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Genetic Background (genetic + background)
Kinds of Genetic Background Selected AbstractsContributions of Mouse Genetic Background and Age on Anterior Lens Capsule ThicknessTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 12 2008Brian P. Danysh Abstract Accurate lens capsule thickness measurements are necessary for studies investigating mechanical characteristics of the capsule. Confocal Z -axis imaging was used to measure the anterior lens capsule thickness of living intact lenses with minimal tissue manipulation. Measurements of the anterior capsule thickness is reported for the first time in young and old mice from four inbred strains, BALB/c, FVB/N, C57BL/6, and 129X1, and the outbred strain ICR. Our data demonstrates that the mouse anterior lens capsule continues to grow postnatally similar to that described in other mammals. It is also shown there is a significant difference in anterior lens capsule thickness between unrelated mouse strains, suggesting that capsule thickness is a quantitative trait shared by strains with common ancestry. Measurements, taken from other regions of FVB/N capsules revealed the anterior pole to be the thickest, followed by the equatorial region and posterior pole. In addition to mouse, anterior capsule measurements taken from intact cattle, rabbit, rat lenses, and human capsulotomy specimens correlated with the overall size of the animal. Anat Rec, 2008. © 2008 Wiley-Liss, Inc. [source] Genetic background of Japanese patients with adult-onset storage diseases in the liverHEPATOLOGY RESEARCH, Issue 10 2007Hisao Hayashi In contrast to primary lysosomal diseases in young subjects, adult-onset liver storage disorders may be explained by non-lysosomal genetic defects. The aim of the present review is to summarize the genetic backgrounds of Japanese patients with hemochromatosis of unknown etiology, Wilson disease of primary copper toxicosis, and the black liver of Dubin,Johnson syndrome. Three patients with middle-age onset hemochromatosis were homozygous for mutations of HJV and two patients were homozygous for mutations of TFR2. Minor genes other than HJV and TFR2 might be involved in Japanese patients. Five of the six patients with Wilson disease were compound heterozygous, while the remaining patient was heterozygous for the mutation in ATP7B responsible for copper toxicosis. Involvement of MURR1 was not proved in the heterozygote of ATP7B. Because of ferroxidase deficiency,most patients had secondary lysosomes shared by cuprothioneins and iron complex. Six patients with Dubin,Johnson syndrome were homozygous or compound heterozygous for mutant MRP2. Despite complex metabolic disorders, the syndrome had a single genetic background. Thus, most patients with adult-onset lysosomal proliferation in the liver had genetic defects in non-lysosomal organelles, named the secondary lysosomal diseases. The proliferating lysosomes in these conditions seemed to be heterogeneous in their matrices. [source] Genetic background of primary biliary cirrhosisHEPATOLOGY RESEARCH, Issue 2007Atsushi Tanaka The clustering of patients in a representative family as well as relatively high concordance rate in monozygotic twins strongly indicate that genetic factors play a crucial role in modulating primary biliary cirrhosis (PBC) by conferring susceptibility to, or providing protection from, the disease. Therefore, much like other autoimmune diseases, intensive investigations have attempted to elucidate which genes are incriminated in the etiology of PBC. So far, a number of genes, including major histocompatibility complex (MHC) class I and II, cytokines and cell surface molecules, have been examined to seek the possibility of whether single nucleotide polymorphisms (SNP) of the gene might be associated with susceptibility to PBC. Nevertheless, it appears that methodologicaldifficulties, mainly the limitation of the number of individuals tested in each study, hamper the detection of a convincing and reproducible link between genetic polymorphisms and the etiology of PBC. Also, the difference in genetic background among several ethnic groups may play a role in concealing the association. In this review, I will highlight the genetic association in PBC, and review the association of genetic polymorphisms with the etiology of PBC, which have been reported in various ethnicities. [source] Introduction Strategies Put to the Test: Local Adaptation versus HeterosisCONSERVATION BIOLOGY, Issue 3 2004PHILIPPINE VERGEER exogamia; introducciones multi-fuente; introducciones uni-fuente; Succisa pratensis Abstract:,Plant biodiversity has declined seriously because of both habitat deterioration and habitat fragmentation. As a result, many species have been forced into small, fragmented, and isolated populations and are believed to suffer from higher extinction risks. Genetic reinforcement and the establishment of new populations are now widely used to prevent extinction. However, the genetic background of transplants may seriously affect the long-term success of these populations because increased genetic variation may reduce the risk of inbreeding or lead to better performance by restored heterozygosity levels (heterosis). Introduced transplants, however, may be poorly adapted to the new local conditions. We tested the initial success of alternative introduction strategies. We evaluated the potential for inbreeding, heterosis, and/or local adaptation after introduction of artificial populations of Succisa pratensis. We introduced individuals from local and distant artificial populations that were created from either small or large populations. We created the artificial populations with the same census population size but varying effective population sizes by adjusting the relatedness of individuals. We analyzed the demographic consequences of inbreeding, heterosis, and/or local adaptation of these artificial populations. Reduced performance after selfing was manifested by a reduction in seed production, seed weight, germination, and flowering percentage. Seed production, seed weight, flowering percentage, and number of flowerheads were negatively affected by small