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PubMed2026

Scaling up orphan crop research: genebank genetics highlight geographic structure in cultivated cowpea from 10 617 global accessions.

Vigna unguiculata (L.) Walp. is a dryland legume crop, providing essential food and nutritional security for millions of people across the semi-arid tropics, in Africa, Asia and Latin America. However, as a typical 'orphan crop', cowpea has long remained underrepresented in global genomic research to support crop improvement. Here, we conducted the largest genetic diversity analysis of cowpea to date, comprising 10 617 accessions sourced from seven international collections. Using genotyping-by-sequencing, we characterised the global patterns of genetic diversity, assessed redundancy within and across collections, and examined the geographic structure of the cowpea global allele pool. Our results revealed nine distinct genetic groups with clear geographic associations and fine-scale population differentiation, reflecting dispersal history, regional adaptation and the influence of modern breeding. Duplication across collections was detected, highlighting the need for improved curation and integration of germplasm resources. Landraces from sub-Saharan Africa do not fully capture the genetic diversity present in several other geographic regions, indicating the existence of abundant and untapped genetic resources worldwide. These findings not only provide insights into the genetic structure and evolutionary history of cowpea but also offer a valuable foundation for harnessing global germplasm diversity to enhance breeding potential and accelerate crop improvement.

Vigna↗
PubMed1999

Genomics, mutations and the Internet: the naming and use of parts.

Mutations are the source of genetic variation and diversity; by their effect, some are neutral, others are pathogenic. In contemporary genetics, mutations appear at the interface between genomics (structural and functional) and genetics (heredity), where they serve gene discovery and mapping (genomics) and generate challenges to modify their phenotypic effects (medical genetics). Assuming the human genome harbours 80,000 transcribed genes each possessing at least 100 different (germline) alleles in a typical population, how then to record and recover data on at least 8 million human alleles? Bioinformatics is the essential resource to create the corresponding accessible digital libraries (genomic and locus-specific mutation databases) for this purpose, a goal to which The HUGO Mutation Database Initiative (Science 279: 10-11, 1998) aspires. Guidelines now exist for naming alleles (Hum Mutat 11: 1-3, 1998). The principles behind the practice are illustrated by PAHdb (http:/(/)www.mcgill.ca/ pahdb), a prototype locus-specific mutation database (NAR 26: 220-225, 1998), and by prototype genomic mutation databases (HGMD (NAR 26: 285-287, 1998), http:/(/)www.uwcm.ac.uk/uwcm/mg/hgmd0.h tml; the EBI mutation database, http:/(/)www2.ebi.ac.uk/mutations/; and OMIM, http:/(/)www.ncbi.nlm. nih.gov/Omim.html).

Databases, Factual↗
PubMed2000

Sequence, expression and reconstitution of an HCV genome from a British isolate derived from a single blood donation.

Morphological analysis of hepatitis C virus and development of antiviral drugs to eradicate this agent have been seriously hampered by the low viraemias observed during natural infection and the unavailability of a cell culture system for virus propagation. Recently a low-grade hepatitis has been reported in chimpanzees after intrahepatic transfection of full-length synthetic HCV RNA and successful infections shown to be critically dependent on the integrity and genetic homogeneity of the reconstituted clone. In this study we describe and characterize a full HCV RNA sequence derived from a case of chronic sporadic hepatitis. The genotype was shown to be 1a with a low level of intraclonal sequence heterogeneity, and processing of both structural and nonstructural proteins has been documented. The assembly of the full genome has also been achieved. The low level of intraclonal variation observed may reflect infection with a single isolate and the fact that cloning was performed on virus obtained from a single blood donation makes this clone a good candidate for future in vivo and in vitro transfection studies.

Animals↗
PubMed2025

Proteomic comparison of epidemic Australian Bordetella pertussis biofilm cells.

