Lambda Ig constant region genes are translocated to chromosome 8 in Burkitt''s lymphoma with t(8;22)

By in situ hybridization of normal human chromosomes with a cloned genomic probe specific for the constant region of the lambda immunoglobulin genes, band 22q11 was preferentially labelled. In two cell lines with t(8;22) derived from Burkitt's lymphoma a strong signal was noted on the 8q+ chromosome derivative, indicating that the constant region of the lambda Ig gene cluster was translocated from chromosome 22 to chromosome 8. In addition, the signal observed on the 22q- derivative chromosome was stronger than the background in one of the two cell lines tested, but not in the other. The implications are that the break point in chromosome 22 in some cases lies within the Ig gene itself or between clusters of such genes, and that different cases have different break points.     

The thyroglobulin gene is syntenic with the MYC and MOS protooncogenes and carbonic anhydrase II and maps to chromosome 14 in cattle

Using a panel of bovine x Chinese hamster hybrid somatic cells, sequences homologous to genes spanning human chromosome arm 8q have been syntenically assigned in cattle. Thyroglobulin (TG), carbonic anhydrase II (CA2), and the protooncogenes MYC and MOS were assigned to a newly identified bovine syntenic group, U23. Additionally, in situ hybridization of the thyroglobulin probe to bovine metaphase chromosomes revealed this syntenic group to be on bovine chromosome 14 and the bovine thyroglobulin gene to reside at 14q12----q15.     

Chromosome 15 uniparental disomy is not frequent in Angelman syndrome.

Genetic imprinting has been implicated in the etiology of two clinically distinct but cytogenetically indistinguishable disorders--Angelman syndrome (AS) and Prader-Willi syndrome (PWS). This hypothesis is derived from two lines of evidence. First, while the molecular extents of de novo cytogenetic deletions of chromosome 15q11q13 in AS and PWS patients are the same, the deletions originate from different parental chromosomes. In AS, the deletion occurs in the maternally inherited chromosome 15, while in PWS the deletion is found in the paternally inherited chromosome 15. The second line of evidence comes from the deletion of an abnormal parental contribution of 15q11q13 in PWS patients without a cytogenetic and molecular deletion. These patients have two maternal copies and no paternal copy of 15q11q13 (maternal uniparental disomy) instead of one copy from each parent. By qualitative hybridization with chromosome 15q11q13 specific DNA markers, we have now examined DNA samples from 10 AS patients (at least seven of which are familial cases) with no cytogenetic or molecular deletion of chromosome 15q11q13. Inheritance of one maternal copy and one paternal copy of 15q11q13 was observed in each family, suggesting that paternal uniparental disomy of 15q11q13 is not responsible for expression of the AS phenotype in these patients.     

Chromosomal localization of human genes required for G1 progression in mammalian cells

Specific probes derived from the human genes that complement the mutations of two independent temperature-sensitive (ts) mutants of the BHK-21 hamster cell line were used to determine the chromosomal locations of the loci in the human genome. The ts11 gene, which complements a mutation that blocks progression through the G1 phase of the cell cycle and which has now been identified as the structural gene for asparagine synthetase, is a member of a small gene/pseudogene family with four members. In a rodent-human somatic cell hybrid panel, the ts11 genomic locus from which the genomic probe derives segregates with human chromosome region 7cen----7q35, proximal to the TCR beta locus. In situ hybridization maps this locus more precisely to the q21-31 region of chromosome 7. Two other members of the gene family detected by the ts11 probe segregate concordantly with chromosome region 8pter----8q24 and chromosome region 21pter----21q22. Similar experiments using the same rodent-human hybrid panel conducted with a probe identifying the tsBN51 gene, which also encodes a function necessary for G1 progression, mapped this locus to human chromosome 8, proximal to the large amplification unit encompassing the c-myc gene of Colo320 cells. Chromosomal in situ hybridization of the tsBN51 probe confirmed the localization of this gene to chromosome 8, with the most likely location of the gene being 8q21.     

Localization of human c-mos to chromosome band 8q11 in leukemic cells with the t(8;21) (q22;q22)

Summary Chromosome in situ hybridization studies locate c-mos to chromosome band 8q11 in leukemic cells carrying the t(8;21) (q22;q22). This amends the previous assignment of c-mos to chromosome band 8q22 and conforms with its recent assignment to 8q11 in normal cells and in a cell line with a structurally abnormal chromosome 8. C-mos lies proximally to, and distant from, the breakpoint at 8q22 in the t(8;21) and is unlikely to have a role in the onset of acute myeloid leukemia characterized by this translocation.     

Regional assignment of six polymorphic DNA sequences on chromosome 21 by in situ hybridization to normal and rearranged chromosomes.

