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At least 523 records · Page 29Linked to original sources
PubMed1987

Genetic analysis of Bacillus subtilis spo mutations generated by Tn917-mediated insertional mutagenesis.

Mutations that cause sporulation defects (spo mutations) often identify developmentally regulated transcription units or genes whose products are required for the expression of sporulation-specific regulons. We report here the isolation, genetic analysis and phenotypic characterization of spo mutations produced by insertional mutagenesis with transposon Tn917, a form of mutagenesis that facilitates genetic and physical manipulation of mutated genes in many ways. Twenty-four insertional spo mutations were studied in detail. On the basis of transformation-mediated and transduction-mediated linkage analysis and a range of phenotypic tests, these mutations were assigned to 20 distinct loci, at least 9 of which are different from the 40 previously described spo loci. The insertional mutations caused blocks at a variety of different stages of sporulation, and therefore probably identify genes active at different times during sporulation. In addition to increasing substantially the total of known spo loci, we anticipate that this collection will include representatives of many of the temporally regulated sets of genes that comprise the overall program of sporulation-specific gene activation in Bacillus subtilis. Given the kinds of manipulations that are possible with genes disrupted by Tn917 insertions, this should significantly facilitate efforts to understand the regulation of these gene sets.

Bacillus subtilis↗
PubMed2004

Protein C levels are regulated by a quantitative trait locus on chromosome 16: results from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project.

OBJECTIVE: Protein C (PC) is a component of the protein C anticoagulant pathway. PC deficiency is a risk factor associated with venous thromboembolism. As part of the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project, we conducted a genome-wide linkage scan to localize genes that influence variation in PC plasma levels. METHODS AND RESULTS: PC levels were measured in 398 individuals belonging to 21 Spanish families. A total of 485 DNA microsatellite markers were genotyped to provide a 7.1-cM genetic map. Variance component linkage methods were used to evaluate linkage and to detect quantitative trait loci (QTL). A region on chromosome 16 (16q23), flanked by markers D16S3106 and D16S516, showed strong evidence of linkage with PC levels (LOD=3.69). This region contains 1 positional candidate gene, the NAD(P)H:dehydrogenase quinone 1 (NQO1), involved in vitamin K metabolism. The association of 1 SNP of this gene with PC levels (P=0.005) strongly supports the implication of NQO1 gene in the variability of PC levels. CONCLUSIONS: These results illustrate the application of genomic scans to identify the genetic determinants of quantitative variation in a component of the hemostatic pathways. They provide strong evidence for a locus (QTL) on chromosome 16 that influences PC levels.

Adolescent↗
PubMed1986

Genetic analysis of thirty-three platelet polypeptides detected in two-dimensional polyacrylamide gels.

Two-dimensional gel electrophoresis followed by silver-staining was utilized to visualize platelet polypeptides for genetic analysis. A subset of 33 polypeptides that were most suited for scoring was selected. Families consisting of father-mother-child trios were studied. Thirty-six polypeptides of a total of 1,413 scored in children's gels exhibited the combination of a normal and a variant polypeptide. The observed index of heterozygosity of 2.55% is comparable to our previously reported findings for red cell proteins.

Blood Platelets↗
PubMed1973

Genetic analysis of ribonucleic acid polymerase mutants of Bacillus subtilis.

Deoxyribonucleic acid-dependent ribonucleic acid polymerase mutants of Bacillus subtilis strain Marburg were isolated after mutagenesis of spores with ethyl methane sulfonate. Genetic analysis by PBS1-mediated transduction and by transformation indicated that mutations responsible for all of the four phenotypic classes studied (rifampin resistance, streptovaricin resistance, streptolydigin resistance, and temperature sensitivity) were clustered close to the cysA14 locus. Three-factor transformation analysis has indicated the most probable marker order as follows: Rif(R)(Stv)(R)-Std(R)-Ts(418)-Ts(427). In addition, further characterization of the classical group I reference marker, cysA14, is reported.

Alkanesulfonates↗
PubMed1980

Search for ribosomal mutants in Podospora anserina: genetic analysis of mutants resistant to paromomycin.

It has recently been shown that paromomycin, an antibiotic of the aminoglycoside family, is also active on eukaryotic cytoplasmic ribosomes. In the fungus Podospora anserina, genetic analysis of ten mutants resistant to high doses of paromomycin shows that this resistance is caused by mutations in two different nuclear genes. These mutants display pleiotropic phenotypes (cold sensitivity, mycelium and spore appearance and coloration, cross-resistance to other antibiotics). Double mutants are either lethal or very altered and unstable. Moreover, the cytochrome spectra of these mutants seem to indicate that cytoplasmic protein synthesis is affected. The mutants also display a slight suppressor effect. We can therefore assume that these mutations affect cytoplasmic ribosomes.

