bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic predictive testing for bowel cancer predisposition: the impact on the individual
Authors: Chapman P.D. , Burn J.
Published: April 2003

When considering the impact of a genetic diagnosis of hereditary predisposition to colon cancer, there are many similarities to other predictive genetic tests, but also many differences. The development and availability of such genetic diagnoses, and the concept of testing being linked to effective prevention, have advanced rapidly, opening up not only unique opportunities but also unique psychosocial situations for the affected families—and unusual ethical issues for the professional. Compared to a diagnosis of sporadic colorectal cancer for a patient, hereditary colorectal cancer requires an understanding of genetics, heredity, and the attendant mathematics of risk calculation, but, most importantly, there must be a belief that it is possible to remain healthy whilst having an increased risk. This paper outlines the possible impact of a genetic diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) or familial adenomatous polyposis (FAP) on both the individual and the family and concludes that genetic testing should be accompanied by genetic counseling. Relevant ethical issues are also introduced, with the opinion presented suggesting that if primary considerations are always for the individual rather than the family or society, then unethical or eugenic decisions are likely to be avoided.
Standard G-, Q-, and R-banded ideograms of the domestic sheep (Ovis aries): homology with cattle (Bos taurus). Report of the committee for the standardization of the sheep karyotype
Authors: Ansari H.A. , Bosma A.A. , Broad T.E. , Bunch T.D. , Long S.E. , Maher D.W. , Pearce P.D. , Popescu C.P.
Published: April 2003

Revised G-, Q- and R-banded karyotypes and ideograms for sheep chromosomes at the 420-band level of resolution are presented. The positions of landmark bands on the sheep chromosomes are defined by their distance relative to the centromere to facilitate comparison with equivalent cattle chromosomes. Chromosome-specific (reference) molecular markers that have been mapped to sheep chromosomes and their equivalent cattle chromosomes are proposed. Reference markers will facilitate genome comparisons between sheep and cattle and minimise confusion due to chromosome nomenclature. Numbering of the Robertsonian translocation chromosomes remains as previously reported.
Cytogenetic mapping of 31 functional genes on chicken chromosomes by direct R-banding FISH
Authors: Suzuki T. , Kurosaki T. , Shimada K. , Kansaku N. , Kuhnlein U. , Zadworny D. , Agata K. , Hashimoto A. , Koide M. , Koike M. , Takata M. , Kuroiwa A. , Minai S. , Namikawa T. , Matsuda Y.
Published: April 2003

Using direct R-banding fluorescence in situ hybridization, we determined the location of 31 functional genes on chicken chromosomes. Replication R-banded chromosomes were obtained by synchronizing splenocyte cultures with excessive thymidine, followed by BrdU treatment. Thirty-one functional genes were directly localized to banded chicken chromosomes using genomic DNA and cDNA fragments as probes. The possibility of conserved linkage homology between chicken and human chromosomes was demonstrated for seven chicken chromosome regions (1p, 1q, 2q, 4p, 4q, and 5q).
Preferential occurrence of chromosome 21 malsegregation in peripheral blood lymphocytes of Alzheimer disease patients
Authors: Migliore L. , Botto N. , Scarpato R. , Petrozzi L. , Cipriani G. , Bonuccelli U.
Published: April 2003

To further investigate our finding of high levels of spontaneous aneuploidy in somatic cells of Alzheimer’s disease (AD) patients (Migliore et al. 1997), we studied the molecular cytogenetics of eight patients with sporadic AD and six healthy controls of similar age. Cytochalasin B-blocked binucleated peripheral blood lymphocytes from the AD patients and unaffected controls were used to measure micronucleus induction or other aneuploidy events, such as the presence of malsegregation in interphase nuclei (representing chromosome loss and gain). Dual-color fluorescence in situ hybridization (FISH) with differential labeled DNA probes was applied. We used a probe specific for the centromeres of chromosomes 13 and 21 combined with a single cosmid for the Down’s syndrome region (21q22.2) to obtain information on spontaneous chromosome loss and gain frequencies for both chromosomes (13 and 21). FISH data showed that AD lymphocytes had higher frequencies of chromosome loss (evaluated as fluorescently labeled micronuclei) for both chromosomes, as well as higher frequencies of aneuploid interphase nuclei, again involving both chromosomes, compared to control lymphocytes. However, aneuploidy for chromosome 21 was more frequent than for chromosome 13 in AD patients. This preferential occurrence of chromosome 21 in malsegregation in somatic cells of AD patients raises the hypothesis that mosaicism for trisomy of chromosome 21 could underlie the dementia phenotype in AD patients, as well as in elderly Down’s syndrome patients.
Genomic structure and chromosome mapping of the genes encoding clathrin-associated adaptor medium chains μ1A (Ap1m1) and μ1B (Ap1m2)
Authors: Nakatsu F. , Kadohira T. , Gilbert D.J. , Jenkins N.A. , Kakuta H. , Copeland N.G. , Saito T. , Ohno H.
Published: April 2003

The protein μ1B is a member of the medium chain family of the clathrin-associated adaptor complex and is expressed exclusively in epithelial cells. We determined the genomic structure of previously cloned murine genes for μ1B (Ap1m2) and its closely related homolog, μ1A (Ap1m1). Comparison of their genomic structures revealed that the positions of introns are identical between these two genes, except for the insertion of an additional intron in Ap1m1 (intron 4). By contrast, these structures are different from that of the more distantly related Ap2m1 gene encoding μ2. Taken together with the similarity of amino acid sequences among these genes, the data presented in this study suggest that Ap1m1/2 and Ap2m1 diverged long before the separation of Ap1m1 and Ap1m2, which most likely resulted from a relatively recent gene duplication. We also mapped AP1M2 to human chromosome 19p13.2 and Ap1m2 to the proximal region of mouse chromosome 9. The results are consistent with the fact that these regions are syntenic.
Physical assignment of microsatellite- containing BACs to bovine chromosomes
Authors: De Donato M. , Gallagher D.S. , Davis S.K. , Ji Y. , Burzlaff J.D. , Stelly D.M. , Womack J.E. , Taylor J.F.
Published: April 2003

