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J Zandberg

Publications and source records attributed to J Zandberg.

At least 19 recordsLinked to original sources

Identification of a new calcitonin gene in the salmon Oncorhynchus gorbuscha.

Three isoforms of calcitonin (CT) exist in salmonids. Isohormones I and II are expressed in the pink salmon Oncorhynchus gorbuscha. We report here the existence in this species of a CT gene and of its transcripts, which encode for a fourth isohormone, the salmon CT (sCT) IV. This new CT gene was identified by PCR from genomic DNA and by sequencing the amplified DNA. The expression of this CT gene was established in ultimobranchial body and brain, by reverse transcription-PCR, hybridization and sequencing. The sCT IV gene, like the sCT I gene, is a complex transcription unit, containing exons encoding for a CT as a calcitonin gene-related peptide (CGRP) molecule. The predicted peptide, sCT IV, has a greater homology with the eel CT and the sCT II than with the sCT I. Alignment of the sCT IV with other fish and chicken CT showed amino acid modifications in similar positions as those found during evolution. The predicted salmon CGRP IV peptide is highly homologous to the known CGRP molecules in other species, confirming the high conservation of the molecule during evolution. This identification of a new salmon CT gene is interesting both for the therapeutic potential represented by the new molecules encoded by this gene and for phylogenetic studies.

Amino Acid Sequence↗

Identification and partial characterization of the salmon calcitonin/CGRP gene by polymerase chain reaction.

The polymerase chain reaction was used to amplify sequences encoding calcitonin and CGRP in the genomic DNA of salmon. Amplification products of the expected length were cloned and sequenced. In this way a new CGRP-coding sequence was identified. The new sequence and the known salmon calcitonin-coding sequence were shown to be part of one gene, implying that alternative gene expression takes place in fish.

Amino Acid Sequence↗

Islet amyloid polypeptide: structure and upstream sequences of the IAPP gene in rat and man.

Islet amyloid polypeptide (IAPP) or amylin is a pancreatic islet hormone which was first found in amyloid in insulinomas and in pancreases of patients with type 2 diabetes. In rat a similar polypeptide occurs; however, pancreatic amyloid in this species has not been described. Here we report the structure of the rat and human IAPP gene. Both consist of three exons and two introns which are very similar. The upstream sequence of the rat IAPP gene contains a TATA-box, a CCAAT-sequence and a GT-element, whereas the upstream sequence of the human IAPP gene contains a TATA-box and a rat insulin enhancer-like sequence. This suggests that the rat and human IAPP gene may be controlled differently at the transcriptional level.

Amyloid↗

Islet amyloid polypeptide: identification and chromosomal localization of the human gene.

Islet or insulinoma amyloid polypeptide (IAPP) is a 37 amino acid polypeptide isolated from pancreatic amyloid. Here, we describe the isolation and partial characterization of the human gene encoding IAPP. The DNA sequence predicts that IAPP is excised from a larger precursor protein and that its carboxy-terminus is probably amidated. The predicted normally occurring IAPP is identical to the reported polypeptides isolated from pancreatic amyloid, except for the amidated carboxy-terminus. IAPP specific polyadenylated RNAs of 1.6 kb and 2.1 kb are present in human insulinoma RNA. The human IAPP gene is located on chromosome 12.

Amino Acid Sequence↗

A third human CALC (pseudo)gene on chromosome 11.

A genomic locus in man (CALC-III) containing nucleotide sequences highly homologous to both exon 2 and exon 3 of the CALC-I and -II genes, is described in this paper. The CALC-I gene produces calcitonin (CT) (encoded by exon 4) or calcitonin gene-related peptide (CGRP) (encoded by exon 5) in a tissue-specific fashion. The CALC-II gene produces a second human CGRP, but probably not a second CT. The CALC-III gene does not seem to encode a CT- or CGRP-related polypeptide hormone and is probably a pseudogene. Like the other two CALC genes, the CALC-III gene is located on human chromosome 11.

Bacteriophage lambda↗

Structure and expression of the human calcitonin/CGRP genes.

Recently, we have reported the isolation of cDNA encoding a second human calcitonin gene-related peptide (hCGRP-II) [(1985) FEBS Lett. 183, 403-407]. In this report we describe the isolation and characterization of the gene encoding hCGRP-II. This gene, designated CALC-II, is structurally closely related to the known CALC-I gene encoding human calcitonin (hCT) and hCGRP-I. In contrast to CALC-I, CALC-II does not seem to be alternatively expressed. The formation of a second, hCT-like mRNA by differential splicing of CALC-II transcripts is unlikely in view of the structure of CALC-II, and could not be demonstrated in tissues known to express CALC-I and CALC-II.

