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PubMed2025

A telomere-to-telomere gap-free genome assembly of the endangered humphead wrasse (Cheilinus undulatus).

Humphead wrasse, Cheilinus undulatus, is an endangered fish species with high economic and ecological value as well as natural sex change from female to male, while sexual selection occurs in breeding aggregations. In our present study, we constructed the first gap-free telomere-to-telomere (T2T) genome assembly for humphead wrasse, by integration of PacBio HiFi, ONT Ultra-long and Hi-C sequencing techniques. With 99% of the entire sequences anchored into 24 chromosomes, this haplotypic genome assembly spans approximately 1.25 Gb and presents a complete set of 48 telomeres and 24 centromeres. In terms of correctness (quality value QV: 53.447) and completeness (BUSCO score: 99.3%), this chromosome-scale assembly is indeed of high quality. We predicted 658.03 Mb of repetitive sequences and annotated 26,609 protein-coding genes in the assembled genome. This high-quality T2T genome assembly not only facilitates the genetic conservation of humphead wrasse, but also offers fundamental genomic data for supporting in-depth investigations on functional genomics, genetic diversity, and selective breeding for this economically important teleost.

Animals↗

PubMed2026

Simulation of CRISPR/Cas9-mediated gene editing for the Vitellogenin gene in Apis mellifera.

CRISPR/Cas9 genome editing provides a powerful framework for interrogating gene function in Apis mellifera. Yet, empirical application remains challenging due to biological constraints, including haplodiploid genetics, narrow embryonic injection window, and the social rearing requirements that complicate functional validation. These constraints necessitate in silico pre-screening to maximize editing success before resource-intensive wet-lab implementation. Within the omnigenic framework, which distinguishes core regulatory genes from peripheral loci buffered by network effects, vitellogenin (Vg) represents an optimal target which is ancestrally dedicated to yolk provisioning; it has been co-opted to orchestrate diverse non-reproductive functions including longevity, stress resistance, immunity, and social behavior. We developed a computational pipeline to design a list of 57 and 56 candidate guide RNAs (gRNA) for targeted Vg knockout, evaluating candidate sites in both functional exons 2 and 3 based on structural accessibility and frameshift efficiency. Comparative analysis revealed complementary strengths in two top-best candidates from initial target pool of predicted gRNAs. The gRNA targeting exon 2 exhibits weaker secondary structure (ΔG = -0.25 kcal/mol versus -2.10 kcal/mol for exon 3), aligning with empirical evidence that sites with ΔG > -1.0 kcal/mol achieve 2-5 × higher Cas9 binding efficiency. This site yielded moderate frameshift frequency (77.8%; 61.9 percentile). Conversely, the predicted editing outcome for the gRNA targeting exon 3, despite stronger structural constraints, demonstrated superior functional disruption metrics demonstrating very high frameshift frequency (88.3%; 95.2 percentile), high in silico editing precision, minimal microhomology-mediated repair bias, and reproducible outcomes wherein nearly all predicted indels disrupt the coding sequence. Protein structure and domain analyses further predict that frameshift edits will generate a truncated protein missing all downstream functional domains. We recommend parallel empirical validation of both exon 2 and exon 3 targets to resolve the trade-off between structural accessibility (favoring higher editing rates) and frameshift efficacy (favoring complete loss-of-function). This dual-target strategy accommodates uncertainty in in vivo performance while maximizing the probability of generating informative phenotypes. Our in silico framework enables rational CRISPR design in non-model organisms by computationally balancing biophysical accessibility with functional impact, accelerating functional genomics in species where empirical optimization faces substantial biological constraints.

Animals↗

PubMed2026

Whole-genome sequences of the dwarf honey bee subgenus Micrapis: Apis andreniformis and Apis florea.

