bluuebunny/crossref_metadata_2025 huggingface dataset:
Cat eye syndrome chromosome breakpoint clustering: identification of two intervals also associated with 22q11 deletion syndrome breakpoints
Authors: McTaggart K.E. , Budarf M.L. , Driscoll D.A. , Emanuel B.S. , Ferreira P. , McDermid H.E.
Published: April 2003

The supernumerary cat eye syndrome (CES) chromosome is dicentric, containing two copies of 22pter→q11.2. We have found that the duplication breakpoints are clustered in two intervals. The more proximal, most common interval is the 450–650 kb region between D22S427 and D22S36, which corresponds to the proximal deletion breakpoint interval found in the 22q11 deletion syndrome (DiGeorge/velocardiofacial syndrome). The more distal duplication breakpoint interval falls between CRKL and D22S112, which overlaps with the common distal deletion interval of the 22q11 deletion syndrome. We have therefore classified CES chromosomes into two types based on the location of the two breakpoints required to generate them. The smaller type I CES chromosomes are symmetrical, with both breakpoints located within the proximal interval. The larger type II CES chromosomes are either asymmetrical, with one breakpoint located in each of the two intervals, or symmetrical, with both breakpoints located in the distal interval. The co-localization of the breakpoints of these different syndromes, plus the presence of low-copy repeats adjacent to each interval, suggests the existence of several specific regions of chromosomal instability in 22q11.2 which are involved in the production of both deletions and duplications. Since the phenotype associated with the larger duplication does not appear to be more severe than that of the smaller duplication, determination of the type of CES chromosome does not currently have prognostic value.
High-resolution mapping of the X-linked lymphoproliferative syndrome region by FISH on combed DNA
Authors: Monier K. , Michalet X. , Lamartine J. , Schurra C. , Heitzmann F. , Yin L. , Cinti R. , Sylla B.S. , Creaven M. , Porta G. , Vourc’h C. , Robert-Nicoud M. , Bensimon A. , Romeo G.
Published: April 2003

X-linked lymphoproliferative syndrome is an inherited immunodeficiency for which the responsible gene is currently unknown. Several megabase-sized deleted regions mapping to Xq25 have been identified in XLP patients, and more recently a 130-kb deletion has been reported (Lamartine et al., 1996; Lanyi et al., 1996). To establish a physical map of this deleted region and to identify the XLP gene, two cosmid contigs were established (Lamartine et al., 1996). However, the physical map of this region is still uncompleted and controversial and three points remain unsolved: (1) the centromeric-telomeric orientation of the whole region, (2) the relative orientation of the two contigs, and (3) the size of the gap between the two contigs. To provide a definitive answer to these questions, high-resolution mapping by fluorescence in situ hybridization on combed DNA and molecular approaches were combined to establish the physical map of the XLP region over 600 kb. Our results identified a gap of 150 kb between the two contigs, established the relative orientation of one contig to the other, and determine the centromeric-telomeric orientation of the whole region. Our results show that the order of the marker over this region is: cen...1D10T7–DF83–DXS982...tel.
Hemizygous deletion of the HPC-1/syntaxin 1A gene (STX1A) in patients with Williams syndrome
Authors: Nakayama T. , Matsuoka R. , Kimura M. , Hirota H. , Mikoshiba K. , Shimizu Y. , Shimizu N. , Akagawa K.
Published: April 2003

HPC-1/syntaxin 1A is a membrane protein that plays an important role in exocytosis of neurotransmitters from neuronal cells. We previously mapped the human HPC-1/syntaxin 1A gene (STX1A) to chromosome 7q11.2, which is within the Williams syndrome (WS) region. Here, we performed FISH analysis on 46 patients with WS to examine the relationship between STX1A and WS. Our results showed a hemizygous deletion of the HPC-1/syntaxin 1A gene in each patient, suggesting that the neurological symptoms of WS may be related to the hemizygous deletion of STX1A.
Analysis of chromosome aberrations in a mammary carcinoma cell line from a dog by using canine painting probes
Authors: Tap O.T. , Rutteman G.R. , Zijlstra C. , de Haan, N.A. , Bosma A.A.
Published: April 2003

A cell line derived from a spleen metastasis of a mammary carcinoma in a female dog was analyzed by fluorescence in situ hybridization with canine chromosome-specific paints. The cell line showed a modal chromosome number of 77, with three (90% of the cells) or four (10% of the cells) biarmed chromosomes. Aberrations observed relate to chromosomes 8 or 11, 13 or 15, 37, 38, and X and include chromosome loss (X), formation of isochromosomes (8 or 11, 13 or 15), and centric fusion (37 and 38). In all aberrations, whole chromosomes are involved. None of the genes known to be related to breast cancer development in humans and that has mapped in the dog is located on one of the aberrant chromosomes. The results of this study show that chromosome painting is a most useful tool for the analysis of canine tumor cells.
Genomic structure of a novel human gene (XYLB) on chromosome 3p22→p21.3 encoding a xylulokinase-like protein
Authors: Tamari M. , Daigo Y. , Ishikawa S. , Nakamura Y.
Published: April 2003

We isolated a novel human cDNA of 1963 nucleotides that included an open reading frame encoding a protein of 528 amino acids. Homology analysis indicated that the predicted gene product, XYLB, bore 22% identity to the xylulokinase of Haemophilus influenzae that plays an important role in energy metabolism. The gene consists of 18 exons and spans about 28 kb of genomic DNA on chromosome 3p21.3.
Genomic analysis of DUSP6, a dual specificity MAP kinase phosphatase, in pancreatic cancer
Authors: Furukawa T. , Yatsuoka T. , Youssef E.M. , Abe T. , Yokoyama T. , Fukushige S. , Soeda E. , Hoshi M. , Hayashi Y. , Sunamura M. , Kobari M. , Horii A.
Published: April 2003

