Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “programmed genetic variation”

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 19 recordsLinked to original sources
PubMed2024

A gene with a thousand alleles: The hyper-variable effectors of plant-parasitic nematodes.

Pathogens are engaged in a fierce evolutionary arms race with their host. The genes at the forefront of the engagement between kingdoms are often part of diverse and highly mutable gene families. Even in this context, we discovered unprecedented variation in the hyper-variable (HYP) effectors of plant-parasitic nematodes. HYP effectors are single-gene loci that potentially harbor thousands of alleles. Alleles vary in the organization, as well as the number, of motifs within a central hyper-variable domain (HVD). We dramatically expand the HYP repertoire of two plant-parasitic nematodes and define distinct species-specific "rules" underlying the apparently flawless genetic rearrangements. Finally, by analyzing the HYPs in 68 individual nematodes, we unexpectedly found that despite the huge number of alleles, most individuals are germline homozygous. These data support a mechanism of programmed genetic variation, termed HVD editing, where alterations are locus specific, strictly governed by rules, and theoretically produce thousands of variants without errors.

Animals↗
PubMed1991

Selection of genetic variants from Plasmodium clones.

Clones of Plasmodium alter their antigenic profile or invasion phenotype when presented with specific challenges. Two examples are reviewed which may represent different genetic mechanisms of adaptation to selection pressures. In one series of experiments, rhesus monkeys were vaccinated with a 143,000/140,000 Mr P. knowlesi merozoite surface protein and then infected with a parasite clone expressing this protein. Primary parasitemia was controlled, but subsequent waves of parasitemia developed from populations of parasites harboring mutations in the 143,000/140,000 Mr gene. Mutations in this gene may be occurring at a continual low rate in the population (as with any normal gene) and particular mutations may have been selected in the vaccinated monkeys. In other experiments, P. falciparum parasite lines were selected from a clone (Dd2) that initially exhibited low rates of invasion into erythrocytes made sialic-acid deficient by neuraminidase treatment. After several growth cycles in neuraminidase-treated erythrocytes, a switch was observed and parasite lines were recovered that invaded neuraminidase-treated and normal erythrocytes at the same rate. The switch mechanism in invasion may represent another aspect of genetic variation, i.e. a programmed response in which certain genes are activated or rearranged. Vaccine trials in the future should include studies on the selection of mutations in the target antigen. Where switching mechanisms exist, knowledge of the genetic mechanisms that produce these adaptive responses will advance analysis of prospective vaccine candidates and contribute to our understanding of parasite biology.

Animals↗
PubMed2026

The paradoxical extinction: Exploring signatures of assortative mating as a possible mechanism that maintains canonical Red Wolf genetic ancestry in the American Gulf Coast canids.

Admixed genomes, particularly those with an evolutionary history of genetic exchange with an endangered or extinct species, are valued for innovative and unconventional conservation actions. Here, we show the substantial conservation value that the admixed canids of the Gulf Coast have as they retain high amounts of contemporary Red Wolf ancestry and unique genetic variation of past Red Wolf lineages (e.g. ghost ancestry). We analyzed 54,439 loci genotyped across the genome of 413 North American canids and investigated the role that assortative mating with respect to ancestry proportions played in the retention of endangered genetic variation. We report high correlations of inter-chromosomal ancestry proportions that varied with geographic location along Texas and Louisiana Gulf Coast populations, with the stronger signatures reported in the latter. We found that models of assortative mating promoted greater ancestry variance compared with random mating leading to increased efficiency of selection for Red Wolf and ghost alleles. Despite the Red Wolf being extinct in the wild, original, and ghost genomic variation persists in Gulf Coast admixed canids. We suggest two conservation strategies that value and preserve this unique and endangered genomic variation through designed breeding programs. Ultimately the incorporation of this ghost genetic variation would be valuable to boost the genetic viability of the ex situ Red Wolf breeding program, create in situ redundancy, and avoid extinction for this endemic American wolf species.

Animals↗
PubMed2025

Vcfexpress: flexible, rapid user-expressions to filter and format VCFs.

