the basic motile behavior and chemotactic responsiveness of individual polymorphonuclear leukocytes (PMNs) of 14 clinically diagnosed SDS patients. It is demonstrated that the basic motile behavior of SDS PMNs is normal in the absence of chemoattractant, that SDS PMNs respond normally to increasing and decreasing temporal gradients of the chemoattractant fMLP, and that SDS PMNs exhibit a normal chemokinetic response to a spatial gradient of fMLP. fMLP receptors were also distributed uniformly through the plasma membrane of SDS PMNs as in control PMNs. SDS PMNs, however, were incapable of orienting in and chemotaxing up a spatial gradient of fMLP. This unique defect in orientation was manifested by the PMNs of every SDS patient tested. The PMNs of an SDS patient who had received an allogenic hematopoietic stem cell transplant, as well as PMNs from a cystic fibrosis patient, oriented normally. These results suggest that the defect in SDS PMNs is in a specific pathway emanating from the fMLP receptor that is involved exclusively in regulating orientation in response to a spatial gradient of fMLP. This pathway must function in parallel with additional pathways, intact in SDS patients, that emanate from the fMLP receptor and regulate responses to temporal rather than spatial changes in receptor occupancy. Cell Motil. Cytoskeleton 57:158,174, 2004. © 2004 Wiley-Liss, Inc. [source] Hoxb3 vagal neural crest-specific enhancer element for controlling enteric nervous system developmentDEVELOPMENTAL DYNAMICS, Issue 2 2005Kwok Keung Chan Abstract The neural and glial cells of the intrinsic ganglia of the enteric nervous system (ENS) are derived from the hindbrain neural crest at the vagal level. The Hoxb3 gene is expressed in the vagal neural crest and in the enteric ganglia of the developing gut during embryogenesis. We have identified a cis -acting enhancer element b3IIIa in the Hoxb3 gene locus. In this study, by transgenic mice analysis, we examined the tissue specificity of the b3IIIa enhancer element using the lacZ reporter gene, with emphasis on the vagal neural crest cells and their derivatives in the developing gut. We found that the b3IIIa-lacZ transgene marks only the vagal region and not the trunk or sacral region. Using cellular markers, we showed that the b3IIIa-lacZ transgene was expressed in a subset of enteric neuroblasts during early development of the gut, and the expression was maintained in differentiated neurons of the myenteric plexus at later stages. The specificity of the b3IIIa enhancer in directing gene expression in the developing ENS was further supported by genetic analysis using the Dom mutant, a spontaneous mouse model of Hirschsprung's disease characterized by the absence of enteric ganglia in the distal gut. The colonization of lacZ -expressing cells in the large intestine was incomplete in all the Dom/b3IIIa-lacZ hybrid mutants we examined. To our knowledge, this is the only vagal neural crest-specific genetic regulatory element identified to date. This element could be used for a variety of genetic manipulations and in establishing transgenic mouse models for studying the development of the ENS. Developmental Dynamics 233:473,483, 2005. © 2005 Wiley-Liss, Inc. [source] Breeding for resistance: conventional breeding for Plum pox virus resistant apricots (Prunus armeniaca L.) in GreeceEPPO BULLETIN, Issue 2 2006I. Karayiannis A large apricot breeding programme has been conducted at NAGREF-Pomology Institute, Naoussa-Greece, for the control of sharka disease, since 1989. Ten apricot cultivars of North American origin: ,Stark Early Orange', ,Stella', ,NJA2', ,Sunglo', ,Veecot', ,Harlayne', ,Henderson', ,Goldrich', ,Orangered' and ,Early Blush', selected for their resistance to the highly virulent local strain of Plum pox virus (PPV)-M (Marcus), have been used as parents in crosses with quality cultivars, mainly with the local cv. Bebecou, from 1989 to 2003. Approximately 7000 hybrids have been created. Resistance to PPV was the main criterion of selection. Most hybrids have been subjected to artificial inoculation by PPV-M and examined for symptom expression for more than five years. Indexing to GF-305, as well as laboratory diagnostic tests, have been applied. The genetic analysis showed that: (1) 50% of the hybrids inherited resistance to PPV in the families where cvs. Stark Early Orange, NJA2, Sunglo, Veecot and Harlayne were used as a parent, and (2) 100% of the hybrids inherited resistance to PPV in the families where cv. Stella was one of the parents. Resistance to PPV appears to be under simple genetic control involving one gene locus. Promising apricot selections resistant to PPV-M have been released. [source] Loss of FOXP3 expression in natural human CD4+CD25+ regulatory T cells upon repetitive in vitro stimulationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2009Petra Hoffmann Abstract The adoptive transfer of CD4+CD25+ natural regulatory T cells (Treg) is a promising strategy for the treatment of autoimmune diseases and the prevention of alloresponses