SEARCH · PubMed Health

Results for “Genomic subtypes”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 91 records · Page 5Linked to original sources

PubMed2002

Full-length genome analysis of HIV-1 subtype C utilizing CXCR4 and intersubtype recombinants isolated in South Africa.

The HIV-1 epidemic in South Africa is largely due to subtype C viruses, which preferentially use CCR5 as a coreceptor for infection. We describe full-length genome sequences of two CXCR4-utilizing HIV-1 subtype C viruses and two intersubtype recombinants from South Africa. Three of the viruses (99ZACM4, 99ZACM9, and 99ZASW7) were isolated in 1999 from AIDS patients in Johannesburg, and a fourth virus (98ZADu178) was isolated in Durban in 1998 from an asymptomatic female sex worker. Isolates 99ZASW7 and 99ZACM9 from Johannesburg were subtype C throughout the genome, 99ZASW7 used the CXCR4 coreceptor, and 99ZACM9 used both CCR5 and CXCR4. Isolate 98ZADu178 from Durban was a novel recombinant between subsubtype A2 and subtype C. The third isolate from Johannesburg, 99ZACM4, was a complex, novel recombinant with multiple breakpoints and contained segments of subtypes A, C, D, G, and K. These results establish the presence of intersubtype recombinants in South Africa, indicating that ongoing surveillance for other subtypes and recombinants is necessary.

Female↗

PubMed1993

Complete nucleotide sequences of six hepatitis B viral genomes encoding the surface antigen subtypes ayw4, adw4q-, and adrq- and their phylogenetic classification.

The complete nucleotide sequences of six hepatitis B viral (HBV) genomes were determined by dideoxy chain termination sequencing of ten overlapping nucleotide fragments obtained by the polymerase chain reaction. Four of the genomes belonged to the two genomic groups E and F of HBV which have been previously identified by us on the basis of sequence divergences within the S gene. Genomic group E encodes the HBsAg subtype ayw4, group F adw4q-. The other two genomes were of Pacific origin within group C and encoded adrq-. The relationship of these complete human HBV genomes to 21 that have been previously published, together with one chimpanzee virus and four rodent hepadnaviral genomes, was investigated by constructing a phylogenetic tree utilizing a combination of distance matrix and approximate parsimonious methods. Thereby, the previously demonstrated segregation of human HBV strains into six genomic groups was confirmed. Both of the representatives of the groups E and F were found to differ by 8.1-13.6% and by 12.8-15.5% from the genomes of the other genomic groups and by 1.5 and 3.7% from each other. Since they differed by more than 8% from the genomes in the other groups, the limit originally used to define HBV, genomic groups their status as new genomic groups was confirmed. The two Pacific group C strains were found to differ by 2.7% from each other and by 4.1 to 5.4% from other group C genomes, suggesting that they diverged early from the other group C genomes. According to both the overall similarity and the phylogenetic dendrogram the F strains formed the most divergent cluster of HBV genomes favoring the concept that they represented the original HBV strains of the New World. The next split in the dendrogram segregated the A, D, E and the chimpanzee strains from the Asian B and C strains. Information on the nucleotide sequences and their encoded products of HBV strains of different genomic groups will provide a basis to understand biological variations of the HBV infection in different parts of the world.

Animals↗

PubMedDate not supplied

Viral genome characterisation by the heteroduplex mobility and heteroduplex tracking assays.

The heteroduplex mobility assay (HMA) is a means of comparing two PCR amplicons or, in the variation known as the heteroduplex tracking assay (HTA), a means of estimating the quasispecies diversity of a viral genome. Heteroduplex assays have many applications including subtyping viral genomes, screening for low frequency variants in a population, scanning the relative genetic diversity across a genome and screening for recombinant clones. They can be used to detect dual infections, superinfections, contaminated blood products and laboratory contaminations. PCR amplicons of about 65% sequence similarity or greater will form heteroduplexes under appropriate conditions, and phylogenetic trees can be drawn from heteroduplex mobility data. While homoduplexes indicate more than 98% similarity between two DNA sequences, heteroduplexes indicate at least seven mismatches in a 500-bp amplicon, or a three-base pair gap in 1000-bp. Minority variants comprising 1% to 5% of the genome population can be detected and quantified by HTA. Thus far, heteroduplex assays have been described for HIV and other lentiviruses, hepatitis C and G viruses, Norwalk-like viruses, influenza, measles and poliovirus. They could be applied to a wide range of other viral species.

