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J Nalbantoglu

Publications and source records attributed to J Nalbantoglu.

At least 73 records · Page 4Linked to original sources
PubMed1991

Beta-amyloid protein in Alzheimer's disease.

Beta-amyloid protein, a 42-43 amino acid polypeptide, accumulates abnormally in senile plaques and the cerebral vasculature in Alzheimer's disease. This polypeptide is derived from a membrane-associated precursor which has several isoforms expressed in many tissues. The precursor protein is processed constitutively within the beta-amyloid domain, leading to the release of the large N-terminal portion into the extracellular medium. beta-amyloid protein may be toxic to certain neuronal cell types and its early deposition may be an important event in the pathogenesis of Alzheimer's disease.

Alzheimer Disease↗
PubMed1990

Structural and functional analysis of the human thymidylate synthase gene.

The complete nucleotide sequence of the human thymidylate synthase (TS) gene was determined. The biologically active unit spans about 16 kilobase pairs (kbp) and is composed of seven exons and six introns. The promoter region and the major transcriptional start sites were located within about 400 base pairs (bp) and 160-180 bp, respectively, upstream from the ATG initiation codon. A minigene consisting of a 5'-flanking sequence of about 4 kbp, a coding sequence of about 1.7 kpb was sufficient for cell cycle-dependent expression of TS when introduced into a TS-deficient mutant of rodent cells. The 5'-flanking region does not contain a "TATA," "CAAT," or the consensus sequence for Sp1 binding (GC box), whereas intron 1 contains three GC boxes. The gene is G + C-rich and the CpG-rich region extends from 5'-flanking region to intron 1. These sequence characteristics were compared with those of the mouse TS gene and other cell cycle-regulated genes.

Animals↗
PubMed1990

Cellular isoform of the scrapie agent protein participates in lymphocyte activation.

The scrapie agent protein (Sp33-37 or PrPSc) is the disease-associated isoform of a normal cellular membrane protein (Cp33-37 or PrPC) of unknown function. We report that normal human lymphocytes and lymphoid cell lines, but not erythrocytes or granulocytes, express PrPC mRNA and protein. PrPC is detectable on the surface of lymphocytes; the surface immunoreactivity is sensitive to phosphatidylinositol-specific phospholipase C, indicating glycosyl-phosphatidylinositol membrane anchorage. Lymphocyte PrPC surface abundance is increased by cell activation, and polyclonal antibodies to PrPC suppress mitogen-induced activation. We conclude that PrPC is a lymphocyte surface molecule that may participate in cell activation.

Animals↗
PubMed1990

DNA cytosine methylation in brain of patients with Alzheimer's disease.

We developed a novel quantitative assay to test the hypothesis that defects in DNA cytosine methylation might be responsible for the brain chromatin abnormalities and transcriptional alterations observed in patients with Alzheimer's disease (AD). We found no significant difference in percent methylation of CCGG sites from brain DNA of 44 patients with AD compared with 20 normal subjects. These results, however, would not exclude genomic redistribution of methylcytosine in AD, or disturbed methylation of a limited population of critical brain-specific genes.

Aged↗
PubMed1990

Lack of association between two restriction fragment length polymorphisms in the genes for the light and heavy neurofilament proteins and Alzheimer's disease.

The etiology of Alzheimer disease (AD) remains unknown. The hypothesis of genetic factors playing a role in the causation of the disease, at least in its familial form, has been borne out by results showing linkage in several early-onset AD families to a locus on the proximal part of the long arm of chromosome 21. Linkage was not detected in several other families using the same markers. The metabolism of neurofilaments is perturbed in AD, as indicated by the presence of neurofilament epitopes in neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit in AD brain. To detect a possible anomaly that might relate to the disease, we have searched for an association between the genes for the light subunit and the heavy subunit of the neurofilament triplet, and AD. Genotypes for restriction fragment length polymorphisms (RFLP) at each of the two loci were determined for an AD group and a control group. Allelic frequencies at a TaqI-defined RFLP for the gene for the light neurofilament subunit were 0.70 for the 3.7 kb allele and 0.30 for the 2.9 kb allele. HincII detected an RFLP for the heavy neurofilament subunit gene with frequencies of 0.31 for the 18.0 kb allele and 0.69 for the 6.8 kb allele. Frequencies were found to be similar in the two groups for both light and heavy neurofilament subunit loci. Although it cannot be excluded that mutations at other sites of the neurofilament genes are relevant to AD, the data reported here do not support an association between these genes and the disease.

