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At least 163 records · Page 9Linked to original sources
PubMed2003

Karyotypic complexity of the NCI-60 drug-screening panel.

We used spectral karyotyping to provide a detailed analysis of karyotypic aberrations in the diverse group of cancer cell lines established by the National Cancer Institute for the purpose of anticancer drug discovery. Along with the karyotypic description of these cell lines we defined and studied karyotypic complexity and heterogeneity (metaphase-to-metaphase variations) based on three separate components of genomic anatomy: (a) ploidy; (b) numerical changes; and (c) structural rearrangements. A wide variation in these parameters was evident in these cell lines, and different association patterns between them were revealed. Analysis of the breakpoints and other specific features of chromosomal changes across the entire set of cell lines or within particular lineages pointed to a striking lability of centromeric regions that distinguishes the epithelial tumor cell lines. We have also found that balanced translocations are as frequent in absolute number within the cell lines derived from solid as from hematopoietic tumors. Important similarities were noticed between karyotypic changes in cancer cell lines and that seen in primary tumors. This dataset offers insights into the causes and consequences of the destabilizing events and chromosomal instability that may occur during tumor development and progression. It also provides a foundation for investigating associations between structural genome anatomy and cancer molecular markers and targets, gene expression, gene dosage, and resistance or sensitivity to tens of thousands of molecular compounds.

Cell Line, Tumor↗
PubMed2025

Polyploidy-mediated variations in glutamate receptor proteins linked to Fusarium wilt resistance in upland cotton.

Cotton production in the US faces a serious threat from Fusarium oxysporum f. sp. vasinfectum race 4 (FOV4), a soil-borne fungus causing Fusarium wilt by infecting the roots and vascular system of susceptible cotton, leading to rapid wilting and death. Here, we investigate genetic mechanisms of resistance to FOV4 in the highly resistant upland cotton genotype "U1" using an early-generation segregating biparental population ("U1" × "CSX8308") with comprehensive genomic resources. Reference-grade genomic assemblies of the parents revealed minor structural variations between "U1" haplotypes, a high degree of collinearity at chromosome synteny and micro-synteny levels, and significant divergence from "CSX8308" with 8.9 million SNPs. QTL analysis identified significant markers on chromosomes D03 and A02 linked to reduced Fusarium wilt severity. Within these regions, two glutamate-receptor-like (GLR) genes showed structural variation and overlapped between translocated segments on A02 and D03, suggesting a rare but important reinforcing effect of parallel evolution between susceptible and resistant genotypes. Transcriptome profiles of "U1" under FOV4 infection reveal activation of calcium-binding proteins and transcription factors regulating plant hormones (ethylene, abscisic acid, jasmonic acid, and salicylic acid), along with enzymes involved in cell wall remodeling and phytoalexin production. Advancing cotton improvement depends on incorporating durable genetic disease resistance into high-yielding, high-quality cultivars.

Fusarium↗
PubMed2025

Extensive longevity and DNA virus-driven adaptation in nearctic Myotis bats.

The genus Myotis is one of the largest clades of bats, and exhibits some of the most extreme variation in lifespans among mammals alongside unique adaptations to viral tolerance and immune defense. To study the evolution of longevity-associated traits and infectious disease, we generated cell lines and near-complete genome assemblies for 8 closely related species of Myotis. Using genome-wide screens of positive selection, analyses of structural variation, and functional experiments in primary cells, we identify new patterns of adaptation contributing to longevity, cancer resistance, and viral interactions in bats. We show that the recurrent evolution of longevity seen in Myotis leads to some of the highest predicted increases in cancer risk across mammals and demonstrate a unique DNA damage response in primary cells of the long-lived M. lucifugus. We also find evidence of abundant adaptation in response to DNA viruses - but not RNA viruses - in Myotis and other bats in sharp contrast with other mammals, potentially contributing to the role of bats as reservoirs of zoonoses. Together, our results demonstrate how genomics and primary cells derived from diverse taxa uncover the molecular bases of extreme adaptations in non-model organisms.

