Showing papers in "Cytogenetic and Genome Research in 2001"
263 citations
TL;DR: A model is proposed that tries to explain – with a minimum number of essential steps – the origin, progression, infiltration, and recurrence of meningiomas.
Abstract: Meningioma is the most frequent tumor of neuroectodermal origin in humans. It is usually benign. Only a minority of cases shows progression to an anaplastic tumor (WHO grade II and III). Meningioma is generally a sporadic tumor. Multiple and familial cases are rare and mostly associated with (hereditary) neurofibromatosis 2 (NF2). Meningiomas show an unexpectedly high recurrence rate. Also, completely removed low-grade tumors can recur. Recurrence and multiplicity are correlated with the formation of a peritumoral edema. On the cytogenetic level, meningioma is the best-studied tumor in humans. Grade I tumors show either uniform monosomy 22 or a diploid karyotype. The majority of high-grade, but only a minority of low-grade, meningiomas show loss of merlin, a cytoskeleton-cytoplasm-linker protein. Merlin is the product of the NF2 gene located on chromosome 22. A second tumor suppressor gene on chromosome 22 has not yet been detected. In contrast to other solid tumors, progression of meningiomas is correlated with increasing hypodiploidy, showing characteristic clonal evolutions that mostly include chromosomes 14, 18, and 19 and, more rarely, 6 and 10. Structural aberrations are infrequent, except for the loss of the short arm of chromosome 1, which appears to be the decisive step for anaplastic growth. Comparative histochemical and molecular cytogenetic studies point to the alkaline phosphatase gene (ALPL, liver-bone-kidney type) located on 1p36.1→p34 as a candidate tumor suppressor gene. A model is proposed that tries to explain – with a minimum number of essential steps – the origin, progression, infiltration, and recurrence of meningiomas.
145 citations
TL;DR: Using comparative mapping of human Y-borne genes, it is directly shown that the eutherian Y is also composed of a conserved and an added region which contains most of the ubiquitously expressed Y-bourne genes.
Abstract: Mapping of human X-borne genes in distantly related mammals has defined a conserved region shared by the X chromosome in all three extant mammalian groups, plus a region that was recently added to the eutherian X but is still autosomal in marsupials and monotremes Using comparative mapping of human Y-borne genes, we now directly show that the eutherian Y is also composed of a conserved and an added region which contains most of the ubiquitously expressed Y-borne genes Little of the ancient conserved region remains, and the human Y chromosome is largely derived from the added region
115 citations
TL;DR: Multi-directional chromosome painting was applied to reconstruct the chromosome phylogeny and evolutionary relationships among the New World monkey species Callithrix argentata, Cebuella pygmaea, Saguinus oedipus, callithrix jacchus and Callimico goeldii and clarified several aspects of New Wold monkey phylogeny.
Abstract: Chromosome rearrangements are considered as “rare genomic changes” and can provide useful markers and even landmarks for reconstructing phylogenies complementary to DNA sequence data and bio-morpholog
94 citations
TL;DR: Two novel genes are identified and characterization, WBSCR20 and WBS CR22, which map to the common WBS deletion region and might contribute to the growth retardation, the myopathy or the premature aging effects in the pathogenesis of WBS.
Abstract: Williams-Beuren syndrome (WBS), due to a contiguous gene deletion of approximately 1.5 Mb at 7q11.23, is a complex developmental disorder with multisystemic manifestations including supravalvular aortic stenosis (SVAS) and a specific cognitive phenotype. Large repeats containing genes and pseudogenes flank the deletion breakpoints, and the mutation mechanism commonly appears to be unequal meiotic crossover. Except for elastin, hemizygosity of which is associated with supravalvular aortic stenosis, it is unknown which of the 18 genes in the deletion area contributes to the phenotype. Here, we report the identification and characterization of two novel genes, WBSCR20 and WBSCR22, which map to the common WBS deletion region. WBSCR22 encodes a putative methyltransferase protein strongly expressed in heart, skeletal muscle and kidney. WBSCR20 encodes a novel protein expressed in skeletal muscle with similarity to p120 (NOL1), a 120-kDa proliferation-associated nucleolar antigen, a member of an evolutionarily conserved protein family. A highly similar putative gene, WBSCR20B, flanks the WBS deletion at the telomeric side. Hemizygous deletion of either of the novel genes might contribute to the growth retardation, the myopathy or the premature aging effects in the pathogenesis of WBS.
