Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “nucleotide polymorphism patterns”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources
PubMed1997

Evolutionary history of the sex-peptide (Acp70A) gene region in Drosophila melanogaster.

In Drosophila the products of the seminal fluid stimulate oviposition and suppress remating in the female. Of all the accessory gland peptides (Acp's) involved in these two responses, the sex-peptide (coded by the Acp70A gene) is among the best characterized at the functional level. A 1.2-kb fragment encompassing the Acp70A gene of nine lines from a natural population of D. melanogaster and one allele of D. sechellia was sequenced to study the forces shaping nucleotide variation within and between species. The coding region of D. simulans and D. mauritiana was also sequenced. A Ser to Ala replacement polymorphism at the last position of the signal peptide was detected in D. melanogaster. The Ser and Ala alleles are at intermediate frequencies. The level of nucleotide variation is lower for the derived Ala allele, which is compatible with a recent origin and an increase in frequency due to positive selection. Variation at the 5' flanking region is structured in two major highly differentiated haplotypes, whose distribution does not conform to neutral expectations. Selective and/or historical factors could contribute to the observed overall patterning of nucleotide variation at the Acp70A region.

Amino Acid Sequence↗
PubMed2006

Association of two functional polymorphisms in the CCR5 gene with juvenile rheumatoid arthritis.

Juvenile rheumatoid arthritis (JRA) is mediated by Th1-immune responses. In children with JRA, synovial T cells express high levels of the Th1-chemokine receptor CC chemokine receptor 5 (CCR5), which has been implicated in susceptibility to rheumatoid arthritis. To test the hypothesis that genetic variation in CCR5 is associated with susceptibility to JRA, we analyzed patterns of variation in the 5'cis-regulatory region of CCR5 in 124 multiplex families from a JRA-affected sibpair registry. After sequencing the upstream region of CCR5, variants were tested for association with JRA by transmission disequilibrium testing. A single nucleotide polymorphism, C-1835T, was significantly undertransmitted to children with early-onset JRA (P<0.01). C-1835T was genotyped in 424 additional simplex and multiplex families. CCR5-1835T allele was undertransmitted in the cohort of all probands with JRA (P<0.02), as well as in those with early-onset (P<0.01) or pauciarticular JRA (P<0.05). Another variant, a 32-bp deletion in the open reading frame of CCR5 (CCR5-Delta32) was also tested in approximately 700 simplex and multiplex families. CCR5-Delta32 was also significantly undertransmitted to probands with early-onset JRA (P<0.05). Both variants are in regions under natural selection, and result in functional consequences. Our results suggest these CCR5 variants are protective against early-onset JRA.

Arthritis, Juvenile↗
PubMed2003

Selection on human genes as revealed by comparisons to chimpanzee cDNA.

To better understand the evolutionary forces that affect human genes, we sequenced 5055 expressed sequence tags from the chimpanzee and compared them to their human counterparts. In conjunction with intergenic chimpanzee DNA sequences and data on human single-nucleotide polymorphisms in the genes studied, this allows us to gauge the extent to which selection affects human genes at a genome-wide scale. The comparison to intergenic DNA sequences indicates that about 39% of silent sites in protein-coding regions are deleterious and subject to negative selection. Further, when the divergence between human and chimpanzee is compared with the extent of nucleotide polymorphisms among humans in the same sequences, there is significantly higher divergence in the 5' untranslated regions (UTRs) but not in other parts of the transcript. This indicates that positive selection may have had a considerable influence on 5'UTRs. The dinucleotide CG (CpG) also exhibits a different substitution pattern within 5'UTRs as compared with other parts of the genome.

Amino Acid Substitution↗
PubMed2002

Single-nucleotide polymorphisms in the lipoprotein lipase gene associated with coronary heart disease in Chinese.

