Search NASA⌕ Search

SEARCH · Search NASA

Results for “sequence polymorphisms”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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

At least 73 records · Page 4

Dissecting Phenotype from Genotype with Clinical Isolates of SARS-CoV-2 First Wave Variants

The emergence and availability of closely related clinical isolates of SARS-CoV-2 offers a unique opportunity to identify novel nonsynonymous mutations that may impact phenotype. Global sequencing efforts show that SARS-CoV-2 variants have emerged and then been replaced since the beginning of the pandemic, yet we have limited information regarding the breadth of variant-specific host responses. Using primary cell cultures and the K18-hACE2 mouse, we investigated the replication, innate immune response, and pathology of closely related, clinical variants circulating during the first wave of the pandemic. Mathematical modeling of the lung viral replication of four clinical isolates showed a dichotomy between two B.1. isolates with significantly faster and slower infected cell clearance rates, respectively. While isolates induced several common immune host responses to infection, one B.1 isolate was unique in the promotion of eosinophil-associated proteins IL-5 and CCL11. Moreover, its mortality rate was significantly slower. Lung microscopic histopathology suggested further phenotypic divergence among the five isolates showing three distinct sets of phenotypes: (i) consolidation, alveolar hemorrhage, and inflammation, (ii) interstitial inflammation/septal thickening and peribronchiolar/perivascular lymphoid cells, and (iii) consolidation, alveolar involvement, and endothelial hypertrophy/margination. Together these findings show divergence in the phenotypic outcomes of these clinical isolates and reveal the potential importance of nonsynonymous mutations in nsp2 and ORF8.

60 APPLIED LIFE SCIENCES↗

Evaluation of genetic diversity, agronomic traits, and anthracnose resistance in the NPGS Sudan Sorghum Core collection

The United States Department of Agriculture (USDA) National Plant Germplasm System (NPGS) sorghum core collection contains 3011 accessions randomly selected from 77 countries. Genomic and phenotypic characterization of this core collection is necessary to encourage and facilitate its utilization in breeding programs and to improve conservation efforts. In this study, we examined the genome sequences of 318 accessions belonging to the NPGS Sudan sorghum core set, and characterized their agronomic traits and anthracnose resistance response. We identified 183,144 single nucleotide polymorphisms (SNPs) located within or in proximity of 25,124 annotated genes using the genotyping-by-sequencing (GBS) approach. The core collection was genetically highly diverse, with an average pairwise genetic distance of 0.76 among accessions. Population structure and cluster analysis revealed five ancestral populations within the Sudan core set, with moderate to high level of genetic differentiation. In total, 171 accessions (54%) were assigned to one of these populations, which covered 96% of the total genomic variation. Genome scan based on Tajima’s D values revealed two populations under balancing selection. Phenotypic analysis showed differences in agronomic traits among the populations, suggesting that these populations belong to different ecogeographical regions. A total of 55 accessions were resistant to anthracnose; these accessions could represent multiple resistance sources. Genome-wide association study based on fixed and random model Circulating Probability (farmCPU) identified genomic regions associated with plant height, flowering time, panicle length and diameter, and anthracnose resistance response. Integrated analysis of the Sudan core set and sorghum association panel indicated that a large portion of the genetic variation in the Sudan core set might be present in breeding programs but remains unexploited within some clusters of accessions. The NPGS Sudan core collection comprises genetically and phenotypically diverse germplasm with multiple anthracnose resistance sources. Population genomic analysis could be used to improve screening efforts and identify the most valuable germplasm for breeding programs. The new GBS data set generated in this study represents a novel genomic resource for plant breeders interested in mining the genetic diversity of the NPGS sorghum collection.

59 BASIC BIOLOGICAL SCIENCES↗

Maast: genotyping thousands of microbial strains efficiently

Existing single nucleotide polymorphism (SNP) genotyping algorithms do not scale for species with thousands of sequenced strains, nor do they account for conspecific redundancy. Here we present a bioinformatics tool, Maast, which empowers population genetic meta-analysis of microbes at an unrivaled scale. Maast implements a novel algorithm to heuristically identify a minimal set of diverse conspecific genomes, then constructs a reliable SNP panel for each species, and enables rapid and accurate genotyping using a hybrid of whole-genome alignment and k-mer exact matching. We demonstrate Maast’s utility by genotyping thousands of Helicobacter pylori strains and tracking SARS-CoV-2 diversification.

