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Results for “genomic characterization”

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PubMed2006

Genomic characterization of ribitol teichoic acid synthesis in Staphylococcus aureus: genes, genomic organization and gene duplication.

BACKGROUND: Staphylococcus aureus or MRSA (Methicillin Resistant S. aureus), is an acquired pathogen and the primary cause of nosocomial infections worldwide. In S. aureus, teichoic acid is an essential component of the cell wall, and its biosynthesis is not yet well characterized. Studies in Bacillus subtilis have discovered two different pathways of teichoic acid biosynthesis, in two strains W23 and 168 respectively, namely teichoic acid ribitol (tar) and teichoic acid glycerol (tag). The genes involved in these two pathways are also characterized, tarA, tarB, tarD, tarI, tarJ, tarK, tarL for the tar pathway, and tagA, tagB, tagD, tagE, tagF for the tag pathway. With the genome sequences of several MRSA strains: Mu50, MW2, N315, MRSA252, COL as well as methicillin susceptible strain MSSA476 available, a comparative genomic analysis was performed to characterize teichoic acid biosynthesis in these S. aureus strains. RESULTS: We identified all S. aureus tar and tag gene orthologs in the selected S. aureus strains which would contribute to teichoic acids sythesis. Based on our identification of genes orthologous to tarI, tarJ, tarL, which are specific to tar pathway in B. subtilis W23, we also concluded that tar is the major teichoic acid biogenesis pathway in S. aureus. Further analyses indicated that the S. aureus tar genes, different from the divergon organization in B. subtilis, are organized into several clusters in cis. Most interesting, compared with genes in B. subtilis tar pathway, the S. aureus tar specific genes (tarI,J,L) are duplicated in all six S. aureus genomes. CONCLUSION: In the S. aureus strains we analyzed, tar (teichoic acid ribitol) is the main teichoic acid biogenesis pathway. The tar genes are organized into several genomic groups in cis and the genes specific to tar (relative to tag): tarI, tarJ, tarL are duplicated. The genomic organization of the S. aureus tar pathway suggests their regulations are different when compared to B. subtilis tar or tag pathway, which are grouped in two operons in a divergon structure.

Amino Acid Sequence↗

PubMed2005

Genomic characterization and physical mapping of two fucosyltransferase genes in Medicago truncatula.

Fucosyltransferases catalyse fucose transfer onto oligosaccharides. Two fucosylated structures have been identified in plants: the alpha1,4-fucosylated Lewis-a epitope and the alpha1,3-fucosylated core. Here we report the cloning, genomic characterization, and physical mapping of two genes encoding proteins similar to alpha1,4-fucosyltransferase (EC 2.4.1.65, MtFUT1) and alpha1,3-fucosyltransferase (EC 2.4.1.214, MtFUT2) in Medicago truncatula. Analysis of the genomic organization of the fucosyltransferase genes in M. truncatula, revealed the presence of two genomic variants of the MtFUT1 gene coding sequence, one containing a single intron and the other intronless, whereas in MtFUT2, the gene coding region is interrupted by four introns. Using for the first time fluorescence in situ hybridization (FISH) to physically map fucosyltransferase genes in plants, this study reveals a high genomic dispersion of these genes in Medicago. The MtFUT1 genes are mapped on chromosomes 4, 7, and 8, colocalizing on three of the five MtFUT2 loci. Chromosomes 1 and 5 carry the additional MtFUT2 loci. Moreover, the intensity of the FISH signals reveals marked differences in the number of gene copies per locus for both genes. Simultaneous mapping of rRNA genes on chromosome 5 shows that several MTFUT2 gene loci are inserted within the rDNA array. Insertions of coding DNA sequences into the rDNA repeats were never reported to date.