Ascomycota↗
PubMed2001

A genetic analysis of neural progenitor differentiation.

Genetic mechanisms regulating CNS progenitor function and differentiation are not well understood. We have used microarrays derived from a representational difference analysis (RDA) subtraction in a heterogeneous stem cell culture system to systematically study the gene expression patterns of CNS progenitors. This analysis identified both known and novel genes enriched in progenitor cultures. In situ hybridization in a subset of clones demonstrated that many of these genes were expressed preferentially in germinal zones, some showing distinct ventricular or subventricular zone labeling. Several genes were also enriched in hematopoietic stem cells, suggesting an overlap of gene expression in neural and hematopoietic progenitors. This combination of methods demonstrates the power of using custom microarrays derived from RDA-subtracted libraries for both gene discovery and gene expression analysis in the central nervous system.

Animals↗
PubMed1999

Genetic analysis of human immunodeficiency virus in Abidjan, Ivory Coast reveals predominance of HIV type 1 subtype A and introduction of subtype G.

To better understand the molecular epidemiology of HIV genetic diversity in Abidjan, Ivory Coast, we performed a genetic analysis of 170 HIV-1-seropositive specimens representing newly diagnosed tuberculosis patients (n = 143) and women monitored in a mother-to-child transmission cohort study (n = 27). Preliminary screening with RFLP presumptively classified 162 (95.3%) of these as subtype A. The envelope region of 108 specimens was subtyped by sequence analysis: 102 (94.4%) were subtype A, 2 (1.9%) were subtype D, and 4 (3.7%) were subtype G. Subtyping gag and env regions of the genome suggested that five of the six nonsubtype A isolates exhibited a potentially mosaic structure. A comparative phylogenetic analysis of HIV-1 subtype A C2V3 from 27 Ivory Coast and 21 Ugandan sequences revealed a striking clustering among Ivory Coast variants, and an independent segregation from Ugandan subtype A. Despite independent clustering with other subtype A specimens, limited variability of the V3 loop apex was observed; the globally predominant V3 motif, GPGQ, represented 90.1% of the HIV-1 strains. This study demonstrates that clade A is the predominant HIV-1 subtype in HIV-seropositive individuals in Abidjan, Ivory Coast and that these strains are phylogenetically distinct from other subtype A strains observed in East Africa.

Amino Acid Sequence↗
PubMed1997

Female germline mosaicism in tuberous sclerosis confirmed by molecular genetic analysis.

We have investigated a family in which three siblings with the autosomal dominant disorder tuberous sclerosis had unaffected parents. The family were typed for polymorphic markers spanning the two genes known to cause tuberous sclerosis located at 9q34 (TSC1) and 16p13.3 (TSC2). TSC1 markers showed different maternal and paternal haplotypes in affected children, excluding a mutation in TSC1 as the cause of the disease. For the TSC2 markers all the affected children had the same maternal and paternal haplotypes, as did three of their unaffected siblings. Mutation screening by RT-PCR and direct sequencing of the TSC2 gene identified a 4 bp insertion TACT following nucleotide 2077 in exon 18 which was present in the three affected children but not in five unaffected siblings or the parents. This mutation would cause a frameshift and premature termination at codon 703. Absence of the mutation in lymphocyte DNA from the parents was consistent with germline mosaicism and this was confirmed by our finding of identical chromosome 16 haplotypes in affected and unaffected siblings, providing unequivocal evidence of two different cell lines in the gametes. Molecular analysis of the TSC2 alleles present in the affected subjects showed that the mutation had been inherited from the mother. This is the first case of germline mosaicism in tuberous sclerosis proven by molecular genetic analysis and also the first example of female germline mosaicism for a characterized autosomal dominant gene mutation apparently not associated with somatic mosaicism.

Adult↗
PubMed1991

Activity rhythms in inbred mice. I. Genetic analysis with recombinant inbred strains.

Rhythm of activity of inbred mice was recorded automatically by a set of actographs. This rhythm was characterized by six indices in the temporal and frequency domains. Two methods of genetic analysis were applied to these indices using parental strains BALB/c and C57BL/6, the reciprocal F1's, and the seven recombinant inbred strains (RI). Findings on the F1's show no maternal effect but indicate dominance and heterosis. The RI method successfully rejects the hypothesis of a monogenetic correlate for all measures. In line with F1 data, it demonstrates the presence of a polygenetic correlate: at least one other locus is involved in each of the six outcome parameters.

Activity Cycles↗
PubMed2004

Use of structured antedependence models for the genetic analysis of growth curves.

