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Gene Effects (gene + effects)
Selected AbstractsGene Transfer Strategies for the PhysiologistEXPERIMENTAL PHYSIOLOGY, Issue 6 2000Liang-Fong Wong Foreign genes can be introduced into whole animals using methods of germline transgenesis and somatic gene delivery. While germline transgenesis can generate useful animal models for genetic studies, it can be costly, time-consuming and requires the use of a large number of animals. An alternative means of gene transfer is to deliver genes to somatic cells using non-viral and viral technologies. Non-viral methods such as naked DNA injection, electroporation and liposome/cation lipid-mediated gene transfer are relatively inefficient. In contrast, viruses are effective vehicles that carry foreign genes into a cell rapidly and efficiently. Here we illustrate the usefulness of adenoviral vectors to express a potent and specific inhibitor of cAMP-dependent protein kinase (PKA) to study the role of cyclic 3,,5,-cyclic AMP (cAMP) in the osmotic regulation of the vasopressin gene in a transgenic rat model. The ability to modify endogenous systems within specific cells in a whole animal model allows gene effects to be studied with physiological relevance. The combination of molecular biology and integrative physiology is a powerful application that can aid in the elucidation of how gene function can translate into complex systems in an organism [source] The evolution of senescence from a comparative perspectiveFUNCTIONAL ECOLOGY, Issue 3 2008R. E. Ricklefs Summary 1Comparative studies of ageing address the evolutionary lability of the rate of ageing as an indication of potential for, and constraints on, the extension of life span. 2Experimental studies on ageing have focused on damage induced by reactive oxygen species (ROS) and other stresses, and on the mechanisms to prevent or repair this damage. Research on animal models has revealed genes with large effects on life span. However, the relevance of some animal models to human ageing is unclear and it is not known whether evolved differences in ageing involve such major gene effects. 3Studies on the demography of populations of vertebrates in the wild show that animals suffer from senescence in nature. Variation in the rate of ageing is consistent with evolutionary theory in that senescence is delayed in populations that suffer relatively low extrinsic mortality. 4Populations of longer-lived individuals suffer a higher proportion of ageing-related mortality, and thus stronger selection against early ageing. The presence of ageing-related deaths in these populations suggests a lack of suitable mechanisms that would further extend life span. 5Similar patterns of ageing-related mortality in wild and captive or domesticated populations indicate that most ageing-related death is caused by intrinsic factors, such as tumours and cardiovascular failure, rather than increasing vulnerability to extrinsic causes of mortality. 6Studies of several wild populations of long-lived birds suggest that ageing-related mortality is often catastrophic, with individuals maintaining high levels of condition until shortly before their demise. 7Comparative studies of many species suggest connections between early development and the pattern of ageing later in life, consistent with laboratory studies on variation within individual species. The physiological connections across the life span are not well understood. 8Comparative studies have provided important insights into the ageing process. However, we still lack information on important issues, including the causes of death in natural populations, the relationship of within- and between-population variation in the rate of ageing, the genetic basis of variation in rate of ageing in natural populations, and detailed longitudinal studies of individual health and reproductive success in relation to age at death. [source] A novel method to identify gene,gene effects in nuclear families: the MDR-PDTGENETIC EPIDEMIOLOGY, Issue 2 2006E.R. Martin Abstract It is now well recognized that gene,gene and gene,environment interactions are important in complex diseases, and statistical methods to detect interactions are becoming widespread. Traditional parametric approaches are limited in their ability to detect high-order interactions and handle sparse data, and standard stepwise procedures may miss interactions that occur in the absence of detectable main effects. To address these limitations, the multifactor dimensionality reduction (MDR) method [Ritchie et al., 2001: Am J Hum Genet 69:138,147] was developed. The MDR is wellsuited for examining high-order interactions and detecting interactions without main effects. The MDR was originally designed to analyze balanced case-control data. The analysis can use family data, but requires a single matched pair be selected from each family. This may be a discordant sib pair, or may be constructed from triad data when parents are available. To take advantage of additional affected and unaffected siblings requires a test statistic that measures the association of genotype with disease in general nuclear families. We have developed a novel test, the MDR-PDT, by merging the MDR method with the genotype-Pedigree Disequilibrium Test (geno-PDT)[Martin et al., 2003: Genet Epidemiol 25:203,213]. MDR-PDT allows identification of single-locus effects or joint effects of multiple loci in families of diverse structure. We present simulations to demonstrate the validity of the test and evaluate its power. To examine its applicability to real data, we applied the MDR-PDT to data from candidate genes for Alzheimer disease (AD) in a large family dataset. These results show the utility of the MDR-PDT for understanding the genetics of complex diseases. Genet. Epidemiol. 