Bordetella pertussis causes whooping cough, a severe respiratory infectious disease. Studies have compared the currently dominant single nucleotide polymorphism (SNP) cluster I (pertussis toxin promoter allele, ptxP3) and previously dominant SNP cluster II (ptxP1) strains as planktonic cells. Since biofilm formation is linked with B. pertussis pathogenesis in vivo, this study compared the biofilm formation capabilities of representative strains of cluster I and cluster II. Confocal laser scanning microscopy found that the cluster I strain had a denser biofilm structure compared to the cluster II strain. Differences in protein abundance of the biofilm cells were then compared using tandem mass tagging and high-resolution multiple reaction monitoring. In total, 1,453 proteins were identified, of which 40 proteins had significant differential abundance between the two strains in biofilm conditions. Of particular interest was a large increase in the abundance of energy metabolism proteins (cytochrome proteins PetABC and BP3650) in the cluster I strain. When the abundance of these proteins was compared between six additional strains from each cluster, it was found that the protein abundance varied between all strains. These findings suggest that there are large levels of individual proteomic diversity between B. pertussis strains in biofilm conditions despite the highly conserved genome of the species. Overall, this study revealed visual differences in biofilm structure between B. pertussis strains and highlighted strain-specific variation in protein abundance that dominates potential cluster-specific changes that may be linked with the dominance of cluster I strains.IMPORTANCEBordetella pertussis causes whooping cough. The currently circulating cluster I strains have taken over previously dominant cluster II strains. It is important to understand the reasons behind this evolution to develop new strategies against the pathogen. Recent studies have shown that B. pertussis can form biofilms during infection. This study compared the biofilm formation capabilities of a cluster I and a cluster II strain and identified visual differences in the biofilms. The protein abundance between these strains grown in biofilms was compared, and proteins identified with varied abundance were measured with additional strains from each cluster. It was found that despite the highly conserved genetics of the species, there was varied protein abundance between the additional strains. This study highlights that strain-specific variation in protein abundance during biofilm conditions may dominate the cluster-specific changes that may be linked to the dominance of cluster I strains.

Bordetella pertussis↗
PubMed2026

A Cis-Regulatory Duplication in a Hox Hotspot Implicated in Mimetic Convergence in the Bumble Bee Bombus flavifrons.

Several species of North American bumble bees spanning the Pacific Coastal and Rocky Mountain regions converge onto distinct mimetic abdominal colour forms for each region by switching abdominal coloration from black to red. Previous genome-wide association studies (GWAS) of red and black transitions in two mimics (Bombus melanopygus and Bombus vancouverensis) revealed that black forms were generated by independently deleting a portion of the same cis-regulatory region near the Hox gene Abdominal-B (Abd-B). Here, we test the genetic basis of these mimetic colour forms in a third co-mimic, Bombus flavifrons, that has continuous variation in red and black that is shifted posteriorly one segment compared to its co-mimics. Using genome-wide association of red and black forms, we identified a structural variant <&#x2009;50&#x2009;bp away from the deletions in B. melanopygus and B. vancouverensis that was strongly associated with the colour phenotype. Sequencing across mimicry zones and closely related taxa revealed that all red forms of B. flavifrons and monomorphic red close relative Bombus centralis have a 319&#x2009;bp tandem duplication at this locus that has extensive modification to the duplicated copy. Black forms of B. flavifrons from the Cascades also have this duplication but without the modifications, while black forms in the western Rockies mostly lack this duplication, similar to ancestral black forms. This suggests independent mechanisms may regulate the black phenotypes in different populations and that ancestral sorting of variation and/or adaptive introgression generated these phenotypes. This study strengthens support for this Abd-B cis-regulatory region being a hotspot for regulating abdominal coloration in bumble bees, and features the role of regulatory region duplication in creating novel phenotypes.

Animals↗
PubMed1994

The relationship between DNA structural variation and activities of P elements in P and Q strains of Drosophila melanogaster.