DUSP6 (alias PYST1), one of the dual-specificity tyrosine phosphatases, is localized on 12q21, one of the regions of frequent allelic loss in pancreatic cancer. This gene is composed of three exons, and two forms of alternatively spliced transcripts are ubiquitously expressed. Although no mutations were observed in 26 pancreatic cancer cell lines, reduced expressions of the full-length transcripts were observed in some cell lines, which may suggest some role for DUSP6 in pancreatic carcinogenesis.
Human chromosome 9 pericentric homologies: implications for chromosome 9 heteromorphisms
Authors: Park J.P. , Wojiski S.A. , Spellman R.A. , Rhodes C.H. , Mohandas T.K.
Published: April 2003

Pericentromeric polymorphisms of chromosome 9 include variations in the size of heterochromatin, pericentric inversions, and, more rarely, additional C-band-negative, G-band-positive material in either the proximal short arm or long arm or within the heterochromatin. It has been postulated that rearrangements involving the different classes of satellite DNA present in this relatively unstable region of the human genome constitute a mechanism for the origin of these variants. We report the identification, by molecular cytogenetic investigations, of homologous stretches of euchromatin shared by the proximal short and long arms of chromosome 9 that suggest that exchanges involving these regions may be an additional mechanism for the origin of chromosome 9 polymorphisms.
The genomic breakpoint and chimeric transcripts in the EWSR1–ETV4/E1AF gene fusion in Ewing sarcoma
Authors: Ishida S. , Yoshida K. , Kaneko Y. , Tanaka Y. , Sasaki Y. , Urano F. , Umezawa A. , Hata J. , Fujinaga K.
Published: April 2003

Chromosome translocation creates a fusion between the EWSR1 gene and an ETS family gene. The fusion between these two genes is a characteristic feature of Ewing sarcoma. We previously identified a fourth translocation, t(17;22)(q12;q12), in genomic DNA isolated from cells of patients affected with Ewing sarcoma. The discovery of this translocation suggested that there might be a novel EWSR1–ETV4 fusion gene. In the present study, we determined the genomic breakpoint and characterized the chimeric transcript of the EWSR1–ETV4 fusion gene in two t(17;22) Ewing sarcomas. Reverse transcriptase-PCR assay showed an in-frame fusion between the 5′-terminal region of EWSR1 and the 3′ end of ETV4 (alias E1AF, PEA3); the chimeric transcript could thus serve as a template for expression of a protein composed of the N-terminal portion of EWSR1 fused to the DNA-binding domain of ETV4. Long PCR and sequence analysis of genomic DNA revealed that either exon 8 or intron 7 of EWSR1 is fused to the same intron of ETV4 in both tumors. Several palindromic oligomer sequences were found close to the breakpoints in both genes. The 159-bp Alu-like sequence was repeated in the breakpoint region of the ETV4 gene. These observations suggest a mechanism of EWSR1–ETV4 gene fusion.
The gene encoding the transcriptional repressor BERF-1 maps to a region of conserved synteny on mouse chromosome 16 and human chromosome 3 and a related pseudogene maps to mouse chromosome 8
Authors: Antona V. , Cammarata G. , De Gregorio L. , Dragani T.A. , Giallongo A. , Feo S.
Published: April 2003

We have recently identified and characterized a Kruppel-like zinc finger protein (BERF-1), that functions as a repressor of β enolase gene transcription. By interspecific backcross analysis the gene encoding BERF-1 was localized 4.7 cM proximal to the Mtv6 locus on mouse chromosome 16, and an isolated pseudogene was localized to mouse chromosome 8, about 5.3 cM distal to the D8Mit4 marker. Nucleotide sequence identity and chomosome location indicate that the gene encoding BERF-1 is the mouse homologue (Zfp148) of ZNF148 localized to human chromosome 3q21, a common translocation site in acute myeloid leukemia patients.
Mapping and molecular characterization of five HMG1-related DNA sequences
Authors: Rogalla P. , Borda Z. , Meyer-Bolte K. , Tran K.H. , Hauke S. , Nimzyk R. , Bullerdiek J.
Published: April 2003

Recently, the high mobility group (HMG) proteins have attracted a lot of interest since it was shown that some members of that group can causally be involved in tumorigenesis. One HMG protein gene member is HMG1 for which the number of related DNA sequences has been estimated to be approximately 20–30. Nevertheless, besides the gene for HMG1 only one retropseudogene has been molecularly characterized. It was the aim of this study to map and characterize further sequences related to HMG1. PCR-screening of a PAC library resulted in 25 very strongly positive clones apparently containing HMG1-like cDNA sequences. Of eight clones which were further investigated five were distinguishable from each other based on their chromosome assignment and DNA sequence. Due to their homology to the HMG1 gene the DNA sequences were designated as HMG1L1, HMG1L3, HMG1L4, HMG1L5, and HMG1L6. By FISH experiments they were assigned to 2q32, 2q35, 3p24, 15q22, and 20q13, respectively. Except for one sequence, they did not show mutations leading to a frame shift or a new termination codon. Thus, we cannot exclude that these four HMG1-related DNA sequences represent active genes or can at least be activated e.g. by chromosome rearrangements in tumor cells. So far, the existence of six genes encoding HMG proteins has been described but because of a high frequency of closely related DNA sequences in the human genome it can be assumed that some of them are either pseudogenes or very similar genes.
Localization of 5-methylcytosine in metaphase chromosomes of diploid and triploid pacu fish, Piaractus mesopotamicus (Pisces, Characiformes)
Authors: de Almeida-Toledo L.F. , Viegas-Péquignot E. , Coutinho-Barbosa A.C. , Foresti F. , Niveleau A. , de Almeida Toledo-Filho S.
Published: April 2003

