SEARCH · PubMed Health

Results for “Genetic Variation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources

PubMed2001

Genetic variation in Australian isolates of myxoma virus: an evolutionary and epidemiological study.

Myxoma virus and the European rabbit have been coevolving in Australia since the introduction of the Standard Laboratory Strain (SLS) of myxoma virus as a biological control agent for rabbits in 1950. To examine the degree of genetic variation that has occurred in the virus between 1950 and 1995 and to find genetic markers to use for epidemiological studies, we have examined 37 recent field isolates of myxoma virus for restriction fragment length polymorphisms (RFLPs) by comparision with the progenitor SLS released in 1950. Fifteen RFLPs in Australian isolates have been identified and characterized by mapping and partial DNA sequence analysis. The RFLPs that are most common are deletion and insertion events in regions of tandem repeats. Some of these RFLPs have been investigated by using polymerase chain reaction to identify them in archival tissue samples. In epidemiological studies we characterized two polymorphisms which occur in the Lausanne strain of myxoma virus (widely introduced into Australia from the 1970s) but not in SLS and showed that all of the viruses we isolated were derived from the SLS.

Amino Acid Sequence↗

PubMed2006

Genetic variation in Drosophila melanogaster resistance to infection: a comparison across bacteria.

Insects use a generalized immune response to combat bacterial infection. We have previously noted that natural populations of D. melanogaster harbor substantial genetic variation for antibacterial immunocompetence and that much of this variation can be mapped to genes that are known to play direct roles in immunity. It was not known, however, whether the phenotypic effects of variation in these genes are general across the range of potentially infectious bacteria. To address this question, we have reinfected the same set of D. melanogaster lines with Serratia marcescens, the bacterium used in the previous study, and with three additional bacteria that were isolated from the hemolymph of wild-caught D. melanogaster. Two of the new bacteria, Enterococcus faecalis and Lactococcus lactis, are gram positive. The third, Providencia burhodogranaria, is gram negative like S. marcescens. Drosophila genotypes vary highly significantly in bacterial load sustained after infection with each of the four bacteria, but mean loads are largely uncorrelated across bacteria. We have tested statistical associations between immunity phenotypes and nucleotide polymorphism in 21 candidate immunity genes. We find that molecular variation in some genes, such as Tehao, contributes to phenotypic variation in the suppression of only a subset of the pathogens. Variation in SR-CII and 18-wheeler, however, has effects that are more general. Although markers in SR-CII and 18-wheeler explain >20% of the phenotypic variation in resistance to L. lactis and E. faecalis, respectively, most of the molecular polymorphisms tested explain <10% of the total variance in bacterial load sustained after infection.

Animals↗

PubMed2004

A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms.

We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms (SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds (a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines--in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases.

Alleles↗

PubMed1998

Genetic variation of mitochondrial cytochrome b genes among the subspecies of koala, Phascolarctos cinereus.

A conserved DNA region among the subspecies of koala, of mitochondrial cytochrome b gene, was employed to analyze the genetic variation among 3 available subspecies of koala. This conserved sequence, 307 bp DNA, was sequenced using polymerase chain reaction and direct DNA sequencing technique. Substitutions in the nucleotide sequences were observed, with which koalas can be divided into 3 DNA haplotypes subspecies, but the molecular data provided inconsistency with current classification of the 3 subspecies of koala.

Amino Acid Sequence↗

PubMed2004

Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population.

Homozygosity for mutations in ABC transporter A1 (ABCA1) causes Tangier disease, a rare HDL-deficiency syndrome. Whether heterozygosity for genetic variation in ABCA1 also contributes to HDL cholesterol (HDL-C) levels in the general population is presently unclear. We determined whether mutations or single-nucleotide polymorphisms (SNPs) in ABCA1 were overrepresented in individuals with the lowest 1% (n=95) or highest 1% (n=95) HDL-C levels in the general population by screening the core promoter and coding region of ABCA1. For all nonsynonymous SNPs identified, we determined the effect of genotype on lipid traits in 9,259 individuals from the general population. Heterozygosity for ABCA1 mutations was identified in 10% of individuals with low HDL-C only. Three of 6 nonsynonymous SNPs (V771M, V825I, and R1587K) were associated with increases or decreases in HDL-C in women in the general population and some with consistent trends in men, determined as isolated single-site effects varying only at the relevant SNP. Finally, these results were consistent over time. In conclusion, we show that at least 10% of individuals with low HDL-C in the general population are heterozygous for mutations in ABCA1 and that both mutations and SNPs in ABCA1 contribute to HDL-C levels in the general population.