We have assigned six polymorphic DNA segments to chromosomal subregions and have established the physical order of these sequences on the long arm of chromosome 21 by in situ hybridization of cloned probes to normal metaphase chromosomes and chromosomes 21 from individuals with three different structural rearrangements: an interstitial deletion, a ring chromosome, and a reciprocal translocation involving four different breakpoints in band 21q22. Segments D21S1 and D21S11 map to region 21q11.2----q21, D21S8 to 21q21.1----q22.11, and D21S54 to 21q21.3----q22.11; D21S23 and D21S25 are both in the terminal subband 21q22.3, but they are separated by a chromosomal breakpoint in a ring 21 chromosome, a finding that places D21S23 proximal to D21S25. The physical map order D21S1/D21S11-D21S8-D21S54-D21S23-D21S25 agrees with the linkage map, but genetic distances are disproportionately larger toward the distal end of 21q.     

Frequent gains on chromosome arms 1q and/or 8q in human endometrial cancer

Comparative genomic hybridization (CGH) was employed to survey genomic regions with increased and decreased copy number of the DNA sequence in 15 endometrial cancers [10 cases with microsatellite instability positive (MI+) and 5 cases with MI–]. Twelve of these 15 tumors (80%) showed abnormalities in copy number at one or more of the chromosomal regions. There were no regions with frequent chromosomal losses. Conversely, 11 of 15 cases (73%) showed gains on chromosome arms 1q (8/15; 53%) and/or 8q (6/15; 40%). Concordant gains of both chromosome arms 1q and 8q were observed in all three endometrial cancers of histological grade 3. These results suggest that these two chromosomal regions may contain genes whose increased expression contributes to development and/or progression of endometrial carcinogenesis. Two cases were further analyzed by fluorescence in situ hybridization (FISH) using three probes on chromosome 1 and two probes on chromosome 8 to more accurately determine increases in copy number. We found gains of chromosome 1q to 2.9–3.6 copies per cell and on 8q to 4.4 copies per cell. Received: 9 March 1997 / Accepted: 2 June 1997     

Comparative FISH mapping of Gab1 and Gab2 genes in human, mouse and rat.

Gab1 and Gab2 are members of the Gab family which act as adapters for transmitting various signals in response to stimuli through cytokine and growth factor receptors, and T- and B-cell antigen receptors. We determined chromosome locations of the two genes in human, mouse and rat by fluorescence in situ hybridization. The Gab1 gene was localized to chromosome 4q31.1 in human, 8C3 in mouse and 19q11.1--> q11.2 in rat, and the Gab2 gene was located on chromosome 11q13.4-->q13.5 in human, 7E2 in mouse and 1q33.2-->q33.3 in rat. All human, mouse and rat Gab1 and Gab2 genes were localized to chromosome regions where conserved homology has been identified among the three species.     

Molecular cloning of a DNA fragment from human chromosome 14(14q11) involved in T-cell malignancies.

To isolate DNA segments specific to chromosome band 14q11, which has been implicated in a number of human T-cell malignancies, a genomic DNA library was prepared from a variant cell subline of the human lymphoblastic KE37 cell line. This subline (KE37-R) bears a t(8;14) (q24;q11) translocation, and the breakpoint on the resulting chromosome 8q+ has been located at the 3' end of the third c-myc exon. Three molecular clones were isolated by screening the library with a c-myc exon 3 probe, and one of them (lambda K40) was analyzed in detail. It contains a 15-kb insert consisting of 4.5 kb of sequence from chromosome 8 (e.g., downstream of c-myc exon 3) and sequences from chromosome 14. The origin of these latter sequences was established by hybridizing DNA from chromosomes sorted by flow cytometry to a lambda K40 subclone containing only chromosome 14 presumptive sequences and by Southern blot analysis of rodent X human somatic hybrid cell DNA with the same probe. No cross-hybridization was found between the lambda K40 clone and a cDNA clone for the alpha chain T-cell receptor gene which is also located in 14q11. A preliminary survey of DNAs from human T-cell malignancies with a probe corresponding to chromosome 14 sequences of lambda K40 clone revealed for some of them restriction patterns different from those of the germ line DNA. The fact that the rearrangement observed in a leukemic patient was not found in DNA from lymphocytes obtained during remission excluded any polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chromosomal mapping of human adenylyl cyclase genes type III,type V and type VI

Adenylyl cyclase activity plays a central role in the regulation of most cellular processes. At least eight different adenylyl cyclases have been identified, which are endowed with various and sometimes opposing regulatory properties. Recently we have localized the human genes encoding two of these adenylyl cyclases: the gene for type 11 adenylyl cyclase is located on chromosome 2 (sub-band 2p15.3), the gene for type VIII is located on chromosome 8 (sub-band 8824.2). More recently the type I gene has been located on chromosome 7 (sub-band 7pl2–7p13). Using in situ hybridization, we have now localized the genes for three other adenylyl cyclases: the type III gene has been localized on chromosome 2 in the sub-band 2p22–2p24, the type V gene on chromosome 3 at position 3q13.2–3q21, and the type VI gene on chromosome 12 at position 12q12–12q13. It therefore appears that all adenylyl cyclase genes, known at present are located on different chromosomes and thus are likely to be independently regulated.     

