| 1. |
- Abrahamson, Magnus, et al.
(author)
-
Structure and expression of the human cystatin C gene
- 1990
-
In: Biochemical Journal. - 1470-8728. ; 268:2, s. 287-294
-
Journal article (peer-reviewed)abstract
- The structural organization of the gene for the human cysteine-proteinase inhibitor cystatin C was studied. Restriction-endonuclease digests of human genomic DNA hybridized with human cystatin C cDNA and genomic probes produced patterns consistent with a single cystatin C gene and, also, the presence of six closely related sequences in the human genome. A 30 kb restriction map covering the genomic region of the cystatin C gene was constructed. The positions of three polymorphic restriction sites, found at examination of digests of genomic DNA from 79 subjects, were localized in the flanking regions of the gene. The gene was cloned and the nucleotide sequence of a 7.3 kb genomic segment was determined, containing the three exons of the cystatin C structural gene as well as 1.0 kb of 5'-flanking and 2.0 kb of 3'-flanking sequences. Northern-blot experiments revealed that the cystatin C gene is expressed in every human tissue examined, including kidney, liver, pancreas, intestine, stomach, antrum, lung and placenta. The highest cystatin C expression was seen in seminal vesicles. The apparently non-tissue-specific expression of this cysteine-proteinase inhibitor gene is discussed with respect to the structure of its 5'-flanking region, which shares several features with those of housekeeping genes.
|
|
| 2. |
|
|
| 3. |
- Klar, Joakim, et al.
(author)
-
RAR-related orphan receptor A isoform 1 (RORa1) is disrupted by a balanced translocation t(4;15)(q22.3;q21.3) associated with severe obesity.
- 2005
-
In: Eur J Hum Genet. - 1018-4813.
-
Journal article (peer-reviewed)abstract
- We have identified a family comprising a mother and two children with idiopathic and profound obesity body mass index (BMI) 41-49 kg/m(2). The three family members carry a balanced reciprocal chromosome translocation t(4;15). We present here the clinical features of the affected individuals as well as the physical mapping and cloning of the chromosomal breakpoints. A detailed characterisation of the chromosomal breakpoints at chromosomes 4 and 15 revealed that the translocation is almost perfectly balanced with a very short insertion/deletion.The chromosome 15 breakpoint is positioned in intron 1 of the RAR-related orphan receptor A isoform 1 (RORa1) and the chromosome 4 breakpoint is positioned 133 kb telomeric to the transcriptional start of the unc-5 homolog B (UNC5C) and 154 kb centromeric of the transcriptional start of the pyruvate dehydrogenase (lipoamide) alpha 2 (PDHA2). The rearrangement creates a fusion gene, which includes the RORa1 exon 1 and UNC5C that is expressed in frame in adipocytes from the affected patients. We also show that this transcript is translated into a protein. From previous reports, it is shown that RORa1 is implicated in the regulation of adipogenesis and lipoprotein metabolism. We hypothesise that the obesity in this family is caused by (i) haploinsufficiency for RORa1 or, (ii) a gain of function mechanism mediated by the RORa1-UNC5C fusion gene.
|
|
| 4. |
- Ulvsbäck, Magnus
(author)
-
Structure and organization of genes for the predominant seminal plasma proteins semenogelin I, semenogelin II and beta-microseminoprotein
- 1999
-
Doctoral thesis (other academic/artistic)abstract
- In man, the predominant proteins in the seminal plasma include semenogelin I, semenogelin II and b-microseminoprotein (MSP). Semenogelin I and II are both synthesized in the seminal vesicles and are the backbone of the gel formed upon semen coagulation. MSP is synthesized in the prostate, but its role has not yet been defined. The genes and cDNA of semenogelin I and II and of MSP were cloned and characterized . A cDNA encoding human MSP was isolated from a prostate cDNA library. The nucleotide sequence was found to be identical to that of prostatic secretory protein of 94 amino acids. Using the cloned cDNA as probe, transcripts of 0.6 kb were detected in human prostate, trachea, bronchi, lung, and gastric mucosa A human genomic clone was isolated, encompassing exons 2, 3, and 4 of the MSP gene. These exons were 106 bp, 106 bp, and 240 bp long respectively, interrupted by introns of 1 and 5.2 kb. The gene is present at one copy per genome and is located on chromosome 10. The human semenogelin I and II genes were isolated. The transcription units of the two genes, 2.7 kb and 3.1 kb respectively, are separated by 11.5 kb of intergenic DNA. Both genes are composed of three-exon transcriptional units with nucleotide sequence similarity ranging from 80% in introns to close to 90% in exons. In both genes exon 1 codes for the signal peptide, exon 2 for the secreted protein, and exon 3 contains non-coding nucleotides only. In contrast to the majority of highly expressed human genes, codons in the second exon of the semenogelin genes prefer A and T bases in the third position instead of G and C. The location of the human semenogelin locus was assigned to chromosome 20q12.q-13.1. The rhesus monkey semenogelin II gene was cloned and consists of three exons of 97, 2086 and 124 bp organized in the same way as the human semenogelin II gene. Due to the larger size of the second exon the translation product from the rhesus monkey gene is 124 amino acid residues longer than its human counterpart. Old World monkeys probably carry semenogelin I genes of the same size as in man, while the semenogelin II gene has evolved to yield proteins that are extended by 120 amino acid residues from man to rhesus monkey to baboon. Semenogelin genes are also present in New World monkeys. The semenogelin genes, and genes related to them, have undergone very rapid evolution and all encode substrates for the enzyme transglutaminase. Hence they constitute a novel gene family: the REST gene family (rapidly evolving substrates for transglutaminase). The gene of the protease inhibitor SKALP/elafin fulfilled all criteria of being a REST gene. The gene for secretory leukocyte protease inhibitor is probably also a member.
|
|