MOTIVATION: Variant call format (VCF) files are the standard output format for various software tools that identify genetic variation from DNA sequencing experiments. Downstream analyses require the ability to query, filter, and modify them simply and efficiently. Several tools are available to perform these operations from the command line, including BCFTools, vembrane, slivar, and others. RESULTS: Here, we introduce vcfexpress, a new, high-performance toolset for the analysis of VCF files, written in the Rust programming language. It is nearly as fast as BCFTools, but adds functionality to execute user expressions in the lua programming language for precise filtering and reporting of variants from a VCF or BCF file. We demonstrate performance and flexibility by comparing vcfexpress to other tools using the vembrane benchmark. AVAILABILITY AND IMPLEMENTATION: vcfexpress is available under the MIT license at https://github.com/brentp/vcfexpress with code used for the manuscript deposited in https://doi.org/10.5281/zenodo.14756838.

Software↗
PubMed2026

The potential of considering photosynthesis parameters in crop yield breeding by genomic prediction.

To meet the growing demand for agricultural products, optimizing photosynthesis is a promising strategy to improve crop yields. Phenotypic variance in photosynthesis has been observed within or between species. To explore the potential of integrating photosynthetic parameters into crop breeding programs, we explored the genetic variation in photosynthesis by assessing photosynthesis-related parameters across plant development in 631 barley recombinant inbred lines (RILs) from eight HvDRR subpopulations under field conditions. The genetic complexity of these parameters was resolved by analyses of bi-parental and multi-parental quantitative trait loci (QTLs). Finally, we examined the merit of integrating photosynthesis-related parameters in genomic prediction of yield and its components. Significant genotypic variations of the photosynthesis-related parameters were found among the RILs, with their heritability ranging from 0.38 to 0.54. The multiple QTLs and dynamic QTLs for photosynthesis observed across different developmental stages underlined the complexity of the genetics of photosynthesis in barley. The considerably higher percentage of phenotypic variance explained for genomic prediction than multi-parental QTL analysis illustrates that the photosynthesis-related parameters are inherited in a more complex way than classical agronomic traits. Notably, the prediction ability for yield was increased by integrating the photosynthesis-related parameters of some developmental stages into genomic prediction models. Thus, our results suggest a novel perspective on increasing the efficiency of crop breeding programs by integrating photosynthesis-related parameters into prediction models.

Photosynthesis↗
PubMed2025

CNV-Finder: Streamlining Copy Number Variation Discovery.

Copy Number Variations (CNVs) play pivotal roles in the etiology of complex diseases and are variable across diverse populations. Understanding the association between CNVs and disease susceptibility is significant in disease genetics research and often requires analysis of large sample sizes. One of the most cost-effective and scalable methods for detecting CNVs is based on normalized signal intensity values, such as Log R Ratio (LRR) and B Allele Frequency (BAF), from Illumina genotyping arrays. In this study, we present CNV-Finder, a novel pipeline integrating deep learning techniques on array data, specifically a Long Short-Term Memory (LSTM) network, to expedite the large-scale identification of CNVs within predefined genomic regions. This facilitates efficient prioritization of samples for time-consuming or costly subsequent analyses such as Multiplex Ligation-dependent Probe Amplification (MLPA), short-read, and long-read whole genome sequencing. We incorporate four genes to establish our methods-Parkin (PRKN), Leucine Rich Repeat And Ig Domain Containing 2 (LINGO2), Microtubule Associated Protein Tau (MAPT), and alpha-Synuclein (SNCA)-which may be relevant to neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Progressive Supranuclear Palsy (PSP), or related disorders such as essential tremor (ET). By training our models on expert-annotated samples and validating them across diverse cohorts, including those from the Global Parkinson's Genetics Program (GP2) and additional dementia-specific databases, we demonstrate the efficacy of CNV-Finder in accurately detecting deletions and duplications. Our pipeline outputs app-compatible files for visualization within CNV-Finder's interactive web application. This interface enables researchers to review predictions and filter displayed samples by model prediction values, LRR range, and variant count in order to explore or confirm results. Our pipeline integrates this human feedback to enhance model performance and reduce false positive rates. Through a series of comprehensive analyses and validations using visual inspection, MLPA, short-read, and long-read sequencing data, we demonstrate the robustness and adaptability of CNV-Finder in identifying CNVs with regions of varied size, probe density, and noise. Our findings highlight the significance of contextual understanding and human expertise in enhancing the precision of CNV identification, particularly in complex genomic regions like 17q21.31. The CNV-Finder pipeline is a scalable, publicly available resource for the scientific community, available on GitHub (https://github.com/GP2code/CNV-Finder; DOI 10.5281/zenodo.14182563). CNV-Finder not only expedites accurate candidate identification but also significantly reduces the manual workload for researchers, enabling future targeted validation and downstream analyses in regions or phenotypes of interest.

