Showing papers on "Chromosome 22 published in 2003"

DNA sequence and analysis of human chromosome 9

Abstract: Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Microduplication 22q11.2, an Emerging Syndrome: Clinical, Cytogenetic, and Molecular Analysis of Thirteen Patients

Abstract: Chromosome 22, particularly band 22q11.2, is predisposed to rearrangements due to misalignments of low-copy repeats (LCRs). DiGeorge/velocardiofacial syndrome (DG/VCFS) is a common disorder resulting from microdeletion within the same band. Although both deletion and duplication are expected to occur in equal proportions as reciprocal events caused by LCR-mediated rearrangements, very few microduplications have been identified. We have identified 13 cases of microduplication 22q11.2, primarily by interphase fluorescence in situ hybridization (FISH). The size of the duplications, determined by FISH probes from bacterial artificial chromosomes and P1 artificial chromosomes, range from 3–4 Mb to 6 Mb, and the exchange points seem to involve an LCR. Molecular analysis based on 15 short tandem repeats confirmed the size of the duplications and indicated that at least 1 of 15 loci has three alleles present. The patients’ phenotypes ranged from mild to severe, sharing a tendency for velopharyngeal insufficiency with DG/VCFS but having other distinctive characteristics, as well. Although the present series of patients was ascertained because of some overlapping features with DG/VCF syndromes, the microduplication of 22q11.2 appears to be a new syndrome.

The transcriptional activity of human Chromosome 22

Abstract: A DNA microarray representing nearly all of the unique sequences of human Chromosome 22 was constructed and used to measure global-transcriptional activity in placental poly(A) + RNA. We found that many of the known, related and predicted genes are expressed. More importantly, our study reveals twice as many transcribed bases as have been reported previously. Many of the newly discovered expressed fragments were verified by RNA blot analysis and a novel technique called differential hybridization mapping (DHM). Interestingly, a significant fraction of these novel fragments are expressed antisense to previously annotated introns. The coding potential of these novel expressed regions is supported by their sequence conservation in the mouse genome. This study has greatly increased our understanding of the biological information encoded on a human chromosome. To facilitate the dissemination of these results to the scientific community, we have developed a comprehensive Web resource to present the findings of this study and other features of human Chromosome 22 at http://array.mbb.yale.edu/chr22.

Genetics of dermatofibrosarcoma protuberans family of tumors: from ring chromosomes to tyrosine kinase inhibitor treatment.

Abstract: Dermatofibrosarcoma protuberans (DP) is a rare, slow-growing, infiltrating dermal neoplasm of intermediate malignancy, made up of spindle-shaped tumor cells often positive for CD34. The preferred treatment is wide surgical excision with pathologically negative margins. At the cytogenetic level, DP cells are characterized by either supernumerary ring chromosomes, which have been shown by using fluorescence in situ hybridization techniques to be derived from chromosome 22 and to contain low-level amplified sequences from 17q22-qter and 22q10–q13.1, or t(17;22), that are most often unbalanced. Both the rings and linear der(22) contain a specific fusion of COL1A1 with PDGFB. Similar to other tumors, the COL1A1-PDGFB fusion is occasionally cryptic, associated with complex chromosomal rearrangements. Although rings have been mainly observed in adults, translocations have been reported in all pediatric cases. DP is therefore a unique example of a tumor in which (i) the same molecular event occurs either on rings or linear translocation derivatives, (ii) the chromosomal abnormalities display an age-related pattern, and (iii) the presence of the specific fusion gene is associated with the gain of chromosomal segments, probably taking advantage of gene dosage effects. In all DP cases that underwent molecular investigations, the breakpoint localization in PDGFB was found to be remarkably constant, placing exon 2 under the control of the COL1A1 promoter. In contrast, the COL1A1 breakpoint was found to be variably located within the exons of the α-helical coding region (exons 6–49). No preferential COL1A1 breakpoint and no correlation between the breakpoint location and the age of the patient or any clinical or histological particularity have been described. The COL1A1-PDGFB fusion is detectable by multiplex RT-PCR with a combination of forward primers designed from a variety of COL1A1 exons and one reverse primer from PDGFB exon 2. Recent studies have determined the molecular identity of “classical” DP, giant cell fibroblastoma, Bednar tumor, adult superficial fibrosarcoma, and the granular cell variant of DP. In approximately 8% of DP cases, the COL1A1-PDGFB fusion is not found, suggesting that genes other than COL1A1 or PDGFB might be involved in a subset of cases. It has been proposed that PDGFB acts as a mitogen in DP cells by autocrine stimulation of the PDGF receptor. It is encouraging that inhibitory effects of the PDGF receptor tyrosine kinase antagonist imatinib mesylate have been demonstrated in vivo; such targeted therapies might be warranted in the near future for treatment of the few DP cases not manageable by surgery. © 2003 Wiley-Liss, Inc.