The Micrapis subgenus, which includes the black dwarf honey bee (Apis andreniformis) and the red dwarf honey bee (Apis florea), remains underrepresented in genomic studies despite its ecological significance. Here, we present high-quality de novo genome assemblies for both species, generated using a hybrid sequencing approach combining Oxford Nanopore Technologies long reads with Illumina short reads. The final assemblies are highly contiguous, with contig N50 values of 5.0 Mb (A. andreniformis) and 4.3 Mb (A. florea), representing a major improvement over the previously published A. florea genome. Genome completeness assessments indicate high quality, with BUSCO scores exceeding 98.5% using the Hymenoptera database and k-mer analyses supporting base-level accuracy. Repeat annotation revealed a relatively low repetitive sequence content (∼6%), consistent with other Apis species. Using RNA sequencing data, we annotated 12,189 genes for A. andreniformis and 12,207 genes for A. florea, with ∼98% completeness in predicted proteomes. These genome assemblies provide a valuable resource for comparative and functional genomic studies, with the potential to offer new insights into the genetic basis of dwarf honey bee adaptations.

Male↗

PubMed1991

Frequent rearrangements of rRNA-encoding chromosomes in Giardia lamblia.

The ribosomal RNA (rRNA) genes in Giardia lamblia are present as short tandem arrays of a 5.6 Kb repeat unit on at least six telomeres. Four of these telomeres have the same overall organisation comprising a domain ranging in size from 25 to 300 Kb, delineated chromosome internally by a conserved island of restriction enzyme sites. Cloned lines of G. lamblia derived from the WB strain contain polymorphic subsets of chromosomes encoding rRNA genes. However, changes in the size of the rRNA telomere domains of these polymorphic chromosomes alone cannot account for the total size changes in the chromosomes. The rearrangement events are very frequent: 60% of subcloned lines had discrete rearranged karyotypes that differed from each other, suggesting either an estimated rearrangement rate that may be as high as 3% per division or a cloning-induced rearrangement event. The extreme plasticity of the genome has obvious implications for the maintenance of a functional genome and the control of gene expression in Giardia.

Animals↗

PubMed2004

In silico genetics: identification of a functional element regulating H2-Ealpha gene expression.

Computational tools can markedly accelerate the rate at which murine genetic models can be analyzed. We developed a computational method for mapping phenotypic traits that vary among inbred strains onto haplotypic blocks. This method correctly predicted the genetic basis for strain-specific differences in several biologically important traits. It was also used to identify an allele-specific functional genomic element regulating H2-Ealpha gene expression. This functional element, which contained the binding sites for YY1 and a second transcription factor that is probably serum response factor, is located within the first intron of the H2-Ealpha gene. This computational method will greatly improve our ability to identify the genetic basis for a variety of phenotypic traits, ranging from qualitative trait information to quantitative gene expression data, which vary among inbred mouse strains.

Alleles↗

PubMed2004

Anaerobic microbial dehalogenation.

The natural production and anthropogenic release of halogenated hydrocarbons into the environment has been the likely driving force for the evolution of an unexpectedly high microbial capacity to dehalogenate different classes of xenobiotic haloorganics. This contribution provides an update on the current knowledge on metabolic and phylogenetic diversity of anaerobic microorganisms that are capable of dehalogenating--or completely mineralizing--halogenated hydrocarbons by fermentative, oxidative, or reductive pathways. In particular, research of the past decade has focused on halorespiring anaerobes, which couple the dehalogenation by dedicated enzyme systems to the generation of energy by electron transport-driven phosphorylation. Significant advances in the biochemistry and molecular genetics of degradation pathways have revealed mechanistic and structural similarities between dehalogenating enzymes from phylogenetically distinct anaerobes. The availability of two almost complete genome sequences of halorespiring isolates recently enabled comparative and functional genomics approaches, setting the stage for the further exploitation of halorespiring and other anaerobic dehalogenating microbes as dedicated degraders in biological remediation processes.

Amino Acid Sequence↗

PubMed2004

Potential role of a novel transcriptional coactivator PELP1 in histone H1 displacement in cancer cells.