population size. Local adaptation increased biomass and flowering percentage for local individuals. Seed weight and seed production exhibited significant heterosis. Our results demonstrate that threatened populations can benefit from introduction and genetic reinforcement of individuals from related populations. Significant differences among the artificial populations for several measured performance components suggest that introduction or reinforcement is best achieved through material from a local population or, when unavailable, from several large populations. Resumen:,La biodiversidad de plantas ha declinado seriamente tanto por el deterioro como la fragmentación de hábitats. Como resultado, muchas especies han sido relegadas a poblaciones pequeñas, fragmentadas y aisladas cuyos riesgos de extinción se piensa que son mayores. El reforzamiento genético y el establecimiento de poblaciones nuevas se utilizan ampliamente en la actualidad para prevenir la extinción. Sin embargo, los antecedentes genéticos de transplantes pueden afectar seriamente el éxito de estas poblaciones a largo plazo debido a que el incremento en la variación genética puede reducir el riesgo de endogamia o puede conducir a un mejor rendimiento por lograr niveles de heterocigosidad restaurados (heterosis). No obstante, los trasplantes introducidos pueden adaptarse deficientemente a las nuevas condiciones locales. Probamos el éxito inicial de estrategias de introducción alternativas. Evaluamos el potencial de endogamia, heterosis y/o adaptación local después de la introducción de poblaciones artificiales de Succisa pratensis. Introdujimos individuos de poblaciones locales y de poblaciones artificiales distantes que fueron creadas a partir de poblaciones tanto pequeñas como grandes. Las poblaciones artificiales fueron creadas con el mismo tamaño poblacional censal pero variaron en tamaños poblacionales efectivos al ajustar la parentela de los individuos. Analizamos las consecuencias demográficas de la endogamia, heterosis y/o adaptación local de estas poblaciones artificiales. Después de la autofecundación se manifestó una reducción en el rendimiento por reducción en la producción y peso de semillas y en el porcentaje de germinación y floración. La producción y peso de semillas, el porcentaje de floración y el número de botones florales fueron afectados negativamente por el tamaño poblacional pequeño. La adaptación local incrementó la biomasa y el porcentaje de floración en individuos locales. El peso y producción de semillas mostró heterosis significativa. Nuestros resultados demuestran que las poblaciones amenazadas pueden beneficiarse de la introducción y del reforzamiento genético de individuos de poblaciones emparentadas. Las diferencias significativas entre las poblaciones artificiales en varios de los componentes de rendimiento medidos sugiere que la introducción o reforzamiento se logra mejor con material de una población local o, cuando no disponible, con material de varias poblaciones grandes. [source] Shb null allele is inherited with a transmission ratio distortion and causes reduced viability in uteroDEVELOPMENTAL DYNAMICS, Issue 9 2007Vitezslav Kriz Abstract SHB is an Src homology 2 domain-containing adapter protein that has been found to be involved in numerous cellular responses. We have generated an Shb knockout mouse. No Shb,/, pups or embryos were obtained on the C57Bl6 background, indicating an early defect as a consequence of Shb - gene inactivation on this genetic background. Breeding heterozygotes for Shb gene inactivation (Shb+/,) on a mixed genetic background (FVB/C57Bl6/129Sv) reveals a distorted transmission ratio of the null allele with reduced numbers of Shb+/+ and Shb,/, animals, but increased number of Shb+/, animals. The Shb, allele is associated with various forms of malformations, explaining the relative reduction in the number of Shb,/, offspring. Shb,/, animals that were born were viable, fertile, and showed no obvious defects. However, Shb+/, female mice ovulated preferentially Shb, oocytes explaining the reduced frequency of Shb+/+ mice. Our study suggests a role of SHB during reproduction and development. Developmental Dynamics 236:2485,2492, 2007. © 2007 Wiley-Liss, Inc. [source] Refining the results of a whole-genome screen based on 4666 microsatellite markers for defining predisposition factors for multiple sclerosisELECTROPHORESIS, Issue 14 2004René Gödde Abstract Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a complex genetic background. In order to identify loci associated with the disease, we had performed a genome screen initially using 6000 microsatellite markers in pooled DNA samples of 198 MS patients and 198 controls. Here, we report on the detailed reanalysis of this set of data. Distinctive features of microsatellites genotyped in pooled DNA causing false-positive association or masking existing association were met by improved evaluation and refined correction factors in the statistical analyses. In order to assess potential errors introduced by DNA pooling and genotyping, we resurveyed the experiment in a subset of microsatellite markers using de novo -composed DNA pools. True MS associations of markers were verified via genotyping all individual DNA samples comprised in the pools. Microsatellites share characteristically superb information content but they do not lend themselves to automation in very large scale formats. Especially after DNA pooling many artifacts of individual marker systems require special attention and treatment. Therefore, in the near future comprehensive whole-genome screens may rather be performed by typing single nucleotide polymorphisms on chip-based platforms. [source] Therapeutic approaches to epileptogenesis,Hope on the horizonEPILEPSIA, Issue 2010Asla Pitkänen Summary Prevention of epileptogenesis is an unmet need in medicine. During the last 3 years, however, several preclinical studies have demonstrated remarkable favorable effects of novel treatments on genetic and acquired epileptogenesis. These include the use of immunosuppressants and treatments that modify cellular adhesion, proliferation, and/or plasticity. In addition, the use of antiepileptic drugs in rats