Human Chromosome 7: DNA Sequence and Biology

Abstract: DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.

Further genetic evidence for a panic disorder syndrome mapping to chromosome 13q

Abstract: Substantial evidence supports that there is a genetic component to panic disorder (PD). Until recently, attempts at localizing genes for PD by using standard phenotypic data have not proven successful. Previous work suggests that a potential subtype of PD called the panic syndrome exists, and it is characterized by a number of medical conditions, most notably bladder/renal disorders. In the current study, a genome scan with 384 microsatellite markers was performed on 587 individuals in 60 multiplex pedigrees segregating PD and bladder/kidney conditions. Using both single-locus and multipoint analytic methods, we found significant linkage on chromosome 22 (maximum heterogeneity logarithm of odds score = 4.11 at D22S445) and on chromosome 13q (heterogeneity logarithm of odds score = 3.57 at D13S793) under a dominant-genetic model and a broad phenotypic definition. Multipoint analyses did not support the observation on chromosome 22. The chromosome 13 findings were corroborated by multipoint findings, and extend our previous findings from 19 of the 60 families. Several other regions showed elevated scores by using when one analytic method was used, but not the other. These results suggest that there are genes on chromosome 13q, and possibly on chromosome 22 as well, that influence the susceptibility toward a pleiotropic syndrome that includes PD, bladder problems, severe headaches, mitral valve prolapse, and thyroid conditions.

A P-element insertion screen identified mutations in 455 novel essential genes in Drosophila.

Abstract: With the completion of the nucleotide sequences of several complex eukaryotic genomes, tens of thousands of genes have been predicted. However, this information has to be correlated with the functions of those genes to enhance our understanding of biology and to improve human health care. The Drosophila transposon P-element-induced mutations are very useful for directly connecting gene products to their biological function. We designed an efficient transposon P-element-mediated gene disruption procedure and performed genetic screening for single P-element insertion mutations, enabling us to recover 2500 lethal mutations. Among these, 2355 are second chromosome mutations. Sequences flanking >2300 insertions that identify 850 different genes or ESTs (783 genes on the second chromosome and 67 genes on the third chromosome) have been determined. Among these, 455 correspond to genes for which no lethal mutation has yet been reported. The Drosophila genome is thought to contain approximately 3600 vital genes; 1400 are localized on the second chromosome. Our mutation collection represents approximately 56% of the second chromosome vital genes and approximately 24% of the total vital Drosophila genes.

Cloning of human centromeres by transformation-associated recombination in yeast and generation of functional human artificial chromosomes.

Abstract: Human centromeres remain poorly characterized regions of the human genome despite their importance for the maintenance of chromosomes. In part this is due to the difficulty of cloning of highly repetitive DNA fragments and distinguishing chromosome-specific clones in a genomic library. In this work we report the highly selective isolation of human centromeric DNA using transformation-associated recombination (TAR) cloning. A TAR vector with alphoid DNA monomers as targeting sequences was used to isolate large centromeric regions of human chromosomes 2, 5, 8, 11, 15, 19, 21 and 22 from human cells as well as monochromosomal hybrid cells. The alphoid DNA array was also isolated from the 12 Mb human mini-chromosome ΔYq74 that contained the minimum amount of alphoid DNA required for proper chromosome segregation. Preliminary results of the structural analyses of different centromeres are reported in this paper. The ability of the cloned human centromeric regions to support human artificial chromosome (HAC) formation was assessed by transfection into human HT1080 cells. Centromeric clones from ΔYq74 did not support the formation of HACs, indicating that the requirements for the existence of a functional centromere on an endogenous chromosome and those for forming a de novo centromere may be distinct. A construct with an alphoid DNA array from chromosome 22 with no detectable CENP-B motifs formed mitotically stable HACs in the absence of drug selection without detectable acquisition of host DNAs. In summary, our results demonstrated that TAR cloning is a useful tool for investigating human centromere organization and the structural requirements for formation of HAC vectors that might have a potential for therapeutic applications.

