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Results for “Genetic Variation”

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PubMed2004

Genetic variation among age-classes of the mangrove Avicennia marina in clean and contaminated sediments.

An examination was made of the genetic variation with age in mangrove populations in two estuaries in south-east Australia, one contaminated, the other uncontaminated. Sediment nutrient and metal levels, and isozyme/allozyme complements were measured in three age-classes in four stands in each estuary, to identify site and intergenerational genetic composition, and influences of sediment contamination. Within each river, there were greater genetic distances among the age-classes than among sampling sites. A downstream gradient of genetic distance was found in the uncontaminated river, but not the contaminated one, where genetic distances seemed to reflect site-specific factors, though apparently not the present sediment metal or nutrient levels. It appears that genetic distances in the polluted river may reflect past fluctuations in pollution pressures. In both rivers, genetic distances indicate that the mangroves within one estuary form one population, with 'neighbourhood' differentiation.

Avicennia↗

PubMed1988

Apolipoprotein genetic variation and human disease.

Atherosclerosis is the major public health problem in much of the world today. The information summarized in this review, based on the recognized apolipoprotein structural variants appreciated at both the protein and gene levels, indicates that apolipoprotein genetic variation plays a major role in determining human genetic susceptibility to this disease. With the use of cloned apolipoprotein genes, it should, in the near future, be possible to determine how their expression is regulated; this should provide insight into other classes of mutations of a regulatory nature that might have clinical significance. In addition, the many association and linkage studies currently being undertaken will provide the rationale for cloning defective alleles and determining specific causative mutations. Both structural and regulatory mutations can then be described either with restriction enzymes and Southern blotting or by direct oligonucleotide hybridization techniques in the general population. This will allow the identification of presymptomatic atherosclerosis-susceptible individuals who would be targets for primary preventative therapy.

Apolipoproteins↗

PubMed2002

A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity.

Variants of different Class I alcohol dehydrogenase (ADH) genes have been shown to be associated with an effect that is protective against alcoholism. Previous work from our laboratory has shown that the two sites showing the association are in linkage disequilibrium and has identified the ADH1B Arg47His site as causative, with the ADH1C Ile349Val site showing association only because of the disequilibrium. Here, we describe an initial study of the nature of linkage disequilibrium and genetic variation, in population samples from different regions of the world, in a larger segment of the ADH cluster (including the three Class I ADH genes and ADH7). Linkage disequilibrium across approximately 40 kb of the Class I ADH cluster is moderate to strong in all population samples that we studied. We observed nominally significant pairwise linkage disequilibrium, in some populations, between the ADH7 site and some Class I ADH sites, at moderate values and at a molecular distance as great as 100 kb. Our data indicate (1) that most ADH-alcoholism association studies have failed to consider many sites in the ADH cluster that may harbor etiologically significant alleles and (2) that the relevance of the various ADH sites will be population dependent. Some individual sites in the Class I ADH cluster show Fst values that are among the highest seen among several dozen unlinked sites that were studied in the same subset of populations. The high Fst values can be attributed to the discrepant frequencies of specific alleles in eastern Asia relative to those in other regions of the world. These alleles are part of a single haplotype that exists at high (>65%) frequency only in the eastern-Asian samples. It seems unlikely that this haplotype, which is rare or unobserved in other populations, reached such high frequency because of random genetic drift alone.

Alcohol Dehydrogenase↗

PubMed2003

Genetic variation in cyclooxygenase 1: effects on response to aspirin.