Aging↗
PubMed2006

Structural variation on the short arm of the human Y chromosome: recurrent multigene deletions encompassing Amelogenin Y.

Structural polymorphism is increasingly recognized as a major form of human genome variation, and is particularly prevalent on the Y chromosome. Assay of the Amelogenin Y gene (AMELY) on Yp is widely used in DNA-based sex testing, and sometimes reveals males who have interstitial deletions. In a collection of 45 deletion males from 12 populations, we used a combination of sequence-tagged site mapping, and binary-marker and Y-short tandem repeat haplotyping to understand the structural basis of this variation. Of the 45 deletion males, 41 carry indistinguishable deletions, 3.0-3.8 Mb in size. Breakpoint mapping strongly implicates a mechanism of non-allelic homologous recombination between the proximal major array of TSPY gene-containing repeats, and a single distal copy of TSPY; this is supported by the estimation of TSPY copy number in deleted and non-deleted males. The remaining four males carry three distinct non-recurrent deletions (2.5-4.0 Mb), which may be due to non-homologous mechanisms. Haplotyping shows that TSPY-mediated deletions have arisen seven times independently in the sample. One instance, represented by 30 chromosomes mostly of Indian origin within haplogroup J2e1*/M241, has a time-to-most-recent-common-ancestor of approximately 7700+/-1300 years. In addition to AMELY, deletion males all lack the genes PRKY and TBL1Y, and the rarer deletion classes also lack PCDH11Y. The persistence and expansion of deletion lineages, together with direct phenotypic evidence, suggests that absence of these genes has no major deleterious effects.

Amelogenin↗
PubMed2026

Pan-genomics and multi-omics for deciphering genetic variation and accelerating genetic improvement in ruminant livestock.

Livestock reference genomes have transformed the discovery of variants associated with production, reproduction, health, and environmental adaptation. Nevertheless, a single linear reference represents only one mosaic haplotype and incompletely captures sequence diversity within a species, particularly structural variants, copy-number changes, repeat-rich regions, and breed-specific sequences. Pangenomes address this limitation by integrating multiple high-quality assemblies or population-scale variants into a unified sequence or graph representation. Concurrently, multi-omics approaches connect genomic variation with transcriptomic, epigenomic, manuscriptproteomic, metabolomic, and microbiome responses, thereby improving biological interpretation of genotype-phenotype relationships. This review synthesizes recent progress in livestock pangenomics and multi-omics, with emphasis on cattle, goats, sheep, water buffalo, and chickens. It describes advances in long-read and haplotype-resolved sequencing, graph construction, structural-variant discovery and genotyping, functional annotation, and integrative analysis. Recent pangenome studies have uncovered substantial non-reference sequence, reduced reference bias, identified breed- and population-specific structural variants, and resolved candidate variants underlying pigmentation, body size, tail morphology, cashmere production, altitude adaptation, and other economically relevant traits. However, translation into routine breeding remains constrained by uneven population representation, inconsistent structural-variant definitions, limited functional annotation, computational demands, and insufficient validation across environments. Future progress will depend on diverse near-complete assemblies, graph-aware imputation and genomic prediction, long-read transcriptomics, single-cell and spatial omics, rigorous causal validation, and open, interoperable resources. Together, these developments can support more accurate, resilient, and biologically informed livestock improvement. Importantly, current dairy-cattle evidence indicates that pangenome-derived structural variants can substantially improve variant discovery and functional interpretation while yielding only marginal average gains in routine genomic prediction, favoring targeted augmentation rather than wholesale replacement of established SNP-based evaluations.

Animals↗
PubMed1987

HLA-DP and HLA-DO genes in presumptive HLA-identical siblings: structural and functional identification of allelic variation.

