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Results for “simple sequence repeat”

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PubMedDate not supplied

Genome survey for loci that influence successful aging: sample characterization, method validation, and initial results for the Y chromosome.

OBJECTIVE: A systematic genome survey was initiated to identify loci that affect the likelihood of reaching age 90 with preserved cognition. This communication describes the clinical characterization and comparison of the experimental groups, validation of the experimental method, and results for the Y chromosome. METHODS: The genome survey was conducted at 10 cM resolution for simple sequence tandem repeat polymorphisms (SSTRPs) that identify genes for successful aging by virtue of linkage disequilibrium. Efficiency was enhanced by genotyping pools of DNA from 100 cognitively intact elders (50 men/50 women) and 100 young (age 18-25 years) adults matched for sex, race, ethnicity, and geographic location. RESULTS: Elders (94 nonagenarians, 6 centenarians) manifested preserved cognition, as reflected by clinical and psychometric assessments; "good" average capacity to carry out their activities of daily living; and the majority were living independently despite multiple medical conditions. None had a history of mental disorders in early or middle adulthood, only one was a current smoker, and 80% consumed alcohol less than once each month. The genome survey method detected the expected elevation of the APOE epsilon2 allele frequency, and reciprocal reduction in the epsilon4 frequency, among the elders, compared with the young adults. It also detected significant differences in the allelic distributions of DYS389 and DYS390, which are separated by only 2.6 Mb near the centromere of Yq. CONCLUSIONS: These results suggest that several behavioral and genetic factors may contribute to the likelihood of achieving exceptional longevity with preserved cognition.

Adolescent↗

PubMed2002

Identification of zygotic and nucellar seedlings in citrus interploid crosses by means of isozymes, flow cytometry and ISSR-PCR.

'Milam' (a purported hybrid of Citrus jambhiri Lush) + 'Femminello' lemon (Citrus limon L. Burm. f.) allotetraploid somatic hybrids were used as pollen parents in interploid crosses with diploid 'Femminello' lemon to achieve mal secco tolerance in different populations of seedless triploid lemon types with good fruit quality. A total of 137 plantlets were obtained and subjected to screening experiments, in order to distinguish zygotic embryos from nucellars. Here we report on and discuss the results obtained with three techniques: flow cytometry, isozyme analysis and ISSR-PCR (the inter-simple sequence repeats-polymerase chain reaction). ISSR-PCR resulted to be a very efficient and reliable technique for the identification of zygotic plantlets.

Citrus↗

PubMed2006

Genetic diversity and recombination within populations of Fusarium pseudograminearum from western Canada.

Genetic diversity within populations of Fusarium pseudograminearum isolated from wheat grains from the Canadian provinces of Alberta and Saskatchewan was investigated. Three restriction enzymes (EcoRI, HaeIII, and PstI) were used to carry out restriction analysis of the nuclear ribosomal DNA (nrDNA) intergenic spacer region (IGS region) and eight primers were used to generate inter-simple sequence-repeat (ISSR) molecular markers. Our study indicated substantially high genetic diversity within these two populations, but low genetic differentiation and frequent gene flow among populations. The IGS data showed no genetic distinction between the two Alberta populations and only minor genetic differentiation between the Saskatchewan and Alberta populations. Analysis of molecular variance indicated that most genetic variability resulted from differences among isolates within populations. Multilocus linkage disequilibrium analysis suggested a panmictic population genetic structure and the occurrence of significant recombination in F. pseudograminearum. Regular gene flow and random mating between isolates from different populations could result in novel genotypes with both improved pathological and biological traits.

Canada↗

PubMed1996

Microsatellite instability analysis of primary human brain tumors.