The Origin of Human Chromosome 1 and Its Homologs in Placental Mammals

Abstract: Developing ordered gene maps from multiple mammalian species coupled with chromosome-painting data provide a powerful resource for resolving the evolutionary history of chromosomes and whole genomes. In this work, we recapitulate the evolutionary history of human chromosome 1 and its homologs in placental mammals, putatively the largest physical unit in the ancestral placental genome. Precise definition of translocation exchange breakpoints in human, carnivore, cetartiodactyl, and rodent-ordered gene maps demonstrate that chromosome breakpoints, previously considered as equivalent, actually represent distinct chromosome positions and exchange events. Multidirectional chromosome painting, using probes from homologs to chromosome 1 in seven mammal species from six orders of placental mammals, confirm the gene-mapping results and indicate that the multiple human chromosome 1 homologs in these species are derived from independent fissions of a single ancestral chromosome. Chromosome painting using human chromosome 1 probes identifies a single human chromosome 1 homolog in phylogenetically distant taxa, the two-toed sloth, cetaceans, and higher primates. The diverse phylogenetic occurrence of a single Hsa1 synteny among the major clades of placental mammals suggests that human chromosome 1 represents an intact ancestral chromosome, which was variously fissioned in the majority of placental species. We find that the number of human chromosome 1 fissions in a specific lineage reflects its general rate of genomic evolution. Further, historic chromosome exchange appears to have been disproportionately clustered in two breakpoint hotspots on the long arm.

The DNA sequence of chromosome I of an African trypanosome: gene content, chromosome organisation, recombination and polymorphism.

Abstract: The African trypanosome, Trypanosoma brucei, causes sleeping sickness in humans in sub-Saharan Africa. Here we report the sequence and analysis of the 1.1 Mb chromosome I, which encodes approximately 400 predicted genes organised into directional clusters, of which more than 100 are located in the largest cluster of 250 kb. A 160-kb region consists primarily of three gene families of unknown function, one of which contains a hotspot for retroelement insertion. We also identify five novel gene families. Indeed, almost 20% of predicted genes are members of families. In some cases, tandemly arrayed genes are 99-100% identical, suggesting an active process of amplification and gene conversion. One end of the chromosome consists of a putative bloodstream-form variant surface glycoprotein (VSG) gene expression site that appears truncated and degenerate. The other chromosome end carries VSG and expression site-associated genes and pseudogenes over 50 kb of subtelomeric sequence where, unusually, the telomere-proximal VSG gene is oriented away from the telomere. Our analysis includes the cataloguing of minor genetic variations between the chromosome I homologues and an estimate of crossing-over frequency during genetic exchange. Genetic polymorphisms are exceptionally rare in sequences located within and around the strand-switches between several gene clusters.

The giant B chromosome of the cyprinid fish Alburnus alburnus harbours a retrotransposon-derived repetitive DNA sequence.

Abstract: The cyprinid fish Alburnus alburnus possesses one of the largest supernumerary chromosomes in all vertebrates In the present study, amplified fragment length polymorphism analyses (AFLP) and fluorescence in-situ hybridization (FISH) were performed in order to characterize these extraordinary chromosomes in detail Sequence analysis of the B chromosome-specific DNA revealed a strong homology to a Drosophila Gypsy/Ty3 retrotransposon and also to a medaka (Oryzias latipes) one The sequence is highly abundant on the B chromosome but undetectable in the normal A chromosome complement It is also absent from the B chromosome of the closely related species, Rutilus rutilus, suggesting a specific spreading of the mobile element during evolution of the giant supernumerary chromosome within A alburnus Meitotic chromosomes were in-situ hybridized with the B chromosome-specific probe, documenting that the additional chromosome behaves as an autopaired ring chromosome in diakineses Our results suggest that the supernumerary chromosome of A alburnus is not derived from the normal chromosome complement but has evolved independently

Identification of recurrent regions of chromosome loss and gain in vestibular schwannomas using comparative genomic hybridisation.