To characterize the relationship between P element activities and their structures, we cloned P elements from genomic libraries of three isogenic P and Q strains derived from natural populations in Japan. These P elements were mapped with BamHI, AvaII and PstI and were classified by their size. The majority of P elements cloned were classified as either complete or relatively small P elements rather than medium size. The numbers of full length (2.9 kb) P elements per haploid genome of NP280 (P), AK194 (weak P) and WY113 (Q) were at least four, five and one, respectively. However, the 2.9 kb P element of WY113 was thought to be defective since this strain has no transposase activity. In our previous work, we demonstrated that the ORF 3-deleted P element is essential for P cytotype determination in WY113. A similar P element also exists in NP280, and this may have an important role for P cytotype determination in this strain. Two and one copies of the KP element, a deletion derivative of the P element, were found in NP280 and AK194, respectively. One of four complete P elements in NP280 was fully sequenced, and the base sequence was completely identical to that of p pi 25.1 originally derived from the U.S.A. This result is consistent with the notion that these P elements have a relatively recent origin in Drosophila melanogaster.

Animals↗
PubMed1997

How Escherichia coli can bias the results of molecular cloning: preferential selection of defective genomes of hepatitis C virus during the cloning procedure.

Cloned PCR products containing hepatitis C virus (HCV) genomic fragments have been used for analyses of HCV genomic heterogeneity and protein expression. These studies assume that the clones derived are representative of the entire virus population and that subsets are not inadvertently selected. The aim of the present study was to express HCV structural proteins. However, we found that there was a strong cloning selection for defective genomes and that most clones generated initially were incapable of expressing the HCV proteins. The HCV structural region (C-E1-E2-p7) was directly amplified by long reverse transcription-PCR from the plasma of an HCV-infected patient or from a control plasmid containing a viable full-length cDNA of HCV derived from the same patient but cloned in a different vector. The PCR products were cloned into a mammalian expression vector, amplified in Escherichia coli, and tested for their ability to produce HCV structural proteins. Twenty randomly picked clones derived from the HCV-infected patient all contained nucleotide mutations leading to absence or truncation of the expected HCV products. Of 25 clones derived from the control plasmid, only 8% were fully functional for polyprotein synthesis. The insertion of extra nucleotides in the region just upstream of the start codon of the HCV insert led to a statistically significant increase in the number of fully functional clones derived from the patient (42%) and from the control plasmid (72-92%). Nonrandom selection of clones during the cloning procedure has enormous implications for the study of viral heterogeneity, because it can produce a false spectrum of genomic diversity. It can also be an impediment to the construction of infectious viral clones.

Animals↗
PubMed2026

Utilization of long-read sequencing for the detection of structural rearrangements with AgileStructure.

MOTIVATION: Changes in genome organisation contribute to genetic disease when they disrupt gene function or regulation. Structural rearrangements may interrupt coding sequence or alter expression through promoter loss or gain, chromatin changes, copy-number variation, or disruption of short-range regulatory elements. Although short-read sequencing excels at detecting small variants, it performs poorly at resolving breakpoints of large rearrangements, especially in repetitive or low-complexity regions. Long-read sequencing overcomes these limitations, but analytical tools have not kept pace, making accurate identification and annotation of large structural variants challenging. RESULTS: We developed AgileStructure, a desktop application for locating and annotating large&#x2011;scale genomic rearrangements using aligned long&#x2011;read data. The software enables user&#x2011;guided exploration of breakpoint&#x2011;spanning reads, supporting accurate interpretation of complex events and filling a key gap in current structural variant analysis workflows. AVAILABILITY AND IMPLEMENTATION: Source code, binaries, user guide, and example aligned read data, are available on GitHub: https://github.com/msjimc/AgileStructure. An archived version is also available on Zenodo at https://doi.org/10.5281/zenodo.18610110.

Software↗
PubMed1995

Genetic variability in mitochondrial DNA of the screwworm, Cochliomyia hominivorax (Diptera: Calliphoridae), from Brazil.

Restriction fragment length polymorphism (RFLP) analysis of mitochondrial DNA (mtDNA) was used to examine genetic variation and population structure of screwworm flies in four populations from São Paulo State, Brazil. The total DNA of 405 individuals was digested with 15 restriction endonucleases and probed with five cloned HindIII fragments representing the entire mitochondrial genome of Cochliomyia hominivorax. The survey revealed that four enzymes (HaeIII, HindIII, MspI, and PvuII) were suitable to detect mtDNA variation among all populations. Based on the fragment patterns obtained for these four enzymes, a total of 15 haplotypes in combination was detected. Heteroplasmic individuals for the PvuII pattern were obtained in one of the populations. The estimated average for nucleotide sequence divergence (delta) was 0.92%. The cladogram of the geographical distribution among the observed haplotypes suggests that the sampled screwworms probably belong to a single evolutionary lineage with populations interconnected by reduced gene flow.