BACKGROUND: A critical clinical application of the Human Genome Project is to identify functional variation in genes related to disease or responses to xenobiotics. This study moved toward that goal by combining polymorphism detection with functional assays for the therapeutic target gene cyclooxygenase 1 (COX-1). Cyclooxygenase 1 (prostaglandin endoperoxide G/H synthase [PTGS1]) catalyzes the metabolism of arachidonic acid to prostaglandin H(2), which is subsequently metabolized to thromboxane A(2). METHODS: Thirty-eight healthy participants were enrolled in this study to correlate functional and genetic variation of cyclooxygenase 1. Arachidonic acid, with and without aspirin (acetylsalicylic acid) and ethanol pretreatment, was used to stimulate the formation of prostaglandin H(2), measured as prostaglandin F(2 alpha) (PGF(2 alpha)), in human platelets. The cyclooxygenase 1 complementary deoxyribonucleic acid coding sequence and genomic deoxyribonucleic acid upstream from the cyclooxygenase 1 transcription start site (2.9 kilobases) were sequenced in 38 individuals, with 9 single-nucleotide polymorphisms identified. RESULTS: Two single-nucleotide polymorphisms, A-842G and C50T, were in complete linkage disequilibrium. Participants who were heterozygous for the A-842G/C50T haplotype showed significantly (P =.01) greater inhibition of prostaglandin H(2) formation by acetylsalicylic acid (30 micromol/L) compared with common allele homozygotes. CONCLUSIONS: The discovery of a functional single-nucleotide polymorphism in the cyclooxygenase 1 locus may ultimately improve the safe and effective use of acetylsalicylic acid by better tailoring of dosage with an individual's genetic variation.

Adult↗

PubMed1975

Population genetics of euphydryas butterflies. I Genetic variation and the neutrality hypothesis.

Twenty-one populations of the checkerspot butterfly, Euphydryas editha, and ten populations of Euphydryas chalcedona were sampled for genetic variation at eight polymorphic enzyme loci. Both species possessed loci that were highly variable from population to population and loci that were virtually identical across all populations sampled. Our data indicate that the neutrality hypothesis is untenable for the loci studied, and therefore selection is indicated as the major factor responsible for producing these patterns. Thorough ecological work allowed gene flow to be ruled out (in almost all instances) as a factor maintaining similar gene frequencies across populations. The Lewontin-Krakauer test indicated magnitudes of heterogeneity among standardized variances of gene frequencies inconsistent with the neutrality hypothesis. The question of whether or not to correct this statistic for sample size is discussed. Observed equitability of gene frequencies of multiple allelic loci was found to be greater than that predicted under the neutrality hypothesis. Genetic differentiation persisting through two generations was found between the one pair of populations known to exchange significant numbers of individuals per generation. Two matrices of genetic distance between populations, based on the eight loci sampled, were found to be significantly correlated with a matrix of environmental distance, based on measures of fourteen environmental parameters. Correlations between gene frequencies and environmental parameters, results of multiple regression analysis, and results of principle component analysis showed strong patterns of association and of "explained" variation. The correlation analyses suggest which factors might be further investigated as proximate selective agents.

Animals↗

PubMed2006

Roles of genetic variations in signalling/immunoregulatory molecules in susceptibility to systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a complex genetic basis that includes many susceptibility genes on multiple chromosomes. As complex human diseases like SLE involve multiple, interacting genetic and environmental determinants, identifying genes for complex traits is challenging and has had limited success so far. However, recent advances in genetic resources and technology have been providing new tools to identify the novel pathways or the sequence variants that contribute to autoimmune diseases. During the past several years, several new candidate genes have been implicated in development of SLE though association studies. In this article we describe an overview of the latest findings in the genetics of SLE, especially focusing on the genetic variations in the signalling or immunoregulatory molecules including CD28 and IRF family members.

Animals↗

PubMed2005

Beyond affect: a role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task.