2006. © 2005 Wiley-Liss, Inc. [source] Linkage and QTL mapping for Sus scrofa chromosome 1JOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 2003P. Beeckmann Summary Linkage maps of Sus scrofa chromosome 1 (SSC1) have been produced using 10 markers in three different F2 families based on crosses of Meishan (M), Pietrain (P) and Wild Boar (W). The maps were similar for the different families and show higher paternal recombination, especially in the interval SW2130,SW803. Quantitative trait loci (QTLs) affecting body conformation, carcass composition, fat deposition and numbers of teats were identified in all three families. Major QTLs were mapped in chromosomal intervals centred at approximately 60, 120 and 170 cM. The QTLs explain up to 8.4% of phenotypic variance in the F2 generation. Pietrain QTL alleles were superior in comparison with Wild Boar and Meishan alleles for most of the trait values. Meishan alleles were associated with highest fat deposition. Additive gene effects were generally larger than dominance effects. QTL profiles on SSC1 differed between families, with the W × P family being most distinct. Zusammenfassung Kopplungskarten für Chromosom 1 (SSC1), die durch die Analyse von 10 Markern erstellt wurden, stimmten in drei untersuchten F2 -Familien (basierend auf Kreuzungen mit Meishan (M), Pietrain (P) und Wildschwein (W)) wie auch mit den bisher publizierten Karten überein. Die geschlechtsspezifischen Karten zeigten eine höhere Frequenz der Rekombinationen in der paternalen Meiose als in der maternalen, besonders im Intervall SW2130 bis SW803. Auf SSC1 konnten bedeutsame QTL-Effekte mit Wirkung auf Wachstum, Schlachtkörperzusammensetzung und Fettansatz sowie die Zitzenzahl in allen drei Familien kartiert werden, insbesondere in den Regionen um 60, 120 und 170 cM. Sie erklärten bis zu 8,4% der phänotypischen Varianz in der F2 -Generation. Pietrain-Allele zeigten positive Auswirkungen auf die meisten Fleischleistungsmerkmale. Meishan-Allele waren mit einer stärkeren Verfettung assoziiert. Es wurden Unterschiede zwischen den QTL-Profilen in den Familien beobachtet, wobei die Familie W × P besonders stark von den QTL-Profilen in den beiden anderen Familien abwich. [source] Relationship between the IQ of people with Prader,Willi syndrome and that of their siblings: evidence for imprinted gene effectsJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 5 2009J. Whittington Abstract Background Genetic disorders occasionally provide the means to uncover potential mechanisms linking gene expression and physical or cognitive characteristics or behaviour. Prader,Willi syndrome (PWS) is one such genetic disorder in which differences between the two main genetic subtypes have been documented (e.g. higher verbal IQ in one vs. higher performance IQ in the other; slower than normal reaction time in one vs. normal in the other). In a population study of PWS, the IQ distribution of people with PWS was approximately normal. This raises the question of whether this distribution arose from a systematic effect of PWS on IQ (hypothesis 1) or whether it was the fortuitous result of random effects (hypothesis 2). Method The correlation between PWS and sibling IQ was determined in order to discriminate between the two hypotheses. In the first case we would expect the correlation to be similar to that found in the general population (0.5); in the second case it would be zero. Results It was found that the overall PWS,sibling IQ correlation was 0.3 but that the two main genetic subtypes of PWS differed in their familial IQ relationships. As expected, the IQs of normal siblings correlated 0.5, and this was also the case with one genetic subtype of PWS (uniparental disomy) and their siblings, while the other subtype IQ correlated ,0.07 with sibling IQ. Conclusions This is a potentially powerful result that gives another clue to the role of genes on chromosome 15 in the determination of IQ. It is another systematic difference between the genetic subtypes of PWS, which needs an explanation in terms of the very small genetic differences between them. [source] Polymorphisms of Alcohol Dehydrogenase-1B and Aldehyde Dehydrogenase-2 and the Blood and Salivary Ethanol and Acetaldehyde Concentrations of Japanese Alcoholic MenALCOHOLISM, Issue 7 2010Akira Yokoyama Background:, The effects of genetic polymorphism of aldehyde dehydrogenase-2 (ALDH2) on alcohol metabolism are striking in nonalcoholics, and the effects of genetic polymorphism of alcohol dehydrogenase-1B (ADH1B) are modest at most, whereas genetic polymorphisms of both strongly