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E. Danciger

Bio: E. Danciger is an academic researcher from Weizmann Institute of Science. The author has contributed to research in topics: Gene & Chromosome 21. The author has an hindex of 8, co-authored 10 publications receiving 418 citations.

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Journal ArticleDOI
TL;DR: The unusual splice junction is functional in vivo since it was detected in both alleles of the SOD‐1 gene, which were defined by differences in the length of restriction endonuclease fragments (RFLPs) that hybridize to the cDNA probe.
Abstract: The SOD-1 gene on chromosome 21 and approximately 100 kb of chromosomal DNA from the 21q22 region have been isolated and characterized. The gene which is present as a single copy per haploid genome spans 11 kb of chromosomal DNA. Heteroduplex analysis and DNA sequencing reveals five rather small exons and four introns that interrupt the coding region. The donor sequence at the first intron contains an unusual variant dinucleotide 5'-G-C, rather than the highly conserved 5'-GT. The unusual splice junction is functional in vivo since it was detected in both alleles of the SOD-1 gene, which were defined by differences in the length of restriction endonuclease fragments (RFLPs) that hybridize to the cDNA probe. Genomic blots of human DNA isolated from cells trisomic for chromosome 21 (Down's syndrome patients) show the normal pattern of bands. At the 5' end of gene there are the 'TATA' and 'CAT' promoter sequences as well as four copies of the -GGCGGG- hexanucleotide. Two of these -GC- elements are contained within a 13 nucleotide inverted repeat that could form a stem-loop structure with stability of -33 kcal. The 3'-non coding region of the gene contains five short open reading-frames starting with ATG and terminating with stop codons.

227 citations

Journal ArticleDOI
TL;DR: Clinical and pathologic studies of adult patients with Down syndrome reveal that many of these persons develop progressive dementia and a variety of neurologic abnormalities identical to those of Alzheimer’s dementia, suggesting an association between the two condition; that is, genes on chromosome 21 could play a role in the development of Alzheimer's disease.
Abstract: About one in 1000 newborn babies carries an extra chromosome 21, a condition technically known as trisomy 2 1 . ’ ~ ~ This chromosome imbalance is the cause of Down syndrome,’ a disease characterized by severe mental retardation as well as a wide variety of physiological defects such as reduced viability, abnormalities of morphogenesis, increased incidence of leukemia, high susceptibility to infection, and some signs of premature a g i ~ ~ g . ~ . ~ In addition, clinical and pathologic studies of adult patients with Down syndrome reveal that many of these persons develop progressive dementia and a variety of neurologic abnormalities identical to those of Alzheimer’s dementia, suggesting an association between the two condition^^-'^; that is, genes on chromosome 21 could play a role in the development of Alzheimer’s disease. In most cases, the patients with Down’s syndrome have a karyotype with 47 chromosomes (46 plus one additional 21). However, cases of Down syndrome have been identified in which only a portion of chromosome 21 is present in triplicate, usually translocated to another chromosome. This finding enabled the localization of the region “responsible” for the syndrome on segment 21q22-the distal portion of the long arm of chromosome 21.13-2’ Seven genes have been assigned, so far, to human chromosome 21: ribosomal RNA (rRNA)22.23; interferon receptor (IFRC)24; cytoplasmic superoxide dismutase (SOD 1)24; glycineamide phosphoribonucleotide synthetase (GARS)25; aminoimidazol ribonucleotide synthetase (AIRS)26; liver-type 6-phosphofructokinase

42 citations

Journal ArticleDOI
01 Dec 1989
TL;DR: It was found that while relative amount of PFKL mRNA in adult brain was one-fourth of that detected in fetal brain the level of PFPM mRNA inadult brain was slightly higher than in fetal tissue, suggesting that PFK expression might be controlled at the transcriptional level.
Abstract: The complete mRNA sequence of the human liver-type phosphofructokinase (hPFKL) was determined. The sequence included 55 nucleotides of 5' and 515 of 3' noncoding regions, as well as 2,337 nucleotides encoding the 779 amino acids of the hPFKL. Extensive similarity (approximately 90%) in the coding region was observed between the hPFKL and the mouse PFKL, whereas the degree of similarity between different types of PFK, i.e., hPFKL and human muscle-type PFK (hPFKM), was merely 68%. Nevertheless, striking similarity between these different types of PFK was noticed when the amino acid residues creating the various active sites of the enzyme were compared. Human PFK L- and M-specific probes were constructed and used to quantitate the mRNA levels in fetal and adult brains and fetal liver. It was found that while relative amount of PFKL mRNA in adult brain was one-fourth of that detected in fetal brain the level of PFKM mRNA in adult brain was slightly higher than in fetal tissue, suggesting that PFK expression might be controlled at the transcriptional level.