5' Untranslated Regions↗

PubMed2003

Isolation, genetic variation and expression of TIR-NBS-LRR resistance gene analogs from western white pine ( Pinus monticola Dougl. ex. D. Don.).

Western white pine ( Pinus monticola Dougl. ex. D. Don., WWP) shows genetic variation in disease resistance to white pine blister rust ( Cronartium ribicola). Most plant disease resistance (R) genes encode proteins that belong to a superfamily with nucleotide-binding site domains (NBS) and C-terminal leucine-rich repeats (LRR). In this work a PCR strategy was used to clone R gene analogs (RGAs) from WWP using oligonucleotide primers based on the conserved sequence motifs in the NBS domain of angiosperm NBS-LRR genes. Sixty-seven NBS sequences were cloned from disease-resistant trees. BLAST searches in GenBank revealed that they shared significant identity to well-characterized R genes from angiosperms, including L and M genes from flax, the tobacco N gene and the soybean gene LM6. Sequence alignments revealed that the RGAs from WWP contained the conserved motifs identified in angiosperm NBS domains, especially those motifs specific for TIR-NBS-LRR proteins. Phylogenic analysis of plant R genes and RGAs indicated that all cloned WWP RGAs can be grouped into one major branch together with well-known R proteins carrying a TIR domain, suggesting they belong to the subfamily of TIR-NBS-LRR genes. In one phylogenic tree, WWP RGAs were further subdivided into fourteen clusters with an amino acid sequence identity threshold of 75%. cDNA cloning and RT-PCR analysis with gene-specific primers demonstrated that members of 10 of the 14 RGA classes were expressed in foliage tissues, suggesting that a large and diverse NBS-LRR gene family may be functional in conifers. These results provide evidence for the hypothesis that conifer RGAs share a common origin with R genes from angiosperms, and some of them may play important roles in defense mechanisms that confer disease resistance in western white pine. Ratios of non-synonymous to synonymous nucleotide substitutions (Ka/Ks) in the WWP NBS domains were greater than 1 or close to 1, indicating that diversifying selection and/or neutral selection operate on the NBS domains of the WWP RGA family.

Amino Acid Sequence↗

PubMedDate not supplied

Genetic variation for seasonal adaptation in Peromyscus leucopus: nonreciprocal breakdown in a population cross.

The genetic basis for adaptations to the diverse environments encountered by a wide-ranging species should be reflected in the phenotypes of hybrids between differentiated populations. We crossed mice from two ecologically different populations to determine whether adaptations to seasonality in Peromyscus leucopus, the white-footed mouse, display directional dominance or whether they are affected by specific interactions between genes. Connecticut mice (C) have many adaptations to seasonality that are reduced or absent in Georgia mice (G) and that affect both reproductive and thermoregulatory traits. Because these adaptations are cued by photoperiod, temperature, or both, parental and hybrid mice were acclimated to 13 degrees C in either long-day or short-day photoperiod, and several morphological, reproductive, and thermoregulatory traits were measured. Several traits, especially those involved in response to the environment, such as nest size at 13 degrees C, reproductive regression under short-day photoperiod, and molt to winter pelage, showed a non-Mendelian pattern of inheritance. However, there was a pronounced difference between maternal lineages in the F2 generation in that C-maternal F2 mice were less responsive to short-day photoperiod and cold than were the G-maternal F2 mice. Because these two classes of F2 mice are genetically equivalent, this breakdown cannot be explained as a disruption of epistatic gene interactions unless recombination rates are higher in the C-maternal lineage.

Adaptation, Physiological↗

PubMed1992

Genetic variation at fibrinogen loci and plasma fibrinogen levels.

In view of the controversy regarding genetic variation at the fibrinogen loci and plasma fibrinogen levels, we have analysed DNA polymorphisms at the alpha (TaqI), beta (BclI and HaeIII), and gamma (KpnI/SacI) fibrinogen loci in 247 subjects whose plasma fibrinogen was determined by clotting and nephelometric assays. Strong linkage disequilibrium was found between the alpha/TaqI and gamma/KpnI/SacI markers and between the beta/BclI and beta/HaeIII markers. A lesser association was found between the alpha/TaqI and beta/BclI loci, beta/BclI and gamma/KpnI/SacI markers, alpha/TaqI and beta/HaeIII markers, and the gamma/KpnI/SacI and beta/HaeIII markers. This is consistent with the known physical order of these loci and suggests a relative excess of recombination in the alpha/gamma to beta interval. Plasma fibrinogen levels, by either assay method, when corrected or uncorrected for age, sex, and smoking habit, did not show any statistically significant associations with the four fibrinogen polymorphisms examined at the alpha, beta, and gamma fibrinogen loci either singly or when analysed as a haplotype.

