Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “allele frequency changes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 91 records · Page 5Linked to original sources
PubMed1984

Genetic structure of natural populations of the red-spotted newt, Notophthalmus viridescens.

Genetic variation is described at 15 loci in 2 neotenic and 12 nonneotenic populations of red-spotted newts. Though high levels of genetic similarity (I = 0.990) were found among all populations, allele frequencies at six of the eight most polymorphic loci show significant heterogeneity across populations. Change in allele frequencies at two of these loci (Pep-2 and Ldh-1) is significantly correlated with latitude. Interspecific homologies are established for newt peptidases based on substrate specificities and lactate dehydrogenases based on tissue distribution, thermal stability, and kinetic properties. Nonneotenic populations are highly variable (H = 0.157) and neotenic populations are only slightly, but significantly, less variable (H = 0.120). The high levels of heterozygosity detected in nonneotenic populations may result from large effective population size and/or environmental heterogeneity. The unexpectedly high heterozygosity values obtained for the neotenic populations may indicate adult dispersal or the presence of some previously undetected red efts at these localities. In any case, a major change in life history has apparently had little effect on the genetic structure of these populations.

Alleles↗
PubMed1994

Genetic variability of the beta-tubulin genes in benzimidazole-susceptible and -resistant strains of Haemonchus contortus.

Benzimidazole anthelmintics are the most common chemotherapeutic agents used to remove intestinal helminths from farm animals. The development of drug resistance within helminth populations is wide-spread and can render these drugs essentially useless. The mechanism of benzimidazole resistance appears to be common to many species ranging from fungi to nematodes and involves alterations in the genes encoding beta-tubulin. During the selection process resulting in resistance, there must be quantitative changes in the population gene pool. Knowledge of these changes would indicate the mechanisms underlying the spread of resistance in the population, which in turn could be used to design more effective drug administration strategies. To this end we have identified allelic variation at two beta-tubulin genes in Haemonchus contortus using restriction map analysis of individual adults. Extremely high levels of variation were identified at both loci within a susceptible strain. In two independently derived benzimidazole resistant strains, allele frequencies at both loci were significantly different from the susceptible strain but not from each other. The same alleles at both loci, in both resistant strains, were favored by selection with benzimidazoles, suggesting that both loci are involved in determining benzimidazole resistance. These data confirm that changes in allele frequency, rather than novel genetic rearrangements induced by exposure to the drug, explain the changes associated with benzimidazole resistance. These results also show that any DNA based test for the development of benzimidazole resistance must take into account the frequency of alleles present in the population and not simply test for the presence or absence of specific allelic types.

Alleles↗
PubMed2004

Methodological problems in genetic association studies of longevity--the apolipoprotein E gene as an example.

BACKGROUND: Cross-sectional genetic association studies are now widely employed to look for genes which confer longevity. Such studies are based on two assumptions; (a) initial relative allele frequencies in the different age cohorts are similar, and (b) the risk of mortality conferred by genotypes does not depend on year of birth. METHODS: We explored the validity of these assumptions and reviewed 15 cross-sectional studies of common apolipoprotein E (APOE) polymorphisms and longevity. RESULTS: Higher relative epsilon2 frequencies, and lower relative epsilon4 allele frequencies were observed in elderly versus younger populations. If assumptions (a) and (b) were correct the estimates for epsilon2 and epsilon4 alleles respectively versus epsilon3 alleles would be 1.34 (95% CI: 1.19, 1.35) and 0.54 (95% CI: 0.46, 0.63) in elderly versus younger individuals. However, there was an association between relative epsilon4 allele frequency in controls and APOE epsilon4 effect (beta = -0.45, 95% CI: -0.89, 0.00). In relation to assumption (a) there is substantial variation in relative APOE allele frequencies (4-21%), with considerable heterogeneity evident within geographically proximate populations, population admixture is likely to have resulted in changes in allele frequency over time, and assumption (b) APOE related causes of death are context specific and have changed considerably over the last 30 years. CONCLUSION: The validity of case-control type studies of the genetic basis of longevity based on the above assumptions is questionable, especially when considerable differences exist in allele frequency by population and when the genes in question interact with environmental factors, which vary by time and place.

