Assignment of the rat genes coding for DOPA decarboxylase (DDC) and glutamic acid decarboxylases (GAD1 and GAD2)

By use of rat cDNA probes and a panel of cell hybrids segregating rat chromosomes, the genes encoding three pyridoxal 5-phosphate (PLP)-dependent decarboxylases—namely, DOPA-decarboxylase (Ddc), glutamic acid decarboxylase 1 and 2 (Gad1 and Gad2)—were assigned to rat Chromosomes (Chrs) 14, 3, and 17, respectively. If one takes into account chromosome localizations in the human and the mouse, the present results (i) show that a synteny group is retained on rat Chr 14, human Chr 7, and mouse Chr 11 (Ddc); (ii) strengthen the homology relation known between rat Chr 3 and human and mouse Chrs 2 (Gad1); (iii) suggest that rat Chr 17 has no extensive homology to any human chromosome; and (iv) suggest the order (Prl, Fdp)-Tpl2-Gad2 on the rat Chr 17.     

Assignment of rat Jun family genes to Chromosome 19 (Junb), Chromosome 5q31–33 (Jun), and Chromosome 16 (Jund)

By means of somatic cell hybrids segregating rat chromosomes, we determined the chromosome localization of three rat genes of the Jun family: Jumb (Chr 19), Jun (=c-Jun) (Chr 5) and Jund (Chr 16). The Jun gene was also localized to the 5q31–33 region by fluorescence in situ hybridization. These rat gene assignments reveal two new homologies with mouse and human chromosomes, and provide a new example of synteny conserved in the human and a rodent species (the mouse), but split between the two rodent species.     

Mapping of the calcium-sensing receptor gene (CASR) to human Chromosome 3q13.3-21 by fluorescence in situ hybridization,and localization to rat Chromosome 11 and mouse Chromosome 16

The calcium-sensing receptor (CASR), a member of the G-protein coupled receptor family, is expressed in both parathyroid and kidney, and aids these organs in sensing extracellular calcium levels. Inactivating mutations in the CASR gene have been described in familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT). Activating mutations in the CASR gene have been described in autosomal dominant hypoparathyroidism and familial hypocalcemia. The human CASR gene was mapped to Chromosome (Chr) 3q13.3-21 by fluorescence in situ hybridization (FISH). By somatic cell hybrid analysis, the gene was localized to human Chr 3 (hybridization to other chromosomes was not observed) and rat Chr 11. By interspecific backcross analysis, the Casr gene segregated with D16Mit4 on mouse Chr 16. These findings extend our knowledge of the synteny conservation of human Chr 3, rat Chr 11, and mouse Chr 16.     

Mapping of the structural gene for S-adenosyl homocysteine hydrolase to mouse Chromosome 2, and related sequences to Chromosomes 8 and X

Comparative mapping studies in human and mouse have shown that, to date, human Chromosome (Chr) 20 is completely syntenic with distal mouse Chr 2. The structural locus for S-adenosyl-l-homocysteine hydrolase (EC 3.3.1.1) in human, AHCY, maps to 20 qterq13.1, and we report here that the homologous locus in the mouse, Ahcy, maps to distal mouse Chr 2 with gene order Pcna-Ahcy-Ada. Analysis of 123 progeny of an interspecific backcross between a laboratory stock, AN, and Mus spretus using a rat cDNA probe revealed the presence of at least two other Ahcy-related sequences segregating independently in the mouse genome. One, Ahcy-rs1, was mapped to Chr 8 in the BXH recombinant inbred strains, and the other, Ahcy-rs2, shows a pattern of inheritance consistent with X-linkage.     