with genetic epilepsy or proconvulsants in acquired epilepsy models has provided somewhat unexpected favorable effects. This review summarizes these studies, and introduces some caveats when interpreting the data. In particular, the effect of genetic background, the severity of epileptogenic insult, the method and duration of seizure monitoring, and size of animal population are discussed. Furthermore, a novel scheme for defining epileptogenesis-related terms is presented. [source] Valproate teratogenicity and epilepsy syndromeEPILEPSIA, Issue 12 2008Edward B. Bromfield Summary Maternal valproate (VPA) use is associated with a significant risk for congenital malformations in the exposed fetus. Since VPA is commonly used in epilepsy syndromes with a presumed genetic cause (idiopathic epilepsies), it is possible that maternal genetic background contributes to this outcome. We reviewed responses to telephone questionnaires and medical records, when available, of enrollees in the North American Antiepileptic Drug Pregnancy Registry, classifying reason for treatment as idiopathic generalized epilepsy (IGE), partial epilepsy (PE), nonclassifiable epilepsy (NCE), or not epilepsy (NE). Of 284 VPA-exposed pregnancies, 30 (11.0%) were associated with malformations: IGE = 15/126 (12%), PE = 4/28 (14%), NCE = 9/105 (9%), NE = 2/25 (8%) (p > 0.7 for all comparisons). There was a trend toward increased malformation risk with higher VPA doses (p = 0.07). VPA, and not the underlying genetic syndrome, seems to be associated with the elevated risk for malformations in the drug-exposed fetus. [source] Historical Aspects of Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Peter Wolf Summary:, Early in these proceedings, the origin of the three terms in the title, "idiopathic generalized epilepsy," is discussed with respect to their significance over time, and typical misunderstandings. In the mid-20th century, a rather chaotic use of a multitude of often loosely defined terms had developed, which increasingly became an obstacle to a meaningful international discussion. The International League against Epilepsy (ILAE) took the initiative to develop an internationally accepted terminology with a classification system consisting of a classification of seizures (1981) and a classification of syndromes (1989). The Idiopathic Generalized Epilepsies are one of its four major groups emerging from a double dichotomy of generalized versus localization-related and idiopathic versus symptomatic. The inclusion of biologic aspects such as syndrome-specific ages of onset ("age-related syndromes") or syndrome-specific relations of seizure occurrence to the sleep,wake cycle ("Epilepsy with Grand Mal on Awaking") meant that the syndrome classification merged the more biological views of the German school with the more neurophysiological ones of the French. Apart from establishing a common international language concerning epilepsy, the International Classification of Epilepsies and Epileptic Syndromes became an important stimulator of research, especially concerning the idiopathic epilepsies. In particular, genetic and functional imaging investigations aim at a better understanding of these conditions. It is now understood that most idiopathic syndromes have a,sometimes complex,genetic background, but we are also becoming aware of the inappropriateness of the time-honored term "generalized" and part of our dichotomies. Both localization-related and "generalized" idiopathic epilepsies seem to share a principle of ictogenesis based on functional anatomic pathogenic networks, and we seem to move toward understanding them as functional system disorders of the brain. [source] A region on equine chromosome 13 is linked to recurrent airway obstruction in horsesEQUINE VETERINARY JOURNAL, Issue 3 2007U. JOST Summary Reasons for study: Equine recurrent airway obstruction (RAO) is probably dependent on a complex interaction of genetic and environmental factors and shares many characteristic features with human asthma. Interleukin 4 receptor , chain (IL4RA) is a candidate gene because of its role in the development of human asthma, confirmation of this association is therefore required. Methods: The equine BAC clone containing the IL4RA gene was localised to ECA13q13 by the FISH method. Microsatellite markers in this region were investigated for possible association and linkage with RAO in 2 large Warmblood halfsib families. Based on a history of clinical signs (coughing, nasal discharge, abnormal breathing and poor performance), horses were classified in a horse owner assessed respiratory signs index (HOARSI 1,4: from healthy, mild, moderate to severe signs). Four microsatellite markers (AHT133, LEX041, VHL47, ASB037) were analysed in the offspring of Sire 1 (48 unaffected HOARSI 1 vs. 59 affected HOARSI 2,4) and Sire 2 (35 HOARSI 1 vs. 50 HOARSI 2,4), age ,7 years. Results: For both sires haplotypes could be established in the order AHT133-LEX047-VHL47-ASB37. The distances in this order were estimated to be 2.9, 0.9 and 2.3 centiMorgans, respectively. Haplotype association with mild to severe clinical signs of chronic lower airway disease (HOARSI 2,4) was significant in the offspring of Sire 1 (P = 0.026) but not significant for the offspring of Sire 2 (P = 0.32). Linkage analysis showed the ECA13q13 region containing IL4RA to be linked to equine chronic lower airway disease in one family (P<0.01), but not in the second family. Conclusions: This supports a genetic background for equine RAO and indicates that IL4RA is a candidate gene with possible locus heterogeneity for this disease. Potential relevance: Identification of major genes for RAO may provide a basis for breeding and individual prevention for this important disease. [source] Development of three different neoplasias in a patient in an 18-year period of timeEUROPEAN JOURNAL OF CANCER CARE, Issue 3 2010P. HERAS md HERAS P., GEORGOPOULOU A.P., HATZOPOULOS A. & KRITIKOS K. (2010) European Journal of Cancer Care 19, 413,416 Development of three different neoplasias in a patient in an 18-year period of time This study presents a rare case of a patient who developed three different types of neoplasia in an 