59 BASIC BIOLOGICAL SCIENCES↗

Genetic Subtypes and Natural Resistance Mutations in HCV Genotype 4 Infected Saudi Arabian Patients

This study aimed to characterize the HCV genetic subtypes variability and the presence of natural occurring resistance-associated substitutions (RASs) in Saudi Arabia patients. A total of 17 GT patients were analyzed. Sequence analysis of NS3, NS5A, and NS5B regions was performed by direct sequencing, and phylogenetic analyses were used to determine genetic subtypes, RAS, and polymorphisms. Nine patients were infected by GT 4a, two with GT 4o and three with GT 4d. Two patients were infected with apparent recombinant virus (4a/4o/4a in NS3/NS5A/NS5B), and one patient was infected with a previously unknown, unclassifiable, virus of GT 4. Natural RASs were found in six patients (35%), including three infected by GT 4a, two by GT 4a/GT 4o/GT 4a, and one patient infected by an unknown, unclassifiable, virus of GT 4. In particular, NS3-RAS V170I was demonstrated in three patients, while NS5A-RASs (L28M, L30R, L28M + M31L) were detected in the remaining three patients. All patients were treated with sofosbuvir plus daclatasvir; three patients were lost to follow-up, whereas 14 patients completed the treatment. A sustained virological response (SVR) was obtained in all but one patient carrying NS3-RAS V170I who later relapsed. GT 4a is the most common subtype in this small cohort of Saudi Arabia patients infected with hepatitis C infection. Natural RASs were observed in about one-third of patients, but only one of them showed a treatment failure.

60 APPLIED LIFE SCIENCES↗

Direct Determination of 3C/4H Silicon Carbide Heterophase Interfaces by Electron Ptychography

Silicon carbide is a technologically relevant material that can exist in various structural polymorphs, each with its own electronic properties. Through the controlled growth of abrupt interfaces between the polymorphs, systems with emergent properties arise from differences in local bonding and stacking sequences. Determining the structure of these interfaces provides important insights into predicting and ultimately controlling their properties. Here, in this study, we use multislice electron ptychography (MEP) to qualitatively and quantitatively analyze interfaces between 3C and 4H silicon carbide in three dimensions. Two distinct interfaces are investigated: a coherent interface between $(1\bar{1}1)$ (3C) and $(0001)$ (4H) , and an incoherent interface between $(1\bar{1}2)$ (3C) and $(1\bar{1}00)$ (4H) . At the coherent interface, MEP enables direct quantification of a sharp boundary with an inclined step, whereas at the incoherent interface, local atomic displacements are determined along dislocation cores. By quantifying the spatial distribution and atomic-scale structure of these interfaces in three dimensions, this study provides insight into the complexity of silicon carbide heteropolytype interfaces, paving the way for theoretical modeling and the development of design rules to achieve desired properties.

heterophase interface↗

Comprehensive SNP Data for 1,323 GWAS Population in Populus trichocarpa and Combined Annotation Files for P. trichocarpa v3.0 and v3.1

The VCF dataset includes genetic variations found in 1,323 Populus trichocarpa genotypes, providing valuable information for scientists studying plant genetics. Researchers have generated this dataset using whole-genome DNA short-read sequencing on the Illumina Genome Analyzer, HiSeq 2000, and HiSeq 2500 platforms. This sequencing effort ensured a minimum expected sequencing depth of 15×. The dataset comprises more than 9.7 million single nucleotide polymorphisms (SNPs) and indel variants. The combined annotation files are derived from P. trichocarpa v3.0 and v3.1. We merged these files to create a comprehensive annotation file used for GWAS analysis. In total, 38,830 genes overlapped between the two versions. For overlapping genes, we defined the start as the smaller and the end as the larger among the two versions to increase the likelihood of locating candidate genetic loci. Additionally, we included 2,505 unique genes from v3.0 and 4,120 unique genes from v3.1, resulting in a total of 45,455 genes in the updated annotation file.

09 BIOMASS FUELS↗

Development and Assessment of SNP Genotyping Arrays for Citrus and Its Close Relatives

Rapid advancements in technologies provide various tools to analyze fruit crop genomes to better understand genetic diversity and relationships and aid in breeding. Genome-wide single nucleotide polymorphism (SNP) genotyping arrays offer highly multiplexed assays at a relatively low cost per data point. We report the development and validation of 1.4M SNP Axiom® Citrus HD Genotyping Array (Citrus 15AX 1 and Citrus 15AX 2) and 58K SNP Axiom® Citrus Genotyping Arrays for Citrus and close relatives. SNPs represented were chosen from a citrus variant discovery panel consisting of 41 diverse whole-genome re-sequenced accessions of Citrus and close relatives, including eight progenitor citrus species. SNPs chosen mainly target putative genic regions of the genome and are accurately called in both Citrus and its closely related genera while providing good coverage of the nuclear and chloroplast genomes. Reproducibility of the arrays was nearly 100%, with a large majority of the SNPs classified as the most stringent class of markers, “PolyHighResolution” (PHR) polymorphisms. Concordance between SNP calls in sequence data and array data average 98%. Phylogenies generated with array data were similar to those with comparable sequence data and little affected by 3 to 5% genotyping error. Both arrays are publicly available.

