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At least 19 recordsLinked to original sources

The effects of genotype frequency and population density on fitness differentials in Escherichia coli.

Two strains of Escherichia coli K-12, a lac+ wild type and a lac- auxotroph, were grown both as pure and mixed cultures, using a serial transfer procedure. Four different growth media were employed, consisting of the same minimal salts solution, but different total concentrations of the sugars lactose, arabinose, and glucose (in proportions 5:4:1). Population densities and genotypic frequencies were assayed every 48 hours, at the time of transfer. Population density of the pure lac+ culture was greater than that of the pure lac- culture for all media; this was expected, since the latter cannot utilize lactose. Mixed cultures quickly approached the same density as the corresponding lac+ controls, and the frequency of the lac+ genotype increased steadily for all media. Trajectories of lambda = log (P divided by Q) were strictly nonlinear, indicating a dependence of the selective differential on population density and genotypic frequency. The rate of substitution decreased slightly with increasing sugar concentration, contrary to theoretical expectation. It was speculated that either the generation interval was longer for denser cultures (higher substrate concentrations) of that buildup of organic by-products reduced the selective differential in denser cultures. For a single medium, however, the behavior of completing genotypic strains was reasonably well predicted by theoretical models of frequency and density-dependent selection, the parameters of which may be related to the experimental inputs.

Culture Media

Genetics and asexual reproduction of the sea anemone Metridium senile.

1. Metridium senile was studied for phosphohexose-isomerase variation at three locations on Cape Cod, Massachusetts: Woods Hole, Cape Cod Canal, and Barnstable Town Boat Harbor. 2. All three locations exhibited significant polymorphism for PHI. 3. Mapping of individual polyps was performed at Barnstable to analyze spatial distributions of clones and genotypes. 4. In Barnstable, PHI does not depart significantly from Hardy-Weinberg expectations at the time of establishment of new polyps, and establishment of larvae is spatially random with respect to PHI genotype. 5. Asexual reproduction was uses as a meausre of the relative success of different PHI genotypes. There are indications that not all genotypes are equally likely to produce large clones. 6. There is significant heterogeneity among the three locations with respect to PHI genotype frequencies, suggesting that there may be geographical differentiation of the populations. 7. Sessile, asexual organisms provide powerful tools for examining the dynamic aspects of genetic structure in natural populations.

Animals

Replication analysis of the PRKN V380L (rs1801582) variant in a Japanese cohort of spinocerebellar ataxia type 3.

BACKGROUND: Spinocerebellar ataxia type 3 (SCA3) is caused by CAG repeat expansion in ATXN3, which inversely correlates with age at onset but does not fully account for interindividual variability. A recent study in a mixed European/South and North&#xa0;American cohort suggested that the PRKN V380L variant (rs1801582), particularly in C/C homozygotes, was associated with earlier disease onset. We therefore performed a replication analysis to evaluate the frequency and potential clinical relevance of rs1801582 in a Japanese SCA3 cohort. METHODS: rs1801582 genotypes were determined by Sanger sequencing in 228 genetically confirmed SCA3 patients and 260 SCA6 patients as convenience disease controls. Genotype frequencies were additionally compared with East Asian reference populations from the 1000 Genomes Project Phase 3 dataset. Associations with age at onset were evaluated using multivariable linear regression adjusted for expanded ATXN3 CAG repeat length, normal ATXN3 CAG repeat length, and sex. RESULTS: Genotype frequencies in SCA3 (G/G: 86.0%, G/C: 13.2%, C/C: 0.9%) were similar to those in controls (G/G: 85.8%, G/C: 13.5%, C/C: 0.8%) and closely resembled those reported in East Asian reference populations. Because of the extremely small number of C/C carriers (n&#x2009;=&#x2009;2), subsequent analyses focused on G/G and G/C carriers. In SCA3, median age at onset was comparable between genotypes (42 vs. 41&#xa0;years), and median expanded ATXN3 CAG repeat lengths did not differ between groups (71 vs. 71 repeats). Multivariable regression analysis adjusting for expanded ATXN3 CAG repeat length, normal ATXN3 CAG repeat length, and sex demonstrated that rs1801582 was not independently associated with age at onset (&#x3b2;&#x2009;= -&#x2009;0.42&#xa0;years, p&#x2009;=&#x2009;0.84), whereas expanded CAG repeat length remained a strong predictor (&#x3b2;&#x2009;= -&#x2009;1.68&#xa0;years per repeat, p&#x2009;<&#x2009;0.0001). CONCLUSIONS: The rs1801582 C/C genotype is extremely rare in Japan; therefore, the present cohort had limited statistical power to directly evaluate the previously proposed recessive modifier effect. No detectable association between rs1801582 genotype and age at onset was identified among G/G and G/C carriers in this Japanese cohort. These findings highlight the importance of population-specific validation and adequately powered replication studies when evaluating candidate genetic modifiers in SCA3.