Coronary heart disease is a complex disease reflecting the interaction of multiple genes with the environment (e.g. diet, life style). Lipoprotein lipase (LPL) plays an important role in lipid metabolism and the pathogenesis of coronary atherosclerosis. Recent associations between single-nucleotide polymorphisms in the LPL gene and heart disease have been reported, but little is known in Chinese. The LPL gene spans >26 kb, with an mRNA of 3549 bp. In the present study, we screened 5155 bp (565 bp of 5' flanking region, nine exons and donor- and acceptor-splice sites, and some intronic bases) in 160 Chinese patients with confirmed coronary heart disease and 150 age- and gender-matched controls. Thirteen of the sixteen single-nucleotide polymorphisms that we found have not been previously reported. In males, significant (P<0.05) differences between the coronary heart disease patients and controls were found for five single-nucleotide polymorphisms: -421G>A (5' flanking region); +13,577C>A (intron 2); +16,052G>A, R192Q (exon 5); +16,173C>G and +16,177T>C (intron 5). In females, significant differences between the patients with coronary heart disease and controls were found for only the -421G>A and +16,052G>A (R192Q) mutations. Among the coronary heart disease males, significant (P<0.05) associations were found between the low-HDL high-triglyceride (LHDL/HTG) phenotype and the non-LHDL/HTG trait for the 5' flanking-421G, the intron 2+13,577C, and the exon 5+16,052G mutations, with odds-ratios (ORs)[confidence intervals] of 3.90[1.12-13.66], 3.38[1.22-9.40], and 3.22[1.04-10.01], respectively; no corresponding associations were found in females. There were 69, 51, 57 and 41 unphased haplotype patterns in male coronary heart disease, male control, female coronary heart disease and female control groups, respectively; the computer program PM-Plus found the heterogeneity model by far the best fit (P<0.0001 in males, >0.01 in females). These data show that some single-nucleotide polymorphisms in the LPL gene among Chinese are associated with abnormal lipid and lipoprotein profiles and predisposition to coronary heart disease, a genetically heterogeneous complex disease, and that they are gender-specific.

Adult↗
PubMed1996

Three novel mutations of the NF1 gene detected by temperature gradient gel electrophoresis of exons 5 and 8.

We screened a total of 100 unrelated patients with neurofibromatosis type 1 (NF1) for mutations on exons 5 and 8 of the NF1 gene using temperature gradient gel electrophoresis (TGGE). Careful interpretation of exon 5 TGGE patterns was necessary due to interference by an exonic polymorphism. Three novel mutations were identified: a stop mutation in exon 5 (Q239X) caused by a C-->T transition at cDNA nucleotide position 715, a transition at the invariant G of the splice acceptor site in the intron 4c (G655-1A), and a transversion at the invariant G of the splice donor site in intron 8 (G1185 + 1T). Analysis of mRNA revealed the predicted abnormal splice products. While skipping of exon 5 causes a shift in the reading frame with a premature stop codon downstream in the middle of exon 6, skipping of exon 8 leads to an in-frame deletion with the predicted protein product being shortened by 41 amino acids.

Electrophoresis, Polyacrylamide Gel↗
PubMed1994

Molecular basis for subtypic differences of the "a" subunit of coagulation factor XIII with description of the genesis of the subtypes.

The "a" subunit of human coagulation factor XIII (F13A) exhibits genetic polymorphism defined by four common alleles, F13A*1A, *1B, *2A, and *2B. We have previously suggested on the basis of the isoelectric focusing patterns of the four allele products that point mutations at two separate sites and one intragenic crossing over might be involved in the genes of F13A polymorphism. Here, we report nucleotide substitutions associated with F13A polymorphism. A C/T transition of the second nucleotide of codon 564 in exon 12 is responsible for the difference between F13A*1A and *1B and that between F13A*2A and *2B, and a set of two base changes in codons 650 and 651 in exon 14 leads to the differences between F13A*1A and *2A and those between F13A*1B and *2B. The four combinations of the point mutations at the two exons thus correspond to the four alleles, two of which were generated by the point mutations from ancestral monomorphic gene. The results suggest strongly that intragenic crossing over must be involved in the genesis of the fourth allele. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods discriminating these base changes in exons 12 and 14 are also presented.

Alleles↗
PubMed2001

Polymorphisms in the coding region of mtDNA and effects on clinical outcome of unrelated bone marrow transplantation.

The entire protein-coding region was divided into 45 fragments, separately amplified and analyzed for polymorphism by the PCR-SSCP (single-strand conformation polymorphism) method. The effect of polymorphism mismatching on the clinical outcome of unrelated bone marrow transplantation was studied to clarify whether products from mtDNA become minor antigens. Variability in PCR-SSCP pattern combinations of the 45 fragments suggests that each individual has a different polymorphism combination in the protein-coding region if all the coding regions were compared at the nucleotide sequence level. Nonsynonymous polymorphisms were found at relatively high frequency in MTATP8 and MTND3. Both the polymorphisms with and without substitution matched the peptide-binding motifs of HLA-A*0201. The effects of the polymorphism matching were retrospectively analyzed in 340 recipients transplanted with HLA-A, -B, -DRB1 allele-matched bone marrow from unrelated donors. There were no effects of polymorphism matching on the incidence of acute GVHD and cumulative disease-free survival. These results suggest that polymorphisms which generate peptides, with and without substitutions, that bind the same HLA molecule hardly influence GVHD because the difference between the HLA-peptide complexes is minute.