Aging↗
PubMed1998

Haemonchus contortus: selection at a glutamate-gated chloride channel gene in ivermectin- and moxidectin-selected strains.

Anthelmintic resistance in nematode parasites of livestock is a serious problem worldwide. Ivermectin, an avermectin, and moxidectin, a milbemycin, are potent endectocides commonly used to control these parasites. The proposed mode of action of avermectins and possibly the milbemycins involves the binding of the drug to the alpha-subunit of a glutamate-gated chloride channel, which opens or potentiates gating of the channel and leads to the hyperpolarization of the target neuromuscular cell. Glutamate gates the channel by binding to the beta-subunit. We have cloned a fragment of a putative alpha-subunit gene from Haemonchus contortus. The sequence of the beta subunit is available from GenBank. Genetic variability of this fragment was analysed by single-strand conformation polymorphism in five strains of H. contortus: two strains passaged without drug selection, two strains selected with ivermectin, and one strain selected with moxidectin. One allele of the putative alpha-subunit gene appeared to be associated with resistance to the drugs, increasing in frequency in the three drug-selected strains relative to the unselected strains. Another allele appeared to be associated with susceptibility, decreasing in frequency in the three drug-selected strains relative to the unselected strains. A similar analysis of the beta-subunit gene showed no significant differences in allele frequencies between the unselected and drug-selected strains. Our findings suggest a correlation between changes in allele frequencies of the putative alpha-subunit gene and resistance to ivermectin and moxidectin.

Amino Acid Sequence↗
PubMedDate not supplied

Selection effects on a linked neutral locus.

Selection changes the frequency of alleles at a linked locus as well as at those under selection if the population is not in linkage equilibrium. The magnitude of this frequency change depends on the tightness of the linkage, the selection intensity, and the deviation from linkage equilibrium. Allowing a population to mate randomly without selection brings the population closer to linkage equilibrium. This decreases the effect of selection on allelic frequencies at a linked neutral locus. However, if linkage is very tight it can take many generations to make a large difference in the effect of the linked locus. The loss due to undesirable changes in allelic frequencies at linked loci when the population is not in linkage equilibrium must be weighed against the time and effort saved by beginning intense selection for the primary trait in an early generation. Effects of selection intensity, linkage intensity, and delayed selection on changes in allelic frequency at a neutral linked locus are demonstrated.

Alleles↗
PubMed2000

The genetic contribution of single male immigrants to small, inbred populations: a laboratory study using Drosophila melanogaster.

This study examined the genetic contribution of single male immigrants to small, inbred laboratory populations of Drosophila melanogaster. Genetic contribution was assessed by measuring the relative frequency of immigrant marker alleles in the first and second generations after immigration, while controlling for any selection effects at the marker locus, and for the experience of male immigrants. When immigrants were outbred, the mean frequency of the immigrant allele was significantly higher than its initial frequency, in both the first and second generations after immigration. There was no significant change in allele frequency for populations receiving inbred immigrants. The increase in allele frequency for outbred immigrants was attributed to an initial outbred vigour fitness advantage of immigrant males over resident males experiencing inbreeding depression. Hybrid vigour of immigrant progeny and the rare-male effect did not have a statistically significant role in the fitness advantage of the immigrant allele. The results suggest that inbreeding may have a considerable impact on the contribution of immigrants to the genetic diversity of populations.

Alleles↗
PubMed2003

Molecular studies on genetic integrity of open-pollinating species rye (Secale cereale L.) after long-term genebank maintenance.

