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At least 685 records · Page 38Linked to original sources
PubMed2003

[Molecular genetics in nephrology. Genetic kidney diseases provide clues for understanding the pathogenesis of proteinuria].

Recent progress in defining the genetic basis of inherited glomerular diseases has provided a completely new understanding of the glomerular filter of the kidney and has helped illuminate the pathogenesis of acquired and inherited renal proteinuric diseases. Based on the findings of molecular genetics in nephrology we will discuss the current understanding of the glomerular filter and provide an idea how genetic testing in the future may help to guide therapy in patients suffering from nephrotic syndrome and progressive renal failure.

Adult↗
PubMed2001

Plague dynamics and population genetics of the desert locust: can turnover during recession maintain population genetic structure?

The desert locust (Schistocerca gregaria) undergoes crowding-induced phase transformation from solitary form to gregarious form. The transformations involves changes in behaviour, colour, development, morphometry, fecundity and endocrine physiology. Recession populations of the desert locust exist primarily in the solitary phase as small populations in patchy environments and are prone to extinction because of climatic events. Significant genetic differentiation among recession populations along the Red Sea coast of Eritrea was previously reported. It was hypothesized that despite the mixing effect of recurrent swarms, metapopulation dynamics could have produced genetic divergence among these highly scattered recession populations. A Monte Carlo simulation of the population dynamics of the desert locust in a metapopulation setting, with a realistic range of parameter values clearly demonstrated that this is possible. Population growth was represented by a discrete-time logistic equation. The duration of recessions and swarms was sampled from normal distributions whose means and standard deviations were varied based on reported estimates. An average recession duration of 10 +/- 3 generations and swarm periods half as long but almost twice as variable produced a partitioning of the total genetic variance most similar to that in the empirical study. In conventional metapopulation analysis, whether turnover leads to increased or reduced divergence is dependent on the number of colonists relative to the number of recurrent migrants, and on whether the colonists arise from a single patch or many patches. In the case of locusts, the stochastic boom and bust cycle is the overriding factor. Divergence between patches during recession due to founder effect and recurrent drift is balanced by the high rate of mixing during plagues.

Alleles↗
PubMed2003

Genetics of drought adaptation in Arabidopsis thaliana: I. Pleiotropy contributes to genetic correlations among ecological traits.

We examined patterns of genetic variance and covariance in two traits (i) carbon stable isotope ratio delta13C (dehydration avoidance) and (ii) time to flowering (drought escape), both of which are putative adaptations to local water availability. Greenhouse screening of 39 genotypes of Arabidopsis thaliana native to habitats spanning a wide range of climatic conditions, revealed a highly significant positive genetic correlation between delta13C and flowering time. Studies in a range of C3 annuals have also reported large positive correlations, suggesting the presence of a genetically based trade-off between mechanisms of dehydration avoidance (delta13C) and drought escape (early flowering). We examined the contribution of pleiotropy by using a combination of mutant and near-isogenic lines to test for positive mutational covariance between delta13C and flowering time. Ecophysiological mutants generally showed variation in delta13C but not flowering time. However, flowering time mutants generally demonstrated pleiotropic effects consistent with natural variation. Mutations that caused later flowering also typically resulted in less negative delta13C and thus probably higher water use efficiency. We found strong evidence for pleiotropy using near-isogenic lines of Frigida and Flowering locus C, cloned loci known to be responsible for natural variation in flowering time. These data suggest the correlated evolution of delta13C and flowering time is explained in part by the fixation of pleiotropic alleles that alter both delta13C and time to flowering.

Adaptation, Biological↗
PubMed2001

Genetic counseling issues in predictive genetic testing for familial adult-onset neurologic diseases.

Genetic counseling is important in any genetic testing situation in order to address the various issues related to obtaining a genetic diagnosis. Presymptomatic testing for adult-onset neurodegenerative disease, in particular, presents a complex counseling scenario. It is imperative to discuss the potential impact of test results on patients' family dynamics, insurability and employability, family planning, and future health in addition to ascertaining a complete understanding of recurrence, inheritance, and testing parameters. The Huntington disease presymptomatic testing protocol is well-defined and has been used for more than 10 years. These guidelines, which protect both patient and provider, can now be applied to other diseases as further presymptomatic testing capabilities are realized.

Adult↗
PubMed2000

Genetic analysis of a bacterial genetic exchange element: the gene transfer agent of Rhodobacter capsulatus.

