| 1. |
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| 2. |
- Amarger, V, et al.
(författare)
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Comparative sequence analysis of the PRKAG3 region between human and pig : evolution of repetitive sequences and potential new exons
- 2003
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Ingår i: Cytogenetic and Genome Research. - : S. Karger AG. - 1424-8581 .- 1424-859X. ; 102:1-4, s. 163-172
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Tidskriftsartikel (refereegranskat)abstract
- The PRKAG3 gene encodes the gamma3 chain of AMP-activated protein kinase (AMPK). A non-conservative missense mutation in the PRKAG3 gene causes a dominant phenotype involving abnormally high glycogen content in pig skeletal muscle. We have determined >126 kb (in 13 contigs) of porcine genomic sequence surrounding the PRKAG3 gene and the corresponding mouse region covering the gene. A comparison of these PRKAG3 sequences and the human sequence was conducted and used to predict evolutionarily conserved regions, including regulatory regions. A comparison of the human genomic sequence and a porcine BAC sequence containing the PRKAG3 gene, revealed a conserved organization and the presence of three additional genes, CYP27A1 (cytochrome P450, family 27, subfamily A, polypeptide 1), STK36 (Serine Threonine Kinase 36), and the homolog of the unidentified human mRNA KIAA0173. Interspersed repetitive elements constituted 51.4 and 38.6% of this genomic region in human and pig, respectively. We were able to reliably align 12.6 kb of orthologous repeats shared between pig and human and these showed an average sequence identity of 72.4%. Our analysis revealed that the human KIAA0173 gene harbors alternative 5' untranslated exons originating from repetitive elements. This provides an obvious example how transposable elements may affect gene evolution.
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| 3. |
- Arnason, Ulfur, et al.
(författare)
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Mitogenomic analyses of eutherian relationships
- 2002
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Ingår i: Cytogenetic and Genome Research. - : S. Karger AG. - 1424-859X .- 1424-8581. ; 96:1-4, s. 20-32
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Tidskriftsartikel (refereegranskat)abstract
- Reasonably correct phylogenies are fundamental to the testing of evolutionary hypotheses. Here, we present phylogenetic findings based on analyses of 67 complete mammalian mitochondrial (mt) genomes. The analyses, irrespective of whether they were performed at the amino acid (aa) level or on nucleotides (nt) of first and second codon positions, placed Erinaceomorpha (hedgehogs and their kin) as the sister group of remaining eutherians. Thus, the analyses separated Erinaceomorpha from other traditional lipotyphlans (e.g., tenrecs, moles, and shrews), making traditional Lipotyphla polyphyletic. Both the aa and nt data sets identified the two order-rich eutherian clades, the Cetferungulata (comprising Pholidota, Carnivora, Perissodactyla, Artiodactyla, and Cetacea) and the African clade (Tenrecomorpha, Macroscelidea, Tubulidentata, Hyracoidea, Proboscidea, and Sirenia). The study corroborated recent findings that have identified a sister-group relationship between Anthropoidea and Dermoptera (flying lemurs), thereby making our own order, Primates, a paraphyletic assembly. Molecular estimates using paleontologically well-established calibration points, placed the origin of most eutherian orders in Cretaceous times, 70-100 million years before present (MYBP). The same estimates place all primate divergences much earlier than traditionally believed. For example, the divergence between Homo and Pan is estimated to have taken place approximate to 10 MYBP, a dating consistent with recent findings in primate paleontology. Copyright
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| 4. |
- Behboudi, Afrouz, 1967, et al.
(författare)
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Evolutionary aspects of the genomic organization of rat chromosome 10.
- 2002
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Ingår i: Cytogenetic and genome research. - : S. Karger. - 1424-8581 .- 1424-859X. ; 96:1-4, s. 52-9
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Tidskriftsartikel (refereegranskat)abstract
- Using FISH and RH mapping a chromosomal map of rat chromosome 10 (RNO10) was constructed. Our mapping data were complemented by other published data and the final map was compared to maps of mouse and human chromosomes. RNO10 contained segments homologous to mouse chromosomes (MMU) 11, 16 and 17, with evolutionary breakpoints between the three segments situated in the proximal part of RNO10. Near one of these breakpoints (between MMU17 and 11) we found evidence for an inversion ancestral to the mouse that was not ancestral to the condition in the rat. Within each of the chromosome segments identified, the gene order appeared to be largely conserved. This conservation was particularly clear in the long MMU11-homologous segment. RNO10 also contained segments homologous to three human chromosomes (HSA5, 16, 17). However, within each segment of conserved synteny were signs of more extensive rearrangements. At least 13 different evolutionary breakpoints were indicated in the rat-human comparison. In contrast to what was found between rat and mouse, the rat-human evolutionary breaks were distributed along the entire length of RNO10.