after transplantation. Clinical trials exploring this strategy require efficient in vitro expansion of this rare cell population. Protocols developed thus far rely on high-grade purification of Treg prior to culture initiation, a process still hampered by the lack of Treg cell-specific surface markers. Depletion of CD127+ cells was shown to separate activated conventional T cells from natural Treg cell populations allowing the isolation of highly enriched FOXP3+ cells with all functional and molecular characteristics of natural Treg. Here, we demonstrate that upon in vitro expansion, CpG methylation in a conserved region within the FOXP3 gene locus increased in CD4+CD25+CD127low Treg, correlating with loss of FOXP3 expression and emergence of pro-inflammatory cytokines. Further analysis identified CD45RA,FOXP3+ memory-type Treg as the main source of converting cells, whereas CD45RA+FOXP3+ Treg from the same donors showed no conversion within 3,wk of in vitro expansion. Thus, Treg cell lineage differentiation does not seem to represent a final fate decision, as natural Treg can lose their cell-type-specific characteristics after repetitive TCR stimulation. [source] Inhibition of Notch signaling biases rat thymocyte development towards the NK cell lineageEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2004Jens van den Brandt Abstract Notch receptors are involved in directing the choice between alternative cell fates in developmental scenarios such as thymopoiesis. By pharmacological interference in rat fetal thymus organ culture we show that inhibition of Notch signaling arrests T,cell development at an early double-negative stage and is accompanied by a dramatic increase in the number of NK cells. These cells show an activated phenotype, lack recombination of the TCR, gene locus and express perforin. Similarly, in thymic lobes reconstituted with fetal liver cells, progenitors predominantly develop into NK cells both after pharmacological interference of Notch and after treatment with a recombinant rat Notch1/Fc chimera. Collectively, this identifies the lineage decision of NK/T precursor cells as an important site of Notch action in rat thymocytes. [source] Association of psoriasis to PGLYRP and SPRR genes at PSORS4 locus on 1q shows heterogeneity between Finnish, Swedish and Irish familiesEXPERIMENTAL DERMATOLOGY, Issue 2 2009Kati Kainu Abstract:, A susceptibility locus for psoriasis, PSORS4, has been mapped to chromosome 1q21 in the region of the epidermal differentiation complex. The region has been refined to a 115 kb interval around the loricrin (LOR) gene. However, no evidence of association between polymorphisms in the LOR gene and psoriasis has been found. Therefore, we have analysed association to three candidate gene clusters of the region, the S100, small proline-rich protein (SPRR) and PGLYRP (peptidoglycan recognition protein) genes, which all contain functionally interesting psoriasis candidate genes. In previous studies, the SPRR and S100 genes have shown altered expression in psoriasis. Also polymorphisms in the PGLYRP genes have shown to be associated with psoriasis. We genotyped altogether 29 single nucleotide polymorphisms (SNPs) in 255 Finnish psoriasis families and analysed association with psoriasis using transmission disequilibrium test. A five-SNP haplotype of PGLYRP SNPs associated significantly with psoriasis. There was also suggestive evidence of association to SPRR gene locus in Finnish families. To confirm the putative associations, selected SNPs were genotyped also in a family collection of Swedish and Irish patients. The families supported association to the two gene regions, but there was also evidence of allelic heterogeneity. [source] Alteration of enhancer of polycomb 1 at 10p11.2 is one of the genetic events leading to development of adult T-cell leukemia/lymphomaGENES, CHROMOSOMES AND CANCER, Issue 9 2009Shingo Nakahata Adult T-cell leukemia/lymphoma (ATLL) is a malignant tumor caused by latent human T-lymphotropic virus 1 (HTLV-1) infection. We previously identified a common breakpoint cluster region at 10p11.2 in acute-type ATLL by spectral karyotyping. Single nucleotide polymorphism array comparative genomic hybridization analysis of the breakpoint region in three ATLL-related cell lines and four patient samples revealed that the chromosomal breakpoints are localized within the enhancer of polycomb 1 (EPC1) gene locus in an ATLL-derived cell line (SO4) and in one patient with acute-type ATLL. EPC1 is a human homologue of the E(Pc) enhancer of polycomb gene of Drosophila. Inappropriate expression of the polycomb group gene family has been linked to the loss of normal gene silencing pathways, which can contribute to the loss of cell identity and malignant transformation in many kinds of cancers. In the case of the SO4 cell line, which carried a der(10)t(2;10)(p23;p11.2) translocation, EPC1 was fused with the additional sex combs-like 2 (ASXL2) gene at 2p23.3 (EPC1/ASXL2). In the case with an acute-type ATLL, who carried a