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PubMed2006

Nutrigenomics and nutrigenetics: the 'omics' revolution in nutritional science.

The execution of the Human Genome Project has brought forth a wealth of information about the structure of the genome, which can now be used to study how the interplay between our genes and factors from the environment such as nutrition relate to a state of health or disease. To enable such studies, novel technologies have been designed in particular to monitor the activity of multiple genes simultaneously at the level of the RNA by transcriptomics, or the level of the proteins by proteomics. In addition, genome information has boosted approaches to study the role of genetic variation to explain individual differences in responses to nutrition, underlying in part the susceptibility for nutrition-related disorders. These new areas of science referred to as 'nutrigenomics' and 'nutrigenetics' respectively, will increase our fundamental knowledge of the interaction between life processes and our diet or specific components thereof, which may in time lead to the development of novel functional foods to improve the health status of the general population, and to the personalized diet to prevent the onset of nutrition-related disorders in genetically predisposed individuals.

Genetics↗
PubMed2003

Pseudogenes contribute to the extreme diversity of nuclear ribosomal DNA in the hard coral Acropora.

One characteristic of Indo-Pacific Acropora spp. is extremely high diversity in rDNA sequences at both the species and individual levels. In order to test the hypothesis that pseudogenes may contribute to this diversity, three kinds of analyses were conducted. First, for A. millepora (the species containing the most diverse suite of rDNA types), RT-PCR was used to determine which 5.8S rDNA types are expressed. Second, as previous studies have indicated that interspecific hybridization has occurred in the genus Acropora and silencing of rDNA loci via nucleolar dominance has been shown in some cases to involve methylation, patterns of variation were examined at methylation-susceptible sites. Third, patterns of substitution at conserved sites (including those that are likely to contribute to secondary structure in rRNA) in the 5.8S rDNA were examined. These analyses consistently indicated that one rDNA sequence type present in a broad range of Indo-Pacific Acropora species is likely to consist predominantly of pseudogenes. Patterns of variation also suggest that species may differ with respect to which rDNA sequence types have been silenced and which are active. These pseudogenes are likely to have arisen as a consequence of the introduction of highly divergent rDNA types into single genomes by interspecific hybridization events, and we attribute the extreme rDNA diversity characteristic of many Acropora species to both the independent evolution of these silenced rDNA types and to the suppressive effects of high sequence diversity on homogenization processes acting on functional loci.

Animals↗
PubMed2026

Analyzing Meiosis in Maize.

Meiosis is central to sexual reproduction and the main source of genetic diversity in plants. Understanding how meiotic processes are regulated has direct relevance to agriculture. As meiotic recombination is the vehicle of plant breeding, gaining the ability to influence recombination patterns can accelerate crop improvement. Maize is a powerful model for studying plant meiosis, thanks to its large chromosomes, well-developed genetics, and the availability of diverse cytogenetic and molecular tools. Insights gained from maize studies can extend to other species. In this review, we describe a variety of approaches for examining meiosis and meiotic recombination in maize. Cytological techniques, including protein immunolocalization and fluorescence in situ hybridization (FISH), enable visualization of chromosome structure and behavior, as well as crossover (CO) formation. Chromatin immunoprecipitation (ChIP) is used in meiosis research to determine locations of recombination proteins, identify recombination sites, and elucidate chromatin features, such as histone modifications. Quantification of COs at specific genomic sites through pollen typing by droplet digital PCR allows precise high-resolution measurement of recombination rates. Combining cytology, protein localization, and molecular assays provides a multiscale picture of meiosis, linking molecular mechanisms to chromosome behavior and, ultimately, to genetic variation.

Journal Article↗
PubMedDate not supplied

Structural variations in the H-2 genes of AKR lymphomas.

