PubMed Health⌕ Search

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 1,225 records · Page 68Linked to original sources
PubMed2024

Association of disease severity and genetic variation during primary Respiratory Syncytial Virus infections.

BACKGROUND: Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death. Studies have shown a statistical association between RSV subtype or phylogenic lineage and RSV disease severity, although these results have been inconsistent. Associations between variation within RSV gene coding regions or residues and RSV disease severity has been largely unexplored. METHODS: Nasal swabs from children (<&#x2009;8&#xa0;months-old) infected with RSV in Rochester, NY between 1977-1998 clinically presenting with either mild or severe disease during their first cold-season were used. Whole-genome RSV sequences were obtained using overlapping PCR and next-generation sequencing. Both whole-genome phylogenetic and non-phylogenetic statistical approaches were performed to associate RSV genotype with disease severity. RESULTS: The RSVB subtype was statistically associated with disease severity. A significant association between phylogenetic clustering of mild/severe traits and disease severity was also found. GA1 clade sequences were associated with severe disease while GB1 was significantly associated with mild disease. Both G and M2-2 gene variation was significantly associated with disease severity. We identified 16 residues in the G gene and 3 in the M2-2 RSV gene associated with disease severity. CONCLUSION: These results suggest that phylogenetic lineage and the genetic variability in G or M2-2 genes of RSV may contribute to disease severity in young children undergoing their first infection.

Humans↗
PubMed1987

Genetic variation in the human hepatic cytochrome P-450 system.

Studies in rodents indicate that the cytochrome P-450 system consists of a superfamily of heme proteins, produced by clusters of structural genes on different chromosomes. Equivalent P-450s of different species show more homologies than members of different P-450 families within a species. The Ah receptor serves the induction of members of one of the cytochrome families. The human structural gene for the methylcholanthrene-inducible P1-450 is located on Chromosome 15. This gene has been completely sequenced. The human Ah receptor is also measurable. New methods to measure inducibility in man involve new lymphocyte bioassays and mRNA determinations, while in vivo biotransformation studies of caffeine allow estimates of the state of induction. Structural genes for phenobarbital-inducible cytochromes have been localized to Chromosome 19. The deficiency of biotransformation of debrisoquine and sparteine continues to be explored intensely. Linkage studies indicate the gene for the variable cytochrome P-450 to be located on Chromosome 22. The deficiency is more likely due to structural variation than absence of the cytochrome. Inhibiting drugs can mimic the genetic defect. Many pharmacological and toxicological consequences of the deficiency have been defined. The main characteristics of the genetic deficiencies affecting the metabolisms of mephenytoin, phenytoin, tolbutamide, nifedipine and of methyl cysteine were outlined briefly.

Animals↗
PubMed1996

Genetic variation and covariation for ewe reproduction, lamb growth, and lamb scrotal circumference in a fall-lambing sheep flock.

Genetic parameters for female reproduction, lamb growth, and lamb scrotal circumference in a composite population of 50% Dorset, 25% Rambouillet and 25% Finnsheep breeding selected for ability to lamb in fall were estimated by REML using various animal models. Traits considered were spring fertility, litter size, weight at weaning (WWT), 90 d (WT90), and 120 d (WT120), and scrotal circumference at weaning (WSC), 90 d (SC90), and 120 d (SC120). Fertility was defined as 1 or 0 for ewes that lambed or failed to lamb, respectively, in fall and averaged .59 for adults (3 yr and older), .45 for second-lambing ewes, .18 for 19-mo-old ewes, and .11 for 12-mo-old ewes. Heritability estimates for fertility varied among models from .07 to .11. Heritability of fall litter size was .10. For body weights, estimates of additive direct, additive maternal, permanent environmental maternal, and litter effects as proportions of phenotypic variance were .04, .10, .05, and .11, respectively, for WWT, .09, .05, .14, and .01 for WT90, and .18, .0, .13, and .06 for WT120. Heritability estimates for WSC, SC90, and SC120 were .15, .25, and .02, respectively. Estimates of genetic correlations among body weights ranged from .77 to unity. Estimates of genetic correlations of fertility with fall litter size, WT90, and SC90 were .56, -.31, and .29, respectively. Genetic correlations of fall litter size with WT90 and SC90 were .33 and .36, respectively. Estimated genetic correlations revealed no major genetic antagonisms with ability to lamb in fall.