18-year period of time. The case presents a 31-year-old man with a history of treated Hodgkin's lymphoma in the neck region at the age of 13 years. The patient was admitted at the General Hospital of Nafplio for differential diagnosis of pain in the right subcostal region initiated 1 month before his admission and normochromic, normocytic anaemia. The laboratory examinations lead to the diagnosis of a sarcoma in the cardioesophageal junction. The patient was subjected to total gastrectomy. Nine months later he is admitted with a palpable firm lump in the nipple of the right breast, which suggested a malignant neoplasia. The patient was subjected to modified radical mastectomy. The appearance of three different types of neoplasia in three different organ systems in the same patient and the infrequency of the specific neoplasias individually and in combination present a special interest considering the patient's genetic background and the uniqueness of the case in the international literature. [source] A narrow deletion of 7q is common to HCL, and SMZL, but not CLLEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2004Claus Lindbjerg Andersen Abstract: To further characterise the genetic background of the two closely related B-lymphocytic malignancies hairy cell leukaemia (HCL), and splenic marginal zone lymphoma (SMZL) we have identified characteristic copy number imbalances by comparative genomic hybridisation (CGH). Based on these findings, areas of special interest were fine mapped, and relevant probes constructed for use in interphase-fluorescence in situ hybridisation (FISH) investigations. Thus, using the CGH data from 52 HCL and 61 SMZL patients, we identified the characteristic profiles of copy number imbalances for both diseases. These were a gain of 5q13-31 (19%) and loss of 7q22-q35 (6%) for HCL, and gain of 3q25 (28%), loss of 7q31 (16%), and gain of 12q15 (16%) for SMZL. A partial loss of 7q unsual for low-malignant B-cell diseases was found to be common to the two diseases. This loss was therefore fine mapped with BAC/PAC clones. Fine mapping revealed that in SMZL the minimal lost region covers 11.4 Mb spanning from 7q31.33 to 7q33 located between sequence tagged site (STS)-markers SHGC-3275 and D7S725. This area was distinct from the commonly deleted 7q region of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML). A FISH probe specific for the 7q region was constructed. Using this probe in an interphase-FISH investigation we showed the minimal lost 7q-region of HCL and SMZL to be one and the same. In one HCL case, this investigation furthermore showed the extent of the deleted region to be below the detection limit of CGH, whereas interphase-FISH screening of 36 chronic lymphocytic leukaemia (CLL) cases showed no deletion of the 7q area. In conclusion, we have identified characteristic profiles of copy number imbalances in HCL and SMZL and fine mapped the minimal extent of a commonly lost 7q area of special interest. We hypothesise that this region may contain (a) gene(s) important for the pathology of HCL and SMZL. [source] Functional C3435T polymorphism of MDR1 gene: an impact on genetic susceptibility and clinical outcome of childhood acute lymphoblastic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2004Krzysztof Jamroziak Abstract: The significance of genetic background in childhood acute lymphoblastic leukemia (ALL) is not well understood. Polymorphisms of genes encoding for xenobiotics and drug transporters are potential factors, which can influence the risk of developing ALL and its clinical outcome. P-glycoprotein (P-gp) is an adenosine triphosphate-binding cassette (ABC)-family transporter involved in protection against xenobiotics and multi-drug resistance. Recently, the single-nucleotide polymorphism C3435T of MDR1 gene has been found to be associated with altered tissue expression and function of P-gp. To evaluate whether C3435T MDR1 polymorphism is associated with the occurrence and outcome of ALL, 113 children with ALL (median age 5.1 yr) and 175 healthy individuals of Polish Caucasian origin were studied by polymerase chain reaction-restriction fragment-length polymorhism (PCR-RFLP) assay. The mutant homozygous TT genotype was found to be associated with occurrence of ALL (OR, 95% CI; 1.8, 1.1,3.1; P = 0.037). Besides, the analysis of factors influencing clinical outcome of our ALL patient cohort showed that CC genotype carriers had significantly lower event-free survival probability (pEFS) (0.62 vs. 0.87; P = 0.007) and overall survival probability (pOS) (0.72 vs. 0.91; P = 0.006). The Cox proportional hazards model-based analysis revealed that the hazard ratios for lower pEFS and lower pOS among CC homozygous subjects were 3.9 (P = 0.008) and 3.3 (P = 0.02), respectively. In conclusion, the results of the present study provide evidence that C3435T MDR1 polymorphism may involve both the susceptibility to and the clinical outcome of childhood ALL. Carriers of the TT genotype are more at risk of developing ALL than other individuals, whereas CC genotype carriers are supposed to have worse prognosis. [source] PRECLINICAL STUDY: Mice lacking Gad2 show altered behavioral effects of ethanol, flurazepam and gabaxadolADDICTION BIOLOGY, Issue 1 2010Yuri A. Blednov ABSTRACT ,-Aminobutyric acid (GABA) is synthesized in brain by two isoforms of glutamic acid decarboxylase (Gad), Gad1 and Gad2. Gad1 provides most of the GABA in brain, but Gad2 can be rapidly activated in times of high GABA demand. Mice lacking Gad2 are viable whereas deletion of Gad1 is lethal. We produced null mutant mice for Gad2 on three different genetic backgrounds: predominantly C57BL/6J and one or two generations of backcrossing to 129S1/SvimJ (129N1, 129N2). We used these mice to determine if actions of alcohol are regulated by synthesis of GABA from this isoform. We also studied behavioral responses to a benzodiazepine (flurazepam) and a GABAA receptor agonist (gabaxadol). Deletion of Gad2 increased ethanol palatability and intake and slightly reduced the severity of ethanol-induced withdrawal, but these effects depended strongly on genetic background. Mutant mice on the 129N2 background showed the above three