59 BASIC BIOLOGICAL SCIENCES↗

Dynamic compression of [100] MgF 2 single crystals: Shock-induced polymorphism to highly coordinated structures

AX 2 -type compounds exhibit a rich and complex series of phase transitions under compression. The high-pressure polymorphism of rutile-type AX 2 difluorides can be characterized by a typical sequence from rutile type → Ca Cl 2 type → HP – Pd F 2 type → cotunnite type . Relative to dioxides, the reduced valence and ionic radius of the F – anion in rutile-type MgF 2 (sellaite) results in lowered transition pressures, making it a useful analog for SiO 2 and other dioxides. In this work, MgF 2 single crystals were shock-compressed along the [100] direction to 24 to 120 GPa using plate impact techniques, and wave profiles were measured using laser interferometry. At low stresses (24 to 44 GPa), we observe features consistent with an elastic–inelastic response, followed by a phase transformation. Peak stress-density states in this stress range are consistent with those expected for the modified fluorite-type (HP- PdF 2 ) phase or a related structure. At higher stresses (69 to 91 GPa), we observe a two-wave structure with peak stress-density states consistent with transformation to a denser and likely more highly coordinated phase such as the cotunnite-type structure. Furthermore, at 120 GPa, only a single wave structure is observed, indicating that the wave profile features observed at lower stresses are overdriven.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Structure and sequence evolution in the pennycress ( Thlaspi arvense ) pangenome

Eukaryotic genomes harbor many forms of variation, including nucleotide diversity and structural polymorphisms, which experience natural selection and contribute to genome evolution and biodiversity. Harnessing this variation for agriculture hinges on our ability to detect, quantify, catalog, and deploy genetic diversity. Here, we explore seven complete genomes of the emerging biofuel crop pennycress ( Thlaspi arvense ) drawn from across the species' current genetic diversity to catalog variation in genome structure and content. Across this new pangenome resource, we find contrasting evolutionary modes in different genomic zones. Gene-poor, repeat-rich pericentromeric regions experience frequent rearrangements, including repeated centromere repositioning. By contrast, conserved gene-dense chromosome arms maintain large-scale synteny across accessions even in fast-evolving NOD-like receptor immune genes, where microsynteny breaks down across species, but gene cluster positioning macrosynteny is maintained. Our findings highlight that multiple elements of the genome experience dynamic evolution that conserves functional content on the chromosome scale but allows repositioning and presence–absence variation on a local scale. This diversity is invisible to classical reference-based strategies and highlights the strength and utility of pangenomic resources. These results provide a valuable case study of rapid genomic structural evolution within a species and powerful resources for crop development in an emerging biofuel crop.

Thlaspi arvense↗

Three pairs of fungal Trametes strains isolated from distinct geographic origins show conserved genomic features and adaptive response to plant biomass

The genomes of white-rot fungi hold extended repertoires of enzymes active on virtually all the chemical bonds that intertwine lignocellulose polymers, and several Trametes species have been identified as powerful tools for biorefinery or bioremediation. However, only few studies have addressed the intra-species polymorphism one would expect from fungal strains collected in contrasted environments. We compared the genome sequence of pairs of strains collected in different geographic areas, for each of three fungal species. Using an updated list of the predicted functions for fungal ligno- and cellulolytic enzymes (CAZymes), we observed a high conservation of the gene repertoires among the six strains. We compared the adaptative response of the fungi grown on crystalline cellulose, wheat straw, aspen or pine sawdust by transcriptomics and secretomics. The gene regulation profiles were determined by the species and the substrates, rather than the strain. The secretomes did not show marked differences in the sets of secreted CAZymes after 3 day-growth on the substrates. We identified five transcription factor genes and two sesquiterpenoid synthesis genes induced during growth on lignocellulose. Wider studies using larger sets of strains will be necessary to evaluate the genericity of our findings, and to assess the phenotype diversity one could expect from geographic diversity as compared to taxonomic diversity in Trametes fungi.