An unusual system of genetic exchange exists in the purple nonsulfur bacterium Rhodobacter capsulatus. DNA transmission is mediated by a small bacteriophage-like particle called the gene transfer agent (GTA) that transfers random 4.5-kb segments of the producing cell's genome to recipient cells, where allelic replacement occurs. This paper presents the results of gene cloning, analysis, and mutagenesis experiments that show that GTA resembles a defective prophage related to bacteriophages from diverse genera of bacteria, which has been adopted by R. capsulatus for genetic exchange. A pair of cellular proteins, CckA and CtrA, appear to constitute part of a sensor kinase/response regulator signaling pathway that is required for expression of GTA structural genes. This signaling pathway controls growth-phase-dependent regulation of GTA gene messages, yielding maximal gene expression in the stationary phase. We suggest that GTA is an ancient prophage remnant that has evolved in concert with the bacterial genome, resulting in a genetic exchange process controlled by the bacterial cell.

Amino Acid Sequence↗
PubMed2004

Genetic interactions between Brca1 and Gadd45a in centrosome duplication, genetic stability, and neural tube closure.

GADD45a is a transcription target of the breast tumor suppressor gene BRCA. It was recently shown that mouse embryonic fibroblast cells carrying a targeted deletion of exon 11 of Brca1 (Brca1(Delta11/Delta11)) or a Gadd45A-null mutation (Gadd45a(-/-)) suffer centrosome amplification. To study genetic interactions between these genes during centrosome duplication, we generated Brca1(Delta11/Delta)(11)Gadd45a(-/-) mice by crossing each mutant. We found that all Brca1(Delta11/Delta11)Gadd45a(-/-) embryos at embryonic days 9.5-10.5 were exencephalic and exhibited a high incidence of apoptosis accompanied by altered levels of BAX, BCL-2, and p53. The trigger for these events is likely the genetic instability arising from centrosome amplification that is associated, at least in part, with decreased expression of the NIMA-related kinase NEK2. We demonstrate that small interfering RNA-mediated suppression of Brca1 decreased Nek2 more dramatically in Gadd45a(-/-) cells than in wild-type cells and, conversely, that overexpression of Brca1 and/or Gadd45a up-regulated transcription of Nek2. Furthermore, we show that overexpression of Nek2 in Brca1-specific small interfering RNA-treated wild-type and Gadd45a(-/-) cells repressed abnormal centrosome amplification. These observations suggest that NEK2 plays a role in mediating the actions of BRCA1 and GADD45a in regulating centrosome duplication and in maintaining genetic stability.

Animals↗
PubMedDate not supplied

Dogrib Indians of the Northwest Territories, Canada: genetic diversity and genetic relationship among subarctic Indians.

Phenotypes and gene frequencies of genes at the ABO, Rhesus, MNSs, Diego, Duffy, Kell, Kp, Kidd and P blood group systems are presented for three villages of Dogrib Indians. This population resides between Great Slave and Great Bear Lakes in the Northwest Territories of Canada. Until recently they pursued an exclusively hunting-gathering-fishing lifestyle in the subarctic forest. Maximum European admixture in the Dogrib is 8.7%. Nei's coefficient of gene diversity, GST is 0.0121. Blood group data from other Athapaskan-speaking Indians were also examined. GST for Kutchin villages is approximately 1.1%. GST obtained over five tribes of Northern Athapaskans is 0.0264, a figure slightly lower than that found in comparable groups of Mexican Indians. Overall genetic differentiation (HT) in Northern Athapaskans was greater than in the Mexicans, presumably because of high, though nonquantifiable European admixture in some of the tribes. The bulk of the genetic variability in Athapaskans exists within tribes, and then within villages of the same tribe. Genetic distance analysis with Nei's standard distance D shows that Dogrib and Kutchin Indians are very close. Geographic proximity has no significant influence on inter-tribal gene flow, but is significantly associated with intra-tribal gene flow.

Adult↗
PubMed2000

Early detection of genetic hemochromatosis: should all young adults be offered the genetic test?

Genetic hemochromatosis (GH) is a late-onset, autosomal recessive disorder. The majority of those at risk from iron overload and its clinical consequences may be detected by a simple genetic test. Furthermore, treatment by phlebotomy, if instituted early, removes excess iron and prevents the complications of iron overload which include arthralgia, diabetes, and cirrhosis of the liver. GH seems to be an obvious candidate for inclusion in national screening programs. However, important questions remain concerning the proportion of individuals with the high-risk genotype who eventually show clinical manifestations of iron overload and the significance of heterozygosity for haemochromatosis in terms of morbidity. Until these questions are resolved, the introduction of widespread genetic screening cannot be justified.

