Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 2.6-kilobase (kb) EcoRI restriction endonuclease fragment containing human growth hormone (hGH; somatotropin) gene sequences and a 2.8-kb EcoRI fragment containing human chorionic somatomammotropin (hCS; choriomammotropin) gene sequences have been identified by hybridization to cloned cDNA. Human DNA was cleaved with EcoRI and fractionated by preparative agarose gel electrophoresis; DNA in the size range 2--3 kb was ligated to lambda gt WES.lambda B DNA and viable recombinant bacteriophage were recovered by in vitro packaging. After infection of Escherichia coli and screening of phage plaques, single isolates of hGH and hCS gene sequences were obtained. Restriction endonuclease mapping showed that the hGH gene contains three intervening sequences interrupting the coding sequence. Partial DNA sequence analysis of the hGH gene, obtained by the chain termination method, confirmed the location of the intervening sequences and the identity of the fragment.
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PMID:Structure of genes for human growth hormone and chorionic somatomammotropin. 29 65

Familial isolated growth hormone deficiency type IA results from homozygosity for either a 6.7-kb or a 7.6-kb hGH-1 gene deletion. Genomic DNA was extracted from circulating lymphocytes of 78 subjects with severe isolated growth hormone deficiency (height less than -4.5 SD score) and studied by polymerase chain amplification and by restriction endonuclease analysis looking for gene deletions within the hGH-gene cluster. The individuals analyzed were broadly grouped into three different populations (North-European, n = 32; Mediterranean, n = 22; and Turkish, n = 24). Ten out of 78 patients studied presented with an hGH-1 gene deletion; eight out of these 10 showed a 6.7-kb gene deletion, the remaining two a 7.6-kb hGH-1 gene deletion. Five of the 10 subjects developed anti-hGH antibodies to hGH replacement followed by a stunted growth response. Family studies of the affected patients were performed, revealing consanguinity in all the families, and the corresponding heterozygosity for the deletion was present in each of the parents. The results of our study revealed a prevalence for an hGH-1 gene deletion in three out of 32 North-European, three out of 22 Mediterranean, and four out of 24 Turkish patients with growth hormone deficiency (height less than 4.5 SD score). These data are important for prenatal diagnosis of at-risk pregnancies and for families at risk for recurrence and underline clearly the fact that the hGH-I gene deletion represents a common cause for growth hormone deficiency associated with severe growth retardation (height less than -4.5 SD score).
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PMID:Prevalence of human growth hormone-1 gene deletions among patients with isolated growth hormone deficiency from different populations. 160 35

Isolated GH deficiency (IGHD) cannot be distinguished on the grounds of anti-human (h) GH antibodies and stunted growth response to exogenous hGH. DNA analysis was proposed to classify children with IGHD. Genomic DNA was extracted and studied by restriction endonuclease analysis after extraction from the circulating lymphocytes of 53 children with IGHD. These children included 5 pairs of siblings and 5 individuals from 10 families, whose parents (n = 20) and brothers and sisters (n = 5) were also analyzed. Twenty-five adults, including individuals from 3 families of normal height, were studied as controls. No deletion within the hGH gene cluster was identified using a [32P]hGH cDNA clone as a probe. A compound heterozygosity for a hGH-1 deletion or a mutation have not been found. The allelic frequencies for 5 common restriction fragment length polymorphisms were similar in patients and controls. The distribution and frequency of the distinct haplotypes in the hGH gene family revealed no differences between IGHD (n = 30 chromosomes) and controls (n = 48 chromosomes). No deletion or restriction fragment length polymorphisms could be found using a hGH-releasing hormone cDNA clone as a probe in patients or controls. This large volume of data gathered from a caucasian population indicates that the great majority of patients with IGHD has no structural abnormalities of the hGH gene cluster, particularly no hGH-1 gene deletion. In addition, they have no gross deletions within the hGH-releasing hormone gene.
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PMID:Isolated growth hormone deficiency: analysis of the growth hormone (GH)-releasing hormone gene and the GH gene cluster. 196 79