The distribution of 5-methylcytosine (5-MeC) was investigated in fish chromosomes by indirect immunofluorescence using a highly specific 5-MeC monoclonal antibody. Diploid and artificially produced triploid specimens of the pacu fish, Piaractus mesopotamicus, were analyzed. The strong immunofluorescent signals were coincident with the heterochromatic regions of both diploids and triploids in a pattern that matched the C-banding pattern. In the euchromatin, heterogeneous labeling was observed along the chromatids. The weakness of this labeling hindered comparison of the fluorescence labeling of homologous chromosomes from diploid and triploid individuals. However, no striking differences were observed. The possibility that the euchromatin labeling by the 5-MeC antibody is related to the occurrence of mildly repetitive sequences in the genome of Piaractus is discussed.
Polyclonal expansion of cells with trisomy 7 in synovia from patients with osteoarthritis
Authors: Broberg K. , Höglund M. , Lindstrand A. , Toksvig-Larsen S. , Mandahl N. , Mertens F.
Published: April 2003

Trisomy 7 as the single chromosome aberration has been found in a variety of neoplasms and in normal tissue in the proximity of tumors, as well as in non-neoplastic lesions. Recently, we described a nonrandom pattern of chromosome aberrations, in particular, a gain of chromosome 7, in synovia, cartilage, and osteophytes from patients with osteoarthritis. To study the clonal origin of trisomy 7 in osteoarthritis, multiple synovial samples were collected from five women, all of whom were informative heterozygotes with regard to the X-linked human androgen receptor gene (AR). From each case, three to four independent cell cultures were initiated. Trisomic cell populations were subcloned from the individual cultures, and it was established whether or not the same allele of AR was inactivated in trisomic cells from different parts of the same joint. The finding of a polyclonal X-inactivation pattern in two of the cases provides strong evidence that gain of an extra copy of chromosome 7 occurs independently in multiple cells.
Comparative genomics: tracking chromosome evolution in the family Ursidae using reciprocal chromosome painting
Authors: Nash W.G. , Wienberg J. , Ferguson-Smith M.A. , Menninger J.C. , O’Brien S.J.
Published: April 2003

The Ursidae family includes eight species, the karyotype of which diverges somewhat, in both chromosome number and morphology, from that of other families in the order Carnivora. The combination of consensus molecular phylogeny and high-resolution trypsin G-banded karyotype analysis has suggested that ancestral chromosomal fissions and at least two fusion events are associated with the development of the different ursid species. Here, we revisit this hypothesis by hybridizing reciprocal chromosome painting probes derived from the giant panda (Ailuropoda melanoleuca), domestic cat (Felis catus), and man (Homo sapiens) to representative bear species karyotypes. Comparative analysis of the different chromosome segment homologies allowed reconstruction of the genomic composition of a putative ancestral bear karyotype based upon the recognition of 39 chromosome segments defined by painting as the smallest conserved evolutionary unit segments (pSCEUS) among these species. The different pSCEUS combinations occurring among modern bear species support and extend the postulated sequence of chromosomal rearrangements and provide a framework to propose patterns of genome reorganization among carnivores and other mammal radiations.
Meiotic products of two reciprocal translocations studied by multicolor fluorescence in situ hybridization
Authors: Estop A.M , Cieply K.M. , Wakim A. , Feingold E.
Published: April 2003

The sperm products of two male carriers of reciprocal translocations were studied by fluorescence in situ hybridization (FISH) using a combination of three probes for each translocation. One patient carried a t(2;18)(p21;q11.2), the other a t(8;9)(q24.2;q32). The probes selected included a centromeric marker for each chromosome involved in the translocation plus a third probe distal to the translocation breakpoint of one of the translocation chromosomes. This assay identifies alternate, adjacent 1, adjacent 2, and 3:1 types of meiotic products. It allows the identification of recombination events and also estimation of the frequency of diploidy. For the t(2;18), the frequency of normal and balanced sperm and of adjacent 1, adjacent 2, and 3:1 products was 43.6%, 29.8%, 10.5%, and 12.8%, respectively. Similar segregation patterns had been reported for this donor by direct sperm karyotyping of sperm cells. For the t(8;9), the frequency of normal and balanced sperm and of adjacent 1, adjacent 2, and 3:1 products was 44.4%, 41%, 3.1%, and 9.4%, respectively. The frequency of complementary adjacent 1 products was statistically different in both the t(2;18) (P < 0.0001) and the t(8;9) (P < 0.0001) carrier. When the number of adjacent 2 products with one translocation chromosome (regardless of normal or derivative) was compared to the number of adjacent 2 products with the second translocation chromosome (again, regardless of normal or derivative), no statistical difference was noted for either the t(2;18) (P = 0.32) or the t(8;9) (P = 0.69). Recombination events within the interstitial segment of chromosome 2 were statistically higher than those seen in chromosome 18 (P < 0.0001), whereas in chromosomes 8 and 9, recombination in the interstitial segments was similar (P = 0.64). The rate of diploidy was similar in both the t(2;18) (0.5%) and the t(8;9) (0.6%). Thus, FISH provides chromosome information on the sperm products produced by translocation carriers, although it cannot provide an assessment of the full chromosome complement of the spermatozoon.
Development of arm-specific and subtelomeric region-specific painting probes for Chinese hamster chromosomes and their utility in chromosome identification of Chinese hamster cell lines
Authors: Xiao Y. , Natarajan A.T.
Published: April 2003