Bone Marrow Transplantation↗
PubMed1994

Genetic polymorphism between and within Meloidogyne species detected with RAPD markers.

Genetic analyses were conducted on root-knot nematode populations belonging to the four major species of the genus Meloidogyne and originating from many countries throughout the world. Discrete genetic markers used in this study were random genomic DNA sequences amplified by the polymerase chain reaction (RAPD). Primers of 17-30 nucleotides with 30-55% G + C content were tested. Five of them generated a total of 74 scorable markers that provided reliable polymorphisms both between and within species. Using RAPD patterns alone or in combination, all the Meloidogyne species and populations studied could be unambiguously discriminated. Based on the presence or absence of bands, maximum-parsimony analysis of the data resulted in clustering of species and populations congruent with previous isoenzymatic and molecular data. The resulting tree confirmed the early divergence of M. hapla from the other species and also that M. arenaria is closer to M. javanica than it is to M. incognita. The boot-strap analysis significantly supported most of the specific branching observed in the topology but did not identify the three M. arenaria populations as a monophyletic group.

Animals↗
PubMed2001

The human genome project: implications for the endocrinologist.

The sequencing of the human genome is a major achievement of our time. This article reviews the process and current status of the working draft sequence, ways to predict genes and assign function, and conclusions for human biology. Gene density is uneven and related to chromosome banding patterns, and the estimate of approximately 30,000 genes is lower than expected. Genetic maps for men and women differ from each other and from the physical map. Single nucleotide polymorphisms occur at an average spacing of 1 kb. Human populations are 99.99% identical, and most sequences are shared between people from different continents. To illustrate the tools for accessing the human genome sequence, searches were performed for genes encoding three categories of growth-related proteins, insulin-like growth factor-I (IGF-I) receptor, IGF-binding proteins and growth hormone receptor. The results revealed novel details about their genomic organization and new predicted transcripts. Impacts on medicine are promised in the fields of diagnostics (development of new tests), therapeutics (identification of new potential drug targets) and pharmacogenomics (streamlining of drug discovery and personalized medicine). Associated ethical, legal and social implications and controversies include genetic determinism, informed consent, privacy and confidentiality, ownership of genetic information in the biotechnology marketplace, and access to genetic healthcare.

Endocrinology↗
PubMed2002

A single thymine nucleotide deletion responsible for congenital deficiency of plasmin inhibitor.

Plasma plasmin inhibitor (PI) is a physiological inhibitor of plasmin-mediated fibrinolysis and constitutes a hemostatic component in blood plasma; hence its deficiency results in a severe hemorrhagic diathesis. We have carried out molecular analysis of American family members with congenital PI deficiency, and detected a single thymine deletion at nucleotide position 332 in exon 5. The deletion was found in both alleles of the homozygotes and in one allele of the heterozygotes, and the patterns of restriction fragment length polymorphism created by the mutation in the family members were compatible with their phenotypes. The deletion caused a frameshift leading to an alteration and shortening of the deduced amino acid sequence. The amino acid sequence consists of the first 83 amino acids of the N-terminal sequence of the normal PI and additional new amino acids, resulting in a mutant composed of 94 amino acids in contrast to 464 amino acids of the normal PI. In transient expression analysis, the mutant PI whose molecular size was compatible with the predicted amino acid sequence was detected in the lysates of the cells transfected with the mutated PI expression vector. The mutant PI was retained and underwent progressive degradation within the cells, and was minimally excreted into the media. These data indicate that this mutation is the cause of PI deficiency in this pedigree.

Cloning, Molecular↗
PubMedDate not supplied

Isolation and characterization of a novel antigenic subtype of infectious bronchitis virus serotype DE072.

Three infectious bronchitis virus (IBV) isolates, CU82792, CU82805, and CU82808, were recovered from sentinel chickens placed with three different layer flocks of a large commercial poultry farm in New York State. The three isolates were classified as members of the DE072 serotype on the basis of 1) their S1 genes could be amplified with only a modified primer designed for the DE072 serotype and 2) their restriction fragment length polymorphism patterns, after digestion with endonucleases HaeIII, BstyI and XcmI, were indistinguishable from that of DE072 virus. Additional characterization of one of the isolates, CU82805, revealed that its S1 gene bears approximately 96% identity at the nucleotide level and 94% identity at the amino acid level with DE072. Yet, in an in vitro reciprocal virus neutralization test, only a one-way neutralization was observed, i.e., antiserum to CU82805 neutralized DE072, whereas CU82805 was not neutralized by DE072 antiserum. Implications of these findings with regard to IBV diagnosis and immunization are discussed.