K36.16 is an AKR H-2k thymoma which expresses an aberrant H-2Dd-like allospecificity, does not have a detectable amount of the H-2Kk syngeneic antigen and grows very easily in syngeneic mice. By DNA-mediated gene transfer experiments, we were able to obtain transformed clones which do express the H-2Kk molecules and are rejected by AKR mice. Southern hybridization was performed to assess whether any gross changes had occurred in the K36.16 H-2K locus or elsewhere in the MHC, which might explain the lack of H-2K expression and/or the presence of the aberrant H-2Dd-like allospecificity. Specific H-2 class I DNA probes were used to compare the K36.16 genomic DNA with normal AKR thymus DNA after digestion with a variety of restriction enzymes. After hybridization with the pH-2IIa probe a 2.8 kb 'Hind III' fragment was identified in the K36.16 genomic DNA which is absent from AKR DNA. The pH-2IIa probe detects the third, transmembrane and cytoplasmic domains of class I genes. Although these changes are indicative of MHC genome modifications it is not yet possible to link these specific Southern blot pattern variations with the phenotypic changes mentioned above.

Animals↗
PubMedDate not supplied

[Antibodies to the structural proteins of the measles virus studied in some chronic diseases].

The qualitative and quantitative analysis of antibodies to measles virus (MV) structural proteins (SP) in sera from patients with chronic glomerulonephritis (CGN), chronic active hepatitis (CAH), and liver cirrhosis (LC) was done. The patients were shown to have neutralizing antibody titres (NAT) higher than those in healthy subjects. An analysis of antibodies to SP was carried out by the radioimmunoprecipitation assay. Antibodies were detected to hemagglutinin, nucleoprotein (NP), fusion protein and to matrix protein (M) both in sera from the patients with these chronic diseases, healthy subjects, and patients with active measles. (The two latter groups were selected for comparison). However, some patients with CAH and LC had no antibodies to M protein in spite of very high NAT. The quantitative analysis of MV antibodies to SP was done only for NP because this antibody had the least individual variations. The quantity of anti-NP antibodies was higher in most sera from patients with chronic diseases than in those from healthy subjects, and reached the level of that in patients with active measles. The presence of MV genome in the peripheral blood lymphocytes from patients CAH, CGN, and LC had been shown earlier. So it is assumed that MV persists in lymphoid tissue where the expression of all SP genes is realized.

Antibodies, Viral↗
PubMed2006

A new rubisco-like protein coexists with a photosynthetic rubisco in the planktonic cyanobacteria Microcystis.

Two genes encoding proteins related to large subunits of Rubisco were identified in the genome of the planktonic cyanobacterium Microcystis aeruginosa PCC 7806 that forms water blooms worldwide. The rbcL(I) gene belongs to the form I subfamily typically encountered in cyanobacteria, green algae, and land plants. The second and newly discovered gene is of the form IV subfamily and widespread in the Microcystis genus. In M. aeruginosa PCC 7806 cells, the expression of both rbcL(I) and rbcL(IV) is sulfur-dependent. The purified recombinant RbcL(IV) overexpressed in Escherichia coli cells did not display CO(2) fixation activity but catalyzed enolization of 2,3-diketo-5-methylthiopentyl-1-phosphate, and the rbcL(IV) gene rescued a Bacillus subtilis MtnW-deficient mutant. Therefore, the Microcystis RbcL(IV) protein functions both in vitro and in vivo and might be involved in a methionine salvage pathway. Despite variations in the amino acid sequences, RbcL(IV) shares structural similarities with all members of the Rubisco superfamily. Invariant amino acids within the catalytic site may thus represent the minimal set for enolization, whereas variations, especially located in loop 6, may account for the limitation of the catalytic reaction to enolization. Even at low protein concentrations in vitro, the recombinant RbcL(IV) assembles spontaneously into dimers, the minimal unit required for Rubisco forms I-III activity. The discovery of the coexistence of RbcL(I) and RbcL(IV) in cyanobacteria, the ancestors of chloroplasts, enlightens episodes of the chaotic evolutionary history of the Rubiscos, a protein family of major importance for life on Earth.

Amino Acid Sequence↗
PubMed1999

Genomic instability and recurrent breakpoints are main cytogenetic findings in Hodgkin's disease.