Adult

The non-reciprocality of organelle gene recombination in Chlamydomonas reinhardtii and Saccharomyces cerevisiae: some new observations and a restatement of some old problems.

Organelle recombinant genotype frequencies, derived from analysis of individual mitotic zygote clones of Chlamydomonas reinhardtii and Saccharomyces cerevisiae, were subjected to two types of statistical tests in an attempt to detect the occurrence of reciprocal recombination: (i) calculation of correlation coefficients for the frequencies of two recombinant genotypes (reciprocal or non-reciprocal pairs) within individual zygote clones, and (ii) application of the chi-square test for independence to the frequencies of zygotes yielding one or the other, neither, or both of a given recombinant pair. Applying test (i), the strongest correlations are found for non-reciprocal rather than reciprocal pairs. When the data are analyzed by method (ii), some reciprocal as well as non-reciprocal pairs appear to be produced concurrently in zygote clones. However, such deviations from independence are greatest for non-reciprocal pairs. These tests yield comparable results for yeast mitochondrial and Chlamydomonas chloroplast gene recombination, and provide no convincing evidence for reciprocal genetic exchange. Explanations for the observed lack of reciprocality are discussed with reference both to our present understanding of the molecular events responsible for genetic recombination, and to the problems which may be unique to the analysis of organelle gene recombination.

Chlamydomonas

Genetic susceptibility to wild and vaccine polio virus: genotypes and their frequency.

The frequency of proposed genotypes which predispose to poliomyelitis, is tabled. Susceptibility is due to a gene or linkage group of genes with a frequency of 2% for the homozygote and 24% for the heterozygote. Two subgroups are identified where a second gene might make the persons susceptible to vaccine strains of virus. Cutter vaccinees might form a third group with increased susceptibility under special circumstances. The age at which genetic susceptibility changes to phenotypic susceptibility may be modified by physical factors such as those due to congenital syphilis and Salvarsan, and thalidomide.

Adult

The frequency of the ACTN3 polymorphism in Brazil: a systematic review and meta-analysis.

BACKGROUND: The ACTN3 gene encodes the protein alpha-actinin-3, which is crucial for fast-twitch muscle fibers, contributing to rapid and forceful contractions. The distribution of these genotypes and their impact on sports performance in Brazilian populations are not well-documented. This study aimed to determine the allelic and genotypic frequency of the ACTN3 R/X polymorphism in Brazil and its association with sports performance. METHODS: A systematic review was conducted, including studies sourced from PubMed, Scielo, LILACS, LIPECS, Coleciona SUS, CUMED, BINACIS, IBECS, and MEDLINE databases, resulting in 42 studies included. The quality of these studies was assessed using the Strengthening the Reporting of Genetic Association (STREGA) guidelines. RESULTS: Among all the 8,746 participants, 35.2% had the RR genotype, 46.2% had the RX genotype, and 18.6% had the XX genotype. Regarding allelic frequency, 58.3% were R allele carriers, while 41.7% were X allele carriers. Meta-analysis showed that there was no consistent association between the ACTN3 genotypes and sports performance, although some data suggested potential benefits in athletic performance. CONCLUSION: This study revealed that the RX genotype of the ACTN3 R577X polymorphism is the most prevalent in Brazil, followed by the RR and XX genotypes. While the R allele was more frequent, the meta-analysis did not confirm a consistent association between ACTN3 genotypes and sports performance, suggesting that other genetic and environmental factors contribute to athletic success.

Actinin

Forensic applicability of genetic profile generation from hair roots and shafts: Integration of retrotransposon polymorphisms and morphological predictors.

Genetic profiles were successfully obtained from hair samples both directly plucked from the scalp and indirectly from personal items such as combs and hairbrushes. Additionally, 100 genetic profiles were generated from buccal swabs from all donors, allowing the calculation of population allele and genotype frequencies. Complete genetic profiles were recovered from samples containing less than 0.012&#x202f;ng of total nuclear DNA. Nuclear DNA yield per hair root was highly variable, whereas hair shafts yielded up to 2&#x202f;ng of total nuDNA and in some cases less than 0.1&#x202f;ng. Multiple correspondence analysis (MCA) revealed that hair growth phase and the presence of a root were not significantly associated with successful profile recovery; instead, greater hair thickness and direct sampling correlated with higher success rates. In certain cases, the Insertion/Null (INNUL) markers system, InnoTyper 21, outperformed the Power Plex Fusion 6&#x202f;C STR kit. For forensic purposes, using the entire hair shaft provided better profiling outcomes than using the root alone. All Insertion/Null (INNUL) markers were in Hardy-Weinberg equilibrium, except for a few loci showing minor linkage disequilibrium. These results highlight the analytical potential of INNUL markers for obtaining nuclear DNA profiles from hair, even in challenging forensic contexts.