Amino Acid Sequence↗
PubMed1990

A simple and rapid method for HLA-DRB and -DQB typing by digestion of PCR-amplified DNA with allele specific restriction endonucleases.

The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, which we previously reported as an efficient and convenient typing technique for accurate definition of the HLA-DQA1 and -DPB1 alleles, is now extended and applied to HLA-DRB and -DQB typing. The second exon of the HLA-DRB (B1 and B3 or B4) and DQB (B1 and B2) genes was selectively amplified from genomic DNAs of 70 HLA-homozygous B cell lines by PCR. Amplified DNAs were digested with the restriction endonucleases, which can recognize allelic variations specific for HLA-DR, -DQ, and -Dw allospecificities and then subjected to electrophoresis in polyacrylamide gel. Of DRB genes, FokI, HinfI, HhaI, HphI, KpnI and SacII were selected and the 20 different polymorphic patterns of the restriction fragments thus obtained were found to correlate with each HLA-DR and -Dw type defined by serological and cellular typing. Of the DQB genes, FokI, HaeIII, HhaI, RsaI and Sau3AI produced nine different polymorphic patterns of the restriction fragments, correlating with the HLA-DQ and -Dw types. This PCR-RFLP method provides a simple and rapid technique for accurate definition of the HLA-DR, -DQ and -Dw types at the nucleotide level, eliminating the need for radioisotope as well as allele specific oligonucleotide probes.

Alleles↗
PubMed2003

Identification of a polymorphic gene, BCL2A1, encoding two novel hematopoietic lineage-specific minor histocompatibility antigens.

We report the identification of two novel minor histocompatibility antigens (mHAgs), encoded by two separate single nucleotide polymorphisms on a single gene, BCL2A1, and restricted by human histocompatibility leukocyte antigen (HLA)-A*2402 (the most common HLA-A allele in Japanese) and B*4403, respectively. Two cytotoxic T lymphocyte (CTL) clones specific for these mHAgs were first isolated from two distinct recipients after hematopoietic cell transplantation. Both clones lyse only normal and malignant cells within the hematopoietic lineage. To localize the gene encoding the mHAgs, two-point linkage analysis was performed on the CTL lytic patterns of restricting HLA-transfected B lymphoblastoid cell lines obtained from Centre d'Etude du Polymorphisme Humain. Both CTL clones showed a completely identical lytic pattern for 4 pedigrees and the gene was localized within a 3.6-cM interval of 15q24.3-25.1 region that encodes at least 46 genes. Of those, only BCL2A1 has been reported to be expressed in hematopoietic cells and possess three nonsynonymous nucleotide changes. Minigene transfection and epitope reconstitution assays with synthetic peptides identified both HLA-A*2402- and B*4403-restricted mHAg epitopes to be encoded by distinct polymorphisms within BCL2A1.

Amino Acid Sequence↗
PubMed1991

Mitochondrial DNA polymorphisms in the two subspecies of Drosophila sulfurigaster: relationship between geographic structure of population and nucleotide diversity.

Recent empirical and theoretical studies on mitochondrial DNA (mtDNA) variation in higher animals have suggested that the extent of mtDNA polymorphism is largely affected by spatial population subdivision. To examine this we studied mtDNA polymorphism in two subspecies of Drosophila sulfurigaster: D. s. albostrigata and D. s. bilimbata. Drosophila sulfurigaster albostrigata is mainly distributed on the mainland of Southeast Asia. In contrast, D. s. bilimbata forms discontinuous populations on many islands scattered in the Pacific Ocean. Because of the difference in their distribution patterns, the two subspecies are thought to be different in the extent of spatial population subdivision. mtDNA was isolated from greater than 50 isofemale strains for each subspecies and were analyzed by eight restriction endonucleases. Nucleotide diversity within a population was higher in D. s. albostrigata than in D. s. bilimbata. However, haplotype diversity was 1.6 times greater in D. s. bilimbata (0.85) than in D. s. albostrigata (0.53). The large difference in overall heterogeneity was attributed to the difference in interpopulational nucleotide diversity. For the two subspecies the proportion of interpopulational gene diversity in a subdivided population was calculated to be 0.54 in D. s. bilimbata and 0.40 in D. s. albostrigata. These observations indicate that spatial population subdivision is a major factor in determining mtDNA polymorphism in these subspecies. The extent of mtDNA divergence between the subspecies was very high. The average nucleotide divergence between them was 7.6%, which is almost the interspecific level reported for other Drosophila species. The cause of the high degree of mtDNA divergence is discussed.