The genetic integrity of six accessions represented by 14 sub-populations of the open-pollinating species rye ( Secale cereale L.) was investigated. Seeds available from a herbarium collection (first regeneration) and from the cold store (most recent regeneration) were multiplied two to fourteen times and fingerprinted using microsatellite markers. Four accessions had significantly different allele frequencies. These were multiplied seven to thirteen times. Nearly 50% of the alleles discovered in the original samples were not found in the material present in the cold store. However alleles were detected in the most recently propagated sub-populations, that were not observed in the investigated plants of the original one. The change in allele frequencies is a continuous process. Reasons for the occurrence of genetic changes and consequences for managing open pollinating species maintained in ex situ genebanks are discussed.

Gene Frequency↗
PubMed2005

Ethnic variation in CYP2A6*7, CYP2A6*8 and CYP2A6*10 as assessed with a novel haplotyping method.

Cytochrome P450 2A6 is the main human nicotine metabolizing enzyme coded for by a highly polymorphic gene, CYP2A6. CYP2A6*7, CYP2A6*8 and CYP2A6*10 are variant alleles common to Asian ethnicities. The CYP2A6*7 and CYP2A6*8 alleles each contain a non-synonymous single nucleotide polymorphism (SNP) 6558T>C and 6600G>T, respectively, whereas the CYP2A6*10 haplotype allele contains both. We have developed the first haplotyping assay; it can unambiguously distinguish the CYP2A6*7, CYP2A6*8 and CYP2A6*10 alleles. The allele frequencies of these three variants were assessed using the novel haplotyping assay in Chinese-Canadian (n=112), Chinese-American (n=221), Taiwanese (n=319), Korean-American (n=207) and Japanese-Canadian (n=64) populations, as well as in Caucasian (n=110) and African-Canadian (n=113) populations. Our new method demonstrated higher frequencies of CYP2A6*7 and CYP2A6*10, and a lower frequency of CYP2A6*8 in Asian populations, but no significant change of allele frequencies in Caucasian or African-Canadian populations.

Africa↗
PubMed1975

Clines in the colour polymorphism of Philaenus spumarius in Eastern Central Europe.

Populations of Philaemus spumarius (Homoptera) have been investigated in the Baltic States of the USSR, in Czechoslovakia and in Hungary. Colour morph frequencies in these highly polymorphic populations are compared with those reported earlier from northern Italy. Gradual changes in allele frequencies (clines) transect the study area, which lies in the most central part of the range of Philaenus in Europe. From north to south the allele pM increases, but pO decreases, in frequency. In their distribution, some of the other alleles also showed regional gradients. The possibility that visual selection varies regionally is dismissed on indirect grounds. Gradients in climatic severity, or in other environmental variables changing concomitantly with climate, are regarded as the primary cause of the observed clines and other differences between regions.

Alleles↗
PubMed1998

Striped bass population subdivision within the santee-cooper system, south carolina

Population subdivision was indicated in striped bass (Morone saxatilis) from the Santee-Cooper system, South Carolina. Samples from the two major spawning grounds, the Congaree River (n = 273) and Wateree River (n = 111), and from the Santee River, the source of hatchery broodstock (n = 128), were collected during the 1992, 1993, and 1994 spawning seasons. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assays of three independently segregating loci were used to screen population samples from the system. An allele frequency difference among samples from the three rivers was detected at the SB83 locus. In addition, the SB14 locus showed a significant temporal change in allele frequencies in the Santee River sample. Furthermore, a heterozygote deficiency was observed in the Santee and Congaree River samples, suggesting either inbreeding due to hatchery augmentation or admixture of two distinct populations. These data suggest that there is population substructure in the Santee-Cooper system and that future hatchery augmentation efforts should recognize this population subdivision.

Journal Article↗
PubMed2006

Predicted declines in sickle allele frequency in Jamaica using empirical data.