Fine mapping of the muscular dystrophy (AM) gene on chicken chromosome 2q

Our previous studies revealed that the genetic locus for chicken muscular dystrophy of abnormal muscle (AM) mapped to chromosome 2q, and that the region showed conserved synteny with human chromosome 8q11-24.3. In the current study, we mapped the chicken orthologues of genes from human chromosome 8q11-24 in order to identify the responsible gene. Polymorphisms in the chicken orthologues were identified in the parents of the resource family. Twenty-three genes and expressed sequence tags (ESTs) were mapped to chicken chromosome 2 by linkage analysis. The detailed comparative map shows a high conservation of synteny between chicken chromosome 2q and human chromosome 8q. The AM locus was mapped between [inositol(myo)-1(or4)-monophosphatase 1] (IMPA1) gene and [core-binding factor, runt domain, alpha-subunit 2; translocated to 1; cyclin D-related] (CBFA2T1) gene. The genes located between IMPA1 and CBFA2T1 are the most likely candidates for chicken muscular dystrophy.     

Trisomy 8p due to the 3:1 segregation of the balanced translocation t(8;15)mat

Summary An additional small G-like chromosome was found in a newborn female with multiple abnormalities and hemorrhagic diathesis. G banding showed that the index patient was trisomic for the short arm of chromosome 8 and revealed the anomaly t(8;15)(q12;q11) in her mother. The relationship between chromosome 8 and multiple hemorrhages is discussed.     

Deficiency,transposition, and duplication of one 15q region may be alternatively associated with Prader-Willi (or a similar) syndrome. Analysis of seven cases after varying ascertainment

Seven patients are described who have some or all of the symptoms of Prader-Willi syndrome. They were ascertained by varying criteria starting either from the clinical picture or from the identification of a chromosome abnormality involving the proximal portion of the long arm of chromosome 15. The chromosome abnormalities consisted of two balanced translocations (15;18 and 8;15), three unbalanced ones (15;18, 15;19, and 9;15), and one interstitial deletion of bands 15q11 and q12. The seventh case had an unidentified extra chromosome. These data and a review of the literature led to the conclusion that deficiency, transposition, and even duplication of the region(s) 15q11-q13 may all result in a syndrome which is identifiable with or similar to the Prader-Willi syndrome.     

Allelotype of human thyroid tumors: loss of chromosome 11q13 sequences in follicular neoplasms.

Two classes of genes are the targets of mutations involved in human tumorigenesis: oncogenes, the activation of which leads to growth stimulation, and tumor suppressor genes, which become tumorigenic through loss of function, often through allelic deletion. To obtain evidence for a role for tumor suppressor genes in thyroid tumorigenesis, we examined DNA from 80 thyroid neoplasms for loss of heterozygosity in multiple chromosomal loci using 19 polymorphic genomic probes. None of the informative thyroid tumors studied had allelic loss detected with probes for chromosome 2q (D2S44), 3p (D3F15S2, D3S32), 3q (D3S46), 4p (D4S125), 6p (D6S40), 8q (D8S39), 9q (D9S7), 12p (D12S14), 13q (D13S52), 17p (D17S30), or 18q (D18S10). One of eight of the follicular adenomas had a 10q deletion detected with marker D10S15, and one of 26 had a 10q deletion detected with D10S25. One of two of the follicular carcinomas had an 11p deletion in the H-ras locus. The most significant findings were on chromosome 11q13, the site containing the putative gene predisposing to multiple endocrine neoplasia type I. Four of 27 follicular adenomas had loss of heterozygosity for probes in this region. Allelic deletions were detected with the following probes: D11S149, PYGM, D11S146, and INT2. None of 13 informative papillary carcinomas and none of two follicular carcinomas had loss of heterozygosity detectable with these 11q13 markers. Allelic loss is a relatively infrequent event in human thyroid tumors. Deletions of chromosome 11q13 are present in about 14% of follicular, but not papillary, neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Constitutional duplication 11q23 de novo involving the MLL gene

We report a child with mental retardation, brain anomalies and congenital heart defect. His karyotype, after G-banding and FISH with a whole chromosome probe for chromosome 11 and a locus-specific probe for the MLL gene, was 46,XY,dup(11)(q23q23).ish dup(11)(q23q23)(wcp11+, MLL++) de novo; i.e., he had a pure partial 11q23 duplication. Clinical and cytogenetic findings of the present case were compared with the 7 previously reported cases with pure partial trisomy 11q; in 6/8 cases the region 11q23 was involved. We conclude that the scarce number of cases and their heterogeneity do not allow to establish a reliable genotype-phenotype correlation.     