Arm-specific and subtelomeric region-specific painting probes for Chinese hamster chromosomes have been generated by microdissection and use of the degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR). Fluorescence in situ hybridization (FISH) analyses using these probes demonstrated their specificity. These probes painted every chromosome arm and a total of 15 subtelomeric regions, namely, both ends of chromosomes 1, 2, 3, 4, and 8 and one end of chromosome arms 5q, 6q, 7q, 9p, and Xp. Many cryptic chromosomal rearrangements in the CHO-9 and V79 cell lines that were not detectable with whole chromosome paints could be recognized when these newly developed probes were used.
Molecular cloning, mapping, and characterization of two novel human genes, ORCTL3 and ORCTL4, bearing homology to organic-cation transporters
Authors: Nishiwaki T. , Daigo Y. , Tamari M. , Fujii Y. , Nakamura Y.
Published: April 2003

Through a large-scale sequencing of genomic DNA at 3p22→p21.3, we have isolated two human genes (ORCTL3 alias OCTL1 and ORCTL4 alias OCTL2) encoding novel members of the family of organic-cation transporter molecules. The predicted proteins revealed the highest similarities to recently- isolated organic-cation transporter proteins, rat OCT-1r, rat NLT and mouse NKT. The transcripts of both genes were expressed ubiquitously in various human tissues, but some tissue-specific transcripts were also observed in kidney, testis, or skeletal muscle. The two genes are clustered within a 52-kb region of genomic DNA and ORCTL4 lies about 27 kb telomeric to ORCTL3 in the genomic DNA sequence in a tail-to-head orientation.
Cytogenetic study of some tissues and age-related changes in cell proportions in a goat-sheep chimera
Authors: Jaszczak K. , Parada R. , Guszkiewicz A.
Published: April 2003

Different percentages of cells with a female sheep or male goat karyotype were found in kidney (12.0% vs. 88.0%) and lung (42.6% vs. 57.4%) cell cultures from a 10-year-old chimera. Skin biopsies from patches with goat hair or sheep wool showed different, age-related goat-to-sheep fibroblast ratios. Karyotypic analysis of lymphocytes obtained from peripheral blood of the chimera at 6 and 10 yr of age showed no chimerism. Two weeks after birth, however, lymphocytes with both sheep (54,XX) and goat (60,XY) karyotypes were apparent in the blood of this chimera. Twenty percent of the blood cells examined at 2 wk had a caprine karyotype; this proportion declined with time, until it was totally eliminated at age 6.
Mapping of the α-1,6-fucosyltransferase gene, FUT8, to human chromosome 14q24.3
Authors: Yamaguchi Y. , Fujii J. , Inoue S. , Uozumi N. , Yanagidani S. , Ikeda Y. , Egashira M. , Miyoshi O. , Niikawa N. , Taniguchi N.
Published: April 2003

α-1,6-Fucosyltransferase (α1,6FucT) is involved in the biosynthesis of asparagine-linked glycoprotein oligosaccharides. In this study, we isolated a genomic clone for the human α1,6FucT gene (FUT8) and mapped it by fluorescence in situ hybridization to chromosome 14q24.3. This study suggests a distinct localization of FUT8 from genes for other human fucosyltransferases reported to date.
The karyotype of the Iberian imperial eagle (Aquila adalberti) analyzed by classical and DNA replication banding
Authors: Padilla J.A. , Martinez-Trancón M. , Rabasco A. , Fernández-García J.L.
Published: April 2003

We report here for the first time the karyotype of the Iberian imperial eagle (Aquila adalberti). All eagles examined had a diploid number of 82 chromosomes and a greater number of microchromosomes (12 pairs) than has been found in all other species of the Accipitridae family. This karyotypic evidence corroborates the recent separation of A. adalberti from A. heliaca on the basis of molecular data. RB-FPG banding induced a specific banding pattern that allowed us to identify homologous chromosome pairs and revealed features about late and early replicating regions. Several chromosome banding techniques (C-, CMA3-, and restriction endonuclease banding and silver staining) were used to characterize the karyotype more accurately. Two GC-rich, late-replicating heterochromatin regions were found in the W chromosome. These regions are AluI resistant and can be used for sex determination in this species. All microchromosomes were heterochromatic, GC rich, and late replicating. Silver staining revealed active nucleolus organizing regions on a pair of microchromosomes that were entirely heterochromatic and stained intensely after CMA3-banding. Different chromosome rearrangements are discussed in order to establish the phylogenetic relationship between A. adalberti and its most closely related species, A. heliaca.
Splice variants of the mouse Tec gene are differentially expressed in vivo
Authors: Merkel A.L. , Atmosukarto I.I.C. , Stevens K. , Rathjen P.D. , Booker G.W.
Published: April 2003

Tec is a cytoplasmic protein tyrosine kinase that participates in the signalling pathways of a broad range of cytokines. Up to five different Tec isoforms have been reported in the literature. We report here the genomic organisation of the mouse Tec gene and the tissue expression pattern of the two predominant transcripts, TecIII and TecIV. The mouse Tec gene consists of 18 exons, spans more than 86 kb, and is 2.6 kb 5′ to the gene for Txk, a Tec family member. Comparison of mouse and human Btk, human TXK, and mouse Tec genomic structures shows a high level of conservation of exon/intron boundaries. Compared with TecIV, the TecIII transcript has a 66-bp deletion in the SH3 domain encoding region and is revealed here to arise by alternative splicing of exon 8. We show that both TecIII and TecIV are expressed as early as embryonic day 10.5 in mouse development, as well as in adult and embryonic organs. The ratio of TecIV to TecIII expression is markedly reduced in adult liver and kidney tissues and d16 embryonic limb.
Reciprocal chromosome painting shows that genomic rearrangement between rat and mouse proceeds ten times faster than between humans and cats
Authors: Stanyon R. , Yang F. , Cavagna P. , O’Brien P.C.M. , Bagga M. , Ferguson-Smith M.A. , Wienberg J.
Published: April 2003