Drula, E. [French National Research Institute for ↗

Construction of Reconfigurable and Polymorphic DNA Origami Assemblies with Coiled‐Coil Patches and Patterns

Abstract DNA origami nanodevices achieve programmable structure and tunable mechanical and dynamic properties by leveraging the sequence‐specific interactions of nucleic acids. Previous advances have also established DNA origami as a useful building block to make well‐defined micron‐scale structures through hierarchical self‐assembly, but these efforts have largely leveraged the structural features of DNA origami. The tunable dynamic and mechanical properties also provide an opportunity to make assemblies with adaptive structures and properties. Here the integration of DNA origami hinge nanodevices and coiled‐coil peptides are reported into hybrid reconfigurable assemblies. With the same dynamic device and peptide interaction, it is made multiple higher‐order assemblies (i.e., polymorphic assembly) by organizing clusters of peptides into patches or arranging single peptides into patterns on the surfaces of DNA origami to control the relative orientation of devices. The coiled‐coil interactions are used to construct circular and linear assemblies whose structure and mechanical properties can be modulated with DNA‐based reconfiguration. Reconfiguration of linear assemblies leads to micron scale motions and ≈2.5‐10‐fold increase in bending stiffness. The results provide a foundation for stimulus‐responsive hybrid assemblies that can adapt their structure and properties in response to nucleic acid, peptide, protein, or other triggers.

59 BASIC BIOLOGICAL SCIENCES↗

Linkage map construction using limited parental genotypic information

Abstract Genetic linkage maps based on single nucleotide polymorphisms (SNPs) represent an essential tool for a variety of genomic analyses. Today, next-generation sequencing (NGS) enables rapid genotyping of different mapping populations based on thousands of SNPs and the construction of highly saturated linkage maps. Nevertheless, missing data in the genotyping of the parental lines creates a bottleneck that determines the number of SNPs that can be used for the linkage map. As a proof of concept, a highly saturated genetic linkage map was constructed using the imputed genotypic data of a recombinant inbred line (RIL) population and the limited genotypic information of its parental lines. Two ABH genotype files were created from a pseudo-parental genotypic data set that includes all the SNPs present in the RIL population. In the first ABH file pseudo-parental 1 was considered parental A, while in the second pseudo-parental 1 was considered parental B. These two duplicate ABH genotype files were merged by chromosome and subjected to linkage map analysis. Since the ABH data were duplicated, two mirrored linkage groups were generated per chromosome. The correct linkage map was identified and selected based on the partial genotypic data of the parental lines. This strategy was effective for constructing a highly saturated linkage map of 33,421 SNPs based on the genotyping of 205 RILs and a limited number of 100 SNPs present in the parental lines. This strategy enables the use of all the NGS SNP data obtained from a low-coverage sequencing experiment in the mapping population.

59 BASIC BIOLOGICAL SCIENCES↗

Elevated breast cancer risk in irradiated BALB/c mice associates with unique functional polymorphism of the Prkdc (DNA-dependent protein kinase catalytic subunit) gene

Female BALB/c mice are unusually radiosensitive and more susceptible than C57BL/6 and other tested inbred mice to ionizing radiation (IR)-induced mammary tumors. This breast cancer susceptibility is correlated with elevated susceptibility for mammary cell transformation and genomic instability following irradiation. In this study, we report the identification of two BALB/c strain-specific polymorphisms in the coding region of Prkdc, the gene encoding the DNA-dependent protein kinase catalytic subunit, which is known to be involved in DNA double-stranded break repair and post-IR signal transduction. First, we identified an A --> G transition at base 11530 resulting in a Met --> Val conversion at codon 3844 (M3844V) in the phosphatidylinositol 3-kinase domain upstream of the scid mutation (Y4046X). Second, we identified a C --> T transition at base 6418 resulting in an Arg --> Cys conversion at codon 2140 (R2140C) downstream of the putative leucine zipper domain. This unique PrkdcBALB variant gene is shown to be associated with decreased DNA-dependent protein kinase catalytic subunit activity and with increased susceptibility to IR-induced genomic instability in primary mammary epithelial cells. The data provide the first evidence that naturally arising allelic variation in a mouse DNA damage response gene may associate with IR response and breast cancer risk.

