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Results for “Genetic Variation”

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PubMed2003

Genetic variation in northern Japanese populations of the starfish Asterina pectinifera.

The starfish Asterina pectinifera of the family Asterinidae is endemic Japanese species and commonly found in Japanese waters. In order to examine the degree of genetic variation and the maintenance mechanism of polymorphism within population, we studied the allozyme variation in five northern Japanese local populations of the starfish by electrophoresis. The species showed much higher genetic variability than many other shallow water echinoderms. Based on other allozyme studies and the ecological data, it was suggested that the high genetic variation of the starfish was closely related to the population size. Additionally, the relation between the degree of enzyme variation and the quaternary structure of enzymes was also examined, and the results suggested the close relation between the enzyme variability and functional constraints.

Animals↗

PubMed1997

Molecular genetic variation in Echinococcus and Taenia: an update.

An update on our understanding of molecular variation in Echinococcus and Taenia is provided. Genetic variation within certain species of Echinococcus is now a well accepted phenomenon and a number of intraspecific variants or strains of E. granulosus, in particular, have been characterized hitherto using a range of procedures. Newly acquired molecular information has now been used in epidemiological studies with E. granulosus and in phylogenetic analysis of the genus Echinococcus. Similarly, DNA approaches have been applied for taxonomic characterization of the recently recognized Asian Taenia, a third form of human Taenia, which occurs in Southeast Asia, and which is distinguishable from, but closely related to, Taenia saginata.

Animals↗

PubMed2004

Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits.

Phenotypic plasticity and the exposure of hidden genetic variation both affect the survival and evolution of new traits, but their contributing molecular mechanisms are largely unknown. A single factor, the yeast prion [PSI(+)], may exert a profound effect on both. [PSI(+)] is a conserved, protein-based genetic element that is formed by a change in the conformation and function of the translation termination factor Sup35p, and is transmitted from mother to progeny. Curing cells of [PSI(+)] alters their survival in different growth conditions and produces a spectrum of phenotypes in different genetic backgrounds. Here we show, by examining three plausible explanations for this phenotypic diversity, that all traits tested involved [PSI(+)]-mediated read-through of nonsense codons. Notably, the phenotypes analysed were genetically complex, and genetic re-assortment frequently converted [PSI(+)]-dependent phenotypes to stable traits that persisted in the absence of [PSI(+)]. Thus, [PSI(+)] provides a temporary survival advantage under diverse conditions, increasing the likelihood that new traits will become fixed by subsequent genetic change. As an epigenetic mechanism that globally affects the relationship between genotype and phenotype, [PSI(+)] expands the conceptual framework for phenotypic plasticity, provides a one-step mechanism for the acquisition of complex traits and affords a route to the genetic assimilation of initially transient epigenetic traits.

Biological Evolution↗

PubMed2000

Patterns of genetic variation in rare and widespread plant congeners.

Rare species are typically considered to maintain low levels of genetic variation, and this view has been supported by several reviews of large numbers of isozyme studies. Although these reviews have provided valuable data on levels of variability in plant species in general, and rare species in particular, these broad overviews involve comparisons that may confound the effects of rarity with a multitude of other factors that affect genetic variability. Additionally, the statistical analyses employed assume the data to be independent, which is not the case for organisms that share a common phylogenetic history. As the role of evolutionary history and historical constraints has become better understood, more researchers have studied widespread congeners when investigating the genetic diversity of rare species in an effort to control for these effects. We summarize the available data from such studies, comparing for rare and widespread congeners (1) the levels of genetic variability at the population and species levels and (2) measures of population substructuring. At the population level, we summarized data for percentage polymorphic loci (%P(pop)), mean number of alleles per locus (A(pop)), and observed heterozygosity (H(o)). Species-level measures used were percentage polymorphic loci (%P(spp)), mean number of alleles per locus (A(spp)), and total genetic diversity (H(T)). Indices of population subdivision (either F(ST) or G(ST)) were also examined. Using Wilcoxon signed rank tests, we found significant, but small, differences between rare and widespread species for all diversity measures except H(T). However, there does not appear to be a difference between rare and widespread congeners in terms of how genetic variation is partitioned within and among populations. Levels of diversity, for all measures examined, between rare and widespread congeners are highly correlated.