ethanol behavioral phenotypes, but the C57BL/6J inbred background did not show any of these phenotypes. Effects on ethanol consumption also depended on the test as the mutation did not alter consumption in limited access models. Deletion of Gad2 reduced the effect of flurazepam on motor incoordination and increased the effect of extrasynaptic GABAA receptor agonist gabaxadol without changing the duration of loss of righting reflex produced by these drugs. These results are consistent with earlier proposals that deletion of Gad2 (on 129N2 background) reduces synaptic GABA but also suggest changes in extrasynaptic receptor function. [source] Risk factors for alcoholic liver diseaseADDICTION BIOLOGY, Issue 3 2000Stefano Bellentani Alcoholic liver disease (ALD) is still a frequent disorder, even though its incidence appears to be decreasing. In spite of intense investigation, the precise mechanisms leading to ALD are still imprecisely known. This is due in part to the lack of a reliable animal model; in part to the difficulty of obtaining clinical data of adequate sample size and derived from unblased populations and finally from the lack of uniformity of the criteria used to define ALD. This paper will review what is known of the various pieces of this puzzle, with particular emphasis not only on the total amount of alcohol consumed, but also on drinking patterns and type of alcoholic beverage ingested. The other potential factors such as age, gender, genetic background, nutritional status, occupational hazards and viral diseases (especially HCV infection) will be touched upon. [source] New genomic avenues in behavioural neuroendocrinology ,EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2002S. L. Lightman Abstract Neuroendocrine systems play a key role not only in the maintenance of whole-body homeostasis but also as the link between behavioural, endocrine and autonomic responses to environmental stimuli. It is becoming increasingly clear that neuroendocrine regulatory mechanisms are under the control of a combination of factors including genetic background, environment and early-life programming. Patterns of gene expression are increasingly being used to provide information on the genotypes associated with particular behaviours, and modulation of specific parts of the genome allow investigation of the contribution of particular genes. The sequencing of the genome provides a unique opportunity to elucidate the genetic contribution to neuroendocrine and behavioural processes, and to investigate the interactions between genetic and environmental factors. Although drugs can be used to activate or inhibit neurotransmitters and receptors, they lack specificity. New technologies now permit the activation or inactivation of both neurotransmitters and receptors in specific areas of the brain for defined periods, including crucially important developmental windows when activation appears to have long-term consequences. The future challenges are to define the critical mechanisms through which the genetic constitution of an individual human or experimental animal interacts with environmental cues to result in altered physiological or even pathological behaviour and endocrine function. [source] Strain differences in the behavioural outcome of neonatal ventral hippocampal lesions are determined by the postnatal environment and not genetic factorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2001Graham K. Wood Abstract It has been demonstrated that not only do rats neonatally lesioned in the ventral hippocampus (VH) develop behavioural hypersensitivity to amphetamine postpubertally, but also that the expression of the sensitivity is strain specific. For example, excitotoxic VH lesions at postnatal day (PD) 7 lead to significant increases in amphetamine-induced locomotion in postpubertal Fischer rats, but not in Lewis rats. However, as it is likely that the effect of strain differences are due to a combination of genetics and environment, we examined the contributions of the environment of the pups in determining the behavioural outcome following neonatal VH lesions. Fisher and Lewis rat pups were cross-fostered at birth, and then at PD7 lesioned bilaterally in the VH with ibotenic acid. anova analysis of postpubertal amphetamine-induced locomotor data revealed a significant effect of the strain of the dams raising the pups but no effect of the strain of the pup. In addition, a post hoc analysis revealed that lesioned Fisher or Lewis rats raised by Fisher, but not those raised by Lewis, dams demonstrated amphetamine-induced hyperlocomotion relative to nonlesioned controls. Observations of the maternal behaviour of Fischer and Lewis dams revealed significant differences in the frequency of arched-back nursing between the two strains. Interestingly, a correlation of the frequency of arched back nursing vs novelty- or amphetamine-induced locomotion revealed that the lesioned rats were significantly more affected by increases in arched-back nursing compared to the controls. The results suggest that the genetic background of the pups does not significantly affect the behavioural outcome following neonatal VH lesions; however, the results do suggest an important role of early environmental variables on the behavioural outcome of neonatal VH lesions. [source] Enlarged cholinergic forebrain neurons and improved spatial learning in p75 knockout miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2000Ursula Greferath Abstract The p75 low affinity neurotrophin receptor (p75) can induce apoptosis in various neuronal and glial cell types. Because p75 is expressed in the cholinergic neurons of the basal forebrain, p75 knockout mice may be expected to show an increased number of neurons in this region. Previous studies, however, have produced conflicting results, suggesting that genetic background and choice of control mice are critical. To try to clarify the conflicting results from previous reports, we undertook a further study of the basal forebrain in p75 knockout mice, paying particular attention to the use of genetically valid controls. The genetic backgrounds of p75 knockout and control mice used in this study were identical at 