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An estimate of the amount of genetic variation in the common mussel Mytilus edulis.

Allozyme variation in a population of the common mussel Mytilus edulis in Mumbles, South Wales, has been studied by starch gel electrophoresis. On the basis of data obtained for 34 loci, we estimate the proportion of loci polymorphic to be 30%. Using only the 29 loci for which individual genotypes can be accurately typed, the average heterozygosity is estimated to be 9.5 +/- 3.6%. The calculated expected average heterozygosity based on Hardy-Weinberg expectations is identical with the observed value. Allele frequency data at six polymorphic loci are given for several other British populations. There is no significant geographic heterogeneity. The results are discussed in relation to genetic adaptive strategies and are shown to be inconsistent with the predictions of the neutral hypothesis.

Alleles↗

AFLP to assess genetic variation in laboratory gerbils (Meriones unguiculatus).

The amplified fragment length polymorphism (AFLP) technique has been increasingly employed for characterizing inbred breeds of animals and detecting strain-specific polymorphisms. The majority of animals studies conducted in biomedical research are performed on rodent species, among which laboratory-reared Mongolian gerbils can be included. Despite the wide use of gerbils in scientific studies, their genetics has rarely been studied. Therefore we investigated the genetic differentiation of laboratory bred gerbils by means of AFLP markers. Six EcoRI/TaqI primer combinations were selected among 13 different combinations to assess the genetic polymorphisms in four stocks of animals: Charles River (CR), Harlan (Ha), Parma (Pr), and Crossbred (Cb). CR and Ha gerbils were purchased from commercial vendors, while Pr and Cb were derived from animals bred in our animal colony. A total of 228 fragments ranging between 70 and 650 bp were obtained. The mean percentage of polymorphic loci across primer combinations was 7.5%. Calculation of genetic distances through application of different algorithms (Nei's, BSI, and Jaccard's indexes) confirmed the poor genetic diversity between stocks. Nevertheless, a differentiation of the Pr and Cb stocks from the more homogeneous CR and Ha was revealed, in agreement with the different breeding derivation and management of the stocks.

Animals↗

Genetic variation associated with differences in the response of plasma apolipoprotein B levels to dietary fibre.

1. We hypothesized that differences within genes whose protein products are involved in apolipoprotein B metabolism could influence the response of plasma apolipoprotein B-containing lipoprotein concentrations to increases in dietary fibre. 2. We studied 67 subjects (43 men and 24 women) who had taken part in parallel 2 week metabolic dietary studies involving either wheat bran or oat bran supplementation. Fasting blood lipid, lipoprotein and apolipoprotein concentrations were measured at the start and end of the 2 week metabolic period. Genotypes were determined using DNA markers for the low-density lipoprotein receptor, apolipoprotein B, apolipoprotein CIII and hepatic lipase gene loci. 3. Reductions in plasma concentrations of apolipoprotein B were significantly different depending on genotype determined with a low-density lipoprotein receptor DNA marker (P = 0.03). There was no significant variation in the reduction of plasma total cholesterol, low-density lipoprotein cholesterol or apolipoprotein B concentrations for alleles of other genes tested. 4. Thus, genetic variability is associated with interindividual differences in the fibre-related reduction in plasma apolipoprotein B and apolipoprotein B-containing lipoprotein concentrations. Implementation of current dietary recommendations to reduce plasma lipoprotein levels with fibre may have variable effects in different individuals in part because of structural differences in candidate genes whose products are involved in lipoprotein metabolism.

Apolipoproteins B↗

Genetic variation in the conservative gene region of Norovirus genogroup II strains in environmental and stool samples.

Noroviruses (NoVs) have been one of leading etiological agents for infectious gastroenteritis over the world. Gastroenteritis caused by NoVs is prevalent in winter season, and the contamination of the water environment with NoVs in the epidemic cold season is frequently reported. In contrast, the number of gastroenteritis patients and NoVs in the water environment are reduced during the nonepidemic summer season, and the year-round fate of NoVs has remained to be elucidated. In this study, we collected nucleotide sequences of NoV genogroup II (GII) from domestic sewage, sewage sludge, treated wastewater, river water, and stool samples of gastroenteritis patients in geographically close areas. Phylogenetic analysis of the obtained NoV gene revealed that six out of seven isolates from environmental samples and 10 out of 11 isolates from stool samples belong to genotype 3 (NoV GII.3) or 4 (NoV GII.4), which have been prevalent throughout the world. Genetic distances between the conservative gene region of NoV GII.4 variants implied that genetically diverse strains are likelyto occur in environmental samples. The evaluation of the evolutionary change of NoV gene obtained from environmental samples would make it possible to elucidate the year-round fate of NoVs.