Molecular cytogenetic characterization of pancreas cancer cell lines reveals high complexity chromosomal alterations

Karyotype analysis can provide clues to significant genes involved in the genesis and growth of pancreas cancer. The genome of pancreas cancer is complex, and G-band analysis cannot resolve many of the karyotypic abnormalities seen. We studied the karyotypes of 15 recently established cell lines using molecular cytogenetic tools. Comparative genomic hybridization (CGH) analysis of all 15 lines identified genomic gains of 3q, 8q, 11q, 17q, and chromosome 20 in nine or more cell lines. CGH confirmed frequent loss of chromosome 18, 17p, 6q, and 8p. 14/15 cell lines demonstrated loss of chromosome 18q, either by loss of a copy of chromosome 18 (n = 5), all of 18q (n = 7) or portions of 18q (n = 2). Multicolor FISH (Spectral Karyotyping, or SKY) of 11 lines identified many complex structural chromosomal aberrations. 93 structurally abnormal chromosomes were evaluated, for which SKY added new information to 67. Several potentially site-specific recurrent rearrangements were observed. Chromosome region 18q11.2 was recurrently involved in nine cell lines, including formation of derivative chromosomes 18 from a t(18;22) (three cell lines), t(17;18) (two cell lines), and t(12;18), t(15;18), t(18;20), and ins(6;18) (one cell line each). To further define the breakpoints involved on chromosome 18, YACs from the 18q11.2 region, spanning approximately 8 Mb, were used to perform targeted FISH analyses of these lines. We found significant heterogeneity in the breakpoints despite their G-band similarity, including multiple independent regions of loss proximal to the already identified loss of DPC4 at 18q21.     

De novo balanced complex chromosome rearrangement (CCR) involving chromosome 8, 11 and 16 in a boy with mild developmental delay and psychotic disorder

Congenital Complex Chromosome rearrangements (CCRs) compatible with life are rare in humans. We report a de novo CCR involving chromosomes 8, 11 and 16 with 4 breakpoints in a patient with mild dysmorphic features, acquisition delay and psychotic disorder. Conventional cytogenetic analysis revealed an apparently balanced 8;16 translocation. Further FISH analysis with WCP 8 and WCP 16 probes revealed the presence of a third chromosome involved in the translocation. The multicolour karyotype confirmed the complexity of the rearrangement and showed that the derivative chromosome 8 was composed of 3 distinct segments derived from chromosomes 8, 16 and 11. The breakpoints of this complex rearrangement were located at 8q21, 11q14, 11q23 and 16q12. Comparative genomic hybridization (CGH) and array-CGH were performed to investigate the possibility of any genomic imbalance as a result of the complex rearrangement. No imbalance was detected by these two techniques. Our study showed: i) the necessity to confirm reciprocal translocations with FISH using painting probes, particularly when the karyotype resolution is weak; ii) the usefulness of multicolour karyotype for the characterization of structural chromosomal rearrangements, particularly when they are complex; iii) the usefulness of CGH and array-CGH in cases of abnormal phenotype and apparently balanced rearrangement in order to explore the breakpoints and to detect additional imbalances.     

Physical mapping of the bovine, caprine and ovine homologues of the paired box gene PAX8.

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.     

The complex history of distal human chromosome 1q

Human chromosome 1 has been claimed to be a conserved ancestral chromosome of eutherian mammals. However, two small regions from distal 1q (with orthology to mouse chromosome 11) appear to have a different history. These two regions are proposed to have been added to the ancestor of human chromosome 1 as a single block that was subsequently disrupted by a paracentric inversion. The translocation and inversion appear to have occurred at some time after the primate lineage diverged from a common ancestor with rodents. Reconstruction of the history of distal human chromosome 1q is complicated by the "reuse" of breakpoints in different mammalian lineages and by coincidental shared synteny between humans and cats.     

Demonstration of two different regions of lateral asymmetry in human Y chromosomes

Summary Two differently stained regions of lateral asymmetry were observed in the long arm of the human Y chromosome, following FPG staining. The first asymmetry was confined to band q12 of the long arm. The second asymmetrically stained region was located at the junction between bands q11 and q12. In the non-fluorescent Y chromosomes only one region of lateral asymmetry was found at the end of the long arm and its staining properties were similar to the region situated at the junction between q11 and q12 bands in the fluorescent Ys. The two morphologically distinguishable regions of lateral asymmetry are presumed to indicate sites containing different satellite DNAs in the human Y chromosome.