Base Sequence↗

PubMed2026

Phenotypic and genomic characterization of a blaOXA-181-producing ST656 Klebsiella pneumoniae isolate from China.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a major global health threat due to its rapid dissemination and severely limited treatment options. Here, we report the phenotypic and genomic characterization of an ST656 K. pneumoniae clinical isolate carrying blaOXA-181 in China. Antimicrobial susceptibility testing confirmed carbapenem resistance, whereas the isolate remained susceptible to aztreonam, amikacin and trimethoprim/sulfamethoxazole, with a colistin MIC of ≤0.5 μg/mL. Whole-genome sequencing identified the blaOXA-181 gene on a 51,391-bp ColKP3/IncX3 plasmid co-harboring multiple resistance determinants. Conjugation assays yielded blaOXA-181 -positive transconjugants at a recovery frequency of 2 × 10-4. Following serial passage, blaOXA-181 was stably maintained for 100 generations. Comparative genomic analysis showed that the blaOXA-181-carrying plasmid shared a highly conserved backbone with plasmids from geographically diverse isolates, while KP413706 represents a distinct ST656 lineage. These findings expand the genomic evidence for blaOXA-181-carrying ST656 K. pneumoniae in China and underscore the urgent need for enhanced genomic surveillance and stringent infection control strategies.

Carbapenem-resistant Klebsiella pneumoniae↗

PubMed2026

Genomic characterization of novel human-associated CTX-M-15-producing Serratia nevei ST625 lineage infecting a vulnerable loggerhead sea turtle.

BACKGROUND: Serratia nevei is a newly classified and opportunistic bacterial species belonging to the Serratia marcescens complex (SMC). Genomic data from this species is highly relevant for public health and epidemiological tracking. OBJECTIVE: To report the first identification and genomic characterization of extended-spectrum β-lactamase (CTX-M-15)-producing S. nevei sequence type (ST) ST625 lineage infecting a vulnerable loggerhead sea turtle. METHODS: Strain BP02 was recovered from the coelomic cavity of a loggerhead sea turtle (Caretta caretta) admitted to a rehabilitation center in southeastern Brazil. MALDI-TOF MS was initially used for species identification and was further confirmed by whole-genome sequencing on the Illumina HiSeq platform, followed by ANI, dDDH, multilocus sequence typing, resistome, plasmidome, virulome, and SNP-based phylogenomic analyses. RESULTS: Strain BP02 exhibited a multidrug-resistant profile, including resistance to third- and fourth-generation cephalosporins. Genomic analyses identified BP02 as S. nevei ST625 carrying blaCTX-M-15 within the ISEcp1-blaCTX-M-15-wbuC-ΔTn2 genetic environment, in addition to multiple AMR determinants and the IncC plasmid replicon. Phylogenomic analysis demonstrated close relatedness between BP02 and human clinical ST625 strains, previously reported in São Paulo, Brazil, including a urine-derived strain isolated in 2019, differing by only 27 SNPs. Notably, all publicly available ST625 genomes were associated with human clinical sources and displayed multidrug resistance genotypes. CONCLUSION: This study expands the current knowledge regarding the ecology and genomic features of S. nevei, demonstrating the emergence of a human multidrug-resistant clone in marine wildlife. Our findings reinforce the importance of monitoring clinically relevant SMC members across distinct ecological niches within a One Health perspective.

ESBL↗

PubMed2026

Genomic characterization of blaIMP-harboring plasmids in Klebsiella spp.

UNLABELLED: The spread of carbapenem-resistant Klebsiella spp. poses a significant public health threat, partly due to the acquisition of the blaIMP genes, which encode IMP-type metallo-β-lactamases. These enzymes confer resistance to a broad spectrum of β-lactam antibiotics, including carbapenems, thereby complicating treatment options. This study aims to provide a comprehensive genomic characterization of blaIMP-harboring plasmids across different species within the genus Klebsiella, based on the genomic characteristics of the plasmid pT117-2 of Klebsiella variicola strain T117 isolated from clinical settings in China, along with all available blaIMP-harboring plasmids of Klebsiella spp. fromthe GenBank database until 26 April 2025. Among the 123 blaIMP-harboring plasmids of Klebsiella spp., nine variants were identified, with blaIMP-4 (carried by 69 plasmids) and blaIMP-1 (carried by 37 plasmids) being the most prevalent. The blaIMP-4 gene was associated with IncN type (~50 kb, conjugative) and untypeable (~300 kb, non-mobilizable) plasmids in China, whereas in Australia, it was linked to IncC (~200 kb) and IncM2 (~80 kb) type conjugative plasmids. Meanwhile, blaIMP-1 was found to be associated with IncN (~50 kb), IncM (~80 kb), and IncFII (80 ~200 kb) type conjugative plasmids mainly in Japan. Notably, our results highlight the prevalence of IncN-type conjugative plasmids, including the plasmid pT117-2 identified in this study, as key vehicles for the dissemination of blaIMP genes. This study provides critical insights into the genetic mechanisms of blaIMP-harboring plasmids persistence and spread in Klebsiella spp., advancing our understanding of their dissemination. IMPORTANCE: Carbapenem-resistant Enterobacterales (CRE) mediated by metallo-β-lactamases (MBLs) pose a major global public health threat that challenges clinical antimicrobial therapy; based on our study, blaIMP-4 in China is predominantly associated with IncN plasmids (forming the "IncN-blaIMP-4-qnrS1" axis), while blaIMP-1 in Japan links to IncN/IncM/IncFII plasmids, with these regional differences highlighting the need for geographically targeted surveillance, and notably, the high-risk ST146 Klebsiella variicola carrying blaIMP-4 on a conjugative IncN plasmid serves as an underrecognized reservoir for resistance genes, extending surveillance beyond common pathogenic Enterobacterales; limitations of this study include restricted sample size and geographic scope, and future research should validate these patterns via multi-center studies, explore plasmid evolution mechanisms, and integrate findings into routine surveillance to optimize antibiotic stewardship and infection control, thereby mitigating the global spread of MBL-mediated CRE.