affect the susceptibility to alcoholism and upper aerodigestive tract (UADT) cancer of drinkers. Methods:, We evaluated associations between ADH1B/ADH1C/ALDH2 genotypes and the blood and salivary ethanol and acetaldehyde levels of 168 Japanese alcoholic men who came to our hospital for the first time in the morning and had been drinking until the day before. Results:, The ethanol levels in their blood and saliva were similar, but the acetaldehyde levels in their saliva were much higher than in their blood, probably because of acetaldehyde production by oral bacteria. Blood and salivary ethanol and acetaldehyde levels were both significantly higher in the subjects with the less active ADH1B*1/*1 genotype than in the ADH1B*2 carriers, but none of the levels differed according to ALDH2 genotype. Significant linkage disequilibrium was detected between the ADH1B and ADH1C genotypes, but ADH1C genotype did not affect the blood or salivary ethanol or acetaldehyde levels. High blood acetaldehyde levels were found even in the active ALDH2*1/*1 alcoholics, which were comparable with the levels of the inactive heterozygous ALDH2*1/*2 alcoholics with less active ADH1B*1/*1. The slope of the increase in blood acetaldehyde level as the blood ethanol level increased was significantly steeper in alcoholics with inactive heterozygous ALDH2*1/*2 plus ADH1B*2 allele than with any other genotype combinations, but the slopes of the increase in salivary acetaldehyde level as the salivary ethanol level increased did not differ between the groups of subjects with any combinations of ALDH2 and ADH1B genotypes. Conclusions:, The ADH1B/ALDH2 genotype affected the blood and salivary ethanol and acetaldehyde levels of nonabstinent alcoholics in a different manner from nonalcoholics, and clear effects of ADH1B genotype and less clear effects of ALDH2 were observed in the alcoholics. Alterations in alcohol metabolism as a result of alcoholism may modify the gene effects, and these findings provide some clues in regard to associations between the genotypes and the risks of alcoholism and UADT cancer. [source] Original Article: A systematic review and meta-analysis of tumor necrosis factor ,-308 polymorphism and Kawasaki diseasePEDIATRICS INTERNATIONAL, Issue 4 2010Sakda Arj-Ong Abstract Background:, There have been genetic studies assessing the association between tumor necrosis factor (TNF)-,-308 and Kawasaki disease (KD) but the results have been conflicting due to lack of power. Therefore, a systematic review and meta-analysis was conducted to increase the power for identifying the association between the TNF-,-308 polymorphism and KD. Method:, Studies were identified from MEDLINE and EMBASE databases and were included if the subjects were children and the frequencies between TNF-,-308 and KD were reported. Data were pooled using a random effect model if heterogeneity between studies was present. Results:, Thirteen studies were identified however only six studies were included. The pooled prevalence of minor A allele was 5.2% (95% confidence interval [CI]: 0.1%,9.5%). Gene effect was assessed using per-allele and per-genotype approaches. The pooled odds ratio of G versus A with the random effect model was 1.13 (95%CI: 0.34,3.27). The genotype effects for GG versus GA+AA was estimated and the pooled odds ratio was 1.08 (95%CI: 0.42,2.92). Conclusion:, This review suggests a trend of association between the TNF-,-308 G-allele and KD. However, the gene effects are heterogeneous and assessing sources of heterogeneity are limited. An updated meta-analysis is needed if more studies are published. [source] Analysis of resistance mechanism to Atherigona soccata in crosses of sorghumPLANT BREEDING, Issue 5 2009A. Anandan Abstract In sorghum, shoot fly resistance is important for grain yield and fodder value. An experiment was conducted to estimate genetic parameters of sorghum for resistance to shoot fly in 50 hybrids, by crossing 5 × 10 genotypes in line × tester manner. Plant height, number of leaves per plant, number of eggs per plant, trichomes on upper and lower surface per unit area of lamina and dead heart per cent were measured on 14 and 21 days after emergence (DAE) and glossiness of leaves was graded on 14 DAE. The correlation between midparent and hybrid performance, GCA : SCA ratio revealed predominance of non-additive gene effects for the traits studied, which could be exploited through hybrid breeding. Of the parents, SPSFPR 94004A and IS 4777 were the best general combiners for shoot fly resistance. Correlation and path analysis revealed the importance of resistance traits and phenol estimation confirms the resistances against shoot fly. [source] Effect of genome composition and cytoplasm on petal colour in resynthesized amphidiploids and sesquidiploids derived from crosses between Brassica rapa and Brassica oleraceaPLANT BREEDING, Issue 4 2002B. Zhang Abstract The effect of genome composition and cytoplasm on petal colour was studied in Brassica. Three accessions of yellow-petalled B. rapa (2n= 20, AA) were crossed with a white-petalled B. oleracea var. alboglabra (2n= 18, CC) and with three cream-yellow-petalled B. oleracea var. gongylodes (2n= 18, CC) to