Reciprocal chromosome painting between mouse and rat using complete chromosome probe sets of both species permitted us to assign the chromosomal homology between these rodents. The comparative gene mapping data and chromosome painting have a better than 90% correspondence. The reciprocal painting results graphically show that mouse and rat have strikingly different karyotypes. At least 14 translocations have occurred in the 10–20 million years of evolution that separates these two species. The evolutionary rate of chromosome translocations between these two rodents appears to be up to 10 times greater than that found between humans and cats, or between humans and chimpanzees, where over the last 5–6 million years just one translocation has occurred. Outgroup comparison shows that the mouse genome has incorporated at least three times the amount of interchromosomal rearrangements compared to the rat genome. The utility of chromosome painting was also illustrated by the assignment of two new chromosome homologies between rat and mouse unsuspected by gene mapping: between mouse 11 and rat 20 and between mouse 17 and rat 6. We conclude that reciprocal chromosome painting is a powerful method, which can be used with confidence to chart the genome and predict the chromosome location of genes. Reciprocal painting combined with gene mapping data will allow the construction of large-scale comparative chromosome maps between placental mammals and perhaps other animals.
Physical mapping of the bovine, caprine and ovine homologues of the paired box gene PAX8
Authors: Lòpez-Corrales N.L. , Sonstegard T.S. , Smith T.P.L.
Published: April 2003

The PAX8 gene, a member of the human paired box gene family, was mapped by FISH to chromosome 11 in cattle and goat and to the short arm of chromosome 3 in sheep. The cytogenetic position of PAX8 on BTA 11 and on its homologue OAR 3p lies in the region where the interleukin beta (IL1B) gene has been previously located, (BTA 11q22.1→q22.3 and OAR 3p25→q26 respectively; Lòpez-Corrales et al., 1998). The results indicated that PAX8 as well as interleukin beta and interleukin alpha (IL1B and IL1A) genes detected on the human chromosome segment HSA 2q13→q21 maintain a similar order and location in these three related species. In addition, the breakpoint in conserved synteny can now be narrowed to a position between the protein C (PROC) and PAX8 genes, which lie in close proximity on HSA 2.
A novel human gene, encoding a potential membrane protein conserved from yeast to man, is strongly expressed in testis and cancer cell lines
Authors: Veitia R.A. , Ottolenghi C. , Bissery M.-C. , Fellous A.
Published: April 2003

We have characterized a novel human gene (C14orf1) which codes for a polypeptide homologous to the yeast protein Yer044c. Both the human and yeast proteins are predicted to be highly basic and to present several potential, evolutionarily conserved, transmembrane domains. C14orf1 mRNA was found to be particularly abundant in the adult testis and in several cancer cell lines. The gene maps to chromosome band 14q24. Further investigations should be performed to understand the role of C14orf1 in the testis and the significance of its strong expression in the cell lines studied here.
Structure and chromosome location of human OGG1
Authors: Ishida T. , Hippo Y. , Nakahori Y. , Matsushita I. , Kodama T. , Nishimura S. , Aburatani H.
Published: April 2003

OGG1 (alias MMH) encodes an 8-hydroxyguanine glycosylase, functionally homologous to bacterial mutM. Here, we report its genomic structure and fine chromosome location. The human OGG1 gene corresponding to the isoform 1 transcripts, consists of seven exons, spanning 7,421 bps, while an alternative additional exon, utilized for isoform 2, is located approximately 9 kb downstream. TATA-like sequence was not found in the 5′-upstream region, common in so-called “housekeeping” genes. The last 55 bases of the 3′ untranslated region in exon 7 were unexpectedly conserved among species, presumably because the 3′ end of the CAMK1 gene, which is transcribed convergently on the opposite strand, is overlapped at the 3′ end. By radiation hybrid panel mapping, OGG1 was localized between WI-4179 and AFMA216ZG1 at 3p26, proximal to the VHL gene.
International System for Standardized Avian Karyotypes (ISSAK): standardized banded karyotypes of the domestic fowl (Gallus domesticus)
Authors: Ladjali-Mohammedi K. , Bitgood J.J. , Tixier-Boichard M. , Ponce de Leon F.A.
Published: April 2003

The chicken genetic map is becoming very detailed. The genetic and physical maps need to be integrated in more detail. It is important to have a consensus banded karotype to permit this integration. An international committee met to develop a karyotype for the eight largest chromosomes and the Z and W chromosomes of the domestic fowl (Gallus domesticus). This map is presented in this report.
Exon structure and promoter identification of STIM1 (alias GOK), a human gene causing growth arrest of the human tumor cell lines G401 and RD
Authors: Sabbioni S. , Veronese A. , Trubia M. , Taramelli R. , Barbanti-Brodano G. , Croce C.M. , Negrini M.
Published: April 2003

The stromal interaction molecular 1 gene (STIM1) encodes a type I trans-membrane protein of unknown function, which induces growth arrest and degeneration of the human tumor cell lines G401 and RD but not HBL100 and CaLu-6, suggesting a role in the pathogenesis of rhabdomyosarcomas and rhabdoid tumors. Here, we describe the STIM1 genomic organization including the identification of the promoter region. The gene consists of 12 exons that span a region larger than 250 kb between the genes RRM1 and NUP98. Nucleotide sequences of all exon-intron boundaries were determined and oligonucleotide primers for the amplification of individual exons were designed. The promoter region was identified within a 1.8-kb SacI fragment at the 5′ end of the gene. In vitro CpG methylation of the promoter region indicated that transcription can be downregulated by this mechanism. The genetic tools developed in the present work will help to determine whether pathogenetic mechanisms that associate STIM1 with tumorigenesis involve mutations in coding sequences and/or promoter, and whether methylation could determine STIM1 transcriptional down-regulation in tumor samples.
Mechanisms of APC-driven tumorigenesis: lessons from mouse models
Authors: Fodde R. , Smits R. , Hofland N. , Kielman M. , Meera Khan P.
Published: April 2003