Abstract: Background: Schwannomas are benign tumours of the nervous system that are usually sporadic but also occur in the inherited disorder neurofibromatosis type 2 (NF2). The NF2 gene is a tumour suppressor on chromosome 22. Loss of expression of the NF2 protein product, merlin, is universal in both sporadic and NF2 related schwannomas. The GTPase signalling molecules RhoA and Rac1 regulate merlin function, but to date only mutation in the NF2 gene has been identified as a causal event in schwannoma formation. Methods: Comparative genomic hybridisation (CGH) was used to screen 76 vestibular schwannomas from 76 patients (66 sporadic and 10 NF2 related) to identify other chromosome regions that may harbour genes involved in the tumorigenesis. Results: The most common change was loss on chromosome 22, which was more frequent in sporadic than in NF2 related tumours. Importantly, eight tumours (10%) showed gain of copy number on chromosome 9q34. Each of the two NF2 patients who had received stereotactic radiotherapy had non-chromosome 22 changes, whereas only one of eight non-irradiated NF2 patients had any chromosome changes. Three tumours had gain on 17q, which has also been reported in malignant peripheral nerve sheath tumours that are associated with neurofibromatosis type 1. Other sites that were identified in three or fewer tumours were regions on chromosomes 10, 11, 13, 16, 19, 20, X, and Y. Conclusions: These findings should be verified using techniques that can detect smaller genetic changes, such as microarray-CGH.

New Classification Scheme for the Prognostic Stratification of Meningioma on the Basis of Chromosome 14 Abnormalities, Patient Age, and Tumor Histopathology

Abstract: Purpose: Meningiomas are usually considered benign tumors. However, relapses occur in 10% to 20% of all patients, including both histopathologically aggressive and benign tumors. This study explored the value of numerical abnormalities for 10 different chromosomes in meningiomas for predicting relapse-free survival (RFS). Patients and Methods: This study prospectively analyzed the frequency of numerical abnormalities of chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y in 70 meningioma patients by fluorescence in situ hybridization and their relationship with disease characteristics at diagnosis and patients’ outcome. Results: Results showed the presence of numerical abnormalities for one or more chromosomes in most patients (77%). Chromosome 22 in the whole series and chromosome Y in males were those more frequently altered, followed by chromosomes 1, 14, and X in females. Patients with abnormalities of chromosomes 1, 9, 10, 11, 14, 15, 17, the sex chromosomes, and gains of chromosome 22 were associated...

Engineered chromosome regions with altered sequence composition demonstrate hierarchical large-scale folding within metaphase chromosomes

Abstract: Mitotic chromosome structure and DNA sequence requirements for normal chromosomal condensation remain unknown. We engineered labeled chromosome regions with altered scaffold-associated region (SAR) sequence composition as a formal test of the radial loop and other chromosome models. Chinese hamster ovary cells were isolated containing high density insertions of a transgene containing lac operator repeats and a dihydrofolate reductase gene, with or without flanking SAR sequences. Lac repressor staining provided high resolution labeling with good preservation of chromosome ultrastructure. No evidence emerged for differential targeting of SAR sequences to a chromosome axis within native chromosomes. SAR sequences distributed uniformly throughout the native chromosome cross section and chromosome regions containing a high density of SAR transgene insertions showed normal diameter and folding. Ultrastructural analysis of two different transgene insertion sites, both spanning less than the full chromatin width, clearly contradicted predictions of simple radial loop models while providing strong support for hierarchical models of chromosome architecture. Specifically, an ∼250-nm-diam folding subunit was visualized directly within fully condensed metaphase chromosomes. Our results contradict predictions of simple radial loop models and provide the first unambiguous demonstration of a hierarchical folding subunit above the level of the 30-nm fiber within normally condensed metaphase chromosomes.

W-derived BAC probes as a new tool for identification of the W chromosome and its aberrations in Bombyx mori.

Abstract: We isolated four W chromosome-derived bacterial artificial chromosome (W-BAC) clones from Bombyx mori BAC libraries by the polymerase chain reaction and used them as probes for fluorescence in situ hybridization (FISH) on chromosome preparations from B. mori females. All four W-BAC probes surprisingly highlighted the whole wild-type W sex chromosome and also identified the entire original W-chromosomal region in W chromosome-autosome translocation mutants. This is the first successful identification of a single chromosome by means of BAC-FISH in species with holokinetic chromosomes. Genomic in situ hybridization (GISH) by using female-derived genomic probes highlighted the W chromosome in a similar chromosome-painting manner. Besides the W, hybridization signals of W-BAC probes also occurred in telomeric and/or subtelomeric regions of the autosomes. These signals coincided well with those of female genomic probes except one additional GISH signal that was observed in a large heterochromatin block of one autosome pair. Our results support the opinion that the B. mori W chromosome accumulated transposable elements and other repetitive sequences that also occur, but scattered, elsewhere in the respective genome.