Prior work has highlighted the role of genetic variation within the repetitive sequence in the transcriptional control region of the serotonin (5-HT) transporter gene (5-HTT, SLC6A4) in modulating amygdala and prefrontal activation to negative emotional stimuli. However, these studies have not explicitly tested the assumption that the control condition (neutral baseline) does not itself produce changes in activation as a function of 5-HTT genotype. Using a fixation baseline condition, we show that variation in 5-HTT genotype is associated with differential activation to negative, positive, and neutral stimuli in limbic, striatal, and cortical regions. We replicate earlier reports of increased amygdala activation to negative, relative to neutral, stimuli, but then show that these differences are driven by decreased activation to neutral stimuli, rather than increased activation to negative stimuli, in carriers of the 5-HTT short allele. Using high-resolution structural images and automated processes to test for brain volume and gray matter density, we further report significant differences, as a function of 5-HTT genotype, in frontal cortical regions, anterior cingulate, and cerebellum. These functional and structural differences suggest a much broader role for 5-HT transport efficiency in brain processes than previously thought. 5-HTT genotype affects neural systems controlling affective, cognitive, and motor processes.

Analysis of Variance↗

PubMed2026

Global downstream BMP15 pathway analysis in human ovarian granulosa cells reveals novel genetic variations associated with primary ovarian insufficiency.

OBJECTIVES: Primary ovarian insufficiency (POI) is a fertility disorder with a well-established genetic component, but many cases still remain idiopathic. Approximately 1.5-12% of patients with POI can carry a variant in the BMP15 gene, depending on the population and the diagnostic criteria. We hypothesize that genetic variations within pathways downstream of BMP15 activity in ovarian granulosa cells (GCs) may contribute to unexplained cases of POI. The main goal of this study is to identify novel variants associated with POI in genes induced by BMP15 in GCs. STUDY DESIGN: Primary cultures of human GCs were stimulated with recombinant human BMP15. Microarray analysis profiled the BMP15-induced transcriptome in GCs. Validation was achieved by qPCR and immunoblot. Further, target exome sequencing of the differentially expressed genes was performed on 64 women with early POI onset in search of novel variants. MAIN OUTCOME MEASURES: Transcriptome profiling of human GCs stimulated with BMP15 and target exome sequencing in women with early onset of POI. RESULTS: Transcriptome analysis revealed significant upregulation of 19 genes (p < 0.05). Ontology analysis of these genes converged towards two main pathways: TGF-beta signaling and regulation of stem cell pluripotency. Target exome sequencing identified six novel rare variants in five BMP15-induced genes (SAMD11, SMAD6, ID1, USP35, GPCR137C) in 9 of the 64 women with early POI (14%). CONCLUSIONS: BMP15 action in human ovarian GCs defines TGF-beta signaling and pluripotency fate in ovarian follicles. In addition, this study uncovers new potential candidate genes for the pathogenesis of POI.

Humans↗

PubMed2005

High resolution DNA fingerprinting by AFLP to study the genetic variation among Oesophagostomum bifurcum (Nematoda) from human and non-human primates from Ghana.

An AFLP approach was established to investigate genetic diversity within Oesophagostomum bifurcum (order Strongylida) from human and non-human primates. Evaluation of different combinations of restriction enzymes (n = 8) and primers (n = 29) demonstrated that the use of HindIII/BglII digested templates and primers with the selective nucleotides + AG/ +AC, respectively, was the most effective for the analysis of O. bifurcum DNA. A total of 63 O. bifurcum adults from human, Patas monkey, Mona monkey and Olive baboon hosts from different geographical regions in Ghana were subjected to analysis using this method. Cluster analysis revealed 4 genetically distinct groups, namely O. bifurcum from the Patas monkey (I), from the Mona monkey (II), from humans (III) and from the Olive baboon (IV). These findings were concordant with those achieved previously using RAPD analysis and supports population genetic substructuring within O. bifurcum according to host species. The results demonstrated the effectiveness of the present AFLP method for establishing genetic variation within O. bifurcum, and indicates its applicability to other parasitic nematodes of human and/or veterinary health importance.

Animals↗

PubMed1992

Microgeographic and temporal genetic variation in populations of the bluetongue virus vector Culicoides variipennis (Diptera: Ceratopogonidae).