BACKGROUND AND OBJECTIVE: Successful cytogenetic studies in Hodgkin's disease (HD) are rare, and, except for hyperdiploidy, no chromosome changes typical for this disorder have been described. The purpose of this study was to collect cytogenetic information from a new series of lymphoid neoplasms diagnosed either as classical HD or as Hodgkin's-like anaplastic large cell lymphoma (HD-like ALCL), according to the REAL Classification. DESIGN AND METHODS: We studied 27 cases of HD and 10 cases of HD-like ALCL. Cytogenetic investigations were performed on lymph nodes (35 cases), bone marrow or pleural effusion. A large screening of slides was performed to detect abnormal metaphases despite the low mitotic index of Reed-Sternberg cells. In addition to ours, available published data were analyzed in detail to identify recurring cytogenetic events. RESULTS: Metaphases which could be analyzed were obtained in 86.5% of cases, with 59.4% showing abnormal clones. We found a peculiar kind of cytogenetic instability in which, despite variations in the type of structural rearrangements, chromosome breakpoints were non-randomly distributed. Moreover, from our data plus those collected from literature on HD (total 177 cases), the number of breakpoints was higher in patients in a more advanced clinical stage. INTERPRETATION AND CONCLUSIONS: Cytogenetic studies in HD are highly informative regarding clonality, provided large numbers of metaphases are examined. Based on karyotype, genetic changes in HD and HD-like ALCL are similar. Results are consistent with a high degree of chromosomal instability and predominance of hyperdiploid complex karyotypes. Chromosome breakpoints are non-randomly distributed and more numerous in advanced clinical stages.

Adolescent↗
PubMed1993

Chromosome bands--flavours to savour.

The mammalian chromosome is longitudinally heterogeneous in structure and function and this is the basis for the specific banding patterns produced by various chromosome staining techniques. The two most frequently used techniques are G, or Giemsa banding and R, or reverse banding. Each type of stained band is characterised by variations in gene density, time of replication, base composition, density of repeat sequences, and chromatin packaging. It is increasingly apparent that R and G bands, which are complementary to each other, represent separate compartments of the euchromatic human genome, with R bands containing the vast majority of genes. R bands are also more GC-rich, contain a higher density of Alu repeats, and replicate earlier in S phase, than G bands. These properties may be interdependent and may have coevolved.

Base Composition↗
PubMed2006

The effect of assortative mating upon genetic association studies: spurious associations and population substructure in the absence of admixture.

Spurious associations due to confounding factors are an often cited and intensely debated concern for genetic association studies. Great attention has been focused upon the specific threat of confounding due to population stratification. This emphasis has spurred the development of many statistical genetic methods to detect and correct for the potentially confounding effects of admixture. Unfortunately, this emphasis on admixture has led some authors to suggest that if ethnically homogenous populations are used, spurious associations are unlikely to occur. We show that under small and realistic degrees of assortative mating over time, spurious associations arise even in ethnically homogeneous populations. We demonstrate that structured association and genomic control tests can, under certain conditions, correct for these spurious associations. We conclude that investigators should not assume spurious associations will not occur in association studies using ethnically homogenous populations and recommend the use of genomic control methods and/or family-based association tests within genetic association studies.

Chromosome Mapping↗
PubMed2004

Characterization of the Anaplasma marginale msp2 locus and its synteny with the omp1/p30 loci of Ehrlichia chaffeensis and E. canis.

Major surface protein 2 (MSP2) is an immunodominant and antigenically variant protein in the outer membrane of the rickettsia Anaplasma marginale. MSP2 variation is generated by recombination into a single operon-linked genomic expression site. The complete 5.6-kb msp2 locus was identified by sequencing a 90-kb region of the St. Maries strain of A. marginale. The locus encoded, in a 5' to 3' direction, a transcriptional regulator followed by five outer membrane proteins, OMP1, OpAG3, OpAG2, OpAG1, and MSP2. The sequences of this entire locus were analyzed using six genetically and phenotypically distinct strains of A. marginale. The overall locus structure was highly conserved with 100% identity among strains in the transcriptional regulator. Synonymous and nonsynonymous exchanges were infrequent in omp1 and rare in opag1 and opag2 among the six strains without strong bias for either type of exchange (neutral mutations). In contrast, mutations in opag3 seem to underlie purifying (negative) selection reflecting pressure to retain protein structure, in marked contrast to the highly antigenically variant MSP2. Interestingly, the 5' structure of this A. marginale msp2 locus is conserved in the omp1 gene locus of Ehrlichia chaffeensis and p30 gene locus of E. canis despite marked divergence between genera in the structure of the 3' region of the loci. This supports the hypothesis that the expression sites of these important immunogenic proteins are derived from a common precursor with later divergent evolution along genus lines.