Microsatellite instability, as shown by the presence of additional alleles or shifts of electrophoretic mobility at simple sequence tandem repeat loci, has been demonstrated in hereditary and sporadic colorectal tumors and many other tumor types. To study microsatellite instability in human brain tumors, we examined a total of 144 sporadic neoplasms. These included 33 astrocytic tumors, 23 oligodendrogliomas, six gangliogliomas, 41 meningiomas, 10 vestibular schwannomas and 31 pituitary adenomas. Di-, tri- and tetranucleotide repeat microsatellite markers localized on chromosome 4 and 9, X, 13 and 22, respectively, were used to assess whether instability was a significant aspect of their abnormal chromosomal pattern. Instability of microsatellite markers was detected in four oligodendrogliomas (17.4%), one pituitary adenoma (3.2%), one meningioma (2.4%), one astrocytic tumor (3.0%) and not at all in gangliogliomas and schwannomas. Therefore, our results suggest that the microsatellite instability which occurs in colorectal cancers with defective mismatch repair is infrequent in many types of human brain tumors and that the lower level of instability observed in brain tumors may be reflective of other mechanisms of genetic instability.

Base Sequence↗

PubMed1998

Initial results of a genome survey for novel Alzheimer's disease risk genes: association with a locus on the X chromosome.

As the initial step in a systematic genome survey, 16 simple sequence tandem repeat polymorphisms that span the X chromosome at an average spacing of 10 cM were examined for allelic associations with typical-onset Alzheimer's disease (AD). The efficiency of this survey was substantially enhanced by genotyping pools of genomic DNA from 50 autopsy-confirmed AD cases and 50 autopsied controls who were similar in sex ratio, race, and age at death. The frequency of the DXS1047 202-bp allele was twice as common among AD cases (0.45 +/- S.E. 0.06) than controls (0.22 +/- S.E. 0.05), a finding that was reproduced in an independent and geographically disparate sample. Consistent with Hardy-Weinberg equilibrium, the proportion of women with AD who carried the 202-bp allele, 73% was nearly double that observed for men with AD, 38%. However, the frequency of the 202-bp allele was similar for men and women and the presence of this allele did not affect the age at onset of dementia in either sex. Furthermore, the frequency of the DXS1047 202-bp allele in AD cases and controls was unaffected by the APOE genotype, indicating that these two loci modulate AD risk independently. Finally, the frequency of the 202-bp allele among 50 autopsy-confirmed cases of Parkinson's disease (0.29 +/- S.E. 0.06) was indistinguishable from the control value, reflecting relative specificity for this allelic association with AD.

Adult↗

PubMed1998

Linkage and association analysis of chromosomal regions containing genes related to neuroendocrine or serotonin function in families with early-onset, recurrent major depression.

Recurrent unipolar depression with an early age of onset is a severe form of unipolar depression that has both genetic and environmental components. We genotyped the members of 16 families identified by probands with early onset (< or = 25 years), recurrent unipolar, major depression for 38 simple sequence tandem repeat polymorphisms (SSTRPs) from chromosomal regions containing 12 genes involved in neuroendocrine or serotonergic functioning. Pairwise linkage analysis was performed with the software package FASTLINK. The affected phenotype was defined four ways, and both dominant and recessive models of depression were analyzed. Seven SSTRPs showed lod scores > 1.00 at theta values between 0.10-0.20. The members of an additional 18 families were genotyped for these seven SSTRPs, and the complete sample of 34 families was evaluated using lod score analysis, affected pedigree member linkage analysis, and within-family association analysis. Evidence for linkage between D11S929 and affective illness remained positive, necessitating the analysis of four additional SSTRPs within 3 cM of D11S929. After all confirmatory analyses were completed, no evidence suggestive of linkage remained between any of the 38 SSTRPs and the affected phenotypes.

Depressive Disorder↗

PubMed1997

Cancers of the papilla of vater: mutator phenotype is associated with good prognosis.