der(10)del(10)(p11.2)del(10)(q22q24) translocation, a putative truncated EPC1 gene (EPC1tr) was identified. Overexpression of EPC1/ASXL2 enhanced cell growth in T-leukemia cells, and a GAL4-EPC1/ASXL2 fusion protein showed high transcriptional activity. Although a GAL4-EPC1tr fusion protein did not activate transcription, overexpression of EPC1tr accelerated cell growth in leukemia cells, suggesting that the EPC1 structural abnormalities in the SO4 cell line and in the patient with acute-type ATLL may contribute to leukemogenesis. © 2009 Wiley-Liss, Inc. [source] A BCR,JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a patient with a clinically typical chronic myeloid leukemiaGENES, CHROMOSOMES AND CANCER, Issue 3 2005Frank Griesinger Chronic myeloid leukemia (CML) is characterized by the presence of a t(9;22)(q34;q11.2), which leads to the well-known BCR,ABL1 fusion protein. We describe a patient who was diagnosed clinically with a typical CML but on cytogenetic analysis was found to have a t(9;22)(p24;q11.2). Chromosomal fluorescence in situ hybridization showed that the BCR gene locus spanned the breakpoint at band 22q11.2 but that the ABL1 gene was not rearranged. By means of a candidate gene approach, the JAK2 gene, at 9p24, was identified as the fusion partner of BCR in this case. The BCR,JAK2 fusion protein contains the coiled-coil dimerization domain of BCR and the protein tyrosine kinase domain (JH1) of JAK2. The patient's disease did not respond to Imatinib, and this unresponsiveness was most likely a result of the BCR,JAK2 fusion protein. © 2005 Wiley-Liss, Inc. [source] Association of a single nucleotide polymorphism in the steroid and xenobiotic receptor (SXR) gene (IVS1-579A/G) with bone mineral densityGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2 2007Tomohiko Urano Vitamin K2 plays an important role in the bone metabolism. The steroid and xenobiotic receptor (SXR) as a nuclear receptor activated by vitamin K2 as well as rifampicin could increase bone markers such as alkaline phosphatase in human osteoblastic cells. Thus, the SXR could mediate vitamin K2 signaling pathway in bone cells. Therefore, we analyzed expression of the SXR mRNA in human primary osteoblasts and chondrocytes. We also studied association of a single nucleotide polymorphism (SNP) in the SXR gene with bone mineral density (BMD). Expression levels of the SXR mRNA were analyzed during the culture course of human primary osteoblasts and chondrocytes. Association of a SNP in the SXR gene in intron 1 (IVS1-579A>G) with BMD was examined in 294 healthy postmenopausal Japanese women. The SXR mRNA increased at day 5 and then decreased at day 10 in human primary osteoblasts. Its mRNA gradually increased in human primary chondrocytes until day 10. As an association study of a SNP in the SXR gene (IVS1-579A/G), the subjects without the A allele (GG; n = 47) had significantly higher total BMD than the subjects bearing at least one A allele (AA + AG; n = 247) (Z score ± SD; 0.635 ± 1.031 versus 0.268 ± 1.061; P = 0.0298). The SXR mRNA was expressed and regulated in primary human osteoblasts and chondrocytes. A genetic variation at the SXR gene locus is associated with BMD, suggesting an involvement of the SXR gene in human bone metabolism. [source] Association of estrogen receptor , polymorphisms with susceptibility to chronic hepatitis B virus infectionHEPATOLOGY, Issue 2 2004Guohong Deng Several studies have demonstrated that estrogen receptor , (ESR1) participates in the pathogenesis of persistent hepatitis B virus (HBV) infection. To examine whether polymorphisms at the ESR1 gene locus are associated with persistent HBV infection, we resequenced ESR1 genomic region for single nucleotide polymorphisms (SNPs) in 27 unrelated Chinese. Two haplotype-tagged SNPs (htSNP), T29C and A252966G, were selected for genotyping in 1,277 persistent HBV-infected cases, 748 spontaneously recovered controls, and 293 nuclear families using polymerase chain reaction (PCR)-restriction fragment length polymorphism (PCR-RFLP) analysis. We observed that the subjects bearing ESR1 29T/T genotype had an increased susceptibility to persistent HBV infection compared to those bearing at least one 29C allele (odds ratio 1.41; 95% CI, 1.17-1.71, P < .001). Consistent with the results of population-based association study, a significantly greater than expected transmission of the 29T allele (56.4%) from heterozygous parents to offspring with persistent HBV infection was observed (,2 = 4.60, P = .033) using the transmission-disequilibrium test (TDT) in 293 nuclear families. Linkage disequilibrium (LD) mapping analysis indicated that the T29C polymorphism contained within a LD block located from promoter region to intron 3 of ESR1, suggesting that the strong association detected with T29C in ESR1 originated from ESR1 itself. In conclusion, our results suggest that the genetic variation at the ESR1 locus influences susceptibility to persistent HBV infection in a Chinese population. (HEPATOLOGY 2004;40:318,326.) 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