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Results for “Genetic Variation”

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PubMed2006

Environmental heterogeneity and the maintenance of genetic variation for reproductive diapause in Drosophila melanogaster.

Drosophila melanogaster has colonized temperate habitats on multiple continents over a historical time period, and many traits vary predictably with latitude. Despite considerable attention paid to clinal variation in Drosophila, the mechanisms generating such patterns in nature remain largely unidentified. In D. melanogaster, the expression of reproductive diapause can be induced by exposure to low temperatures and shortened photoperiods. Both diapause expression itself and the underlying genetic variance for diapause expression have widespread impacts on organismal fitness, and diapause incidence exhibits a 60% cline in frequency in the eastern United States. The major aim of this study was to evaluate whether the relative fitness of diapause and nondiapause genotypes varies predictably with environment. In experimental population cages in the laboratory, the frequency of genotypes that express diapause increased over time when flies were exposed to environmental stress, whereas the frequency of nondiapause genotypes increased when flies were cultured under benign control conditions. Other fitness traits correlated with the genetic variance for diapause expression (longevity, mortality rates, stress resistance, lipid content, preadult viability, fecundity profiles, and development time) also diverged between experimental treatments. Similarly, sampling of isofemale lines from natural populations revealed that the frequency of diapause incidence cycled over time in seasonal habitats: diapause expression was at high frequency following the winter season and subsequently declined throughout the summer months. In contrast, diapause expression was low and temporally homogeneous in isofemale line collections from human-associated urban habitats. These data suggest that genetic variation underlying the diapause-nondiapause dichotomy may be actively maintained by selection pressures that vary spatially and temporally in natural populations.

Animals↗

PubMed2000

Contribution of genetic variations in estradiol biosynthesis and metabolism enzymes to osteoporosis.

The occurrence of osteoporosis is closely related to serum estradiol level. CYP19 is the most important biosynthesis enzyme and CYP1A2, CYP3A4, and 17 beta-HSD are important metabolism enzymes. Any changes in these enzymes activity affects estradiol biosynthesis or metabolism, and changes the estradiol serum level. By reviewing the recent literature, it was found that the genetic variations of CYP19, CYP1A2, CYP3A4, and 17 beta-HSD are important factors affecting the estradiol serum level, and may be closely related to the development of osteoporosis.

Animals↗

PubMed1987

Genetic variation in survival of chinook salmon (Oncorhynchus tshawytscha) alevins exposed to an unidentified agent of mortality.

Mortality of an unknown etiology occurs after hatching and before emergence among Harrison River chinook salmon (Oncorhynchus tshawytscha) alevins incubated in the Chehalis River Hatchery, British Columbia. Inter- and intra-stock genetic variation for alevin survival and time to death was investigated at Chehalis Hatchery in factorial crosses among chinook salmon from the Harrison and Capilano rivers. Alevin survival by family ranged from 0 to 100%, with a mean value of 35.2%. The mean family survival of pure Harrison alevins (13.0%) was significantly lower than that of Capilano alevins (64.1%). For the Harrison stock, estimates of the heritability of survival were 1.05 +/- 0.62 (sire component) and 0.03 +/- 0.07 (dam component). For the Capilano stock, the corresponding estimates were 0.79 +/- 0.53 and 0.80 +/- 0.54. Family means of time to death ranged from 7.5 to 48 days after exposure to mortality-inducing agents. The mean times to death for pure Harrison (15.3 days) and Capilano (21.8 days) families were not significantly different. Sire and dam component heritability estimates for time to death were high for the Harrison stock (1.39 +/- 0.87 and 0.71 +/- 0.46) but low for the Capilano stock (0.06 +/- 0.11 and 0.17 +/- 0.18). Values of survival and time to death for the reciprocal interstock hybrid alevins generally fell between those of the parental stocks. Neither survival nor time to death differed significantly between the reciprocal hybrids, but both traits were more strongly influenced by sire than by dam. The possibility of asynchronous paternal and maternal allele activation during embryonic development was proposed as an explanation for the strong paternal effects observed in this study.

Animals↗

PubMed2002

Genetic variation in foraging traits among inbred lines of a predatory mite.