Plasmids↗

PubMed2005

Genomic characterization and linkage mapping of the apple allergen genes Mal d 2 (thaumatin-like protein) and Mal d 4 (profilin).

Four classes of apple allergens (Mal d 1, -2, -3 and -4) have been reported. By using PCR cloning and sequencing approaches, we obtained genomic sequences of Mal d 2 (thaumatin-like protein) and Mal d 4 (profilin) from the cvs Prima and Fiesta, the two parents of a European reference mapping population. Two copies of the Mal d 2 gene (Mal d 2.01 A and Mal d 2.01 B) were identified, which primarily differed in the length of a single intron (378 or 380 nt) and in one amino acid in the signal peptide. Both Mal d 2.01 A and Mal d 2.01 B were mapped at identical position on linkage group 9. Genomic characterization of four Mal d 4 genes (Mal d 4.01 A and B, Mal d 4.02 A and Mal d 4.03 A) revealed their complete gDNA sequences which varied among genes in length from 862 to 2,017 nt. They all contained three exons of conserved length: 123, 138, and 135 nt. Mal d 4.01 appeared to be duplicated in two copies and located on linkage group 9. Mal d 4.02 A and Mal d 4.03 A were single copy genes located on linkage group 2 and 8, respectively.

Allergens↗

PubMed2026

Genomic characterization of carbapenemase-producing Enterobacterales from wastewater reveals the convergence of KPC-2 and GES-16 in Brazil.

Carbapenemase-producing Enterobacterales (CPE) pose a significant public health concern due to the limited therapeutic options and increasing dissemination outside clinical settings. Wastewater treatment plants (WWTPs) have been proposed as relevant environmental reservoirs for antimicrobial-resistant bacteria and mobile genetic elements. In this study, we performed genomic characterization of CPE strains recovered from raw wastewater samples from the influents of different WWTPs. Antimicrobial susceptibility testing revealed multidrug resistance, including coresistance to carbapenems and polymyxins, among Klebsiella pneumoniae, Enterobacter asburiae, and Enterobacter kobei strains. Whole-genome sequencing identified the convergence of the blaKPC-2 and blaGES-16 genes, as well as the presence of blaGES-5 in E. kobei sequence type (ST) 540 strains. Moreover, the blaKPC-2 gene was detected in K. pneumoniae strains belonging to high-risk clones ST11 (capsular types KL64 and KL15) and ST307 (capsular type KL102), and E. asburiae ST384. The blaGES-5 and blaGES-16 genes were associated with class 1 integrons, while the blaKPC-2 gene was embedded within transposons (Tn4401a, Tn4401i, and Tn3-like) and insertion sequences (ISKpn27 and ISKpn6). Notably, genomic analyses and literature review demonstrated that the blaGES-16 gene remains unique to Brazil. The putative pathogenic potential of carbapenem-resistant K. pneumoniae ST11 was also assessed. These findings support the environmental circulation of clinically relevant Enterobacterales genotypes and emphasize the potential role of WWTPs as conduits for CPE dissemination, if not adequately operated. Therefore, genomic surveillance in extra-hospital settings may contribute to a better understanding of antimicrobial resistance ecology and inform One Health mitigation strategies.