DNA, Viral↗

PubMed1998

Genomic polymorphism among Blastocystis hominis strains and development of subtype-specific diagnostic primers.

Genomic polymorphisms among nine strains of Blastocystis hominis were examined by random amplified polymorphic DNA (RAPD) using four different arbitrary polymerase chain reaction (PCR) primers. Based on the RAPD patterns, nine strains were classified into three groups. The specific primers designed from the unique bands yielded a single band from within each same group, but did not amplify between all the groups examined. Specificity of these diagnostic primers was tested against several common intestinal parasites and a yeast, and no amplification was confirmed. Since the current criteria indicates that Blastocystis organisms isolated from humans are designated as B. hominis, the authors propose to classify several subtypes among B. hominis groups based on the difference of genomic DNA using three diagnostic primers.

Animals↗

PubMed2006

Hepatitis C virus complete genome sequences identified from China representing subtypes 6k and 6n and a novel, as yet unassigned subtype within genotype 6.

Here, the complete genome sequences for three hepatitis C virus (HCV) variants identified from China and belonging to genotype 6 are reported: km41, km42 and gz52557. Their entire genome lengths were 9430, 9441 and 9448 nt, respectively; the 5' untranslated regions (UTRs) contained 341, 342 and 339 nt, followed by single open reading frames of 9045, 9045 and 9057 nt, respectively; the 3' UTRs, up to the poly(U) tracts, were 41, 51 and 52 nt, respectively. Phylogenetic analyses showed that km41 is classified into subtype 6k and km42 into subtype 6n. Although gz52557 clustered distantly with subtype 6g, it appeared to belong to a distinct subtype. Analysis with 53 and 105 partial core and NS5B region sequences, respectively, representing 17 subtypes from 6a to 6q and three unassigned isolates of genotype 6 in co-analyses demonstrated that gz52557 was equidistant from all of these isolates, indicating that it belongs to a novel subtype. However, based on a recent consensus that three or more examples are required for a new HCV subtype designation, it is suggested that gz52557 remains unassigned to any subtype.

China↗

PubMed2005

Comparison of the full-length genome sequence of avian metapneumovirus subtype C with other paramyxoviruses.

We determined the nucleotide (nt) sequence of the small hydrophobic (SH), attachment glycoprotein (G), and RNA polymerase (L) genes, plus the leader and trailer regions of the Colorado strain of Avian metapneumovirus subtype C (aMPV/C) in order to complete the genome sequencing. The complete genome comprised of 13,134 nucleotides, with a 40 nt leader at its 3' end and a 45 nt trailer at its 5' end. The aMPV/C L gene was the largest with 6173 nt and consisting of a single open reading frame encoding a 2005 amino acids (aa) protein. Comparison of the aMPV/C SH, G, and L nt and predicted aa sequences with those of Human metapneumoviruses (hMPV) revealed higher nt and aa sequence identities than the sequence identities between the aMPV subtypes A, B, C, and D, supporting earlier finding that aMPV/C was closer evolutionary to hMPV than the other aMPV subtypes.

Amino Acid Sequence↗

PubMed2005

A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes.