Response of predators to herbivore-induced plant volatiles can affect the length of time a predator spends in a prey patch and the probability of a predator finding a new prey patch. Variation in response to herbivore-induced plant volatiles may lead to different foraging decisions among individuals, thereby affecting both within-patch dynamics and between-patch dispersal. We found significant phenotypic and additive genetic variation in two behavioral assays of response to herbivore-induced plant volatiles among inbred isofemale lines of the predatory mite, Phytoseiulus persimilis. In wind-tunnel tests to measure patch residence time, adult female predators from certain lines left prey patches sooner than others when a distant source of herbivore-induced plant volatiles was presented; whereas such variation disappeared when no distant volatiles were presented. In a measure of patch location, certain lines were more likely than others to locate a prey-infested leaf disc; again there was no difference when uninfested leaf discs were used. Patch location was negatively correlated with patch residence. That is, lines that were more likely to leave a prey patch in the presence of distant volatiles were also more likely to find an odor source (ie, prey patch) from a distance of 20 cm. These two foraging-related behaviors are heritable. A continuous distribution of both behaviors indicated that several to many loci may be responsible for these behavioral traits. Our line-crossing experiments suggested that maternal influence could be excluded. Substantial phenotypic variation in two other foraging-related traits, consumption and oviposition, were also detected among inbred lines. Consumption and oviposition were positively correlated; however, the relationship (slope) varied among inbred lines, suggesting that predatory mites vary in food conversion efficiency. A relationship was detected between patch residence and consumption. Patch location, as one important foraging trait, appeared to be negatively related to consumption, suggesting a trade-off between searching for patches and reproduction.

Animals↗

PubMed2002

Flower and cotyledon asymmetry in Brassica cretica: genetic variation and relationships with fitness.

Plants of the partially self-incompatible perennial herb Brassica cretica, derived from controlled cross- and self-pollinations within each of seven populations, were raised under uniform conditions and scored for two measures of developmental stability, flower asymmetry (quantified as the difference in length and width between opposite petals) and cotyledon asymmetry (quantified as the difference in the area of the two lobes of each cotyledon). The primary goals were to assess the level of heritable variation in asymmetry, the effect of selfing on mean asymmetry, and the relationship between asymmetry and components of fitness. A paternal half-sibling analysis of data on flower asymmetry failed to detect significant levels of genetic variation at the within-population level, whereas the between-population component reached significance for all measures of asymmetry. Analysis of family-structured data from another crossing experiment revealed significant between-population variation in cotyledon asymmetry and a tendency for inbred progeny to produce more asymmetric cotyledons than outbred progeny. However, the response to inbreeding was weak and differed in magnitude between populations. Judging from the ranking of populations, we found no support for the hypothesis that the mean expression of developmental stability is controlled by genomewide characteristics such as the level of inbreeding. Correlations between measures of asymmetry and fitness were too low to be declared statistically or biologically significant. The present study provides little evidence that flower and cotyledon asymmetry serve as more appropriate predictors of genetic health than conventional (direct) measures of fitness.

Analysis of Variance↗

PubMed2005

Genetic variation at the human alpha2B-adrenergic receptor locus: role in blood pressure variation and yohimbine response.

Exaggerated response to alpha2-adrenergic receptor (alpha2-AR) blockade by yohimbine in normotensive subjects is an intermediate phenotype that predicts increased risk for development of hypertension. Here, we assessed the 3 alpha2-AR loci (alpha2A, alpha2B, alpha2C) as candidate genes for their influence on baseline and yohimbine-mediated increase in mean arterial pressure. Because initial results with 173 individuals implicated a possible association of yohimbine response with genetic variation at a site in the alpha2B-AR gene, but not at sites in the other 2 alpha2-AR, we sequenced the alpha2B-AR gene (4.4 kb, including 1.2 kb upstream and 1.9 kb distal to the coding sequence) in those subjects and an additional 81 individuals to search for other alpha2B-AR variants. We identified 25 polymorphisms, of which 14 are previously unreported, and 2 major haplotypes that differ by the presence/absence of a 9-bp in-frame deletion that encodes Glu301 to Glu303. Frequency differences in haplotypes were observed between blacks and whites but did not predict response to yohimbine. Genotyping of 2 additional white cohorts, including 1269 individuals with extremes in blood pressure selected from >50,000 subjects, also failed to reveal an association of the 2 major alpha2B-AR haplotypes with differences in blood pressure. Thus, despite considerable polymorphism in alpha2-AR genes, such variation is not a major determinant of variability in yohimbine response and by inference, in susceptibility to essential hypertension.

Adrenergic alpha-Antagonists↗

PubMed1997

Expression and genetic variation of the Aplysia egg-laying hormone gene family in the atrial gland.