95% of loci. There was a small decrease in the number of cholinergic basal forebrain neurons in p75 knockout mice at four months of age compared with controls. This difference was no longer apparent at 15 months due to a reduction in numbers in control mice between the ages of 4 and 15 months. Cholinergic cell size in the basal forebrain was markedly increased in p75 knockout mice compared with controls. Spatial learning performance was consistently better in p75 knockout mice than in controls, and did not show any deterioration with age. The results indicate that p75 exerts a negative influence on the size of cholinergic forebrain neurons, but little effect on neuronal numbers. The markedly better spatial learning suggests that the function, as well as the size, of cholinergic neurons is negatively modulated by p75. [source] The 3020insC mutation of the NOD2/CARD15 gene in patients with periodontal diseaseEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 4 2004Matthias Folwaczny The 3020insC mutation of the NOD2/CARD15 gene leads to impaired activation of nuclear factor-kappa B (NF- ,B) in vitro. As the destruction of periodontal tissue is mediated via activation of NF- ,B, with subsequent transcription of proinflammatory cytokines, the c-insertion mutation of the NOD2/CARD15 gene might contribute to the proposed genetic background of periodontitis. The present study analysed the frequency of this mutation in 80 patients with chronic periodontal disease and 122 healthy controls. The 3020insC mutation was identified by employing the polymerase chain reaction followed by restriction fragment length polymorphism analysis. The prevalence of the 3020insC mutation of the NOD2/CARD15 protein in patients with periodontitis was 1.9% (three of 160) and that for the control group was 2.0% (five of 244) (P = 0.942). Hence, unlike in Crohn's disease, the 3020insC mutation of the NOD2/CARD15 gene does not seem to influence the pathophysiology of periodontitis. [source] HOW REPEATABLE IS ADAPTIVE EVOLUTION?EVOLUTION, Issue 8 2008THE ROLE OF GEOGRAPHICAL ORIGIN AND FOUNDER EFFECTS IN LABORATORY ADAPTATION The importance of contingency versus predictability in evolution has been a long-standing issue, particularly the interaction between genetic background, founder effects, and selection. Here we address experimentally the effects of genetic background and founder events on the repeatability of laboratory adaptation in Drosophila subobscura populations for several functional traits. We found disparate starting points for adaptation among laboratory populations derived from independently sampled wild populations for all traits. With respect to the subsequent evolutionary rate during laboratory adaptation, starvation resistance varied considerably among foundations such that the outcome of laboratory evolution is rather unpredictable for this particular trait, even in direction. In contrast, the laboratory evolution of traits closely related to fitness was less contingent on the circumstances of foundation. These findings suggest that the initial laboratory evolution of weakly selected characters may be unpredictable, even when the key adaptations under evolutionary domestication are predictable with respect to their trajectories. [source] HOST SHIFTS AND THE BEGINNING OF SIGNAL DIVERGENCEEVOLUTION, Issue 1 2008Rafael L. Rodríguez Divergence between populations adapting to different environments may be facilitated when the populations differ in their sexual traits. We tested whether colonizing a novel environment may, through phenotypic plasticity, change sexual traits in a way that could alter the dynamics of sexual selection. This hypothesis has two components: changes in mean phenotypes across environments, and changes in the genetic background of the phenotypes that are produced,or genotype × environment interaction (G × E). We simulated colonization of a novel environment and tested its effect on the mating signals of a member of the Enchenopa binotata species complex of treehoppers (Hemiptera: Membracidae), a clade that has diverged in a process involving host plant shifts and signal diversification. We found substantial genetic variation and G × E in most signal traits measured, with little or no change in mean signal phenotypes. We suggest that the expression of extant genetic variation across old and novel environments can initiate signal divergence. [source] THE EVOLUTION OF GENETIC ARCHITECTURE UNDER FREQUENCY-DEPENDENT DISRUPTIVE SELECTIONEVOLUTION, Issue 8 2006Michael Kopp Abstract We propose a model to analyze a quantitative trait under frequency-dependent disruptive selection. Selection on the trait is a combination of stabilizing selection and intraspecific competition, where competition is maximal between individuals with equal phenotypes. In addition, there is a density-dependent component induced by population regulation. The trait is determined additively by a number of biallelic loci, which can have different effects on the trait value. In contrast to most previous models, we assume that the allelic effects at the loci can evolve due to epistatic interactions with the genetic background. Using a modifier approach, we derive analytical results under the assumption of weak selection and constant population size, and we investigate the full model by numerical simulations. We find that frequency-dependent disruptive selection favors the evolution of a highly asymmetric genetic architecture, where most of the genetic variation is concentrated on a small number of loci. We show that the evolution of genetic architecture can be understood in terms of the ecological niches created by competition. The phenotypic distribution of a population with an adapted genetic architecture closely matches this niche structure. Thus, evolution of the genetic architecture seems to be a plausible way for populations to adapt to regimes of frequency-dependent disruptive selection. As such, it should be seen as a potential evolutionary pathway to discrete polymorphisms and as a potential alternative to other evolutionary responses, such as the evolution of sexual dimorphism or assortative mating. [source] PERSPECTIVE: SIGN EPISTASIS AND