The estrogen receptor plays an important role in breast cancer progression. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), also called modulator of nongenomic activity of estrogen receptor (MNAR), a novel coactivator of estrogen receptor, modulates estrogen receptor transactivation functions. The mechanisms by which PELP1 modulates estrogen receptor genomic functions is not known. Here, using biochemical and scanning confocal microscopic analysis, we have demonstrated nuclear localization and functional implications of PELP1. Subnuclear fractionation showed PELP1 association with chromatin and nuclear matrix fractions. Ligand stimulation promoted recruitment of PELP1 to 17beta-estradiol responsive promoters, its colocalization with acetylated H3, and increased PELP1-associated histone acetyltransferase enzymatic activity. Far Western analysis revealed that PELP1 interacts with histone 1 and 3, with more preference toward histone 1. Using deletion analysis, we have identified the PELP1 COOH-terminal region as the histone 1 binding site. The PELP1 mutant lacking histone 1-binding domain acts as a dominant-negative and blocks estrogen receptor alpha-mediated transcription. Chromatin immunoprecipitation analysis showed a cyclic association and dissociation of PELP1 with the promoter, with recruitment of histone 1 and PELP1 occurring in opposite phases. PELP1 overexpression increased the micrococcal nuclease sensitivity of estrogen response element-containing nucleosomes. Our results provide novel insights about the transcription regulation of PELP1 and suggest that PELP1 participates in chromatin remodeling activity via displacement of histone 1 in cancer cells.

Bone Neoplasms↗

PubMedDate not supplied

Defining the mandate of tuberculosis research in a postgenomic era.

The identification of Mycobacterium tuberculosis by Robert Koch in 1882 as the causative agent of tuberculosis, the release of the drug rifampicin in 1970 and the sequencing of the M. tuberculosis genome in 1998 are three major events that have revolutionized tuberculosis research. In spite of these breakthroughs, the continued status of tuberculosis as the largest killer amongst infectious diseases is an issue of major concern. Although directly observed short course chemotherapy exists to treat the disease, the emergence of drug-resistant strains has severely threatened the efficacy of the treatment. The recent sequencing of the M. tuberculosis genome holds promise for the development of new vaccines and the design of new drugs. This is all the more possible when the information from the genome sequence is combined with proteomics and structural and functional genomics. Such an integrated approach has led to the birth of a new field of research christened 'postgenomics' that holds substantial promise for the identification of novel drug targets and the potential to aid the development of new chemotherapeutic compounds to treat tuberculosis. The challenge before the scientific community therefore lies in elucidation of the wealth of information provided by the genome sequence and its translation into the design of novel therapies for the disease. All the major developments in the field of tuberculosis research after the sequencing of the M. tuberculosis genome will be discussed in this review.

Biomedical Research↗

PubMed2003

Virus-induced gene silencing.

In the postgenomic era, large-scale functional genomic approaches are necessary for converting sequence information into functional information. A para-genetic approach, called virus-induced gene silencing (VIGS), offers a rapid means of gaining insight into gene function in plants. VIGS system could be used to suppress endogenous gene expression by infecting plants with a recombinant virus vector (VIGS vector) carrying host-derived sequence. Here, we describe the use of tobacco rattle virus (TRV)-based VIGS technique to study gene function in Nicotiana benthamiana and tomato.

Gene Silencing↗

PubMed1999

A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat.

The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of two genomic maps: a dense genetic linkage map of the rat and the first radiation hybrid (RH) map of the rat. The genetic map was constructed in two F2 intercrosses (SHRSP x BN and FHH x ACI), containing a total of 4736 simple sequence length polymorphism (SSLP) markers. Allele sizes for 4328 of the genetic markers were characterized in 48 of the most commonly used inbred strains. The RH map is a lod >/= 3 framework map, including 983 SSLPs, thereby allowing integration with markers on various genetic maps and with markers mapped on the RH panel. Together, the maps provide an integrated reference to >3000 genes and ESTs and >8500 genetic markers (5211 of our SSLPs and >3500 SSLPs developed by other groups). [Bihoreau et al. (1997); James and Tanigami, RHdb (http:www.ebi.ac.uk/RHdb/index.html); Wilder (http://www.nih.gov/niams/scientific/ratgbase); Serikawa et al. (1992); RATMAP server (http://ratmap.gen.gu.se)] RH maps (v. 2.0) have been posted on our web sites at http://goliath.ifrc.mcw.edu/LGR/index.html or http://curatools.curagen.com/ratmap. Both web sites provide an RH mapping server where investigators can localize their own RH vectors relative to this map. The raw data have been deposited in the RHdb database. Taken together, these maps provide the basic tools for rat genomics. The RH map provides the means to rapidly localize genetic markers, genes, and ESTs within the rat genome. These maps provide the basic tools for rat genomics. They will facilitate studies of multifactorial disease and functional genomics, allow construction of physical maps, and provide a scaffold for both directed and large-scale sequencing efforts and comparative genomics in this important experimental organism.