Blotting, Southern↗

PubMed2005

Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica.

Intervertebral disc disease (IDD) characterized by sciatica is a common disorder affecting about 5% of individuals. Environmental factors can predispose to this disease, but IDD has a strong genetic background. Recent evidence suggests that inflammation is one of the key factors in the etiology of IDD. Here, a possible role of the inflammatory mediator genes was studied in 155 patients with IDD-related sciatica and 179 controls. Forty-eight patients were analyzed for mutations in the IL1A, IL1B, IL6 and TNFA genes, and 16 polymorphisms in 10 candidate cytokine genes (IL1A, IL1B, IL1RN, TNFA, IL2, IL4, IL4R, IL6, IL10, IFNG) were genotyped from all subjects. No disease-causing mutations were identified in IL1A, IL1B, IL6 or TNFA. Allele frequencies were, however, significantly different between the two groups for IL6 SNP, T15A in exon 5 (P=0.007). Furthermore, the genotypes AA and AT of the exon 5 SNP were more common in the patients (P=0.011; OR=4.4, 95% CI=1.2-15.7; AR=7.5%, 1.6-13.1%). Haplotypes were then generated for four IL6 SNPs, G-597A, G-572C, G-174C, and T15A in exon 5. Haplotype GGGA was more common in the patients (P=0.011; OR=4.8, 95% CI=1.6-14.5). To evaluate attributable risk, haplotype pairs were assigned for the individuals. The presence of GGGA/GGGA or GGGA/other genotypes had an OR of 5.4 (95% CI=1.5-19.2). Association of GGGA with disease was highly significant (P=0.0033), and the associated AR was 6.8% (1.9-11.5%). These findings support the role of IL-6 genetic variations in discogenic pain.

Adult↗

PubMedDate not supplied

Genetic variation within the Tupi linguistic group: new data on three Amazonian tribes.

A total of 505 individuals belonging to four populations of three Brazilian Indian tribes were variously studied in relation to 34 genetic systems, and the results were compared with South American Indian averages and five other Tupi populations. Rare variants (CdE of the Rh system, PGM211-1, Cp A-CAY1, serum cholinesterase2 C5+ and some Gm combinations) were observed with varying prevalences, and the three tribes showed different degrees of departure (28%-40% of differences of 10% or more in gene frequencies) from South American Indian averages. People from two communities who speak the same language and are labelled as belonging to the same tribe (Asurini) showed a large degree of genetic differentiation. Another of the tribes studied (Urubu-Kaapor) link through genetic distance analyses with two other tribes from the north of the continent, forming a distinct microevolutionary unit. These features emphasize the peculiarities of the genetic variation in populations with a hunter-gatherer, rudimentary agriculture type of economy.

Alleles↗

PubMed2004

Neither single-marker nor haplotype analyses support an association between genetic variation near NOTCH4 and bipolar disorder.

Markers near the NOTCH4 locus on chromosome 6p21.3 have been reported to be associated with schizophrenia in some studies. Since schizophrenia and bipolar affective disorder (BPAD) may share genetic determinants, we tested markers in and near NOTCH4 in a sample of 153 parent-offspring triads ascertained through a sibling pair with BPAD for evidence of association. This sample would have 80% power to detect an association at or above a genotype relative risk of 2.4 at the 10(-7) level of significance. In addition to the two markers previously showing the most significant association with schizophrenia, three additional nearby markers were studied. The five markers were genotyped using validated methods. Both single-marker and 3-marker haplotype data was analyzed using family-based association methods. No genome-wide significant association was detected between any of the five SNP-markers and BPAD in this sample. One marker showed nominal evidence of association (P = 0.049), but this evidence was not supported by haplotype analyses including nearby flanking markers or by case-control analysis using 93 Caucasian controls. These results do not support an association between genetic variation near NOTCH4 and BPAD in this sample.

Alleles↗

PubMed2006

Genetic variation in the renin-angiotensin system and autonomic nervous system function in young healthy Japanese subjects.