We have screened an Aplysia atrial gland cDNA library using an egg-laying hormone (ELH) precursor probe and have isolated and characterized five different clones, four of which are full-length and approximately 0.8 kb in size. The characterization of these cDNA clones firmly established the genetic variation of the ELH-related precursors expressed in the atrial gland and provided a rational basis for their revised nomenclature proposed herein. The five precursor ELH-related cDNA sequences obtained predicted the following genetically distinct polypeptide precursors designated as: A, [Asp143]A, [Glu94,Gln139]A, [Pro25]B, and [Phe96,Asp107]BT. The [Phe96,Asp107]Br cDNA sequence predicted a truncated form of a B-type precursor. Northern blot analysis of atrial gland RNA identified two transcripts of about equal intensity of 0.9 kb and 1.1 kb. Polymerase chain reaction of genomic DNA, together with DNA sequence analysis, resolved previously reported discrepancies between genomic and cDNA sequences of the ELH-related precursors. Taken together the results obtained identified the expression of five ELH-related precursor genes in the atrial gland of Aplysia from at least two genetic loci per haploid genome.

Alternative Splicing↗

PubMed2006

NR4A2 genetic variation in sporadic Parkinson's disease: a genewide approach.

The NR4A2 gene, which may cause autosomal dominant Parkinson's disease (PD), has also been reported to be a susceptibility factor for sporadic PD. Here, we use a haplotype-tagging approach in 802 PD patients and 784 controls and demonstrate that common genetic variation, including NR4A2 haplotypes, does not influence the risk of PD in the Caucasian population.

Case-Control Studies↗

PubMed1992

Genetic variation of human aspartic proteinases.

The human aspartic proteinases include pepsinogen A, pepsinogen C, cathepsin D, cathepsin E and renin. Comparative analysis of the proteinase genes reveals a high degree of similarity with regard to their respective coding sequences and the location of exon-intron junctions. Despite strong conservation of the regions containing the active site aspartyl groups, genetic polymorphisms have been identified for each of the proteinase genes with the exception of cathepsin D. These genetic polymorphisms are useful for localization of genes on linkage maps as well as determination of gene copy number. The chromosomal location of each aspartyl proteinase has been determined by a variety of gene mapping methods employing recombinant DNA probes including; analysis of somatic cell hybrid mapping panels, in situ hybridization to metaphase chromosome preparations and family linkage analysis with polymorphic markers. Pepsinogen A exhibits the most extensive polymorphism among aspartic proteinases which can be detected by either by protein electrophoresis or by DNA analysis. Southern blot hybridization with respective DNA probes and polymerase chain reaction (PCR) amplification have revealed nucleotide differences located within the coding and noncoding portions of the aspartic proteinase genes. These polymorphisms can be used to investigate potential roles of each proteinase in genetically influenced clinical conditions. The development of additional highly polymorphic markers detected by PCR amplification of divergent nucleotide sequence repeats will greatly assist with documentation of the effect of genetic variation of the aspartic proteinases may have in specific clinical diseases such as ulcer and hypertension.

Amino Acid Sequence↗

PubMed2000

High stressful temperature and genetic variation of five quantitative traits in Drosophila melanogaster.

Variation of five quantitative traits (thorax length, wing length, sternopleural bristle number, developmental time and larva-to-adult viability) was studied in Drosophila melanogaster reared at standard (25 degrees C) and high stressful (32 degrees C) temperatures using half-sib analysis. In all traits, both phenotypic and environmental variances increased at 32 degrees C. For genetic variances, only two statistically significant differences between temperature treatments were found: the among-sire variance of viability and the among-dam variance of developmental time were higher under stress. Among-sire genetic variances and evolvabilities were generally higher at 32 degrees C but narrow sense heritabilities were not. The results of the present work considered in the context of other studies in D. melanogaster indicate different patterns of genetic variation between stressful and nonstressful environments for the traits examined. Data on thorax length and viability agree with the hypothesis that genetic variance can be increased under extreme environmental conditions.

Animals↗

PubMed2003

Comparative analysis of mitochondrial genome data for Necator americanus from two endemic regions reveals substantial genetic variation.