Colorectal cancer still represents one of the most common causes of morbidity and mortality among Western populations. The adenomatous polyposis coli (APC) gene, originally identified as the gene responsible for familial adenomatous polyposis (FAP), an inherited predisposition to multiple colorectal tumors, is now considered as the true “gatekeeper” of colonic epithelial proliferation. It is mutated in the vast majority of sporadic colorectal tumors, and inactivation of both APC alleles occurs at early stages of tumor development in man and mouse. The study of FAP has also led to one of the most consistent genotype-phenotype correlations in hereditary cancer. However, great phenotypic variability is still observed not only among carriers of the identical APC mutation from unrelated families but also from within the same kindred. The generation of several mouse models carrying specific Apc mutations on the same inbred genetic background has confirmed the genotype-phenotype correlations initially established among FAP patients, as well as provided important insights into the mechanisms of colorectal tumor formation. Here we review the major features of the available animal models for FAP and attempt the formulation of a hypothetical model for APC-driven tumorigenesis based on the observed genetic and phenotypic variability in mouse and man.
Molecular pathology of colorectal cancer
Authors: Bosman F.T.
Published: April 2003

The identification of several types of familial colorectal cancer has led to the discovery of some of the genes involved in these diseases. It was subsequently shown that somatic mutations of these genes (APC, mismatch repair genes, TP53, KRAS, and DCC) also occur in sporadic colorectal cancer. Gradually, this molecular information is being incorporated into the standard histopathological analysis of colorectal cancer and can be used for the characterization of primary tumors. Although attempts have been made to use molecular parameters to better define dysplasia grades, differentiate between adenoma and carcinoma, and subtype carcinomas, histological parameters remain the standard for the classification of primary tumors. Nonetheless, molecular parameters may help define subgroups of colorectal carcinoma differing in prognosis and requiring individualized treatment regimens. Interesting possibilities are predicting the response to chemotherapy or radiotherapy at a molecular level and the search for metastasis by looking for molecular markers in lymph nodes or circulating blood. Other pathological tests being developed include the detection of KRAS, TP53, or APC mutations in stool and plasma. Such approaches will have a significant impact on the clinical management of colorectal cancer.
Comparative genomic hybridization analysis of hepatoblastomas: additional evidence for a genetic link with Wilms tumor and rhabdomyosarcoma
Authors: Steenman M. , Tomlinson G. , Westerveld A. , Mannens M.
Published: April 2003

We applied the technique of comparative genomic hybridization (CGH) to a series of 16 hepatoblastomas. Our goals were (1) to identify all quantitative chromosome abnormalities that appear in this type of tumor and (2) to compare the results with data from similar studies on other tumors associated with the Beckwith-Wiedemann syndrome (BWS). We found that the most commonly detected (> 30%) chromosome abnormalities were gains of chromosomes 1, 2, 7, 8, and 17. Losses of chromosomes were found in only a few cases. On comparing our results with those from studies on the BWS-associated tumors, Wilms tumor and rhabdomyosarcoma, it became clear that three chromosome regions, namely, 7q, 8q, and 17q, were the ones most commonly involved in all three types of tumors. These regions, therefore, may harbor genes that play a role in the etiology of BWS-associated tumors in general.
Lack of tumor suppression but induced loss of copies of indigenous chromosome 10 in vitro following microcell-mediated transfer of a deleted human der(9)t(X;9) chromosome to Syrian hamster BHK-191-5C cells
Authors: Islam M.Q. , Islam K.
Published: April 2003

We have previously shown that microcell-mediated transfer of a der(9)t(X;9) chromosome, containing an almost complete human chromosome (HSA) 9 derived from the human fibroblast strain GM0705, into the Syrian hamster (Mesocricetus auratus) cell line BHK-191-5C suppressed the anchorage independence and tumorigenicity of the hybrids. Transfer of a normal HSA X did not have any effect on these phenotypes. Although the recipient cell line contained a 1:1 ratio of near-diploid and near-tetraploid cells, all hybrids retaining the der(9) chromosome were near-tetraploid, in contrast to hybrids retaining a normal X chromosome. In the present study, we have generated microcell hybrids by transferring another der(9)t(X;9) chromosome derived from the human fibroblast strain GM01429. This derivative chromosome contained a deletion on the short arm of HSA 9 and was also missing the distal part of the long arm of HSA 9 due to the involvement in a reciprocal (constitutive) translocation of this chromosome with HSA X. Cytogenetic analysis showed that all hybrid clones were near-tetraploid, confirming our previous finding. We also observed that the introduction of the deleted der(9) chromosome forced the hybrids to lose Syrian hamster chromosome 10. A soft agar test and nude mice assay indicated that none of the hybrids was suppressed for either anchorage independent growth or tumor formation. These data suggest that there is an antagonistic relationship between growth-promoting genes and antiproliferative genes. The observed dosage effects of both growth-promoting and growth-suppressing genes indicate that cellular growth may be a quantitative trait.
ULS: a versatile method of labeling nucleic acids for FISH based on a monofunctional reaction of cisplatin derivatives with guanine moieties
Authors: Wiegant J.C.A.G. , van Gijlswijk R.P.M. , Heetebrij R.J. , Bezrookove V. , Raap A.K. , Tanke H.J.
Published: April 2003

