A high-resolution genetic map of mouse Chromosome 15 encompassing the Dominant megacolon (Dom) locus

Dominant megacolon (Dom) is one of four mutations in the mouse that can produce a phenotype similar to Hirschsprung disease in human. The Dom gene product is not known, and no candidate region has been defined for a possible human homolog. In this publication we report mapping the Dom locus with high definition, using several intra- and interspecific crosses and a set of 16 Chr 15-specific microsatellites flanking this locus.     

A high-resolution map around the locus Om on mouse Chromosome 11

The locus Om (ovum mutant) identified in the mouse strain DDK affects the viability of (DDK |m~ non-DDK)F₁ preimplantation embryos. We previously located this locus on Chromosome (Chr) 11 close to Scya2 (Baldacci et al. Mamm. Genome 2, 100–105, 1992). Here we report a high-resolution map of the region around Om based on a large number of backcross individuals. The same region has been analyzed on the EUCIB backcross, and the two maps have been compared. The results define the proximal and distal boundaries for the Om mutation as Scya2 and D11Mit36 respectively. The distance between these two markers is about 2 cM. These data should facilitate the positional cloning and molecular characterization of Om. Received: 10 July 1995 / Accepted: 11 September 1995     

A high-resolution comparative RH map of porcine Chromosome (SSC) 2

A high-resolution comparative map was constructed for porcine Chromosome (SSC) 2, where a QTL for back fat thickness (BFT) is located. A radiation hybrid (RH) map containing 33 genes and 25 microsatellite markers was constructed for this chromosome with a 3000-rad porcine RH panel. In total, 16 genes from human Chromosome (HSA) 11p, HSA19p, and HSA5q were newly assigned to SSC2. One linkage group was observed at LOD 3.0, and five linkage groups at LOD 4.0. Comparison of the porcine RH map with homologous human gene orders identified four conserved segments between SSC2 and HSA11, HSA19, and HSA5. Concerning HSA11, a rearrangement of gene order is observed. The segment HSA11p15.4-q13 is inverted on SSC2 when compared with the distal tip of SSC2p, which is homologous to HSA11p15.5. The boundaries of the conserved segments between human and pig were defined more precisely. This high-resolution comparative map will be a valuable tool for further fine mapping of the QTL area. Received: 10 November 2000 / Accepted: 23 January 2001     

A high-resolution radiation hybrid map of the proximal region of rat Chromosome 4

Radiation hybrid (RH) mapping has been used to produce genome maps in the human and mouse, but as yet the technique has been applied little to other species. We describe the use of RH mapping in the rat, using a newly available rat/hamster RH panel, to construct an RH map of the proximal part of rat Chromosome (Chr) 4. This region is of interest because quantitative trait loci (QTLs) for defective insulin and catecholamine action, hypertension, and dyslipidemia map to this region. The RH map includes 23 rat genes or microsatellites previously mapped to this part of Chr 4, one rat gene not previously mapped in the rat, and markers for four new genes, homologs of which map to the syntenic region of the mouse genome. The RH map integrates genetic markers previously mapped on several rat crosses, increases the resolution of existing maps, and may provide a suitable basis for physical map construction and gene identification in this chromosomal region. Our results demonstrate the utility of RH mapping in the rat genome and show that RH mapping can be used to localize, in the rat genome, the homologs of genes from other species such as the mouse. This will facilitate identification of candidate genes underlying QTLs on this chromosomal segment. Received: 4 December 1998 / Accepted: 19 January 1999     

Genetic map of the region surrounding the retrovirus restriction locus,Fv1, on mouse Chromosome 4

The Friend virus susceptibility-1 (Fvl) gene maps to mouse Chromosome (Chr) 4 close to a cluster of four endogenous murine leukemia viruses (MLVs). To investigate the feasibility of cloning Fvl by a positional approach, we have performed an extensive genetic analysis of this region of Chr 4. We have typed 368 backeross mice for the four proviruses, Nppa, Lck, and D4Smh6b. Recombinant animals were screened in a hierarchical fashion with a variety of other markers, including Fvl and the isozyme marker Gpd1. A detailed genetic map of the region surrounding Fvl was derived. Three markers, Xmv9, Nppa, and Iap3rc11, were identified that showed no recombination with Fvl. By combining backcross and recombinant inbred strain data, we estimated that Xmv9 and Nppa must lie within 0.6 cM of one another and Fvl.     

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.     