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| 5. |
- Bentz, M, et al.
(författare)
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Chromosome imbalances in papillary renal cell carcinoma and first cytogenetic data of familial cases analyzed by comparative genomic hybridization
- 1996
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Ingår i: Cytogenetics and cell genetics. - : S. Karger AG. - 0301-0171. ; 75:1, s. 17-21
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Tidskriftsartikel (refereegranskat)abstract
- We used comparative genomic hybridization to analyze 17 tumor samples from 11 patients with papillary renal cell carcinoma (RCC), including three patients with hereditary papillary RCC. Whereas the most frequent aberrations confirmed data obtained by banding analyses, copy number increases on 5q, which previously were considered characteristic of nonpapillary RCC, were identified in two cases. In two complex cases belonging to the same family, a characteristic pattern of chromosomal aberrations was found: five of the six imbalances present in the less complex case were included in the karyotype of the other case, suggesting a genetically determined mechanism resulting in genomic instability of specific chromosomes or chromosomal subregions and/or selection of specific mutations.
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| 6. |
- Bonassi, S, et al.
(författare)
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Chromosomal aberrations and risk of cancer in humans: an epidemiologic perspective
- 2004
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Ingår i: Cytogenetic and Genome Research. - : S. Karger AG. - 1424-859X .- 1424-8581. ; 104:1-4, s. 376-382
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Tidskriftsartikel (refereegranskat)abstract
- The pioneering papers published more than one century ago by Theodor Boveri opened the way to extensive research on the mechanism linking chromosomal abnormalities to the pathogenesis of cancer. As a result of this effort, robust theoretical and empirical evidence correlating cytogenetic damage to early stages of cancer in humans was consolidated, and an increased cancer risk was postulated in healthy subjects with high levels of chromosomal aberrations (CA). The first epidemiological investigation aimed at validating CA as predictor of cancer risk was carried out in the early 1990s. In that report the Nordic Study Group described an 80% increased risk of cancer in healthy subjects with high frequencies of CA. The results of this first study were replicated a few years later in a parallel research initiative carried out in Italy, and the subsequent pooled analysis of these two cohorts published in 1998 contributed to refine the quantitative estimate of the CA/cancer association. A small case-control study nested in a cohort of subjects screened for CA in Taiwan found an increased risk in subjects with high frequency of chromosome-type CA, while in 2001 a significant increase of cancer incidence associated with high levels of CA was described in a new independent cohort of radon exposed workers from the Czech Republic. Despite some common limitations affecting study design, the studies cited above have provided results of great interest both for the understanding of mechanisms of early stages of carcinogenesis, and for their potential implication for cancer prevention. The recent evolution of molecular techniques and the refinement of high throughput techniques have the potential to improve the knowledge about the role of specific sub-types of CA and to provide further insight into the mechanisms. Finally, the most challenging perspective in the field is the passage from research to regulation, with the implementatlon of preventive policies based on the accumulated knowledge.
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| 7. |
- Bondestam, Jonas, et al.
(författare)
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cDNA cloning, expression studies and chromosome mapping of human type I serine/threonine kinase receptor ALK7 (ACVR1C)
- 2001
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Ingår i: Cytogenetics and Cell Genetics. - : S. Karger AG. - 0301-0171 .- 1421-9816. ; 95:3-4, s. 157-162
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Tidskriftsartikel (refereegranskat)abstract
- Transforming growth factor-beta (TGF-beta) superfamily related growth factors signal by binding to transmembrane type I and type II receptor serine/threonine kinases (RSTK), which phosphorylate intracellular Smad transcription factors in response to ligand binding. Here we describe the cloning of the human type I RSTK activin receptor-like kinase 7 (ALK7), an orthologue of the previously identified rat ALK7. Nodal, a TGF-beta member expressed during embryonic development and implicated in developmental events like mesoderm formation and left-right axis specification, was recently shown to signal through ALK7. We found ALK7 mRNA to be most abundantly expressed in human brain, pancreas and colon. A cDNA encoding the open reading frame of ALK7 was obtained from a human brain cDNA library. Furthermore, a P1 artificial chromosome (PAC) clone containing the human ALK7 gene was isolated and fluorescent in situ hybridization (FISH) on metaphase chromosomes identified the gene locus as chromosome 2q24.1-->q3. To test the functionality of the ALK7 signaling, we generated recombinant adenoviruses containing a constitutively active form of ALK7 (Ad-caALK7), which is capable of activating downstream targets in a ligand independent manner. Infection with Ad-caALK7 of MIN6 insulinoma cells, in which ALK7 has previously been shown to be endogenously expressed, led to a marked increase in the phosphorylation of Smad2, a signaling molecule also used by TGF-betas and activins.