Humans

Role of OPRM1 A118G polymorphism in tramadol analgesia following third molar surgery: a pharmacogenomic study.

BACKGROUND: The OPRM1 A118G (rs1799971) polymorphism has been implicated in interindividual variability in opioid analgesic response, but its influence on tramadol efficacy remains uncertain. This study evaluated the association between OPRM1 A118G and postoperative analgesic response to tramadol following mandibular third molar surgery. METHODS: In this prospective pharmacogenomic study, 53 adults undergoing impacted mandibular third molar extraction were enrolled. Genomic DNA was analyzed for OPRM1 A118G (rs1799971) using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). All procedures were performed under 2% lignocaine with adrenaline. Tramadol (50&#x2009;mg) was administered after the onset of postoperative pain. Pain intensity was assessed using the Visual Analogue Scale (VAS) and Short-Form McGill Pain Questionnaire at 2, 4, and 6&#x2009;hours. The primary outcome was summed pain intensity difference (SPID, 2-6&#x2009;hours). RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium. No significant association was observed between OPRM1 genotype and SPID, VAS reduction, Pain Rating Index change, or responder status during the 6-hour observation period (all p&#x2009;>&#x2009;0.05). CONCLUSION: OPRM1 A118G was not significantly associated with early tramadol analgesic response following third molar surgery. Larger studies incorporating both OPRM1 and CYP2D6 genotyping are needed to clarify the genetic determinants of tramadol analgesia as CYP2D6 gene is required for tramadol metabolism.

OPRM1

Close association between particular I region-determined cell surface antigens and Ir gene-controlled immune responsiveness to synthetic polypeptides in wild rats.

The relationship between major histocompatibility complex (MHC) and genetic control of immune responsiveness to the synthetic polypeptides (T,G)-A--L [poly-(LTyr,LGlu)-poly(DLAla)--poly(LLys)] and (H,G)-A--L [poly(LHis,L-Glu)-poly-(DLAla)--poly(LLys)] has been studied in 26 wild rats. The major histocompatibility complex (MHC) genotype frequencies observed were not different from those expected according to the Hardy-Weinberg formula. More than half of the wild rats carried MHC-linked responder Ir-TGAL and Ir-HGAL genes. High or intermediate responsiveness to (T,G)-A--L and high responsiveness to (H,G)-A--L were always found to be associated with particular I region-determined cell surface antigens. These antigens could be identified serologically and by primary and secondary mixed lymphocyte reactions, and were similar or identical to I region products of (T,G)-A--L high responder or (H,G)-A--L intermediate responder inbred rat strains. The strong association between cell surface antigens and immune responsiveness could be due to linkage disequilibrium or to pleiotropy. Since the same I region-determined cell surface structure could be associated either with high or intermediate anti-(T,G)-A--L antibody titers, the presence of the Ia antigen(s) identified did not seem to guarantee high antibody responsiveness to the test antigen.

Animals

Frequency and Distribution of KIR Genotypes of Donors-Recipient Pairs in the Haploidentical Haematopoietic Stem Cell Transplantation Setting: Collaborative Study by the Spanish Working Group in Histocompatibility and Transplant Immunology (GETHIT) and the Spanish Haematopoietic Transplantation and Cell Therapy Group (GETH-TC).

There is limited information regarding the influence of KIR genotype, compared to the HLA system, in haploidentical haematopoietic stem cell transplantation (haplo-HSCT). This study aimed to determine the frequencies of KIR genotypes in Spanish haematologic patients undergoing haplo-HSCT. A study was conducted on 113 oncohaematological patients and their donors, treated across five centres that are members of the Spanish Working Group in Histocompatibility and Transplant Immunology (GETHIT) and the Spanish Haematopoietic Transplantation and Cell Therapy Group (GETH-TC). KIR typing was performed using PCR-rSSO or PCR-SSP. KIR genotypes were identified using the KIR Allele Frequency Net Database. Among donors, the most frequent KIR genotypes were Type 1 (28.3%), Type 2 (12.4%) and Type 4 (10.6%). In patients, Genotypes 1 (23.9%), 4 (23%) and 2 (14.2%) were most prevalent. Donors exhibited AA centromeric (46%) and telomeric (59.3%) types, while patients had a higher AB centromeric frequency (52.2%). Differences were observed in the BB centromeric type (3.5% patients; 16.8% donors, p&#x2009;=&#x2009;0.002). The AB KIR genotype was the most common (70.8% donors; 75.2% patients). Most were classified as 'neutral' (61.9% donors; 73.5% patients). B-content score1 was the most common (48.7% patients; 33.6% donors). Notably, classification as best was rare (2.7% patients; 16.8% donors, p&#x2009;=&#x2009;0.002). The study highlights the distribution of KIR genotypes in haplo-HSCT patients and donors, with Genotypes 1, 2 and 4 being the most prevalent. AB KIR genotypes and B-content score 1 were dominant. Moreover, KIR genotypes ID may serve as criteria for future investigation about the immunogenetic predisposition to malignant haematological diseases.

