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At least 937 records · Page 52Linked to original sources
PubMed2004

A single-amino-acid change of the gustatory receptor gene, Gr5a, has a major effect on trehalose sensitivity in a natural population of Drosophila melanogaster.

Variation in trehalose sensitivity and nucleotide sequence polymorphism of the Gr5a gene encoding the gustatory receptor to sugar trehalose were investigated in 152 male lines of Drosophila melanogaster collected from a natural population. Among the observed 59 segregating sites, some pairs of sites showed significant linkage disequilibrium. A single SNP, which results in the Ala218Thr amino acid change, was significantly associated with trehalose sensitivity, as previously suggested. Threonine at amino acid position 218 was found to be the ancestral form in D. melanogaster, suggesting that low trehalose sensitivity was an ancestral form with respect to the receptor function. There was large genetic variation in trehalose sensitivity. It was continuously distributed, indicating that trehalose sensitivity measured by the behavioral assay is a quantitative trait. These results suggest that apart from the Gr5a gene, other genetic factors contribute to variation in trehalose sensitivity. Nucleotide diversity (pi) and nucleotide variation (theta) per site were 0.00874 and 0.00590, respectively. Fu and Li's test and the MK test showed no significant departure from the expectation of selective neutrality in the Gr5a gene. However, we rejected selective neutrality by Tajima's test and Fay and Wu's test with the observed level of recombination. We discuss possible causes of the observed pattern of nucleotide variation in the gustatory receptor Gr5a gene.

Amino Acid Substitution↗
PubMed1987

Polymorphism and gene conversion in mouse alpha-globin haplotypes.

We have cloned and characterized three distinct alpha-globin haplotypes obtained from inbred strains of the mouse, Mus domesticus. We report here the complete nucleotide sequence of the six alpha-globin genes that the haplotypes contain. Our analysis of these genes and those from one other previously described haplotype indicates that recurrent gene conversion events have played a major role in their history. The pattern of nucleotide substitutions suggests that conversions have occurred both within and between haplotypes. Limited segments of coding and noncoding DNA have been involved in these gene conversion events. In two of the haplotypes, the nonallelic genes of each maintain DNA sequence identity over discrete intervals and encode the same alpha-globin polypeptide. On the other hand, the coding regions of some genes have accumulated replacement changes that result in distinct alpha-globins. In one instance, these changes appear to reflect positive selection of advantageous mutations.

Amino Acid Sequence↗
PubMed2006

Assessment of genomic imprinting of SLC38A4, NNAT, NAP1L5, and H19 in cattle.

BACKGROUND: At present, few imprinted genes have been reported in cattle compared to human and mouse. Comparative expression analysis and imprinting status are powerful tools for investigating the biological significance of genomic imprinting and studying the regulation mechanisms of imprinted genes. The objective of this study was to assess the imprinting status and pattern of expression of the SLC38A4, NNAT, NAP1L5, and H19 genes in bovine tissues. RESULTS: A polymorphism-based approach was used to assess the imprinting status of four bovine genes in a total of 75 tissue types obtained from 12 fetuses and their dams. In contrast to mouse Slc38a4, which is imprinted in a tissue-specific manner, we found that SLC38A4 is not imprinted in cattle, and we found it expressed in all adult tissues examined. Two single nucleotide polymorphisms (SNPs) were identified in NNAT and used to distinguish between monoallelic and biallelic expression in fetal and adult tissues. The two transcripts of NNAT showed paternal expression like their orthologues in human and mouse. However, in contrast to human and mouse, NNAT was expressed in a wide range of tissues, both fetal and adult. Expression analysis of NAP1L5 in five heterozygous fetuses showed that the gene was paternally expressed in all examined tissues, in contrast to mouse where imprinting is tissue-specific. H19 was found to be maternally expressed like its orthologues in human, sheep, and mouse. CONCLUSION: This is the first report on the imprinting status of SLC38A4, NAP1L5, and on the expression patterns of the two transcripts of NNAT in cattle. It is of interest that the imprinting of NAP1L5, NNAT, and H19 appears to be conserved between mouse and cow, although the tissue distribution of expression differs. In contrast, the imprinting of SLC38A4 appears to be species-specific.

