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PubMed2000

Genomic structure of the human tetratricopeptide repeat-containing gene, TTC4, from chromosome region 1p31 and mutation analysis in breast cancers.

Loss of heterozygosity (LOH) in 1p31 is a frequent genetic alteration in breast tumors indicating the site of a tumor suppressor gene. We recently isolated a new member of the human tetratricopeptide repeat-containing family of genes, TTC4, which maps to this region. Other members of this gene family have been implicated in tumorigenesis suggesting that TTC4 may represent a breast cancer tumor suppressor gene. We now report the exon/intron structure of TTC4 and single strand conformation polymorphism (SSCP) analysis of DNA from 20 sporadic breast tumors. Although polymorphic variations were identified no mutations affecting the open reading frame of TTC4 were detected. Since the overall region of chromosome 1p31 which undergoes LOH can be relatively large, excluding involvement of newly isolated genes from this region in breast cancer tumorigenesis is an important process for the successful identification of the critical gene. Understanding the structure of TTC4 now makes mutation analysis possible for other cancers and diseases that map to this region.

Breast Neoplasms↗
PubMed2006

Genetic variability of fragmented stands of pedunculate oak (Quercus robur) in Finland.

The genetic structure of 33 natural Quercus robur stands in Finland was studied using 13 allozyme loci to analyze the effects of fragmentation in a wind-pollinated tree species. The present fragmented and discontinuous distribution of oak is a result of both short-term human impact and long-term climatic and geological change, including post-glacial land uplift. In accordance with general expectations, genetic diversity in small populations was lower than that in large populations, and differentiation among small populations was higher than that among large populations. Heterozygote deficiency was more pronounced in large populations, which is proposed to be a Wahlund effect created by either spatial sub-structuring or the existence of synchronized flowering lineages. Also genetic differentiation was higher and diversity lower in Finland than the estimates reported for Central Europe. There were differences in the genetic structure on sites of different geological age. We suggest that on most geologically old sites drift has a prominent effect whereas on younger sites also founder effects may be important.

Age Factors↗
PubMed2005

Gambol and Tc1 are two distinct families of DD34E transposons: analysis of the Anopheles gambiae genome expands the diversity of the IS630-Tc1-mariner superfamily.

Tc1 is a family of DNA transposons found in diverse organisms including vertebrates, invertebrates and fungi. Tc1 belongs to the IS630-Tc1-mariner superfamily, which is characterized by common 'TA' target site and conserved D(Asp)DE(Glu) or DDD catalytic triad. All functional Tc1-like transposons contain a transposase with a DD34E catalytic triad. We conducted a systematic analysis of DD34E transposons in the African malaria mosquito, Anopheles gambiae, using a reiterative and exhaustive search program. In addition to previously described Tc1-like elements, we uncovered 26 new DD34E transposons including a novel family that we named gambol. Designation of family status to gambol is based on phylogenetic analyses of transposase sequences that showed gambol and Tc1 transposons as distinct clades that were separated by mariner and other families of the IS630-Tc1-mariner superfamily. The distinction between Tc1 and gambol is also consistent with the unique TIRs in gambol elements and the presence of a 'W[I/L/V]DEDC' signature near their N-termini. This signature is predicted as part of the 'RED' domain, a component of the 'PAI' and 'RED' DNA binding domains in Tc1 and possibly mariner. Although gambol appears to be related to a few DD34E transposons from cyanobacteria and fungi, no gambol has been reported in any other insects or animals thus far. Several gambol and Tc1 elements have intact ORFs and different genomic copies with high sequence identity, which suggests that they may have been recently active.

Amino Acid Sequence↗
PubMed2005

PHACCS, an online tool for estimating the structure and diversity of uncultured viral communities using metagenomic information.