Brazil↗

PubMed2004

Genomic characterization of a Brazilian TT virus isolate closely related to SEN virus-F.

SEN virus (SENV) is a circular, single stranded DNA virus that has been first characterized in the serum of a human immunodeficiency virus type 1 (HIV-1)-infected patient. Eight genotypes of SENV (A-H) have been identified and further recognized as variants of TT virus (TTV) in the family Circoviridae. Here we describe the first genomic characterization of a SENV isolate (5-A) from South America. Using 'universal' primers, able to amplify most, if not all, TTV/SENV genotypes, a segment of > 3 kb was amplified by polymerase chain reaction from the serum of an HIV-1 infected patient. The amplicon was cloned and a 3087-nucleotide sequence was determined, that showed a high (85%) homology with the sequence of the Italian isolate SENV-F. Proteins encoded by open reading frames (ORFs) 1 to 4 consisted of 758, 129, 276, and 267 amino acids, respectively. By phylogenetic analysis, isolate 5-A was classified into TTV genotype 19 (phylogenetic group 3), together with SENV-F and TTV isolate SAa-38.

Adult↗

PubMed2001

CUX2, a potential regulator of NCAM expression: genomic characterization and analysis as a positional candidate susceptibility gene for bipolar disorder.

We have previously reported cosegregation of bipolar affective disorder and Darier disease, a dominant skin disorder with a neuropsychiatric component. The gene for Darier disease was mapped to chromosome 12q23-q24.1 and linkage studies have subsequently implicated this region as harboring a susceptibility gene for bipolar affective disorder. We have genomically characterized the human homologue of murine Cux-2, a neuronal-specific transcription factor potentially involved in the regulation of neural cell adhesion molecule expression that maps to this region. Also, in a panel of 15 unrelated bipolar patients from multiply affected families showing increased allele sharing at markers in the 12q23-q24.1 region, we performed mutational screening of the CUX2 coding sequence, and 5' untranslated region (5' UTR). Resulting sequence were analyzed in a large sample of bipolar patients (n = 218) and control subjects (n = 218). No evidence was found for the involvement of variants within the CUX2 coding, or 5' UTR sequence in producing susceptibility to bipolar disorder.

Adult↗

PubMed2004

Immunomagnetic enrichment, genomic characterization, and prognostic impact of circulating melanoma cells.

PURPOSE: The finding of melanoma cells in the peripheral blood, thus far mainly inferred from the PCR-based demonstration of tyrosinase mRNA, has been associated with metastatic melanoma. Neither the malignant nature nor the prognostic significance of circulating cells could be established. To address this question, we analyzed immunomagnetically isolated circulating melanoma cells for chromosomal aberrations and performed a clinical follow-up study of the enrolled patients. EXPERIMENTAL DESIGN: In a prospective study, blood samples were taken from 164 melanoma patients and 50 donors without malignant disease. Circulating melanoma cells were enriched by immunomagnetic cell sorting using a murine monoclonal antibody against the melanoma-associated chondroitin sulfate proteoglycan. To prove the malignant origin of the positive cells and to define their chromosomal aberrations, we analyzed the genomes of 15 individually isolated cells from seven patients by single-cell comparative genomic hybridization (SCOMP). RESULTS: Absolute and relative frequencies of circulating melanoma cells were associated with stage and with the presence or absence of detectable tumor. The detection of two or more cells correlated significantly with a reduced survival of patients with metastatic melanoma. All of the cells that were analyzed by SCOMP displayed multiple chromosomal changes and carried aberrations typical for melanoma. CONCLUSIONS: Immunomagnetic enrichment enables isolation and genomic characterization of circulating melanoma cells. The prognostic impact on survival of metastatic patients apparently reflects the aggressiveness of an ongoing tumor spread. Direct genomic analysis of the enriched and isolated cells will help to clarify the molecular-genetic basis of the establishment of generalized melanoma.

Antibodies, Monoclonal↗

PubMed2001

Genomic characterization of wild-type measles viruses that circulated in different states in Brazil during the 1997 measles epidemic.