Humans

Polymorphism at the alpha-glycerophosphate dehydrogenase locus in Drosophila melanogaster. I. Properties of adult allozymes.

A biochemical comparison was made between alpha-glycerophosphate dehydrogenase allozymes from Drosophila melanogaster. Enzymes extracted from the three major genotypes were indistinguishable in terms of their pH optima and thermal stabilities. Distinctive differences were observed for three parameters; temperature dependence of specific activity, temperature dependence of K-m, and reaction rate constancy over a physiological temperature range. These results are discussed in terms of a model of balancing selection and the existence of spatial and temporal allele frequency clines in natural populations.

Alleles

MetaGLIMPSE: Meta-imputation of low-coverage sequencing data for modern and ancient genomes.

The advent of efficient and accurate imputation for low-coverage sequencing offers an unbiased alternative to SNP array imputation, increasing the accuracy of rare variant imputation across all populations. Since imputation accuracy generally increases with larger reference panels and closer ancestry match between target and reference samples, leveraging imputation from multiple reference panels improves imputation accuracy; however, individual reference panel genotypes are often privacy protected. Meta-imputation bypasses individual-level data by combining single-panel imputed genotypes through estimating panel- and marker-specific weights. We present a meta-imputation method, MetaGLIMPSE, that combines estimates from multiple reference panels for low-coverage sequencing imputation. Across all our scenarios, for both modern and ancient DNA samples, MetaGLIMPSE consistently outperforms the best single-panel imputation for coverages of 0.1&#xd7;-8&#xd7; and across all minor-allele frequencies, equaling the combined panel imputation for some parameters. Finally, MetaGLIMPSE is computationally efficient, meta-imputing 500 whole genomes in 16% of the time of GLIMPSE2.

Humans

[Study of the distribution of haptoglobin groups in Marseilles, in normal and in cancer subjects].

Authors have studied 758 sera from normal subjects in Marseille area. The genotype frequencie Hp 1 is 0,39, similar that of France in general. The phenotype repartition is 16% for Hp 1-1, 45% for Hp 2-1 and 39% for Hp 2-2. People with carcinoma have shown a increase of the frequencie of the phenotype Hp 2-2 and a decrease of the frequencie of genotype Hp 1, mostly in lung carcinoma (Hp 1 = 0,29) and in carcinoma of digestive track (Hp 1 = 0,19). However, a control group, which is constituted by people hospitalized in the Anti-Cancerous Center, has a Hp 1 frequencie of 0,29 a well as lung carcinoma, no explication was found.

France

Mitochondrial recombination in crosses of iso- and anisomitochondrial Saccharomyces cerevisiae.

Mitochondrial mutants resistant to erythromycin, neomycin and monomycin were isolated. Mitochondria were transmitted from different natural strains to the cells of the same nuclear genotype. In bifactorial crosses of such isochromosomal and anisomitochondrial yeasts we tested random samples of diploid colonies. The distribution of mitochondrial markers in parent and recombinant classes has been shown to occur unequally. The asymmetry of parent and the polarity of recombinant classes were observed to differ in different mitochondrial mutants. Anisomitochondrial strain crosses proved that mitochondrial origin essentially influenced both the parent and recombinant classes distribution and the susceptibility of the transmission to the effect of mating type locus. One can distinguish between 'homo- and heterosexual' cross combinations in terms of recombination polarity. The new type of mitochondria was found to occur with high frequency of transmission to the zygote progeny of markers resistant to erythromycin but not of markers resistant to neomycin. The problem of 'sex' in mitochondria is discussed.

Crosses, Genetic

The Spatial and Temporal Repeatability of Genomic Responses to Natural Selection as Demonstrated in Stickleback Populations Experiencing Highly Dynamic Environments.