We analyzed HLA class II genomic polymorphisms in three families in which bone marrow transplantation was performed between individuals presumed to be HLA identical, but in which unexplained mixed lymphocyte culture reactivity was observed. These families were characterized by classical HLA serology, MLC, and DP typing. In each family, a pair of "HLA-identical" siblings demonstrated a small proliferative response in bidirectional MLC. Southern blotting analysis performed with cDNA probes for DQ alpha, DP alpha, and DP beta identified DP genomic differences in each case. Hybridization of Bgl II-digested genomic DNA with a DP alpha cDNA probe revealed three prominent polymorphic fragments (7.7, 5.8, and 3.7 kb), which discriminated between presumptive identical siblings and indicated crossover events within HLA. Similarly, hybridization of SstI-digested genomic DNA with a DP beta cDNA probe, although resulting in a more complex pattern, identified DP genomic disparity between the presumed HLA identical siblings. Hybridization of SstI-digested DNA from two families with evidence of DP recombination was performed by using an oligonucleotide probe specific for the newly described HLA class II gene DO beta. Two major polymorphic fragments, at 6.2 and 3.3 kb, segregated in these families and localized the crossovers flanking the DO beta gene between the DQ and DP loci. The contribution of the antigenic differences marked by these HLA DP and DO DNA polymorphisms to allorecognition in MLR and in graft-vs-host disease are discussed.

Alleles↗
PubMed2005

Bioinformatics approaches and resources for single nucleotide polymorphism functional analysis.

Since the initial sequencing of the human genome, many projects are underway to understand the effects of genetic variation between individuals. Predicting and understanding the downstream effects of genetic variation using computational methods are becoming increasingly important for single nucleotide polymorphism (SNP) selection in genetics studies and understanding the molecular basis of disease. According to the NIH, there are now more than four million validated SNPs in the human genome. The volume of known genetic variations lends itself well to an informatics approach. Bioinformaticians have become very good at functional inference methods derived from functional and structural genomics. This review will present a broad overview of the tools and resources available to collect and understand functional variation from the perspective of structure, expression, evolution and phenotype. Additionally, public resources available for SNP identification and characterisation are summarised.

Algorithms↗
PubMed1995

Developing microsatellite markers for insect population structure: complex variation in a checkerspot butterfly.

We isolated and characterized two microsatellite markers from the genome of the endangered checkerspot butterfly Melitaea cinxia L. In Finland, this species only survives on the Aland islands, where it exhibits a highly fragmented metapopulation structure on small meadows. Four alleles were observed at the locus CINX1 and nine at CINX4; the total gene diversities at the two loci were HT = 0.34 and 0.80, respectively. A pilot survey showed moderate gene frequency differentiation among meadows (local populations; FLM = 0.1) and among metapopulations c. 30 km apart (FMT = 0.2). Contrary to prior expectation, distinct feeding larval groups collected in the spring did not represent offspring of single females. There was a conspicuous excess of homozygotes within local populations (FIL = 0.35), which can hardly be attributed to population structure alone; this urges caution in straightforward interpretation of microsatellite phenotype data.

Animals↗
PubMed2026

Comparisons Between Large-Scale Genomic Variants and SNPs in Driving Population Divergence and Local Adaptation.

Genomic variations, such as indels (2-49 bp) and structural variants (SVs, ≥50 bp), are larger-scale mutations than single nucleotide polymorphisms (SNPs) and can substantially impact evolutionary processes, including speciation, adaptation, and phenotypes. Despite their functional importance, integrative population genetic analyses that jointly consider genome-wide SNPs, indels, and SVs remain under-explored. The ground tit (Pseudopodoces humilis), an endemic species to the Qinghai-Tibet Plateau (QTP), exhibits divergence across distinct glacial refugia, accompanied by habitat and morphological divergence, making it an excellent example for investigating how different types of genomic variants contribute to population divergence and local adaptation. Here, by retrieving 81 whole-genome sequence data, over 13 million SNPs, 2 million indels, and 22,101 SVs were identified. Variants were unevenly distributed across the genome, characterized by distinct hotspot regions. Indels and SVs revealed four genetic clusters consistent with previous SNP-based results, thereby validating the reliability of our variant datasets. FST and genotype-environment association (GEA) analyses independently revealed numerous candidate indels and SVs; each showed minimal overlap with previously identified SNPs, and were enriched in similar functional pathways such as signal transduction, skeletal muscle development, water transport, DNA repair, reproduction, nervous system development, and immunity. Collectively, our results demonstrated that indels and SVs could capture additional signatures besides SNPs. Furthermore, similar but distinct gene functions among different types of genomic variants collectively and complementarily drive genomic divergence across environmental gradients in such a high-elevation endemic species, underscoring its evolutionary relevance in local adaptation.