BACKGROUND: Phages, viruses that infect prokaryotes, are the most abundant microbes in the world. A major limitation to studying these viruses is the difficulty of cultivating the appropriate prokaryotic hosts. One way around this limitation is to directly clone and sequence shotgun libraries of uncultured viral communities (i.e., metagenomic analyses). PHACCS http://phage.sdsu.edu/phaccs, Phage Communities from Contig Spectrum, is an online bioinformatic tool to assess the biodiversity of uncultured viral communities. PHACCS uses the contig spectrum from shotgun DNA sequence assemblies to mathematically model the structure of viral communities and make predictions about diversity. RESULTS: PHACCS builds models of possible community structure using a modified Lander-Waterman algorithm to predict the underlying contig spectrum. PHACCS finds the most appropriate structure model by optimizing the model parameters until the predicted contig spectrum is as close as possible to the experimental one. This model is the basis for making estimates of uncultured viral community richness, evenness, diversity index and abundance of the most abundant genotype. CONCLUSION: PHACCS analysis of four different environmental phage communities suggests that the power law is an important rank-abundance form to describe uncultured viral community structure. The estimates support the fact that the four phage communities were extremely diverse and that phage community biodiversity and structure may be correlated with that of their hosts.

Algorithms↗
PubMed2002

Hepatitis E and its emergence in non-endemic areas.

In areas with a tropical or subtropical climate and poor sanitary conditions, hepatitis E is the major cause of enterically transmitted non-A, non-B hepatitis, and is responsible for both waterborne outbreaks of variable magnitude and sporadic cases of acute hepatitis. The causative agent is the hepatitis E virus (HEV), a non-enveloped, single-stranded, positive-sense RNA molecule of approximately 7.2 kb in length. Recently, HEV strains have been isolated from swine in industrialized countries. In addition, cases of acute hepatitis due to novel HEV variants have been reported in humans without recognized risk factors for hepatitis E in the US, Japan and Europe. Some of the novel strains were found to be closely related to swine HEV isolates from the same area, suggesting that hepatitis E is a zoonotic disease. Thus hepatitis E is becoming an issue in countries where HEV is not, traditionally, believed to be endemic. This review summarizes the current knowledge on the transmission, structure and biology of the virus as well as diagnosis of the infection, and describes the present status in areas with a low incidence of acute hepatitis E.

Animals↗
PubMed1988

Structure and function of endogenous feline leukemia virus long terminal repeats and adjoining regions.

The nucleotide sequence of the 5' long terminal repeat (LTR) of three independent loci (CFE-6, CFE-16, and CF-14) of endogenous feline leukemia virus (FeLV) DNAs of the domestic cat genome was determined. The 3' LTR of the CFE-6 clone was also sequenced. The endogenous FeLV LTRs, which were very similar to each other in sequence and in organization of the functional domains, differed considerably from the exogenous FeLV LTR in the U3 region. The major differences in U3 included variations in sets of small (14 to 19 base pair) direct repeats, altered location of the simian virus 40 core enhancer-like sequence, and occurrence of three segments of largely nonhomologous sequences. There was extensive homology between endogenous and exogenous FeLV LTRs in sequences beginning from the TATA box through the R region down to the 3' end of the U5 region. The DNA sequence downstream of the 5' LTR encompassing the primer-binding site, leader, and almost to the end of the p15gag coding region, a point up to which the sequencing was carried out, also revealed a high degree of conservation. However, the detection of frameshift and nonsense mutations in this region of a nearly full-length endogenous provirus sequence (CFE-6) predicted its defectiveness and correlated with the lack of infectivity of this DNA. The functional studies of the endogenous LTRs, based on linkage to the bacterial cat gene and transient expression in feline cell lines, indicated that although the basic characteristics for promotion and enhancement of transcription were retained in each LTR, there was a significant variation in the activity of the cat constructs. Reconstruction and deletion analyses with the CFE-6 5' LTR revealed the presence of strong transcription regulatory sequences in the 702-base-pair region immediately upstream of the 5' boundary of the endogenous LTR. These and related data suggest that in addition to the transcription-modulating elements occurring within the LTR, the cis-acting nucleotide sequences in the upstream cellular DNA may determine the overall efficiency of transcription of the defective endogenous FeLV provirus loci of the felid genome.

