Genetic maps of mouse chromosome 17 including 12 new anonymous DNA loci and 25 anchor loci.

An interspecific backcross between lab mice and Mus spretus was used to construct a multilocus map of Chromosome 17 consisting of 12 new anonymous loci and 9 anchor loci. In addition, 7 anonymous DNA loci were added to the Chr 17 map for the BXD strains. Although we were able to identify readily the most likely gene order in the interspecific backcross, we found no evidence for an unambiguous gene order using the BXD recombinant inbred strains. Comparison of the interspecific backcross map and the BXD RI strain map revealed evidence in the interspecific backcross for a longer total genetic length, enhanced recombination distal to H-2, a segment showing suppressed recombination, and strong interference.     

The mouse alpha 1(XII) and human alpha 1(XII)-like collagen genes are localized on mouse chromosome 9 and human chromosome 6.

Type XII collagen is a member of the FACIT (fibril-associated collagens with interrupted triple helices) group of extracellular matrix proteins. Like the other members of this group, collagen types IX and XIV, type XII has alternating triple-helical and non-triple-helical domains. Because of its structure, its association with collagen fibrils, and its distribution in dense connective tissues, type XII is thought possibly to act as a cross-bridge between fibrils and resist shear forces caused by tension. A portion of the ffuse gene was isolated by screening a genomic library with a chicken alpha 1 (XII) cDNA probe, followed by subcloning and sequence analysis. Comparison of exon sequences with the sequence of a mouse cDNA clone allowed the mouse gene to be identified as the alpha 1 (XII) collagen gene. In the mouse, Col12a1 is located on chromosome 9, as determined by linkage analysis using DNA from interspecific backcrosses with Mus spretus. Screening of a human genomic library also allowed the isolation of a human alpha 1(XII)-like gene (CoL12A1). This gene was mapped to chromosome 6 by blot hybridization to DNA from human/hamster hybrid cell lines. This information should prove useful in determining the role of type XII collagen genes as candidate genes in inheritable connective tissue diseases.     

Position of Igl-1, md,and Bst loci on chromosome 16 of the mouse

The experiments described here delineate the position of the chromosome 16 markers Igl-1(immunoglobulin ₁ light chain), md (mahoganoid), and Bst (belly spot and tail), and suggest their location relative to the endogenous proviral locus Akv-2, which is linked within 5.9 centimorgans to Igl-1 (Epstein et al. 1984). The data from an intercross and a three-point backcross detailed herein show the order of these three genes and distances between them to be: centromere-md –10.4 ± 1.6 - Igl-1 –15.6 ± 2.6 - Bst. Using a recombinant chromosome recovered in the intercross, we have constructed a stock homozygous for md and Igl-1 ^b(KpnI^–), that will aid in mapping other genes on chromosome 16.In previous publications, alleles at the structural locus have been referred to as + and –. To conform to standard mouse nomenclature, we propose here the allele symbols a for + and b for –. We refer to genes encoding immunoglobulin molecules (i. e., v, c) in lower case letters, while the gene products are capitalized     

Comparisons of genomic structures and chromosomal locations of the mouse aldose reductase and aldose reductase-like genes.

Aldose reductase (AR), best known as the first enzyme in the polyol pathway of sugar metabolism, has been implicated in a wide variety of physiological functions and in the etiology of diabetic complications. We have determined the structures and chromosomal locations of the mouse AR gene (Aldor1) and of two genes highly homologous to Aldor1: the fibroblast growth factor regulated protein gene (Fgfrp) and the androgen regulated vas deferens protein gene (Avdp). The number of introns and their locations in the mouse Aldor1 gene are identical to those of rat and human AR genes and also to those of Fgfrp and Avdp. Mouse Aldor1 gene was found to be located near the Cald1 (Caldesmon) and Ptn (Pleiotropin) loci at the proximal end of chromosome 6. The closely related genes Fgfrp and Avdp were also mapped in this region of the chromosome, suggesting that these three genes may have arisen by a gene duplication event.     

The ADAM1a and ADAM1b genes,instead of the ADAM1 (fertilin alpha) gene,are localized on mouse chromosome 5

Fertilin is reported to be a heterodimeric protein composed of A Disintegrin And Metalloprotease 1 (ADAM1, fertilin alpha) and ADAM2 (fertilin beta) located on the sperm surface. In the process of clarifying the molecular basis of mouse ADAM1, we have identified two intron-less mouse genes encoding different isoforms of ADAM1, termed ADAM1a and ADAM1b. The amino acid sequences of ADAM1a and ADAM1b deduced from the DNA sequences were homologous to each other (99% identity) in the pro- and metalloprotease domains, whereas the C-terminal half region of ADAM1a, including the disintegrin and Cys-rich domains, shared only a low degree of identity (37%) with that of ADAM1b. These two genes were both localized on mouse chromosome 5 as a single copy gene, and were expressed specifically in the testis. These data demonstrate the presence of the ADAM1a (Adam1a) and ADAM1b (Adam1b) genes in mouse, instead of the ADAM1 gene, and may imply different roles of ADAM1a and ADAM1b in spermatogenesis, sperm maturation, and/or fertilization.     