Journal Article↗

PubMed1987

The genetic variation of compatibility in Biomphalaria glabrata and Schistosoma mansoni.

Interactions between different Biomphalaria glabrata stocks and Schistosoma mansoni strains were studied. A series of inbred stocks of B. glabrata were characterized as to genetic variations in susceptibility at different ages to a series of different S. mansoni strains. A series of inbred strains of S. mansoni were characterized as to genetic variations in infectivity for B. glabrata stocks at different ages. Also described is a process of selection for substrains from a single S. mansoni isolate that differ genetically in snail infectivity.

Animals↗

PubMed2002

Pleiotropic model of maintenance of quantitative genetic variation at mutation-selection balance.

A pleiotropic model of maintenance of quantitative genetic variation at mutation-selection balance is investigated. Mutations have effects on a metric trait and deleterious effects on fitness, for which a bivariate gamma distribution is assumed. Equations for calculating the strength of apparent stabilizing selection (V(s)) and the genetic variance maintained in segregating populations (V(G)) were derived. A large population can hold a high genetic variance but the apparent stabilizing selection may or may not be relatively strong, depending on other properties such as the distribution of mutation effects. If the distribution of mutation effects on fitness is continuous such that there are few nearly neutral mutants, or a minimum fitness effect is assumed if most mutations are nearly neutral, V(G) increases to an asymptote as the population size increases. Both V(G) and V(s) are strongly affected by the shape of the distribution of mutation effects. Compared with mutants of equal effect, allowing their effects on fitness to vary across loci can produce a much higher V(G) but also a high V(s) (V(s) in phenotypic standard deviation units, which is always larger than the ratio V(P)/V(m)), implying weak apparent stabilizing selection. If the mutational variance V(m) is approximately 10(-3)V(e) (V(e), environmental variance), the model can explain typical values of heritability and also apparent stabilizing selection, provided the latter is quite weak as suggested by a recent review.

Genetic Variation↗

PubMed1991

Soft selection and quantitative genetic variation: a laboratory experiment.

The effect of environmental heterogeneity on the genetic variation of different quantitative characters was studied in two laboratory and two recently captured populations of Drosophila melanogaster. Two different culture media (habitats R and G) were used. Coarse-grained heterogeneity with independent density control in each habitat (R + G), and fine-grained (R/G) heterogeneity were simulated in population cages. Control populations in both R and G habitats were also maintained. Genetic differences for oviposition-site preference, larval preference and/or within-habitat viability were found between subpopulations sampled from different media. This happened in all four populations maintained on R + G, two populations maintained on R/G, and one control population. Thus, environmental heterogeneity seems to protect genetic variability responsible for between-habitat genetic differentiation, particularly when such heterogeneity corresponds to the 'soft selection' model (R + G). However, for the quasi-neutral trait sternopleural bristle number, no genetic between-habitat differentiation, nor increased heritability were observed in populations maintained under any kind of environmental heterogeneity. Hence, although soft selection seems to be a real force in determining adaptation to heterogeneous environments, the genetic variability maintained may be small in relation to the whole genome.

Animals↗

PubMed1987

Role of genetic variation at the fibrinogen locus in determination of plasma fibrinogen concentrations.

Three restriction fragment length polymorphisms (RFLPs) of the fibrinogen genes were used in 91 individuals to investigate the role of genetic variation at this locus in the determination of plasma fibrinogen. The strongest association was with a polymorphism detected with the beta-fibrinogen probe and the enzyme BclI. The probe detects two alleles, designated B1 and B2. The individuals with the genotype B1B1 had a mean fibrinogen of 2.74 g/l; those with B2B2 had a mean fibrinogen of 3.69 g/l (a level previously associated with a strongly increased risk of ischaemic heart disease); and those heterozygous for the two alleles, with the genotype B1B2, had a mean of 2.98 g/l. Genetic variation at the fibrinogen gene locus accounted for 15% of the total phenotypic variance in fibrinogen.

Female↗

PubMed1993

Genetic variation in outbred rats and mice and its implications for toxicological screening.