91 citations
TL;DR: Results show that the raccoon dog does not share a single biarmed autosome in common with the Arctic fox, red fox, or domestic cat, andComparative analysis of the distribution patterns of conserved chromosome segments revealed by dog paints in the genomes of the canids, cats, and human reveals 38 ancestral autosome segments.
Abstract: Chromosome homologies between the Japanese raccoon dog ( Nectereutes procyonoides viverrinus, 2n = 39 + 2–4 B chromosomes) and domestic dog ( Canis familiaris, 2n =
91 citations
TL;DR: Fluorescent in situ hybridization was employed to locate the breakpoint in a translocation used to produce a mouse model for Down syndrome, showing that the Chr 17 breakpoint is distal to the heterochromatin of Chr 17 and that the Ts65Dn chromosome contains >80% of the human Chr 21 homologs.
Abstract: Fluorescent in situ hybridization (FISH) -- using mouse chromosome paints, probes for the mouse major centromeric satellite DNA, and probes for genes on chromosomes (Chr) 16 and 17 -- was employed to locate the breakpoint in a translocation used to produce a mouse model for Down syndrome. The Ts65Dn trisomy is derived from the reciprocal translocation T(16;17)65Dn. The Ts65Dn mouse carries a marker chromosome containing the distal segment of Chr 16, a region that shows linkage conservation with human Chr 21, and the proximal end of Chr 17. This chromosome confers trisomy for most of the genes in the Chr 16 segment and Ts65Dn mice show many of the phenotypic features characteristic of Down syndrome. We used FISH on metaphase chromosomes from translocation T65Dn/+ heterozygotes and Ts65Dn mice to show that the Chr 17 breakpoint is distal to the heterochromatin of Chr 17, that the Ts65Dn marker chromosome contains a small portion of Chr 17 euchromatin, that the Chr 16 breakpoint lies between the Ncam2 and Gabpa/App genes, and that the Ts65Dn chromosome contains >80% of the human Chr 21 homologs. The significance of this finding is discussed in terms of the utility of this mouse model.
91 citations
TL;DR: It is speculated that more than two rearrangements are contained in the centromeric region of chromosome 4, and that chromosome homology is highly conserved between chicken and Japanese quail and that few chromosome rearranged occurred in the evolution of the two species.
Abstract: In order to construct a chicken (Gallus gallus) cytogenetic map, we isolated 134 genomic DNA clones as new cytogenetic markers from a chicken cosmid DNA library, and mapped these clones to chicken chromosomes by fluorescence in situ hybridization. Forty-five and 89 out of 134 clones were localized to macrochromosomes and microchromosomes, respectively. The 45 clones, which localized to chicken macrochromosomes (Chromosomes 1-8 and the Z chromosome) were used for comparative mapping of Japanese quail (Coturnix japonica). The chromosome locations of the DNA clones and their gene orders in Japanese quail were quite similar to those of chicken, while Japanese quail differed from chicken in chromosomes 1, 2, 4 and 8. We specified the breakpoints of pericentric inversions in chromosomes 1 and 2 by adding mapping data of 13 functional genes using chicken cDNA clones. The presence of a pericentric inversion was also confirmed in chromosome 8. We speculate that more than two rearrangements are contained in the centromeric region of chromosome 4. All 30 clones that mapped to chicken microchromosomes also localized to Japanese quail microchromosomes, suggesting that chromosome homology is highly conserved between chicken and Japanese quail and that few chromosome rearrangements occurred in the evolution of the two species.