Adolescent↗
PubMed2003

Genetic Network Analyzer: qualitative simulation of genetic regulatory networks.

MOTIVATION: The study of genetic regulatory networks has received a major impetus from the recent development of experimental techniques allowing the measurement of patterns of gene expression in a massively parallel way. This experimental progress calls for the development of appropriate computer tools for the modeling and simulation of gene regulation processes. RESULTS: We present Genetic Network Analyzer (GNA), a computer tool for the modeling and simulation of genetic regulatory networks. The tool is based on a qualitative simulation method that employs coarse-grained models of regulatory networks. The use of GNA is illustrated by a case study of the network of genes and interactions regulating the initiation of sporulation in Bacillus subtilis. AVAILABILITY: GNA and the model of the sporulation network are available at http://www-helix.inrialpes.fr/gna.

Bacillus subtilis↗
PubMed2003

Dynamic modeling of genetic networks using genetic algorithm and S-system.

MOTIVATION: The modeling of system dynamics of genetic networks, metabolic networks or signal transduction cascades from time-course data is formulated as a reverse-problem. Previous studies focused on the estimation of only network structures, and they were ineffective in inferring a network structure with feedback loops. We previously proposed a method to predict not only the network structure but also its dynamics using a Genetic Algorithm (GA) and an S-system formalism. However, it could predict only a small number of parameters and could rarely obtain essential structures. In this work, we propose a unified extension of the basic method. Notable improvements are as follows: (1) an additional term in its evaluation function that aims at eliminating futile parameters; (2) a crossover method called Simplex Crossover (SPX) to improve its optimization ability; and (3) a gradual optimization strategy to increase the number of predictable parameters. RESULTS: The proposed method is implemented as a C program called PEACE1 (Predictor by Evolutionary Algorithms and Canonical Equations 1). Its performance was compared with the basic method. The comparison showed that: (1) the convergence rate increased about 5-fold; (2) the optimization speed was raised about 1.5-fold; and (3) the number of predictable parameters was increased about 5-fold. Moreover, we successfully inferred the dynamics of a small genetic network constructed with 60 parameters for 5 network variables and feedback loops using only time-course data of gene expression.

Algorithms↗
PubMed1985

The molecular through ecological genetics of abnormal abdomen in Drosophila mercatorum. I. Basic genetics.

The abnormal abdomen syndrome (aa) in Drosophila mercatorum is characterized by the persistence of juvenilized cuticle on the adult abdomen. The aa phenotype is shown to depend on at least two X-linked genetic elements that are about one map unit apart near the centromeric end of the X chromosome. These two genetic elements are necessary for aa expression; one behaves as a dominant element and the other as a recessive. Overlaying these genetic studies upon molecular work reported elsewhere, it is argued that the dominant element is the presence of a 5 kb insertion in a majority of the X-linked repeats coding for the 28S ribosomal RNA. The recessive element appears to be a locus controlling differential replication of noninserted over inserted 28S genes during polytenization. The aa syndrome requires both the presence of the inserted repeats and the failure to preferentially amplify noninserted repeats. Given the necessary X-linked elements for aa, a variety of modifiers are revealed. First, aa expression in males is Y-linked, apparently corresponding to a deletion of the 18S/28S rDNA gene cluster normally found on the Y. Moreover, all major autosomes can modify the penetrance of aa.

Abdomen↗
PubMed1995

Genetics of male sterility in gynodioecious Plantago coronopus. II. Nuclear genetic variation.

Inheritance of male sterility was studied in the gynodioecious species Plantago coronopus using five plants and their descendants from an area of approximately 50 m2 from each of four locations. In each location, crosses between these five plants yielded the entire array of possible sex phenotypes. Both nuclear and cytoplasmic genes were involved. Emphasis is placed on the nuclear (restorer) genetics of two cytoplasmic types. For both types, multiple interacting nuclear genes were demonstrated. These genes carried either dominant or recessive restorer alleles. The exact number of genes involved could not be determined, because different genetic models could be proposed for each location and no common genetic solution could be given. At least five genes, three with dominant and two with recessive restorer allele action, were involved with both cytoplasmic types. Segregation patterns of partially male sterile plants suggested that they are due to incomplete dominance at restorer loci. Restorer genes interact in different ways. In most instances models with independent restorer gene action were sufficient to explain the crossing results. However, for one case we propose a model with epistatic restorer gene action. There was a consistent difference in the segregation of male sterility between plants from the two cytoplasmic types. Hermaphrodites of cytoplasmic type 2 hardly segregated male steriles, in contrast to plants with cytoplasmic type 1.