The high frequency of the sickle allele in some parts of Africa is understood to be a consequence of high malarial endemicity. One corollary of this is that the sickle allele frequency should be declining in populations of African ancestry that are no longer exposed to malaria. We have previously shown that there has been no change in sickle allele frequency in malaria-free Jamaica between two large-scale neonatal screening exercises conducted in 1973-1981 and 1995-2003. To evaluate the determinants of, and derive expected values for, sickle allele frequency in Jamaica, local empirical data were used to estimate the parameters of deterministic models of allele frequency decline. We found that although model predictions were broadly consistent with observed values in the 1973-1981 cohort, the predicted change in allele frequency between the two cohorts was larger than the observed, nonsignificant, reduction. Close agreement between predicted and observed values was only achieved by simulating a recent, marked increase in HbSS fitness. Thus, the "unexpected" persistence of the sickle allele in Jamaica may reflect the fact that the actual fitness among SS individuals is higher than that previously realized. If true, our models suggest that without substantial changes in current screening and counseling practice, there will be little "natural" reduction in sickle allele frequency for several hundred years. Better estimates of relative fitness will be helpful in refining these predictions and may aid in assigning health care priorities in Jamaica and the African Diaspora.

Alleles↗
PubMed2006

Simultaneous estimation of mixing rates and genetic drift under successive sampling of genetic markers with application to the mud crab (Scylla paramamosain) in Japan.

In stock enhancement programs, it is important to assess mixing rates of released individuals in stocks. For this purpose, genetic stock identification has been applied. The allele frequencies in a composite population are expressed as a mixture of the allele frequencies in the natural and released populations. The estimation of mixing rates is possible, under successive sampling from the composite population, on the basis of temporal changes in allele frequencies. The allele frequencies in the natural population may be estimated from those of the composite population in the preceding year. However, it should be noted that these frequencies can vary between generations due to genetic drift. In this article, we develop a new method for simultaneous estimation of mixing rates and genetic drift in a stock enhancement program. Numerical simulation shows that our procedure estimates the mixing rate with little bias. Although the genetic drift is underestimated when the amount of information is small, reduction of the bias is possible by analyzing multiple unlinked loci. The method was applied to real data on mud crab stocking, and the result showed a yearly variation in the mixing rate.

Animals↗
PubMed1993

Geographical clinal variation at seven esterase-coding loci in Indian populations of Zaprionus indianus.

Twelve Indian natural populations of Zaprionus indianus, collected along 22 degrees latitudinal range, were analysed electrophoretically for allozymic variation of esterase gene-enzyme system. Interestingly, all the seven Est loci were found to be highly polymorphic in all the populations of Z. indianus. The genetic structure of Z. indianus populations was characterized by extensive inter-populational genotypic as well as allelic frequency heterogeneity and higher genic differentiation at all the esterase-coding loci. All the polymorphic loci in geographical populations of Z. indianus revealed latitudinal clines, and changes in allelic frequencies were found to correlate with latitude. The occurrence of higher genetic variability in Z. indianus populations was in agreement with its habitat-generalist or broad niche-width characteristics, i.e., the species populations utilized diverse food resources and displayed adaptation to variable climatic conditions. Thus, the observed genic divergence patterns in colonizing populations of Z. indianus could be maintained by balancing natural selection varying spatially along the north-south axis of the Indian sub-continent.

Animals↗
PubMed1991

Selection and mutation at a diallelic X-linked locus.

Equilibria and convergence of gene frequencies are studied in the case of a diallelic X-linked locus under the influence of selection and mutation. The model used is that of an infinite diploid population with nonoverlapping discrete generations and random mating. It is proved that if the mutation rates and fitnesses are constant and the mutation rates are less than one-third, then global convergence of gene frequencies to equilibria occurs. The phase portraits of the dynamical system describing the change of allelic frequencies from one generation to the next are determined. Convergence of gene frequencies is monotone from a certain generation on if every other generation is skipped. In the case without mutation, our proof of this monotone convergence simplifies G. Palm's original proof.