Cancer of the papilla (ampulla) of Vater is an uncommon disease that kills 60% of affected patients. There is general agreement that local spread of the tumor (T stage) is the only significant and independent prognostic factor for this cancer, whereas the predictive value of tumor grade and lymph node metastases is controversial. The genetic anomalies involved in this process have the potential to serve as additional prognostic markers. We explored 25 ampullary cancers for the occurrence of instability at simple repeat DNA sequences (microsatellites) of the type seen in replication error phenotype (RER-positive) cancers. Ten microsatellites from five different chromosomes were amplified by PCR from both normal and cancer tissue DNA of the same patients. A tumor was defined as RER-positive when microsatellite instability was found in the majority (>/=6) of the loci analyzed. Five cancers (20%) showed a RER phenotype and were associated with long survival of patients (32-96 months), whereas RER-negative cancers had a significantly poorer prognosis (Mantel-Cox test; P = 0.0084), with a median actuarial survival of 17 months. We also report that three (12%) patients belonged to cancer-prone families and four (16%) were cancer-prone individuals.

Actuarial Analysis↗

PubMed1997

Transmembrane domain sequence requirements for activation of the p185c-neu receptor tyrosine kinase.

The receptor tyrosine kinase p185c-neu can be constitutively activated by the transmembrane domain mutation Val664-->Glu, found in the oncogenic mutant p185neu. This mutation is predicted to allow intermolecular hydrogen bonding and receptor dimerization. Understanding the activation of p185c-neu has assumed greater relevance with the recent observation that achondroplasia, the most common genetic form of human dwarfism, is caused by a similar transmembrane domain mutation that activates fibroblast growth factor receptor (FGFR) 3. We have isolated novel transforming derivatives of p185c-neu using a large pool of degenerate oligonucleotides encoding variants of the transmembrane domain. Several of the transforming isolates identified were unusual in that they lacked a Glu at residue 664, and others were unique in that they contained multiple Glu residues within the transmembrane domain. The Glu residues in the transforming isolates often exhibited a spacing of seven residues or occurred in positions likely to represent the helical interface. However, the distinction between the sequences of the transforming clones and the nontransforming clones did not suggest clear rules for predicting which specific sequences would result in receptor activation and transformation. To investigate these requirements further, entirely novel transmembrane sequences were constructed based on tandem repeats of simple heptad sequences. Activation was achieved by transmembrane sequences such as [VVVEVVA]n or [VVVEVVV]n, whereas activation was not achieved by a transmembrane domain consisting only of Val residues. In the context of these transmembrane domains, Glu or Gln were equally activating, while Lys, Ser, and Asp were not. Using transmembrane domains with two Glu residues, the spacing between these was systematically varied from two to eight residues, with only the heptad spacing resulting in receptor activation. These results are discussed in the context of activating mutations in the transmembrane domain of FGFR3 that are responsible for the human developmental syndromes achondroplasia and acanthosis nigricans with Crouzon Syndrome.

Amino Acid Sequence↗

PubMed1992

CpG suppression in vertebrate genomes does not account for the rarity of (CpG)n microsatellite repeats.

Simple microsatellite repetitive sequences are widely distributed in eukaryotic genomes. Using the GCG Find program, the distribution of each type of mono- and dinucleotide repetitive sequence has been examined in GenBank sequences. Examples of each type of simple satellite sequence could be found, although the frequency of (CpG)n greater than or equal to 8 repeats was extremely low. The suppression of CpG dinucleotides in vertebrates does not adequately explain the rarity of this repeat since (CpG)n repeats are also extremely infrequent in species genomes where CpG dinucleotides are not suppressed. Instead, it is proposed that (CpG)n repeats must possess a DNA conformation that has a deleterious structural effect.

Animals↗

PubMed2005

SVM classification of human intergenic and gene sequences.