Amino Acid Transport System A↗
PubMed2004

Allelic polymorphism of TCRalpha chain constant domain genes in the bicolor damselfish.

T cell receptor (TCR) chains are composed of two extracellular domains, the membrane-distal variable domain and the membrane-proximal constant domain. Data presented here show that the TCRA 'constant' (C) domain of damselfish exhibits considerable allelic polymorphisms that appear to be positively selected. Each of 32 damselfish TCRAC clones showed different patterns of atypical polymorphism in the constant region. Twenty-three of the 121 TCRalpha constant region amino acid residues show substitutions, clustered mainly in the loops between the beta strands. Coding regions of the TCRAC genes differ by up to 8% at the nucleotide level and 20% at the amino acid level. Southern hybridization, polymorphism segregation, and genomic cloning data suggest allelic polymorphism at two TCRAC genes, distinguished by a single amino acid. KA/KS ratios suggest that balancing selection is acting to maintain polymorphisms at the variable sites of one of these genes, but not the other, in a manner comparable to the peptide binding regions of MHC. Nonetheless, each TCRAC gene is spliced to variable and joining segments similar to those described in other species. These data suggest that our understanding of the function of the TCR constant domains of these vertebrates is incomplete.

Alleles↗
PubMed1999

Genetic variation of Cryphonectria hypoviruses (CHV1) in Europe, assessed using restriction fragment length polymorphism (RFLP) markers.

A total of 72 hypovirus-infected isolates of the chestnut blight fungus Cryphonectria parasitica were sampled from nine European countries between 1975 and 1997. The double-stranded RNA of the Cryphonectria hypoviruses (CHV1) was isolated and reverse transcription (RT)-PCR products were obtained for two different regions of the viral genome (ORF A and ORF B) using primer sequences of the type species CHV1-EP713. Both PCR products of each viral isolate were digested with four restriction endonucleases recognizing sequences of four nucleotides. The restriction fragment length polymorphism (RFLP) analysis revealed 41 genetically distinct RFLP types of CHV1 with 10 types occurring more than once. Identical RFLP types were detected nine times among viruses collected in the same location. Cluster analysis based on the RFLP banding patterns separated the viral isolates into five CHV1 clusters or subtypes. Most viral isolates (64 out of 72) grouped into one large cluster which comprised all viruses from Italy (including CHV1-EP747), Switzerland, Crotia, Bosnia, Hungary, Greece, and the French island Corsica, as well as five out of 11 isolates from continental France. Two additional subtypes of CHV1 were found in France (one related to CHV1-EP713) and one each in Spain and Germany. The Swiss samples collected over a period of 20 years showed that very little RFLP variation has evolved during this time. The results of this study are consistent with the hypothesis of multiple introductions of CHV1 into Europe.

Ascomycota↗
PubMed2001

Regions of lower crossing over harbor more rare variants in African populations of Drosophila melanogaster.

A correlation between diversity levels and rates of recombination is predicted both by models of positive selection, such as hitchhiking associated with the rapid fixation of advantageous mutations, and by models of purifying selection against strongly deleterious mutations (commonly referred to as "background selection"). With parameter values appropriate for Drosophila populations, only the first class of models predicts a marked skew in the frequency spectrum of linked neutral variants, relative to a neutral model. Here, we consider 29 loci scattered throughout the Drosophila melanogaster genome. We show that, in African populations, a summary of the frequency spectrum of polymorphic mutations is positively correlated with the meiotic rate of crossing over. This pattern is demonstrated to be unlikely under a model of background selection. Models of weakly deleterious selection are not expected to produce both the observed correlation and the extent to which nucleotide diversity is reduced in regions of low (but nonzero) recombination. Thus, of existing models, hitchhiking due to the recurrent fixation of advantageous variants is the most plausible explanation for the data.

Africa↗
PubMed2002

BCL10 mutation does not represent an important pathogenic mechanism in gastric MALT-type lymphoma, and the presence of the API2-MLT fusion is associated with aberrant nuclear BCL10 expression.