Anaplasma marginale↗
PubMed1998

Rates and patterns of chromosome evolution in enteric bacteria.

Although several types of large-scale alterations potentially affect the structure and organization of bacterial genomes, recent analyses of physical maps and complete genomic sequences reveal that chromosome heterogeneity in enteric bacteria has resulted from the acquisition and deletion of large segments of DNA. These acquired sequences can provide novel functions immediately upon their introduction and play a significant role in the diversification of bacterial species.

Biological Evolution↗
PubMed2003

Distinct geographic patterns of genetic diversity are maintained in wild barley (Hordeum vulgare ssp. spontaneum) despite migration.

Mutations arise in a single individual and at a single point in time and space. The geographic distribution of mutations reflects both historical population size and frequency of migration. We employ coalescence-based methods to coestimate effective population size, frequency of migration, and level of recombination compatible with observed genealogical relationships in sequence data from nine nuclear genes in wild barley (Hordeum vulgare ssp. spontaneum), a highly self-fertilizing grass species. In self-fertilizing plants, gamete dispersal is severely limited; dissemination occurs primarily through seed dispersal. Also, heterozygosity is greatly reduced, which renders recombination less effective at randomizing genetic variation and causes larger portions of the genome to trace a similar history. Despite these predicted effects of this mating system, the majority of loci show evidence of recombination. Levels of nucleotide variation and the patterns of geographic distribution of mutations in wild barley are highly heterogeneous across loci. Two of the nine sampled loci maintain highly diverged, geographic region-specific suites of mutations. Two additional loci include region-specific haplotypes with a much shallower coalescence. Despite inbreeding, sessile growth habit, and the observation of geographic structure at almost half of sampled loci, parametric estimates of migration suggest that seed dispersal is sufficient for migration across the approximately 3,500-km range of the species. Recurrent migration is also evident based on the geographic distribution of mutational variation at some loci. At one locus a single haplotype has spread rapidly enough to occur, unmodified by mutation, across the range of the species.

Biological Evolution↗
PubMed1998

The hepatitis B virus post-transcriptional regulatory element contains two conserved RNA stem-loops which are required for function.

Human Hepatitis B Virus (HBV) RNAs contain a cis -acting sequence, the post-transcriptional regulatory element (HPRE), which facilitates the cytoplasmic localization of intronless transcripts. Our previous studies have shown that the HPRE is composed of at least two independent sub-elements, HPREalpha and HPREbeta, which co-activate a reporter for RNA export in a greater than additive manner. Utilizing deletion, mutation and co-variational analyses, we have identified three regions important for full HPRE activity. The three separate regions of the HPRE function can function independently in a dose-dependent manner when multimerized. Two of these regions contain stem loops, HSLalpha and HSLbeta1, which are necessary for full HPRE function. These structures are conserved throughout the mammalian Hepadnaviruses. Disruption of either stem-loop structure by mutagenesis decreases HPRE function while compensatory mutations restore activity. The location of the stem-loops in the genome reveal that they are present in all of the HBV transcripts. HSLalpha and HSLbeta1 are likely to contain the binding sites for the cellular factor(s) which mediates HPRE function.

Base Sequence↗
PubMed2002

The cyanobacterial tRNA(Leu) (UAA) intron: evolutionary patterns in a genetic marker.

Cyanobacterial tRNA(Leu) (UAA) intron sequences from natural populations of Nostoc and other cyanobacteria were compared. Variation between the different introns was not randomly distributed but strongly restricted by the secondary and tertiary structure of the intron. Although all Nostoc sequences examined shared high similarity, differences were observed in one stem-loop. This stem-loop could be divided into two classes, both built up from two base pairing heptanucleotide repeats. Size variation was primarily caused by different numbers of repeats, but some strains also contained additional sequences in this stem-loop not following the heptanucleotide repeat motif. Several sequences showing similarity with these additional sequences were identified in the Nostoc punctiforme genome. Furthermore, the regions flanking these sequences contained the same, or similar, heptanucleotide repeats as those flanking the corresponding sequences in the intron. It is proposed that both slipped strand mispairing during replication and homologous recombination among different loci in the genome are important processes causing variation between introns.