CONTEXT: The renin-angiotensin system (RAS) interacts with the autonomic nervous system (ANS) in the regulation of blood pressure and cardiovascular function. Several genetic polymorphisms in the RAS have been identified and have been implicated as a cause of hypertension and cardiovascular disease. OBJECTIVE: The aim of the present study was to evaluate the relation between genetic polymorphisms of the RAS (M235T of AGT gene, insertion/deletion of ACE gene, A1166C of AT1R gene, and A1675G of AT2R gene) and ANS function. SUBJECTS: One hundred forty-nine young healthy Japanese males were genotyped for each RAS polymorphism. MAIN OUTCOME MEASURES: ANS function was evaluated by power spectral analysis of heart rate variability (HRV) during supine rest and in a standing position. RESULTS: In a supine position, subjects homozygous for the AGT 235T allele had a higher HRV sympathetic index than 235M allele carriers, whereas the orthostatic change in this index was relatively blunted in AGT 235TT carriers. In the analysis of gene-gene interaction, these effects of the AGT 235T homozygotes on HRV sympathetic index were more apparent in the presence of the ACE D allele. Meanwhile, the AT1R 1166C allele was significantly associated with higher HRV low-frequency power and sympathetic index in a standing position. These data suggest that the AGT M235T polymorphism is associated with sympathetic predominance at rest, and AT1R 1166C allele carriers have potentially increased sympathetic response. CONCLUSIONS: Cardiac autonomic function can be modulated by genetic variation in the RAS even in young and healthy states.

Adolescent↗

PubMed1980

Quantitative genetic variation of enzyme activities in natural populations of Drosophila melanogaster.

The genetic component of variation of enzyme activity in natural populations of Drosophila melanogaster was investigated by using two sets of chromosome substitution lines. The constitution of a line of each type is: i(1)/i(1);+(2)/ +(2);i(3)/i(3) and i(1)/i(1);i(2)/ i(2);+(3)/+(3), where i refers to a chromosome from a highly inbred line and + refers to a chromosome from a natural population. The + but not the i chromosomes vary within a set of lines. By use of a randomized block design to test and estimate components of variance, 50 of the second- and 50 of the third- chromosome substitution lines have been screened for variation in the activity levels of seven enzymes. Six of the seven enzymes show a significant genetic component in at least one set of lines, and five of the seven enzymes show activity variations attributable to factors that are not linked to the structural gene. These unlinked activity modifiers identify possible regulatory elements. Analyses of covariance show that most of the genetic variation of enzyme activities cannot be accounted for by genetic variation of live weight or protein content. These results and the lack of strong correlations between the genetic effects on the activities of different enzymes indicate that the effects are mainly specific for individual enzymes.

Journal Article↗

PubMed1994

Genetic variation estimated in three Shorea species by the RAPD analysis.

Three species of Shorea (S. leprosula, S. acuminata and S. cursitii) were collected from a natural forest reserve of Malaysia and analyzed for genetic variation using the technique of random amplification of polymorphic DNA (RAPD) by the polymerase chain reaction (PCR). The average number of nucleotide substitutions was estimated. The nucleotide diversities within species were very similar and larger than those found in Drosophila melanogaster. The nucleotide divergences between these species are about 1.5 times the nucleotide diversities within the species, indicating that these species diverged from a common ancestor relatively recently.

Base Sequence↗

PubMed1975

Genetic variation as a test of natural selection.

Allozymic variation encoded by 26 loci was analyzed electrophoretically in 507 specimens representing 12 populations of green toads, Bufo viridis, in Israel and the Vis Adriatic Island. Genetic variation in Bufo viridis is higher than in any vertebrate yet studied. Mean heterozygosity per locus per individual (H) is 0.133 (range, 0.105 to 0.159). H is higher in central populations as compared with isolates, and varies among four major protein classes, being highest in transferases and hydrolases and lowest in oxidoreductases and nonenzymatic proteins. Differential gene frequencies among polymorphisms was tested as an indicator of natural selection. Significant heterogeneity between loci in their apparent inbreeding coefficients Fe=S-2p/P(1-p) was found for all alleles and for each of the four major classes of proteins tested, which may be taken as evidence of selection. Both uniform and diversifying selection are suggested by the low and high Fe values, respectively. The general pattern of high heterozygosity in Bufo viridis is best explained as an adaptive strategy in heterogeneous environments.

Alleles↗

PubMed2006

Genetic variation in pea seed globulin composition.