Animals↗
PubMed2003

Identification of a novel mutation in the ARSB gene that is frequent among Brazilian MPSVI patients.

Mucopolysaccharidosis type VI, or Maroteaux-Lamy syndrome, is an autosomal recessive disease caused by the deficiency of arylsulfatase B (ARSB; N-acetyl-galactosamine-4-sulfatase, E.C.3.1.6.12), which is involved in the stepwise degradation of dermatan sulfate and chondroitin sulfate. The deficiency of this enzyme causes storage in the lysozomes and excretion in the urine of partially degraded dermatan sulfate. Twenty patients with MPSVI were analyzed, including 2 siblings. Genomic DNA from patients was extracted and amplified by PCR followed by analysis by single-strand conformation polymorphism (SSCP), which detects altered patterns in the single-stranded DNA. Amongst the patients analyzed for exon 8 of the ARSB gene, 5 patients presented an altered band pattern when compared to controls. After sequencing, we have detected a 23-bp deletion, extending from nucleotides 1,533 to 1,555, causing a frameshift and changing 2 amino acids before creating a premature stop codon at amino acid 514.

Brazil↗
PubMed2006

A novel statistical method to estimate the effective SNP size in vertebrate genomes and categorized genomic regions.

BACKGROUND: The local environment of single nucleotide polymorphisms (SNPs) contains abundant genetic information for the study of mechanisms of mutation, genome evolution, and causes of diseases. Recent studies revealed that neighboring-nucleotide biases on SNPs were strong and the genome-wide bias patterns could be represented by a small subset of the total SNPs. It remains unsolved for the estimation of the effective SNP size, the number of SNPs that are sufficient to represent the bias patterns observed from the whole SNP data. RESULTS: To estimate the effective SNP size, we developed a novel statistical method, SNPKS, which considers both the statistical and biological significances. SNPKS consists of two major steps: to obtain an initial effective size by the Kolmogorov-Smirnov test (KS test) and to find an intermediate effective size by interval evaluation. The SNPKS algorithm was implemented in computer programs and applied to the real SNP data. The effective SNP size was estimated to be 38,200, 39,300, 38,000, and 38,700 in the human, chimpanzee, dog, and mouse genomes, respectively, and 39,100, 39,600, 39,200, and 42,200 in human intergenic, genic, intronic, and CpG island regions, respectively. CONCLUSION: SNPKS is the first statistical method to estimate the effective SNP size. It runs efficiently and greatly outperforms the algorithm implemented in SNPNB. The application of SNPKS to the real SNP data revealed the similar small effective SNP size (38,000 - 42,200) in the human, chimpanzee, dog, and mouse genomes as well as in human genomic regions. The findings suggest strong influence of genetic factors across vertebrate genomes.

Algorithms↗
PubMed1997

Biodiversity of a Burkholderia cepacia population isolated from the maize rhizosphere at different plant growth stages.

A Burkholderia cepacia population naturally occurring in the rhizosphere of Zea mays was investigated in order to assess the degree of root association and microbial biodiversity at five stages of plant growth. The bacterial strains isolated on semiselective PCAT medium were mostly assigned to the species B. cepacia by an analysis of the restriction patterns produced by amplified DNA coding for 16S rRNA (16S rDNA) (ARDRA) with the enzyme AluI. Partial 16S rDNA nucleotide sequences of some randomly chosen isolates confirmed the ARDRA results. Throughout the study, B. cepacia was strictly associated with maize roots, ranging from 0.6 to 3.6% of the total cultivable microflora. Biodiversity among 83 B. cepacia isolates was analyzed by the random amplified polymorphic DNA (RAPD) technique with two 10-mer primers. An analysis of RAPD patterns by the analysis of molecular variance method revealed a high level of intraspecific genetic diversity in this B. cepacia population. Moreover, the genetic diversity was related to divergences among maize root samplings, with microbial genetic variability markedly higher in the first stages of plant growth; in other words, the biodiversity of this rhizosphere bacterial population decreased over time.

Base Sequence↗