Clustered regularly interspaced short palindromic repeats (CRISPRs) are a family of DNA direct repeats found in many prokaryotic genomes. Repeats of 21-37 bp typically show weak dyad symmetry and are separated by regularly sized, nonrepetitive spacer sequences. Four CRISPR-associated (Cas) protein families, designated Cas1 to Cas4, are strictly associated with CRISPR elements and always occur near a repeat cluster. Some spacers originate from mobile genetic elements and are thought to confer "immunity" against the elements that harbor these sequences. In the present study, we have systematically investigated uncharacterized proteins encoded in the vicinity of these CRISPRs and found many additional protein families that are strictly associated with CRISPR loci across multiple prokaryotic species. Multiple sequence alignments and hidden Markov models have been built for 45 Cas protein families. These models identify family members with high sensitivity and selectivity and classify key regulators of development, DevR and DevS, in Myxococcus xanthus as Cas proteins. These identifications show that CRISPR/cas gene regions can be quite large, with up to 20 different, tandem-arranged cas genes next to a repeat cluster or filling the region between two repeat clusters. Distinctive subsets of the collection of Cas proteins recur in phylogenetically distant species and correlate with characteristic repeat periodicity. The analyses presented here support initial proposals of mobility of these units, along with the likelihood that loci of different subtypes interact with one another as well as with host cell defensive, replicative, and regulatory systems. It is evident from this analysis that CRISPR/cas loci are larger, more complex, and more heterogeneous than previously appreciated.

Genes, Archaeal↗

PubMed1999

Genetic differences in endocrine pancreatic tumor subtypes detected by comparative genomic hybridization.

The molecular pathogenesis as well as histogenesis of endocrine pancreatic tumors (EPTs) is not well understood, and the clinical behavior of EPTs is difficult to predict using current morphological criteria. Thus, more accurate markers of risk and better understanding of tumor initiation and progression are needed to allow a precise classification of EPTs. We have studied 44 benign and malignant EPTs by comparative genomic hybridization to correlate the overall number of genetic alterations with clinical and histopathological parameters and to identify chromosomal regions which might harbor genes involved in EPT pathogenesis and progression. Aberrations were found in 36 EPTs, and chromosomal losses (mean, 5.3) were slightly more frequent than gains (mean, 4. 6). The most frequent losses involved Y (45% of male EPTs), 6q (39%), 11q (36%), 3p, 3q, 11p (each 30%), 6p (27%), and 10q and Xq (each 25%), whereas most common gains included 7q (43%), 17q (41%), 5q and 14q (each 32%), 7p, 9q, 17p, 20q (each 27%), and 12q and Xp (each 25%). A correlation was found between the total number of genetic changes per tumor and both tumor size and disease stage. In particular, losses of 3p and 6 and gains of 14q and Xq were found to be associated with metastatic disease. Furthermore, characteristic patterns of genetic changes were found in the various EPT subtypes, eg, 6q loss in malignant insulinomas, indicating that these groups might evolve along genetically different pathways. The highlighted genetic aberrations, including the newly found involvement of 6q losses and sex chromosome alterations, should stimulate the further analysis of these chromosomal regions, which may lead to the discovery of novel genes important in the tumorigenesis and evolution of EPTs.

Chromosome Aberrations↗

PubMed1999

Transmission of human immunodeficiency type 1 viruses with intersubtype recombinant long terminal repeat sequences.

Retroviruses such as human immunodeficiency virus type 1 (HIV-1) contain two RNA strands per virion, and recombination can occur frequently during reverse transcription. Recombination may occur between HIV-1 genomes of the same subtype or among genomes of two or more distinct subtypes present in an individual. In the current study, we found that recombinatorial events were not limited to viral structural genes such as gag and env, but rather, recombination could likewise occur within the 5' long terminal repeat (LTR). Intersubtype recombinant LTRs among HIV-1 subtypes A, C, and D were found in Tanzanian infants. By introducing novel LTR sequences, these recombinant LTR viruses may further increase the adaptive potential and fitness of HIV-1.

Base Sequence↗

PubMed1991

A subtype of human papillomavirus 5 (HPV-5b) and its subgenomic segment amplified in a carcinoma: nucleotide sequences and genomic organizations.

A subtype of human papillomavirus 5 (HPV-5b) is closely associated with carcinomas in the disease epidermodysplasia verruciformis (EV). The complete genome was cloned from virus particles in benign lesions of a patient with EV and sequenced: it was 7779 nucleotides long and consisted of six open reading frames (ORFs) (E6, E7, E1, E2, E4, and E5) in the early region, three ORFs (L2, L3, and L1) in the late region, and a noncoding region, all existing on one DNA strand. The 40% segment of the HPV-5b genome specifically amplified in carcinomas was cloned from a primary carcinoma of the same EV patient and sequenced: it was 3143 nucleotides long and corresponded to a segment of the original HPV-5b genome containing the entire sequences of E6, E7, and the noncoding region and portions of E1 and L1. Compared to the whole genomic DNA, no mutations were detected in this probable malignancy-associated viral subgenomic segment cloned from carcinoma. These results suggest that amplification of the viral segment containing E6, E7, and the noncoding region may play a role in the malignant conversion of HPV-5b-infected benign lesions and that mutations in these genes or regions are not necessarily required.