Alleles↗
PubMedDate not supplied

The genetic associate: a career option in genetic counseling.

Eleven training programs designed to prepare genetic associates (genetic counselors) at the master's degree level are compared and contrasted. Sarah Lawrence College developed the first such program in 1969; currently, most genetic associate programs are housed in medical schools in major universities across the nation. The newest program (at the University of South Carolina) accepted its first class in the fall of 1985. Data provided herein will enable college and university faculty to advise interested students about this viable career option.

Allied Health Personnel↗
PubMedDate not supplied

The genetics of host-pathogen coevolution: implications for genetic resource conservation.

The results of long-term studies of coevolution in the Hordeum vulgare-Rhynchosporium secalis pathosystem are summarized. The genetic systems of barley (host) and R. secalis (pathogen) are complementary: Gene-for-gene interactions among loci affect many traits, leading to self-regulating adjustments over generations between host and pathogen populations. Different pathotypes differ widely in their ability to damage the host, and different host-resistance alleles differ widely in their ability to protect the host from the pathogen. Among 29 resistance loci in the specific host population studied, several played major roles in providing stable resistance, but many had net detrimental effects on the yield and reproductive ability of the host. Resistance alleles that protected against the most damaging pathotypes increased sharply in frequency in the host populations. It is concluded that the evolutionary processes that take place in genetically variable populations propagated under conditions of cultivation can be highly effective in increasing the frequency of desirable alleles and useful multilocus genotypes. This enhances the value of the evolving populations as sources of genetic variability in breeding for disease resistance and other characters that affect adaptedness.

Biological Evolution↗
PubMed2006

The mef(E)-carrying genetic element (mega) of Streptococcus pneumoniae: insertion sites and association with other genetic elements.

The structure of the macrolide efflux genetic assembly (mega) element, its genomic locations, and its association with other resistance determinants and genetic elements were investigated in 16 Streptococcus pneumoniae isolates carrying mef(E), of which 1 isolate also carried tet(M) and 4 isolates also carried tet(M) and erm(B). All isolates carried a mega element of similar size and structure that included the operon mef(E)-msr(D) encoding the efflux transport system. Among tetracycline-susceptible isolates, six different integration sites were identified, five of which were recognized inside open reading frames present in the R6 genome. In the five isolates also carrying tet(M), mega was inserted in different genetic contexts. In one isolate, it was part of previously described Tn916-like element Tn2009. In another isolate, mega was inserted in a transposon similar to Tn2009 that also included an erm(B) element. This new composite transposon was designated Tn2010. Neither Tn2009 nor Tn2010 could be transferred by conjugation to pneumococcal or enterococcal recipients. In the three isolates in which mega was not physically linked with tet(M), this gene was associated with erm(B) in transposon Tn3872, a Tn916-like element. Homologies between the chromosomal insertions of these composite transposons and sequences of multidrug-resistant pneumococcal genomes in the databases indicate the presence of preferential sites for the integration of composite Tn916-like elements carrying multiple resistance determinants in S. pneumoniae.

Bacterial Proteins↗
PubMed2001

Distribution and genetic diversity of suilysin in Streptococcus suis isolated from different diseases of pigs and characterization of the genetic basis of suilysin absence.