Animals↗
PubMed1999

An empirical test of the significance of an observed quantitative trait locus effect that preserves additive genetic variation.

We propose a constrained permutation test that assesses the significance of an observed quantitative trait locus effect against a background of genetic and environmental variation. Permutations of phenotypes are not selected at random, but rather are chosen in a manner that attempts to maintain the additive genetic variability in phenotypes. Such a constraint maintains the nonindependence among observations under the null hypothesis of no linkage. The empirical distribution of the lod scores calculated using permuted phenotypes is compared to that obtained using phenotypes simulated from the assumed underlying multivariate normal model. We make comparisons of univariate analyses for both a quantitative phenotype that appears consistent with a multivariate normal model and a quantitative phenotype containing pronounced outliers. An example of a bivariate analysis is also presented.

Alcoholism↗
PubMed2005

Genetic variation and lipid metabolism: modulation by dietary factors.

Cardiovascular diseases (CVD) result from complex interactions between genetic and environmental factors. The evidence supports that gene-environment interactions modulate plasma lipid concentrations and potentially CVD risk. The findings from studies examining gene-diet interactions and lipid metabolism have been promising. Several loci (eg, APOA1, APOE, LIPC) are providing proof of concept for the application of genetics in the context of personalized nutrition for CVD prevention. The spectrum of candidate genes has been expanding to incorporate those involved in intracellular lipid metabolism (eg, iPPARs, CYP7A1). However, the practical application of these findings is not ready for prime time. There is a compelling need for replication using a higher level of scientific evidence. Moreover, we need to evolve from the simple scenarios examined nowadays (ie, one single dietary component, SNP, and risk factor) to more realistic situations involving multiple interactions. In summary, there is need for both large population studies and well-standardized intervention studies.

Cardiovascular Diseases↗
PubMed2002

Genetic variation in memory functioning.

On the basis of a review of the literature the contribution of genetic factors for individual differences in memory performance is discussed. Explorations of such influences on memory have just begun. Most of those studies that have been conducted in order to find a quantitative trait locus for memory have focused on ApolipoproteinE (ApoE). One form of this gene is strongly associated with cardiovascular disease in middle age and to late-onset Alzheimer's disease. Some studies have demonstrated an association between ApoE and memory even in non-demented individuals. Other studies have failed to demonstrate this association. Based on data from a prospective cohort study (Betula) in our own laboratory, we have assessed and examined associations between three different forms of ApoE and performance on episodic memory tests. Cross-sectional comparisons revealed non-significant differences in episodic memory performance between carriers of the three alleles. Analyses of change scores in longitudinal data revealed that allele epsilon 4 was related to a lower level of memory performance than alleles epsilon 2 and epsilon 3. This effect was most pronounced in tasks providing cognitive support at both encoding and retrieval, suggesting a deficit in utilizing such support in carriers of the epsilon 4 allele.

Aging↗
PubMed1999

Toward reconciling inferences concerning genetic variation in senescence in Drosophila melanogaster.

Standard models for senescence predict an increase in the additive genetic variance for log mortality rate late in the life cycle. Variance component analysis of age-specific mortality rates of related cohorts is problematic. The actual mortality rates are not observable and can be estimated only crudely at early ages when few individuals are dying and at late ages when most are dead. Therefore, standard quantitative genetic analysis techniques cannot be applied with confidence. We present a novel and rigorous analysis that treats the mortality rates as missing data following two different parametric senescence models. Two recent studies of Drosophila melanogaster, the original analyses of which reached different conclusions, are reanalyzed here. The two-parameter Gompertz model assumes that mortality rates increase exponentially with age. A related but more complex three-parameter logistic model allows for subsequent leveling off in mortality rates at late ages. We find that while additive variance for mortality rates increases for late ages under the Gompertz model, it declines under the logistic model. The results from the two studies are similar, with differences attributable to differences between the experiments.