35 citations

Journal ArticleDOI
01 May 1990-Genomics
TL;DR: The structure and organization of the human liver-type PFK gene are shown to be extremely similar to those of the rabbit muscle-types PFK, and five possible sites of polymorphism have been found.

31 citations

Journal ArticleDOI
TL;DR: Four distinct human Cu/Zn superoxide dismutase (SOD1; EC 1.15.1.1)-related sequences were isolated from genomic DNA libraries and comparisons suggested that they integrated into the genome about 25 million years ago.
Abstract: Four distinct human Cu/Zn superoxide dismutase (SOD1; EC 1.15.1.1)-related sequences were isolated from genomic DNA libraries. Genomic blots, heteroduplex analyses, and DNA sequencing showed that they are processed pseudogenes not residing on chromosome 21. Three of them originated from the 0.7-kilobase SOD1 mRNA, while the fourth was derived from the 0.9-kilobase mRNA species. Comparison between the coding sequences of the functional gene and two of the processed genes suggested that they integrated into the genome about 25 million years ago.

30 citations


Cited by
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Journal ArticleDOI
01 May 1986-Nature
TL;DR: It is likely that most vertebrate genes are associated with ‘HTF islands’—DNA sequences in which CpG is abundant and non-methylated; however, highly tissue-specific genes, though, usually lack islands.
Abstract: It is likely that most vertebrate genes are associated with 'HTF islands'--DNA sequences in which CpG is abundant and non-methylated. Highly tissue-specific genes, though, usually lack islands. The contrast between islands and the remainder of the genome may identify sequences that are to be constantly available in the nucleus. DNA methylation appears to be involved in this function, rather than with activation of tissue specific genes.

3,673 citations

Journal ArticleDOI
TL;DR: It is shown that CpG islands in methylated genomes are maintained, despite a tendency for 5mCpG to mutate by deamination to TpG+CpA, by the structural stability of a high G+C content alone, and that C pG islands associated with exons result from some selective importance of the arginine codon CGX.

3,321 citations

Journal ArticleDOI
TL;DR: Three unique and highly compartmentalized mammalian superoxide dismutases have been biochemically and molecularly characterized to date and a molecular understanding of each of these genes has proven useful toward the deciphering of their biological roles.

1,870 citations

Journal ArticleDOI
TL;DR: The role of each SOD in vascular biologies, physiologies, and pathophysiologies such as atherosclerosis, hypertension, and angiogenesis is updated and the importance of metal cofactors in the activity of SODs is discussed.
Abstract: Excessive reactive oxygen species Revised abstract, especially superoxide anion (O2•−), play important roles in the pathogenesis of many cardiovascular diseases, including hypertension and atherosclerosis Superoxide dismutases (SODs) are the major antioxidant defense systems against O2•−, which consist of three isoforms of SOD in mammals: the cytoplasmic Cu/ZnSOD (SOD1), the mitochondrial MnSOD (SOD2), and the extracellular Cu/ZnSOD (SOD3), all of which require catalytic metal (Cu or Mn) for their activation Recent evidence suggests that in each subcellular location, SODs catalyze the conversion of O2•− H2O2, which may participate in cell signaling In addition, SODs play a critical role in inhibiting oxidative inactivation of nitric oxide, thereby preventing peroxynitrite formation and endothelial and mitochondrial dysfunction The importance of each SOD isoform is further illustrated by studies from the use of genetically altered mice and viral-mediated gene transfer Given the essential role

1,464 citations

Journal ArticleDOI
TL;DR: A novel gene, AIRE, encoding for a putative nuclear protein featuring two PHD-type zinc-finger motifs is isolated, suggesting its involvement in transcriptional regulation in APECED, suggesting the molecular basis of autoimmunity.
Abstract: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is the only described systemic autoimmune disease with established monogenic background, and the first autoimmune disorder localized outside the major histocompatibility complex (MHC) region. The primary biochemical defect in APECED is unknown. We have isolated a novel gene, AIRE, encoding for a putative nuclear protein featuring two PHD-type zinc-finger motifs, suggesting its involvement in transcriptional regulation. Five mutations in AIRE are reported in individuals with this disorder. This is the first report of a single-gene defect causing a systemic human autoimmune disease, providing a tool for exploring the molecular basis of autoimmunity.

1,110 citations