Base Sequence↗

Genetic variation between Helicobacter pylori strains: gene acquisition or loss?

Previously identified strain-specific genes of Helicobacter pylori were analysed for GC content and preference in codon usage. The results indicate that in H. pylori strain specificity is mainly driven by gene uptake. Incoming strains of Helicobacter or other species can occasionally donate genes but the identification of the donor species is hampered by ongoing evolutionary processes and the lack of an adequate number, or indeed a total absence, of gene homologues.

Codon↗

Genetic variation in mRNA coding sequences of highly conserved genes.

The frequency and distribution of genetic polymorphism in the human genome is a question of major importance. We have studied this in highly conserved genes, which encode crucial functions such as DNA replication, mRNA transcription, and translation. Evolutionary comparisons suggest that these genes are under particularly strong selective pressure, and their frequency of nucleotide sequence polymorphism would be expected to represent a minimum estimate for sequence variation throughout the genome. We have analyzed the complete coding sequence and the 3'-untranslated region (3'-UTR) of 22 human genes, most of which have homologs in all cellular organisms and all of which are at least 25% amino acid identical to homologs in yeast. Comparisons with similar studies of less conserved human disease genes indicate that 1) evolutionarily conserved genes are, on average, less polymorphic than disease related genes; 2) the difference in polymorphism levels is attributable almost entirely to reduced levels of variation in protein coding sequences, whereas noncoding sequences have similar levels of polymorphism; and 3) the character of polymorphism, in terms of the spectrum and frequency of mutational changes, is similar.

Cell Line↗

The causes and consequences of genetic variation in dengue virus.

Despite the fact that dengue is one of the most prevalent viral infections of humans, the mechanisms responsible for its pathogenesis remain uncertain. Evolutionary studies of dengue virus have revealed that its genetic diversity is increasing. This, coupled with evidence that viral strains could naturally differ in virulence, suggests that in the future we might be exposed to viruses with an expanded range of pathogenic properties.

Dengue↗

Patterns of molecular genetic variation among African elephant populations.

The highly threatened African elephants have recently been subdivided into two species, Loxodonta africana (savannah or bush elephant) and L. cyclotis (forest elephant) based on morphological and molecular studies. A molecular genetic assessment of 16 microsatellite loci across 20 populations (189 individuals) affirms species level genetic differentiation and provides robust genotypic assessment of species affiliation. Savannah elephant populations show modest levels of phylogeographic subdivision based on composite microsatellite genotype, an indication of recent population isolation and restricted gene flow between locales. The savannah elephants show significantly lower genetic diversity than forest elephants, probably reflecting a founder effect in the recent history of the savannah species.

Africa South of the Sahara↗

Genetic Variation and Evolutionary Characteristics of Coxsackievirus B1: F3 Subtype Associated With Hand, Foot and Mouth Disease in China.

Coxsackievirus B1 (CV-B1) is primarily associated with meningitis but can also cause localized outbreaks of hand, foot, and mouth disease (HFMD). This study analyzed the genetic diversity of the VP1 gene in 39 strains of the CVB1 virus isolated from HFMD children across 15 provinces in China between 2010 and 2024, as well as 179 strains from 17 countries. Based on the average nucleotide difference of VP1 gene, we classified CVB1 virus into six genotypes A to F, Notably, genotype F is newly classified. Since 2010, genotype F guadually replaced genotype E as the dominant genotype in China and has further subdivided into three subtypes: F1, F2, and F3, with F3 being the most prevalent subtype in China currently. We specifically study the mild and severe cases within the F3 subtype. Temperature-sensitivity experiments revealed no differences between mild and severe cases of the F3 subtype, and they all belong to temperature-sensitive strains. Interestingly, we found that mild cases of the F3 subtype did not involve recombination, whereas all severe cases of the F3 subtype showed recombination with Coxsackievirus B4 (CVB4). CVB4 has consistently been the primary pathogen responsible for severe neonatal illnesses, suggesting that recombination between the F3 subtype and CVB4 may be associated with the development of severe HFMD. These findings provide fundamental scientific data for further investigation into the epidemiology and genetic characteristics of variants of Coxsackievirus B1 in China.