Adult↗
PubMed1989

Ascertainment of informative Alzheimer disease families from the IMAGE Project registry for genetic linkage analysis studies.

Genetic linkage analysis requires the identification and documentation of large families with many affected members present, preferably in more than one generation. The IMAGE Project has been establishing a population-based Alzheimer disease (AD) registry in the Saguenay - Lac-Saint-Jean region of the Province of Quebec. The population of this region has a well-documented ancestry, with reliable genealogical records (since 1842) computerized by SOREP. We have recently begun to investigate the pedigrees of selected probands (definite, probable and possible) from the IMAGE registry in order to identify informative pedigrees for genetic linkage analysis. Interviews were carried out with close relatives of the probands (at least one informant per sibship) to identify secondary AD cases. The questionnaires used pertain to the accuracy of genealogical records, to family medical history and to a retrospective diagnosis of AD for people with cognitive deficits. By these means, we have documented a large extended pedigree in which a total of 15 individuals with cognitive deficits were ascertained over three generations. Of these cases, 7 are still living and there is autopsy confirmation in another one. Computer simulations using the program SIMLINK revealed that this is a potentially informative family for linkage analysis. Horizontal extension of the pedigree to second cousins of the proband is now being carried out. This will render the family IMAGE/1 even more informative in genetic linkage analysis studies.

Alzheimer Disease↗
PubMed1989

Identification and characterization of an L1 family sequence with a very long open reading frame in the third intron of the human thymidylate synthase gene.

A long L1 repetitive sequence (3.6 kilobase pairs) was found in the third intron of the human thymidylate synthase gene. This L1 family sequence is unique in that it possesses the longest open reading frame (1.7 kilobase pairs) of all L1 family members identified in sequences associated with specific genes that have been cloned thus far. Furthermore, the amino acid sequence deduced from the open reading frame of the L1 sequence was found to be highly homologous (90%) to that encoded by a known human teratocarcinoma L1 RNA species, and to contain several blocks of sequences homologous to ones in RNA-dependent DNA polymerases of various origins.

Amino Acid Sequence↗
PubMed1988

Insertion of unique and repetitive DNA fragments into the aprt locus of hamster cells.

Two insertion mutations occurring at the aprt locus of Chinese hamster ovary cells were analyzed at the nucleotide level by cloning and sequencing the mutant genes. The insertions are similar with respect to events at the target site in that both are accompanied by small deletions. The nature of the DNA introduced, on the other hand, is very different, a unique fragment in a spontaneously occurring mutant and a highly dispersed, repetitive fragment in a gamma radiation-induced strain. The inserts are small (285 and 58 base-pairs) and have none of the structural features or sequences related to putative mobile sequences in mammalian cells. The mechanism of transposition was further examined by cloning the unique donor fragment of the spontaneous mutant. These analyses revealed that the insert in the mutant gene was a precise duplicate of the donor DNA fragment.

Animals↗
PubMed1988

Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease.

The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected in DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease.

Alleles↗
PubMed1987

Next-nucleotide effects in mutations driven by DNA precursor pool imbalances at the aprt locus of Chinese hamster ovary cells.

Imbalances of the intracellular pools of the precursors of DNA synthesis, the deoxyribonucleoside triphosphates, produce marked shifts in the spectrum of mutations at the aprt locus of Chinese hamster ovary cells. Mutations induced by excess dTTP or dCTP are dominated by misincorporation of the nucleotide in excess, as determined by sequence analysis of cloned mutant genes. The shift in spectrum is also apparently influenced by the nucleotides surrounding the one altered--those 3' to the nucleotide misincorporated being present in excess in most of the mutant genes characterized. Since next-nucleotide effects are a property of DNA polymerases with "proofreading" activities, our data suggest that this function is part of the mammalian DNA replication complex.