Amino Acid Sequence↗
PubMed2002

Genomic profiles of clinical and environmental isolates of Vibrio cholerae O1 in cholera-endemic areas of Bangladesh.

Diversity, relatedness, and ecological interactions of toxigenic Vibrio cholerae O1 populations in two distinctive habitats, the human intestine and the aquatic environment, were analyzed. Twenty environmental isolates and 42 clinical isolates were selected for study by matching serotype, geographic location of isolation in Bangladesh, and season of isolation. Genetic profiling was done by enterobacterial repetitive intergenic consensus sequence-PCR, optimized for profiling by using the fully sequenced V. cholerae El Tor N16961 genome. Five significant clonal clusters of haplotypes were found from 57 electrophoretic types. Isolates from different areas or habitats intermingled in two of the five significant clusters. Frequencies of haplotypes differed significantly only between the environmental populations (exact test; P < 0.05). Analysis of molecular variance yielded a population genetic structure reflecting the differentiating effects of geographic area, habitat, and sampling time. Although a parameter confounding the latter differences explained 9% of the total molecular variance in the entire population (P < 0.01), the net effect of habitat and time could not be separated because of the small number of environmental isolates included in the study. Five subpopulations from a single area were determined, and from these we were able to estimate a relative differentiating effect of habitat, which was small compared with the effect of temporal change. In conclusion, the resulting population structure supports the hypothesis that spatial and temporal fluctuations in the composition of toxigenic V. cholerae populations in the aquatic environment can cause shifts in the dynamics of the disease.

Bangladesh↗
PubMed1992

Heterogeneity of feline herpesvirus type 1 strains.

Heterogeneity of 9 feline herpesvirus type 1 (FHV-1) strains consisting of the prototype C27 strain, one French isolate, six Japanese isolates, and the attenuated vaccine F2 strain was examined by biological, immunological, and molecular biological methods. No significant difference was observed in virus growth and antigenic properties among the strains in Crandell feline kidney cell cultures. Hemagglutination activity was also detected in all extracts of cells infected with each strain. However, in immunoblot analysis, a virus-structural immunogenic protein with an M(r) of 36 kDa was lacking in 2 strains, one of which was the vaccine F2 strain, whereas the other immunogenic proteins including three kinds of major glycoproteins were detected in all strains without differences in electrophoretic mobilities. Furthermore, when restriction endonuclease analysis was performed to examine the genomic heterogeneity of strains, the cleavage patterns with the enzyme MluI showed a genomic heterogeneity between wild and vaccine strains. In contrast, only a slight variation in the sizes of some fragments was shown with most of the 7 other enzymes used. These results indicated that the lack of the 36 kDa protein and the MluI cleavage pattern could be used as markers of the vaccine F2 strain. The specific markers are important not only to control the quality of the vaccine but also to evaluate the vaccine immunity in FHV-1 infection in cats.

Animals↗
PubMed1998

Structure and organization of the cardiotoxin genes in Naja naja sputatrix.

We report the genomic structure, organization and the presence of multiple isoforms of the gene encoding cardiotoxins (CTX) of Naja naja sputatrix. The cardiotoxin gene consists of six CTX isoforms, each (2.2 kb) having three exons and two introns. Two possible transcription initiation sites as well as consensus TATA boxes and transcription factor binding motifs, AP-2, NFIL-6/C/EBP, NF-kappaB and PuF have been identified in the 5'-region of the gene. The CTX gene isoforms show nucleotide variations at specific segments in exon 2 and exon 3, which correspond to the functional domains in the three-finger loop structure of the cardiotoxin molecule. The diverse functions of cardiotoxins together with our findings suggest that the cardiotoxin gene isoforms may have evolved under adaptive pressure through a positive Darwinian selection process.