Despite the marked reduction in the incidence of measles in Brazil, a measles epidemic occurred in this country in 1997. The measles cases observed during this epidemic began to reappear in large numbers in São Paulo, and spread to Rio de Janeiro and other Brazilian states. In the present study molecular biology techniques were used for the detection and genomic characterization of measles viruses from clinical samples such as urine and nasopharyngeal secretions collected in the states of Rio de Janeiro, Minas Gerais and Paraná, during the 1997 epidemic. RT-PCR and nucleotide sequence analysis of part of the carboxyl-terminal region of the nucleoprotein gene of measles viruses obtained directly from clinical samples or from infected cell cultures during this epidemic classified all as wild-type of genotype D6. As the genotype D6 was identified in different Brazilian states, this study demonstrated that this genotype was circulating in Brazil during the 1997 epidemic.

Adult↗

PubMed2004

Genomic characterization of a novel pair of ID genes in the rainbow trout (Oncorhynchus mykiss).

The ID (inhibitors of DNA binding/differentiation) proteins represent a family of dominant negative regulators of the basic helix-loop-helix transcription factors whose activities result in delayed cell differentiation and prolonged proliferation. A pair of expressed sequence tag clones with homologies to the ID proteins were identified and used to screen a rainbow trout bacterial artificial chromosome (BAC) library to identify clones containing homologues sequences. Phylogenetic analysis of the predicted amino acid sequences revealed close similarities to the rainbow trout ID1 protein, the genes were therefore classified as rainbow trout ID1B and ID1C. Genome characterization based on BAC sequencing showed each gene to have two exons separated by a small intron. The genes are 83% similar in their transcribed regions, yet they are only 64 and 65% similar in the upstream and downstream sequences, respectively. Using reverse transcription polymerase chain reaction, we found both genes to be expressed in a variety of tissues in the adult rainbow trout.

Animals↗

PubMed2003

Molecular cloning, genomic characterization and over-expression of a novel gene, XRRA1, identified from human colorectal cancer cell HCT116Clone2_XRR and macaque testis.

BACKGROUND: As part of our investigation into the genetic basis of tumor cell radioresponse, we have isolated several clones with a wide range of responses to X-radiation (XR) from an unirradiated human colorectal tumor cell line, HCT116. Using human cDNA microarrays, we recently identified a novel gene that was down-regulated by two-fold in an XR-resistant cell clone, HCT116Clone2_XRR. We have named this gene as X-ray radiation resistance associated 1 (XRRA1) (GenBank BK000541). Here, we present the first report on the molecular cloning, genomic characterization and over-expression of the XRRA1 gene. RESULTS: We found that XRRA1 was expressed predominantly in testis of both human and macaque. cDNA microarray analysis showed three-fold higher expression of XRRA1 in macaque testis relative to other tissues. We further cloned the macaque XRRA1 cDNA (GenBank AB072776) and a human XRRA1 splice variant from HCT116Clone2_XRR (GenBank AY163836). In silico analysis revealed the full-length human XRRA1, mouse, rat and bovine Xrra1 cDNAs. The XRRA1 gene comprises 11 exons and spans 64 kb on chromosome 11q13.3. Human and macaque cDNAs share 96% homology. Human XRRA1 cDNA is 1987 nt long and encodes a protein of 559 aa. XRRA1 protein is highly conserved in human, macaque, mouse, rat, pig, and bovine. GFP-XRRA1 fusion protein was detected in both the nucleus and cytoplasm of HCT116 clones and COS-7 cells. Interestingly, we found evidence that COS-7 cells which over-expressed XRRA1 lacked Ku86 (Ku80, XRCC5), a non-homologous end joining (NHEJ) DNA repair molecule, in the nucleus. RT-PCR analysis showed differential expression of XRRA1 after XR in HCT116 clones manifesting significantly different XR responses. Further, we found that XRRA1 was expressed in most tumor cell types. Surprisingly, mouse Xrra1 was detected in mouse embryonic stem cells R1. CONCLUSIONS: Both XRRA1 cDNA and protein are highly conserved among mammals, suggesting that XRRA1 may have similar functions. Our results also suggest that the genetic modulation of XRRA1 may affect the XR responses of HCT116 clones and that XRRA1 may have a role in the response of human tumor and normal cells to XR. XRRA1 might be correlated with cancer development and might also be an early expressed gene.