78 citations
TL;DR: Zoo-FISH probes from flow-sorted chromosomes of the Japanese raccoon dog are used to examine two phylogenetically divergent canids, indicating an ancestral episode of extensive centric fission leading to an ancestral canid genome organization that was subsequently reorganized by multiple chromosome fusion events in some but not all Canidae lineages.
Abstract: Canidae species fall into two categories with respect to their chromosome composition: those with high numbered largely acrocentric karyotypes and others with a low numbered principally metacentric karyotype. Those species with low numbered metacentric karyotypes are derived from multiple independent fusions of chromosome segments found as acrocentric chromosomes in the high numbered species. Extensive chromosome homology is apparent among acrocentric chromosome arms within Canidae species; however, little chromosome arm homology exists between Canidae species and those from other Carnivore families. Here we use Zoo-FISH (fluorescent in situ hybridization, also called chromosomal painting) probes from flow-sorted chromosomes of the Japanese raccoon dog (Nyctereutes procyonoides) to examine two phylogenetically divergent canids, the arctic fox (Alopex lagopus) and the crab-eating fox (Cerdocyon thous). The results affirm intra-canid chromosome homologies, also implicated by G-banding. In addition, painting probes from domestic cat (Felis catus), representative of the ancestral carnivore karyotype (ACK), and giant panda (Ailuropoda melanoleuca) were used to define primitive homologous segments apparent between canids and other carnivore families. Canid chromosomes seem unique among carnivores in that many canid chromosome arms are mosaics of two to four homology segments of the ACK chromosome arms. The mosaic pattern apparently preceded the divergence of modern canid species since conserved homology segments among different canid species are common, even though those segments are rearranged relative to the ancestral carnivore genome arrangement. The results indicate an ancestral episode of extensive centric fission leading to an ancestral canid genome organization that was subsequently reorganized by multiple chromosome fusion events in some but not all Canidae lineages.
70 citations
TL;DR: The mouse zinc finger gene, Dnmt3l (DNA cytosine-5-methyltransferase 3-like), is isolated and sequenced on mouse chromosome 10, showing similarity to members of the DNMT3/DnMT3 family.
Abstract: We have isolated and sequenced the mouse zinc finger gene, Dnmt3l (DNA cytosine-5-methyltransferase 3-like), on mouse chromosome 10, showing similarity to members of the DNMT3/Dnmt3 family. The Dnmt3l protein contains an ADD zinc finger, which Dnmt3l shares with other Dnmt3 family members and Atrx. RT-PCR analysis showed Dnmt3l expression in testis, thymus, ovary, and heart, as well as in 7-day, 15-day, and 17-day mouse embryos.
69 citations
TL;DR: This study provides a framework for the fine-mapping and ultimate cloning of a novel vascular gene at 8q22.3 or 14q13 in a patient with a vascular and tissue overgrowth syndrome consistent with KTS.
Abstract: Klippel-Trenaunay syndrome (KTS) is a disorder primarily characterized by capillary-venous vascular malformations associated with altered limb bulk and/or length. We report the identification of a bal
TL;DR: The various multicolor approaches to cohybridize multiple DNA probes in different colors are summarized and the application of the individual technologies are discussed.
Abstract: In recent years a fascinating evolution of different multicolor fluorescence in situ hybridization (FISH) technologies could be witnessed. The various approaches to cohybridize multiple DNA probes in different colors opened new avenues for FISH-based automated karyotyping or the simultaneous analysis of multiple defined regions within the genome. These developments had a remarkable impact on microscopy design and the usage of highly sensitive area imagers. In addition, they led to the introduction of new fluorochromes with appropriate filter combinations, refinements of hybridization protocols, novel probe sets, and innovative software for automated chromosome analysis. This paper attempts to summarize the various multicolor approaches and discusses the application of the individual technologies.