Here we report the physical assignment of 40 microsatellite markers by fluorescence in situ hybridization to 13 different bovine chromosomes. This information will be valuable in providing physically anchored landmarks for the construction of contigs throughout the bovine genome. It also is useful for the purpose of integrating the linkage maps of these chromosomes to their physical maps and determining the physical coverage of these linkage groups.
Comparative chromosome analysis (R- and C-bands) of two South African murid species, Lemniscomys rosalia and Rhabdomys pumilio (Rodentia, Murinae)
Authors: Ducroz J.-F. , Granjon L. , Lombard M. , Volobouev V.
Published: April 2003

We carried out a comparative chromosome analysis (R- and C-bands) on two South African murid rodent species, Lemniscomys rosalia and Rhabdomys pumilio, whose banded karyotypes are reported here for the first time. The study revealed that, in spite of minor differences in diploid number and the number of autosomal arms (48 vs. 46 and 58 vs. 60, respectively), these species differ by at least 10 structural rearrangements, comprising seven Robertsonian translocations (two of which share monobrachial homology), two tandem translocations, and one pericentric inversion. Despite the high level of chromosomal differentiation observed, almost complete homologous banding patterns were detected between the two species. The present study therefore strengthens the hypothesis about the close phylogenetic affinities between L. rosalia and R. pumilio and their belonging to a set of genera referred to as “arvicanthine” rodents.
Characterization and chromosome location of the mouse link protein gene (Crtl1)
Authors: Deák F. , Mátés L. , Krysan K. , Liu Z. , Szabó P.E. , Mann J.R. , Beier D.R. , Kiss I.
Published: April 2003

Link protein (LP) plays an essential role in endochondral bone formation by stabilizing the supramolecular assemblies of aggrecan and hyaluronan. We have isolated and characterized the mouse link protein gene (Crtl1). It is longer than 40 kb and transcribed from two alternative promoters, leading to heterogenous mRNAs between 5.3 and 1.3 kb in size. Apart from the coding sequence, the 5′ flanking region is also highly conserved in mammals. Immunostaining revealed high levels of LP expression in the cartilaginous primordia of skeletal elements and low levels in other tissues. Using single-strand conformation polymorphism analysis, Crtl1 was assigned to mouse chromosome 13, tightly linked to Dhfr.
Structure and chromosome mapping of the human SIX4 and murine Six4 genes
Authors: Ozaki H. , Yamada K. , Kobayashi M. , Asakawa S. , Minoshima S. , Shimizu N. , Kajitani M. , Kawakami K.
Published: April 2003

Six4, a member of the homeobox gene subfamily (Six), is expressed in a developmentally regulated fashion, and supposed to be involved in embryogenesis. We cloned the human SIX4 and murine Six4 genomic DNAs and determined their structures. The structure, including the 5′ upstream region of both genes, was well conserved suggesting the conserved function and regulation of these genes. Human SIX4 was mapped to chromosome 14q23.
Centric fusion differences among Oryx dammah, O. gazella, and O. leucoryx (Artiodactyla, Bovidae)
Authors: Kumamoto A.T. , Charter S.J. , Kingswood S.C. , Ryder O.A. , Gallagher Jr. D.S.
Published: April 2003

G- and C-banded karyotypes of the genus Oryx were compared using the standard karyotype of Bos taurus. Chromosomal complements were 2n = 56 in O. gazella gazella, 2n = 58 in O. g. beisa and O. g. callotis, 2n = 56–58 in O. dammah, and 2n = 57–58 in O. leucoryx. The number of autosomal arms in all karyotypes was 58. Nearly all variation in diploid number was the result of three independent centric fusions, but one 2n = 57 specimen of O. g. gazella deviated from the normal complement of 2n = 56 due to XXY aneuploidy. A 2;17 centric fusion was fixed in O. g. gazella, whereas O. g. beisa and O. g. callotis lacked this fusion and had indistinguishable karyotypes. Oryx dammah was polymorphic for a 2;15 centric fusion, and O. leucoryx was polymorphic for an 18;19 centric fusion. The five Oryx taxa shared a fixed 1;25 centric fusion; the small acrocentric element involved in the 1;25 fusion was identified by fluorescence in situ hybridization using a cosmid specific to Bos chromosome 25. The X and Y chromosomes were also conserved among the five taxa. Oryx g. gazella differed from the other Oryx species because of the fixed 2;17 centric fusion. This difference reflects an apparently longer period of geographic isolation between O. g. gazella and other populations of Oryx, and it is consistent with the classification of O. gazella and O. beisa as distinct species (see Kingdon, 1997). The lack of monobrachial relationships among the Oryx taxa indicates that sterility barriers between species have not developed. Viability of hybrid offspring constitutes a threat to captive breeding programs designed for endangered species conservation; in the case of Oryx, the 2;15, 2;17, and 18;19 metacentrics could serve as marker chromosomes for assessing hybridization between certain Oryx taxa.
Monosomy 6 in human cultured fibroblast-like cells permanently stimulated by fibroblast growth factor 1: evidence for selection
Authors: Kehrer-Sawatzki H. , Röck H. , Götz H. , Siegel A. , Krone W.
Published: April 2003