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| 8. |
- Boyadjiev, SA, et al.
(författare)
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Physical map of the chromosome 6q22 region containing the oculodentodigital dysplasia locus: analysis of thirteen candidate genes and identification of novel ESTs and DNA polymorphisms
- 2002
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Ingår i: Cytogenetic and genome research. - : S. Karger AG. - 1424-8581 .- 1424-859X. ; 98:1, s. 29-37
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Tidskriftsartikel (refereegranskat)abstract
- Oculodentodigital dysplasia (ODDD) is an autosomal dominant condition with congenital anomalies of the craniofacial and limb regions and neurodegeneration. Genetic anticipation for the dysmorphic and neurologic features has been inferred in a few families. Our previous linkage studies have refined the ODDD candidate region to chromosome 6q22→q23. In an attempt to clone the ODDD gene, we created a yeast artificial chromosome contig with 31 redundant clones spanning the region and identified and ordered candidate genes and markers. Fluorescent <i>in situ</i> hybridization mapped two of these YAC clones to chromosome 6q22.2 telomeric to a known 6q21 fragile site, excluding it as a possible cause of the suggested anticipation. We performed mutation analysis on thirteen candidate genes – GRIK2, HDAC2, COL10A1, PTD013, KPNA5, PIST, ROS1, BRD7, PLN, HSF2, PKIB, FABP7, and HEY2. Although no mutations were found, we identified 44 polymorphisms, including 28 single nucleotide polymorphisms. Direct cDNA selection was performed and fifty-five clones were found to contain sequences that were not previously reported as known genes or ESTs. These clones and polymorphisms will assist in the further characterization of this region and identification of disease genes.
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| 9. |
- Bylund, L, et al.
(författare)
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Analysis of the cytogenetic stability of the human embryonal kidney cell line 293 by cytogenetic and STR profiling approaches
- 2004
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Ingår i: Cytogenetic and genome research. - : S. Karger AG. - 1424-859X .- 1424-8581. ; 106:1, s. 28-32
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Tidskriftsartikel (refereegranskat)abstract
- We have characterized the cytogenetic alterations of the human embyronal cell line 293 by spectral karyotyping and G-banding analysis. To investigate its genomic stability, we compared the karyotypes of 293 and its daughter line EcR-293. Genotype profiling through short tandem repeats complemented the analysis. While displaying almost identical STR profiles and thus verifying their origin and their close relation, the two lines were remarkably different in their number of chromosomes and setup of aberrant chromosomes. However, the cell lines retained a stable karyotype in long term culture. The establishment of subclones from EcR-293, expressing inducible <i>lacZ</i> or MEN1 transgenes, only added minor changes to the karyotype. Our study shows that the cytogenetic constitution of a clonal cell line of the 293 origin appears to be sufficiently stable. However, care should be taken when comparing the properties of independent 293 lineages, since clonal variations might be substantial.
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| 10. |
- Calcagnile, O., et al.
(författare)
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Telomere dysfunction and telomerase activation in cancer - a pathological paradox?
- 2007
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Ingår i: Cytogenetic and Genome Research. - : S. Karger AG. - 1424-859X .- 1424-8581. ; 118:2-4, s. 270-276
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Tidskriftsartikel (refereegranskat)abstract
- Telomerase is expressed in more than 90% of human cancers. Telomere maintenance by this enzyme is believed to safeguard genomic integrity in neoplastic cells. Nevertheless, many telomerase-expressing tumours exhibit chromosomal instability triggered by short, dysfunctional telomeres, implying that active telomerase is not sufficient for preserving a functional telosomic nucleoprotein complex in cancer cells. We here examine three possible solutions to this ostensible paradox. First, prior to telomerase activation, telomere erosion may have evolved to a level where telomeric repeat sequences are too short to provide a functional substrate for telomerase enzyme activity. Second, mechanisms other than the continuous telomere erosion counteracted by telomerase may contribute to rapid shortening of telomere repeats. Third, dysfunction of telomere-regulating proteins may result in direct telomere uncapping. Moreover, telomerase may contribute to tumour development also through mechanisms unrelated to telomere length maintenance. Taken together, the available data on the role of telomerase in cancer strongly support that inhibition of this enzyme is a feasible strategy for cancer therapy. Copyright (C) 2007 S. Karger AG, Basel.
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