Despite constant improvement in prediction accuracy, gene-finding programs are still unable to provide automatic gene discovery with the desired correctness. This paper presents an analysis of gene and intergenic sequences from the point of view of language analysis, where gene and intergenic regions are regarded as two different subjects written in the four-letter alphabet {A,C,G,T}, and high frequency simple sequences are taken as keywords. A measurement alpha(l(tau)) was introduced to describe the relative repeat ratio of simple sequences. Threshold values were found for keyword selections. After eliminating 'noise', 178 short sequences were selected as keywords. DNA sequences are mapped to 178-dimensional Euclidean space, and SVM was used for prediction of gene regions. We showed by cross-validation that the program we developed could predict 93% of gene sequences with 7% false positives. When tested on a long genomic multi-gene sequence, our method improved nucleotide level specificity by 21%, and over 60% of predicted genes corresponded to actual genes.

Algorithms↗

PubMed2005

Finding keywords for intergenic and gene regions for human genome.

The analysis of functionally related sequences for conserved patterns is important for further research of different functional regions. This paper presents an analysis of genes and intergenic sequences from the point of view of linguistics analysis, where gene and intergenic regions are regarded as two different subjects written in the four-letter alphabet [A, C, G, T] and high-frequency simple sequences are taken as keywords. A measurement alpha[l(tau)] was introduced to describe the relative repeat ratio of simple sequences. Cutoff values were found for keywords selection. After eliminating "noise," 87 short sequences were selected as keywords for intergenic regions and 76 for gene regions.

Base Sequence↗

PubMed1991

Oligonucleotide fingerprinting using simple repeat motifs: a convenient, ubiquitously applicable method to detect hypervariability for multiple purposes.

A panel of simple repetitive oligonucleotide probes has been designed and tested for multilocus DNA fingerprinting in some 200 fungal, plant and animal species as well as man. To date at least one of the probes has been found to be informative in each species. The human genome, however, has been the major target of many fingerprinting studies. Using the probe (CAC)5 or (GTG)5, individualization of all humans is possible except for monozygotic twins. Paternity analyses are now performed on a routine basis by the use of multilocus fingerprints, including also cases of deficiency, i.e. where one of the parents is not available for analysis. In forensic science stain analysis is feasible in all tissue remains containing nucleated cells. Depending on the degree of DNA degradation a variety of oligonucleotides are informative, and they have been proven useful in actual case work. Advantages in comparison to other methods including enzymatic DNA amplification techniques (PCR) are evident. Fingerprint patterns of tumors may be changed due to the gain or loss of chromosomes and/or intrachromosomal deletion and amplification events. Locus-specific probes were isolated from the human (CAC)5/(GTG)5 fingerprint with a varying degree of informativeness (monomorphic versus truly hypervariable markers). The feasibility of three different approaches for the isolation of hypervariable mono-locus probes was evaluated. Finally, one particular mixed simple (gt)n(ga)m repeat locus in the second intron of the HLA-DRB genes has been scrutinized to allow comparison of the extent of exon-encoded (protein-) polymorphisms versus intronic hypervariability of simple repeats: adjacent to a single gene sequence (e.g. HLA-DRB1*0401) many different length alleles were found. Group-specific structures of basic repeats were identified within the evolutionarily related DRB alleles. As a further application it is suggested here that due to the ubiquitous interspersion of their targets, short probes for simple repeat sequences are especially useful tools for ordering genomic cosmid, yeast artificial chromosome and phage banks.

Animals↗

PubMed1978

Chromosomal localization of complex and simple repeated human DNAs.

Complex repeating restriction multimers and a simple AT rich satellite isolated with Hoechst 33258 ( less than or equal to 0.5% of the human genome) were localized by in situ hybridization to human chromosomes. The complex repeats were clustered at the centromeres, consonant with their integration in tandem arrays at these loci; these sequences were very prominent on chromosomes 7, 10 and 19, sites not previously identified with any specific human repeated sequence. The Hoechst simple satellite labelled predominantly the long arms of the Y chromosome. Although this simple satellite and the complex restriction multimers did not hybridize with each other, and did not contain detectable ribosomal sequences, both isolates additionally labelled the nucleolus organizing regions (NORs) of acrocentric chromosomes.--The possible relationship of complex and simple repeated DNAs, and their assignment to specific chromosomal domains, is discussed.