The appearance of cells with monosomy 6 (mono6 cells) in cultures of human fibroblast-like cells during long-term stimulation with acidic fibroblast growth factor (FGF1) was confirmed in five of the six lines newly investigated. Aneugenic pretreatment at the start of the cultures accelerated the emergence of mono6 cells, as would be expected if selection, rather than induction, is the main mechanism involved. This could be confirmed by using an incidental rearrangement, der(8)t(6p;8p), that emerged in one of the lines by monitoring the proliferation of the mono6 cells (here monosomic for 6p22.1→qter) in mixtures with normal cells. During growth in the presence of FGF1, the proportion of mono6 cells increased six fold, whereas in the absence of FGF1, it declined to background levels. Selection rather than induction of the mono6 cells is further supported by their clonal origin, as ascertained on the basis of X-inactivation patterns in three informative cases. In addition, colonies grown in the presence of FGF1 from single cells did not reveal higher proportions of mono6 cells by fluorescence in situ hybridization analysis than those grown without the growth factor. During permanent stimulation with FGF1, the growth of mono6 cells did not become dependent on FGF1, nor did these cells lose their responsiveness to FGF1. Although evidence in favor of selection of preexistent mono6 cells by FGF1 is provided in this study, the contribution of a primary inducing mechanism cannot be entirely excluded.
Hybridization-based karyotyping of mouse chromosomes: hybridization-bands
Authors: Liechty M.C. , Carpio C.M. , Aytay S. , Clase A.C. , Puschus K.L. , Sims K.R. , Davis L.M. , Hozier J.C.
Published: April 2003

We have developed a method, which we have named hybridization-banding, to identify simultaneously all chromosomes in a mouse metaphase spread. The method uses a combination of hybridization probes labeled with a single fluor to yield a simple, unique, readily identifiable hybridization pattern on each chromosome. The method is superior to Giemsa- or fluorescence-based banding methods for chromosome identification because the hybridization patterns are simpler and easier to identify, and unique patterns can be designed at will for each chromosome. Analysis can be performed with a standard fluorescence microscope, and images can be recorded on film with an ordinary 35-mm camera, making the method useful to many investigators. The method can also be applied to any species for which chromosomes and probes can be prepared.
Cytogenetic assignment of 29 functional genes to chicken microchromosomes by FISH
Authors: Suzuki T. , Kurosaki T. , Agata K. , Koide M. , Shimada K. , Kansaku N. , Namikawa T. , Matsuda Y.
Published: April 2003

We assigned 29 functional genes to chicken microchromosomes by fluorescence in situ hybridization (FISH). Two linkage groups in the genetic linkage map of the East Lansing breed were identified in this study by localizing the genes AGRN and H2FA to microchromosomes. The frequency of the genes mapped on 30 pairs of microchromosomes, which account for roughly 30% of the whole chicken genome, was about 40% of the 73 genes randomly mapped in our laboratory. This result confirms the important role of microchromosomes for avian genome function and supports the likelihood of a high gene density on avian microchromosomes.
The integrin α10 subunit: expression pattern, partial gene structure, and chromosomal localization
Authors: Lehnert K. , Ni J. , Leung E. , Gough S. , Morris C.M. , Liu D. , Wang S.-X. , Langley R. , Krissansen G.W.
Published: April 2003

Herein we report the cloning of cDNAs and incompletely processed hnRNAs from endothelia and heart that encode the α10 subunit forming part of the novel collagen type II-binding integrin α10β1 of chondrocytes. Analysis of hnRNA clones and reported expressed sequence tags revealed the positions of 17 putative intron-exon splice junctions shared with those of the p150,95 (ITGAX) gene. Human α10 transcripts of 5.4 and 1.8 kb were not restricted to chondrocytes but, instead, were widely expressed in a panel of 24 tissue types, where the highest expression was found in muscle and heart. The human α10 subunit gene (ITGA10) was localized to band q21 of chromosome 1.
Generation of whole-chromosome painting probes specific to each chicken macrochromosome
Authors: Guillier-Gencik Z. , Bernheim A. , Coullin Ph.
Published: April 2003

The realization of physical and genetic maps of the chicken genome is dependent on progress in cytogenetic knowledge of its karyotype. To help achieve this goal, we constructed amplified representative DNA samples of the chicken chromosomes 1, 2, 3, 4, 5, 6, 7, 8, Z, W and of the terminal heterochromatin part of Zq by chromosome microdissection and DOP-PCR amplification. These chromosome DNA samples, which represent about 75% of the chicken genome, were used to generate whole chromosome painting probes for FISH. The direct application of these chromosome specific probes is dual FISH localization and characterization of panels of chicken interspecific somatic hybrids. We discuss some aspects of the chicken genome and its repeated sequences.
cDNA cloning, characterization and chromosome mapping of the gene encoding human cartilage associated protein (CRTAP)
Authors: Tonachini L. , Morello R. , Monticone M. , Skaug J. , Scherer S.W. , Cancedda R. , Castagnola P.
Published: April 2003

We have recently isolated and characterized cDNA clones coding for a novel developmentally regulated avian and mouse embryo protein, CASP for Cartilage Associated Protein. Here we describe the isolation and characterization of the gene coding for the human CASP. The comparison of the putative human and mouse protein sequences with the chick sequence revealed an overall high identity (89% and 51%, respectively). Homology search with known DNA and protein sequences showed that CASPs are related to two mammalian nuclear proteins. Here we demonstrate definitively that CASPs are distinct from these nuclear proteins. However, sequence comparison analyses suggest that all of these proteins belong to a new family. In all human tissues examined two CASP mRNA species were detected, whereas a single mRNA and three mRNAs were found in chick and mouse, respectively. The human CASP gene (CRTAP) was assigned to chromosome 3p22 by fluorescence in situ hybridization.
Replication banding patterns of the diploid-tetraploid treefrogs Hyla chrysoscelis and H. versicolor
Authors: Wiley J.E. , Little M.L.
Published: April 2003