The evolution of genotypic parallelism under shared environmental conditions provides strong evidence for the role of natural selection. However, analyses typically examine genomic signatures of selection long after the putative selection event and only assess the repeatability of responses across spatial population replicates. This impedes our ability to attribute a particular response to a given selection pressure and to distinguish non-parallel responses caused by stochastic processes from those caused by local selection. As such, the consistency of natural selection over space and time is unknown, and the role of persistent local selection pressures is unclear. Here, we leveraged the natural bar-built estuary system of Santa Cruz, California, to examine the repeatability of seasonal genomic change in threespine stickleback (Gasterosteus aculeatus) over space and time. By comparing allele-frequency shifts that are shared across locations (spatial repeatability) with those that are shared across years within locations (temporal repeatability), we identified both spatially shared and local components of putative selection. We found that repeated seasonal outlier responses occurred more often than expected under a neutral null model. Although repeatability declined as the number of estuaries sharing an outlier increased, enrichment above neutral expectations increased with broader spatial sharing, particularly for outliers repeated across both years. While the precise outlier SNPs varied across years, estuary-specific patterns of responses were broadly consistent, suggesting an important role for local conditions. Together, our findings show that temporal sampling can reveal components of putative selection that would be missed from spatial comparisons alone. More broadly, they highlight the importance of examining repeatability over both space and time to understand the parallel and non-parallel components of adaptive genomic change.

Animals

Immunogenetic diversity of two South Asian cohorts: From Pakistan and India.

Having critical roles in immune defense and reproduction, killer cell immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) class I ligands are encoded by the most polymorphic regions in the human genome. South Asia comprises over one quarter of the global population and harbors rich genomic diversity. Limiting our understanding of population-specific variation and disease susceptibility, high-resolution immunogenetic studies of South Asian ancestry individuals are lacking. Here, we characterize KIR and HLA class I diversity in two South Asian cohorts: sampling an urban population from Karachi, Pakistan (n&#xa0;=&#xa0;79), and a Dravidian-speaking Yadav population from southern India (n&#xa0;=&#xa0;70). Targeted sequencing identified 151 distinct KIR alleles across 13 genes, including 11 previously uncharacterized allotypes. Over 75% of the genotypes were KIR-Bx. We identified 98 HLA class I alleles and extensive haplotypic diversity, with all major KIR binding motifs represented, and a mean of seven potential inhibitory KIR-HLA interactions per individual (6.6 in Karachi, 7.4 in Yadav). Together, these results demonstrate substantial immunogenetic diversity and population-specific KIR and HLA variation within the two studied cohorts. This study expands knowledge of KIR and HLA diversity and offers a framework for further evolutionary and disease-focused in South Asia.

Humans

alpha1-Antitrypsin deficiency in twins and parents-of-twins.

Serum-trypsin-inhibitory-capacity (STIC) and alpha1-antitrypsin (AAT) genotypes were evaluated in 83 twins and 112 paired parents-of-twins. An increased prevalence (17.0--21.9%) of intermediate AAT deficiency (STIC less than 0.95 units/ml) was detected in both of these groups as compared to a prevalence of 4.1% in 1,841 healthy controls. PiS and PiZ molecular variants of AAT were also found more frequently in the twin and parent groups, but this was not statistically significant. Low levels of protease inhibition may enhance fertility and a tendency towards twinning, since proteolytic enzymes are involved in fertilization of ova by sperm and in gametogenesis. Increased fertility and twinning may be heterozygous advantages for AAT deficiency.

Female

Gluten-sensitive enteropathy: genetic analysis and organ culture study in 35 families.

The genetic marker histocompatibility antigen HLA-B8 is present in 80% of patients with gluten-sensitive enteropathy (GSE). We studied 35 families with at least one affected member to determine whether an HLA-region gene alone could determine susceptibility to GSE. The incidence of HLA-B8 in the patients was 69% vs 22% for normals (P less than 0.001). The incidence of GSE in HLA-genotype-identical siblings of patients was only 8%, and in HLA-B8-haplotype-identical siblings and parents of patients was only 14% and 5%, respectively. In addition, intestinal biopsies of HLA-identical or partially identical relatives of patients were studied in an in vitro organ culture system capable of detecting gluten sensitivity in subjects ingesting a normal diet. The results confirmed the low incidence of gluten sensitivity in these individuals. The organ culture system could not differentiate mucosa obtained from unaffected parents or siblings of patients with GSE (who presumably carry the HLA-associated genetic information) from mucosa obtained from normals. We conclude that the genetic material inherited with HLA-B8 alone is not sufficient to produce clinical or subclinical disease. Other genetic and environmental factors appear to be important for disease pathogenesis.

Adolescent