Humans↗

Kinetics and in vivo induction of genetic variation of vlsE in Borrelia burgdorferi.

The Lyme disease agent, Borrelia burgdorferi, is able to persistently infect humans and animals for months or years in the presence of an active immune response. It is not known how the organisms survive immune attack in the mammalian host. vlsE, a gene localized near one end of linear plasmid lp28-1 and encoding a surface-exposed lipoprotein in B. burgdorferi B31, was shown recently to undergo extensive genetic and antigenic variation within 28 days of initial infection in C3H/HeN mice. In this study, we examined the kinetics of vlsE sequence variation in C3H/HeN mice at 4, 7, 14, 21, and 28 days and at 7 and 12 months postinfection. Sequence changes were detected by PCR amplification and sequence analysis as early as 4 days postinfection and accumulated progressively in both C3H/HeN and CB-17 severe combined immunodeficient (SCID) mice throughout the course of infection. The sequence changes were consistent with sequential recombination of segments from multiple silent vls cassette sites into the vlsE expression site. No vlsE sequence changes were detected in organisms cultured in vitro for up to 84 days. These results indicate that vlsE recombination is induced by a factor(s) present in the mammalian host, independent of adaptive immune responses. The possible inducing conditions appear to be present in various tissue sites because isolates from multiple tissues showed similar degrees of sequence variation. The rate of accumulation of predicted amino acid changes was higher in the immunologically intact C3H/HeN mice than in SCID mice, a finding consistent with immune selection of VlsE variants.

Amino Acid Sequence↗

Unified approach to the analysis of genetic variation in serotonergic pathways.

Serotonin is a key neurotransmitter in the central nervous system, and dysregulation of serotonergic pathways has been implicated in the pathogenesis of many complex psychiatric diseases. Polymorphisms of many of the genes involved in serotonin biosynthesis, catabolism, and response have been reported, suggesting that genetic variability may underlie the development of diseases such as schizophrenia, obsessive compulsive disorder, and suicide. A number of single-gene polymorphisms in serotonergic pathways have been examined in these and other diseases, but to date results from this candidate gene approach have been disappointing. Although this may be because the detection of a small effect may require the analysis of large numbers of patients and controls, an alternative explanation is that the clinical importance of a single subtle genetic variant may be overlooked unless other functionally related genes are studied in tandem. To facilitate an integrated analysis, we have developed a PCR-SSP-based assay that permits the simultaneous genotyping of 13 single nucleotide polymorphisms in 9 serotonergic genes under identical conditions. These genes include tryptophan hydroxylase, tryptophan dioxygenase, monoamine oxidase A, and the serotonin receptors 5HT1A, 5HT1D-alpha, 5HT1D-beta, 5HT2A, 5HT2C, and 5HT5A. Using this technology, we have genotyped 100 Caucasoid control individuals and demonstrate that this approach is reliable, quick, cheap, and easy to interpret. We anticipate that this will facilitate the analysis of the genetic basis of susceptibility and phenotypic variability of a number of complex psychiatric diseases. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:621-627, 1999.

Codon↗

Using genetic variation to optimize nutritional preemption.

One of the promises of nutritional genomics is a set of dietary recommendations that leverage our understanding of nutrient-gene interaction in the preemptive dietary management of complex chronic diseases. Whether nutritional genomics can deliver on this promise is a matter of debate and controversy. Although nutritional genomics is often viewed as an extension of pharmacogenomics, the pharmacogenomics paradigm is a disease-centric reductionistic model that overshadows both the complexities and opportunities to be leveraged in preemptive nutritional pharmacology. Moreover, the pharmacogenomics model tends to set clinical expectations that nutritional genomics may not be able to achieve. The biological boundaries of nutritional pharmacology are being tested in many areas of preventive medicine such as cardiovascular disease and cancer. In this regard, the lessons learned in one disease may be germane to the other. Recent results from the Vitamin Intervention for Stroke Prevention (VISP), the Norwegian Vitamin (NORVIT), and the Heart Outcomes Prevention Evaluation (HOPE) 2 trials underscore the incertitude of translating epidemiologic data into preemptive nutritional guidance. Moving ahead, the genetic determinism of the nutrigenomic model needs to take on a more holistic and phenotypic focus. To the extent this can be done, preemptive nutrition may one day become a safe and practical reality.

Diet↗