GENETIC COSTRAINT ON EVOLUTIONARY TRAJECTORIESEVOLUTION, Issue 6 2005Daniel M. Weinreich Abstract Epistasis for fitness means that the selective effect of a mutation is conditional on the genetic background in which it appears. Although epistasis is widely observed in nature, our understanding of its consequences for evolution by natural selection remains incomplete. In particular, much attention focuses only on its influence on the instantaneous rate of changes in frequency of selected alleles via epistatic contribution to the additive genetic variance for fitness. Thus, in this framework epistasis only has evolutionary importance if the interacting loci are simultaneously segregating in the population. However, the selective accessibility of mutational trajectories to high fitness genotypes may depend on the genetic background in which novel mutations appear, and this effect is independent of population polymorphism at other loci. Here we explore this second influence of epistasis on evolution by natural selection. We show that it is the consequence of a particular form of epistasis, which we designate sign epistasis. Sign epistasis means that the sign of the fitness effect of a mutation is under epistatic control; thus, such a mutation is beneficial on some genetic backgrounds and deleterious on others. Recent experimental innovations in microbial systems now permit assessment of the fitness effects of individual mutations on multiple genetic backgrounds. We review this literature and identify many examples of sign epistasis, and we suggest that the implications of these results may generalize to other organisms. These theoretical and empirical considerations imply that strong genetic constraint on the selective accessibility of trajectories to high fitness genotypes may exist and suggest specific areas of investigation for future research. [source] EVOLUTION OF WOLBACHIA-INDUCED CYTOPLASMIC INCOMPATIBILITY IN DROSOPHILA SIMULANS AND D. SECHELLIAEVOLUTION, Issue 9 2002Sylvain Charlat Abstract., The intracellular bacterium Wolbachia invades arthropod host populations through various mechanisms, the most common of which being cytoplasmic incompatibility (CI). CI involves elevated embryo mortality when infected males mate with uninfected females or females infected with different, incompatible Wolbachia strains. The present study focuses on this phenomenon in two Drosophila species: D. simulans and D. sechellia. Drosophila simulans populations are infected by several Wolbachia strains, including w Ha and w No. Drosophila sechellia is infected by only two Wolbachia: w Sh and w Sn. In both Drosophila species, double infections with Wolbachia are found. As indicated by several molecular markers, w Ha is closely related to w Sh, and w No to w Sn. Furthermore, the double infections in the two host species are associated with closely related mitochondrial haplotypes, namely si I (associated with w Ha and w No in D. simulans) and se (associated with w Sh and w Sn in D. sechellia). To test the theoretical prediction that Wolbachia compatibility types can diverge rapidly, we injected w Sh and w Sn into D. simulans, to compare their CI properties to those of their sister strains w Ha and w No, respectively, in the same host genetic background. We found that within each pair of sister strains CI levels were similar and that sister strains were fully compatible. We conclude that the short period for which the Wolbachia sister strains have been evolving separated from each other was not sufficient for their CI properties to diverge significantly. [source] Functional characterization of T cells differentiated in vitro from bone marrow-derived CD34+ cells of psoriatic patients with family historyEXPERIMENTAL DERMATOLOGY, Issue 8 2010Kaiming Zhang Please cite this paper as: Functional characterization of T cells differentiated in vitro from bone marrow-derived CD34+ cells of psoriatic patients with family history. Experimental Dermatology 2010; 19: e128,e135. Abstract Background:, The strong but complex genetic background suggests that inherent and intrinsic rather than exogenous factors have a key role in immunopathogenesis of psoriasis. It is reasonable to speculate that the dysfunctional activity of psoriatic T cells may partly originate from the abnormal haematopoietic cells. Objectives:, To test if T cells originated from haematopoietic progenitor cells in psoriasis patients display functional alternations similar to previously reported abnormalities of circulating T cells. Methods:, Bone marrow CD34+ haematopoietic cells were isolated from psoriatic patients with family history and healthy subjects, and differentiated into T cells in vitro in the thymic stromal co-culture system. These cells were further subjected to functional comparisons such as in vitro proliferation, secretion of cytokines such as IL-4, IL-8 and IFN,,, and inducing the production of C-myc, Bcl-xL, and Ki67 proteins in human keratinocytes. Results:, While bone marrow-derived CD34+ cells from both patients and healthy volunteers developed into mature T cells within weeks in the thymic environment in vitro, the differentiated T cells from psoriatic patients showed higher proliferation and stronger capacity to secret TH1 cytokines in response to streptococcal superantigen. The differentiated T cells from psoriatic patients, but not from normal controls, induced overexpression of C-myc and Ki67, but not Bcl-XL, in keratinocytes. Conclusions:, T cells differentiated from CD34+ cells of psoriatic patients, but not normal controls, are functionally similar to psoriatic circulating T cells, suggesting that the dysfunctional activity of T cells in psoriatic patients can be traced back to the early development of haematopoietic cells. [source] Embryonic Stem Cells and Gene TargetingEXPERIMENTAL PHYSIOLOGY, Issue 6 2000Birgit Ledermann The development of gene targeting technology, the exchange of an endogenous allele of a target gene for a mutated copy via homologous recombination, and the application of this technique to murine embryonic stem cells has made it possible to alter the germ-line of mice in a predetermined way. Gene targeting has enabled researchers to