A rat mutation producing demyelination (dmy) maps to chromosome 17

A recessive mutation exhibiting severe myelin breakdown, mainly at the level of the lumbar segments of the spinal cord and without any associated inflammation, was discovered in a partially inbred rat colony. Analysis of the segregation patterns of a set of polymorphic microsatellite markers in two inter-strain crosses allowed the mapping of this autosomal recessive mutation to rat Chromosome (Chr) 17, very close to the prolactin (Prl) locus, in a region homologous to human Chr 6p21.2-22.3 and mouse Chr 13. The pathology of the demyelination process and the chromosomal localization indicate that this mutation has no known equivalent in either mouse or human. Received: 21 March 1996 / Accepted: 22 July 1996     

Synteny conservation of the Huntington's disease gene and surrounding loci on mouse Chromosome 5

The mouse homologs of the Huntington's disease (HD) gene and 17 other human Chromosome (Chr) 4 loci (including six previously unmapped) were localized by use of an interspecific cross. All loci mapped in a continuous linkage group on mouse Chr 5, distal to En2 and Il6, whose human counterparts are located on Chr y. The relative order of the loci on human Chr 4 and mouse Chr 5 was maintained, except for a break between D5H4S115E and Idua/rd, with relocation of the latter to the opposite end of the map. The mouse HD homolog (Hdh) mapped within a cluster of seven genes that were completely linked in our data set. In human these loci span a1.8 Mb stretch of human 4p 16.3 that has been entirely cloned. To date, there is no phenotypic correspondence between human and mouse mutations mapping to this region of synteny conservation.     

Linkage of Agt and Actsk-1 to distal mouse Chromosome 8 loci: a new conserved linkage

Angiotensinogen is an ₂ involved in the maintenance of blood pressure and electrolyte balance. We have refined the position of the mouse angiotensinogen locus (Agt) on Chromosome (Chr) 8 and have also confirmed the assignment of the human angiotensinogen locus (AGT) to Chr 1. The segregation of several restriction fragment length variants (RFLVs) was followed in two interspecific backcross sets and in four recombinant inbred (RI) mouse sets. Analysis of the segregation patterns closely linked Agt to Aprt and Emv-2, which places the angiotensionogen locus on the distal end of mouse Chr 8. Additionally, a literature search has revealed that the strain distribution pattern (SDP) for the mouse skeletal -actin locus 1 (Actsk-1, previously Actal, Acta, or Acts) is nearly identical to the SDP for Agt in two RI sets. On the basis of this information we were able to reassign Actsk-1 to mouse Chr 8. By screening a panel of human-mouse somatic cell hybrids, we confirmed that the human angiotensioogen locus lies on Chr 1. This information describes a new region of conserved linkage homology between mouse Chr 8 and human Chr 1. It also defines the end of a large region of conserved linkage homology between mouse Chr 8 and human Chr 16.     

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.     

Sequence-ready physical map of the mouse Chromosome 16 region with conserved synteny to the human Velocardiofacial syndrome region on 22q11.2

Proximal mouse Chromosome (Chr) 16 shows conserved synteny with human Chrs 16, 8, 22, and 3. The mouse Chr 16/human Chr 22 conserved synteny region includes the DiGeorge/Velocardiofacial syndrome region of human Chr 22q11.2. A physical map of the entire mouse Chr 16/human Chr 22 region of conserved synteny has been constructed to provide a substrate for gene discovery, genomic sequencing, and animal model development. A YAC contig was constructed that extends ca. 5.4 Mb from a region of conserved synteny with human Chr 8 at Prkdc through the region conserved with human Chr 3 at DVL3. Sixty-one markers including 37 genes are mapped with average marker spacing of 90 kb. Physical distance was determined across the 2.6-Mb region from D16Mit74 to Hira with YAC fragmentation. The central region from D16Jhu28 to Igl-C1 was converted into BAC and PAC clones, further refining the physical map and providing sequence-ready template. The gene content and borders of three blocks of conserved linkage between human Chr 22q11.2 mouse Chr 16 are refined. Received: 4 November 1998 / Accepted: 21 December 1998     

Re-localization of Actsk-1 to mouse Chromosome 8, a new region of homology with human Chromosome 1

We present here the genetic mapping of the -skeletal actin locus (Actsk-1) on mouse Chromosome (Chr) 8, on the basis of the PCR analysis of a microsatellite in an interspecific backcross. Linkage and genetic distances were established for four loci by analysis of 192 (or 222) meiotic events and indicated the following gene order: (centromere)-Es-1-11.7 cM-Tat-8.3 cM-Actsk-1-0.5 cM-Aprt. Mapping of ACTSK to human Chr 1 and of TAT and APRT to human Chr 16 demonstrates the existence of a new short region of homology between mouse Chr 8 and human Chr 1. Intermingling on this scale between human and mouse chromosomal homologies that occurred during evolution creates disorders in comparative linkage studies.     