Animals↗
PubMed1999

Identification of novel mutations in the MTM1 gene causing severe and mild forms of X-linked myotubular myopathy.

X-linked myotubular myopathy (XLMTM) is a congenital muscular disease characterized by severe hypotonia and generalized muscle weakness, leading in most cases to early postnatal death. The gene responsible for the disease, MTM1, encodes a dual specificity phosphatase, named myotubularin, which is highly conserved throughout evolution. To date, 139 MTM1 mutations in independent patients have been reported, corresponding to 93 different mutations. In this report we describe the identification of 21 mutations (14 novel) in XLMTM patients. Seventeen mutations are associated with a severe phenotype in males, with death occurring mainly before the first year of life. However, four mutations-three missense (R241C, I225T, and novel mutation P179S) and one single-amino acid deletion (G294del)-were found in patients with a much milder phenotype. These patients, while having a severe hypotonia at birth, are still alive at the age of 4, 7, 13, and 15 years, respectively, and display mild to moderate muscle weakness.

Adolescent↗
PubMed1985

An invertible element of DNA controls phase variation of type 1 fimbriae of Escherichia coli.

The expression of type 1 fimbriae (pili) of Escherichia coli is turned on and off at the transcriptional level at a high frequency (10(-3) per cell per generation) in a process termed phase variation. Using Southern blot and DNA sequence analysis, we have detected a genomic rearrangement in the switch region immediately upstream of the fimbrial structural gene. This rearrangement involves an invertible 314-base-pair segment of DNA whose alternating orientation apparently results in the on-and-off activation of a promoter that determines the state of fimbrial expression.

Base Sequence↗
PubMed1996

ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome.

It was shown recently that mutations of the ATRX gene give rise to a severe, X-linked form of syndromal mental retardation associated with alpha thalassaemia (ATR-X syndrome). In this study, we have characterised the full-length cDNA and predicted structure of the ATRX protein. Comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains. ATRX probably acts as a regulator of gene expression. Definition of its genomic structure enabled us to identify four novel splicing defects by screening 52 affected individuals. Correlation between these and previously identified mutations with variations in the ATR-X phenotype provides insights into the pathophysiology of this disease and the normal role of the ATRX protein in vivo.

Amino Acid Sequence↗
PubMed1987

Alternative splicing generates variants in important functional domains of human slow skeletal troponin T.

We provide the first nucleotide sequence information for the slow isoform of troponin T (TnT). Sequence and hybridization analyses revealed that a single slow TnT gene present in the human genome gives rise to at least two different slow TnT variants by alternative splicing. The observed variations in slow TnT splicing generated major structural differences between the two corresponding slow TnT proteins in a domain that is likely to be involved in critical interactions with troponin C, troponin I, and tropomyosin in the thin filament. Corresponding variations have not been found for fast or for cardiac TnT. The comparison of splicing patterns for fast, cardiac, and slow TnT reveals that the splicing pattern for each isoform is unique. These features raise important questions of why and how all the individual members of the closely related TnT gene family developed such complex but different schemes of alternative splicing to create sets of variant proteins. This unusual familial trait is not known in any other muscle or nonmuscle multigene family.

Amino Acid Sequence↗
PubMedDate not supplied

Sequences homologous to variant antigen mRNA spliced leader in Trypanosomatidae which do not undergo antigenic variation.