Copy Number Variation (CNV)↗
PubMed1989

Selection for disease resistance.

Approaches to disease control are prioritized. Genetic improvement could reduce need for treatment and culling but would not reduce the need for proper management and sanitation. Results of several studies indicate that disease incidence and cost increases with selection for milk yield. The large array of disease resistance mechanisms in animals suggests a large number of loci are involved in disease resistance. A few loci, e.g., the major histocompatibility complex, may account for a major portion of genetic variance in disease. Rate of genetic gain from selection for a major locus alone or in combination with performance is discussed. Four criteria for including traits in a breeding program are outlined, and each is discussed with respect to disease. In spite of low heritabilities for disease traits, genetic variation for disease incidence is economically important and justifies including disease in breeding programs. An industry-wide standard for recording and accumulating field data for disease is lacking. Institutional relationships among segments of the animal breeding and animal health industries are needed to facilitate genetic improvement for disease resistance.

Animals↗
PubMedDate not supplied

[Decoding common mechanisms of cellular genetic-epigenetic control in eukaryotes].

The mechanism of genetic epigenetic operation at genomic and chromosomic levels within the limits of imitation model of eucaryotic cellular compartment is postulated, this compartment including left and right operators. Probable pattern of interactions during reproduction, determination and expression of genes as a manifestation of genetic, epigenetic memory and memory of water is shown. A specific character and rate of transformations of nucleotides and proteins are realized through different operation mechanisms over hierarchic processes directed on the preservation of DNA in the line of cellular generations and also determining dynamics of the genome with DNA variations. The mechanism of programmed provision of genetic-epigenetic interaction lies in the ways of control, regulation, adaptation and modulation of nucleotides and proteins transformations which occur on the basis of specific (complementary, kinetic and tunnel effects) choice of directions, place, time and aim of nucleotide-nucleotide, nucleotide-protein, protein-nucleotide and protein-protein interactions.

DNA↗
PubMed1987

Genetic relationships and additive genetic variation of productive and reproductive traits in Guernsey dairy cattle.

Data were first lactation production and reproduction records initiated from 1958 to 1981 in two experiment station Guernsey herds. Heritability estimates using paternal half sib groups were .24 +/- .12 for milk yield, .27 +/- .12 for fat yield, and .77 +/- .15 for fat percentage. Heritability estimates for reproductive traits ranged from .01 to .04 for number of services, service period, conception rate, and days open, but were higher for days in milk at first breeding (.12) and age at first calving (.13). Except for age at first calving, coefficients of additive genetic variation were larger for reproductive traits than for productive traits. Genetic correlations between measures of production and reproduction were moderate to large and antagonistic, except that the relationship between production and age at first calving was favorable. Breeding value estimates for milk yield and reproduction were negatively correlated for sires with above average breeding values for milk yield. Huge phenotypic variances for reproductive traits masked substantial additive genetic variation for these traits. When all things are considered it seems unwise to ignore reproductive performance in selection programs for dairy cattle.

Animals↗
PubMed2025

The impact of common and rare genetic variants on bradyarrhythmia development.