Base Sequence↗

PubMed2005

Characterization of complete HIV type 1 genomes from non-B subtype infections in U.S. military personnel.

Infections with non-B HIV-1 subtypes are rare in the United States, but comprise a significant percentage of infections among U.S. military personnel. Risk behavior while on overseas deployment correlates with non-B infection in this population. Extensive genetic characterization will be required to define HIV-1 diversity, and to effectively evaluate requirements for HIV-1 vaccines and other prevention strategies in this group. From 1997 to 2000, 520 recent seroconverters, identified through routine HIV-1 testing in the U.S. active military force, volunteered for a prospective study. V3 loop serology or partial genome sequencing identified 28 non- B subtype infections; 14 were studied by full genome sequencing and phylogenetic analysis. Five strains were CRF01_AE. Four of these clustered with CM240 from Thailand, and one clustered with African CRF01_AE. Four strains were CRF02_AG, prevalent in West and West Central Africa. Two strains were subtype C. One strain was a unique recombinant between CRF01_AE and subtype B, and another was a complex unique recombinant between subtype A and D. The final strain was a member of a complex circulating recombinant first identified in Senegal, CRF09_cpx, incorporating subtypes A, F, G, and an unclassified genome. This diversity of non-B subtype HIV-1 strains, encompassing three globally prevalent non-B strains and including rare or even possibly unique strains, illustrates the breadth of U.S. military exposure while deployed and sets the bar higher for breadth of cross-subtype protection to be afforded by an HIV-1 vaccine.

Adult↗

PubMedDate not supplied

Protease inhibition in African subtypes of HIV-1.

Of the 42 million people infected with HIV-1 worldwide, 30 million are in Africa. However, the HIV-1 subtypes prevalent in Africa are not the same that are prevalent in North America and Western Europe. In these developed regions, subtype B is responsible for the vast majority of HIV infections, whereas in sub-Saharan Africa subtypes A and C, and to a lesser extent subtype G, account for most of the infections. These subtypes exhibit genomic differences as large as 30% with respect to subtype B. These differences involve current drug targets, including the HIV-1 protease. Since protease inhibitors have been developed and tested against the HIV-1 B subtype, and proteases from other subtypes carry up to ten amino acid polymorphisms, it is important to assess the influence of these naturally occurring polymorphisms on the potency of existing inhibitors, as well as their synergistic interactions with mutations known to cause drug resistance. This review will examine the effects of naturally occurring polymorphisms on the efficacy of current protease inhibitors and the effects of well characterized drug-resistant mutations within the framework of non-B subtypes. At the biochemical level, non-B-subtype polymorphisms lower the binding affinities of existing clinical inhibitors, but not to the point of causing drug resistance. However, these polymorphisms amplify the effects of mutations causing drug resistance and may play a role in the long-term viability of these inhibitors.

Drug Resistance, Viral↗

PubMed2005

Sequence analysis of a South American HIV type 1 BC recombinant.

We report the characterization of a near full-length sequence of a South American HIV-1 BC intersubtype recombinant, ARE195FL. This isolate contains a C(gag/pol) B(vpr/vpu/gp160(env)) C(gp41(env)/nef) mosaic structure differing from any BC full-length sequence described to date, and is the first full-length sequence obtained from a South American BC strain. Neighbor-joining analysis revealed that subtype C genomic segments of ARE195FL clustered with the South American group of subtype C strains, suggesting a local emergence of the BC recombinant. Despite having dissimilar genomic structures, ARE195FL shares a common recombination breakpoint in vif, which is a "hot spot" for recombinatory events, with the Chinese BC recombinant prototype CRF07_BC. Further full-length sequence analysis of South American HIV-1 C and BC strains is necessary to determine the relevance and spread of emerging HIV-1 BC recombinants in Latin America.