Trypanosomes which parasitize mammals have evolved mechanisms to evade immune attack, such as the occupation of 'safe' intracellular sites (for example, Trypanosoma cruzi), or antigenic variation, exemplified by the salivarian trypanosomes (for example, Trypanosoma brucei). Antigenic variation is mediated by sequential expression of single variant surface glycoprotein (VSG) genes, and often involves transposition of the active gene. Every VSG transcript examined shares the same 5' terminal 35-nucleotide leader sequence. In T. brucei, this leader is encoded within a 1.4-kilobase unit tandemly reiterated to form a large array. It is hypothesized that this array is distantly linked to the expressed VSG gene and functions as a multiple promoter of VSG gene transcription, restricting transcription to that gene which, through genomic rearrangement, is placed downstream from the array. Leader and structural gene sequences are presumably juxtaposed by RNA splicing. Here we show that several trypanosomatids, both those which undergo antigenic variation (Trypanosoma congolense and Trypanosoma vivax) and those which do not (T. cruzi and Leptomonas collosoma), contain reiterated sequences homologous to the T. brucei spliced leader (SL). These results suggest that the SL, although utilized in VSG gene expression, is an ancestral sequence also used in the expression of other trypanosomatid genes.

Animals↗
PubMed2000

Deficiencies of human complement component C4A and C4B and heterozygosity in length variants of RP-C4-CYP21-TNX (RCCX) modules in caucasians. The load of RCCX genetic diversity on major histocompatibility complex-associated disease.

The complement component C4 genes located in the major histocompatibility complex (MHC) class III region exhibit an unusually complex pattern of variations in gene number, gene size, and nucleotide polymorphism. Duplication or deletion of a C4 gene always concurs with its neighboring genes serine/threonine nuclear protein kinase RP, steroid 21-hydroxylase (CYP21), and tenascin (TNX), which together form a genetic unit termed the RCCX module. A detailed molecular genetic analysis of C4A and C4B and RCCX modular arrangements was correlated with immunochemical studies of C4A and C4B protein polymorphism in 150 normal Caucasians. The results show that bimodular RCCX has a frequency of 69%, whereas monomodular and trimodular RCCX structures account for 17.0 and 14.0%, respectively. Three quarters of C4 genes harbor the endogenous retrovirus HERV-K(C4). Partial deficiencies of C4A and C4B, primarily due to gene deletions and homoexpression of C4A proteins, have a combined frequency of 31.6%. This is probably the most common variation of gene dosage and gene size in human genomes. The seven RCCX physical variants create a great repertoire of haplotypes and diploid combinations, and a heterozygosity frequency of 69.4%. This phenomenon promotes the exchange of genetic information among RCCX constituents that is important in homogenizing the structural and functional diversities of C4A and C4B proteins. However, such length variants may cause unequal, interchromosomal crossovers leading to MHC-associated diseases. An analyses of the RCCX structures in 22 salt-losing, congenital adrenal hyperplasia patients revealed a significant increase in the monomodular structure with a long C4 gene linked to the pseudogene CYP21A, and bimodular structures with two CYP21A, which are likely generated by recombinations between heterozygous RCCX length variants.

Adrenal Hyperplasia, Congenital↗
PubMed1995

Structure and evolution of Paramecium hemoglobin genes.

Hemoglobin (Hb) genes have been cloned from three different species of ciliated protists, P. multimicronucleatum, P. triaurelia and P. jenningsi. Southern blotting of the genomic DNAs using the P. caudatum Hb cDNA showed both intraspecies variation in different stocks of P. caudatum and interspecies variation within the genus Paramecium. The isolated Hb genes were composed of 118, 117 and 117 codons, and interrupted by a short intron with 27, 29 and 29 bp at the same position, in P. multimicronucleatum, P. triaurelia and P. jenningsi, respectively. This suggests that the one-intron and two-exon structure has been conserved in the Hb genes in this genus. The amino acid sequences of the Paramecium Hbs were more than 87% identical to one another and homologous to those from the other ciliated protists Tetrahymena thermophila and T. pyriformis, the green alga Chlamydomonas eugametos, and the cyanobacterium Nostoc commune Hbs, all of which consist of about 120 amino acid residues (120-aa group). In particular, the amino acid sequences of the P. triaurelia and P. jenningsi Hbs were the same, although there were 20 nucleotide differences between the coding regions in the two genes. A maximum likelihood inference as to the phylogenetic relationships among these genes suggests that the Paramecium Hbs genes have evolved more rapidly than the other genes in the 120-aa group, and that P. triaurelia and P. genningsi are sibling species and the P. aurelia complex became a small cell after it separated from P. jenningsi.

Amino Acid Sequence↗