Seven Colorado populations of the bluetongue virus vector Culicoides varipennis (Coquillett) were analyzed for genetic variation at 19-21 isozyme loci. Permanent populations, which overwinter as larvae, showed little temporal genetic change at 19 loci. PGD and MDH showed seasonal changes in gene frequencies, attributable to selection at two permanent populations. Two temporary populations showed low heterozygosity compared with permanent populations. Independent estimates of gene flow, calculated using FST and the private allele method, were Nm* = 2.15 and 6.95, respectively. Colorado C. variipennis permanent populations showed high levels of gene flow which prevented significant genetic differentiation due to genetic drift. Temporary populations showed significant gene frequency differences from nearby permanent populations due to the "founder effect" associated with chance colonization.

Animals↗

PubMed1998

Genetic variation in the 3' untranslated region of the neurofibromatosis 1 gene: application to unequal allelic expression.

Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by inactivation of neurofibromin, a protein capable of modulating signal transduction by activating Ras-GTPase activity. We have used cDNA cloning and Northern blot analysis to confirm the NF1 gene produces alternatively polyadenylated mRNAs with 3' untranslated regions (3' UTR) that show striking evolutionary conservation. Scanning of the 3'UTRs for genetic variation revealed three common sequence polymorphisms (> 30% heterozygosity), one less informative polymorphism (approximately 5% heterozygosity) and one rare variant (1/144 chromosomes). These differences were used to examine relative levels of expression of normal and mutant NF1 alleles in lymphoblast cell lines and in one case, autopsy tissue, from patients with NF1. Unequal allelic expression (up to 4-fold) was observed in a subset of both sporadic and familial NF1 cases. Where linkage phase could be determined, the allele segregating with the disorder displayed a relative reduction in expression. However, the magnitude of this effect was variable suggesting the operation of additional, non-genetic factors in determining the degree of relative expression of the mutant allele.

3' Untranslated Regions↗

PubMed2006

Effect of genetic variations of the POU1F1 gene on growth traits of Nanyang cattle.

PCR-RFLP was applied to analyze the effect of the genetic variations of the POU1F1 gene on growth traits of 100 Nanyang cattle. The results showed that the 451 bp PCR product digested with Hinf I demonstrated polymorphism in the population, which was at Hardy-Weinberg equilibrium. Moreover, the frequencies of alleles A/B in the Nanyang population were 0.465/0.535. The association of the variations of the POU1F1 gene with the growth traits in the population was analyzed. The following parameters were greater in individuals with a genotype BB than in those with an genotype AB: birth weight, average weight increase before ablactation, body height at 12 months, body weight, body length, and chest girth at 6 months and 12 months (P<0.05). The body weight at 12 months was higher in the BB individuals than in the AA individuals (P <0.05). The body weight and body sizes also showed a trend of allele B> allele A in the other age groups. Therefore, the genotype BB maybe a dominant genotype and the allele B may be a dominant allele. These results imply that the allele B of the POU1F1 gene is likely to positively affect the growth traits.

Alleles↗

PubMed2004

Genetic variation at the locus encompassing 11-beta hydroxylase and aldosterone synthase accounts for heritability in cortisol precursor (11-deoxycortisol) urinary metabolite excretion.