TL;DR: In agreement with the HUGO Gene Nomenclature Committee, the M4S1 and M1S1 genes have been renamed TACSTD (tumor-associated calcium signal transducer) 1 and 2, respectively.
Abstract: TACSTD1 (alias TROP1, M4S1; OMIM 600718) and TACSTD2 (alias TROP2, M1S1; OMIM 137290) encode cellsurface glycoproteins expressed in epithelial cells. Trops are calcium signal transducers (Ripani et al., 1998), are overexpressed by human carcinomas and play a role in the control of tumor cell growth (manuscript in preparation). TACSTD2 (originally called M1S1; Fornaro et al., 1995) is responsible for the gelatinous drop-like corneal dystrophy (OMIM 204870) (Tsujikava et al., 1999). Although placed within a YAC/BAC/ cosmid contig on 1p (Tsujikava et al., 1999), its chromosome location still is undecided at 1p32→p31 or 1p13→q12 (Linnenbach et al., 1993; UniGene Hs.23582). By fluorescence in situ hybridization (FISH) we assign TACSTD2 to 1p32. The growth-suppressing properties of TACSTD2 and the frequent deletion of 1p32 in human tumors (White et al., 1999) suggest that this gene is a candidate to be a novel oncosuppressor. TACSTD1 (formerly called M4S1) shares a 49%-similar cDNA sequence with TACSTD2. TACSTD1 was localized to 4q by human/rodent somatic cell hybrid analyses (Linnenbach et al., 1993) (UniGene Hs.692). We reassign TACSTD1 to human chromosome 2p21, a region which contains the MSH2 and MSH6 DNA mismatch repair genes (Papadopoulos et al., 1995). In agreement with the HUGO Gene Nomenclature Committee, the M4S1 and M1S1 genes have been renamed TACSTD (tumor-associated calcium signal transducer) 1 and 2, respectively.
TL;DR: The presence of such hitherto undetected chromosomal aberrations corroborate previous findings of spontaneous chromosomal instability in AT and NBS patients, as manifested by an increased rate of open breaks and rearrangements involving chromosomes 7 and 14.
Abstract: The application of fluorescence in situ hybridization (FISH) using whole-chromosome paints (WCPs) is proving to be a very powerful technique for revealing chromosomal instability that, for the most part, has gone undetected by conventional cytogenetic analysis. We have analyzed the frequency of translocations in lymphocytes and lymphoblastoid cell lines from ataxia telangiectasia (AT) and Nijmegen breakage syndrome (NBS) homozygotes and heterozygotes using a three-color chromosome-painting technique (WCP 1, 2, 4). With this assay we were able to detect an increased frequency of spontaneous translocations in AT homozygotes (median, 18.47 ± 10.82 translocations per 1,000 metaphase cells; 10 patients) and AT heterozygotes (median, 7.87 ± 3.15 translocations per 1,000 cells; 7 patients), in comparison to controls (median, 2.26 ± 1.75 translocations per 1,000 cells; 10 controls). Analysis of NBS homozygotes (median, 19.05 ± 11.27 translocations per 1,000 cells; 5 patients) and NBS heterozygotes (median, 6.93 ± 3.04 translocations per 1,000 cells; 6 patients) also showed an increased frequency of translocations in these patients compared to controls. The presence of such hitherto undetected chromosomal aberrations corroborate previous findings of spontaneous chromosomal instability in AT and NBS patients, as manifested by an increased rate of open breaks and rearrangements involving chromosomes 7 and 14. Moreover, we show that the degree of genomic instability in AT and NBS patients is even higher than previously established and that some AT and NBS heterozygotes evidence spontaneous chromosomal instability as well. These increased levels of nonspecific translocations could be an important risk factor for the development of malignancies in homozygotes and heterozygotes for ATM or NBS1 gene mutations.
TL;DR: A novel human type I cytokine receptor from a human T lymphocyte cDNA library is identified, tentatively termed CRLF2, which stands for cytokine receptors-like factor 2, and the biological function of this newly identified receptor is now under investigation.