To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively. Four well-known loci (SCN5A/SCN10A, CCDC141, TBX20 and CAMK2D) were shared for SND and DCD, while others were more specific for SND or DCD. SND and DCD showed a moderate genetic correlation (rg = 0.63). Cardiomyocyte-expressed genes were enriched for contributions to DCD heritability. Rare-variant analyses implicated LMNA for all bradyarrhythmia phenotypes, SMAD6 and SCN5A for DCD and TTN, MYBPC3 and SCN5A for PM. These results show that variation in multiple genetic pathways (for example, ion channel function, cardiac developmental programs, sarcomeric structure and cellular homeostasis) appear critical to the development of bradyarrhythmias.

Humans↗
PubMed1989

Fitness differences among remnant populations of the endangered sonoran topminnow.

Four correlates of fitness were measured in three stocks of the endangered Sonoran topminnow, Poeciliopsis occidentalis, from Arizona. Survival, growth, early fecundity, and developmental stability were greatest in laboratory-reared fish from the most heterozygous natural population studied. Conversely, all four traits were poorest in fish from a population with no electrophoretically detectable genetic variation. These results emphasize the need for genetic as well as demographic information for the development of comprehensive species recovery programs.

Animals↗
PubMed2026

Genetic background influences developmental airway smooth muscle program and susceptibility to airway hyperresponsiveness in mice.

Airway structural remodeling and hyperresponsiveness (AHR), hallmarks of asthma, are influenced by genetic variations and adverse exposures. While intrauterine perturbations in lung development have been linked to adult pulmonary disease, the developmental origins of these abnormalities remain poorly understood. Here, we provide evidence of genetic background playing a key role in this process. Using A/J and C57BL/6J mice known for their distinct susceptibility to AHR, we show that A/J embryos selectively develop an aberrant airway smooth muscle (SM) program and AHR in adulthood when exposed transiently to a vitamin A/retinoic acid (RA)-disrupted intrauterine environment in vivo by maternal BMS493 administration. Single-nucleus multiomics identified a mesenchymal cell population overactivating TGF-β targets in response to BMS493 selectively in A/J lungs. These cells, localized to sites of airway SM initiation and p-SMAD2- and -3, exhibited robust BMS493-mediated upregulation of SMAD2/3 targets, including regulators of SM program Pdgfra and Tnc. Functional analyses in vivo and cultured lungs showed aberrant SM formation in areas of overactive TGF-β of BMS493-exposed lungs. These abnormalities were prevented by inhibiting TGF-β signaling in utero in RA-deficient embryos. These findings underscore how distinct genetic backgrounds respond to intrauterine perturbations that program airway structure and function, with potential lasting consequences in postnatal pulmonary function.

Animals↗
PubMed1988

Constitutional genetic markers of aging.

Constitutional genetic markers of aging can be defined as members of that subset of genes that modulate the times of onset and/or the rates of progression of one or more of the processes of aging, or the response of the target cells, tissues and organisms to a particular process. These genetic factors are classified into: (1) those that control changes in structure and function that may be universally expressed in aging organisms or that are expressed in large taxonomic groups of organisms ("public markers") and (2) those that control changes that are species specific or that reflect polymorphisms or mutations within a species ("private markers"). Both spontaneous and experimentally induced genetic variation can identify and characterize such genetic elements. Recommendations for implementing such a program of research include (1) particularization of the aging phenotype, (2) further development of nonmammalian models amenable to genetic analysis, (3) systematic search for relevant spontaneous mutations in Mus musculus, (4) utilization of recombinant inbred, chimeric, transgenic and interspecific mice and (5) investigations of genetic concomitants of speciation.

Aging↗
PubMed2025

Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences.

Admixed individuals have largely been understudied in medical research due to their complex genetic ancestries. However, the consideration of admixture can help identify ancestry-enriched genetic associations, delineating some of the genetic underpinnings of cross-population phenotypic variation. To this end, we performed local ancestry inference within the All of Us Research Program to identify individuals with recent admixture between African (AFR) and European (EUR) populations (N=48,921). We identified evidence of local AFR ancestry enrichment at the HLA locus, suggestive of putative selection since admixture. Furthermore, we performed the largest admixture mapping (ADM) efforts in AFR-EUR Admixed individuals for 22 traits, identifying 71 associations between inferred local AFR ancestries and a trait. Variants from published GWAS could only account for 18 (25%) of the ADM associations, highlighting novel loci where ancestral haplotypes explained some phenotypic variation. Previous studies likely have not identified these loci due to the low availability of high-powered GWAS in populations genetically similar to AFR. One such loci was 9q21.33, associated with 1.4-fold risk of end-stage kidney disease (ESKD) for carriers of inferred local AFR ancestries at the region. This locus contains the gene SLC28A3, which has previously been linked to kidney function but has never been associated with cross-population ESKD prevalence differences. Together, our results expand upon the existing literature on phenotypic differences between populations, highlighting loci where genetic ancestries play a critical role in the genetic architecture of disease.