Amino Acid Sequence↗
PubMed1999

Strategies of retrovirus survival in the cat.

Retroviruses establish persistent infections in their hosts which often lead to serious and fatal diseases after a long incubation period. The molecular basis of this persistence is the integration of a copy of the viral genome into cellular chromosomal DNA. At the level of the whole animal, however, each retrovirus genus has evolved a different strategy to ensure its survival. This variety is well illustrated in the cat. Feline leukaemia virus, an oncovirus, has a simple genomic structure and survives in its host by suppressing the immune response to the virus. As a result, this virus is antigenically highly conserved. By contrast, feline immunodeficiency virus and feline foamy virus, representatives of the lentiviruses and spumaviruses, respectively, have more complex genomes which include genes responsible for maintaining the virus in a latent state thereby avoiding elimination in the face of a powerful antiviral immune response. In the lentiviruses, this response drives the selection of viruses exhibiting variation in antigenicity and pathogenicity.

Animals↗
PubMed2006

A high-resolution map of Arabidopsis recombinant inbred lines by whole-genome exon array hybridization.

Recombinant populations were the basis for Mendel's first genetic experiments and continue to be key to the study of genes, heredity, and genetic variation today. Genotyping several hundred thousand loci in a single assay by hybridizing genomic DNA to oligonucleotide arrays provides a powerful technique to improve precision linkage mapping. The genotypes of two accessions of Arabidopsis were compared by using a 400,000 feature exon-specific oligonucleotide array. Around 16,000 single feature polymorphisms (SFPs) were detected in approximately 8,000 of the approximately 26,000 genes represented on the array. Allelic variation at these loci was measured in a recombinant inbred line population, which defined the location of 815 recombination breakpoints. The genetic linkage map had a total length of 422.5 cM, with 676 informative SFP markers representing intervals of approximately 0.6 cM. One hundred fifteen single gene intervals were identified. Recombination rate, SFP distribution, and segregation in this population are not uniform. Many genomic regions show a clustering of recombination events including significant hot spots. The precise haplotype structure of the recombinant population was defined with unprecedented accuracy and resolution. The resulting linkage map allows further refinement of the hundreds of quantitative trait loci identified in this well-studied population. Highly variable recombination rates along each chromosome and extensive segregation distortion were observed in the population.

Arabidopsis↗
PubMed2005

High genetic variability and evidence for plant-to-plant transfer of Banana mild mosaic virus.

A total of 154 partial nucleotide sequences within the Banana mild mosaic virus (BanMMV) ORF1, which encodes the viral RNA-dependent RNA polymerase (RdRp), was obtained from 68 distinct infected banana accessions originating from various locations worldwide. The 310 nt sequences displayed a high level of variability with a mean pairwise nucleotide sequence divergence level of 20.4 %. This situation resulted essentially from a high rate of synonymous mutations. A similar analysis was performed for a limited selection of 10 banana accessions (30 sequences) on the region comprising approximately the last 310 nt of the BanMMV genome. This region corresponds to the 3' end of ORF5, which encodes the coat protein (234 nt), and to the 3' non-coding region. This analysis confirmed the high level of diversity observed in the RdRp dataset, characterized by a high level of synonymous mutations. Analysis of intra-host diversity indicated the existence of two distinct situations, with some plants containing only closely related sequence variants, whereas others contained widely divergent isolates. Analyses indicated that BanMMV genetic diversity is not structured by the geographical origin of the infected Musa accessions or by their genotype. This situation may be, in part, explained by the exchange of banana germplasm between different parts of the world and also by plant-to-plant transfer of virus isolates, the evidence for which is, for the first time, provided by this study.

Base Sequence↗
PubMed2006

A genomic scan for divergent selection in a secondary contact zone between Atlantic and Gulf of Mexico oysters, Crassostrea virginica.