Populations of the diploid-tetraploid treefrogs Hyla chrysoscelis and H. versicolor can be defined by the polymorphic positions of the nucleolar organizing regions (NORs) on their chromosomes. Evidence from NOR positions and interstitial telomere sequence data shows that gene flow between H. chrysoscelis populations appears to be restricted, with contact occurring only in narrow “hybrid” zones. Hyla versicolor appears to have had multiple origins from H. chrysoscelis populations, and this, too, is reflected in the NOR positions. We used replication banding to determine if genetic isolation of H. chrysoscelis populations was accompanied by karyotype evolution in the populations or in contact zones. We also sought to detect karyotype alteration or replication differences associated with polyploidy in H. versicolor. Homologous chromosome pairs of all H. chrysoscelis studied displayed no differences in replication banding patterns, nor did they differ from those of H. versicolor. Although NOR positions differed between the populations studied, no disturbance of the replication banding patterns was found, indicating that structural rearrangements were not involved in creating the multiple NOR positions seen in populations of H. versicolor and H. chrysoscelis.
Physical linkage of the lysyl oxidase-like (LOXL1) gene to the PML gene on human chromosome 15q22
Authors: Goy A. , Gilles F. , Remache Y. , Zelenetz A.D.
Published: April 2003

A contig was constructed centered on the PML (promyelocytic leukemia) gene. Using an exon-trapping approach to identify potential genes from a pool of cosmids located 5′ of the PML gene, four exons were identified that showed 100% sequence homology with the previously cloned lysyl oxydase-like (LOXL1) gene. An exon probe identified a single transcript of 2.4 kb on a multitissue Northern blot with a pattern identical to the one reported for the LOXL1 gene. Pulsed-field gel electrophoresis showed comigrating bands for both the PML cDNA and LOXL1 probes, demonstrating a physical linkage between these two genes. These data provide physical mapping information to complement the previous cytogenetic localization of LOXL1.
Cloning and mapping of murine superoxide dismutase copper chaperone (Ccsd) and mapping of the human ortholog
Authors: Moore S.D.P. , Chen M.M. , Cox D.W.
Published: April 2003

Copper does not exist in a free state within cells but is found consistently bound to metalloproteins. Specific metallochaperones escort copper to numerous targets within the cell, providing protection from the toxic effects of intracellular free copper. Many metallochaperones have been characterized in yeast, mouse, and human. To further characterize mouse metallochaperones, we cloned murine Ccsd from an adult mouse cDNA brain library, including both the coding region and the 5′ and 3′ UTRs. We obtained a 1,174-bp cDNA with an 825-bp open reading frame, translating a 274 amino acid protein that is 86.9% identical to human CCS. Using a mouse × hamster radiation hybrid panel, we mapped Ccsd to a proximal position on mouse chromosome 19. We mapped human CCS to 11q13 (homologous with mouse chromosome 19), utilizing a human × hamster radiation hybrid panel. The human and mouse metallochaperones are ubiquitously expressed in the major tissues of the body but seem to have different transcription products.
HMG20A and HMG20B map to human chromosomes 15q24 and 19p13.3 and constitute a distinct class of HMG-box genes with ubiquitous expression
Authors: Sumoy L. , Carim L. , Escarceller M. , Nadal M. , Gratacòs M. , Pujana M.A. , Estivill X. , Peral B.
Published: April 2003

The HMG box encodes a conserved DNA binding domain found in many proteins and is involved in the regulation of transcription and chromatin conformation. We describe HMG20A and HMG20B, two novel human HMG box-containing genes, discovered within the EURO-IMAGE Consortium full-length cDNA sequencing initiative. The predicted proteins encoded by these two genes are 48.4% identical (73.9% within the HMG domain). The HMG domain of both HMG20 proteins is most similar to that of yeast NHP6A (38% to 42%). Outside of this domain, HMG20 proteins lack any significant homology to other known proteins. We determined the genomic structure and expression pattern of HMG20A and HMG20B. Both genes have several alternative transcripts, expressed almost ubiquitously. HMG20A maps to chromosome 15q24 (near D15S1227) and HMG20B to 19p13.3 (between D19S209 and D19S216). The HMG20 genes define a distinct class of mammalian HMG box genes.
Evidence for suppression of cellular growth in vitro and selection against the indigenous mouse X chromosome in A9 cell hybrids after microcell-mediated transfer of an X from other mammalian species
Authors: Islam M.Q. , Islam K.
Published: April 2003

Introduction of a human or Syrian hamster X chromosome (derived from BHK-191-5C cell hybrids) into tumorigenic mouse A9 cells via microcell fusion induced changes in cellular morphology and a retardation of cellular growth. The suppression of growth of the hybrids could be abolished, however, by daily changes of medium containing 20% serum. G-banding analysis showed the absence of a single, cytogenetically identifiable, indigenous X chromosome (marker Z) in two of four hybrid clones after an X chromosome was transferred from either hamster or human cells. All hybrids were tumorigenic when tested in nude mice. Together, these data suggest that the loss of the mouse X chromosome took place probably because of growth inhibitory effects imposed on hybrid cells due to the increase in X chromosome dosage. In addition, our results show a lack of association between the phenotype of cellular growth suppression in vitro and the phenotype of suppression of tumorigenicity in vivo.
Structure of the human glutamate-L-cysteine ligase catalytic (GLCLC) subunit gene
Authors: Gipp J.J. , Mulcahy R.T.
Published: April 2003

Glutamate-L-cysteine ligase (GLCL [EC 6.3.2.2], also referred to as γ-glutamylcysteine synthetase) catalyzes the rate-limiting reaction in the synthesis of the important cellular antioxidant glutathione. GLCL is a heterodimer consisting of a catalytic (GLCLC) and a regulatory (GLCLR) subunit. The structure of the human GLCLC subunit gene, GLCLC, which has been mapped to chromosome 6p12, spans 51.4 kb and consists of 16 exons separated by 15 introns.
Identification of a novel β-tubulin subfamily with one member (TUBB4Q) located near the telomere of chromosome region 4q35
Authors: van Geel M. , van Deutekom J.C.T. , van Staalduinen A. , Lemmers R.J.L.F. , Dickson M.C. , Hofker M.H. , Padberg G.W. , Hewitt J.E. , de Jong P.J. , Frants R.R.
Published: April 2003