indels↗
PubMed1994

Molecular basis of antigenic variation in infectious bursal disease virus.

Four antigenically different strains of infectious bursal disease virus (IBDV), characterized by their reactivities with a panel of neutralizing monoclonal antibodies (MAbs), were selected to determine the molecular basis of antigenic variation. The large genome segment A, encoding the structural proteins of the U.S. variants GLS, DS326, E/Del and the vaccine strain D78, was cloned and sequenced. Comparison of the deduced amino acid sequences of the U.S. variants with other IBDV strains showed that most of the amino acid substitutions occur in the central region between residues 212 to 332, especially in the two hydrophilic regions between residues 212 to 223 and residues 314 to 324 of VP2 protein. By comparing the amino acid sequences of these variant viruses and their reactivities with IBDV specific MAbs, the putative amino acids involved in the formation of virus-neutralizing epitopes were identified. Comparison of the D78 versus PBG98 sequence showed that Gln at position 249 (Gln249) appears to be critical in binding with MAb B69. Similarly, comparison of the U.S. variant sequences with other serotype 1 sequences showed unique substitution(s) at residue Glu321 in GLS, residues Ile286, Asp318, Glu323 in E/Del, and residues Glu311 and Gln320 in DS326, which could be potential residue(s) involved in the recognition of MAb57, MAb67, and MAb179 epitopes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed2004

Cloning, genomic organization, expression, and effect on beta-casein promoter activity of a novel isoform of the mouse Oct-1 transcription factor.

The ubiquitously expressed transcription factor Oct-1, a member of the POU domain factors, is involved in the regulation of expression of many tissue-specific and house-keeping genes. Multiple alternatively spliced isoforms of Oct-1 have been identified in human and mouse cells. The expression patterns of these isoforms and the analysis of their genomic organization and structure have suggested that the structural variation of Oct-1 isoforms may be important in conferring target and tissue specificity to its transcriptional activity. In this study, we have cloned and sequenced a new mouse Oct-1 isoform, named mOct-1Z. This novel isoform differs markedly at the C-terminus from the previously identified Oct-1 isoforms A, B, and C. It is generated by alternative splicing from the Oct-1 gene and its transcript exhibits a frameshift followed by an early stop codon, thus, its predicted protein has a distinct, much shorter C-terminal tail. However, this truncated isoform could still effectively bind to a consensus Oct-1 motif oligonucleotide and, like Oct-1B, activated the basal promoter activity of the mouse beta-casein gene. Oct-1Z is another ubiquitously expressed Oct-1 isoform, its transcript being detected in all mouse tissues examined, including the mammary gland, liver, lung, kidney, spleen, small intestine mucosa, uterus, and ovary.

5' Flanking Region↗
PubMed2004

Association of extensive polymorphisms in the SLAM/CD2 gene cluster with murine lupus.