The broad extension of an existing chemical DNA labeling technique for molecular cytogenetics is described. Called the Universal Linkage System (ULSTM), it is based on the capability of monoreactive cisplatin derivatives to react at the N7 position of guanine moieties in DNA. Simple repetitive probes, cosmids, PACs, and chromosome-specific painting probes were labeled by ULS and used in a series of multicolor fluorescence in situ hybridization experiments on interphase and metaphase cells. It is demonstrated that ULS-labeled probes, in general, perform as well as the more conventional enzymatically labeled probes. The advantage of ULS labeling over enzymatic labeling techniques is that it is a fast and simple procedure, and that the labeling can easily be scaled up for bulk probe synthesis. In addition, with ULS labeling it is possible to label degraded DNA, a situation in which enzymatic labeling is known to perform unsatisfactorily.
Multiple mono- and polymorphic Y-linked copies of the SRY  HMG-box in Microtidae
Authors: Bullejos M. , Sánchez A. , Burgos M. , Jiménez R. , Díaz de la Guardia R.
Published: April 2003

Sex determination in mammals is controlled by SRY (sex-determining region of the Y chromosome), a single-copy gene located on the Y-specific region. Several exceptions to this rule have been described: some rodent species present Y-specific multiple copies (either mono- or polymorphic) of this gene, and two Ellobius species and one Tokudaia species determine sex without a Y chromosome or the SRY gene. Recently, we have described multiple polymorphic copies of the SRY gene in both males and females of the vole species Microtus cabrerae. The female location and the presence of stop codons in some copies from males and females also suggest that they are nonfunctional copies of this gene (pseudogenes). We have investigated the SRY HMG-box in nine species of the family Microtidae; we report here the presence, in eight of these species, of multiple mono- or polymorphic copies of the SRY gene located on the Y chromosome.
Isolation and characterization of the novel gene, TU3A, in a commonly deleted region on 3p14.3→p14.2 in renal cell carcinoma
Authors: Yamato T. , Orikasa K. , Fukushige S. , Orikasa S. , Horii A.
Published: April 2003

We previously identified a 700-kb region of common allelic loss on 3p14.3→p14.2 in renal cell carcinoma (RCC). We further analyzed this region and constructed a sequence ready bacterial artificial chromosome (BAC) contig. This region was totally covered by six overlapping BAC clones and was roughly estimated to be 700 kb. Furthermore, we isolated a gene in this region that we termed TU3A. This gene encodes a protein consisting of 144 amino acids. Homology search did not show any significant similarities with known genes or proteins. Northern analysis with normal tissue identified a 3.0-kb transcript that was expressed ubiquitously. Although our mutation search using 37 primary RCCs as well as five RCC cell lines failed to detect any somatic alterations in the TU3A gene, two of five RCC cell lines had totally lost its expression. Considering the fact that we found no genetic alterations in TU3A, it is possible that some epigenetic alteration may have suppressed its expression.
Assignment of Pdnp2, the gene encoding phosphodiesterase I/nucleotide pyrophosphatase 2, to mouse Chromosome 15D2
Authors: Piao J.-H. , Matsuda Y. , Nakamura H. , Sano K.
Published: April 2003

We have isolated cDNA and genomic DNA encoding mouse PDNP2 (PD-Iα). The mouse Pdnp2 cDNA contains a 2,589-nucleotide open reading frame encoding a polypeptide of 863 amino acids. The 5′ region of the mouse Pdnp2 gene contains Sp1, Max1, HNF-3B, and AP1 putative transcription factor binding sites, without typical TATA or CAAT boxes. Fluorescence in situ hybridization showed that Pdnp2 is located at Chromosome 15D2, as expected based on mouse-human conserved regions.
Alterations of DNA methylation patterns in germ cells and Sertoli cells from developing mouse testis
Authors: Coffigny H. , Bourgeois C. , Ricoul M. , Bernardino J. , Vilain A. , Niveleau A. , Malfoy B. , Dutrillaux B.
Published: April 2003

In situ alterations of DNA methylation were studied between 14 d postcoitum and 4 d postpartum in Sertoli cells and germ cells from mouse testis, using anti-5-methylcytosine antibodies. Compared to cultured fibroblasts, Sertoli cells display strongly methylated juxtacentromeric heterochromatin, but hypomethylated chromatids. Germ cells always possess hypomethylated heterochromatin, whereas their euchromatin passes from a demethylated to a strongly methylated status between days 16 and 17 postcoitum. This hypermethylation occurs in the absence of DNA replication, germ cells being blocked in the G₀-G1 phase from day 15 postcoitum to birth. The DNA hypermethylation of germ cells is maintained until birth and could be visualized on both chromatids of metaphase chromosomes at the first postpartum cell division. Subsequently, the DNA hypermethylation is lost semiconservatively, being replaced by a methylation pattern recalling the typical fibroblast pattern. These alterations of DNA methylation follow a strict chronology, are chromosome structure and cell-type dependent, and may underlie profound changes of genome function.
VPREB3: cDNA characterization and expression in human and chromosome mapping in human and mouse
Authors: Rosnet O. , Mattéi M-G. , Delattre O. , Schiff C.
Published: April 2003