A quantitative characterization of seeds from 59 pea (Pisum sativum L.) lines and relative taxa with various external characteristics and wide geographical origin was performed to explore the genetic variation of pea concerning its starch and protein contents and globulin composition. Pea lines, which produce round, wrinkled, flat, and round-dimpled seeds, have starch as the major reserve, with an average content of 46%. Protein content varied from 13.7 to 30.7% of the seed dry matter, with an overall average of 22.3%. Densitometric quantification of the individual globulins (legumin, vicilin, convicilin, and globulin-related proteins) based on SDS-PAGE gels showed no lines lacking any particular globulin. Among the lines tested, variation was shown in both their total globulins content and their globulin composition. The total globulin content ranged from 49.2 to 81.8% of the total pea protein extract (TPPE). Legumin content varied between 5.9 and 24.5% of the TPPE. Vicilin was the most abundant protein of pea, and its content varied between 26.3 and 52.0% of the TPPE. Both processed and nonprocessed vicilins occurred. The processed vicilin was the predominant one, with values between 17.8 and 40.8%, whereas the nonprocessed ones constituted between 3.1 and 13.5% of the TPPE. Convicilin was the least abundant globulin, and its content ranged from 3.9 to 8.3%. Finally, the globulin-related proteins were present in amounts ranging from 2.8 to 17.3%. They were less abundant in comparison with legumin and vicilin, but they showed the largest relative variation of the four globulin classes. Correlations between the different external characteristics and globulin composition were determined. Comparison with soybean showed that pea lines show more variety in the abundance of globulin proteins, enabling a wider range of food application.

Electrophoresis, Polyacrylamide Gel↗

PubMed2006

Genetic variation in IL-8 associated with increased risk and poor prognosis of breast carcinoma.

Interleukin-8 (IL-8), a potent chemoattractant, has been demonstrated to contribute to human cancer progression through its potential functions as a mitogenic, angiogenic, and motogenic factor. We designed a broad study to investigate whether genetic variation in IL-8 has implications for susceptibility to and prognosis in breast carcinoma. We used the allele-specific polymerase chain reaction to characterize the variation of the IL-8 promoter region for 308 unrelated Tunisian patients with breast carcinoma and 236 healthy control subjects. Associations of the clinicopathologic parameters and the genetic marker with the rates of the breast carcinoma-specific overall survival and the disease-free survival were assessed using univariate and multivariate analyses. A significantly increased risk of breast carcinoma was associated with heterozygous IL-8 (-251) TA (OR=1.58, p=0.02) and homozygous IL-8 (-251) AA (OR=1.76, p=0.01) variants. A significant association between the IL-8 (-251) AA homozygous genotype and the aggressive phenotype of breast carcinoma as defined by the high histological grade, auxiliary's lymph node metastasis, and large tumor size was found. The IL-8 (-251) A allele manifested a significant association with decreased overall survival and disease-free survival for breast carcinoma patients. The polymorphism in the promoter region of the IL-8 gene may not only represent a marker for the increased risk of breast carcinoma but also predict the clinical outcome.

Adult↗

PubMed2005

Genetic variation in the mitochondrial cytochrome c oxidase subunit 1 within three species of Progamotaenia (Cestoda: Anoplocephalidae) from macropodid marsupials.

Sequence variation within 3 morphologically defined species of the anoplocephalid cestode genus Progamotaenia (P. ewersi, P. macropodis and P. zschokkei) was investigated using the cytochrome c oxidase subunit 1 gene. The magnitude of genetic variation detected within each morphospecies suggests that, in each instance, several cryptic species are present. Within P. ewersi, 5 genetically distict groups of cestodes were detected, 1 shared by Macropus robustus and M. parryi in Queensland, 1 in M. agilis from Queensland, 1 in Petrogale assimilis from Queensland, 1 in Macropus fuliginosus from South Australia and 1 in Wallabia bicolor from Victoria. In P. macropodis, cestodes from M. robustus from Queensland, Western Australia and the Northern Territory, M. parryi from Queensland and M. eugenii from South Australia were genetically distinct from those in Wallabia bicolor from Queensland and Victoria and from M. fuliginosus from South Australia. P. zschokkei consisted of a number of genetically distinct groups of cestodes, 1 in Lagorchestes conspicillatus and L. hirsutus from Queensland and the Northern Territory respectively, 1 in Petrogale herberti, P. assimilis and M. dorsalis from Queensland, 1 in Onychogalea fraenata from Queensland, 1 in M. agilis from Queensland and 1 in Thylogale stigmatica and T. thetis from Queensland. In general, genetic groups within each morphospecies were host specific and occurred predominantly in a particular macropodid host clade. Comparison of genetic relationships of cestodes with the phylogeny of their hosts revealed examples of colonization (P. zschokkei in M. agilis) and of host switching (P. zschokkei in M. dorsalis).

Amino Acid Sequence↗