Aging↗
PubMed2005

Genetic variation and willingness to participate in epidemiologic research: data from three studies.

The differences in common genetic polymorphism frequencies by willingness to participate in epidemiologic studies are unexplored, but the same threats to internal validity operate as for studies with nongenetic information. We analyzed single nucleotide polymorphism genotypes, haplotypes, and short tandem repeats among control groups from three studies with different recruitment designs that included early, late, and never questionnaire responders, one or more participation incentives, and blood or buccal DNA collection. Among 2,955 individuals, we compared 108 genotypes, 8 haplotypes, and 9 to 15 short tandem repeats by respondent type. Among our main comparisons, single nucleotide polymorphism genotype frequencies differed significantly (P < 0.05) between respondent groups in six instances, with 13 expected by chance alone. When comparing the odds of carrying a variant among the various response groups, 19 odds ratios were </=0.70 or >/=1.40, levels that might be notably different. Among the various respondent group comparisons, haplotype and short tandem repeat frequencies were not significantly different by willingness to participate. We observed little evidence to suggest that genotype differences underlie response characteristics in molecular epidemiologic studies, but a greater variety of genes should be examined, including those related to behavioral traits potentially associated with willingness to participate. To the extent possible, investigators should evaluate their own genetic data for bias in response categories.

Community Participation↗
PubMed1991

A twin study of genetic variation in proportional radiographic alveolar bone height.

The purpose of this study was to estimate the genetic variance for alveolar bone height by means of the classic twin method and the study of monozygous twins reared apart. Panoramic radiographs were obtained from 120 pairs of adult twins (mean age = 40.4 years, S.D. = 10.4 years), for comparison of 62 pairs of monozygous twins reared together (MZT), 25 pairs of like-sexed dizygous twins reared together (DZT), and 33 pairs of monozygous twins reared apart (MZA). Mesial and distal bone heights were determined as a proportion of tooth length. A full-mouth bone score was computed for each twin by averaging these proportions from all measurable teeth. Between-pair (B) and within-pair (W) variances were computed for each twin group. The population variances (B + W) of the MZT and DZT twin groups were similar, which validated a basic assumption of the twin model. Intraclass correlations and heritability estimates were also computed for the reared-together and reared-apart twin groups. Boot-strap sampling was used to provide estimates and confidence limits for these values. The intraclass correlations for the twin groups were: MZT = 0.70, DZT = 0.52, and MZA = 0.55. The results of this study suggest that there is significant genetic variance in the population for proportional alveolar bone height.

Adolescent↗
PubMed2005

Genetic variation in West Nile virus from naturally infected mosquitoes and birds suggests quasispecies structure and strong purifying selection.

Intrahost genetic diversity was analysed in naturally infected mosquitoes and birds to determine whether West Nile virus (WNV) exists in nature as a quasispecies and to quantify selective pressures within and between hosts. WNV was sampled from ten infected birds and ten infected mosquito pools collected on Long Island, NY, USA, during the peak of the 2003 WNV transmission season. A 1938 nt fragment comprising the 3' 1159 nt of the WNV envelope (E) coding region and the 5' 779 nt of the non-structural protein 1 (NS1) coding region was amplified and cloned and 20 clones per specimen were sequenced. Results from this analysis demonstrate that WNV infections are derived from a genetically diverse population of genomes in nature. The mean nucleotide diversity was 0.016 % within individual specimens and the mean percentage of clones that differed from the consensus sequence was 19.5 %. WNV sequences in mosquitoes were significantly more genetically diverse than WNV in birds. No host-dependent bias for particular types of mutations was observed and estimates of genetic diversity did not differ significantly between E and NS1 coding sequences. Non-consensus clones obtained from two avian specimens had highly similar genetic signatures, providing preliminary evidence that WNV genetic diversity may be maintained throughout the enzootic transmission cycle, rather than arising independently during each infection. Evidence of purifying selection was obtained from both intra- and interhost WNV populations. Combined, these data support the observation that WNV populations may be structured as a quasispecies and document strong purifying natural selection in WNV populations.

Animals↗