Igf-I genetic variation and breast cancer: the multiethnic cohort.
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Breast Neoplasms↗
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Results for “Genetic Variation”
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Atypical melting curve resulting from genetic variation in the 3' untranslated region at position 20218 in the prothrombin gene analyzed with the LightCycler factor II (prothrombin) G20210A assay.
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3' Untranslated Regions↗
Genetic variation within and among populations of Arabidopsis thaliana.
We investigated levels of nucleotide polymorphism within and among populations of the highly self-fertilizing Brassicaceous species, Arabidopsis thaliana. Four-cutter RFLP data were collected at one mitochondrial and three nuclear loci from 115 isolines representing 11 worldwide population collections, as well as from seven commonly used ecotypes. The collections include multiple populations from North America and Eurasia, as well as two pairs of collections from locally proximate sites, and thus allow a hierarchical geographic analysis of polymorphism. We found no variation at the mitochondrial locus Nad5 and very low levels of intrapopulation nucleotide diversity at Adh, Dhs1, and Gpa1. Interpopulation nucleotide diversity was also consistently low among the loci, averaging 0.0014. gst, a measure of population differentiation, was estimated to be 0.643. Interestingly, we found no association between geographical distance between populations and genetic distance. Most haplotypes have a worldwide distribution, suggesting a recent expansion of the species or long-distance gene flow. The low level of polymorphism found in this study is consistent with theoretical models of neutral mutations and background selection in highly self-fertilizing species.
Arabidopsis↗
Clinical and genetic variations in the syndrome of adult GM2 gangliosidosis resulting from hexosaminidase A deficiency.
Six patients from three families developed adult GM2 gangliosidosis resulting from severe beta-hexosaminidase A deficiency. The clinical picture varied between and within families and included spinocerebellar, various motor neuron, and cerebellar connection syndromes. Psychosis appeared in each family. Involvement of three generations was recorded in one family. The phenotype of adult GM2 gangliosidosis is variable and cannot form a basis for genetic classification. Detailed hexosaminidase determinations in eight patients from five families revealed all patients to have minor quantities of hexosaminidase A (about 15% of normal), with marked increase in hexosaminidase I isozyme.
Adult↗
Genetic variation over space and time: analyses of extinct and remnant lake trout populations in the Upper Great Lakes.
Lake trout (Salvelinus namaycush) in the upper Laurentian Great Lakes of North America experienced striking reductions in abundance and distribution during the mid-twentieth century. Complete collapse of populations was documented for Lake Michigan, and a few remnant populations remained only in lakes Huron and Superior. Using DNA obtained from historical scale collections, we analysed patterns of genetic diversity at five microsatellite loci from archived historical samples representing 15 populations (range 1940-1959) and from three contemporary remnant populations across lakes Huron and Superior (total n = 893). Demographic declines in abundance and the extirpation of native lake trout populations during the past 40 years have resulted in the loss of genetic diversity between lakes owing to extirpation of Lake Michigan populations and a temporal trend for reduction in allelic richness in the populations of lakes Superior and Huron. Naturally reproducing populations in Lake Superior, which had been considered to be remnants of historical populations, and which were believed to be responsible for the resurgence of lake trout numbers and distribution, have probably been affected by hatchery supplementation.
Alleles↗
Phylogeographical structure, distribution and genetic variation of the green algae Ulva intestinalis and U. compressa (Chlorophyta) in the Baltic Sea area.
The marine algae Ulva intestinalis and U. compressa are morphologically plastic with many overlapping characters and are therefore difficult to distinguish from each other. The present distribution of U. intestinalis and U. compressa is investigated along the salinity gradient in the Baltic Sea area through analyses of internal transcribed spacer (ITS) sequence data. Also, the amount and distribution of intraspecific genetic polymorphism in the ITS region is studied allowing inferences on the phylogeographical pattern and postglacial recolonization of the Baltic Sea area. The data show that of the two species only U. intestinalis occurs in the Baltic Sea. The distribution of U. compressa is more restricted than previously reported, and it was not found in salinities lower than 15 ppt. All of Scandinavia and the Baltic Sea were covered with ice during the last ice age and the organisms in the Baltic Sea must have colonized the area after the ice had started to melt. The genetic diversity of U. intestinalis and U. compressa in the Baltic Sea and the neighbouring area was found to be reduced compared to that in the British Isles. This reduction may be the result of either a historical reduction of diversity or an adaptation of specific clones to the northern environmental conditions.
