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At least 955 records · Page 53Linked to original sources
PubMed1999

Nonrandom distribution of hepatitis C virus quasispecies in plasma and peripheral blood mononuclear cell subsets.

The existence of an extrahepatic reservoir of hepatitis C virus (HCV) is suggested by differences in quasispecies composition between the liver, peripheral blood mononuclear cells, and serum. We studied HCV RNA compartmentalization in the plasma of nine patients, in CD19(+), CD8(+), and CD4(+) positively selected cells, and also in the negatively selected cell fraction (NF). HCV RNA was detected in all plasma samples, in seven of nine CD19(+), three of eight CD8(+), and one of nine CD4(+) cell samples, and in seven of eight NF cells. Cloning and sequencing of HVR1 in two patients showed a sequence grouping: quasispecies from a given compartment (all studied compartments for one patient and CD8(+) and NF for the other) were statistically more genetically like each other than like quasispecies from any other compartment. The characteristics of amino acid and nucleotide substitutions suggested the same structural constraints on HVR1, even in very divergent strains from the cellular compartments, and homogeneous selection pressure on the different compartments. These findings demonstrate the compartmental distribution of HCV quasispecies within peripheral blood cell subsets and have important implications for the study of extrahepatic HCV replication and interaction with the immune system.

Amino Acid Sequence↗
PubMed1990

Immunogenetic study of the response to streptococcal carbohydrate antigen of the cell wall in rheumatic fever.

An immunogenetic study of the response to streptococcal carbohydrate antigen of the cell wall was carried out on members of 15 multiplex families each having more than one sib affected with rheumatic heart disease. They comprised 30 parents and 61 sibs (32 with rheumatic disease and 29 without). Fifty healthy unrelated subjects served as controls. A history was taken and clinical examination carried out. Rheumatic activity was determined and HLA typing was carried out for nine A antigens, 15 B antigens, and six DR antigens. The immune response of lymphocytes to streptococcal polysaccharide antigen of the cell wall of group A beta haemolytic streptococci in vitro was studied by tritiated thymidine uptake. The results were statistically and genetically analysed. It was found that (a) all subjects with rheumatic disease were highly responsive to the streptococcal polysaccharide antigen of the cell wall, the sib pairs being mostly HLA identical; (b) all low responders had no rheumatic disease and their phenotypes were mostly different from those of the rheumatic member of their sib pair; (c) correlation of immune responsiveness (high or low) between HLA-identical sibs was significant, but insignificant between haplotype identical and non-identical sibs; (d) the gene responsible for high responsiveness to the streptococcal polysaccharide antigen of the cell wall is recessive and closely linked to HLA. In conclusion, it was found that exposure to pharyngeal infection with group A beta haemolytic streptococci may lead to acute rheumatic fever in those with an inherited recessive gene responsible for high responsiveness to the streptococcal polysaccharide antigen of the cell wall.

Adolescent↗
PubMed1997

Intrafamilial variation of the phenotype in Bardet-Biedl syndrome.

AIMS: To describe the variation of the phenotype within families with several individuals with Bardet-Biedl syndrome. METHODS: The phenotypes of affected siblings in 11 Scandinavian families with two or more members who had at least three of the features: retinal dystrophy, polydactyly, obesity, hypogenitalism, and mental retardation, were compared [corrected]. Individuals without retinal dystrophy were excluded. RESULTS: Intrafamilial variation of expressivity of the features obesity, polydactyly, abnormal radiograms of the extremities, hypogenitalism, short stature, paraplegia, and dental abnormalities was found. The retinal dystrophy varied with respect to both the onset of symptoms and the course of the disease. The morphology of the fundus, however, was consistent within the families. The disorder showed statistically significant genetic linkage to the BBS4 locus on chromosome 15 in the affected siblings in two of the families, but the clinical features in these patients did not differ from the other cases of Bardet-Biedl syndrome. CONCLUSION: Comparison of siblings with the Bardet-Biedl syndrome showed variation of the typical features. In addition, the course of retinal dystrophy varied. No distinctive clinical features were found to separate the BBS4 phenotype from the remaining patients.

Abnormalities, Multiple↗
PubMed2006

Significant positive correlation between the recombination rate and GC content in the human pseudoautosomal region.

This paper establishes that recombination drives the evolution of GC content in a significant way. Because the human P-arm pseudoautosomal region (PAR1) has been shown to have a high recombination rate, at least 20-fold more frequent than the genomic average of approximately 1 cM/Mb, this region provides an ideal system to study the role of recombination in the evolution of base composition. Nine non-coding regions of PAR1 are analyzed in this study. We have observed a highly significant positive correlation between the recombination rate and GC content (rho = 0.837, p < or = 0.005). Five regions that lie in the distal part of PAR1 are shown to be significantly higher than genomic average divergence. By comparing the intra- and inter-specific AT->GC -GC->AT ratios, we have detected no fixation bias toward GC alleles except for L254915, which has excessive AT-->GC changes in the human lineage. Thus, we conclude that the high GC content of the PAR1 genes better fits the biased gene conversion (BGC) model.