Genetic variation in the gene encoding aldosterone synthase (CYP11B2) has previously been shown to be associated with hypertension and left ventricular hypertrophy. The intermediate phenotype most consistently associated with variation at this locus is that of elevated plasma 11-deoxycortisol (S). However, in normal subjects, aldosterone synthase does not metabolize S, which is converted to cortisol (F) by the enzyme 11 beta hydroxylase, encoded by the gene CYP11B1, which lies adjacent to CYP11B2 on chromosome 8. It is possible that the quantitative trait locus for the phenotype is within CYP11B1 and that linkage disequilibrium across the extended locus could account for these observations. However, variation across the whole CYP11B1/B2 locus had not been extensively characterized with respect to these phenotypes. We genotyped six polymorphisms in the CYP11B2 gene and three polymorphisms in the CYP11B1 gene in 248 Caucasian nuclear families comprising 1428 individuals. We measured plasma levels of S and F in 460 individuals from 86 families and urinary excretion rates of tetrahydrodeoxycortisol (THS) and tetrahydrodeoxycorticosterone in 573 individuals from 105 families. We examined heritability of the phenotypes and their association with genotypes and haplotypes at this locus. All steroid phenotypes except urinary tetrahydrodeoxycorticosterone were highly heritable (P < 0.00001). There was strong linkage disequilibrium across the CYP11B1/B2 locus. There was modest evidence for association between polymorphisms of CYP11B2 and plasma levels of S (P = 0.02 for T4986C polymorphism) and the plasma S to F ratio, reflecting the activity of 11-beta hydroxylase (P = 0.01 for T4986C polymorphism). There was strong evidence for association between polymorphisms of both CYP11B1 and CYP11B2 and urinary THS, which was strongest for the CYP11B1 exon 1 polymorphism (P = 0.00002). Addition of other marker data to CYP11B1 exon 1 did not improve the fit of a log-linear model. Genotype at CYP11B1 explained approximately 5% of the variance in urinary THS excretion in the population. Thus, it is likely that linkage disequilibrium between causative CYP11B1 variants and CYP11B2 polymorphisms account for the previous observations. Further fine-mapping studies across the CYP11B1 locus are required to localize the causative variant(s) for the biochemical phenotype; this may also identify susceptibility alleles for hypertension and left ventricular hypertrophy.

Adrenal Cortex Hormones↗

PubMed2006

High genetic variation in the multidrug transporter cmeB gene in Campylobacter jejuni and Campylobacter coli.

OBJECTIVES: This study was conducted to examine the genetic variation occurring in the cmeB gene encoding the transporter component of the CmeABC efflux pump. METHODS: Expression of the CmeABC pump in 21 strains of Campylobacter jejuni and Campylobacter coli was studied by western-blot analysis. MIC determination was conducted in the presence or absence of an efflux pump inhibitor (EPI). Inactivation of the cmeB gene and sequencing of the cmeABC operon were performed for a single strain. The remaining strains were compared by RFLP analysis of the cmeB-specific PCR amplicon. The cmeB genes of two C. coli strains with different RFLP patterns were sequenced completely. RESULTS: Conflicting results were obtained in the western-blot analysis with anti-CmeB and anti-CmeC antibodies for one strain, whereas MIC determinations with EPI and cmeB gene inactivation confirmed the efflux pump's activity. The cmeB gene of this isolate showed only 78% nucleotide sequence identity with the sequence of reference strains. PCR-RFLP analysis identified 4 different patterns among the 5 C. jejuni and 14 different patterns among the 16 C. coli strains investigated. At the amino acid sequence level, variation was higher in the periplasmic loops of the transporter. CONCLUSIONS: A total of 18 different cmeB-specific PCR-RFLP patterns were detected among the 21 C. jejuni and C. coli strains. These sequence variations might have an impact on the function and substrate recognition of this transporter. The sequence data obtained in this study will help to design suitable tools to study the presence or the expression of the gene cmeB.

Amino Acid Sequence↗

PubMed2001

Genetic variation of Citrus tristeza virus isolates from California and Spain: evidence for mixed infections and recombination.

We examined the population structure and genetic variation of four genomic regions within and between 30 Citrus tristeza virus (CTV) isolates from Spain and California. Our analyses showed that most isolates contained a population of sequence variants, with one being predominant. Four isolates showed two major sequence variants in some genomic regions. The two major variants of three of these isolates showed very low nucleotide identity to each other but were very similar to those of other isolates, suggesting the possibility of mixed infections with two divergent isolates. Incongruencies of phylogenetic relationships in the different genomic regions and statistical analyses suggested that the genomes of some CTV sequence variants originated by recombination events between diverged sequence variants. No correlation was observed between geographic origin and nucleotide distance, and thus from a genetic view, the Spanish and Californian isolates analyzed here could be considered members of the same population.