The degree of population structure within species often varies considerably among loci. This makes it difficult to determine whether observed variance reflects neutral-drift stochasticity or locus-specific selection at one or more loci. This uncertainty is exacerbated when evolutionary equilibrium cannot be assumed and/or admixture potentially inflates genomic variance. Thus, the value of a 'genome scan', where locus-specific summary statistics are compared with a simulated neutral distribution among loci, may be limited in secondary contact zones if the null distribution is sensitive to the timing of secondary contact. Of particular interest here is the wide variance previously observed in locus-specific patterns of population structure between Atlantic and Gulf of Mexico populations of eastern oyster, Crassostrea virginica. To test the robustness of an equilibrium null model, we compared among-locus distributions of F(ST) simulated under migration-drift equilibrium and several nonequilibrium secondary contact histories. We then tested for evidence of divergent selection between two oyster populations on either side of a secondary contact zone using 215 amplified fragment length polymorphism (AFLP) loci. Constant-migration equilibrium and nonequilibrium secondary-contact simulations produced equivalent distributions of F(ST) when anchored by the global mean F(ST) observed in oysters, 0.0917. The 99th quantile of simulated neutral F(ST) encompassed most of the variation among oyster loci. Three AFLP loci exhibited F(ST) values higher than this threshold. Although no locus was significant after correcting for multiple tests, our results show in geographically clinal organisms: AFLPs can efficiently characterize the genomic distribution of F(ST); equilibrium models can be used to evaluate outliers; these procedures help focus research on genomic regions of interest.

Animals↗
PubMed2001

Analysis of PBX1 as a candidate gene for type 2 diabetes mellitus in Pima Indians.

The human proto-oncogene PBX1 codes for a homeodomain containing protein that modulates expression of several genes, including those contributing to regulation of insulin action and glucose metabolism. PBX1 is located on chromosome 1q22, a region linked with type 2 diabetes in Pima Indians, Caucasians, and an Old Order Amish population. We have investigated the PBX1 genomic sequence to identify polymorphisms that may contribute to diabetes susceptibility in the Pimas. PBX1 is composed of nine exons spanning approx. 117 kb and is located within 300 kb of microsatellite D1S1677, which marks the peak of linkage to diabetes susceptibility in the Pima Indians. We detected 16 single nucleotide polymorphisms in PBX1 including one causing a glycine to serine substitution at residue 21. Comparison of the frequencies of the polymorphisms between affected and unaffected Pima Indians did not detect any significant differences, indicating that mutations in PBX1 do not explain the linkage of 1q with type 2 diabetes in this population. The genomic structure of PBX1 provides a basis for similar systematic examinations of this candidate locus in other populations in relation to both type 2 diabetes and other metabolic disorders.

3' Untranslated Regions↗
PubMed2003

Nonrandom distribution of alu elements in genes of various functional categories: insight from analysis of human chromosomes 21 and 22.

The first draft of the human genome has revealed enormous variability in the global distribution of Alu repeat elements. There are regions such as the four homeobox gene clusters, which are nearly devoid of these repeats that contrast with repeat dense regions in other transcriptionally active regions of the genome. Our analysis of the completely sequenced chromosomes 21 and 22 revealed a striking bias in Alu distribution. These elements are more clustered in genes which are involved in metabolism, transport, and signaling processes. In contrast, they are significantly fewer in genes coding for information pathway components as well as structural proteins. This bias in Alu distribution is independent of the effect of Alu density of the flanking genomic region and is also not affected by the GC content of the gene and its upstream and downstream regions. The relative proportions of Alu subfamilies (Alu J, Alu S, and Alu Y) are not significantly different in genes with high Alu density belonging to the functional categories of transport, metabolism, and signaling. However, in the structural proteins and information genes, these proportions are lower than the other three categories. We suggest that Alu elements might be involved in regulatory mechanisms and are therefore differentially selected in primate genomes.