The pre-B cell receptor (pre-BCR) regulates pre-B cell expansion and allelic exclusion at the immunoglobulin (Ig) heavy chain locus and mediates the selection of Ig heavy chain variable gene segments. During the early phase of pre-BCR assembly in the mouse, the membrane Ig μ heavy chain transiently associates with the VPREB3 protein in the endoplasmic reticulum. Here, we present the human VPREB3 cDNA sequence and its B cell-specific expression in hematopoietic cell lines. We have localized this gene to chromosome 22q11 close to IGLL genes in human and to chromosome 10C in mouse.
Jumping translocations in spontaneous abortions
Authors: Levy B. , Dunn T.M. , Hirschhorn K. , Kardon N.
Published: April 2003

Chromosome translocations involving one donor chromosome and multiple recipient chromosomes have been referred to as jumping translocations (JTs). Acquired JTs are commonly observed in cancer patients, mainly involving chromosome 1. Constitutional forms of JTs mostly involve the acrocentric chromosomes and their satellites and have been reported in patients with clinical abnormalities. Recognizable phenotypes resulting from these events have included Down, Prader-Willi, and DiGeorge syndromes. The presence of JTs in spontaneous abortions has not been previously described. The breakpoints of all JTs occur in areas rich in repetitive DNA (telomeric, centromeric, and nucleolus organizing regions). We report two different unstable chromosome rearrangements in samples derived from spontaneous abortions. The first case involved a chromosome 15 donor. The recipient chromosomes were 1, 9, 15, and 21, and the respective breakpoints were in either the heterochromatic regions or the centromeres. FISH studies confirmed that the breakpoints of the jumping 15 rearrangement did not involve the Prader-Willi region but originated at the centromere or in the proximal short arm. A second case of instability was observed with a rearrangement resulting from a presumed de novo 8;21 translocation. Three JT cell lines were observed. They consisted of a deleted 8p chromosome, a dicentric 8;21 translocation, and an 8q isochromosome. The instability regions appeared to be at the pericentromeric region of chromosome 8 and the satellite region of chromosome 21. Both cases proved to be de novo events. The unstable nature of the JT resulting in chromosomal imbalance most likely contributed to the fetal loss. It appears that JT events may predispose to chromosomal imbalance via nondisjunction and chromosomal rearrangement and, therefore, may be an unrecognized cause of fetal loss.
Suppressor genes for malignant and anchorage-independent phenotypes located on human chromosome 9 have no dosage effects
Authors: Islam M.Q. , Islam K.
Published: April 2003

We have previously shown that microcell-mediated transfer of a der(9)t(X;9) human chromosome (HSA), derived from human fibroblast strain GM0705, into the Syrian hamster cell line BHK-191-5C produced only near-tetraploid hybrids, although the recipient cell line contained a 1:1 ratio of near-diploid and near-tetraploid cells. However, the tumorigenicity and the anchorage independence could be suppressed in the near-tetraploid hybrids with one copy of the der(9)t(X;9) chromosome. The introduction of an HSA X chromosome did not suppress either of these phenotypes. We concluded that in addition to two suppressor genes, one for tumorigenicity and another for anchorage independence, HSA 9 might carry a third gene capable of inhibiting cellular growth in vitro, which had dosage effects. In the present study, keeping one copy of the der(9)t(X;9) chromosome, we have increased the hamster background chromosome number beyond hexaploid level by fusing two microcell-generated hybrid cell lines, where both malignant and anchorage-independent phenotypes were suppressed, with the parental malignant BHK-191-5C cell line. Tests with nude mice showed that hybrids containing one copy of the der(9)t(X;9) chromosome against the increased background of chromosomes of malignant parental origin were still suppressed for both phenotypes. These results suggest that the suppressor genes for malignancy and for anchorage independence have no dosage effects, in contrast to the suppressor gene(s) for cellular growth.
Characterization of a new TSPY gene family member in Yq (TSPYq1)
Authors: Ratti A. , Stuppia L. , Gatta V. , Fogh I. , Calabrese G. , Pizzuti A. , Palka G.
Published: April 2003

We investigated subinterval 6E on the human Y chromosome, a region frequently deleted in infertile males. YAC yOX17, mapped within subinterval 6E by STS-PCR, was analyzed for the presence of new genes. TSPYq1, a member of the TSPY multi-copy gene family, was isolated and character- ized from a yOX17 cosmid subclone. PCR and FISH analysis performed on normal subjects and on patients with microdeletions of Yq suggested the presence of multiple copies of TSPY in Yq.
Isolation and characterization of a novel gene encoding a putative seven-span transmembrane protein, TM7SF3
Authors: Akashi H. , Han H.-J. , Iizaka M. , Nakajima Y. , Furukawa Y. , Sugano S. , Imai K. , Nakamura Y.
Published: April 2003

As part of a project involving large-scale sequencing of clones randomly selected from a human cDNA library, we isolated a novel human gene, termed TM7SF3 (transmembrane 7 superfamily member 3). Its open reading frame encodes a 570 amino acid protein containing seven putative transmembrane domains. The transcript of this gene was expressed in all human tissues examined, but most abundantlyin kidney. Immunocytochemical analysis demonstrated subcellular localization of TM7SF3 protein at the plasma membrane. We determined the chromosome location of TM7SF3 as 12q11.2→q12 by a combination of fluorescence in situ hybridization and radiation hybrid mapping.
The eosinophil peroxidase gene forms a cluster with the genes for myeloperoxidase and lactoperoxidase on human chromosome 17
Authors: Sakamaki K. , Kanda N. , Ueda T. , Aikawa E. , Nagata S.
Published: April 2003

Eosinophil peroxidase (EPX) is one of a family of mammalian peroxidases that includes myeloperoxidase (MPO), lactoperoxidase (LPO), and thyroid peroxidase (TPO). Here we show that the human EPX gene maps to chromosome 17q23.1, which localizes 34 kb from the LPO and MPO genes. Our results demonstrate that the EPX, LPO, and MPO genes form a cluster on human chromosome 17.