California↗

PubMed2001

Echinococcus granulosus: intraspecific genetic variation assessed by a DNA repetitive element.

A 186 bp Echinococcus granulosus-specific repetitive element, TREg, was used to assess genetic variation between strains. In G7 genotype (pig strain) it has the characteristics of a satellite DNA element with a copy number of 23000 per haploid genome. Analysis, by sequencing of TREg monomers, showed a great degree of identity within them. In the G1 genotype (common sheep strain) TREg-like repetitive elements were found in an interspersed distribution throughout the genome and in only 120 copies. The sequences of these monomers showed a great degree of variation between them and with TREg of G7 origin. The G6 genotype (camel strain) showed a pattern of distribution and copy number similar to the G7 genotype, and the G2 genotype (Tasmanian sheep strain) similar to the G1 genotype. Isolates from the G5 (cattle strain) and G4 (horse strain) genotypes also showed unique hybridization patterns in Southern blot experiments. The genomic plasticity of E. granulosus, which may have important consequences in the epidemiology and control of cystic hydatid disease is reflected in the results of this work.

Animals↗

PubMed2001

Southern Mexican minnows of the genus Notropis (Actinopterygii, Cyprinidae): genetic variation, phylogenetic relationships and biogeographical implications.

Allozyme analyses were performed to determine patterns of genetic variation and phylogenetic relationships within the genus Notropis in southern Mexico. Products of 28 gene loci were resolved in 24 geographic samples belonging to four putative species. These species represent the southern limit of the Cyprinidae in North America. Five loci were found monomorphic and 11 were diagnostic among species when the outgroup, Phoxinus phoxinus, was not taken into account. Four groups were identified, but these do not correspond perfectly to the four nominal species. Notropis sallaei was identified by allozyme analyses being the most basal among southern Mexican Notropis and the most genetically divergent. Notropis imeldae, was also diagnosed on the basis of allozymic variation, however a population sample representing the Balsas drainage was genetically divergent and is considered as an undescribed new species (N. n. sp.). No genetic differences were found between the samples of N. boucardi and N. moralesi. Therefore, we recommend that N. moralesi should be considered as a junior synonym of N. boucardi. A broad geographic sampling strategy was employed across all the distribution range of N. boucardi representing rivers from three different drainages, which cover both Mexican slopes. The slight divergence found among the headwater populations of N. boucardi permitted us to predict a model of paleohydrographic relationships of these three drainages. Two alternative hypotheses are postulated to explain the current distribution pattern of populations of N. boucardi in southern Mexico.

Journal Article↗

PubMed2003

Genetic variation of resistance to mercury poisoning in steelhead (Oncorhynchus mykiss) alevins.

Newly hatched steelhead alevins were obtained from the factorial breeding of 24 male and 10 female steelhead trout, Oncorhynchus mykiss. Each set of offspring were in a separate cell. They were tested for resistance to intoxication by methylmercuric chloride (CH3HgCl) in water at a nearly constant mercury concentration of 8 microg l(-1). High mortality (81% of the tested alevins) occurred within 2 weeks. Resistance to intoxication, as measured by the time to death, as well as by the survival rate, shared high paternal and maternal variation with negligible interaction. Heritability of time to death was 0.59 +/- 0.17; heritability of survival (all-or-none trait) was lower (0.26 +/- 0.09). Mercury in dead alevins increased with time to death, exhibiting a large environmental variation and (comparatively) negligible genetic influence. At the end of the bioassay, the mercury content in survivors varied widely (3-21 microg g(-1) wet weight). The content was greater than, but correlated with that of dead alevins from the same cells, and it showed little relation with survival rate. Thus, it seems that resistance to poisoning implies a tolerance to high levels of mercury rather than a limitation of its accumulation.

Animals↗