Chromosomal localization of three human genes encoding bone morphogenetic protein receptors

Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily that play a pivotal role in bone formation during embryogenesis and fracture repair. BMP signaling occurs via hetero-oligomeric serine/threonine kinase complexes of BMP type I (BMPR-IA or BMPR-IB) and type II receptors (BMPR-II). BMPR-IA and IB are closely related receptors, with sequence differences conserved between different species, suggesting that they serve distinct functions. Here we report the cDNA cloning of human BMPR1B and the chromosomal localization of all three BMPR genes. Using somatic cell hybrid and FISH analyses, the BMPR1A, BMPR1B, and BMPR2 genes were assigned to 10q23, 4q22-24, and 2q33-34, respectively. A processed BMPR1A pseudogene was mapped to 6q23. Received: 17 February 1997 / Accepted: 15 October 1998     

Chromosomal localization of zinc finger protein genes in man and mouse

We have determined the mouse and human chromosomal location of a gene (Zfp-3) that codes for a protein that contains potential DNA zinc-binding fingers. An analysis of the segregation of restriction fragment length polymorphisms in recombinant inbred strains and in an interspecific backcross demonstrated that Zfp-3 is located on mouse chromosome 11. Zfp-3 is very closely linked to the Trp53-1 locus but unlinked to another finger protein gene Zfp-4 located on mouse chromosome 8. In humans ZFP3 has been localized to chromosome 17p12-17pter and thus is part of the conserved linkage group between this chromosome and the distal half of mouse chromosome 11.     

Chromosomal localization of three pulmonary surfactant protein genes in the mouse.

Pulmonary surfactant, a protein-phospholipid mixture, maintains surface tension at the lung epithelium/air interface preventing alveolar collapse during respiration. For mammals appropriate developmental production of surfactant is necessary for adaptation to the air breathing environment. Deficiency of pulmonary surfactant results in respiratory distress syndrome (RDS), a leading cause of death in premature infants. Recently, three lung-specific pulmonary surfactant proteins designated SP-A, SP-B, and SP-C have been described. Cloned sequences for the genes that encode each of these proteins have been partially characterized in humans and other species. Analysis of interspecific backcross mice has allowed us to map the chromosomal locations of these three genes in the mouse. The gene encoding SP-A (Sftp-1) and the gene encoding SP-C (Sftp-2) both map to mouse chromosome 14, although at separate locations, while the gene encoding SP-B (Sftp-3) maps to chromosome 6. The mouse map locations determined in this study for the Sftp genes are consistent with the locations of these genes on the human genetic map and the syntenic relationships between the human and the mouse genomes.     

Chromosomal localization of mouse and human neurotensin receptor genes

Neurotensin is a tridecapeptide that plays several neurotransmitter or neuromodulatory roles both in the central nervous system and in the periphery. These actions are mediated by a high-affinity receptor (Ntsr). Both rat and human cDNAs encoding high-affinity receptors have been recently cloned. The availability of Ntsr probes allowed us to localize the corresponding genes on the mouse and human chromosomes. The present data demonstrate that the Ntsr gene is assigned to the H region of the mouse Chromosome (Chr) 2 and to the long arm of the human Chr 20.     

Chromosomal localization of acidic and basic keratin genes of the domestic dog

Our laboratories are interested in characterizing genes involved in the myriad of heritable diseases affecting the domestic dog, Canis lupus familiaris, and in development of detailed genetic and physical maps of the canine genome. Included in these efforts is examination of conservation of the genetic organization, structure, and function of gene families involved in diseases of the canine skin, skeleton, and eye. To that end, study of the highly conserved keratin gene family was undertaken. Keratins belong to the superfamily of intermediate filaments and are the major structural proteins of the epidermis, hair, and nail. The keratins are highly conserved throughout vertebrate evolution both at the DNA and amino acid sequence levels. Mutations in genes encoding epithelial keratins are known to cause various diseases in humans, and similar histopathological presentations have been reported in the dog. The keratins are divided into two groups, type I (acidic) and type II (basic). In the human, the genes encoding the acidic and basic keratins are clustered on Chrs 17 and 12, respectively. The same genetic arrangement is seen in the mouse with the acidic and basic keratin gene clusters found on Chrs 11 and 15, respectively. Reported here are the chromosomal localization of acidic and basic canine keratin genes as well as supportive sequence data. Fluorescence in situ hybridization (FISH) experiments with clones isolated from a canine genomic library suggest that the acidic keratin gene cluster resides on CFA9 and the basic keratin gene cluster is located on CFA27. Received: 25 September 1998 / Accepted: 1 December 1998     