Cyanobacteria↗
PubMed2006

Selective constraint and genetic differentiation in geographically distant barley yellow dwarf virus populations.

Numerous studies have documented molecular variability in plant virus populations, but few have assessed the relative contribution of natural selection and genetic drift in generating the observed pattern of diversity. To this end, gene function, environment and phylogenetic history were examined to observe the effect on genetic diversity and population structure of the PAV and PAS species of Barley yellow dwarf virus (family Luteoviridae). Three functional classes of gene were analysed: transcription-related (RdRp), structural (CP) and movement-related (MP). The results indicate that there were no inherent differences, in terms of total diversity or diversity at synonymous or non-synonymous nucleotide sites, between functional classes of genes or populations. Rather, selective constraints on a gene may be more or less relaxed depending on its function and the phylogenetic history of the population sampled. The CP of the PAS species, but not the PAV species, was differentiated genetically between regions. This is probably due to genetic drift, as there was no evidence that any gene deviated from a neutral model of evolution or is under positive selection. In general, the MP was under considerably less functional constraint than structural or replication-related proteins and four positively selected codon sites were identified. Mutations at these sites differentiate species and geographical subpopulations, so presumably they have aided the virus in adaptation to its host environment and contributed to intra- and interspecies diversification.

Biological Evolution↗
PubMed2000

MHC class II pseudogene and genomic signature of a 32-kb cosmid in the house finch (Carpodacus mexicanus).

Large-scale sequencing studies in vertebrates have thus far focused primarily on the genomes of a few model organisms. Birds are of interest to genomics because of their much smaller and highly streamlined genomes compared to mammals. However, large-scale genetic work has been confined almost exclusively to the chicken; we know little about general aspects of genomes in nongame birds. This study examines the organization of a genomic region containing an Mhc class II B gene in a representative of another important lineage of the avian tree, the songbirds (Passeriformes). We used a shotgun sequencing approach to determine the sequence of a 32-kb cosmid insert containing a strongly hybridizing Mhc fragment from house finches (Carpodacus mexicanus). There were a total of three genes found on the cosmid clone, about the gene density expected for the mammalian Mhc: a class II Mhc beta-chain gene (Came-DAB1), a serine-threonine kinase, and a zinc finger motif. Frameshift mutations in both the second and third exons of Came-DAB1 and the unalignability of the gene after the third exon suggest that it is a nonfunctional pseudogene. In addition, the identifiable introns of Came-DAB1 are more than twice as large as those of chickens. Nucleotide diversity in the peptide-binding region of Came-DAB1 (Pi = 0.03) was much lower than polymorphic chicken and other functional Mhc genes but higher than the expected diversity for a neutral locus in birds, perhaps because of hitchhiking on a selected Mhc locus close by. The serine-threonine kinase gene is likely functional, whereas the zinc finger motif is likely nonfunctional. A paucity of long simple-sequence repeats and retroelements is consistent with emerging rules of chicken genomics, and a pictorial analysis of the "genomic signature" of this sequence, the first of its kind for birds, bears strong similarity to mammalian signatures, suggesting common higher-order structures in these homeothermic genomes. The house finch sequence is among a very few of its kind from nonmodel vertebrates and provides insight into the evolution of the avian Mhc and of avian genomes generally.

Animals↗
PubMed2006

Microbial biochemistry, physiology, and biotechnology of hyperthermophilic Thermotoga species.

High-throughput sequencing of microbial genomes has allowed the application of functional genomics methods to species lacking well-developed genetic systems. For the model hyperthermophile Thermotoga maritima, microarrays have been used in comparative genomic hybridization studies to investigate diversity among Thermotoga species. Transcriptional data have assisted in prediction of pathways for carbohydrate utilization, iron-sulfur cluster synthesis and repair, expolysaccharide formation, and quorum sensing. Structural genomics efforts aimed at the T. maritima proteome have yielded hundreds of high-resolution datasets and predicted functions for uncharacterized proteins. The information gained from genomics studies will be particularly useful for developing new biotechnology applications for T. maritima enzymes.

Bacterial Proteins↗