Abstract: In a search for a human sequence related to a recently identified type I cytokine receptor δ1, which turned out to be a receptor subunit for a cytokine called TSLP, we have now identified a novel huma
TL;DR: The recently developed multicolor banding (MCB) probe set for all human chromosomes was applied in the present study to reanalyze the chromosomes of Gorilla gorilla (GGO), and the breakpoints for the pericentric inversion on GGO 3 were defined more precisely.
Abstract: The origin of the human and great ape chromosomes has been studied by comparative chromosome banding analysis and, more recently, by fluorescence in situ hybridization (FISH), using human whole-chromosome painting probes. It is not always possible, however, to determine the exact breakpoints and distribution or orientation of specific DNA regions using these techniques. To overcome this problem, the recently developed multicolor banding (MCB) probe set for all human chromosomes was applied in the present study to reanalyze the chromosomes of Gorilla gorilla (GGO). While the results agree with those of most previous banding and FISH studies, the breakpoints for the pericentric inversion on GGO 3 were defined more precisely. Moreover, no paracentric inversion was found on GGO 14, and no pericentric inversions could be demonstrated on GGO 16 or 17.
TL;DR: The Y chromosome in chinook salmon, Oncorhynchus tshawytscha, was identified using fluorescence in situ hybridization (FISH) with a probe to a male-specific repetitive sequence isolated from this species.
Abstract: The Y chromosome in chinook salmon, Oncorhynchus tshawytscha, was identified using fluorescence in situ hybridization (FISH) with a probe to a male-specific repetitive sequence isolated from this species. The probe highlights the distal end of the short arm of an acrocentric chromosome with a DAPI-bright interstitial band of variable size. The proximal portion of the short arm of the Y chromosome contains 5S rDNA sequences, which are also found on the short arms of six other acrocentric chromosomes in this species.
TL;DR: An early stage of sex chromosome differentiation is reported to occur in the electric eel Eigenmannia virescens from populations of two tributaries of the Paraná river system (Brazil).
Abstract: An early stage of sex chromosome differentiation is reported to occur in the electric eel Eigenmannia virescens (Pisces, Sternopygidae) from populations of two tributaries of the Parana river system (Brazil). Cytogenetic studies carried out in the two populations showed that the Mogi-Guacu population is characterized by 2n = 38 chromosomes and undifferentiated sex chromosomes and the Tiete population presents 2n = 38 both for males and females and an XX:XY sex chromosome system. The X-chromosome is acrocentric, easily recognized by the presence of a conspicuous heterochromatin block in its distal portion; the Y-chromosome is probably one of the medium sized acrocentrics present in the male karyotype. BrdU induced R-bands of the two populations did not reveal any difference in the euchromatic regions of the chromosomes. AluI and HaeIII restriction enzyme digestion patterns and chromomycin A3 staining of the X-chromosome are presented. The possible role of heterochromatinization in the evolution of sex chromosomes in fish is discussed.
TL;DR: The data suggest that RET isoforms are evolutionarily highly conserved over a broad range of species, which may indicate that each isoform has a distinct role in normal RET function.
Abstract: The RET proto-oncogene encodes a receptor tyrosine kinase required for development of the kidney and neural crest-derived cell types. Alternative splicing of the 3′ exons of human RET results in three
TL;DR: The combination of new data/reagents from the Human Genome Project plus the use of novel molecular cytological technology will provide answers to gaps in knowledge of the loop structure and how it regulates gene expression.
Abstract: It is commonly accepted that the loop domain represents the basic structural unit of eukaryotic chromatin associated with DNA replication, gene expression and higher order packaging. However, molecular-cytological information defining the loop domain is lacking. There are gaps in our knowledge of the loop structure and how it regulates gene expression. The combination of new data/reagents from the Human Genome Project plus the use of novel molecular cytological technology will provide answers. Here we briefly review the status of chromatin loop research and pose questions that need to be addressed. New experimental systems are also presented to target some long-standing issues regarding the structure and function of the chromatin loop domain and its relationship with the nuclear matrix. This new knowledge will have a profound impact for modern genetics and molecular medicine.