Base Sequence↗
Distinguishing the forces controlling genetic variation at the Xdh locus in Drosophila pseudoobscura.
Fifty-eight isochromosomal lines sampled from two natural populations of Drosophila pseudoobscura in California and one from Bogota, Colombia, were examined using four-cutter restriction mapping. A 4.6-kb region of the xanthine dehydrogenase locus was probed and 66 of 135 restriction sites scored were polymorphic. This predicts that on average every 12th bp would be polymorphic in this region for the genes surveyed if polymorphism occurred randomly along the coding region. In addition, there were 12 insertion/deletion polymorphisms. Forty-nine distinct haplotypes were recognized in the 58 lines examined. The most common haplotype obtained a frequency of only 5%. Measures of base pair heterozygosity (0.0097) and linkage disequilibrium lead to a predicted population size in the range of 1.2-2.4 X 10(6) for the species. High levels of recombination (including gene conversion) can be inferred from the presence of all four gametic types in the data set.
Animals↗
Genetic variation in neuraminidase genes of influenza A (H3N2) viruses.
Nucleotide sequences of the neuraminidase (NA) genes of 33 influenza A (H3N2) epidemic strains isolated between 1968 and 1995 were analyzed to determine their evolutionary relationships. Phylogenetic analysis using the DNA maximum-likelihood method indicates that the NA genes of recent H3N2 field strains, like their hemagglutinin genes (HA), have evolved as two distinct lineages represented by the vaccine strains. A/Beijing/353/89 and A/Beijing/32/92 for A/Shanghai/24/ 90). Furthermore, genetic reassortment of NA genes between the two lineages occurred during their circulation. Genetic reassortants, which bear an A/Beijing/32/92-like HA and an A/Beijing/353/89-like NA, have circulated worldwide and are representative of current influenza A (H3N2) epidemic strains. The mutation rate of the NA gene was found to be 2.28 x 10(-3) per nucleotide site per year with 4.2% of the mutations resulting in amino acid substitutions. Thirty-five percent of the amino acid substitutions was located in sites previously suggested to be reactive to antibody. Amino acid residues involved in NA enzyme activity have been conserved. Seven potential glycosylation sites identified in the NA of A/Hong Kong/8/68 virus were conserved by the majority of isolates, with more recently circulating viruses having an additional glycosylation site. Comparison of the rate of amino acid substitutions in the NA stalk to that of entire NA revealed high variability in this region. These findings demonstrate the importance of closely monitoring both the HA and the NA genes of influenza viruses to aid vaccine strain selection.
Amino Acid Sequence↗
An improved method for the detection of genetic variations in DNA with denaturing gradient gel electrophoresis.
We have examined the feasibility of denaturing gradient gel electrophoresis (DGGE) of RNA:DNA duplexes to detect variations in genomic and cloned DNAs. The result has demonstrated that employment of RNA:DNA duplexes makes DGGE much more practical for screening a large number of samples than that of DNA:DNA heteroduplexes originally developed by Lerman et al. (1986), because preparation of RNA probes is easier than that of DNA probes. Three different 32P-labeled RNA probes were produced. Genomic or cloned DNAs were digested with restriction enzymes and hybridized to labeled RNA probes, and resulting RNA:DNA duplexes were examined by DGGE. The presence of mismatch(es) was detected as a difference in mobility of bands on the gel. The experimental conditions were determined using DNA segments from cloned normal and 3 thalassemic human beta-globin genes. The results of the experiments on the cloned DNAs suggest that DGGE of RNA:DNA duplexes will detect nucleotide substitutions and deletions in DNA. In the course of these studies, a polymorphism due to a single-base substitution at position 666 of IVS2 (IVS2-666) of the human beta-globin gene was directly identified using genomic DNA samples. A study of 59 unrelated Japanese from Hiroshima was made in which the frequency of the allele with C at IVS2-666 was 0.48 and that of the allele with T was 0.52. This approach was found to be very effective for the detection of heritable variation and should be a powerful tool for the detection of fresh mutations in DNA, which occur outside the known restriction sites.