Amino Acid Sequence↗

PubMed2026

First Isolation and Genomic Characterization of BVDV-1c in Przewalski's Gazelle (Procapra przewalskii) from the Qinghai-Tibet Plateau, China.

Przewalski's gazelle (Procapra przewalskii) is an endangered ungulate endemic to the Qinghai-Tibet Plateau of China. Increasing habitat alteration and close contact with domestic livestock have raised concerns about cross-species pathogen transmission, yet infectious disease studies in this species remain limited. To determine the etiology of illness in two deceased gazelles from a conservation facility in Qinghai Province, we screened samples for a panel of pathogens, including Mycoplasma ovipneumoniae, Clostridium perfringens toxin genes, Mannheimia haemolytica, Klebsiella pneumoniae, Mycoplasma capricolum subsp. capripneumoniae, Pasteurella multocida, Peste des petits ruminants virus (PPRV), Bovine viral diarrhea virus (BVDV), and Infectious bovine rhinotracheitis virus (IBRV), using PCR and RT-PCR. BVDV-specific nucleic acids were detected in tissue samples from both individuals, whereas all other targeted pathogens tested negative. The virus was successfully isolated in Madin-Darby Bovine Kidney (MDBK) cells and confirmed by RT-PCR, followed by whole-genome sequencing of the isolate, which was designated QH PSYL 2026. Phylogenetic analysis based on the full-length genome and 5'UTR sequences assigned the isolate to the BVDV-1c subgenotype. Notably, its 5'UTR sequence shared 100% identity with those of local cattle-derived BVDV strains, providing molecular evidence suggestive of an epidemiological linkage between wildlife and livestock. Integrating clinical signs, gross pathology, and laboratory results, the cases were consistent with BVDV infection as the primary presumptive etiology. To our knowledge, this is the first report of BVDV infection, virus isolation, and genomic characterization in Przewalski's gazelle. The detection of a BVDV-1c strain in this endangered species highlights the potential threat that livestock-associated pathogens pose to wildlife on the Qinghai-Tibet Plateau. These findings furnish crucial baseline data for disease surveillance, molecular epidemiology, and conservation management of Przewalski's gazelle and provide valuable scientific evidence for wildlife disease prevention and control in plateau ecosystems.

BVDV-1c↗

PubMed2003

Genomic characterization and expression of mouse prestin, the motor protein of outer hair cells.

We previously identified the gerbil gene (gPres) that encodes prestin, the putative motor protein responsible for outer hair cell (OHC) electromotility. Here we report the cloning and characterization of the complete genomic structure of the mouse Prestin (mPres) gene. We performed 5'- and 3'-RACE to determine the size and identity of the full-length mRNA transcript. The mPres gene encodes a protein 96% identical to the gPres gene product. The prestin open reading frames are 91% identical at the nucleotide level. Using an antibody raised against the N-terminus of gerbil Prestin, we observed mPrestin expression by immunofluorescence in the lateral membrane of mouse OHCs and found no detectable expression elsewhere in the organ of Corti. On the basis of the available genomic sequence from mouse Chromosome (Chr) 5, we concluded that the mPres gene is centromerically related to and resides within 19 kb of, the Reln gene. We were also able to characterize the exon/intron junctions of mPres by using cDNA/genomic sequence comparisons, as well as exon-exon PCR and sequencing. The mPres gene has 18 exons that encode protein and two exons in the 5' UTR. A CpG island, located at the start of exon 1, is a potential transcription start site. Sequence analysis of the ~500 bp upstream from exon 1 revealed multiple potential transcription factor binding sites, including both TATA and GC boxes, as well as other regulatory-element binding sites.

Amino Acid Sequence↗

PubMed2001

DACH: genomic characterization, evaluation as a candidate for postaxial polydactyly type A2, and developmental expression pattern of the mouse homologue.