Multiple meningiomas: Investigating the molecular basis of sporadic and familial forms

Abstract: Meningiomas are common tumors of the coverings of the central nervous system (CNS), comprising 20% of intracranial neoplasms. The only genes known to be associated with sporadic meningiomas are NF2 on chromosome 22 and the related cytoskeleton element DAL-1 on chromosome 18. Between 1 and 8% of patients with meningiomas develop multiple meningiomas, a trait transmitted occasionally in an autosomal dominant fashion. We investigated the DAL-1 and NF2 loci in 7 unrelated multiple meningioma patients without clinical evidence of NF2 by mutational and pathological analysis. Five novel intragenic microsatellite polymorphisms were developed for specific detection of loss of heterozygosity (LOH) at the DAL-1 locus. Three of 7 patients had affected relatives and all affected individuals were female. No tumors from familial patients were of a fibroblastic subtype. Truncating NF2 mutations were detected in 3 tumor specimens, but were not present in the corresponding blood samples. Two tumors showed LOH at the NF2 locus. All tumors showing mutations at the NF2 locus originated from patients without affected relatives and were of the fibroblastic subtype. Five non-truncating alterations in the DAL-1 gene were found, however, LOH of chromosome 18 markers was not seen in any tumor. In contrast to the NF2 results, all DAL-1 alterations were found in paired blood specimens. Our findings provide further evidence that the molecular basis of sporadic and familial multiple meningiomas is fundamentally different and extend this dichotomy to pathologic subtypes. DAL-1 does not function as a true tumor suppressor in these patients. © 2002 Wiley-Liss, Inc.

Arrangement of chromosome 11 and 22 territories, EWSR1 and FLI1 genes, and other genetic elements of these chromosomes in human lymphocytes and Ewing sarcoma cells.

Abstract: Standard and repeated fluorescence in situ hybridization and high-resolution cytometry were used to study topographical parameters of chromosome 11 and 22 territories, EWSR1 and FLI1 genes, and other genetic elements of these chromosomes in human lymphocytes and Ewing sarcoma cells. HSA 11 and its elements (BCL1, FLI1, centromere) were found, on average, more peripherally in comparison with HSA 22 and investigated elements (BCR, EWSR1, centromere). After the elimination of fluctuations of chromosome territories in nuclear volume, it was found that genetic elements in most cases adhered to their territories. The investigated genetic elements of HSA 11 were found close to each other relative to the large molecular lengths among them. This finding indicates a higher degree of chromatin condensation of at least a part of HSA 11 compared with HSA 22. In general, there is no correlation between the physical and molecular distance of two loci of the same chromosome territory. The topographical parameters of the EWSR1 and FLI1 genes do not differ substantially for G0-lymphocytes, stimulated lymphocytes and Ewing sarcoma cells. The fusion genes pertaining to both derivative chromosomes 11 and 22 in Ewing sarcoma cell nuclei are shifted to the midway position between the native EWSR1 and FLI1 genes. Comparing results obtained for the EWSR1/FLI1 and ABL1/BCR genes in samples of patients suffering from Ewing sarcoma or chronic myelogenous leukaemia, it can be concluded that the mean positions of the fusion genes are determined by the final structure of the chimeric chromosomes and do not depend on the location of the translocation event.