Animals↗
PubMed1975

Genetic analysis of a population of Tribolium. V. Viability of the unsaturated fatty acid sensitive mutant.

The viability pattern of the unsaturated fatty acid sensitive mutant (cos/cos) of Tribolium castaneum was examined with reference to the normal genotype from egg hatching through adult emergence. The beetles were cultured on diets with 0, 3, or 5% corn oil in growth chambers maintained at 33 +/- 1 degree C and either 42 +/- 6% or 75 +/- 3% relative humidity. The pattern of the mutant was altered during the larval stage and was dependent on both the concentration of dietary fatty acid and the relative humidity of the culture chamber. Values of the viability component of fitness were assigned to the cos/cos, +/-/cos and +/-/+/- genotypes for multiple environments based on the number of eggs surviving to pupation. In large, random mating populations segregating at this locus, a stable genetic polymorphism is forecast. Predicted rates of change of allele frequency are dependent upon the culture conditions.

Animals↗
PubMed1977

Recombination values and their errors.

Two four-point testcrosses comprising 87,000 tomato plants were grown and the data collected from 28 subgroups. Each subgroup consisted of 2,000 or 5,000 plants and should give a valid estimate of the three recombination values. The 28 values for each interval give more outlyers (23% are outside the 95% limits set by the standard deviation calculated by the binomial formula square root of p q/n) than would be expected by chance. If each subgroup was regarded as the control and the other groups tested against this, then 42% of the time the two subgroups would be significantly different. It is suggested that there are many cases in the literature where this comparison has been made and the significant difference wrongly ascribed to treatment. While the causes of these changes in recombination value are unknown and therefore uncontrollable, they must be anticipated in all such studies. Control and treatment must be replicated enough that chance extreme values will not be attributed to treatment.

Crosses, Genetic↗
PubMed1990

Replicate differences in lines of mice selected for body composition.

Replicate differences were studied in lines of mice selected at 12 weeks of age for high (HF1, HF2) or low (LF1, LF2) right epididymal fat pad weight as a percentage of body weight (%EFP); for high (HL1, HL2) or low (LL1, LL2) hind carcass weight as a percentage of body weight (%HC); and randomly (RC1, RC2). Correlated traits were subcutaneous fat pad weight as a percentage of body weight (%SFP), water weight in hind carcass as a percentage of hind carcass weight (%WAT), body weights at 3, 6, and 12 weeks of age, and 3- to 6-week weight gain. Individual and maternal effects contributed to significant genetic drift for selected and correlated traits. No evidence indicated that drift was greater in selection treatments than in controls. Significant heterosis in replicate crosses within selection treatments was found for %HC in HL, LL, and LF and for %EFP in HF. Heterosis was insignificant in crosses of control replicates. Divergence in parental lines and replicate crosses was similar, indicating that differences in heterosis between high and low lines were small relative to divergence. Asymmetry tended to be greater between replicate crosses and parental lines, because selected replicates have greater average heterosis than control replicates. Multivariate discriminant function and Mahalanobis distance analysis of selected traits showed that divergence between replicates within selection treatments was much less than among selection treatments.

Adipose Tissue↗
PubMed2005

Recurrence time statistics: versatile tools for genomic DNA sequence analysis.

With the completion of the human and a few model organisms' genomes, and with the genomes of many other organisms waiting to be sequenced, it has become increasingly important to develop faster computational tools which are capable of easily identifying the structures and extracting features from DNA sequences. One of the more important structures in a DNA sequence is repeat-related. Often they have to be masked before protein coding regions along a DNA sequence are to be identified or redundant expressed sequence tags (ESTs) are to be sequenced. Here we report a novel recurrence time-based method for sequence analysis. The method can conveniently study all kinds of periodicity and exhaustively find all repeat-related features from a genomic DNA sequence. An efficient codon index is also derived from the recurrence time statistics, which has the salient features of being largely species-independent and working well on very short sequences. Efficient codon indices are key elements of successful gene finding algorithms, and are particularly useful for determining whether a suspected EST belongs to a coding or non-coding region. We illustrate the power of the method by studying the genomes of E. coli, the yeast S. cervisivae, the nematode worm C. elegans, and the human, Homo sapiens. Our method requires approximately 6 . N byte memory and a computational time of N log N to extract all the repeat-related and periodic or quasi-periodic features from a sequence of length N without any prior knowledge on the consensus sequence of those features, hence enables us to carry out sequence analysis on the whole genomic scale by a PC.

Algorithms↗
PubMed2005

Discovery of highly differentiative gene groups from microarray gene expression data using the gene club approach.