DNA↗
Genetic variation in trophectoderm function in parthenogenetic mouse embryos.
The developing oocyte constitutes the source of a unique and essential molecular legacy that supports embryo metabolism for a substantial period after fertilization and that also directs important epigenetic events that prepare the embryonic genome for transcription and faithful execution of the developmental program. Parthenogenetically activated embryos provide a useful tool with which to examine how maternally derived factors contribute to early development. They also provide a means for evaluating genetic effects on the maternal genomic imprinting process. We report here that the genetic background of the oocyte affects trophectoderm function at the blastocyst stage. Parthenogenetic embryos obtained from activated (B6D2)F1 oocytes hatch efficiently in culture, whereas parthenogenones from C57BL/6 oocytes hatch less efficiently. Fertilized embryos of both strains hatch efficiently. The (B6D2)F1 parthenogenones also undergo blastocoel re-expansion after treatment with cytoskeletal inhibitors more rapidly than do C57BL/6 parthenogenones and exhibit a moderately greater abundance of the Na+, K(+)-ATPase alpha 1 subunit mRNA. Surprisingly, parthenogenones of both strains undergo blastocoel re-expansion more rapidly than do their normal fertilized counterparts. Parthenogenones of both types are able to attach efficiently in culture after removal of the zona pellucida. These observations indicate that significant genetic effects of maternal genotype on trophectoderm function are revealed in the absence of a paternal genetic contribution and that trophectoderm function also differs between parthenogenetic embryos and fertilized embryos. The differences observed between parthenogenetic and fertilized embryos indicate a likely role for one or more imprinted genes in the development of hatching and blastocoel expansion ability. The effect of maternal genotype on parthenogenetic embryo phenotype is consistent with possible differences in maternal genome imprinting or differences in ooplasm composition that have long-term effects on development. The specific differences in hatching and blastocoel re-expansion between parthenogenones of the two strains may be the result of differences in the activity or expression of a hatching enzyme or other molecules that affect fluid accumulation within the blastocyst, such as components of junctional complexes or proteins that regulate Na+, K(+)-ATPase activity.
Animals↗
Genetic variation of populations of Pinus oocarpa revealed by resistance gene analog polymorphism (RGAP).
Primers based on conserved motifs of plant resistance genes were used to generate multilocus molecular markers--referred to as resistance gene analog polymorphisms (RGAPs)--in Pinus oocarpa subsp. oocarpa. Ten populations from three regions of Nicaragua were analyzed with 53 RGAPs. The aim of this study was to determine the levels of within- and between-population diversity with this kind of marker, and to compare estimates with previously obtained results based on RAPD and AFLP. All populations showed high levels of diversity. GST values and the analysis of molecular variance (AMOVA) revealed most variation to be within populations, although significant differences between populations and regions were also detected. This pattern of genetic diversity was similar to that obtained for RAPD and AFLP, which suggests that variation at RGAP loci as detected in this work is mostly influence by non-selective forces.
Analysis of Variance↗
Genetic variation in natural populations of maté (Ilex paraguariensis A. st.-hil., aquifoliaceae) using RAPD markers.
This study characterized the genetic diversity of four populations of Ilex paraguariensis, a plant species native to South America, using random amplified polymorphic DNA (RAPD) markers. A total of 341 different RAPD bands were generated by the 15 primers analysed. High genetic variability was detected within each population, with an average diversity of 0.163. The within-population variation was large, probably as a result of the life history characteristics of I. paraguariensis. The average distance between individuals from each population was 0.392 and that between populations was 0.433, indicating a low between-population divergence. Most bands were common to all populations and the population-specific bands occurred at low frequencies. Partitioning of the genetic diversity indicated that 85% of the variation occurred within populations and only 15% between populations. Although most of the variability is within populations, clusterings of plants in each population were observed in the dendrogram.
Base Sequence↗
Genetic variation in vulnerability to the behavioral effects of neonatal hippocampal damage in rats.