Two recurrent translocations have been associated with mucosa-associated lymphoid tissue (MALT)-type lymphoma, t(11;18)(q21;q21) and t(1;14)(p22;q32). The first, t(11;18)(q21;q21), results in the fusion protein API2-MLT (API2-MALT1). Through t(1;14)(p22;q32), the BCL10 gene is entirely transferred to the IgH gene, resulting in its overexpression. Wild-type BCL10 is implicated in apoptosis, and it has been suggested that mutated forms gain oncogenic activity. The occurrence of genomic BCL10 mutations in 35 gastric MALT-type lymphomas with or without t(11;18)(q21;q21) (10 and 25 cases, respectively) was investigated. DNA extracted from either whole tissue sections or microdissected clusters of tumor cells was used. Five polymerase chain reactions amplifying the coding exons were performed and were followed by direct sequencing of the products. Twenty differences with the published BCL10 sequence, all single nucleotide substitutions, were detected in 16 cases. Of these, 12 represented known polymorphisms, either at codon 8, 213, or 5. Of the remaining 8 substitutions, 2 were silent and 6 resulted in amino acid substitutions. Mutation analysis results were correlated with the BCL10 expression pattern. Aberrant nuclear BCL10 expression was detected in 14 cases. No association could be demonstrated between the latter and the presence of BCL10 mutations. In contrast, all 10 cases carrying t(11;18)(q21;q21) showed nuclear expression, whereas this staining pattern was absent in 21 of 25 cases without t(11;18)(q21;q21). These results demonstrate that BCL10 mutations are rare in gastric MALT-type lymphoma and are not related to the aberrant nuclear expression of BCL10. In contrast, they indicate that the presence of the API2-MLT fusion protein is associated with aberrant nuclear BCL10 expression.

Adaptor Proteins, Signal Transducing↗
PubMed2007

Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms.

Phenotypic variation between human populations in skin pigmentation correlates with latitude at the continental level. A large number of hypotheses involving genetic adaptation have been proposed to explain human variation in skin colour, but only limited genetic evidence for positive selection has been presented. To shed light on the evolutionary genetic history of human variation in skin colour we inspected 118 genes associated with skin pigmentation in the Perlegen dataset, studying single nucleotide polymorphisms (SNPs), and analyzed 55 genes in detail. We identified eight genes that are associated with the melanin pathway (SLC45A2, OCA2, TYRP1, DCT, KITLG, EGFR, DRD2 and PPARD) and presented significant differences in genetic variation between Europeans, Africans and Asians. In six of these genes we detected, by means of the EHH test, variability patterns that are compatible with the hypothesis of local positive selection in Europeans (OCA2, TYRP1 and KITLG) and in Asians (OCA2, DCT, KITLG, EGFR and DRD2), whereas signals were scarce in Africans (DCT, EGFR and DRD2). Furthermore, a statistically significant correlation between genotypic variation in four pigmentation candidate genes and phenotypic variation of skin colour in 51 worldwide human populations was revealed. Overall, our data also suggest that light skin colour is the derived state and is of independent origin in Europeans and Asians, whereas dark skin color seems of unique origin, reflecting the ancestral state in humans.

Asian People↗
PubMed2002

Genetic and functional analysis of single nucleotide polymorphisms in the beta2-neuronal nicotinic acetylcholine receptor gene (CHRNB2).

The beta2-neuronal nicotinic acetylcholine receptor gene (CHRNB2) is a logical candidate for influencing smoking behavior and nicotine dependence. We discovered six single nucleotide polymorphisms (SNPs) in the CHRNB2 gene by surveying 15.4 kb of genomic sequence including a previously undescribed 3' untranslated region that extends 4.0 kb downstream of the coding region. One of the SNPs causes an amino acid substitution in exon 5, one occurs in the promoter region, one changes an intronic base, and three occur in the 3' untranslated region. The ethnically dependent allele frequencies and the marker-to-marker linkage disequilibrium patterns of five of these polymorphisms were determined. The SNPs were assayed in 743 individuals for whom information on smoking history and lifelong nicotine dependence was available. No significant associations of the individual markers or their haplotypes to smoking behavior or level of nicotine dependence were found.