Necator americanus is a blood-sucking, intestinal nematode of major human health importance in many tropical and subtropical regions of the world. The aim of the present study was to compare the complete mitochondrial genome sequence from one N. americanus individual from Togo with another from China, in order to estimate the magnitude of genetic variability for different mitochondrial genes and non-coding regions. For the 12 protein genes, this comparison revealed sequence differences at both the nucleotide (3-7%) and amino acid (1-7%) levels. The most conserved of these was the nad4L gene, whereas the nad1 gene was least conserved at both the nucleotide and amino acid levels. Nucleotide differences were also detected in 14 of the 22 transfer RNAs (trns) (1-13%), the AT-rich region ( approximately 8%), non-coding regions (8-25%) and in the small (rrnS) and large (rrnL) subunits of mitochondrial ribosomal RNA (rrn) ( approximately 1%). Comparison of the rrnL sequences among multiple individual worms revealed nine unequivocal nucleotide differences between N. americanus from the two countries. Consistent with previous studies, these findings provide evidence for substantial genetic variation within N. americanus, which may have implications for the transmission and control of hookworm disease.

Amino Acid Sequence↗

PubMed2000

Genetic variation among European strains of Saccharomyces paradoxus: results from DNA fingerprinting.

We used microsatellite fingerprinting and RAPD analysis to characterize 28 wild European strains of Saccharomyces paradoxus. In contrast to our results from a previous allozyme survey [Naumov et al. Int. J. Syst. Bacteriol. 47: 341-344 (1997a)], these methods revealed extensive genetic variation. The RAPD primers 5'AATCGGGCTG and 5'GGGTAACGCC and the microsatellite primer (GTG)5 yielded reproducible amplification patterns of sufficient clarity and variability to distinguish individual strains from the wild. UPGMA analysis tended to group the strains according to climatic and geographic origin. A comparative study of Ty1 sequence having multiple chromosomal location was also done. Each wild S. paradoxus isolate shows a unique hybridization pattern allowing discrimination to the strain level.

Blotting, Southern↗

PubMed2005

Genetic variations related to hypertension: a review.

Hypertension is a complex multifactorial disorder with genetic, environmental and demographic factors contributing to its prevalence. The genetic element contribution to blood pressure variation ranges from 30 to 50%. Therefore, identifying hypertension susceptibility genes will help understanding the pathophysiology of the disease. In addition to the potential impact of genomic information in selecting antihypertensive drug therapy, it may also help in recognizing those at risk of developing the disease, which may lead to new preventive approaches. Several strategies and methods have been used to identify hypertension susceptibility genes. Currently, genetic analysis of such data produced complex results, which makes it difficult to draw final conclusion on the use of genomic data in management of hypertension. This review attempts to summarize present known genetic variations that may be implicated in the pathogenesis of hypertension and to discuss various research strategies used to identify them. It also highlights some of the opportunities and challenges, which may be encountered in interpreting the value of these genetic variations to improve management of hypertension.

Genetic Predisposition to Disease↗

PubMed2003

Mapping the genetic variation of executive attention onto brain activity.

Brain imaging data have repeatedly shown that the anterior cingulate cortex is an important node in the brain network mediating conflict. We previously reported that polymorphisms in dopamine receptor (DRD4) and monoamine oxidase A (MAOA) genes showed significant associations with efficiency of handling conflict as measured by reaction time differences in the Attention Network Test (ANT). To examine whether this genetic variation might contribute to differences in brain activation within the anterior cingulate cortex, we genotyped 16 subjects for the DRD4 and MAOA genes who had been scanned during the ANT. In each of the two genes previously associated with more efficient handling of conflict in reaction time experiments, we found a polymorphism in which persons with the allele associated with better behavioral performance showed significantly more activation in the anterior cingulate while performing the ANT than those with the allele associated with worse performance. The results demonstrate how genetic differences among individuals can be linked to individual differences in neuromodulators and in the efficiency of the operation of an appropriate attentional network.

Adolescent↗

PubMed1998

Genetic variation in the PRRS virus.

Porcine reproductive and respiratory syndrome (PRRS) is characterized by late-term abortions and stillbirths in sows and respiratory difficulties in nursery pigs. The disease appeared in Europe and North America at approximately the same time between 1985 and 1990. The PRRS virus was isolated shortly thereafter and demonstrated unexpectedly profound differences between European (Lelystad) and North American (VR2332) isolates as measured by serological crossreactivity and nucleotide sequence similarity. In order to determine the amount of genetic variation in the PRRS virus and to understand the molecular mechanisms of viral evolution, nucleotide sequences of PRRS virus strains were determined. Comparisons among ten U.S. strains showed that variation in primary nucleotide sequence between isolates ranged from 2.5% to 7.9% for ORFs 2-7. In contrast, Lelystad virus was, on average, 35% different from US clones. These results provided direct molecular evidence that US and European PRRSV isolates represented genetically distinct groups of the same viral family. A further analysis of more than 150 isolates in the United States and Canada demonstrated that the PRRS virus in North America represents a single large and diverse genetic group that is distinct from European forms of the virus.