There are two basic types of laboratory rodent used in toxicological screening. Isogenic (inbred) strains are rather like clones of genetically identical individuals whereas outbred stocks are usually more variable, though the amount of variability depends on the previous history of the colony. In some cases outbred stocks may be genetically quite uniform. Many different strains of both types are available. Both types and a variety of strains are used for toxicological screening. There is clear evidence of important genetic variation both in spontaneous disease and in response to toxic agents, yet little account is taken of this in choosing suitable animals. Three options appear to be available. The first is to ignore genetic variation and use a single isogenic strain. However, if the strain happens to be insensitive to the test chemical, a toxic chemical may be judged to be relatively safe. The second option would be to synthesize a genetically heterogeneous stock by crossing two or more strains. However, this could lead to both increased false positive and false negative results as experimental "noise" either obscures true treatment effects, or is mistaken for a treatment effect. The third option is to use more than one strain, but without increasing the total number of animals used. This would provide a broad range of genotypes, so reducing the chance that they are all insensitive, without increasing experimental noise. This appears to be the only sensible way of broadening the genetic base in toxicological screening. Where strain differences are found, they may provide a tool for studying toxic mechanisms, which may be helpful in extrapolating to human populations.

Animals↗

PubMed2006

DRD2 genetic variation in relation to smoking and obesity in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

OBJECTIVES: Cigarette smoking is the leading cause of morbidity and mortality worldwide. We investigated the association between smoking behavior and genetic variations in the D2 dopamine receptor (DRD2), which mediates nicotine dependence. To assess the specificity of genetic effects, we also investigated other reward-motivated characteristics (obesity, alcohol consumption). METHODS: Four single nucleotide polymorphisms in DRD2 were genotyped in 2374 participants selected randomly from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial after stratifying by sex, age, and smoking status. Smoking, obesity, and alcohol consumption were assessed by questionnaire. Single nucleotide polymorphism and haplotype associations were estimated using odds ratios (ORs) and 95% confidence intervals derived from conditional logistic regression models, adjusted for race/ethnicity. RESULTS: DRD2 polymorphisms were associated with the risk of remaining a current smoker and obesity. Current smokers were more likely than former smokers to possess the variant TaqIA allele (rsmusical sharp1800497) in a dose-dependent model (ORCT=1.2, ORTT=1.5, P for linear trend=0.007). The DRD2 haplotype T-C-T-A [TaqIA(C/T)-957(T/C)-IVS6-83(G/T)- -50977(A/G)] was more common among current than former smokers (OR=1.3, P=0.006), particularly among heavy smokers (21+ cigarettes per day; OR=1.6, P=0.006), and was more common among obese than normal weight individuals (OR=1.4, P=0.02). CONCLUSIONS: Genetic variation in DRD2 is a modifier of the reward-motivated characteristics, smoking and obesity. As fewer than 15% of smokers who attempt to quit are able to maintain abstinence for greater than 3 months, our results support that DRD2 is an appropriate molecular target for smoking cessation treatments. Our results further support evaluation of DRD2 antagonists for obesity therapies.

Aged↗

PubMedDate not supplied

Molecular genetic variation in the East Midlands, England: analysis of VNTR, STR and Alu insertion/deletion polymorphisms.

BACKGROUND: Short tandem repeats (STRs) and variable number of tandem repeats (VNTRs) have been used successfully in disease analysis and studies of human evolution and population genetic diversity. However DNA-based comprehensive population genetic studies of the East Midlands, England are limited. SUBJECTS AND METHODS: To enlarge our understanding of genetic variation in the East Midlands, a study was conducted on five regional populations: north-west Derbyshire,north-east Derbyshire, south Derbyshire, Nottinghamshire and Leicestershire. Blood samples were collected from donors whose ancestors had lived in the region for at least three generations. Seven VNTRs (MSI (DIS7), MS31 (D7S21), MS43A (D12SII) and YNH24 (D2S44), DIS0, APOB, YNZ22 (D17S5)), six STRs (HumTHOI, HumVWA31A, HumF13AOl1, HumFESFPS, HumCSFIPO, HumTPOX) and six Alu insertion/deletion polymorphisms (TPA25, ACE, PV92, F13B, APO, DI) were analysed in approximately 500 individuals. Allele or bin frequencies were calculated using gene counting and fixed bin methods. The chi-square method and exact tests were used to assess Hardy-Weinberg equilibrium. Genetic distances were calculated using Nei's DA method and correspondence analysis was used to assess population affinities. RESULTS: The overall pattern of allele frequencies was similar to many European and UK populations for a number of genetic systems. Overall heterogeneity was observed for five loci: MS43A, MS31, HumF13A0l, HumFESFPS and HumTHOI. Twenty-three of 190 pairwise population comparisons were also statistically significant at the 5% level. Average molecular genetic system heterozygosity was 1.5 times higher than observed with conventional blood group systems. GsT values for molecular systems were also higher than conventional systems (0.012 vs 0.005) and suggest a low to moderate level of differentiation. CONCLUSION: The allele frequency spectrum and inter-population comparisons show that there is significant genetic variation in the five contiguous regional populations of the East Midlands. Some of this variation may be due to local geographical barriers, genetic drift and possibly the settlement patterns of Continental European invaders.