TL;DR: It is concluded that MLH1 foci are good markers of crossing over in bird (chicken) meiocytes.
Abstract: The frequency and distribution of the mismatch repair protein MLH1 was analyzed on synaptonemal complex spreads of chicken oocytes using indirect immunofluorescence. MLH1 foci appeared in late zygotene and their number remains constant throughout pachytene. The average number of foci on autosomal synaptonemal complexes (65.02 ± 4.02) is in agreement with the number of chiasmata estimated from lampbrush chromosomes. The distribution of foci along the synaptonemal complexes is shown to be nonrandom and nonuniform in terms of the distances between them. It is concluded that MLH1 foci are good markers of crossing over in bird (chicken) meiocytes.
TL;DR: Comparative genomic hybridization suggests further that not only the COL1A1/PDGFB fusion gene formation but also the role of DNA copy number gains in the 17q and 22q regions is crucial per se in the pathogenesis of DFSP.
Abstract: Dermatofibrosarcoma protuberans (DFSP) is a tumor of low or intermediate malignant potential with a tendency for recurrence, but low rate of metastasis. The tumorigenesis of DFSP has recently been shown to be associated with the fusion of the collagen type I alpha 1 (COL1A1) and platelet-derived growth factor B-chain (PDGFB) genes, often as a consequence of translocation t(17;22)(q22;q13). Cytogenetically, DFSP is often characterized by supernumerary ring chromosomes containing material from chromosomes 17 and 22. A subset of DFSPs undergo fibrosarcomatous transformation de novo or upon recurrence, and contain components indistinguishable from fibrosarcoma (FS-DFSP). The fibrosarcomatous transformation appears to carry an increased risk for recurrence and metastasis, and is considered to represent tumor progression. The molecular cytogenetic events contributing to tumor progression are unknown. We used comparative genomic hybridization to analyze DNA copy number changes in 11 cases of typical DFSP and 10 cases of FS-DFSP. All cases in both groups were found to exhibit a gain or high-level amplification on chromosome 17q and the majority also on 22q. This finding is in line with previous studies, and suggests further that not only the COL1A1/PDGFB fusion gene formation but also the role of DNA copy number gains in the 17q and 22q regions is crucial per se in the pathogenesis of DFSP. Even though FS-DFSPs displayed a trend toward increase in the number of DNA copy number changes, the difference was not statistically significant, which indicates that mechanisms other than copy number changes are important in the transformation process of DFSP.
TL;DR: The preferential expression of ABCA7 in the spleen, thymus, and fetal liver is consistent with the finding, in both human and mouse promoter, of sites targeted by lymphomyeloid-specific transcription factors, suggesting thatABCA7 may play a pivotal role in the developmental specification of hematopoietic cell lineages.
Abstract: We report here the genomic and transcriptional characterization in mouse and man of a novel transporter of the ABCA subclass, named ABCA7. As it is the case for other ABCA genes, the predicted protein encoded by ABCA7 is a full symmetric transporter, highly conserved across species. The ABCA7 gene maps to human chromosome 19 and to the homologous region at band B4-C1 on mouse chromosome 10. The preferential expression of ABCA7 in the spleen, thymus, and fetal liver is consistent with the finding, in both human and mouse promoter, of sites targeted by lymphomyeloid-specific transcription factors. This suggests that ABCA7 may play a pivotal role in the developmental specification of hematopoietic cell lineages.
TL;DR: By screening 26 chicken breeds and lines, DNA polymorphisms were identified in the IGF2 and MPR1 genes, of which mammalian homologues are parentally imprinted, and the GAPD gene, a housekeeping control, demonstrating conserved linkage homology between mammals and birds.