DNA Primers↗
PubMed2000

HLA-B*8202 identified in a Caucasoid potential bone marrow donor.

Sequence analysis of HLA class I alleles has continued to reveal the true extent of polymorphism, particularly for B-locus alleles. This diversity can arise through reshuffling of polymorphic sequences generated by point mutation, resulting in interallelic recombination or intergenic recombination (1). Here we describe a new B-locus allele, B*8202, which is structurally most similar to B*8201, having only one nucleotide difference in exon 3 at nucleotide 557, resulting in an amino acid change of aspartic acid to glycine at residue 162. Glycine is the consensus amino acid for B-locus alleles, which suggests that B*8202 is older than B*8201 in evolutionary terms. B*8201 was found to be a hybrid of B*4501 and B*5602 that may have arisen through recombination events, explaining the serological patterns observed with these allotypes. The importance of high-resolution typing is emphasised here as routine typing suggested the presence of B*8201 and the new variant allele may have been missed had it not been typed further by sequence-based typing.

Alleles↗
PubMedDate not supplied

Molecular characterization of seven field isolates of infectious bursal disease virus obtained from commercial broiler chickens.

Specific-pathogen-free sentinel birds were used as an initial biological system to isolate infectious bursal disease virus (IBDV) field isolates from commercial broiler farms exhibiting recurrent respiratory problems and poor performance. Reverse transcription (RT)-polymerase chain reaction (PCR) was used to amplify a 248-bp product encompassing the hypervariable region of the IBDV VP2 gene. Restriction fragment length polymorphism (RFLP) analysis of the RT-PCR products was performed with the restriction endonucleases DraI, SadI, TaqI, StyI, BstNI, and SspI. Two isolates (619 and 850) exhibited a RFLP pattern characteristic of Delaware variant E IBDV. Restriction enzyme digestion for four isolates (625, 849, 853, and 11,153) revealed unmatched RFLP patterns when compared with reference IBDV strains. Nucleotide and deduced amino acid sequence analyses of the VP2 hypervariable region for these six isolates revealed identity (96.3% up to 98%) with Delaware E variant IBDV strain. However, serine at position 254, which is characteristic of Delaware variant strains, was substituted by asparagine in these six isolates. The seventh IBDV isolate (9109) also exhibited a unique RFLP pattern, which included the SspI restriction site, which is characteristic of very virulent (vv) IBDV strains. Nucleotide and amino acid sequence analyses of the hypervariable region for this isolate revealed identity (90%) with the standard challenge strain. However, the leucine residue at position 294 was substituted by isoleucine. This substitution corresponds to one of the amino acids that are conserved in the vvIBDV strains. Antigenic index studies of the predicted amino acid sequence of the hypervariable region of VP2 from isolates 619, 625, 849, 850, 853, and 11,153 exhibited a profile almost identical to variant E, whereas the isolate 9109 exhibited a profile characteristic of standard IBDV strains.

Amino Acid Sequence↗
PubMed1985

The complete primary structure of HLA-Bw58.

Serological studies indicate that HLA-B17 molecules are unusually cross-reactive with products of the HLA-A locus. In particular, a mouse monoclonal antibody MA2.1 defines an epitope that is shared by HLA-A2 and the two subtypes (Bw57 and Bw58) of B17. To investigate these relationships at the structural level, we have isolated a gene coding for Bw58 from the WT49 B cell line. The gene was transfected into mouse L cells and its protein product was characterized with a panel of monoclonal anti-HLA antibodies. The nucleotide sequence of 3520 base pairs of DNA encompassing the seven exons coding for Bw58 and associated introns was determined. The deduced protein sequences for Bw58 and eight other HLA-A,B,C molecules were compared. In the first polymorphic domain (alpha 1), Bw58 is unusual in that it is as homologous to HLA-A locus products as to HLA-B locus products. In the second polymorphic domain (alpha 2), Bw58 has greater homology to B locus products. In the alpha 1 domain of Bw58, small segments of amino acid and nucleotide sequence homology with A2 (residues 62-65) and with Aw24 (residues 75-83) are found in the major region of polymorphic diversity (residues 62-83). These similarities provide structural correlates for the serological relationships between Bw58 and A locus molecules, with residues 62-65 possibly being involved in the MA2.1 epitope. From comparisons of four HLA-A and four HLA-B sequences, there is a difference in the patterns of variation for A and B locus molecules. For B locus molecules there is greater variation in the alpha 1 domain than in the alpha 2 domain. For A locus molecules, variation in the two domains is similar and like that for B locus alpha 2 domains. In comparison to other HLA-A,B,C genes, novel inverted repeat sequences were found in the nucleotide sequence of HLA-Bw58. These sequences flank the putative RNA splicing sites at the 3' end of the exons encoding the alpha 2 and alpha 3 protein domains.