Adenine Phosphoribosyltransferase↗
PubMed1987

DNA sequence analysis of spontaneous mutations at the aprt locus of hamster cells.

To determine the nature of spontaneous mutational events in cellular genes in hamster cells, mutant adenine phosphoribosyltransferase (aprt) genes were cloned and the regions to which we mapped alterations were sequenced. A variety of nucleotide changes were found to occur in the 12 mutant genes analyzed. Most mutations were simple base-pair substitutions-transitions (both G X C----A X T and A X T----G X C) and transversions. The only multiple mutation was a simple transition next to a single-base-pair insertion. Of the 12 mutations, 4 were more complex, involving small deletions or duplications. Two of these were similar to previously described deletions in that they occurred between short direct sequence repeats. No hot spots were detected. Three independent mutations were characterized at one restriction endonuclease site, although no other mutations were detected in the nucleotides surrounding this site in other mutant strains. At a functional level, sequence changes were either in exons (resulting in missense and, in one instance, nonsense mutations) or at splicing sites.

Adenine Phosphoribosyltransferase↗
PubMed1986

Structure and sequence of mutations induced by ionizing radiation at selectable loci in Chinese hamster ovary cells.

The spectrum of mutations induced by ionizing radiation at two non-essential genetic loci varies markedly. Those at the adenine phosphoribosyl transferase (aprt) locus predominantly have no detectable alterations of gene structure on Southern blots, while those at the hypoxanthine guanine phosphoribosyl transferase (hprt) locus are largely massive deletions eliminating all coding sequence. Insertion mutations were detected at both loci. To characterize the sequence alterations producing the minor changes at the aprt locus, two mutant genes were cloned from lambda genomic libraries and sequenced. One of these mutants proved to be a 20 base-pair deletion formed between two short (3 base-pair) direct repeat sequences, while the second was the result of a 58 base-pair insertion accompanied by a 13 base-pair deletion.

Animals↗
PubMed1986

DNA amplification--deletion in a spontaneous mutation of the hamster aprt locus: structure and sequence of the novel joint.

In a collection of spontaneous mutants of Chinese hamster ovary cells selected for deficiency in adenine phosphoribosyl transferase (aprt) activity, one was detected having not only a deletion of aprt coding sequences but also an apparent amplification of remaining sequences. The HindIII fragment bearing the novel joint was cloned and sequenced revealing a complex gene rearrangement. A deletion of at least 9 kb extending upstream from the aprt locus is accompanied by an inverted duplication of flanking sequences 672 bp downstream from the novel joint. This unit is amplified three to four times with the net result of some sequences being increased as much as eight fold in copy number because of the duplication. The fidelity of the sequences involved is preserved. We propose a model which could account for this inverted duplication.

Adenine Phosphoribosyltransferase↗
PubMed1986

Spontaneous deletion formation at the aprt locus of hamster cells: the presence of short sequence homologies and dyad symmetries at deletion termini.

To examine the factors governing the generation of DNA sequence rearrangements in mammalian somatic cells, we have cloned and sequenced novel junctions produced by six spontaneous deletion mutations at the aprt locus of Chinese hamster ovary cells. Our analyses indicate that these rearrangements were produced by non-homologous recombinational events occurring between short (2-7 bp) sequence repeats at the two termini of the deletion which leave one copy of the repeat in the mutant gene. Certain tri- and tetranucleotides recur at the deletion termini, suggesting that these may possibly be a recognition sequence for an enzyme involved in the event. No other gene structural alterations were found at the novel junctions or in neighbouring sequences. The deletions are not randomly distributed over the aprt gene; four termini clustered in a 40-bp sequence. This region of aprt is unusual as it contains both significant stretches of dyad symmetry which could potentially form stable DNA secondary structures and short direct repeats. Regions of dyad symmetry were also found at at least one terminus of all the deletions. In view of the similar properties of this set of deletions, possible mechanisms for the formation of this type of gene rearrangement are considered.

Adenine Phosphoribosyltransferase↗