Localization of two mouse genes encoding the protein tyrosine kinase receptor-related protein RYK

We have mapped the gene encoding the murine RYK growth factor receptor protein tyrosine kinase by genetic linkage analysis with recombinant inbred strains of mouse. Two distinct Ryk loci (Ryk-1 and Ryk-2) were identified. Ryk-1 mapped to Chromosome (Chr) 9, whereas Ryk-2 mapped to Chr 12. A similar arrangement of RYK-related loci was previously determined in the human. Synteny has already been established between murine Chr 9 in the region of Ryk-1, and human chromosome 3q11–12, the location of the human RYK-1 gene. However, the Ryk-2/RYK-2 loci on murine Chr 12 and human chr 17p13.3 define a new region of synteny.     

Chromosomal localization of opioid peptide and receptor genes in the mouse

Opiate receptors are the primary targets for the drugs of abuse morphine and heroin. In this study, we completed the localization on mouse chromosomes of the genes encoding mu (Oprm) and kappa (Oprk) receptors, as well as the genes for the opioid propeptides proenkephalin (Penk) and prodynorphin (Pdyn). The genetic mapping was performed using a panel of DNA samples from an interspecific cross [C3H/HeJ-gld and (C3H/HeJ-gld x Mus spretus)Fi] that has been characterized for more than 800 markers throughout the genome. The genes are localized on mouse Chr 1 (Oprk, 10 cM from the centromere), Chr 2 (Pdyn, 75 cM from the centromere), Chr 4 (Penk, 1 cM from the centromere) and Chr 10 (Oprm, 10 cM from the centromere). Interestingly, the gene for the mu receptor is located in the same region as a Quantitative Trait Locus for high morphine consumption, thus raising the possibility of its direct role in drug abuse mechanisms.     

Chromosomal localization of the genes encoding two forms of the G protein beta polypeptide, beta 1 and beta 3, in man

The signal-transducing G proteins are heterotrimers composed of three subunits, alpha, beta, and gamma. Multiple distinctive forms of the alpha, beta, and gamma subunits, each encoded by a distinct gene, have been described. To investigate further the structural diversity of the beta subunits, we recently cloned and characterized a novel cDNA encoding a third form of the G protein beta subunit, which we have termed beta 3. The protein corresponding to beta 3 has not yet been identified. The three forms of the beta subunit show 81-90% amino acid sequence identity. Previous studies had localized the human genes for the beta 1 and beta 2 subunits to chromosomes 1 and 7, respectively. The present studies were designed to determine whether the gene encoding beta 3 is linked to either the beta 1 or the beta 2 gene. Genomic DNA was isolated from a panel of rodent-human hybrid cell lines and analyzed by hybridization to cDNAs for beta 1 and beta 3. Discordancy analysis allowed assignment of the beta 3 gene to chromosome 12 and confirmed the previous assignment of the beta 1 gene to chromosome 1. These results were confirmed and extended by using in situ chromosome hybridization, which permitted the regional localization of the beta 1 gene to 1pter----p31.2 and the beta 3 gene to 12pter----p12.3. Digestion of human genomic DNA with 10 restriction enzymes failed to disclose a restriction fragment length polymorphism for the beta 3 gene. These data indicate that there is considerable diversity in the genomic organization of the beta subunit family.     

Chromosomal localization, expression pattern, and promoter analysis of the mouse gene encoding adipocyte-specific secretory protein Acrp30

Acrp30 is an abundantly expressed secretory protein exclusively synthesized in adipose tissue. Due to the dysregulation in various forms of obesity in humans and mice and its strong structural similarity to TNFalpha, it is currently under study as an important molecule involved in whole body energy homeostasis. Here we describe the sequence of mouse Acrp30 locus, define the intron/exon boundaries and map the gene to the telomere of mouse chromosome 16, syntenic to the human chromosomal locus 3q27. We demonstrate that alternative polyadenylation gives rise to two distinct mRNA species. We also show that Acrp30 expression is induced only at the late stages of mouse embryonic development. Finally, we have characterized the mouse Acrp30 promoter in tissue culture cells. We propose that Acrp30 promoter has the potential to drive strong adipocyte specific heterologous gene expression in transgenic mice.     