Alleles↗

PubMed2006

[Latest progress on the chicken genome project].

The publication of draft sequence of the chicken genome in early 2004 marks expressly the start of functional genomics of poultry. Chicken is not only a widely raised economic farm animal, but also a valuable model organism for the study of life sciences. The draft sequence of the chicken genome has significant impact on both animal breeding and basic biological research. The current progress of the chicken genome research is reviewed in this paper, which includes data from the chicken genome, its physical map, genetic linkage map and comparative genome map, as well as expressed sequence tags and bioinformatics. Potential applications of chicken genome research are also envisaged.

Animals↗

PubMed2005

CoGenT++: an extensive and extensible data environment for computational genomics.

MOTIVATION: CoGenT++ is a data environment for computational research in comparative and functional genomics, designed to address issues of consistency, reproducibility, scalability and accessibility. DESCRIPTION: CoGenT++ facilitates the re-distribution of all fully sequenced and published genomes, storing information about species, gene names and protein sequences. We describe our scalable implementation of ProXSim, a continually updated all-against-all similarity database, which stores pairwise relationships between all genome sequences. Based on these similarities, derived databases are generated for gene fusions--AllFuse, putative orthologs--OFAM, protein families--TRIBES, phylogenetic profiles--ProfUse and phylogenetic trees. Extensions based on the CoGenT++ environment include disease gene prediction, pattern discovery, automated domain detection, genome annotation and ancestral reconstruction. CONCLUSION: CoGenT++ provides a comprehensive environment for computational genomics, accessible primarily for large-scale analyses as well as manual browsing.

Chromosome Mapping↗

PubMed2005

Bioinformatic methods for integrating whole-genome expression results into cellular networks.

Extracting a comprehensive overview from the huge amount of information arising from whole-genome analyses is a significant challenge. This review critically surveys the state of the art methods that are used to connect information from functional genomic studies to biological function. Cluster analysis methods for inferring the correlation between genes are discussed, as are the methods for integrating gene expression information with existing information on biological pathways and the methods that combine cluster analysis with biological information to reconstruct novel biological networks.

Cluster Analysis↗

PubMed2006

Regulation of nucleosome stability as a mediator of chromatin function.

Interactions among regulatory proteins, enzymes and DNA are required to use the information encoded in genomes. In eukaryotes, the location and timing of interactions between these proteins and DNA is determined in large part by whether DNA at a given locus is packaged into a nucleosome. Given the central role of nucleosome formation in regulating genome function, many mechanisms have evolved to control nucleosome stability at loci across the genome. New conclusions about the role of the DNA sequence itself in the regulation of nucleosome stability have come from two new types of experiment: high-resolution mapping of in vivo nucleosome occupancy on a genomic scale; and in vivo versus in vitro comparisons of nucleosome stability on natural DNA templates. These new types of data raise intriguing questions about the evolutionary constraints on DNA sequence with regard to nucleosome formation, and at long last might enable the derivation of DNA sequence-based rules that produce reliable predictions of nucleosome behavior.

Animals↗

PubMed2004

Comparative genomics.

The genomes from three mammals (human, mouse, and rat), two worms, and several yeasts have been sequenced, and more genomes will be completed in the near future for comparison with those of the major model organisms. Scientists have used various methods to align and compare the sequenced genomes to address critical issues in genome function and evolution. This review covers some of the major new insights about gene content, gene regulation, and the fraction of mammalian genomes that are under purifying selection and presumed functional. We review the evolutionary processes that shape genomes, with particular attention to variation in rates within genomes and along different lineages. Internet resources for accessing and analyzing the treasure trove of sequence alignments and annotations are reviewed, and we discuss critical problems to address in new bioinformatic developments in comparative genomics.