Alleles↗
PubMed2006

Changes in disease gene frequency over time with differential genotypic fitness and various control strategies.

A spreadsheet model was constructed to describe the change in allelic frequency over time for a lethal recessive mutation in an animal population. The model allowed relative fitness to differ between genotypes, between sexes, and over time. Whereas a lethal recessive allele is naturally eliminated very slowly from a population, a small selective disadvantage of the heterozygote results in a large increase in the rate of elimination. With selective advantage of the heterozygote through linkage with a production trait or pleiotropy, the allele is never naturally eliminated but tends toward a stable equilibrium frequency. The model was used to investigate various alternative control programs based on the detection of heterozygotes by genotyping and their exclusion from breeding. The programs (genotyping males only, genotyping males and 50% of females, and genotyping all breeding animals) were modeled for various initial heterozygote frequencies, and the results were described in terms of the number of generations, number of tests, and number of culls required to reduce the heterozygote frequency to a predefined level. The model can be used to compare the feasibility and cost of various control strategies and to illustrate clearly to breeders the expected outcomes, as well as the danger of prematurely terminating a control program when there is a selective advantage of the heterozygote.

Animal Husbandry↗
PubMed2004

Effects of genetic drift on variance components under a general model of epistasis.

We analyze the changes in the mean and variance components of a quantitative trait caused by changes in allele frequencies, concentrating on the effects of genetic drift. We use a general representation of epistasis and dominance that allows an arbitrary relation between genotype and phenotype for any number of diallelic loci. We assume initial and final Hardy-Weinberg and linkage equilibrium in our analyses of drift-induced changes. Random drift generates transient linkage disequilibria that cause correlations between allele frequency fluctuations at different loci. However, we show that these have negligible effects, at least for interactions among small numbers of loci. Our analyses are based on diffusion approximations that summarize the effects of drift in terms of F, the inbreeding coefficient, interpreted as the expected proportional decrease in heterozygosity at each locus. For haploids, the variance of the trait mean after a population bottleneck is var(delta(z)) = sigma(n)k=1 FkV(A(k)), where n is the number of loci contributing to the trait variance, V(A(1)) = V(A) is the additive genetic variance, and V(A(k)) is the kth-order additive epistatic variance. The expected additive genetic variance after the bottleneck, denoted (V*(A)), is closely related to var(delta(z)); (V*(A)) = (1 - F) sigma(n)k=1 kFk-1V(A(k)). Thus, epistasis inflates the expected additive variance above V(A)(1 - F), the expectation under additivity. For haploids (and diploids without dominance), the expected value of every variance component is inflated by the existence of higher order interactions (e.g., third-order epistasis inflates (V*(AA. This is not true in general with diploidy, because dominance alone can reduce (V*(A)) below V(A)(1 - F) (e.g., when dominant alleles are rare). Without dominance, diploidy produces simple expressions: var(delta(z)) = sigma(n)k=1 (2F)kV(A(k)) and (V(A)) = (1 - F) sigma(n)k=1 k(2F)k-1V(A(k)). With dominance (and even without epistasis), var(delta(z)) and (V*(A)) no longer depend solely on the variance components in the base population. For small F, the expected additive variance simplifies to (V*(A)) approximately equal to (1 - F)V(A) + 4FV(AA) + 2FV(D) + 2FC(AD), where C(AD) is a sum of two terms describing covariances between additive effects and dominance and additive X dominance interactions. Whether population bottlenecks lead to expected increases in additive variance depends primarily on the ratio of nonadditive to additive genetic variance in the base population, but dominance precludes simple predictions based solely on variance components. We illustrate these results using a model in which genotypic values are drawn at random, allowing extreme and erratic epistatic interactions. Although our analyses clarify the conditions under which drift is expected to increase V(A), we question the evolutionary importance of such increases.

Analysis of Variance↗