A genetic,physical, and comparative map of rat chromosome 10

A map of rat Chromosome (Chr) 10 was generated from 21 markers, mostly of conserved structural genes, by linkage analysis and fluorescence in situ hybridization. The study emphasizes the proximal third of the chromosome which, until now, has been relatively devoid of markers. Based on comparative analysis, our data suggest that genes on rat Chr 10 are conserved on mouse Chr 11, 16, 17 and human Chr 16, 5, and 17. Received: 22 November 1995 / Accepted: 29 January 1996     

Identification of a new quantitative trait locus on Chromosome 7 controlling disease severity of collagen-induced arthritis in rats

 Autoimmune diseases, such as rheumatoid arthritis, Crohn's disease, and multiple sclerosis, are regulated by multiple genes. Major histocompatibility complex (MHC) genes have the strongest effects, but non-MHC genes also contribute to disease susceptibility/severity. In this paper, we describe a new non-MHC quantitative trait locus, Cia8, on rat Chromosome (Chr) 7 that controls collagen-induced arthritis severity in F2 progeny of DA and F344 inbred rats, and present an updated localization of Cia4 on the same chromosome. We also describe the location of mouse and human genes, orthologous to the genes in the genomic intervals containing Cia4 and Cia8, and provide evidence that the segment of rat Chr 7 containing Cia4 and Cia8 is homologous to segments of mouse Chr 10 and 15 and human Chr 8, 12, and 19. Received: 1 November 1998 / Revised: 24 January 1999     

Assignment of three rat integrin genes to Chromosome 19 (ITGB1), Chromosome 3 (ITGA4), and Chromosome 7 (ITGA5)

By means of somatic cell, hybrids segregating rat chromosomes, we determined the chromosome localization of three rat 1 family integrin genes. ITGB1 was assigned to Chromosome (Chr) 19, ITGA4 to Chr 3, and ITGA5 to Chr 7. These chromosome assignments reveal or confirm homology between two pairs of rat and human chromosomes (rat Chr 3-human Chr 2; rat Chr 7-human Chr 12).     

Comparative sequence analysis of a single-gene conserved segment in mouse and human

Comparative mapping and sequencing of the mouse and human genomes have defined large, conserved chromosomal segments in which gene content and order are highly conserved. These regions span megabase-sized intervals and together comprise the vast majority of both genomes. However, the evolutionary relationships among the small remaining portions of these genomes are not as well characterized. Here we describe the sequencing and annotation of a 341-kb region of mouse Chr 2 containing nine genes, including biliverdin reductase A (Blvra), and its comparison with the orthologous regions of the human and rat genomes. These analyses reveal that the known conserved synteny between mouse Chromosome (Chr) 2 and human Chr 7 reflects an interval containing one gene (Blvra/BLVRA) that is, at most, just 34 kb in the mouse genome. In the mouse, this segment is flanked proximally by genes orthologous to human chromosome 15q21 and distally by genes orthologous to human Chr 2q11. The observed differences between the human and mouse genomes likely resulted from one or more rearrangements in the rodent lineage. In addition to the resulting changes in gene order and location, these rearrangements also appear to have included genomic deletions that led to the loss of at least one gene in the rodent lineage. Finally, we also have identified a recent mouse-specific segmental duplication. These finding illustrate that small genomic regions outside the large mouse–human conserved segments can contain a single gene as well as sequences that are apparently unique to one genome. The nucleotide sequence data reported in this paper have been submitted to GenBank and assigned the accession numbers AC074224 and AC074041.     