Alu Elements↗

PubMed1994

Genetic variation of foot-and-mouth disease virus during persistent infection in cattle.

Genetic variation of foot-and-mouth disease virus O1 Campos has been analyzed in consecutive isolates recovered over a one- or two-year period from four cattle with experimental persistent infection. Comparisons of RNase T1 two-dimensional maps and nucleotide sequences of the VP1-coding region revealed a continual, although irregular, increase in the fixation of mutations as the infection progressed. Most changes were not conserved in consecutive isolates. These results, together with the substantial rates of genomic variation observed between some pairs of strains recovered at close time periods, suggested the coexistence of heterogeneous populations in which variants evolve independently from each other, and predominate at irregular time intervals. Furthermore, non-related patterns of variation were observed in the four animals. Similarly, genetic diversity of representative strains from major serotype O outbreaks in endemic disease regions of southeastern Brazil and central eastern Argentina which occurred between 1958 and 1983, suggested that outbreak strains are also likely to represent fluctuations of heterogeneous populations which evolve independently from each other. The possible role of persistent infections in the introduction of variant populations in the field is discussed.

Amino Acid Sequence↗

PubMed1983

Genetic variation among dengue 2 viruses of different geographic origin.

Genetic variation in dengue 2 isolates from various geographic areas was examined by oligonucleotide fingerprinting of the 40 S genome RNA. Oligonucleotide maps of geographically isolated and epidemiologically unrelated viruses were very distinct. Direct comparison of the oligonucleotide map of the dengue 2 prototype New Guinea 2 virus, isolated in 1944, with the fingerprints of more recent isolates from the South Pacific indicated that the genome of dengue 2 virus had undergone extensive change although the viruses are serologically indistinguishable. The oligonucleotide map of an isolate from a recent case in Jamaica and a mosquito isolate from Upper Volta, Africa, were recognized to be almost identical, suggesting that virus may have been introduced into the Caribbean from West Africa. Likewise, the fingerprints of isolates from Puerto Rico and the South Pacific shared 80 to 95% of their large oligonucleotides, suggesting that the virus involved in these epidemics may have spread throughout Tahiti, American Samoa, Fiji, and to Puerto Rico in the Caribbean or vice versa. On the basis of these studies, five genetic variants or topotypes of dengue 2 virus have been established: (1) Puerto Rico-South Pacific, (2) Burma-Thailand, (3) the Seychelles, (4) the Philippines, and (5) Jamaica-West Africa. Oligonucleotide fingerprinting offers a highly sensitive and reproducible technical approach to the investigation of dengue 2 virus intratypic variation and possibly to the understanding of the biological variation associated with dengue fever and hemorrhagic disease.

Africa, Western↗

PubMed2003

Genetic variation in apolipoprotein D affects the risk of Alzheimer disease in African-Americans.