MOTIVATION: It is commonly believed that suitable analysis of microarray gene expression profile data can lead to better understanding of diseases, and better ways to diagnose and treat diseases. To achieve those goals, it is of interest to discover the gene interaction networks, and perhaps even pathways, underlying given diseases from such data. In this paper, we consider methods for efficiently discovering highly differentiative gene groups (HDGG), which may provide insights on gene interaction networks. HDGGs are groups of genes which completely or nearly completely characterize the diseased or normal tissues. Discovering HDGGs is challenging, due to the high dimensionality of the data. RESULTS: Our methods are based on the novel concept of gene clubs. A gene club consists of a set of genes having high potential to be interactive with each other. The methods can (i) efficiently discover signature HDGGs which completely characterize the diseased and the normal tissues respectively, (ii) find strongest or near strongest HDGGs containing any given gene, and (iii) find much stronger HDGGs than previous methods. As part of the experimental evaluation, the methods are applied to colon, prostate, ovarian, and breast cancer, and leukemia and so on. Some of the genes in the extracted signature HDGGs have known biological functions, and some have attracted little attention in biology and medicine. We hope that appropriate study on them can lead to medical breakthroughs. Some HDGGs for colon and prostate cancers are listed here. The website listed below contains HDGGs for the other cancers. AVAILABILITY: HDGG is implemented in C++ and runs on Unix or Windows platform. The code is available at: http://www.cs.wright.edu/~gdong/hdgg/.

Algorithms↗
PubMed2005

Linear independence of pairwise comparisons of DNA microarray data.

MOTIVATION: For DNA microarrays, the gain in certainty by performing multiple experimental repeats is offset by the high cost of each experiment. In a typical experiment, two independent measurements (that is, data from two separate arrays) are combined to yield a single comparative index per gene. Thus, although one uses 2n arrays and performs 2n independent measurements, one obtains only n comparative measurements. We addressed the question: how many of the potential n2 comparisons derivable from such data are actually independent, and what effect do these additional comparisons have on the false positive rate. RESULTS: We show there are precisely 2n - 1 independent comparisons available from among the n2 possibilities. Applying these additional n - 1 independent comparisons to experimental and simulated data reduced the false positive rate by as much as 10-fold, with excellent agreement between experimental and theoretical false positive rates.

Algorithms↗
PubMed2006

Iterated local least squares microarray missing value imputation.

Microarray gene expression data often contains multiple missing values due to various reasons. However, most of gene expression data analysis algorithms require complete expression data. Therefore, accurate estimation of the missing values is critical to further data analysis. In this paper, an Iterated Local Least Squares Imputation (ILLSimpute) method is proposed for estimating missing values. Two unique features of ILLSimpute method are: ILLSimpute method does not fix a common number of coherent genes for target genes for estimation purpose, but defines coherent genes as those within a distance threshold to the target genes. Secondly, in ILLSimpute method, estimated values in one iteration are used for missing value estimation in the next iteration and the method terminates after certain iterations or the imputed values converge. Experimental results on six real microarray datasets showed that ILLSimpute method performed at least as well as, and most of the time much better than, five most recent imputation methods.

Algorithms↗
PubMed1999

Testing for linkage under robust genetic models.

Robust genetic models are used to assess linkage between a quantitative trait and genetic variation at a specific locus using allele-sharing data. Little is known about the relative performance of different possible significance tests under these models. Under the robust variance components model approach there are several alternatives: standard Wald and likelihood ratio tests, a quasilikelihood Wald test, and a Monte Carlo test. This paper reports on the relative performance (significance level and power) of the robust sibling pair test and the different alternatives under the robust variance components model. Simulations show that (1) for a fixed sample size of nuclear families, the variance components model approach is more powerful than the robust sibling pair approach; (2) when the number of nuclear families is at least approximately 100 and heritability at the trait locus is moderate to high (>0.20) all tests based on the variance components model are equally effective; (3) when the number of nuclear families is less than approximately 100 or heritability at the trait locus is low (<0. 20), on balance, the Monte Carlo test provides the best power and is the most valid. The different testing procedures are applied to determine which are able to detect the known association between low density lipoprotein cholesterol and the common genotypes at the locus encoding apolipoprotein E. Results from this application show that the robust sibling pair method may be more effective in practice than that indicated by simulations.

Alleles↗
PubMedDate not supplied

Apolipoprotein(a) gene polymorphism in the Korean population: is there any relevance to essential hypertension?

OBJECTIVE: To investigate the role of the apolipoprotein(a) [Apo(a)] gene in predicting essential hypertension in the Korean population, we undertook a case-control study using the TTTTA repeat and the Met/Thr polymorphisms of the Apo(a) gene. METHODS: The study subjects consisted of 74 essential hypertensives and 211 normotensive individuals. For polymorphism analysis, DNA was amplified by polymerase chain reaction (PCR). In the case of the Met/Thr polymorphism, amplified PCR products were digested with the restriction enzyme Kspl. Genotyping was performed by a 10% nondenaturing polyacrylamide gel. RESULTS: There were no significant differences in the allele and genotype frequencies of these polymorphisms between normotensive and essential hypertensive subjects (p > 0.05). Furthermore, levels of lipoprotein(a) in the plasma were not significantly associated with the different genotypes of the APO(a) gene in either group (p > 0.05). CONCLUSION: The polymorphisms of these two loci on the Apo(a) gene are unlikely to contribute to the etiology of essential hypertension in the Korean population.

Apolipoproteins A↗