Streptococcus suis is an economically important pathogen of pigs responsible for a variety of diseases including meningitis, septicemia, arthritis, and pneumonia, although little is known about the mechanisms of pathogenesis or virulence factors associated with this organism. Here, we report on the distribution and genetic diversity of the putative virulence factor suilysin, a member of the thiol-activated toxin family of gram-positive bacteria. On the basis of PCR analysis of over 300 isolates of S. suis, the suilysin-encoding gene, sly, was detected in 69.4% of isolates. However, sly was present in a considerably higher proportion of isolates obtained from cases of meningitis, septicemia, and arthritis (>80%) and isolates obtained from asymptomatic tonsillar carriage (>90%) than lung isolates associated with pneumonia (44%). With the exception of serotypes 1, 14, and 1/14, there was no strong correlation between the presence of suilysin and serotype. Analysis of the genetic diversity of suilysin by restriction fragment length polymorphism and sequence analysis found that the suilysin gene, where present, is highly conserved with a maximum of 1.79% diversity at the nucleotide level seen between sly alleles. Assays of hemolytic activity and hybridization analysis provided no evidence for a second member of the thiol-activated toxin family in S. suis. Inverse PCR was used to characterize regions flanking sly, which in turn allowed the first characterization of the equivalent region in a strain lacking sly. Sequence comparison of these regions from sly-positive (P1/7) and sly-negative (DH5) strains indicated that two alternative arrangements are both flanked by genes with highest similarity to haloacid dehalogenase-like hydrolases (5' end) and putative N-acetylmannosamine-6-phosphate epimerases (3' end). However, sly appears to be completely absent from the alternative arrangement, and a gene of unknown function is located in the equivalent position. Finally, PCR analysis of multiple sly-positive and -negative strains indicated that these two alternative genetic arrangements are conserved among many S. suis isolates.

Amino Acid Sequence↗
PubMed1997

Evidence for primary genetic determination of heart rate regulation: chromosomal mapping of a genetic locus in the rat.

BACKGROUND: We investigated whether an accelerated heart rate (HR), observed in the stroke-prone spontaneously hypertensive rat (SHRSP(HD)), is a primary, genetically determined trait and whether it contributes to blood pressure (BP) regulation in this model of polygenic hypertension. METHODS AND RESULTS: We measured BP and HR in SHRSP(HD) and normotensive Wistar-Kyoto rats (WKY), as well as in F2 hybrids bred from crossing the two strains, at baseline and after 12 days of dietary NaCl loading. Random marker genome screening and cosegregation analysis were performed on F2 hybrids derived from SHRSP(HD)/WKY-0(HD) (n=115) and SHRSP(HD)/WKY-1(HD) (n=139) crosses (WKY-0(HD) and WKY-1(HD) are two congenic WKY strains). HR in SHRSP(HD) was significantly higher than in WKY-0(HD) both at baseline (404+/-30 versus 375+/-46 bpm; P=.0034) and after NaCl (437+/-23 versus 364+/-40 bpm; P=10(-9)). BP in F2 hybrids showed no significant correlation with HR either at baseline or after NaCl loading. HR after NaCl loading but not at baseline was significantly linked in a recessive fashion to a locus on chromosome 3: in animals homozygous for the SHRSP(HD) allele, HR was 414+/-49 compared with 383+/-44 bpm in heterozygotes and WKY homozygotes (F(210,1)=19.7, P=1.4x10(-5), lod score=5.9). The putative BP-relevant gene at this locus, termed HR-SP1, showed no evidence of linkage to any of the BP parameters measured. CONCLUSIONS: Our results demonstrate that a genetic locus on rat chromosome 3, HR-SP1, contributes directly to the regulation of HR in SHRSP(HD) but exhibits no effect on BP. Thus, in addition to its modulation by reflex-mediated neurohumoral mechanisms, HR is also under the direct influence of primary genetic factors.

Analysis of Variance↗
PubMed2002

Genetic contribution to circulating levels of hemostatic factors in healthy families with effects of known genetic polymorphisms on heritability.

Levels of fibrinogen, factor VII (FVII), factor XIII (FXIII), plasminogen activator inhibitor (PAI)-1, and tissue plasminogen activator have been associated with coronary artery disease as have genetic polymorphisms. Quantitative genetic analyses allow determination of the genetic contribution to phenotypic variation. We investigated familial influences on these hemostatic factors in 537 adults from 89 randomly ascertained healthy families of white North European origin. We used maximum likelihood analysis to estimate the heritabilities of these factors and effects of covariates on the factors in these families. After adjustment for age and sex, the factors showed considerable heritability, varying from 26% (PAI-1) to 47% (FXIII complex). The influence of known polymorphisms was negligible for fibrinogen and contributed 2% to the variance of the FXIII complex and PAI-1 and 11% to the variance of FVII coagulant activity. Age, sex, body mass index, lifestyle, and metabolic covariates explained between 10% (FXIII) and 44% (PAI-1) of phenotypic variance. Childhood household influences significantly affected FVII (11%) and FXIII (18%). A significant degree of phenotypic variance of several hemostatic factors can be explained by additive genes and known covariates. The impact of certain well-characterized polymorphisms to the heritability is small in this population of healthy families, indicating the need to localize new genes influencing hemostatic factor levels.

Adult↗