Amino Acid Sequence↗
PubMed2005

No evidence for association between 1858 C/T single-nucleotide polymorphism of PTPN22 gene and primary Sjögren's syndrome.

One-third of first-degree relatives of patients with primary Sjögren's syndrome (pSS) suffer from other autoimmune diseases, including type I diabetes, systemic lupus erythematosus and autoimmune thyroiditis. Recently, 1858 C/T polymorphism of PTPN22 gene was reported to predispose to these autoimmune diseases. We decided to investigate whether PTPN22 gene polymorphism was also involved in the genetic predisposition to pSS in a case-control study, including 183 patients with pSS and 172 healthy controls. No significant differences in allele (T allele frequency: 7.7% in patients with pSS vs 7.8% in controls, P=0.9) and genotype frequencies of PTPN22 polymorphism were detected between patients with pSS and controls. PTPN 22 gene polymorphism was not associated with a specific pattern of autoantibody secretion either. Thus, 1858 C/T polymorphism of PTPN22 gene is not involved in genetic predisposition to pSS.

Autoantibodies↗
PubMed2000

Analysis of association at single nucleotide polymorphisms in the APOE region.

The discussion of the prospects of using a dense map of single nucleotide polymorphisms (SNPs) to identify disease genes with association analysis has been extensive. However, there is little empiric evidence to support this strategy. To begin to examine the practical issues surrounding this methodology, we identified 10 SNPs in the region immediately surrounding the apolipoprotein E locus (APOE), an established susceptibility gene for Alzheimer disease. Our goal was to examine patterns of allelic association to begin to investigate the question of whether APOE could have been identified using SNPs. Our strongest evidence of association was at the 2 SNPs immediately flanking APOE.

Age of Onset↗
PubMed2004

Identification and functional characterization of a highly polymorphic region in the human TRAIL promoter in multiple sclerosis.

TNF-related apoptosis-inducing ligand (TRAIL) is not only involved in cell death but also in other immunoregulatory mechanisms. So far, the regulation of the TRAIL pathway in physiologic and pathologic conditions remains unclear. Due to the implication in brain damage and the elevated expression in peripheral immune cells of patients with multiple sclerosis (MS), an autoimmune disease of the central nervous system, TRAIL might play a central role in the pathology of this disease. Here, we have identified a highly polymorphic region in the TRAIL promoter. Using single-strand conformation polymorphism analysis, we found four single nucleotide polymorphisms (SNPs) within 111 base pairs. One of these SNPs is located in a binding site for the transcription factor AP-1. However, the RNA and protein expression of TRAIL revealed no obvious differences in relation to the genotypes. Furthermore, investigating samples from both MS patients and healthy controls we could not detect any association of these newly described polymorphisms to the clinical disease pattern. Thus, the TRAIL promoter contains a highly polymorphic area which has, however, no impact on molecule expression, and is neither directly related to increased risk of developing MS nor associated with a certain course of this heterogeneous disease in our population.

Adult↗
PubMed2004

Rapid characterization of avian reoviruses using phylogenetic analysis, reverse transcription-polymerase chain reaction and restriction enzyme fragment length polymorphism.