Animals↗

PubMed2006

A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma.

A novel genome-wide screen that combines patient outcome analysis with array comparative genomic hybridization and mRNA expression profiling was developed to identify genes with copy number alterations, aberrant mRNA expression, and relevance to survival in glioblastoma. The method led to the discovery of physical gene clusters within the cancer genome with boundaries defined by physical proximity, correlated mRNA expression patterns, and survival relatedness. These boundaries delineate a novel genomic interval called the functional common region (FCR). Many FCRs contained genes of high biological relevance to cancer and were used to pinpoint functionally significant DNA alterations that were too small or infrequent to be reliably identified using standard algorithms. One such FCR contained the EphA2 receptor tyrosine kinase. Validation experiments showed that EphA2 mRNA overexpression correlated inversely with patient survival in a panel of 21 glioblastomas, and ligand-mediated EphA2 receptor activation increased glioblastoma proliferation and tumor growth via a mitogen-activated protein kinase-dependent pathway. This novel genome-wide approach greatly expanded the list of target genes in glioblastoma and represents a powerful new strategy to identify the upstream determinants of tumor phenotype in a range of human cancers.

Brain Neoplasms↗

PubMed2002

An efficient algorithm for large-scale detection of protein families.

Detection of protein families in large databases is one of the principal research objectives in structural and functional genomics. Protein family classification can significantly contribute to the delineation of functional diversity of homologous proteins, the prediction of function based on domain architecture or the presence of sequence motifs as well as comparative genomics, providing valuable evolutionary insights. We present a novel approach called TRIBE-MCL for rapid and accurate clustering of protein sequences into families. The method relies on the Markov cluster (MCL) algorithm for the assignment of proteins into families based on precomputed sequence similarity information. This novel approach does not suffer from the problems that normally hinder other protein sequence clustering algorithms, such as the presence of multi-domain proteins, promiscuous domains and fragmented proteins. The method has been rigorously tested and validated on a number of very large databases, including SwissProt, InterPro, SCOP and the draft human genome. Our results indicate that the method is ideally suited to the rapid and accurate detection of protein families on a large scale. The method has been used to detect and categorise protein families within the draft human genome and the resulting families have been used to annotate a large proportion of human proteins.

Algorithms↗

PubMed2005

A CELD-fusion method for rapid determination of the DNA-binding sequence specificity of novel plant DNA-binding proteins.

The current focus of many functional genomic studies is on the elucidation of gene regulatory networks. The functional analyses of transcription factors and their DNA-binding sites, in conjunction with genome-wide expression profiling, are crucial in understanding of gene regulatory networks. This paper describes an efficient and easy method for characterizing the DNA-binding sequence specificity of novel plant transcription factors. This new method is based on the fusion of a DNA-binding protein (DBP) to 6xHis-tagged cellulase D (CELD), which serves both as a means for affinity purification of DBP-DNA complex in the selection of binding sites from a pool of biotinylated random-sequence oligonucleotides and as a reporter for measurement of DNA-binding activity. Thus, it eliminates the use of radioactivity and gel electrophoresis techniques currently used for purification of DBP-DNA complexes and assays of DNA-binding activity. The effectiveness of this method was demonstrated by the success of simultaneous selection of the binding sites of nine plant DBPs from four superfamilies (AP2, bHLH, NAC and MYB). The high-throughput capacity of CELD-based DNA-binding assays allows the quantitative analysis of the binding sequence specificity from a large number of DBP-selected oligonucleotides. The binding sequence specificity of three novel transcription factors (rice OsbHLH66, wheat TaNAC69 and TaMYB80), determined with this method, is presented. This new method provides the capacity of high-throughput analysis on the DNA-binding sequence specificity of a large number of putative transcription factors, predicted on the basis of conserved DNA-binding domains.

Base Sequence↗