The gene deletions responsible for isolated partial deficiency of fetal human chorionic somatomammotropin (hCS) production were characterized by restriction endonuclease analysis of genomic DNA prepared from the leukocytes of an affected child. The phenotypically normal child was the product of a 38-week pregnancy characterized by peak maternal hCS levels of 1.1 micrograms/microliter (normal, 3-9.2 micrograms/ml) and normal levels of other pregnancy-associated hormones. Two genes, termed hCS-A and hCS-B, specify the same mature hCS peptide and are responsible for fetal hCS production. Digestion of the child's DNA with the enzymes Hind III, Eco RI, Bam HI, Bgl II, Hinc II and Msp I disclosed absence of the restriction fragments that normally contain the hCS-A gene. However, the hCS-B gene was present in the child's DNA. The child's DNA digests contained an abnormally large Eco RI fragment of 10.0 kb containing the hCS-L gene. This abnormal fragment is a marker for a deletion that is responsible for complete deficiency of hCS when present in the homozygous state. The child's DNA restriction patterns were consistent with heterozygosity for two different deletions involving hCS genes. The paternal hGH gene cluster lacked the hCS-A, human GH variant, and hCS-B genes, while the maternal cluster lacked only the hCS-A gene. Thus, the child's DNA contained only one of the normal complement of four functional hCS genes per diploid genome. Material hCS levels approximately one fourth as great as those present at comparable stages of normal pregnancies indicated that there was no compensatory increase in expression of the remaining hCS gene.
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PMID:An effect of gene dosage on production of human chorionic somatomammotropin. 298 39

Human placental lactogen (hPL) and growth hormone (hGH) are two hormones thought to have evolved from a common ancestral gene (along with prolactin), yet they have quite different functions and specificities. The nucleic acid sequences of the respective cDNAs of the two genes share considerable homology, as well as the existence of multiple forms of each gene within the genome. In this study we report on the linkage arrangement of several genes from this group. Two hPL-like genes as well as an hGH gene are shown to be linked within a 38-kilobase pair region of DNA. Linkage between a variant hGH gene and an hPL gene is also shown. The orientation and structural organization of these genes was previously established using 5'- and 3'-specific probes from a placental lactogen cDNA clone and detailed restriction endonuclease mapping. Restriction fragments from the overlapping clones were verified by comparison to digests of high molecular weight genomic DNA. In addition, the location of a specific class of repetitive DNA sequences, the Alu family, was mapped on these clones using the recombinant clone BLUR 8. All members of this multigene family have Alu repeat sequences either immediately flanking their 3' or 5' untranslated regions or within their intervening sequences.
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PMID:Linkage arrangement of human placental lactogen and growth hormone genes. 628 68

Prolactin (PRL) and growth hormone (GH) genes derive from a common ancestor and still share some sequence homologies. Their expression in the pituitary gland is regulated in opposite directions by most of the many hormones acting on them. This provides an interesting system to study sequences involved in gene expression. Using a human PRL cDNA clone as a probe, we screened a human genomic DNA library in lambda phage and isolated a single recombinant comprising the whole hPRL gene. It was characterized by restriction endonuclease mapping and cDNA hybridization, by DNA heteroduplex analysis and by nucleotide sequencing. The hPRL gene is present as a single copy per haploid genome, is approximately 10 kb long and contains four introns, three of which interrupt the coding sequence at the same locations as in the known GH and PRL genes. The origin of transcription was determined by S1 mapping on prolactinoma mRNAs. The search for direct and inverted repeats, as well as dyad symmetries was carried out in the 900-bp sequenced in the 5'-flanking region. Sequence homologies between hPRL, hGH and rPRL were derived from computer drawn matrices for these upstream regions.
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PMID:Isolation and characterization of the human prolactin gene. 632 71

A Japanese family is described in which a 7-year-old child had isolated growth hormone deficiency type 1A, as described by Illig et al. He was shown to be homozygous for a deletion of the structural gene for hGH (hGH-N gene). Initially his growth rate responded well to hGH administration, but rapidly he developed high titers of hGH antibodies, and growth ceased. At that time, a somatomedin-C generation test gave negative results, suggesting that the growth arrest was related to the inability of hGH to generate somatomedin. Both parents were heterozygous for the hGH-N gene deletion and had a low hGH response to arginine and L-dopa tolerance tests, but had normal basal somatomedin-C levels and normal somatomedin-C generation tests. This family is the fourth to be reported with IGHD type 1A caused by deletion of the hGH-N gene. This cause of growth hormone deficiency can be distinguished from other severe autosomal recessive types of hGH deficiency by the demonstration of the deletion of hGH-N gene using restriction endonuclease analysis.
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PMID:Isolated growth hormone deficiency type 1A in a Japanese family. 653 75