A reverse transcription-polymerase chain reaction is described, which amplified the full-length sigmaC-encoding and sigmaNS-encoding genes of avian reovirus (ARV). DNA fragments of 1022 and 1152 base pairs were amplified among ARV isolates, respectively, indicating that there were no apparent deletions or insertions in these regions. Fragments amplified from vaccine strains and field isolates were digested with five different restriction enzymes Bcn I, Hae III, Taq I, Dde I, and Hinc II, respectively. Restriction fragment profiles observed on polyacrylamide gels showed heterogeneity between vaccine and Taiwanese isolates. All ARV isolates tested showed different restriction enzyme cleavage patterns and could be clearly distinguished. The strain-typing based on the cleavage sites in the sigmaC-encoding gene of ARV showed that viruses could be classified into four distinct groups. A phylogenetic tree based on the nucleotide sequences of the sigmaC-encoding gene revealed that Taiwanese ARV isolates were classified into four distinct groups, indicating that the genotyping is consistent with typing based on restriction enzyme fragment length polymorphism of the sigmaC-encoding gene of ARV. The results suggested that polymerase chain reaction followed by restriction enzyme analysis provided a simple and rapid approach for characterization of ARV isolates. Also, it is possible to determine whether a new variant strain has been introduced into a flock or a given virus strain has spread from one flock to another.

Animals↗
PubMed2004

A double classification tree search algorithm for index SNP selection.

BACKGROUND: In population-based studies, it is generally recognized that single nucleotide polymorphism (SNP) markers are not independent. Rather, they are carried by haplotypes, groups of SNPs that tend to be coinherited. It is thus possible to choose a much smaller number of SNPs to use as indices for identifying haplotypes or haplotype blocks in genetic association studies. We refer to these characteristic SNPs as index SNPs. In order to reduce costs and work, a minimum number of index SNPs that can distinguish all SNP and haplotype patterns should be chosen. Unfortunately, this is an NP-complete problem, requiring brute force algorithms that are not feasible for large data sets. RESULTS: We have developed a double classification tree search algorithm to generate index SNPs that can distinguish all SNP and haplotype patterns. This algorithm runs very rapidly and generates very good, though not necessarily minimum, sets of index SNPs, as is to be expected for such NP-complete problems. CONCLUSIONS: A new algorithm for index SNP selection has been developed. A webserver for index SNP selection is available at http://cognia.cu-genome.org/cgi-bin/genome/snpIndex.cgi/

Algorithms↗
PubMed2002

Phylogenetic characterization of Histoplasma capsulatum strains based on ITS region sequences, including two new strains from Thai and Chinese patients in Japan.

Two strains of Histoplasma capsulatum var. capsulatum were isolated in Japan: one from a Thai AIDS patient and the other from a Chinese non-immunocompromised patient. The phylogenetical relationship among the two isolates and reference strains of H. capsulatum from other geographical populations was investigated. Random amplified polymorphic DNA (RAPD) analysis of the two H. capsulatum strains showed that they had RAPD band patterns similar to those of the reference Thai isolates and North American strains, although the patterns differed slightly from those of the reference strains. Phylogeny of thirty geographically diverse H. capsulatum isolates representing the three varieties, var. capsulatum, var. duboisii and var. farciminosum were evaluated using nucleotide sequences of the internal transcribed spacer (ITS) region (ITS1-5.8S rDNA -ITS2). We found that the ITS region contained sufficient information to resolve the phylogenetic relationship among the fungal isolates. An unrooted dendrogram constructed from the ITS sequences showed that thirty strains of H. capsulatum could be classified into eight geographic clades; Asia type (i), South America types A (ii) and B (iii), North American types 1 (iv) and 2 (v), H. duboisii types A (vi) and B (vii), and East Asia type (viii). Based on the ITS region sequence analysis, the two strains isolated from the Thai and Chinese patients in Japan were found to be distinct from Asia type (i) in which eight Thai, one Chinese, one English and one Indonesian isolate were included. Some extent of DNA polymorphism was observed between the North America type 1 isolates and the Thai and Chinese strains isolated in Japan. We believe that the Thai and Chinese isolates were unique and propose a new clade, East Asia type (viii) for the two strains. DNA sequence analysis of the ITS region provided useful information to understand the epidemiology and evolution of H. capsulatum.

Base Sequence↗