Animals↗

PubMed2002

Unique genetic variation revealed by a microsatellite polymorphism survey in ten wild-derived inbred strains.

Here we report on a genome polymorphism survey using 254 microsatellite markers in ten recently wild-derived inbred strains. Allele size analysis showed that the rate of polymorphism of these wild-derived mouse strains when compared with any of the common laboratory strains is on average 79.8%. We found 632 wild-derived alleles that were not present in the common laboratory strains, representing a 61% increase over the genetic variation observed in the laboratory strains. We also found that on average 14.5% of the microsatellite alleles of any given wild-derived inbred strain were unique. Our results indicate that the recently wild-derived mouse strains represent repositories of unique naturally occurring genetic variability and may prove invaluable for the study of complex phenotypes and in the construction of new mouse models of human disease.

Alleles↗

PubMed2000

Genetic variation in human stromelysin gene promoter and common carotid geometry in healthy male subjects.

A common variant in the promoter of the human stromelysin gene, causing reduced enzyme expression, has been associated with the progression of coronary atherosclerosis. On the other hand, increased stromelysin activity may promote plaque rupture. The present study was undertaken to investigate the relationship between the genetic variation in the human stromelysin gene promoter and common carotid geometry. Forty-two healthy male subjects without major coronary heart disease risk factors were investigated. The polymorphism in the stromelysin gene promoter was studied through polymerase chain reaction amplification with the use of mutagenic primers. Age, blood pressure, lipids, glucose, viscosity, and body mass index were similar in homozygotes for the 5A allele (5A/5A), heterozygotes (5A/6A), and homozygotes for the 6A allele (6A/6A). Serum matrix metalloproteinase-3 levels did not differ significantly among genotypes. Common carotid diameters and intima-media thickness, measured by noninvasive ultrasonography, were significantly larger in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, diameter at the R wave was 0.63+/-0.09, 0.55+/-0.06, and 0.53+/-0.04 cm [mean+/-SD], P<0.005 by ANOVA; intima-media thickness was 765+/-116, 670+/-116, and 630+/-92 microm [mean+/-SD], P<0.05 by ANOVA). Wall shear stress, calculated as blood velocityxblood viscosity/internal diameter, was significantly lower in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, mean wall shear stress was 10.4+/-2.9, 13.5+/-3.5, and 12.6+/-1.9 dyne/cm(2) [mean+/-SD], P<0.05 by ANOVA). The results demonstrate that the gene polymorphism in the promoter region of stromelysin is associated with structural and functional characteristics of the common carotid artery in healthy male subjects without major risk factors for atherosclerosis. Individuals with the 6A/6A genotype (associated with lower enzyme activity) show a triad of events, namely, increased wall thickness, enlarged arterial lumen, and local reduction of wall shear stress, which might predispose them to atherosclerotic plaque localization.

Adult↗

PubMed2004

Principal component analysis for selection of optimal SNP-sets that capture intragenic genetic variation.

Candidate gene association studies often utilize one single nucleotide polymorphism (SNP) for analysis, with an initial report typically not being replicated by subsequent studies. The failure to replicate may result from incomplete or poor identification of disease-related variants or haplotypes, possibly due to naive SNP selection. A method for identification of linkage disequilibrium (LD) groups and selection of SNPs that capture sufficient intra-genic genetic diversity is described. We assume all SNPs with minor allele frequency above a pre-determined frequency have been identified. Principal component analysis (PCA) is applied to evaluate multivariate SNP correlations to infer groups of SNPs in LD (LD-groups) and to establish an optimal set of group-tagging SNPs (gtSNPs) that provide the most comprehensive coverage of intra-genic diversity while minimizing the resources necessary to perform an informative association analysis. This PCA method differs from haplotype block (HB) and haplotype-tagging SNP (htSNP) methods, in that an LD-group of SNPs need not be a contiguous DNA fragment. Results of the PCA method compared well with existing htSNP methods while also providing advantages over those methods, including an indication of the optimal number of SNPs needed. Further, evaluation of the method over multiple replicates of simulated data indicated PCA to be a robust method for SNP selection. Our findings suggest that PCA may be a powerful tool for establishing an optimal SNP set that maximizes the amount of genetic variation captured for a candidate gene using a minimal number of SNPs.

Adult↗