Growth curve analysis is an important issue for many agricultural and laboratory species, for both phenotypic and genetic studies. The aim of this paper is to present the use of a novel statistical approach, namely the structured antedependence (SAD) models, to deal with this issue. The basic idea of these models is that an observation at time t can be explained by the previous observations. These models are especially appropriate to deal with cumulative traits such as growth, as BW at age t clearly depends on BW measures at ages (t -1), (t -2), etc. These models were applied on an INRA experimental Charolais herd data set. The data comprised BW records for 560 cows born over an 11-yr period (from 1988 to 1998) from 60 sires and 369 dams. The proposed SAD models were compared with the well-known random regression (RR) models that are already widely used in various areas of longitudinal data analysis. It was found that the SAD models fit the growth process better with far fewer parameters than the RR models (9 instead of 16 covariance parameters for the phenotypic analysis, and 14 instead of 21 for the genetic analysis). Despite this smaller number of covariance parameters, the likelihood value was found to be much higher with the SAD vs. the RR models, with a difference of 262.9 for the phenotypic analysis with a quartic polynomial for the RR and 751.5 for the genetic analysis with a cubic polynomial for both the genetic and environmental parts of the RR model. The SAD models also proved to be better able to interpolate missing values. Heritability, genetic, and environmental correlation coefficients were estimated for weights from birth to adulthood. The structured antedependence models proved, in this study, to be very appropriate to model growth data in a parsimonious and flexible way.

Aging↗
PubMed2004

Problems and solutions in the genetic analysis of late-onset Alzheimer's disease.

The identification of the apolipoprotein E gene as a risk factor for late-onset Alzheimer's disease was a spectacularly successful application of genetic analysis to a complex trait, and it led to the hope and expectation that other risk loci for the disease would soon be forthcoming. Twelve years later, despite a huge amount of work, no other loci have been identified. In this article, we discuss the complexity of the problem and the pitfalls in the analytical methods that have been used and how we are approaching this problem.

Age of Onset↗
PubMed2002

Genetic analysis of pigment biosynthesis in Xanthobacter autotrophicus Py2 using a new, highly efficient transposon mutagenesis system that is functional in a wide variety of bacteria.

A highly efficient method of transposon mutagenesis was developed for genetic analysis of Xanthobacter autotrophicus Py2. The method makes use of a transposon delivery vector that encodes a hyperactive Tn 5 transposase that is 1,000-fold more active than the wild-type transposase. In this construct, the transposase is expressed from the promoter of the tetA gene of plasmid RP4, which is functional in a wide variety of organisms. The transposon itself contains a kanamycin resistance gene as a selectable marker and the origin of replication from plasmid R6K to facilitate subsequent cloning of the resulting insertion site. To test the effectiveness of this method, mutants unable to produce the characteristic yellow pigment (zeaxanthin dirhamnoside) of X. autotrophicus Py2 were isolated and analyzed. Transposon insertions were obtained at high frequency: approximately 1 x 10(-3) per recipient cell. Among these, pigment mutants were observed at a frequency of approximately 10(-3). Such mutants were found to have transposon insertions in genes homologous to known carotenoid biosynthetic genes previously characterized in other pigmented bacteria. Mutants were also isolated in Pseudomonas stutzeri and in an Alcaligenes faecalis, demonstrating the effectiveness of the method in diverse Proteobacteria. Preliminary results from other laboratories have confirmed the effectiveness of this method in additional phylogenetically diverse species.

Cloning, Molecular↗
PubMed1980

Population genetic analysis of human hand preference: evidence for generation differences, familial resemblance, and maternal effects.

Hand preference data were collected from 2818 subjects in 616 families using an adapted version of the Edinburgh Inventory. Population genetic analysis of these data and those from previous population studies, altogether encompassing 38,505 subjects in 8572 families, reveals evidence for generation differences, familial resemblance, and maternal effects.

Extrachromosomal Inheritance↗
PubMed2003

Isolation and identification of eight races of powdery mildew of roses (Podosphaera pannosa) (Wallr.: Fr.) de Bary and the genetic analysis of the resistance gene Rpp1.

Powdery mildew, caused by Podosphaera pannosa, is one of the most-severe diseases of roses grown under glass. The differentiation into physiological races and the genetic analysis of resistance in a segregating host population was investigated using single conidial isolates of the pathogen. Using ten rose genotypes, all eight isolates of the pathogen could be ascribed to different races. Five races were isolated from one location, which indicates that populations of P. pannosa exhibit a high racial diversity. Infection experiments in a backcross-population of 114 rose plants resulted in a 1:1 segregation, suggesting control by a single dominant gene. Rpp1 is the first resistance gene against rose powdery mildew to be described.

Ascomycota↗
PubMed2005

Approaches to detecting gene x gene interaction in Genetic Analysis Workshop 14 pedigrees.

