The gene for human growth hormone-releasing factor (GHRF) maps to or near chromosome 20p12.

Growth hormone-releasing factor (GHRF), a hypothalamic releasing factor also named somatocrinin, influences the secretion and synthesis of growth hormone. Human GHRF is encoded by a single gene which was assigned to chromosome 20 by dot-blot analysis of DNA from dual laser sorted chromosomes. Using a radioactive cDNA probe, we localized the GHRF gene to chromosome 20p12 or near band 20p12.     

Regional mapping of the Batten disease locus (CLN3) to human chromosome 16p12

The gene for Batten disease (CLN3) has been mapped to human chromosome 16 by demonstration of linkage to the haptoglobin locus, and its localization has been further refined using a panel of DNA markers. The aim of this work was to refine the genetic and physical mapping of this disease locus. Genetic linkage analysis was carried out in a larger group of families by using markers for five linked loci. Multipoint analysis indicated a most likely location for CLN3 in the interval between D16S67 and D16S148 (Z = 12.5). Physical mapping of linked markers was carried out using somatic cell hybrid analysis and in situ hybridization. A mouse/human hybrid cell panel containing various segments of chromosome 16 has been constructed. The relative order and physical location of breakpoints in the proximal portion of 16p were determined. Physical mapping in this panel of the markers for the loci flanking CLN3 positioned them to the bands 16p12.1----16p12.3. Fluorescent in situ hybridization of metaphase chromosomes by using these markers positioned them to the region 16p11.2-16p12.1. These results localize CLN3 to an interval of about 2 cM in the region 16p12.     

Regional localization of th human EGF-like growth factor CRIPTO gene (TDGF-1) to chromosome 3p21

The CRIPTO gene encodes a novel human growth factor structurally related to epidermal growth factor. We localized the CRIPTO gene to chromosome 3p21 by fluorescence in situ hybridization with a cosmid clone containing 40 kb of the CRIPTO genomic region (TDGF-1). To suppress hybridization to CRIPTO-related sequences, present in multiple copies in the human genome, hybridization was carried out in the presence of unlabeled CRIPTO cDNA in excess over the probe. Our finding confirms the provisional mapping of the CRIPTO gene to chromosome 3, and assigns it precisely to a chromosomal region involved in several rearrangements occurring in malignancy.CRIPTO-specific sequences are present in multiple copies in the human genome (Dono et al. 1991). Two genomic CRIPTO-encoding sequences, TDGF-1 and TDGF-3, have been isolated and characterized. TDGF-1 corresponds to the structural gene encoding the protein expressed in teratocarcinoma cells (Ciccodicola et al. 1989). TDGF-3, possibly a functional pseudogene, corresponds to a complete copy of the TDGF-1 mRNA that contains seven base changes representing both silent and replacement substitutions in the coding region (Dono et al. 1991). By somatic cell hybrid analysis TDGF-1 has been assigned to chromosome 3, and TDGF-3 to the Xq21–22 region (Dono et al. 1991).     

Gene for lymphoid enhancer-binding factor 1 (LEF1) mapped to human chromosome 4 (q23-q25) and mouse chromosome 3 near Egf.

LEF-1 is a 54-kDa nuclear protein that is expressed specifically in pre-B and T-cells. It binds to a functionally important site in the T-cell receptor alpha enhancer and contributes to maximal enhancer activity. LEF-1 is a member of a family of regulatory proteins that share homology with the high mobility group protein 1 (HMG1). The location of the LEF1 gene on human and mouse chromosomes was determined by Southern blot analysis of DNA from panels of interspecies somatic cell hybrids using a murine cDNA probe. Human-specific DNA fragments were detected in all somatic cell hybrids that retained the human chromosomal region 4cen-q31.2. Fluorescent in situ hybridization with two biotin-labeled overlapping human genomic cosmids revealed a specific hybridization signal at 4q23-q25. The homologous locus in the mouse was mapped to chromosome 3 by Southern analysis of rodent x mouse hybrid cell DNA. This chromosomal location was confirmed by the use of a restriction fragment length polymorphism (RFLP) in recombinant inbred mouse strains. The results of this RFLP analysis indicated that the mouse Lef-1 gene was closely linked to Pmv-39 and Egf and was likely placed between these loci, both of which were previously mapped to distal mouse chromosome 3. Our mapping results did not suggest involvement of this gene in previously mapped genetic disorders or in known neoplasia-associated translocation breakpoints.     