Rat Chromosome 1: Regional localization of seven genes (Slc9a3, Srd5a1, Esr, Tcp1, Grik5, Tnnt3, Jak2) and anchoring of the genetic linkage map to the cytogenetic map

Seven genes were regionally localized on rat Chromosome (Chr) 1, from 1p11 to 1q42, and two of these genes were also included in a linkage map. This mapping work integrates the genetic linkage map and the cytogenetic map, and allows us to orient the linkage map with respect to the centromere, and to deduce the approximate position of the centromere in the linkage map. These mapping data also indicate that the Slc9a3 gene, encoding the Na⁺/H⁺ exchanger 3, is an unlikely candidate for the blood pressure loci assigned to rat Chr 1. These new localizations expand comparative mapping between rat Chr 1 and mouse or human chromosomes. Received: 21 March 1997 / Accepted: 3 May 1997     

Map of seven polymorphic markers on rat Chromosome 14: linkage conservation with human Chromosome 4

Seven polymorphic markers identified by polymerase chain reaction (PCR) amplification, including markers for six genes—DRD1L (dopamine receptor, D1-like-2), GLUKA (glucokinase), PF4 (platelet factor 4), ALB (albumin), AFP (-fetoprotein), and BSP (bone sialoprotein)—and one anonymous locus (D14N52), were mapped to a single 67-cM linkage group with F₂ intercross progeny of F344/N and LEW/N inbred rat strains. Two of these markers, ALB and AFP, have previously been assigned to rat Chromosome (Chr) 14, allowing assignment of this entire linkage group. Five of the markers—DRD1L, PF4, ALB, AFP, and PBSP—have been physically mapped to a large region of human Chr 4 encompassing the p arm and the q arm to band q28. Homologs of two of the markers, ALB and AFP, have been mapped to Chr 5 in the mouse. Comparison of human Chr 4 with the homologous regions on Chr 14 of the rat and Chr 5 of the mouse indicated that linkage conservation with human Chr 4 extends over a greater region in the rat than in the mouse. The markers described here were found to be highly polymorphic in twelve inbred strains (F344/N, LEW/N, ACI/N, BUF/N, BN/SsN, LOU/MN, MNR/N, MR/N, SHR/N, WBB1/N, WBB2/N, and WKY/N). These polymorphic markers should be useful in genetic linkage studies of important phenotypes in rats.     

Improved linkage map and thirty new microsatellite markers for rat Chromosome 10

An improved linkage map for rat Chromosome (Chr) 10 with two F₂ populations was constructed. Thirty new microsatellite markers were generated from a Chr 10-specific, small-insert genomic library and mapped to rat Chr 10. Among them were the rat homologs for the mouse gene for light and heavy chains of myeloperoxidase and human neurofibromatosis 1. Eight newly generated markers (D10Mco62, D10Mco63, D10Mco64, D10Mco65, D10Mco67, D10Mco68, D10Mco70, and D10Mco74) were mapped to the region of the rat Chr 10 blood pressure QTL. The availability of such markers may be instrumental in the search for genes responsible for the hypertension. Received: 13 July 1998 / Accepted: 9 September 1998     

A genetic linkage map of rat Chromosome 5 reveals extensive linkage conservation with mouse Chromosome 4

Linkages among three biochemical loci (Acol, Ahd2, and Mup1) and four microsatellite loci (A8, Glut1, Jun, and Pnd) were determined to construct a linkage map of rat Chromosome (Chr) 5. Consequently, an extensive linkage map on rat Chr 5 was constructed with the following gene order: A8-Aco1-Mup1-Jun-Glut1-Ahd2-Pnd. In this linkage map, the Jun and A8 loci are newly placed, and two previously reported linkage groups on rat Chr 5 are connected by the Jun locus. The linkage map indicates an extensive linkage conservation between the loci on rat Chr 5 and those on mouse Chr 4.     

Genetic mapping of the human and mouse phospholipase C genes

To determine chromosome positions for 10 mouse phospholipase C (PLC) genes, we typed the progeny of two sets of genetic crosses for inheritance of restriction enzyme polymorphisms of each PLC. Four mouse chromosomes, Chr 1, 11, 12, and 19, contained single PLC genes. Four PLC loci, Plcb1, Plcb2, Plcb4, and Plcg1, mapped to three sites on distal mouse Chr 2. Two PLC genes, Plcd1 and Plcg2, mapped to distinct sites on Chr 8. We mapped the human homologs of eight of these genes to six chromosomes by analysis of human × rodent somatic cell hybrids. The map locations of seven of these genes were consistent with previously defined regions of conserved synteny; Plcd1 defines a new region of homology between human Chr 3 and mouse Chr 8. Received: 24 January 1996 / Accepted: 2 April 1996