The human β-tubulin supergene family consists of several isotypes with many associated pseudogenes. Here we report the identification of yet another β-tubulin sequence designated TUBB4Q. This tubulin maps 80 kb proximal to the facioscapulohumeral muscular dystrophy (FSHD1) associated D4Z4 repeats on chromosome 4q35. The genomic structure contains four exons encoding a putative protein of 434 amino acids. The TUBB4Q nucleotide and protein sequence show 87% and 86% homology to β2-tubulin, respectively. Although the genomic structure shows all functional aspects of a genuine gene, no transcript could be detected. TUBB4Q-related sequences were identified on multiple chromosomes. Since these sequences mutually exhibit a high nucleotide sequence homology, they presumably belong to a novel subfamily of β-tubulin genes. Although the chromosome 4q35 tubulin-member probably represents a pseudogene, ectopic expression due to a postulated position effect variegation (PEV), makes TUBB4Q an ideal dominant-negative candidate gene for FSHD1.
Identification and expression analysis of C15orf3, a novel gene on chromosome 15q21.1→q21.2
Authors: Carim L. , Sumoy L. , Andreu N. , Estivill X. , Escarceller M.
Published: April 2003

We have isolated C15orf3, a novel human gene that lacks homology to any known gene family. The C15orf3 gene encodes a transcript of 1676 nt with an ORF of 187 amino acids and a predicted protein product size of 20.8 kDa. Northern blot analysis showed ubiquitous expression in adult tissues. EST database searching revealed the presence of C15orf3 homologs in rat and mouse. C15orf3 was mapped to chromosome 15q21.1→q21.2 using the Stanford G3 radiation hybrid panel.
Identification and mapping of swine cyclin-dependent kinase inhibitor CDKN2A and CDKN2B exon 2 sequences
Authors: Le Chalony C. , Hayes H. , Frelat G. , Geffrotin C.
Published: April 2003

We have isolated the swine homologs of human CDKN2A and CDKN2B exon 2 sequences. As in the human and mouse genomes, the exon 2 sequences of these two genes present a high level of sequence homology and are tightly linked. Using fluorescence in situ hybridization, we have mapped swine CDKN2A and CDKN2B to chromosome 1q25. This confirms the comparative mapping data among man, mouse, and swine, showing a conserved synteny among chromosome segments 9p21, 4C3-C6, and 1q25, respectively.
Five human genes encoding F-box proteins: chromosome mapping and analysis in human tumors
Authors: Chiaur D.S. , Murthy S. , Cenciarelli C. , Parks W. , Loda M. , Inghirami G. , Demetrick D. , Pagano M.
Published: April 2003

Members of the f̲-b̲ox p̲rotein (Fbp) family are characterized by an approximately 40 amino acid F-box motif. SCF complexes (formed by s̲kp1, c̲ullin, and one of many f̲bps) act as protein-ubiquitin ligases that control the G1/S transition of the eukaryotic cell cycle. The substrate specificity of SCF complexes is determined by the presence of different Fbp subunits that recruit specific substrates for ubiquitination. Unchecked degradation of cellular regulatory proteins has been observed in certain tumors and it is possible that deregulated ubiquitin ligases play a role in the altered degradation of cell cycle regulators. We have recently identified a family of human Fbps. As a first step aimed at determining if FBP genes could be involved in human neoplasia, we have mapped the chromosome positions of 5 FBP genes by fluorescence in situ hybridization (FISH) to 10q24 (BTRC alias β-TRCP/FBW1a), 9q34 (FBXW2 alias FBW2), 13q22 (FBXL3A alias FBL3a), 5p12 (FBXO4 alias FBX4) and 6q25→q26 (FBXO5 alias FBX5). Since most of these are chromosomal loci frequently altered in tumors, we have screened 42 human tumor cell lines and 48 human tumor samples by Southern hybridization and FISH. While no gross alterations of the genes encoding β-Trcp/Fbw1a, Fbw2, Fbx4 and Fbx5 were found, heterozygous deletion of the FBXL3A gene was found in four of 13 small cell carcinoma cell lines. This is the first evaluation of genes encoding Fbps in human tumors.
cDNA cloning and genomic structure of a novel gene (C11orf9) localized to chromosome 11q12→q13.1 which encodes a highly conserved, potential membrane-associated protein
Authors: Stöhr H. , Marquardt A. , White K. , Weber B.H.F.
Published: April 2003

We have cloned and characterized a novel gene (C11orf9) mapping to chromosome 11q12→q13.1. The transcript was initially identified as a partial cDNA sequence in the course of constructing a transcript map of the region between markers D11S1765 and uteroglobin known to encompass the gene causing Best disease. Using a combination of EST mapping, computational exon prediction, RT-PCR, and 5′-RACE its 5.7-kb full-length cDNA sequence was subsequently obtained. The C11orf9 gene consists of 26 exons spanning 33.1 kb of genomic DNA and is located about 4.3 kb centromeric to FEN1. Biocomputational analysis predicts that its conceptualtranslation product of 1,111 amino acids contains two transmembrane helices as well as two proline-rich regions. Alignment reveals significant homology to hypothetical peptides from several other species including C. elegans and D. melanogaster, indicating a high degree of conservation throughout evolution. Northern Blot and RT-PCR analyses demonstrate widespread expression of a single transcript but varying degrees of abundance among the individual tissues tested. Mutation analysis of the entire coding sequence excluded C11orf9 as the Best disease gene.
Isolation and chromosomal assignment of a novel human gene, CORO1C, homologous to coronin-like actin-binding proteins
Authors: Iizaka M. , Han H.-J. , Akashi H. , Furukawa Y. , Nakajima Y. , Sugano S. , Ogawa M. , Nakamura Y.
Published: April 2003