An Italian family with three children presenting with isolated growth hormone (GH) deficiency type IA is described. Restriction endonuclease analysis revealed that the cause of hGH deficiency was a 45-kb gene deletion within the hGH-chorionic somatomammotropin (CS) gene cluster, encompassing the GH-1, CS-L, CS-A, and GH-2 genes. DNA sequence analysis and polymerase chain reaction amplification between two sequences located on each side of the deletion breakpoint accurately identified the deletion breakpoints and indicated that the regulatory sequences located upstream from the TATA box of the mutant CS-B belong to the GH-2 gene. Two of the affected children developed high-titer anti-hGH antibodies after recombinant hGH treatment with secondary growth arrest, whereas the third one maintained normal growth in the presence of very low-titer antibodies. This is the first report of a large deletional mutation within the hGH-CS gene cluster accompanied by phenotypic heterogeneity in terms of growth response and antibody formation in the different patients.
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PMID:Isolated growth hormone deficiency type IA associated with a 45-kilobase gene deletion within the human growth hormone gene cluster in an Italian family. 787 87

hGH-1 gene deletions are detected by simultaneous PCR amplification along the two homologous DNA sequences flanking the hGH-1 gene on both sides and are differentiated by SmaI restriction enzyme digestion. We have observed that among the SmaI digested PCR products from normal homozygous subjects, from those heterozygous for the 7.6 kb deletion and from those heterozygous for a 6.7 kb deletion, along with the expected fragments there is an unexpected 1470 bp fragment. This fragment arises from the co-amplification of a third homologous sequence located downstream from the hGH-1 gene and it confuses differentiation between normal homozygous and heterozygous for 7.6 kb subjects from the 6.7 kb heterozygous subjects. To overcome this problem we have improved PCR conditions using a different reverse primer. These changes avoid the interaction of the primers with the third homologous sequence located downstream from the hGH-1 gene and prevent the appearance of this additional band that complicates the interpretation of the results. We conclude that the new reverse primer sequence avoids the amplification of the downstream hGH-1 gene sequence and the production of the 1474 bp band after SmaI endonuclease enzyme digestion and makes it possible to differentiate homozygous normal subjects and those who are heterozygous for a 7.6 kb deletion from those who are heterozygous for a 6.7 kb deletion.
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PMID:An improved polymerase chain reaction (PCR) protocol for unambigous detection of growth hormone gene deletions. 977 78

The human growth hormone variant (GH-V) gene is expressed during pregnancy in the syncytiotrophoblast and, as shown recently, in the normal human testis. In addition to the classical transcript encoding for the 22 K major form, intron D-retaining processed mRNAs (GH-V2) have also been described in both tissues. In the present study we analyzed testicular GH-V RNA alternative splicing patterns, a major source of GH variability. We observed three types of GH-V-derived mRNAs by reverse transcription-polymerase chain reaction amplification of GH/placental lactogen mRNA, subsequent cloning into appropriate vectors, vector amplification, restriction-endonuclease map-analysis and double-strand sequencing of GH-V clones. Apart from the conventional splice product encoding classical hGH-V (22K, 191 amino acids (aa)) and intron D-retaining mRNA GH-V2 (230aa), we detected an additional GH-V mRNA variant, GH-Vdelta4, utilizing a competitive splice-donor site 4 bp 5'of the conventional exon 4/intron D splice-donor site, but retaining the genuine intron D/exon 5 splice-acceptor site. This mRNA encodes a putative 25 K protein of 219 amino acids in length, having the first 124 amino acids and, thus, two and a half structural alpha-helices in common with hGH-V.hGH-Vdelta4 has lost the N-glycosylation site at Asn 140 of hGH-V, but acquires a novel site at position 148 as well as a cystein-rich domain in the 65 carboxyl-terminal amino acids, potentially involved in multiple disulfide-bridge formation. Tissue specificity and possible functions for testicular physiology remain to be investigated.
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PMID:Complex alternative splicing of the GH-V gene in the human testis. 982 Jun 9


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