Susceptibility to autoimmunity in B6.Sle1b mice is associated with extensive polymorphisms between two divergent haplotypes of the SLAM/CD2 family of genes. The B6.Sle1b-derived SLAM/CD2 family haplotype is found in many other laboratory mouse strains but only causes autoimmunity in the context of the C57Bl/6 (B6) genome. Phenotypic analyses have revealed variations in the structure and expression of several members of the SLAM/CD2 family in T and B lymphocytes from B6.Sle1b mice. T lymphocytes from B6.Sle1b mice have modified signaling responses to stimulation at 4-6 weeks of age. While autoimmunity may be mediated by a combination of genes in the SLAM/CD2 family cluster, the strongest candidate is Ly108, a specific isoform of which is constitutively upregulated in B6.Sle1b lymphocytes.

Alleles↗
PubMed2001

Isolation and phylogenetic analysis of HERV-K long terminal repeat cDNA in cancer cells.

Long terminal repeat (LTR) elements of human endogenous retrovirus (HERV-K) may have contributed to disease-associated structural change or genetic variation in the human genome. The LTR elements have been found to be coexpressed with sequences of closely located genes. We identified seven HERV-K LTR elements from mRNA of human cancer cells (HepG2, MCF7, and SiHa), using the RT-PCR approach. Four of them are closely related to the human-specific HERV-K LTR elements with a high degree of sequence homology in a neighbor-joining phylogenetic tree. The data suggest that recently proliferated HERV-K LTR elements are expressed actively in various cancer cells. These HERV-K LTR elements deserve further investigation as potential leads in the treatment of human cancer.

Base Sequence↗
PubMed1999

Presence and phylogenetic analysis of HERV-K LTR on human X and Y chromosomes: evidence for recent proliferation.

The K group of human endogenous retroviruses (HERV-K) has been suggested to have a role in disease and has recently been shown to include long terminal repeat (LTR) elements that are human specific. Here we investigated the presence of HERV-K LTRs on the human X and Y chromosomes with the use of PCR on a monochromosomal somatic cell hybrid DNA panel. We report twelve such sequences on the X chromosome and ten sequences on the Y chromosome. Phylogenetic analysis reveals that clones X2, 4, 5, 6, 7, 11, 15 from the X chromosome and clones Y4, 5, 7, 10 from the Y chromosome are closely related to the human-specific members of Medstrand and Mager's cluster 9. The sequence of clone Y7 from the Y chromosome is identical with human-specific HERV-K LTR element (AC002350) from chromosome 12q24. The findings suggest recent proliferation and transposition of HERV-K LTR elements on these chromosomes. Such events may have contributed to structural change and genetic variation in the human genome. We draw attention to evolutionarily recent changes in homologies between X and Y chromosomes as a method of further investigating such transpositions.

DNA, Viral↗
PubMed2001

Phylogeny of SINE-R retroposons in Asian apes.

The SINE-R retroposon family was derived from the long terminal repeats (LTRs) of human endogenous retrovirus K (HERV-K) that had been active during the hominoid evolution. The retroposons and HERV-K LTR elements have potential relevance to structural change and genetic variation of the hominoid genome. In our previous study, we found that the SINE-R retroposons were hominoid specific. Here we identified seventeen new SINE-R retroposons (14 from orangutan and 3 from gibbon) from Asian apes and phylogenetically analysed them in comparison with those of the humans and African great apes. None of the retroposons from Asian apes were closely related to SINE-R.C2 that is human specific, and originally identified in the gene for the C2 component of complement, whereas some retroposons (Ch-M10, Ch-M16, Gor-M, Gor-F1, Gor-M6, and Gor-F9) from African great apes showed very close relationship with that of the SINE-R.C2 retroposon. The phylogenetic tree based on the SINE-R retroposons revealed wide overlap of the retroposons across species, suggesting that the SINE-R retroposons have been evolved parallel pattern in the course of hominoid evolution.

Animals↗
PubMed2002

Comparative genomic analysis of equilibrative nucleoside transporters suggests conserved protein structure despite limited sequence identity.