Partial trisomy of chromosome 22 resulting from an interstitial duplication of 22q11.2 in a child with typical cat eye syndrome

Abstract: Cat eye syndrome (CES) is a rare malformation syndrome with a variable pattern of congenital anomalies. The characteristic features of CES include ocular coloboma, preauricular pits or tags, anal anomalies, and congenital heart and renal malformations. Furthermore, CES may be associated with other craniofacial malformations, skeletal anomalies, and, in some cases, with mental retardation.1,2 In almost all cases CES is associated with the cytogenetic finding of a supernumerary marker chromosome consisting of duplicated material of chromosome 22. The marker is usually bisatellite and dicentric (idic(22)(pter→q11.2::q11.2→pter)) and thus results in tetrasomy of the p arm and a part of 22q11.2.1,3 Cytogenetically detectable intrachromosomal direct or inverted duplications are rare and can arise with equal frequency by rearrangement between sister chromatids or non-sister chromatids both on the maternal or paternal chromosome.4 The proximal part of the long arm of chromosome 22 (22q11.2) has been recognised as a hot spot for chromosomal rearrangements and contains both the cat eye and the DiGeorge critical region (for reviews see Kotzot et al 5 and Edelmann et al 6). Multiple congenital malformations showing overlap with CES can arise from familial translocation t(11;22) in the der(22) syndrome,7,8 and, in rare cases, from interstitial duplication of proximal 22q.9–11 However, none of these patients described so far with interstitial duplications of 22q showed the full CES phenotype including all major clinical features. We report here a patient with an interstitial inverted duplication of 22q11.2 and typical features of cat eye syndrome including coloboma, preauricular anomalies, heart defect, renal anomalies, and anal atresia. ### Key points

Somatic Instability of the NF2 Gene in Schwannomatosis

Abstract: Context Schwannomatosis is a newly described form of neurofibromatosis of unclear pathogenesis. Patient and Methods We studied the NF2 locus on chromosome 22 in 7 tumor specimens resected from a 36-year-old man with schwannomatosis of the right ulnar nerve. Results Unrelated truncating NF2 gene mutations were detected in 4 tumor specimens. None of the NF2 mutations were present in the blood specimen. Loss of heterozygosity at the NF2 locus was seen in all tumors, and in every case the same allele was lost. Loss of distal chromosome 22 markers was variable. Fluorescence in situ hybridization results were consistent with monosomy 22 in 4 tumors and mitotic recombination or nondisjunction in 1. Conclusions Molecular analysis of tumor specimens distinguishes schwannomatosis from other forms of neurofibromatosis. Further work is needed to understand the natural history and molecular biology of this condition.

Origin and differentiation of a sex chromosome system in Parodon hilarii (Pisces, Parodontidae). Satellite DNA, G- and C-banding

Abstract: A satellite DNA sequence of Parodon hilarii (named pPh2004) was isolated, cloned and sequenced This satellite DNA is composed of 200 bp, 60% AT rich In situ hybridization (FISH) results revealed that the satellite DNA pPh2004 is located in the terminal regions of several chromosomes, forming highly evident blocks in some and punctual marks in others The comparison between the FISH and C-banding results showed that the location of this satellite DNA coincides with that of most terminal heterochromatins However, some regions are only marked by FISH whereas other regions are only marked by C-banding The possible existence of more than one satellite DNA family could explain these partial differences The in situ hybridization with the satellite DNA and the G- and C-bandings confirmed the presence of a sex chromosome system of the ZZ/ZW type in P hilarii, as well as the correct identification of the Z chromosome in the karyotype This chromosome displays a segment of terminal heterochromatin in the long arm, similar to the segment observed in the short arm of the W chromosome, also showing a G-banding pattern similar to that of the short arm and part of the long arm of the W chromosome A hypothesis on the origin of the W chromosome from an ancestral chromosome similar to the Z chromosome is presented

Chromosomal abnormalities in human glioblastomas: gain in chromosome 7p correlating with loss in chromosome 10q

Abstract: Various genomic alterations have been detected in glioblastoma Chromosome 7p, with the epidermal growth factor receptor locus, together with chromosome 10q, with the phosphatase and tensin homologue deleted in chromosome 10 and deleted in malignant brain tumors-1 loci, and chromosome 9p, with the cyclin-dependent kinase inhibitor 2A locus, are among the most frequently damaged chromosomal regions in glioblastoma In this study, we evaluated the genetic status of 32 glioblastomas by comparative genomic hybridization; the sensitivity of comparative genomic hybridization versus differential polymerase chain reaction to detect deletions at the phosphatase and tensin homologue deleted in chromosome 10, deleted in malignant brain tumors-1, and cyclin-dependent kinase inhibitor 2A loci and amplifications at the cyclin-dependent kinase 4 locus; the frequency of genetic lesions (gain or loss) at 16 different selected loci (including oncogenes, tumor-suppressor genes, and proliferation markers) mapping on 13 different chromosomes; and the possible existence of a statistical association between any pair of molecular markers studied, to subdivide the glioblastoma entity molecularly Comparative genomic hybridization showed that the most frequent region of gain was chromosome 7p, whereas the most frequent losses occurred on chromosomes 10q and 13q The only statistically significant association was found for 7p gain and 10q loss