Journal Article↗
PubMed1989

Intraspecific genetic variability in mitochondrial DNA of the screwworm fly (Cochliomyia hominivorax).

Mitochondrial DNA variability has been analyzed in the primary screwworm fly (Cochliomyia hominivorax) using restriction endonuclease fragment patterns and restriction site mapping. A total of 30 different screwworm lines originating from Texas to Costa Rica and the Island of Jamaica was examined using 15 restriction endonucleases. Eleven of the restriction enzymes revealed polymorphism and yielded 16 mitochondrial genotypes or haplotypes. Two of the haplotypes were widely distributed, haplotype 1 being found scattered across southern Mexico and haplotype 2 along the west coast of Mexico. Haplotype 1 also appeared paired with several other haplotypes in mixed lines that were most likely the result of collecting an egg mass to which more than one female had contributed or to some form of contamination by haplotype 1 after introduction into the laboratory. These lines became fixed before single insects were examined and thus it is impossible to rule out heteroplasmy. The other 14 haplotypes were found in only a single locale and 12 of these were found in only one line. The average sequence diversity among 27 mainland lines was about 0.5%. The two Jamaican lines and one east coast mainland line differed from the others by greater than 2%. The pattern of geographical distribution, a small number of apparently recurring haplotypes and a substantial number (75%) of the haplotypes unique, bears similarities to patterns observed in other insects such as Drosophila. The high frequency of unique genotypes in southern Mexico suggests a population with a very reduced gene flow, which may have had a positive effect on the sterile male release control program.

Animals↗
PubMed1979

Tolbutamide pharmacogenetics and the UGDP controversy.

We analyzed the relationship between the pharmacogenetics of tolbutamide metabolism and the controversial University Group Diabetes Program (UGDP) study. Before the institution of that study, the extent of genetic control over the variation in the rate of tolbutamide metabolism was unknown, and all subjects included in the tolbutamide treatment group were given 1,500 mg/day of tolbutamide in a fixed dosage. We addressed the hypothesis that high accrued blood levels of tolbutamide in genetically predisposed slow inactivators might have contributed to the toxic effects reported by the UGDP study. This proposal is based on recent findings from population, twin, and family studies that tolbutamide metabolism is under monogenic control, with nearly one fourth of the population classified as slow inactivators.

Alleles↗
PubMed1991

Additive and nonadditive genetic variance in female fertility of Holsteins.

Additive and nonadditive genetic variances were estimated for cow fertility of Holsteins. Measures of fertility were first lactation days open and service period as recorded and with upper bounds of 150 and 91 d, respectively. Six million inseminations from the Raleigh, North Carolina Processing Center were used to form fertility records of 379,009 cows. Data were analyzed with a model accounting for all additive, dominance, and additive by additive covariances traced through sires and maternal grandsires. Variance components were estimated by the tilde-hat approximation to REML. Heritability in the narrow sense was 2% for days open and .8% for service period. Dominance and additive by additive variance as a percentage of phenotypic variation strongly depended on imposition of upper bounds. Heritabilities in the broad sense ranged from 2.2 to 6.6% and were at least twice as large as heritabilities in the narrow sense. Effect of 25% inbreeding was only around an additional 3 d open. Specific combining abilities among bulls were estimated as sums of dominance and additive by additive interactions removing effect of inbreeding depression. Differences between maximum and minimum estimates were in the order of twice the estimated standard deviation, ranging from 1.5 to 6.7 d. Effects of inbreeding and specific combining ability could be jointly considered in mating programs following sire selection.

Animals↗