DNA, Viral↗

PubMed1999

Molecular cloning and phylogenetic analysis of human immunodeficiency virus type 1 subtype C: a set of 23 full-length clones from Botswana.

To better understand the virological aspect of the expanding AIDS epidemic in southern Africa, a set of 23 near-full-length clones of human immunodeficiency virus type 1 (HIV-1) representing eight AIDS patients from Botswana were sequenced and analyzed phylogenetically. All study viruses from Botswana belonged to HIV-1 subtype C. The interpatient diversity of the clones from Botswana was higher than among full-length isolates of subtype B or among a set of full-length HIV-1 genomes of subtype C from India (mean value of 9. 1% versus 6.5 and 4.3%, respectively; P < 0.0001 for both comparisons). Similar results were observed in all genes across the entire viral genome. We suggest that the high level of HIV-1 diversity might be a typical feature of the subtype C epidemic in southern Africa. The reason or reasons for this diversity are unclear, but may include an altered replication efficiency of HIV-1 subtype C and/or the multiple introduction of different subtype C viruses.

Base Sequence↗

PubMed1996

HIV-1 genetic diversity.

BACKGROUND: HIV-1 evolves by rapid mutation and by recombination, both processes actively contributing to its genetic diversity. Most of the multiple genetic subtypes and intersubtype recombinations of HIV-1 that comprise the global pandemic have not been characterized by full genome sequencing. METHODS: DNA from primary virus cultures on donor peripheral blood mononuclear cells was used as template for long polymerase chain reaction amplification, molecular cloning, and automated sequencing of virtually full-length HIV-1 genomes from subtypes A, C, E, G and A/D recombinant forms. Standard phylogenetic analysis methods were employed, and some were modified for the detection and mapping of recombinant breakpoints. RESULTS: Subtypes A, B, C and D are largely, if not entirely, distinguishable throughout the genome and show no clear evidence of intersubtype recombination. In contrast, all available sequences of subtypes E and G are recombinant with subtype A. Full-length sequences of subtypes F, H, I and J are still unavailable. Subtype E and G, and some A/D recombinant HIV, have retained the cytoplasmic domain of gp41 from subtype A. Some recombinants possess the matrix and core of one subtype and the outer envelope of another, resembling pseudotypes. Certain pairs of subtypes may have recombined more often than others. CONCLUSION: Recombinant HIV-1 have already established a global reservoir and are largely responsible for the rapidly expanding subtype E epidemic in Southeast Asia. Recombination may have played a key role in the evolution of HIV-1 and the geographic intermixing of subtypes, which is increasing, may foster the emergence of a even greater variety of recombinant strains.

DNA, Viral↗

PubMed2026

Multimodal analysis of CD38 in T-cell Acute Lymphoblastic Leukemia Identifies Combinatorial Therapeutic Strategies.

Outcomes for pediatric patients with refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) are poor, underscoring the need for improved therapeutic strategies. CD38, a type II transmembrane glycoprotein, is a promising target in T-ALL, with clinical trials evaluating CD38-targeting immunotherapies in frontline and relapsed settings. However, the biological role of CD38 in T-ALL has not been systematically defined. We interrogated CD38 biology through multimodal profiling of pediatric T-ALL samples. Bulk RNA sequencing of 1,335 primary tumors revealed that CD38 expression varies across genomic and immunophenotypic subtypes in T-ALL. Flow cytometry of 150 primary samples and CITE-sequencing of 40 cases demonstrated broad surface expression of CD38. A transcription factor CRISPR-screen identified RUNX1, RUNX3, and TP53 as candidate positive regulators of CD38. Metabolomic profiling of cell lines further revealed disruption of the polyamine pathway following CD38 perturbation. Supporting this finding, co-targeting CD38 with difluoromethylornithine (DFMO), a polyamine metabolism disruptor, improved survival in preclinical models. Across transcriptomic datasets, including primary tumors, cell lines, and patient-derived xenograft models, IL32 expression consistently decreased following CD38 loss or negativity, supporting an association between CD38 and inflammatory signaling pathways. Additionally, CD38 and LCK expression were positively correlated across majority of genomic subtypes, implicating SRC kinase signaling. Consistent with this, daratumumab in cell lines increased LCK phosphorylation, and combination therapy with dasatinib improved survival compared to monotherapy. Collectively, these findings define previously unrecognized interactions between CD38 and targetable pathways and genes in T-ALL and identify rational combinatorial strategies to enhance CD38-directed therapies and reduce relapse risk.