Amino Acid Sequence↗

A second human calcitonin/CGRP gene.

The calcitonin (CT) gene is alternatively expressed in a tissue-specific fashion producing either the calcium regulatory hormone CT in the thyroid or the neuropeptide calcitonin gene related peptide (CGRP) in the brain. In medullary carcinoma of the thyroid both peptides are produced. We present here evidence for the existence in the human genome of a second CT gene, which is also expressed in human medullary thyroid carcinoma. This gene encodes a second human CGRP, differing from the known human CGRP in 3 of the 37 amino acids.

Amino Acid Sequence↗

The second human calcitonin/CGRP gene is located on chromosome 11.

A second human calcitonin/calcitonin gene related peptide (hCT/CGRP) gene has been identified. This second hCT/CGRP gene has been shown to contain sequences highly homologous to exons 3, 5 (CGRP-encoding), and 6 of the first hCT/CGRP gene, but sequences closely related to exon 4 (CT-encoding) could not be demonstrated. Southern blot hybridization analysis of DNA from human-rodent somatic cell hybrids showed that the second hCT/CGRP gene is located in the q12-pter region of chromosome 11. The first hCT/CGRP gene has previously been assigned to the p13-p15 region of chromosome 11.

Animals↗

Localization of the polymorphic human calcitonin gene on chromosome 11.

A molecular probe containing a 584 base pairs sequence corresponding to part of the human calcitonin mRNA was used for the chromosomal assignment of the calcitonin gene. Restriction endonuclease analysis of DNA from human-Chinese hamster and human-mouse somatic cell hybrids, including some containing a translocation of human chromosomes, placed the calcitonin gene in the p14----qter region of chromosome 11. Analysis of human DNA showed that the calcitonin gene has a polymorphic site for restriction endonuclease TaqI.

Animals↗

Expression of the proopiomelanocortin gene in human medullary thyroid carcinoma.

mRNA isolated from medullary carcinoma of the thyroid (MTC) in six patients with the inherited multiple endocrine neoplasia syndrome type 2 and cervical metastases in two patients with sporadic MTC was screened for the presence of calcitonin and proopiomelanocortin (POMC) related sequences by blot hybridization analysis. All tumors were found to contain mRNA hybridizing to a calcitonin-specific probe. However, POMC-related sequences were detected only in RNA preparations purified from the metastases of MTC. Compared with the POMC mRNA occurring in the human pituitary gland, the size of the RNA species hybridizing to the POMC-specific probe was larger in the metastases of both of the patients investigated. cDNA complementary to mRNA from one of the metastases was cloned into pBR 322. From this library two plasmids were isolated containing inserts which were completely homologous to a sequence of 190 nucleotides from the 3'-end of human pituitary POMC mRNA. In conclusion, 1) hybridization and nucleotide sequence analyses demonstrate that the POMC gene is expressed in MTC metastases; 2) the observed length difference between MTC and pituitary mRNAs suggests differences in expression or processing; 3) no expression of the POMC gene was found in six primary tumors.

Adolescent↗

Calcitonin gene related peptide coding sequence is conserved in the human genome and is expressed in medullary thyroid carcinoma.

Nucleotide sequence analysis of part of the human calcitonin (hCT) gene revealed the presence of a region with 90% homology to the region in the corresponding rat gene encoding calcitonin gene related peptide (CGRP). Analysis of RNA isolated from human medullary thyroid carcinoma (MTC) indicated that in these tumors mRNA hybridizing to hCT specific probe, mRNA hybridizing to hCGRP specific probe and larger RNA species hybridizing to both hCT and hCGRP probes occur. These results suggest that alternative splicing of the primary transcripts of the human CT gene may result in hCT or hCGRP mRNA.

Adult↗

A protein of bacteriophage phi X174 carries an oligonucleotide which it can transfer to the 3' -OH of a DNA chain.

The bacteriophage phi X174 gene A encodes two proteins: gene A protein and A* protein. Purified A* protein acts as a single-stranded, DNA-specific endonuclease which remains covalently attached to the 5'-end of the cleavage site. Incubation of A* protein with the synthetic heptamer CAACTTG or with oligonucleotides which yield this heptamer after cleavage with the A* protein yields oligonucleotides with the sequences CAACTTGAG, CAACTTGAGG and CAACTTGAGGA. This indicates that A* protein carries an oligonucleotide with the sequence--AG, -AGG or -AGGA. The oligonucleotide can be transferred to the 3'-end of the heptamer CAACTTG. This suggests that A* protein reacts with a specific DNA sequence in the infected cell.

Bacteriophage phi X 174↗