Equilibrative nucleoside transporters (ENTs) are a recently characterized and poorly understood group of membrane proteins that are important in the uptake of endogenous nucleosides required for nucleic acid and nucleoside triphosphate synthesis. Despite their central importance in cellular metabolism and nucleoside analog chemotherapy, no human ENT gene has been described and nothing is known about gene structure and function. To gain insight into the ENT gene family, we used experimental and in silico comparative genomic approaches to identify ENT genes in three evolutionarily diverse organisms with completely (or almost completely) sequenced genomes, Homo sapiens, Caenorhabditis elegans and Drosophila melanogaster. We describe the chromosomal location, the predicted ENT gene structure and putative structural topologies of predicted ENT proteins derived from the open reading frames. Despite variations in genomic layout and limited ortholog protein sequence identity (< or =27.45%), predicted topologies of ENT proteins are strikingly similar, suggesting an evolutionary conservation of a prototypic structure. In addition, a similar distribution of protein domains on exons is apparent in all three taxa. These data demonstrate that comparative sequence analyses should be combined with other approaches (such as genomic and proteomic analyses) to fully understand structure, function and evolution of protein families.

Alternative Splicing↗
PubMed2026

A haploid wild yeast resource for exploring the natural ecology of Saccharomyces cerevisiae.

Saccharomyces cerevisiae occurs predominantly in the diploid state in nature, limiting genetic analyses of wild populations. Here, we establish a haploid collection from 32 Taiwanese S. cerevisiae isolates through targeted HO disruption. This resource spans predomesticated Asian wild lineages and enables the investigation of reproductive isolation and ecological trait variation. Although all pairwise hybridizations formed zygotes, many yielded reduced spore viability, revealing strong postzygotic barriers. Genome analyses associated reduced hybrid fertility with lineage-specific structural variation, including elevated levels of intra-chromosomal inversions in H413-8/TW1 and inter-chromosomal rearrangements in PD35A/CHN-V, rather than sequence divergence alone. Phenotyping revealed ecological differentiation, with TW1 favoring cooler growth and a natural hybrid exhibiting heterosis with expanded thermotolerance. Most wild strains grew poorly on maltose, whereas anthropogenic strains displayed enhanced utilization linked to MAL + regulatory alleles and maltose-specific transporters. Together, this haploid collection links structural variation and metabolic divergence to ecological and reproductive differentiation in wild S. cerevisiae.

Saccharomyces cerevisiae↗
PubMed2026

Comprehensive genomic and computational insights into Brucella suis: pan-genome analysis, evolutionary perspectives, and in-silico vaccine design.

BACKGROUND: Brucella suis is a zoonotic intracellular pathogen responsible for brucellosis, mainly in swine and humans. Although numerous genome sequences are publicly available, an integrative genomic analysis combining pan-genome architecture, structural organization, evolutionary relationships, and vaccine-associated targets remains limited. RESULTS: In this study, we analyzed 91 publicly available B.suis genomes to characterize their pan-genome composition and genomic structure. The pan-genome exhibited an open configuration, indicating continued genomic diversification. A total of 2,146 core genes were identified, representing conserved functions essential for species maintenance, while the accessory genome reflected strain-level variability. Phylogenetic reconstruction based on single-copy orthologs revealed distinct evolutionary clades among the strains. A complementary phylogenetic analysis of pan-genome gene presence-absence patterns further supported clade differentiation and highlighted variation in accessory gene repertoires. Comparative synteny and genome structural analyses demonstrated largely conserved chromosomal organization with localized rearrangements across strains. Screening of the core proteome identified 64 putative antigenic proteins with predicted surface localization and immunogenic properties. Additionally, resistance-associated determinants related to tetracycline and doxycycline were detected in one genome within the dataset. CONCLUSIONS: This comprehensive genomic analysis defines the pan-genome structure, evolutionary relationships, and genome organization of B.suis. The integration of core and pan-genome-based phylogenies provides complementary insights into strain diversification, while the identified conserved antigenic candidates offer a foundation for future experimental validation and rational vaccine development strategies.

Genome, Bacterial↗