Non-NASA Center↗

Evolutionary Analyses of Gene Expression Divergence in Panicum hallii : Exploring Constitutive and Plastic Responses Using Reciprocal Transplants

Abstract The evolution of gene expression is thought to be an important mechanism of local adaptation and ecological speciation. Gene expression divergence occurs through the evolution of cis- polymorphisms and through more widespread effects driven by trans-regulatory factors. Here, we explore expression and sequence divergence in a large sample of Panicum hallii accessions encompassing the species range using a reciprocal transplantation experiment. We observed widespread genotype and transplant site drivers of expression divergence, with a limited number of genes exhibiting genotype-by-site interactions. We used a modified FST–QST outlier approach (QPC analysis) to detect local adaptation. We identified 514 genes with constitutive expression divergence above and beyond the levels expected under neutral processes. However, no plastic expression responses met our multiple testing correction as QPC outliers. Constitutive QPC outlier genes were involved in a number of developmental processes and responses to abiotic environments. Leveraging earlier expression quantitative trait loci results, we found a strong enrichment of expression divergence, including for QPC outliers, in genes previously identified with cis and cis–environment interactions but found no patterns related to trans-factors. Population genetic analyses detected elevated sequence divergence of promoters and coding sequence of constitutive expression outliers but little evidence for positive selection on these proteins. Our results are consistent with a hypothesis of cis-regulatory divergence as a primary driver of expression divergence in P. hallii.

3′ TagSeq↗

Influence of Polymorphs and Local Defect Structures on NMR Parameters of Graphite Fluorides

In this study, the role of local molecular structure on calculated 13 C and 19 F NMR chemical shifts for graphite fluoride materials was explored by using gauge-including projector augmented wave (GIPAW) computational methods for different periodic crystal polymorphs and density functional theory (DFT) gauge-including atomic orbital (GIAO) computational methods for individual graphite fluoride platelets, i.e., fluorinated graphene (FG). The impact of stacking sequences, d -spacing, and ring conformations on fully fluorinated graphite fluoride structures was investigated. A range of different defects including Stone–Wales, F and C vacancies, void formation, and F inversion were also evaluated using FG structures. These calculations show that distinct chemical shift signatures exist for many of these polymorphs and defects, therefore providing a basis for spectral assignment and development of models describing the mean local CF structure in disordered graphite fluoride materials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

An Atomic View of Cation Diffusion Pathways from Single‐Crystal Topochemical Transformations

Abstract The diffusion pathways of Li‐ions as they traverse cathode structures in the course of insertion reactions underpin many questions fundamental to the functionality of Li‐ion batteries. Much current knowledge derives from computational models or the imaging of lithiation behavior at larger length scales; however, it remains difficult to experimentally image Li‐ion diffusion at the atomistic level. Here, by using topochemical Li‐ion insertion and extraction to induce single‐crystal‐to‐single‐crystal transformations in a tunnel‐structured V 2 O 5 polymorph, coupled with operando powder X‐ray diffraction, we leverage single‐crystal X‐ray diffraction to identify the sequence of lattice interstitial sites preferred by Li‐ions to high depths of discharge, and use electron density maps to create a snapshot of ion diffusion in a metastable phase. Our methods enable the atomistic imaging of Li‐ions in this cathode material in kinetic states and provide an experimentally validated angstrom‐level 3D picture of atomic pathways thus far only conjectured through DFT calculations.

Handy, Joseph V.↗

Space Algae: Understanding the Genomic Impacts on Microalgae After Growth in the International Space Station

Plants and microbes can be used for biological support of crewed space missions. The radiation and microgravity environment of spaceflight is expected to increase genetic mutation of all organisms. It is essential to understand how spaceflight impacts mutation rates in photosynthetic organisms to enable appropriate countermeasures and ensure productivity during long duration and deep space missions. The Space Algae flight experiments to the International Space Station (ISS) are studying the genomic stability of microalgae that could potentially be used in biological life support systems. Space Algae-1 grew ultraviolet light mutagenized Chlamydomonas reinhardtii in the VEGGIE plant growth chamber for approximately 40 mitotic generations over one month on the ISS. Whole genome sequencing from pooled cell samples every 10 generations revealed that spaceflight cultures had an ~50% increase in DNA polymorphisms relative to ground controls. These mutations had a novel base substitution signature and suggested a risk that microalgae may be unstable for long-term production in space. Space Algae-2 is focusing on the edible cyanobacterium Arthrospira platensis, commonly known as Spirulina. This experiment seeks to grow serial cultures to allow the organism to evolve in long-term spaceflight. Biological responses of the cells to spaceflight will be assessed with multi-omics analyses to determine mutation load, gene/protein expression, metabolic/nutritional composition, and cell morphology.

Algae↗