Chromosomal rearrangements in cattle and pigs revealed by chromosome microdissection and chromosome painting

Abstract: A pericentric inversion of chromosome 4 in a boar, as well as a case of (2q-;5p+) translocation mosaicism in a bull were analysed by chromosome painting using probes generated by conventional microdissection. For the porcine inversion, probes specific for p arms and q arms were produced and hybridised simultaneously on metaphases of a heterozygote carrier. In the case of the bovine translocation, two whole chromosome probes (chromosome 5, and derived chromosome 5) were elaborated and hybridised independently on chromosomal preparations of the bull who was a carrier of the mosaic translocation. The impossibility of differentiating chromosomes 2 and der(2) from other chromosomes of the metaphases did not allow the production of painting probes for these chromosomes. For all experiments, the quality of painting was comparable to that usually observed with probes obtained from flow-sorted chromosomes. The results obtained allowed confirmation of the interpretations proposed with G-banding karyotype analyses. In the bovine case, however, the reciprocity of the translocation could not be proven. The results presented in this paper show the usefulness of the microdissection technique for characterising chromosomal rearrangements in species for which commercial probes are not available. They also confirmed that the main limiting factor of the technique is the quality of the chromosomal preparations, which does not allow the identification of target chromosomes or chromosome fragments in all cases.

Quantitative PCR identifies a minimal deleted region of 120 kb extending from the Philadelphia chromosome ABL translocation breakpoint in chronic myeloid leukemia with poor outcome

Abstract: Fluorescence in situ hybridization (FISH) analysis has shown previously that 10–15% of chronic myeloid leukemias (CML) have hemizygous deletions of variable sizes affecting regions that flank the ABL and BCR translocation breakpoints on the derivative chromosome 9, and these patients have a poor outcome. FISH studies using large commercial genomic probes have previously suggested that haploinsufficiency of sequences flanking either ABL or BCR modify the disease process of CML and lead to an unfavorable prognosis. In this present study, real-time quantitative PCR (Q-PCR) analysis was used to identify and map much smaller hemizygous microdeletions in a subset of CML patients that were not deleted using large genomic FISH probes. Microdeletions were identified by Q-PCR in 25 of 71 patients selected based on less favorable outcome (chronic phase duration of less than 96 months and a survival time of less than 84 months). In contrast, no microdeletion was detected in any of 18 CML samples selected from a group with a more favorable outcome. Detailed mapping of the 25 Q-PCR microdeletions showed that the minimal deleted region extended ∼120 kb from the 5′ end of the ABL gene in the centromeric direction on the derivative chromosome 9, and the region 3′ to BCR on chromosome 22 was excluded. Of the four ESTs and/or genes that map to the 120 kb region, the putative tumor suppressor PRDM12 is the strongest candidate gene. The potential role for each sequence in modifying the clinical behavior of CML is presented.

Comparative genomic hybridization and pathological findings in atypical teratoid/rhabdoid tumour of the central nervous system.

Abstract: The atypical teratoid/rhabdoid tumour (AT/RT) is an uncommon tumour of the central nervous system in children, characterized by the presence of a rhabdoid cell component associated with variable combinations of primitive neuroectodermal tumour, mesenchymal and epithelial differentiation. Immunohistochemistry reveals a complex pattern of antigen expression and cytogenetic studies have demonstrated losses from chromosome 22. We have performed comparative genomic hybridization (CGH) on paraffin-embedded material from three cases of AT/RT. Two cases showed losses from chromosome 22 associated with other chromosome imbalances including losses from 1p in both cases. The third case demonstrated a loss from 8p as the sole abnormality. While monosomy or deletion from chromosome 22 is a useful diagnostic marker for AT/RT, it is not present in all cases. The variation in cytogenetic patterns reported for this tumour type raises the possibility that different genetic pathways may underlie this tumour phenotype and warrants the further definition of the cytogenetic spectrum for this rare tumour.