Organization of two genes encoding cytotoxic T lymphocyte-specific serine proteases CCPI and CCPII

The genes encoding two recently described cytotoxic T cell proteases, CCPI and CCPII, have been isolated and sequenced. The organizations of the coding and noncoding portions of the two genes are very similar to each other and also to the gene encoding rat mast cell protease type II. Similarly to other serine protease genes, each of the active-site residues is contained on a separate exon; however, two introns were found in particularly interesting positions. One occurs within the postulated activation dipeptide and the other in a position close to the active-site Asp residue. This latter intron interrupts the amino acid sequence in the invariant core region of the protein. We believe that these genes represent a new subfamily of serine protease genes.     

Chromosomal assignment in mouse of matrix Gla protein and bone Gla protein genes.

Matrix Gla protein (MGLAP) and bone Gla protein (BGLAP) are calcium-binding, vitamin K-dependent proteins produced by cells of the osteoblastic lineage. Sequence homology suggests that the genes for these proteins evolved from a common ancestor. Somatic whole cell hybrids and karyotypically simple microcell hybrids were used to map Mglap to mouse Chromosome 6 and Bglap to mouse Chromosome 3. Human MGLAP has previously been mapped to chromosome 12p, a region with homology to mouse Chromosome 6, and human BGLAP has been mapped to chromosome 1q, a region with homology to mouse Chromosome 3. It appears that BGLAP is the third calcium-binding protein that maps to human chromosome 1q and mouse Chromosome 3.     

Chromosomal location of the genes encoding complement components C5 and factor H in the mouse

Complementary DNA probes corresponding to the factor H and C5 polypeptides have been used to determine the chromosomal localizations of these two complement components. Both probes revealed complex and polymorphic arrays of DNA fragments in Southern blot analysis of mouse genomic DNA. Following the distribution of these bands in panels of somatic cell hybrids carrying various combinations of mouse chromosomes on a constant rat or Chinese hamster background allowed the localization of the C5-associated fragments to proximal chromosome 2 and the localization of the factor H-associated fragments to chromosome 1 or chromosome 3. Following the inheritance of DNA restriction fragment-length polymorphisms revealed by the probes in recombinant inbred mouse strains allowed the factor H-associated fragments to be mapped to Sas-1 on chromosome 1, and the C5-associated fragments to be mapped to Hc. Analysis of three-point crosses, in turn, placed the latter locus 19 cM distal to Sd on chromosome 2. We have designated the two loci Cfh and C5, respectively. This genetic analysis raises the possibility that C5 and factor H are both encoded by complex loci composed of distinct structural and regulatory genes.     

Chromosomal localization of uroplakin genes of cattle and mice

The asymmetric unit membrane (AUM) of the apical surface of mammalian urinary bladder epithelium contains several major integral membrane proteins, including uroplakins IA and IB (both 27 kDa), II (15 kDa), and III (47 kDa). These proteins are synthesized only in terminally differentiated bladder epithelial cells. They are encoded by separate genes and, except for uroplakins IA and IB, appear to be unrelated in their amino acid sequences. The genes encoding these uroplakins were mapped to chromosomes of cattle through their segregation in a panel of bovine x rodent somatic cell hybrids. Genes for uroplakins IA, IB, and II were mapped to bovine (BTA) Chromosomes (Chrs) 18 (UPK1A), 1 (UPK1B), and 15 (UPK2), respectively. Two bovine genomic DNA sequences reactive with a uroplakin III cDNA probe were identified and mapped to BTA 6 (UPK3A) and 5 (UPK3B). We have also mapped genes for uroplakins 1A and II in mice, to the proximal regions of mouse Chr 7 (Upk1a) and 9 (Upk2), respectively, by analyzing the inheritance of restriction fragment length variants in recombinant inbred mouse strains. These assignments are consistent with linkage relationships known to be conserved between cattle and mice. The mouse genes for uroplakins IB and III were not mapped because the mouse genomic DNA fragments reactive with each probe were invariant among the inbred strains tested. Although the stoichiometry of AUM proteins is nearly constant, the fact that the uroplakin genes are unlinked indicates that their expression must be independently regulated. Our results also suggest likely positions for two human uroplakin genes and should facilitate further analysis of their possible involvement in disease.