produce resynthesized B. napus (2n= 38, AACC or CCAA) and sesquidiploids (2n= 29, AAC or CAA). Petal colour was measured with a Hunter automatic colour difference meter. The results revealed that petal colour in Brassica is controlled by nuclear genes and by cytoplasmic factors. Additive and epistatic gene effects were involved in the action of nuclear genes. When crosses were made between yellow-petalled B. rapa and white-petalled B. oleracea var. alboglabra, significant additive, epistatic and cytoplasmic effects were found. White petal colour was partially epistatic over yellow petal colour. When crosses were made between yellow-petalled B. rapa and cream-yellow-petalled B. oleracea var. gongylodes, only epistatic effects were detected. Yellow petal colour was epistatic over cream-yellow. [source] Genetic effects of the soft starch (h) and background loci on volume of starch granules in five inbreds of maizePLANT BREEDING, Issue 2 2000J. A. Wilson Abstract Larger particle volume is beneficial for many aspects of maize starch processing, and may improve the performance of some starch attributes. This study focused on the soft starch (h) locus to identify its potentially influential role in starch particle volume distribution. The objectives were to study the genetic expression of starch particle volume of the h locus in different genetic backgrounds and the gene action conditioning starch particle volume of other loci in both normal-starch and h -starch backgrounds. Forty-five populations (five intra-inbred F1s, 10 hybrid F1s 10 F2s, 10 BC1F1s to h/h parent, and 10 BC1 to h:h conversion of normal parent) were planted in 1993 at two locations and in 1995 at one location. Selfed heterozygotes (±/h) in all generations provided intra-ear comparisons of normal and h starch, and F3 and BC1F2 generations provided inter-ear comparisons. Significant differences were found between normal and h:h genotypes in all intra-ear and inter-ear comparisons. In all cases, general combining ability effects were highly significant, suggesting the presence of additive gene effects. Generation mean analysis of normal and h:h starch materials yielded similar results, indicating the predominance of additive and some dominance effects for other loci on starch particle volume. These results indicate the usefulness of the soft starch gene and additional genetic variation among inbreds in the improvement of starch particle volume for increased starch recovery in wet milling. [source] Gene function beyond the single trait: natural variation, gene effects, and evolutionary ecology in Arabidopsis thalianaPLANT CELL & ENVIRONMENT, Issue 1 2005S. J. TONSOR ABSTRACT The purpose of plant functional genomics is to describe the patterns of gene expression and internal plant function underlying the ecological functions that sustain plant growth and reproduction. Plants function as integrated systems in which metabolic and developmental pathways draw on common resource pools and respond to a relatively small number of signal/response systems. Plants are also integrated with their environment, exchanging energy and matter with their surroundings and are consequently sensitive to changes in energy and resource fluxes. These two levels of integration complicate the description of gene function. Internal integration results in single genes often affecting multiple characteristics (pleiotropy) and interacting with multiple other genes (epistasis). Integration with the external environment leads to gene expression and the genes' phenotypic effects varying across environmental backgrounds (gene,environment interaction). An accurate description of the function of all genes requires an augmentation, already underway, of the study of isolated developmental and metabolic pathways to a more integrated approach involving the study of genetic effects across scales of variation usually regarded as the purview of ecological and evolutionary research. Since the evolution of gene function also depends on this complex of gene effects, progress in evolutionary genetics will also require understanding the nature of gene interactions and pleiotropy and the constraints and patterns they impose on adaptive evolution. Studying gene function in the context of the integrated organism is a major challenge, best met by developing co-ordinated research efforts in model systems. This review highlights natural variation in A. thaliana as a system for understanding integrated gene function in an ecological and evolutionary context. The current state of this research integration in A. thaliana is described by summarizing relevant approaches, current knowledge, and some potentially fruitful future studies. By introducing some of the fundamental questions of ecological and evolutionary research, experimental approaches and systems that can reveal new facets of gene function and gene effect are also described. A glossary is included in the Appendix. [source] Evidence for the multigenic inheritance of schizophreniaAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 8 2001Robert Freedman Abstract Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these