Apolipoprotein D (APOD, gene; apoD, protein) is involved in neuroregenerative and neurodegenerative processes, and is upregulated in late-onset Alzheimer disease (AD) patients compared to nondemented controls. No genetic association studies have yet been carried out to investigate the role of APOD in AD. We have reported recently several sequence variants in the APOD gene, which are present exclusively among African blacks. In the present study we examined the role of four APOD genetic variants (Intron 1, codons 36, 108, 158) in modifying the risk of AD in 70 subjects with AD and 163 nondemented subjects from a population-based African-American cohort in Indianapolis. The Intron 1*2 allele was associated with an increased AD risk with an age, gender and APOE adjusted odds ratio (OR) of 2.29 (95% confidence interval [CI]: 1.19-4.43; P = 0.013), and this risk was confined to APOE*4 carriers (OR 3.12; 95% CI: 1.13-8.60; P = 0.028). The frequency of the codon 36/GT genotype was non-significantly higher in individuals with AD than nondemented subjects (4.3% vs. 1.2%) with an adjusted OR of 4.24 (95% CI: 0.66-27.14; P = 0.13). Our data suggest that the risk of AD among African-Americans may be modified by genetic variation in APOD. Larger population-based or case-control studies are needed to confirm the role of APOD genetic variation in AD.

Aged↗

PubMed2006

Genetic variation is associated with C-reactive protein levels in the Third National Health and Nutrition Examination Survey.

BACKGROUND: Increased serum C-reactive protein (CRP) is an independent risk factor for cardiovascular disease. Previous studies have suggested that genetic variation within the CRP gene is associated with serum CRP. METHODS AND RESULTS: We genotyped CRP genetic variants in 7159 individuals from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is American population-based sample linked to hundreds of phenotypes, including CRP; however, the CRP assay used in this survey is not a high-sensitivity CRP assay, and 65% of participants (n=4679) had CRP measurements at or below the level of detection. Despite these limitations, we identified specific CRP single-nucleotide polymorphisms (SNPs) and haplotypes associated with serum CRP levels in the general population. Two variants were associated with increased levels of serum CRP: SNP rs3093058 (in linkage disequilibrium with a CRP promoter SNP rs3093062) in the non-Hispanic black sample and the triallelic promoter SNP rs3091244 in the non-Hispanic black and Mexican American samples. Two other SNPs were associated with decreased levels of serum CRP in either the non-Hispanic black (rs1205 and rs2808630) or Mexican American (rs1205) samples. Three haplotypes inferred from 7 SNPs (ATTGCGA, TTAGCGA, and AAAGAGA) were associated (P < or = 0.01) with increased levels of serum CRP in the non-Hispanic black sample; 2 haplotypes (ATTGCGA and AAAGCGA) were associated (P < 0.05) with increased levels in the Mexican American sample; and 1 haplotype (AAAGCGA) was associated (P < 0.03) with increased levels in the non-Hispanic white sample. Post hoc analysis suggests that the AA genotype of the triallelic SNP rs3091244, after adjustment for covariates, was associated with prevalent coronary heart disease in the non-Hispanic white population sample. CONCLUSIONS: Genetic variation within CRP is associated with serum CRP levels in the general population and may be associated with prevalent coronary heart disease.

Adult↗

PubMed2004

Genetic variation in a cline in a living intertidal snail arose in the Neogastropoda over 100 million years ago.

To understand how species adapt and evolve it is necessary to appreciate the relationship between genetic variation and the environment. Here, the fossil record and molecular data from different lineages of the marine Gastropoda are used to understand the evolution of genetic variations found in the nuclear gene for mitochondrial malate dehydrogenase (mMDH; EC 1.1.1.37) in the living intertidal Muricid snail, Nucella lapillus. Assuming a molecular clock, DNA sequences of mMDH indicate that two variants found in N. lapillus, mMDH(9) and mMDH(10), may have arisen as long as 144 MY (million years) ago and at least prior to the evolution of the Muricidae approximately 112-90 MY ago. The Muricidae contain by far the greatest majority of the Neogastropoda specialized for life in the intertidal habitat. In N. lapillus the mMDH(9) and mMDH(10) variants covary with variations in other biochemically defined loci, inherited phenotypic traits (shell shape and physiology) and karyotype frequencies to differentiate two distinct nuclear haplotypes that are associated with different temperature environments. The variations in shell shape that are associated with the haplotypes of N. lapillus represent adaptations to temperature stress and similar variations occur in other related intertidal molluscs whose lineages are much older than Nucella, which arose around 25 million years ago. It is suggested that the divergence of the mMDH variants found in N. lapillus may reflect an ancient genetic event, such as a chromosomal mutation, perhaps involving variation in other linked traits that together became important in the subsequent evolution of the marine Gastropoda.