Base Sequence↗

PubMed1987

Characterization of a human 'midisatellite' sequence.

We have examined the structure and DNA sequence of a human genomic locus that consists of a large hypervariable region made up of repeats of a simple sequence. With several restriction enzymes, the locus shows many restriction fragments that vary quantitatively as well as qualitatively. Other restriction enzymes produce only a single, high-molecular-weight fragment at this locus. Almost all of the fragments are revealed with a simple sequence probe. Southern transfers of the high-molecular-weight restriction fragments produced by the restriction enzymes NotI and SfiI, resolved by pulsed-field gel electrophoresis, gave at most two fragments, demonstrated to be allelic, showing that the majority of the restriction fragments seen in the complex patterns are at a single locus. The estimated size of the region homologous to the probe varied from 250 to 500 kilobases. DNA sequencing indicated that the region consists of tandem repeats of a 40-base-pair sequence. Some homology was detected to the tandem repeating units of the insulin gene and the zetaglobin pseudogene hypervariable regions, and to the "minisatellite" DNA at the myoglobin locus.

Base Sequence↗

PubMed1994

Exploiting the informativity of 'meaningless' simple repetitive DNA from indirect gene diagnosis to multilocus genome scanning.

Most eukaryotic genomes are characterized by excessively large amounts of non-coding DNA sequences among which redundant (repetitive) elements constitute a sizable portion. The functional role of an abundant subclass of repetitive sequences--simple, tandemly arranged repeats--remained mysterious so far. Even the biological meaning of most of these elements appears quite refractory to present-day techniques in molecular genetics. Notwithstanding simple repetitive sequences have been developed into superb tools for various aspects of eukaryotic genome research: Using oligonucleotide probes carrying simple repeat motifs multilocus DNA fingerprinting can be applied for individual identification and genetic relationship analyses in plants, animals and humans. Microsatellite analyses via polymerase chain reaction of simple repeat blocks allow for efficient investigations of such divers subject matters as criminal stains, detailed genome maps and indirect gene diagnoses.

Communicable Diseases↗

PubMed1985

Two human gamma-crystallin genes are linked and riddled with Alu-repeats.

A human genomic cosmid clone, pHcos gamma-1, has been isolated containing two closely linked gamma-crystallin genes, oriented in the same direction. The sequence of these genes and their 5' and 3' flanking regions has been determined. The coding regions of both genes are interrupted by two introns. The first introns (94 and 100 bp, respectively) are located in the 5' region of the genes. The second introns (2.82 and 0.95 kb, respectively) divide the genes into two halves, each encoding a structural domain of the gamma-crystallin protein. The coding regions of the two genes show 80% homology. Due to a mutation in the splice acceptor site of the second intron of the first gene, the coding region of its third exon is 3 bp longer than that of the second gene. In the flanking regions several conserved sequence elements were found, including those elements that are known to be necessary for the correct expression of eukaryotic genes. The flanking and intronic regions of the genes contain 'simple sequence' DNA and Alu repeats. The Alu repeats are usually clustered, contain truncated elements, and are often located near simple sequence DNA.

Base Sequence↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed1996

A comprehensive genetic map of the human genome based on 5,264 microsatellites.

The great increase in successful linkage studies in a number of higher eukaryotes during recent years has essentially resulted from major improvements in reference genetic linkage maps, which at present consist of short tandem repeat polymorphisms of simple sequences or microsatellites. We report here the last version of the Généthon human linkage map. This map consists of 5,264 short tandem (AC/TG)n repeat polymorphisms with a mean heterozygosity of 70%. The map spans a sex-averaged genetic distance of 3,699 cM and comprises 2,335 positions, of which 2,032 could be ordered with an odds ratio of at least 1,000:1 against alternative orders. The average interval size is 1.6 cM; 59% of the map is covered by intervals of 2 cM at most and 1% remains in intervals above 10 cM.

Algorithms↗