We have isolated a gene, termed CORO1C (human coronin-like actin-binding protein 1C), that encodes a new member of the coronin-like family of proteins. The cDNA consists of 3,857 nucleotides, with an open reading frame of 1,422 bp encoding a 474 amino acid protein. The deduced amino acid sequence shared 65% identity with p57 (human coronin-like actin-binding protein), as well as 46% identity with coronin, a protein first isolated from the slime mold Dictyostelium discoideum. Computer analysis predicted that the product of the CORO1C gene would contain five WD repeats in its N-terminal region and a coiled-coil motif in its C-terminal region, both of which are conserved among coronin-like proteins. CORO1C was ubiquitously expressed in all human tissues examined, in contrast to other known coronin-like molecules, each of which is expressed in a tissue-specific manner. Immunocytochemical staining demonstrated that CORO1C was co-localized with F-actin; therefore, the gene product is likely to be important in cytokinesis, motility, and signal transduction, as are the other members of this molecular family. We assigned this novel gene to chromosome 12q24.1 by fluorescence in situ hybridization.
Conserved synteny between the chicken Z sex chromosome and human chromosome 9 includes the male regulatory gene DMRT1: a comparative (re)view on avian sex determination
Authors: Nanda I. , Zend-Ajusch E. , Shan Z. , Grützner F. , Schartl M. , Burt D.W. , Koehler M. , Fowler V.M. , Goodwin G. , Schneider W.J. , Mizuno S. , Dechant G. , Haaf T. , Schmid M.
Published: April 2003

Sex-determination mechanisms in birds and mammals evolved independently for more than 300 million years. Unlike mammals, sex determination in birds operates through a ZZ/ZW sex chromosome system, in which the female is the heterogametic sex. However, the molecular mechanism remains to be elucidated. Comparative gene mapping revealed that several genes on human chromosome 9 (HSA 9) have homologs on the chicken Z chromosome (GGA Z), indicating the common ancestry of large parts of GGA Z and HSA 9. Based on chromosome homology maps, we isolated a Z-linked chicken ortholog of DMRT1, which has been implicated in XY sex reversal in humans. Its location on the avian Z and within the sex-reversal region on HSA 9p suggests that DMRT1 represents an ancestral dosage-sensitive gene for vertebrate sex-determination. Z dosage may be crucial for male sexual differentiation/determination in birds.
Genomic sequencing reveals the structure of the Kcnk6 and Map3k11 genes and their close vicinity to the Sipa1 gene on mouse chromosome 19
Authors: Saridaki A. , Ferraz C. , Demaille J. , Scherer G. , Roux A.-F.
Published: April 2003

In this report we present the analysis of two overlapping mouse cosmid clones that contain the entire Kcnk6, Map3k11 and Pcnxl3 genes, as well as part of the Sipa1 gene. The sequence and genomic organisation of the Kcnk6 and Map3k11 genes are described in detail. Sipa1 and Map3k11, which have independently been mapped with low resolution to the centromeric region of mouse chromosome 19, are shown here to lie close to each other and to the Kcnk6 gene, which has not previously been mapped. This gene cluster maps to the vicinity of the Dancer (Dc) mutation, which involves inner ear abnormalities and circling phenotypes. Since potassium channels have been implicated in deafness disorders, we have analysed the Kcnk6 gene, which encodes a two-P domain potassium channel, in the Dc mutant. No Dc-causing mutation in the Kcnk6 coding region could be identified. However, we detected a polymorphism in the Kcnk6 gene that leads to a C-terminal extension of the encoded protein by eight amino acids.
Cloning of ZNF237, a novel member of the MYM gene family that maps to human chromosome 13q11→q12
Authors: Sohal J. , Reiter A. , Goldman J.M. , Cross N.C.P.
Published: April 2003

We have cloned a novel, widely expressed human gene, ZNF237, that shows extensive similarity to the N-terminal region of ZNF198. Two alternatively spliced regions were identified by RT-PCR; the major splice variant is predicted to encode a 383 amino acid protein that contains a single diverged MYM domain. ZNF237 maps to 13q11→q12, immediately proximal to ZNF198.
Genomic structure and chromosome location of the mouse RelA p65 gene (Rela)
Authors: Lemmer E.R. , Welch J.L. , Tsai T. , Keck-Waggoner C.L. , Huh C.-G. , Zimonjic D.B. , Popescu N.C. , Thorgeirsson S.S.
Published: April 2003

The RelA (p65) subunit of transcription factor NF-κB plays a critical role in development, and rela–/– knockout mice die in utero from massive liver apoptosis. Only partial sequences of the mouse Rela gene are available. We have determined the genomic structure of mouse Rela and promoter, and have mapped the gene to chromosome 19B1–3.
Genomic organization of the human ubiquitin-conjugating enzyme gene, UBE2L6 on chromosome 11q12
Authors: Ardley H.C. , Rose S.A. , Tan N. , Leek J.P. , Markham A.F. , Robinson P.A.
Published: April 2003

The human UBE2L6 gene encodes UbcH8Kumar, a ubiquitin-conjugating enzyme (E2) highly simliar in primary structure to UbcH7 which is encoded by UBE2L3. Like UBC4 and UBC5 in yeast, these proteins demonstrate functional redundancy. Herein we report the intron/exon structure of UBE2L6. Comparison of the genomic organization of UBE2L6 with UBE2L3 demonstrates that these genes remain highly conserved at the genomic as well as at the protein level. We also describe the chromosomal localization of UBE2L6, which maps to chromosome 11q12.
An anchored YAC-STS framework for the rat genome
Authors: Cai L. , Lindpaintner K. , Browne J. , Gruetzner F. , Haaf T. , James M.R. , Bihoreau M.-T.
Published: April 2003