Whether driven by the general lack of success in finding single-gene contributions to complex disease, by increased knowledge about the potential involvement of specific biological interactions in complex disease, or by recent dramatic increases in computational power, a large number of approaches to detect locus x locus interactions were recently proposed and implemented. The six Genetic Analysis Workshop 14 (GAW14) papers summarized here each applied either existing or refined approaches with the goal of detecting gene x gene, or locus x locus, interactions in the GAW14 data. Five of six papers analyzed the simulated data; the other analyzed the Collaborative Study on the Genetics of Alcoholism data. The analytic strategies implemented for detecting interactions included multifactor dimensionality reduction, conditional linkage analysis, nonparametric linkage correlation, two-locus parametric linkage analysis, and a joint test of linkage and association. Overall, most of the groups found limited success in consistently detecting all of the simulated interactions due, in large part, to the nature of the generating model.

Alcoholism↗
PubMed1998

Molecular genetic analysis of von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is a dominantly inherited multisystem family cancer syndrome predisposing to retinal and central nervous system haemangioblastomas, renal carcinoma, phaeochromocytoma, pancreatic islet cell tumours and endolymphatic sac tumours. In addition, renal, pancreatic and epididymal cysts occur. Morbidity and mortality from VHL disease can be reduced by the identification and surveillance of affected individuals and at-risk relatives so that complications are diagnosed at an early presymptomatic stage. The detailed mapping and subsequent isolation of the VHL tumour suppressor gene has enabled molecular genetic analysis in families and patients with definite or possible VHL disease. Initially, linked DNA markers were used in informative families to modify individual risks and then to make appropriate alterations in surveillance programs. However, currently most DNA analysis involves the characterisation of germline mutations. World-wide, mutations have been identified in almost 500 families (including 132 in our laboratory). These studies have revealed considerable heterogeneity both in the type and in the location of mutations within the VHL gene. In our experience, most recurrent mutations result from de novo mutations at hypermutable sequences, although a founder effect for the Tyr98His ('Black Forest') mutation has been reported in German and American families. Although many mutations are predicted to impair the ability of pVHL to combine with the elongin regulatory subunits, analysis of genotype-phenotype relationships suggests that the VHL protein has multiple and tissue specific functions. Calculation of tumour risks for different classes of VHL mutations has provided important prognostic information especially with respect to the likelihood of phaeochromocytoma. However, there is evidence that retinal involvement does not correlate with allelic heterogeneity, but that the variability in retinal angiomatosis is influenced by modifier gene effects. VHL gene mutation analysis also provides a basis for investigating the genetic basis of familial phaeochromocytoma and renal cell carcinoma, and apparently isolated retinal angiomas. Results to date suggest that a substantial proportion of patients with familial pheochromocytoma have VHL gene mutations but in contrast, most familial clusters of clear cell renal cell carcinoma (RCC) without evidence of VHL do not have germline VHL mutations.

Age of Onset↗
PubMed2004

Clinical and genetic analysis of a family with PROMM.

PROMM (proximal myotonic myopathy) and DM2 (myotonic dystrophy Type 2) are autosomal dominant multisystem disorders that have both been linked to chromosome 3q. Recently, the genetic basis of DM2 has been defined by a '(CCTG)(n)' expansion mutation in intron 1 of the ZNF9 gene. We identified and studied a multigenerational family in which five members had clinical features consistent with PROMM. Two affected members were available for detailed clinical, electrophysiological, radiological and genetic analysis. Our study confirms that the PROMM phenotype is associated with DM2-(CCTG)(n) expansion mutations. In addition, our results may extend the clinical spectrum of manifestations to include vestibular symptoms.

DNA Mutational Analysis↗
PubMed2002

Genetic analysis of viruses associated with emergence of Rift Valley fever in Saudi Arabia and Yemen, 2000-01.

The first confirmed Rift Valley fever outbreak outside Africa was reported in September 2000, in the Arabian Peninsula. As of February 2001, a total of 884 hospitalized patients were identified in Saudi Arabia, with 124 deaths. In Yemen, 1,087 cases were estimated to have occurred, with 121 deaths. Laboratory diagnosis of Rift Valley fever virus (RVFV) infections included virus genetic detection and characterization of clinical specimens by reverse transcription-polymerase chain reaction, in addition to serologic tests and virus isolation. Genetic analysis of selected regions of virus S, M, and L RNA genome segments indicated little genetic variation among the viruses associated with disease. The Saudi Arabia and Yemen viruses were almost identical to those associated with earlier RVF epidemics in East Africa. Analysis of S, M, and L RNA genome segment sequence differences showed similar phylogenetic relationships among these viruses, indicating that genetic reassortment did not play an important role in the emergence of this virus in the Arabian Peninsula. These results are consistent with the recent introduction of RVFV into the Arabian Peninsula from East Africa.

Antigens, Viral↗