We explored how two independent variables, one genetic (i.e., specific rat strains) and another environmental (i.e., a developmental excitotoxic hippocampal lesion), contribute to phenotypic variation. Sprague-Dawley (SD), Fischer 344 (F344), and Lewis rats underwent two grades of neonatal excitotoxic damage: small and large ventral hippocampal (SVH and LVH) lesions. Locomotion was tested before puberty [postnatal day 35 (P35)] and after puberty (P56) following exposure to a novel environment or administration of amphetamine. The behavioral effects were strain- and lesion-specific. As shown previously, SD rats with LVH lesions displayed enhanced spontaneous and amphetamine-induced locomotion as compared with controls at P56, but not at P35. SVH lesions in SD rats had no effect at any age. In F344 rats with LVH lesions, enhanced spontaneous and amphetamine-induced locomotion appeared early (P35) and was exaggerated at P56. SVH lesions in F344 rats resulted in a pattern of effects analogous to LVH lesions in SD rats--i.e., postpubertal onset of hyperlocomotion (P56). In Lewis rats, LVH lesions had no significant effect on novelty- or amphetamine-induced locomotion at any age. These data show that the degree of genetic predisposition and the extent of early induced hippocampal defect contribute to the particular pattern of behavioral outcome. These results may have implications for modeling interactions of genetic and environmental factors involved in schizophrenia, a disorder characterized by phenotypic heterogeneity, genetic predisposition, a developmental hippocampal abnormality, and vulnerability to environmental stress.
Analysis of Variance↗
Genetic variation of morphological traits in Drosophila melanogaster under poor nutrition: isofemale lines and offspring--parent regression.
Variation of three morphological traits (thorax length, wing length and sternopleural bristle number) was examined in Drosophila melanogaster reared on a medium with low yeast content and on a standard medium using the isofemale line analysis and offspring--parent regression. The aim was to test whether these experimental approaches give different patterns of changes in genetic variability estimates when stressful and nonstressful environments are compared. Heritabilities and genetic and phenotypic variances were generally higher in the isofemale line design than in the offspring--parent regression design under both standard and poor nutritional conditions. For each trait, the response of heritability to stress was similar in both designs: wing length exhibited lower heritability under poor nutrition, whereas heritabilities of thorax length and sternopleural bristle number did not differ between nutritional regimes. Statistically significant differences in the genetic variances and the environmental variances between stressful and nonstressful environments were recorded only in isofemale lines: the genetic variance of thorax length and the environmental variances of thorax length and wing length were higher under poor nutrition. The results are compared to literature data and possible reasons of increased genetic variability estimates in isofemale lines are briefly discussed.
Analysis of Variance↗
Genetic variation in the interleukin-6 gene in relation to risk and outcomes in acute coronary syndrome.
BACKGROUND: The concept of inflammation in the acute coronary syndrome (ACS) is today well established. Interleukin-6 (IL-6), a pleiotropic, proinflammatory cytokine, seems to play an important role in the development and progression of ACS. AIM: The aim was to investigate whether IL6 polymorphisms are associated with patient/control status, outcome in patients with ACS and plasma concentrations of IL-6 and C-reactive protein (CRP). METHODS: Samples for citrated plasma and DNA were obtained on admission from 3027 patients with non-ST-elevation ACS in the FRISC-II study. A group of 447 healthy controls of similar age and gender as the patients was also recruited. Eight IL6 polymorphisms were genotyped and plasma concentrations of IL-6 and CRP measured in patients and controls. RESULTS: No associations between patient/control status, clinical outcome, ST-depression, troponin-T elevation or a history of myocardial infarction and IL6 polymorphisms were observed. In the full patient group, there was a trend towards association of the -572 G>C polymorphism with plasma concentrations of IL-6 (p=0.07). This association was statistically significant in patients with available high-sensitivity measurements of IL-6 (p=0.01). The -572 CG genotype was predictive for IL-6 levels above 5 ng/L in patients with a subsequent cardiovascular event, 2.3 (1.1-4.3) (adjusted odds ratio, 95% confidence interval). Comparison with data from HapMap showed that our panel of polymorphisms covered information on approximately 30 other IL6 variants. CONCLUSION: The -572 G>C and other polymorphisms in the study were not associated with outcome in ACS patients. However, the -572 CG genotype may contribute to a more distinct inflammatory response in patients with ACS.
Acute Disease↗
[Genetic variation of the cholesterol ester transfer protein gene and the prevalence of coronary artery disease. The AtheroGene case control study].