We report here the first YAC-STS framework for the rat genome. A total of 417 anchor microsatellite markers were used to screen a 10-fold redundant YAC library. One or more unambiguous YACs were identified for 372 markers. Assuming the genetic length of the rat genome to be 2,000 cM (Bihoreau et al. 1997b), the YAC-STS framework will provide, on average, one informative YAC clone every 5.4 cM. A total of 111 anchor markers used in this study were derived from known gene regions. We also demonstrated one of the important and immediate uses of this YAC-STS framework, which is to establish a correlation between the genetic and cytogenetic maps in the rat through FISH analysis.
Comparative FISH mapping of bovid X chromosomes reveals homologies and divergences between the subfamilies Bovinae and Caprinae
Authors: Iannuzzi L. , Di Meo G.P. , Perucatti A. , Incarnato D. , Schibler L. , Cribiu E.P.
Published: April 2003

Comparative FISH mapping of river buffalo (Bubalus bubalis, BBU), sheep (Ovis aries, OAR), and cattle (Bos taurus, BTA) X chromosomes revealed homologies and divergences between the X chromosomes in the subfamilies Bovinae and Caprinae. Twenty-four and 17 loci were assigned for the first time to BBU X and OAR X, respectively, noticeably extending the physical map in these two species. Seventeen loci (four of which for the first time) were also FISH mapped to BTA X and used for comparative mapping studies on the three species, which show three morphologically different X chromosomes: an acrocentric (BBU X), an acrocentric with distinct short arms (OAR X), and a submetacentric (BTA X). The same order of loci were found on BTA X and BBU X, suggesting that a centromere transposition, with loss (cattle) or acquisition (river buffalo) of constitutive heterochromatin, differentiated the X chromosomes of these two bovids. Comparison of bovine (cattle and river buffalo) and caprine (sheep) X chromosomes revealed at least five common chromosome segments, suggesting that multiple transpositions, with retention or loss of constitutive heterochromatin, had occurred during their karyotypic evolution.
A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer’s amyloid precursor protein β-secretase
Authors: Solans A. , Estivill X. , de la Luna S.
Published: April 2003

Down syndrome individuals develop abnormalities of most organs, including all the pathological and neurochemical features of Alzheimer’s disease, by the early age of 30 yr. Here, we report the isolation and characterization of BACE2, a gene mapping on human chromosome 21q22.3, which is highly similar to a transmembrane aspartyl protease, BACE (for beta-site APP-cleaving enzyme), which is able to catalyze the β-secretase cleavage of Alzheimer’s amyloid precursor protein (APP). BACE2 is expressed in a wide variety of organs and tissues, with several transcripts due to alternative splicing and the use of two polyadenylation signals. The BACE2 gene product is a 518 amino acid protein with the signature of an aspartic protease, a 20-residue signal peptide, and two putative N-glycosylation sites. In addition, and similarly to BACE, BACE2 differs from the other members of the human aspartic protease family in the number and distribution of putative disulfide bonds and in the presence of an extended C-terminal region which contains a predicted transmembrane segment. BACE2 could be involved in the Alzheimer-like neuropathology of Down syndrome, as well as in Alzheimer’s disease linked to chromosome 21 but not showing mutations in APP.
Characterization and genomic localization of the mouse Extl2 gene
Authors: Wuyts W. , van Hul W.
Published: April 2003

Human EXTL2 is an α1,4-N-acetylhexosaminyltransferase involved in the biosynthesis of heparin/heparan sulfate. We have cloned and characterized the mouse homolog of this gene. Mouse Extl2 encodes a 330 amino acid protein that is 87% identical to its human counterpart. Expression analysis showed that Extl2 is ubiquitously expressed in adult mouse tissues and that the Extl2 transcript is already present in early stages of embryonic development. Determination of the genomic structure revealed that the Extl2 gene spans five exons within a 10-kb region and that the genomic organization between mouse and man is well preserved, with conservation of the number and position of all five exons. By radiation hybrid analysis, Extl2 was mapped to mouse chromosome 3, in a region homologous to the human EXTL2 region on chromosome 1.
The p53-inducible gene EI24/PIG8 localizes to human chromosome 11q23 and the proximal region of mouse chromosome 9
Authors: Gu Z. , Gilbert D.J. , Valentine V.A. , Jenkins N.A. , Copeland N.G. , Zambetti G.P.
Published: April 2003

Activation of the p53 tumor suppressor leads to either a cell cycle arrest or to apoptosis and the factors that influence these responses are poorly understood. It is clear, however, that p53 regulates these processes by inducing a series of downstream target genes. One recently identified p53-target gene, EI24 (alias PIG8), induces apoptosis when ectopically expressed. To better understand the biological properties of EI24 and its potential relevance to disease, in particular cancer, we determined the chromosomal location and pattern of gene expression of EI24. EI24 is widely expressed in adult tissues and throughout mouse embryogenesis. The genomic locus of EI24 was mapped to the proximal region of mouse chromosome 9 and human chromosome 11q23→q24, a region frequently altered in human cancers. These results suggest that EI24 may play an important role in the p53 tumor suppressor pathway.
Genomic structure and chromosome location of the gene encoding mouse CD59
Authors: Holt D.S. , Powell M.B. , Rushmere N.K. , Morgan B.P.
Published: April 2003