Adaptation, Biological↗

PubMed2006

Genetic variation in telomeric repeat binding factors 1 and 2 in aplastic anemia.

OBJECTIVE: Abnormal telomere shortening has been observed in a subset of individuals with aplastic anemia (AA). We hypothesized that genetic variation in two genes critical in telomere biology, TERF1 and TERF2, could be a risk factor for AA. METHODS: The proximal promoter and all coding regions of TERF1 and TERF2 were sequenced in 47 individuals with acquired AA. Regions with genetic variation were sequenced in an additional 95 AA patients and 289 healthy controls. Single nucleotide polymorphism (SNP) frequencies were analyzed using co-dominant and dominant models and haplotypes determined. Functional studies evaluated telomerase activity, telomere and telomeric overhang lengths, and TRF2 protein expression in select patients. RESULTS: Two nonsynonymous amino acid changes were detected, one in exon 9 of TERF1 and another in exon 6 of TERF2. These sequence variants resulted in conservative amino acid changes and were not predicted to alter TRF1 or TRF2 protein expression or function. SNP and haplotype analyses in acquired AA patients suggested that one variant allele, in intron 9 of TERF1, and haplotype could be associated with increased risk for aplastic anemia (OR 1.59, 95% confidence interval 1.06-2.39, p = 0.033). TERF2 SNPs and haplotypes were not significantly associated with aplastic anemia. CONCLUSIONS: It is possible that a common genetic variant in TERF1 is associated with risk for AA but additional studies are required. Highly penetrant, non-synonymous, or insertion-deletion mutations in TERF1 and TERF2 were not identified and therefore are not likely to be major genetic risk factors for the development of AA.

Anemia, Aplastic↗

PubMed2005

Comprehensive survey of common genetic variation at the plasminogen activator inhibitor-1 locus and relations to circulating plasminogen activator inhibitor-1 levels.

BACKGROUND: Using a linkage disequilibrium (LD)-based approach, we sought to comprehensively define common genetic variation at the plasminogen activator inhibitor-1 (PAI-1) locus and relate common single nucleotide polymorphisms (SNPs) and haplotypes to plasma PAI-1 levels. METHODS AND RESULTS: In reference pedigrees, we defined LD structure across a 50-kb genomic segment spanning the PAI-1 locus via a dense SNP map (1 SNP every 2 kb). Eighteen sequence variants that capture underlying common genetic variation were genotyped in 1328 unrelated Framingham Heart Study participants who had plasma PAI-1 antigen levels measured. Regression analyses were used to examine associations of individual SNPs and of inferred haplotypes with multivariable-adjusted PAI-1 levels. Two genetic variants, SNP rs2227631 and the 4G/5G polymorphism, were strongly associated (P<0.0001) with PAI-1 levels. SNP rs2227631 is in tight LD (D'=0.97, r2=0.78) with the 4G/5G polymorphism, which makes it difficult to distinguish which of these 2 polymorphisms is responsible for the association with PAI-1 levels. In stepwise analysis considering all polymorphisms tested, 3 SNPs, rs2227631 (or the correlated 4G/5G polymorphism), rs6465787, and rs2227674, each explained 2.5%, 1%, and 1%, respectively, of the residual variance in multivariable-adjusted PAI-1 levels (stepwise P<0.0001, P=0.04, and P=0.03, respectively). A single common haplotype, at 50% frequency among Framingham Heart Study participants, was strongly associated with higher PAI-1 levels (haplotype-specific P=0.00001). The susceptibility haplotype harbors the minor alleles of SNP rs2227631 and the 4G/5G polymorphism. CONCLUSIONS: Three sequence variants at the PAI-1 locus, in sum, explain approximately 5% of the residual variance in multivariable-adjusted PAI-1 levels. For quantitative cardiovascular traits such as circulating biomarkers, defining LD structure in a candidate gene followed by association analyses with both SNPs and haplotypes is an effective approach to localize common susceptibility alleles.

Aged↗