findings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy-seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome-wide significant linkage (Z,=,3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the ,7-nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z,=,2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci. © 2001 Wiley-Liss, Inc. [source] Genetic control of susceptibility to bacterial infections in mouse modelsCELLULAR MICROBIOLOGY, Issue 5 2003Steven Lam-Yuk-Tseung Summary Historically, the laboratory mouse (Mus musculus) has been the experimental model of choice to study pathophysiology of infection with bacterial pathogens, including natural and acquired host defence mechanisms. Inbred mouse strains differ significantly in their degree of susceptibility to infection with various human pathogens such as Mycobacterium, Salmonella, Legionella and many others. Segregation analyses and linkage studies have indicated that some of these differences are under simple genetic control whereas others behave as complex traits. Major advances in genome technologies have greatly facilitated positional cloning of single gene effects. Thus, a number of genes playing a key role in initial susceptibility, progression and outcome of infection have been uncovered and the functional characterization of the encoded proteins has provided new insight into the molecular basis of antimicrobial defences of polymorphonuclear leukocytes, macrophages, as well as T and B lymphocytes. The multigenic control of susceptibility to infection with certain human pathogens is beginning to be characterized by quantitative trait locus mapping in genome wide scans. This review summarizes recent progress on the mapping, cloning and characterization of genes and proteins that affect susceptibility to infection with major intracellular bacterial pathogens. [source] Growth of Brucella abortus in macrophages from resistant and susceptible mouse strainsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2000J. Sathiyaseelan C57Bl/10 mice have a superior ability to control chronic infections with virulent strains of the intracellular bacteria Brucella abortus compared with BALB/c mice. While a number of differences in the cytokines produced by lymphocytes following infection of these two strains of mice have been shown, macrophages have not been evaluated for their role in conveying relative resistance. The importance of macrophages in control of brucella infections is demonstrated by the observations that intracellular survival of various strains of B. abortus directly correlates with their virulence in vivo, and the ability of macrophages to control brucellae in vitro has been shown to correlate with a brucella-resistant phenotype in ruminants. While both BALB/c and C57Bl are Nramp -susceptible mouse strains, additional differences in macrophage function outside of the Nramp1 gene effects could influence susceptibility to brucellosis. The studies conducted here comparing the ability of macrophages from C57Bl/10 and BALB/c mice indicate that the macrophages from resistant mice did not control intracellular growth of B. abortus strain 2308 more efficiently than those from the susceptible mice, either in the absence of, or following, interferon-gamma activation or iron supplementation. A number of different conditions for culturing macrophages were evaluated to rule out the influence of antibiotics on the conclusions drawn from the results. [source] Clinical involvement in daughters of men with fragile X-associated tremor ataxia syndromeCLINICAL GENETICS, Issue 1 2010W Chonchaiya Chonchaiya W, Nguyen DV, Au J, Campos L, Berry-Kravis EM, Lohse K, Mu Y, Utari A, Hervey C, Wang L, Sorensen P, Cook K, Gane L, Tassone F, Hagerman RJ. Clinical involvement in daughters of men with fragile X-associated tremor ataxia syndrome. Women with the fragile X mental retardation 1 (FMR1) premutation often have concerns about neurological and medical problems, as they become older and if their fathers experience fragile X-associated tremor/ataxia syndrome (FXTAS). We therefore determined the prevalence of these problems in 110 daughters of men with FXTAS [mean age of 44.8 years (SD 8.2)]. We compared them with 43 female controls with normal FMR1 alleles [mean age of 43.8 years (SD 8.1)] and 36 premutation carrier daughters of parents with the premutation, but without FXTAS [mean age of 43.5 years (SD 7.7)]. Overall, daughters of men with FXTAS have a higher prevalence of neurological symptoms including tremor, balance problems, memory problems, and dizziness, menopausal symptoms, and psychiatric involvement including sleep problems and anxiety when compared with non-carrier female controls. Reported balance problems and menopausal symptoms were significantly higher in daughters of men with FXTAS than in carrier daughters of parents without FXTAS, suggesting the potential influence of background gene effects. Therefore, neurological, psychological and gynecological surveillance should be warranted to better provide appropriate counseling, management and care for daughters of men with FXTAS. Biological markers of additional gene effects that predispose individuals with the premutation to FXTAS need to be developed. [source] | |||||||||||||