The gene encoding the mouse analogue of the human complement regulator CD59 was cloned using a combination of long range PCR and genomic library screening. Sequence obtained showed that its genomic structure closely resembled that of the human CD59 gene, comprising 4 exons, each separated by a long intron region. The sizes of introns and exons were comparable to those of the human gene with the exception of the third intron which is 2.5 kb in the mouse compared to 7 kb in the human gene. All exon/intron boundaries conformed to the GT-AG rules for splicing. Radiation hybrid mapping localised mouse Cd59 between D2Mit333 and D2Mit127 on chromosome 2, a region homologous with human chromosome 11p13 where the human CD59 gene is localised. These data have permitted the construction of a gene targeting vector for the generation of transgenic mice deficient in CD59.
Frequency and Determinants of Microembolic Signals on Transcranial Doppler in Unselected Patients with Acute Carotid Territory Ischemia
Authors: Koennecke Hans-Christian , Mast Henning , Trocio Jr. Samuel H. , Sacco Ralph L. , Ma Weidong , Mohr Jay P. , Thompson John L.P.
Published: April 2003

Background and Purpose: Few data exist regarding to the occurrence of microembolic high-intensity transient signals (HITS) on transcranial Doppler ultrasound (TCD) in unselected acute stroke patients. The aim of this study was to investigate prospectively the frequency and determinants of HITS in acute carotid territory ischemia. We hypothesized that carotid artery disease, cardiac abnormalities, and nonlacunar infarcts were independent predictors of HITS in acute stroke. Methods: We investigated 145 consecutive patients with acute internal carotid artery territory ischemia. The median time interval between stroke and TCD examination was 2 days. TCD monitoring was performed for 30 min on each middle cerebral artery. The frequency of HITS was cross-classified with carotid artery status, potential cardiac sources of embolism, and nonlacunar infarct subtype. Multivariate logistic regression models determined the independent relationship of these variables to HITS. Results: Microembolic signals were detected in 35 patients (24.1%), Ipsilateral carotid artery disease was significantly and independently associated with HITS (odds ratio 3.3, 95% confidence interval 1.4–7.8, p = 0.007), whereas potential cardiac sources (OR 1.07, 95% CI 0.48–2.4, p = 0.84) and infarct subtype (OR 0.84, 95% CI 0.29–2.4, p = 0.75) were not. Conclusions: High-intensity transient signals can be found in almost 25% of patients with acute anterior cerebral circulation ischemia and are significantly more prevalent among those with symptomatic carotid artery disease. Future clinical studies are required to determine whether HITS are a marker of increased stroke recurrence and can help to clarify stroke etiology in patients with competing stroke mechanisms.
White Matter Medullary Infarcts: Acute Subcortical Infarction in the Centrum ovale
Authors: Read Stephen J. , Pettigrew Louise , Schimmel Laetitia , Levi Christopher R. , Bladin Christopher F. , Chambers Brian R. , Donnan Geoffrey A.
Published: April 2003

Acute infarction confined to the territory of the white matter medullary arteries is a poorly characterised acute stroke subtype. 22 patients with infarction confined to this vascular territory on CT and/or MRI were identified from a series of 1,800 consecutive admissions to our stroke unit (1.2%) between August 1993 and March 1997. 19 patients had small infarcts (<1.5 cm maximum diameter) and 3 large infarcts (>1.5 cm). Small infarcts were associated with a history of smoking (69%), hypertension (58%), and hyperlipidaemia (37%), and less frequently with atrial fibrillation (21%). Significant (>50%) ipsilateral carotid stenosis (16%) was a less frequent finding in this group. Patients most commonly presented with weakness and/or sensory disturbance affecting mainly the upper limbs, but dysarthria, dysphasia, and ataxia were also seen. Large infarcts were infrequent in our series, but did not differ significantly from small infarcts with respect to clinical presentation or risk factor profiles (p > 0.05 for all comparisons). The majority of symptomatic patients with white matter medullary infarcts are associated with small (<1.5 cm diameter) lesions and a risk factor profile consistent with small vessel disease. More data are required to elucidate the mechanism of larger (>1.5 cm) infarcts. Because of the potential overlap between white matter medullary infarcts and internal watershed infarcts, suggested criteria for each are presented.
Increasing Levels of Leukocyte-Derived Inflammatory Mediators in Plasma and cAMP in Platelets during Follow-Up after Acute Cerebral Ischemia
Authors: Anwaar I. , Gottsäter A. , Ohlsson K. , Mattiasson I. , Lindgärde F.
Published: April 2003

Inflammatory mediators secreted by activated leukocytes play a role in the pathogenesis of atherosclerosis. They may also affect the production of vasodilatory and platelet antiaggregatory factors such as nitric oxide (NO) and prostacyclin (PGI2) from the vascular endothelium. Production of NO and PGI2, the effecs of which are mediated by cyclic 3′,5′-guanosine monophosphate (cGMP) and cyclic 3′,5′-adenosine monophosphate (cAMP), respectively, is disturbed in atherosclerosis, whereas increased NO levels have been found in acute cerebral ischemia. To investigate leukocyte activation and its possible influence upon endothelial function in cerebral ischemia we measured plasma neutrophil gelatinase-associated lipocalin (NGAL) and soluble tumor necrosis factor receptor protein-1 (sTNFR-1) by ELISA, and intraplatelet cAMP and cGMP by radioimmunoassay in 59 patients with acute ischemic stroke or transient ischemic attack (mean age 71 years, 27 males) and after a 1-year follow-up in 57/59 (97%) patients. NGAL (152 ± 58 vs. 126 ± 48 µg/l), sTNFR-1 (3.50 ± 2.2 vs. 2.59 ± 1.31 µg/l), and cAMP (5.12 ± 1.71 vs. 4.06 ± 0.92 pmol/109 platelets) were higher (p < 0.001) after follow-up than in acute cerebral ischemia. At follow-up sTNFR-1 and cGMP partially correlated (r = 0.31; p < 0.05), controlling for age and platelet count. In conclusion, plasma NGAL and sTNFR-1 and intraplatelet AMP increase after acute cerebral ischemia, indicating chronic inflammatory activity and endothelial activation. Plasma sTNFR-1 levels are related to intraplatelet cGMP levels.