The gene DACH is a human homologue of Drosophila melanogaster dachshund (dac), which encodes a nuclear factor essential for determining cell fates in the eye, leg, and nervous system of the fly. To investigate possible connections between DACH and inherited developmental disorders, we have characterized the human DACH genomic structure and investigated the tissue and cellular distribution of the mouse DACH1 protein during development. DACH spans 400 kb and is encoded by 12 exons. The predominant DACH transcript is 5.2 kb and encodes a 706-amino-acid protein with an observed molecular weight of 97 kDa.DACH mRNA was detected in multiple adult human tissues including kidney and heart. The mouse DACH1 protein was immunolocalized to specific cell types within the developing kidneys, eyes, cochleae, and limb buds. Data suggest genetic linkage of the limb bud patterning defect postaxial polydactyly type A (designated PAP-A2, MIM 602085) to a 28-cM interval on chromosome 13 that includes DACH. However, mutation analysis of DACH in this PAP-A2 pedigree revealed no sequence differences in the coding region, splice sites, or proximal promoter region. The data presented will allow for the analysis of DACH as a candidate for other developmental disorders affecting the limbs, kidneys, eyes, ears, and other sites of DACH expression.

Alternative Splicing↗

PubMed2005

Genomic characterization reveals a simple histone H4 acetylation code.

The histone code hypothesis holds that covalent posttranslational modifications of histone tails are interpreted by the cell to yield a rich combinatorial transcriptional output. This hypothesis has been the subject of active debate in the literature. Here, we investigated the combinatorial complexity of the acetylation code at the four lysine residues of the histone H4 tail in budding yeast. We constructed yeast strains carrying all 15 possible combinations of mutations among lysines 5, 8, 12, and 16 to arginine in the histone H4 tail, mimicking positively charged, unacetylated lysine states, and characterized the resulting genome-wide changes in gene expression by using DNA microarrays. Only the lysine 16 mutation had specific transcriptional consequences independent of the mutational state of the other lysines (affecting approximately 100 genes). In contrast, for lysines 5, 8, and 12, expression changes were due to nonspecific, cumulative effects seen as increased transcription correlating with an increase in the total number of mutations (affecting approximately 1,200 genes). Thus, acetylation of histone H4 is interpreted by two mechanisms: a specific mechanism for lysine 16 and a nonspecific, cumulative mechanism for lysines 5, 8, and 12.

Acetylation↗

PubMed2026

Whole-genome characterization of seven multidrug-resistant Neisseria gonorrhoeae isolates from a single tertiary center in Beijing.

BACKGROUND: To characterize the whole-genome features of Neisseria gonorrhoeae clinical isolates collected from a tertiary medical institution in Beijing, with a focus on the genomic basis of ceftriaxone non-susceptibility and multidrug resistance. METHODS: Clinical isolates were collected from April 2023 to November 2024. Of 14 collected isolates, seven were successfully subcultured after revival and included in subsequent analyses. Minimum inhibitory concentrations (MICs) were determined by the Etest method. Whole-genome data were obtained using a combination of second- and third-generation sequencing technologies. The isolates were combined with global and Chinese reference datasets to construct a core-genome single-nucleotide polymorphism (core-SNP) phylogenetic tree. Chromosomal resistance-associated mutations and plasmid characteristics were subsequently analyzed. RESULTS: The seven isolates displayed genomic diversity at the whole-genome level. Four isolates (8087, 8423, 8461, and 8801) carried penA 60.001 and belonged to distinct sequence types, including ST7365, ST8123, and ST7367. One additional isolate (8726) carried penA 273.001; both alleles encode PBP2 proteins sharing the core substitutions A311V, I312M, V316T, and T483S. All five isolates were non-susceptible to ceftriaxone (MIC 0.25-0.5 mg/L). Ceftriaxone non-susceptibility was associated with the co-occurrence of mutations at core penA positions and additional mutations in porB and ponA, with an mtrR mutation present in one isolate. Plasmid collinearity analysis revealed that several multidrug-resistant isolates simultaneously harbored an intact conjugative plasmid and an African-type resistance plasmid carrying bla TEM-1. CONCLUSION: The multidrug-resistant phenotype of Neisseria gonorrhoeae results from the co-existence of chromosomal multi-locus mutations and resistance plasmids. The penA 60.001 isolates in this study did not originate from a single source. This allele appeared in multiple local clonal lineages. This pattern is consistent with horizontal gene transfer of this resistance determinant into multiple endemic lineages.

Neisseria gonorrhoeae↗