Duplication of chromosome 1 [dup(1)(q21q32)] as the sole cytogenetic abnormality in a patient previously treated for AML.

A nonrandom structural gain of 1q may be seen in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and often it is due to an unbalanced translocation. Dup(1)(q21q32) as the sole abnormality has only rarely been reported. Reports have suggested that the dup(1)(q21q32) is predictive of a poor prognosis.

Influence of a nonfragile FHIT transgene on murine tumor susceptibility.

FHIT, at a constitutively active chromosome fragile site, is often a target of chromosomal aberrations and deletion in a large fraction of human tumors. Inactivation of murine Fhit allelessignificantly increases susceptibility of mice to spontaneous and carcinogen-induced tumorigenesis. In this study, transgenic mice, carrying a human FHIT cDNA under control of the endogenous promoter, were produced to determine the effect of Fhit expression, from a nonfragile cDNA transgene outside the fragile region, on carcinogen-induced tumor susceptibility of wildtype and Fhit heterozygous mice.

Murine Spam1 mRNA: involvement of AU-rich elements in the 3'UTR and antisense RNA in its tight post-transcriptional regulation in spermatids.

Sperm adhesion molecule1 (SPAM1), the best characterized hyaluronidase gene, is abundantly expressed in the testis. We attempted to overexpress mouse Spam1 via transgenesis using either the endogenous promoter in a BAC or a heterologous Protamine1 promoter for a Spam1 cDNA transgene. Although transgene-copy numbers ranged from 2 to 15 and transgenic transcripts were expressed, there was a general failure of overexpression of the RNA and protein in the testis of all seven founders.

Homozygous carnitine palmitoyltransferase 1a (liver isoform) deficiency is lethal in the mouse.

To better understand carnitine palmitoyltransferase 1a (liver isoform, gene=Cpt-1a, protein=CPT-1a) deficiency in human disease, we developed a gene knockout mouse model. We used a replacement gene targeting strategy in ES cells that resulted in the deletion of exons 11-18, thus producing a null allele. Homozygous deficient mice (CPT-1a -/-) were not viable.

Spam1-associated transmission ratio distortion in mice: elucidating the mechanism.

Background: While transmission ratio distortion, TRD, (a deviation from Mendelian ratio) is extensive in humans and well-documented in mice, the underlying mechanisms are unknown. Our earlier studies on carriers of spontaneous mutations of mouse Sperm Adhesion Molecule 1 (Spam1) suggested that TRD results from biochemically different sperm, due to a lack of transcript sharing through the intercellular cytoplasmic bridges of spermatids. These bridges usually allow transcript sharing among genetically different spermatids which develop into biochemically and functionally equivalent sperm.

Fhit-deficient normal and cancer cells are mitomycin C and UVC resistant.

To identify functions of the fragile tumour suppressor gene, FHIT, matched pairs of Fhit-negative and -positive human cancer cell clones, and normal cell lines established from Fhit -/- and +/+ mice, were stressed and examined for differences in cell cycle kinetics and survival. A larger fraction of Fhit-negative human cancer cells and murine kidney cells survived treatment with mitomycin C or UVC light compared to matched Fhit-positive cells; approximately 10-fold more colonies of Fhit-deficient cells survived high UVC doses in clonigenic assays. The human cancer cells were synchronised in G1, released into S and treated with UVC or mitomycin C.

High efficiency creation of human monoclonal antibody-producing hybridomas.

The native human antibody repertoire holds unexplored potential for the development of novel monoclonal antibody therapeutics. Current techniques that fuse immortal cells and primary B-lymphocytes are sub-optimal for the routine production of hybridomas that secrete human monoclonal antibodies. We have found that a murine cell line that ectopically expresses murine interleukin-6 (mIL-6) and human telomerase (hTERT) efficiently forms stable human antibody-secreting heterohybridomas through cell fusion with primary human B-lymphocytes.

Partial paternal uniparental disomy of chromosome 6 in an infant with neonatal diabetes, macroglossia, and craniofacial abnormalities.

Neonatal diabetes, which can be transient or permanent, is defined as hyperglycemia that presents within the first month of life and requires insulin therapy. Transient neonatal diabetes mellitus has been associated with abnormalities of the paternally inherited copy of chromosome 6, including duplications of a portion of the long arm of chromosome 6 and uniparental disomy, implicating overexpression of an imprinted gene in this disorder. To date, all patients with transient neonatal diabetes mellitus and uniparental disomy have had complete paternal isodisomy.