Alu Elements↗
PubMed1989

Protein and nucleic acid analysis of influenza B viruses isolated in Italy in 1984.

Genomic and phenotypic analysis of 30 influenza B viruses, isolated in Italy in 1984, antigenically closely related to the B/USSR/100/83 prototype virus, was carried out using T1-oligonucleotide fingerprinting of total RNA and one-dimensional peptide mapping. The results of fingerprinting analysis indicated an oligonucleotide spot homology of 90-96%, corresponding to a nucleotide sequence variation of only 0.75-0.3%. All the strains appear to belong to the same evolutionary line. Nevertheless, heterogeneity was found at the structural and antigenic level, when the viruses were compared by peptide mapping and monoclonal antibody analysis. No correlation between the biochemical variability of the viruses and the epidemiological characteristics of the different strains was established, which is consistent with the hypothesis that distinct variants, arisen at different times from a parental strain, co-circulate during an epidemic, although the additional occurrence of random mutations during the evolution of the epidemic cannot be excluded.

Antibodies, Monoclonal↗
PubMed2006

Molecular characterization of Ph1 as a major chromosome pairing locus in polyploid wheat.

The foundation of western civilization owes much to the high fertility of bread wheat, which results from the stability of its polyploid genome. Despite possessing multiple sets of related chromosomes, hexaploid (bread) and tetraploid (pasta) wheat both behave as diploids at meiosis. Correct pairing of homologous chromosomes is controlled by the Ph1 locus. In wheat hybrids, Ph1 prevents pairing between related chromosomes. Lack of Ph1 activity in diploid relatives of wheat suggests that Ph1 arose on polyploidization. Absence of phenotypic variation, apart from dosage effects, and the failure of ethylmethane sulphonate treatment to yield mutants, indicates that Ph1 has a complex structure. Here we have localized Ph1 to a 2.5-megabase interstitial region of wheat chromosome 5B containing a structure consisting of a segment of subtelomeric heterochromatin that inserted into a cluster of cdc2-related genes after polyploidization. The correlation of the presence of this structure with Ph1 activity in related species, and the involvement of heterochromatin with Ph1 (ref. 6) and cdc2 genes with meiosis, makes the structure a good candidate for the Ph1 locus.

Chromosome Pairing↗
PubMed1997

Lower antigen site density and weak D immunogenicity cannot be explained by structural genomic abnormalities or regulatory defects of the RHD gene.

BACKGROUND: The weak D phenotype is characterized serologically by a weak or negative agglutination reaction with polyclonal anti-D in an immediate-spin test. Agglutination is enhanced in the indirect antiglobulin test. Red cells that are typed weak D have a much lower number of apparently complete D antigens at their cell surface and are associated with considerably weaker immunogenicity than are red cells with normal D. In a previous study, the number of D sites per cell was determined in eight unrelated weak D individuals to range from 490 to 1870 D sites per cell, which corresponded to 4 to 14.2 percent of the number of D sites in CcDee samples. STUDY DESIGN AND METHODS: The RHD gene was investigated for structural abnormalities by Southern blot experiments and polymerase chain reaction-based RHD typing in these individuals. In addition, abnormalities in the transcription process were studied by sequence analysis of RH transcripts and by comparing the relative amounts of RHD mRNA in weak D to those in CcDee, CcDEe, and -D- samples by using a semiquantitative reverse transcriptase-polymerase chain reaction analysis. RESULTS: The RHD gene in weak D phenotypes does not show any abnormalities at either the genomic or the transcriptional level when compared to the RHD gene in normal D phenotypes. CONCLUSION: The weaker immunogenicity of weak D is not explained by structural difference in the RHD gene itself. The weaker expression of D might be caused by factors involved in the Rh-related complex or by an as yet unidentified suppressor gene. This study supports the concept that weak D phenotypes carry complete D polypeptides and reflect a quantitative rather than a qualitative variation of D.

Antibodies, Monoclonal↗