generate mouse strains with defined mutations in their genome allowing the analysis of gene function in vivo. This review presents the essential tools and methodologies used for gene targeting that have been developed over the past decade. Special emphasis has been laid on the available embryonic stem cell lines and the importance of the genetic background. Also, the state-of-the art of gene targeting approaches in species other than mice will be discussed. [source] Diversity of endophytic bacterial communities in poplar grown under field conditionsFEMS MICROBIOLOGY ECOLOGY, Issue 2 2008Kristina Ulrich Abstract Bacterial endophytes may be important for plant health and other ecologically relevant functions of poplar trees. The composition of endophytic bacteria colonizing the aerial parts of poplar was studied using a multiphasic approach. The terminal restriction fragment length polymorphism analysis of 16S rRNA genes demonstrated the impact of different hybrid poplar clones on the endophytic community structure. Detailed analysis of endophytic bacteria using cultivation methods in combination with cloning of 16S rRNA genes amplified from plant tissue revealed a high phylogenetic diversity of endophytic bacteria with a total of 53 taxa at the genus level that included Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. The community structure displayed clear differences in terms of the presence and relative proportions of bacterial taxa between the four poplar clones studied. The results showed that the genetic background of the hybrid poplar clones corresponded well with the endophytic community structure. Out of the 513 isolates and 209 clones identified, Actinobacteria, in particular the family Microbacteriaceae, made up the largest fraction of the isolates, whereas the clone library was dominated by Alpha - and Betaproteobacteria. The most abundant genera among the isolates were Pseudomonas and Curtobacterium, while Sphingomonas prevailed among the clones. [source] The genetic background of Streptococcus pneumoniae affects protection in mice immunized with PspAFEMS MICROBIOLOGY LETTERS, Issue 2 2007Xiangyun He Abstract Anti-PspA antibodies are less efficient at protecting mice against certain pneumococcal strains. Immunization with PspA from EF5668 provided better protection against WU2 (a different capsular serotype and PspA family) than against EF5668. To understand the role of the pneumococcal genetic background in anti-PspA-mediated protection, we constructed a mutant of WU2 expressing pspA from EF5668. Both passive and active immunization demonstrated that the genetic background impacted the protection mediated by anti-PspA antibodies. We localized the protection-eliciting region to the first 122 amino acid residues of the N-termius of the ,-helical domain of PspA/EF5668. [source] DNA methylation of Sleeping Beauty with transposition into the mouse genomeGENES TO CELLS, Issue 8 2005Chang Won Park The Sleeping Beauty transposon is a recently developed non-viral vector that can mediate insertion of transgenes into the mammalian genome. Foreign DNA elements that are introduced tend to invoke a host-defense mechanism resulting in epigenetic changes, such as DNA methylation, which may induce transcriptional inactivation of mammalian genes. To assess potential epigenetic modifications associated with Sleeping Beauty transposition, we investigated the DNA methylation pattern of transgenes inserted into the mouse genome as well as genomic regions flanking the insertion sites with bisulfite-mediated genomic sequencing. Transgenic mouse lines were created with two different Sleeping Beauty transposons carrying either the Agouti or eGFP transgene. Our results showed that DNA methylation in the keratin-14 promoter and Agouti transgene were negligible. In addition, two different genomic loci flanking the Agouti insertion site exhibited patterns of DNA methylation similar to wild-type mice. In contrast, high levels of DNA methylation were observed in the eGFP transgene and its ROSA26 promoter. These results indicate that transposition via Sleeping Beauty into the mouse genome may result in a significant level of de novo DNA methylation. This may depend on a number of different factors including the cargo DNA sequence, chromosomal context of the insertion site, and/or host genetic background. [source] A spontaneous mutation of the Wwox gene and audiogenic seizures in rats with lethal dwarfism and epilepsyGENES, BRAIN AND BEHAVIOR, Issue 7 2009H. Suzuki The lde/lde rat is characterized by dwarfism, postnatal lethality, male hypogonadism, a high incidence of epilepsy and many vacuoles in the hippocampus and amygdala. We used a candidate approach to identify the gene responsible for the lde phenotype and assessed the susceptibility of lde/lde rats for audiogenic seizures. Following backcross breeding of lethal dwarfism with epilepsy (LDE) to Brown Norway rats, the lde/lde rats with an altered genetic background showed all pleiotropic phenotypes. The lde locus was mapped to a 1.5-Mbp region on rat chromosome 19 that included the latter half of the Wwox gene. Sequencing of the full-length Wwox transcript identified a 13-bp deletion in exon 9 in lde/lde rats. This mutation causes a frame shift, resulting in aberrant amino acid sequences at the C-terminal. Western blotting showed that both the full-length products of the Wwox gene and its isoform were present in normal testes and hippocampi, whereas both products were undetectable in the testes and hippocampi of lde/lde rats. Sound stimulation induced epileptic seizures in 95% of lde/lde rats, with starting as wild running (WR), sometimes progressing to tonic,clonic convulsions. Electroencephalogram (EEG) analysis showed interictal spikes, fast waves during WR and burst of spikes during clonic phases. The Wwox protein is expressed in the central nervous system (CNS), indicating that abnormal neuronal excitability in lde/lde rats may be because of a lack of Wwox function. The lde/lde rat is not only useful for understanding the multiple functions of Wwox but is also a unique model for studying the physiological function of Wwox in CNS. [source] | |||||||||||||||||||||||||||||||||||||