Murine chromosome 16 telomeric region, homologous with human chromosome 21q22, contains the osmoregulatory Na(+)/myo-inositol cotransporter (SLC5A3) gene.

The murine Na(+)/myo-inositol cotransporter (SLC5A3) gene (Slc5a3) was cloned, the restriction sites mapped, and the coding region sequenced. Similar to other mammalian counterparts, including human, the gene has a single coding exon, with an open reading frame of 2.2 kb.

The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity.

To expand our understanding of the role of Jak2 in cellular signaling, we used the yeast two-hybrid system to identify Jak2-interacting proteins. One of the clones identified represents a human homologue of the Schizosaccaromyces pombe Shk1 kinase-binding protein 1, Skb1, and the protein encoded by the Saccharomyces cerevisiae HSL7 (histone synthetic lethal 7) gene. Since no functional motifs or biochemical activities for this protein or its homologues had been reported, we sought to determine a biochemical function for this human protein.

High-resolution genetic map of the human glutamyl aminopeptidase gene (ENPEP).

The murine B-lymphocyte differentiation antigen BP-1/6C3 has been identified as glutamyl aminopeptidase (EAP), the gene symbol for which is ENPEP. Using genomic DNA encoding for human EAP as a probe, we identified the ENPEP gene location on human chromosome 4q25 by polymerase chain reaction analysis of a human/rodent somatic cell hybrid mapping panel and by fluorescence in situ hybridization. Using a radiation hybrid panel, the gene order around ENPEP was determined to be centromere-D4S1236-(570 kb)-ENPEP-(210 kb)-D4S262-(270 kb)-D4S953-(270 kb)-D4S474-(570 kb)-IF.

Molecular studies of an ependymoma-associated constitutional t(1;22)(p22;q11.2).

We previously described a patient with a de novo constitutional translocation, t(1;22)(p22;q11.2), who developed a malignant ependymoma at age 5, and we proposed that the translocation predisposed the child to the development of the tumor. As a step toward isolation of a putative cancer gene, we have characterized the breakpoints of the (1;22) translocation at the molecular level.

Integration of physical, breakpoint and genetic maps of chromosome 22. Localization of 587 yeast artificial chromosomes with 238 mapped markers.

Detailed physical maps of the human genome are important resources for the identification and isolation of disease genes and for studying the structure and function of the genome. We used data from STS content mapping of YACs and natural and induced chromosomal breakpoints to anchor contigs of overlapping yeast artificial chromosome (YAC) clones spanning extensive regions of human chromosome 22. The STSs were assigned to specific regions (bins) on the chromosome using cell lines from a somatic hybrid mapping panel defining a maximum of 25 intervals.

Structure, chromosomal localization, and methylation pattern of the human mb-1 gene.

The Ag receptor on B lymphocytes is a multimeric complex that is composed of an Ag-specific component, surface Ig, which is noncovalently associated with at least two other proteins, Ig alpha and Ig beta. These are the glycoprotein products of the B lineage-restricted mb-1 and B29 genes and are crucial for the cell surface expression and function of the Ag receptor on B lymphocytes. To better understand the regulation of mb-1, we have cloned and sequenced a 5.

Assignment of sterol carrier protein X/sterol carrier protein 2 to 1p32 and its exclusion as the causative gene for infantile neuronal ceroid lipofuscinosis.

In the positional cloning of a disease gene with an unknown protein defect a spectrum of molecular biological methods is applied after linkage has been established. It is reasonable to analyze in detail any relevant candidate gene mapping to the particular chromosomal region. We report here the refined chromosomal assignment of SCPx/SCP2, a gene coding for the protein that is believed to have an important role in lipid metabolism by transporting many kinds of lipid molecules between organelles.

Localization of the expressed human p58 protein kinase chromosomal gene to chromosome 1p36 and a highly related sequence to chromosome 15.

The gene for the human p58 protein kinase, a cell division control-related gene, has been mapped by somatic cell hybrid analyses, in situ localization with the chromosomal gene, and nested polymerase chain reaction amplification of microdissected chromosomes. These studies indicate that the expressed p58 chromosomal gene maps to 1p36, while a highly related p58 sequence of unknown nature maps to chromosome 15. Assignment of a p34cdc2-related gene to 1p36 may have implications for numerous tumors that involve deletion of this region, including neuroblastoma, ductal carcinoma of the breast, malignant melanoma, Merkel cell carcinoma, and endocrine neoplasia.