A high-resolution genetic map around waltzer on mouse Chromosome 10 and identification of a new allele of waltzer

A new autosomal recessive mouse mutation characterized by deafness and circling behavior was recovered during mutagenesis experiments with chlorambucil (CHL). On the basis of allelism tests and linkage analyses, this mutation appears to represent a new allele of waltzer (v) that maps to mouse Chromosome (Chr) 10. We have designated this new allele, Albany waltzer (v ^Alb ). A high-resolution map of the region around v was constructed from data from two intersubspecific backcrosses involving Mus musculus castaneus. The analysis of 648 backcross mice has allowed v ^Alb to be localized 1.1 ± 0.4 cM distal to D10Mit60 and 0.2 ± 0.2 cM proximal to a cluster of four markers, D10Mit172, D10Mit112, D10Mit48, and D10Mit196. An independent backcross was used to confirm the map order and distances in the v ^Alb backcross. The two linkage maps were consistent, indicating that the lesion in v ^Alb , which is presumed to be a deletion based on the known action of CHL, is small and has not significantly altered the map at this level of detection. Additionally, three genes (Ros1, Grik2, and Zfa) were eliminated as possible candidates for v ^Alb , and several SSLP markers were separated genetically. Received: 3 July 1996 / Accepted: 13 August 1996     

A high-resolution single nucleotide polymorphism genetic map of the mouse genome

High-resolution genetic maps are required for mapping complex traits and for the study of recombination. We report the highest density genetic map yet created for any organism, except humans. Using more than 10,000 single nucleotide polymorphisms evenly spaced across the mouse genome, we have constructed genetic maps for both outbred and inbred mice, and separately for males and females. Recombination rates are highly correlated in outbred and inbred mice, but show relatively low correlation between males and females. Differences between male and female recombination maps and the sequence features associated with recombination are strikingly similar to those observed in humans. Genetic maps are available from http://gscan.well.ox.ac.uk/#genetic_map and as supporting information to this publication.     

A radiation hybrid map of chicken Chromosome 4

The mapping resolution of the physical map for chicken Chromosome 4 (GGA4) was improved by a combination of radiation hybrid (RH) mapping and bacterial artificial chromosome (BAC) mapping. The ChickRH6 hybrid panel was used to construct an RH map of GGA4. Eleven microsatellites known to be located on GGA4 were included as anchors to the genetic linkage map for this chromosome. Based on the known conserved synteny between GGA4 and human Chromosomes 4 and X, sequences were identified for the orthologous chicken genes from these human chromosomes by BLAST analysis. These sequences were subsequently used for the development of STS markers to be typed on the RH panel. Using a logarithm of the odds (LOD) threshold of 5.0, nine linkage groups could be constructed which were aligned with the genetic linkage map of this chromosome. The resulting RH map consisted of the 11 microsatellite markers and 50 genes. To further increase the number of genes on the map and to provide additional anchor points for the physical BAC map of this chromosome, BAC clones were identified for 22 microsatellites and 99 genes. The combined RH and BAC mapping approach resulted in the mapping of 61 genes on GGA4 increasing the resolution of the chicken–human comparative map for this chromosome. This enhanced comparative mapping resolution enabled the identification of multiple rearrangements between GGA4 and human Chromosomes 4q and Xp.     

The genetic map around the tail kinks (tk) locus on mouse Chromosome 9

Tail kinks (tk) is a classical mouse skeletal mutation, located on Chromosome (Chr) 9. As the first step for the positional cloning of the tk gene, we have established a genetic map of a region surrounding the tk locus by generating a backcross segregating for tk. From this backcross, 1004 progeny were analyzed for the coat-color phenotype of the proximally located dilute (d) gene and for the distally flanking microsatellite marker, D9Mit12. Fifty-six recombinants between d and tk and 75 recombinants between tk and D9Mit12 were identified, completing a panel of 130 recombinants including one double recombinant. This panel allowed us to map five microsatellite loci as well as d and Mod-1 with respect to tk. We show that one of the microsatellite markers mapped, D9Mit9, does not recombine at all with tk in our backcross. This indicates that the D9Mit9 locus will serve as a good starting point for a chromosomal walk to the tk gene.     

A radiation hybrid map of bovine X Chromosome (BTAX)

We present a comprehensive radiation hybrid map of the bovine X chromosome (Chr) containing 20 new markers, including both microsatellites and expressed genes. This study was conducted with a 5000-rad whole genome RH cell panel consisting of 90 hybrid cell lines. Retention frequencies of individual markers range from 7.8% for XIST to 31.1% for TGLA325. Statistical analysis with RHMAPPER placed all the loci into five linkage groups under a LOD score criterion of 6.0. These groups could be oriented relative to each other because they included multiple microsatellite loci from the consensus linkage map of the X Chr. Markers included in both this RH map and the bovine cytogenetic map were in a consistent order. The comparative bovine–human map thus generated consists of five blocks of genes, the order of which is conserved, although in the opposite direction when presented as ideograms with p and q arms. Inversions of three blocks account for the difference in gene order across the entirety of the two X Chrs.