Journal Article↗

PubMed2026

Genomic characterization of avian metapneumovirus subtypes A and B in United States poultry by targeted amplicon sequencing.

Avian metapneumovirus (aMPV) subtypes A and B emerged in United States poultry in late 2023 and early 2024, prompting genome-scale surveillance from clinical samples. Here, we developed and optimized targeted amplicon sequencing (TAS) assays for both subtypes and applied them to 104 subtype-positive clinical samples collected from chicken and turkey farms across nine US states between early 2024 and early 2026. TAS recovered 91 genomes suitable for comparative analysis, including 44 aMPV-A and 47 aMPV-B sequences, with successful recovery extending to Ct values of 34.6 for aMPV-A and 31.2 for aMPV-B. Recovered genomes showed near-complete breadth and high mapping efficiency. Phylogenetic analyses of both G-gene and whole-genome datasets showed that US aMPV-A field strains formed a distinct monophyletic lineage within group IV and resolved into three closely related clusters. Cluster 2, first recognized in North Carolina and later detected in Ohio, spread across 30 turkey and chicken farms. Cluster 2 genomes were defined by a concentrated G-protein hotspot within residues 209-275, and most North Carolina Cluster 2 genomes carried 10-11 nonsynonymous substitutions in this region, including multiple proline substitutions suggestive of local structural change. Missouri Cluster 3 remained cohesive but distinct from both Cluster 1 and Cluster 2 in the G-gene and whole-genome trees. In contrast, US aMPV-B field strains remained highly homogeneous across hosts and states, with more than 99% nucleotide identity by both G-gene and WGS analyses. We also identified 12 vaccine-derived genomes on both vaccinated and nonvaccinated farms. These included six genomes related to aMPV-A vaccine and six related to aMPV-B vaccines (VCO3/50 and 1062), all of which retained vaccine-defining markers together with additional substitutions consistent with continued circulation after vaccine use in the field. Selection analyses showed that the G gene had the highest gene-wise dN/dS ratio in both subtypes. Additional elevated signal was observed in SH and M2, and candidate positively or episodically selected codons were concentrated in the subtype A Cluster 2 G-gene hotspot. These findings show that TAS supports direct-from-sample aMPV genomic surveillance and provides genomic context for field clusters, vaccine-derived lineages, and continued adaptive change in aMPV in US poultry.

Animals↗

PubMed2002

Among 46 near full length HIV type 1 genome sequences from Rakai District, Uganda, subtype D and AD recombinants predominate.

The impact of HIV-1 genetic diversity on candidate vaccines is uncertain. To minimize genetic diversity in the evaluation of HIV-1 vaccines, vaccine products must be matched to the predominant subtype in a vaccine cohort. To that end, full genome sequencing was used to detect and characterize HIV-1 subtypes and recombinant strains from individuals in Rakai District, Uganda. DNA extracted from peripheral blood mononuclear cells (PMBC) was PCR amplified using primers in the long terminal repeats (LTRs) to generate nearly full length genomes. Amplicons were directly sequenced with dye terminators and automated sequencers. Sequences were phylogenetically analyzed and recombinants were detected and mapped with distance scan and bootscan. Among 46 sequences, 54% were subtype D, 15% were subtype A, and 30% were recombinant. All recombinants were individually unique, and most combined subtypes A and D. Subtype D comprised more than 70% of all the HIV-1 genomes in Rakai when both pure subtypes and recombinants were considered. Candidate vaccines based on HIV-1 subtype D would be appropriate for evaluation in Rakai District, Uganda.

Adolescent↗