Abstract: By screening 26 chicken breeds and lines, DNA polymorphisms were identified in the IGF2 and MPR1 genes, of which mammalian homologues are parentally imprinted, and the GAPD gene, a housekeeping control. Using the polymorphisms as genetic markers, we found that all three genes are expressed biallelically in embryonic tissues. IGF2 and MPR1 were mapped on chicken chromosomes 5 and 3, respectively, by fluorescence in situ hybridization, demonstrating conserved linkage homology between mammals and birds.
TL;DR: Glioblastoma cells in vivo are characterized by an extensive tendency to mitotic errors, which may be an important biological constituent of the well-known ability of glioblastomas to preserve viable tumor cell clones under adaptive stress in vivo, in clinical terms to rapidly recur after antitumoral therapy including radio- or chemotherapy.
Abstract: Glioblastoma multiforme (GBM) is characterized by intratumoral heterogeneity as to both histomorphology and genetic changes, displaying a wide variety of numerical chromosome aberrations the most comm
TL;DR: A new ATP-binding cassette (ABC) transporter gene from human and mouse that is highly expressed in the brain and close evolutionary relationship to the ABCG subfamily suggests a potential role for ABCG4 in cholesterol transport processes in this tissue.
Abstract: We characterized a new ATP-binding cassette (ABC) transporter gene from human and mouse that is highly expressed in the brain. The gene, ABCG4, produces several transcripts that differ at the 5′ end and encode proteins of various lengths. The ABCG4 protein is closely related to the Drosophila white and human ABCG1 genes, and belongs to the ABCG subfamily several members of which are involved in cholesterol transport. All representatives of this “reverse transporter” subfamily, including ABCG4, have a single ATP-binding domain at the N-terminus and a single C-terminal set of transmembrane segments. ABCG4 maps to human chromosome 11q23, between the markers D11S939 and D11S924, and Abcg4 to a conserved syntenic region on mouse chromosome 9. The abundant expression of this gene in the brain and close evolutionary relationship to the other members of the subfamily suggests a potential role for ABCG4 in cholesterol transport processes in this tissue.
TL;DR: Four genes deleted in the patient are reviewed – genes whose known functions and sites of expression in the brain and/or bone make them candidates for involvement in autism and/ or the osteodystrophy observed in patients with 2q37.3 deletions.
Abstract: We recently studied a patient who meets criteria for autistic disorder and has a 2q37 deletion. Molecular cytogenetic studies were carried out using DNA isolated from 22 different 2q37 mapped BACs to
TL;DR: Findings using a direct FISH technique showed that 15 out of 16 FA patients had increased loss of telomere signals compared with controls, and in 12 out of the 16 patients, decrease inTelomere signal intensity could also be detected using a Q-FISH approach.
Abstract: Analysis of telomere status in patients with Fanconi anaemia (FA) has previously been carried out by measurement of telomere restriction fragment (TRF) length by Southern blotting and densitometry. Results from these studies indicated that FA patients had significant reduction in telomere length compared with age-matched controls. This paper confirms and extends these findings using a direct FISH technique, which showed that 15 out of 16 FA patients had increased loss of telomere signals compared with controls. In 12 out of the 16 patients, decrease in telomere signal intensity could also be detected using a Q-FISH approach.
TL;DR: The cloning of the human type I RSTK activin receptor-like kinase 7 (ALK7) is described, an orthologue of the previously identified rat ALK7, which is found to be most abundantly expressed in human brain, pancreas and colon.
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.
TL;DR: In ccRCCs, statistical evaluation revealed significant correlations of chromosomal imbalances with tumor stage and grade, i.e., a gain in copy number of chromosome 5 correlated positively with low tumor grade, whereas a gain of chromosomes 10 and 17 correlated negatively with high tumor grade.
Abstract: Comparative genomic hybridization (CGH) has been applied to characterize 61 primary renal cell carcinomas derived histogenetically from the proximal tubulus. The tumor samples comprised 46 clear-cell