PALML, a novel paralemmin-related gene mapping on human chromosome 1p21.

We describe PALML, a novel gene encoding a 551 amino acid protein with similarity to paralemmin and the paralemmin-like amino terminal domain of AKAP2, a protein kinase A anchor protein. PALML mRNA is expressed in many tissues and is most abundant in cardiac and skeletal muscle, while absent from brain and blood. Exogenously expressed PALML fusion protein has a widespread cytoplasmic localization, and it is excluded from the nucleus. Human PALML maps on human chromosome 1p21 (between D1S2767 and D1S223). SSCP-HD analysis of exonic sequences in patients with VUR (familial non-syndromic vesicoureteral reflux syndrome) excluded mutations in the PALML gene from causing this disease. PALML, paralemmin and AKAP2 share the presence of a conserved coiled coil region that may mediate protein interactions with shared partners. Based on its resemblance to paralemmin and AKAP2, PALML is hypothesized to be involved in regulating intracellular signaling and membrane-cytoskeletal interactions.     

The human platelet-derived growth factor alpha chain (PDGFA) gene maps to chromosome 7p22.

The human PDGFA gene has been mapped previously to two different sites on chromosome 7 (7p21----p22 and 7q11.2----q21.1). Using in situ hybridization and human x mouse somatic cell hybrid lines we present data which confirm the localization of PDGFA to the terminal short arm of chromosome 7, at 7p22.     

Assignment of the gene for porcine insulin-like growth factor 1 (IGF1) to chromosome 5 by linkage mapping

Investigation of published sequence data from the porcine insulin-like growth factor 1 (IGF1) gene, resulted in the detection of a microsatellite in the first intron of the gene. Polymerase chain reaction (PCR) primers flanking the (CA)₁₉ repeat were constructed. Polymorphism and Mendelian segregation were documented in a three-generation pedigree and allele frequencies were determined in 74 unrelated animals from four different breeds. Seven alleles were encountered. Linkage analysis was performed in a large pedigree established for gene mapping. Linkage between the IGF1 microsatellite and an anonymous microsatellite marker, S0005, was detected. Furthermore, IGF1 and S0005 was found to be linked to the porcine submaxillary gland mucin (MUC) gene, previously assigned to chromosome 5. The results presented here extend the linkage group on pig chromosome 5 and are in accordance with conserved synteny between human chromosome 12, cattle chromosome 5, mouse chromosome 10 and pig chromosome 5.     

The human homolog of Sex comb on midleg (SCMH1) maps to chromosome 1p34.

Polycomb group genes were originally identified in Drosophila as repressors required to maintain the silenced state of homeotic loci. About ten Polycomb group genes have been cloned in Drosophila, and mammalian homologs have been identified for most of these. Here, we isolate cDNAs encoding two isoforms of a human homolog of Drosophila Sex comb on midleg (Scm), named Sex comb on midleg homolog-1 (SCMH1). Overall, SCMH1 has 94% identity to its mouse counterpart Scmh1, and 41% identity to Scm, and contains two 1(3)mbt domains, and the SPM domain that are characteristic of Scm. SCMH1 is widely expressed in adult tissues, and maps to chromosome 1p34.     

Reassignment of the human macrophage colony stimulating factor gene to chromosome 1p13-21.

Macrophage colony stimulating factor (CSF-1) is a member of a family of glycoproteins that are necessary for the normal proliferation and differentiation of myeloid progenitor cells. The human CSF-1 gene has previously been assigned to chromosome 5 using somatic cell hybrids, and further localized to 5q33 by in situ hybridization with a 3H labelled cDNA probe. However, the murine macrophage colony stimulating factor gene (csfm) has been localized to a region on mouse chromosome 3 which was previously shown to be syntenic with the proximal region of 1p and not 5q. Using a human genomic DNA clone that contains the CSF-1 gene, we have localized CSF-1 to chromosome 1p13-21 by fluorescence in situ hybridization. The reassignment of the CSF-1 gene argues against its involvement in myeloid disorders with deletions of the long arm of chromosome 5.