BACKGROUND: Various functional polymorphisms of the cholesteryl ester transfer protein ( CETP) gene influence CETP activity and the concentration of high-density lipoprotein (HDL) cholesterol. Beside other functional variants mainly the promoter polymorphism CETP/C-629A is currently discussed as a risk factor of coronary artery disease (CAD). We evaluated in a large case-control study the impact of various CETP genotypes and haplotypes on HDL concentration and the prevalence of CAD. METHODS AND RESULTS: In 1214 patients with documented CAD as well as 754 population controls we determined the CETP/C-629A, TaqIB, I405V, R451Q, and A373P polymorphisms. All genotypes have an impact on the HDL concentration; univariate genotype and haplotype analyses demonstrate a significant effect of A-allel carriers on the elevation of HDL concentration. In addition, among all genotypes determined, the C-629A polymorphism is associated with the prevalence of CAD in a codominant fashion. Homozygous A-allel carriers reveal a relative risk of 0.6 (95% CI 0.44-0.82; P = 0.005) compared to the wild type. Adjustment for classical risk factors did not alter this association significantly, whereas after controlling for HDL concentration no independent significance between CETP/C-629A genotype and prevalence of CAD was observed anymore. CONCLUSION: CETP genotypes have an significant but moderate impact on systemic HDL-cholesterol concentration. The A-allel of the CETP/C-629A polymorphism is associated with a reduced CAD risk. This risk reduction is probably mediated by elevated HDL-concentration. Whether genotyping of the CETP/C-629A polymorphism provides information over and above that obtained by HDL-cholesterol measurement has to be further investigated in various prospective studies.
Carrier Proteins↗
Genetic variation in the type 2 insulin-like growth factor receptor gene and disparity in childhood height.
OBJECTIVE: The type 2 insulin-like growth factor receptor (IGF2R) is thought to regulate insulin-like growth factor-II (IGF-II) bioavailability by degrading it in the lysosomes after uptake. We hypothesised that polymorphisms in the IGF2R gene could alter size at birth and childhood growth. DESIGN AND METHODS: The hypothesis was tested in a normal birth cohort (Avon Longitudinal Study of Parents and Children) by genotyping the IGF2R gene gly1619arg polymorphism, which causes a non-conservative amino acid change in the IGF-II binding region, using PCR and restriction fragment length polymorphism analysis. RESULTS: The IGF2R gly1619arg genotype was not associated with any measure of size at birth, but A/A homozygotes grew more slowly, as determined by their change in height standard deviation scores (SDS) over the first three years (-0.70 (0.72); n = 12), than G/G homozygotes (0.00 (1.09); n = 561) (p = 0.03). They remained shorter during childhood and by the age of 7 years respective height SDS were: 0.73 (1.02) (n = 12) and 0.01 (0.99) (n = 634) (p = 0.01). These height differences persisted after adjusting for parental heights and gender. There were no detectable differences in weights at 7 years. CONCLUSION: Allelic variation in the gly1619arg SNP of the IGF2R gene is associated with disparity in childhood stature which could reflect altered binding of IGF-II to its receptor.
Alleles↗
Genetic variation of the GLUT10 glucose transporter (SLC2A10) and relationships to type 2 diabetes and intermediary traits.
The SLC2A10 gene encodes the GLUT10 facilitative glucose transporter, which is expressed in high amounts in liver and pancreas. The gene is mapped to chromosome 20q12-q13.1, a region that has been shown to be linked to type 2 diabetes. The gene was examined in 61 Danish type 2 diabetic patients, and a total of six variants (-27C-->T, Ala206Thr, Ala272Ala, IVS2 + 10G-->A, IVS4 + 18T-->G, and IVS4 + 26G-->A) were identified and investigated in an association study, which included 503 type 2 diabetic patients and 510 glucose-tolerant control subjects. None of the variants were associated with type 2 diabetes. Interestingly, carriers of the codon 206 Thr allele had 18% lower fasting serum insulin levels (P = 0.002) and 20% lower insulinogenic index (P = 0.03) than homozygous carriers of the Ala allele. These results suggest that variation in the coding region of SLC2A10 does not contribute substantially to the pathogenesis of type 2 diabetes in the examined study population. However, the codon 206 polymorphism may be related to the interindividual variation in fasting and oral glucose-induced serum insulin levels.
Aged↗
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