Identification and sequencing the juvenile spermatogonial depletion critical interval on mouse chromosome 1 reveals the presence of eight candidate genes.

In mice, the recessive, non-pleiotropic, juvenile spermatogonial depletion (jsd) mutation results in a single wave of spermatogenesis, followed by failure of type A spermatogonial stem cells to differentiate, rendering adult males sterile. As part of an effort to identify the gene underlying this mutation, we report here the construction of a high-resolution genetic map involving more than 1000 meioses and 24 polymorphic loci. Our data define a critical jsd interval of approximately 0.4 cM at 49 cM on mouse chromosome 1, between D1Mit215 and 257SP6. We have constructed a physical map spanning the region comprising 24 overlapping BACs. Eighteen of these BACs have been fully sequenced, or are in draft form, allowing us to annotate approximately 2.5 Mb of DNA surrounding the jsd locus. The critical 0.4 cM jsd interval corresponds to a physical distance of approximately 1.5 Mb. Eight genes have been identified in this interval, two of which appear to be possible candidates for the jsd mutation.     

Human ubiquitin-activating enzyme (E1): compensation for heat-labile mouse E1 and its gene localization on the X chromosome.

We have constructed interspecific somatic cell hybrids between a temperature-sensitive (ts) mutant cell line of mouse FM3A cells, ts85, that has a heat-labile ubiquitin-activating enzyme (E1) and a human diploid fibroblast cell line, IMR-90. A hybrid clone that could grow stably at a nonpermissive temperature (39 degrees C) was obtained. Segregation of the hybrid cells at a permissive temperature (33 degrees C) gave rise to temperature-sensitive clones. The electrophoresis of extracted histones and karyotype analysis of the segregants revealed a close correlation of the ability to grow at 39 degrees C, the presence of uH2A (ubiquitin-H2A semihistone) at 39 degrees C, and the presence of the human X chromosome. One of the hybrid clones that could grow at the nonpermissive temperature contained the X chromosome as the only human chromosome. The sodium dodecyl sulfate-polyacrylamide gel electrophoretic pattern of affinity-purified E1 showed that this hybrid clone contained both human and mouse type E1. Thus we conclude that the functional gene for human E1 is located on the X chromosome.     

Comparative mapping of chicken anchor loci orthologous to genes on human chromosomes 1, 4 and 9

Comparative mapping of chicken and human genomes is described, primarily of regions corresponding to human chromosomes 1, 4 and 9. Segments of chicken orthologues of selected human genes were amplified from parental DNA of the East Lansing backcross reference mapping population, and the two parental alleles were sequenced. In about 80% of the genes tested, sequence polymorphism was identified between reference population parental DNAs. The polymorphism was used to design allele-specific primers with which to genotype the backcross panel and place genes on the chicken linkage map. Thirty-seven genes were mapped which confirmed the surprisingly high level of conserved synteny between orthologous chicken and human genes. In several cases the order of genes in conserved syntenic groups differs between the two genomes, suggesting that there may have been more frequent intrachromosomal inversions as compared with interchromosomal translocations during the separate evolution of avian and mammalian genomes.     

Human perforin (PRF1) maps to 10q22, a region that is syntenic with mouse chromosome 10.

Perforin (PRF1) is a cytolytic, channel-forming protein of cytolytic T cells, natural killer cells, and granulated metrial gland cells and plays a crucial role in the killer cell-mediated elimination of virally infected host cells, tumor cells, and allotransplants. Two-thirds of the perforin sequence is homologous to the lytic, channel-forming complement proteins C6, C7, C8 alpha, C8 beta, and C9. Using cosmid DNA containing the PRF1 gene as a probe for fluorescence in situ hybridization, we have reevaluated its chromosomal location. Previously assigned to chromosome 17q11-q21, it has now been mapped to 10q22. The human PRF1 locus lies within a conserved synteny segment present on mouse chromosome 10, consistent with the previous chromosomal assignment of mouse perforin. The perforin locus is not linked to any of the genes of the terminal complement system.     

Assignment of 12 loci to rat chromosome 5: evidence that this chromosome is homologous to mouse chromosome 4 and to human chromosomes 9 and 1 (1p arm)

Twelve loci have been assigned to rat chromosome 5: aldolase B (ALDOB), atrial natriuretic factor (ANF = pronatriodilatin, PND), D4RP1, DSI1, galactosyltransferase (GGTB2), glucose transporter (GLUT1), interferon alpha 1 and related interferon alpha (INFA), interferon beta (INFB), lymphocyte-specific protein-tyrosine kinase (LCK), oncogene MOS, alpha 2U-globulin (major urinary protein, MUP), and orosomucoid (ORM, also called alpha 1-acid glycoprotein, AGP). Among these, the interferon alpha and beta genes map in the q22-23 region, which also contains a transformation suppressor gene (SAI1). The other loci reside outside this region. This study also indicated that the rat genome contains 2 LCK genes, unlike the human and murine genomes. These new assignments on rat chromosome 5 demonstrate that this chromosome is highly homologous to mouse chromosome 4 and carries synteny groups conserved on human chromosome 9 (interferon alpha and beta, galactosyltransferase, orosomucoid, and aldolase B genes) and on the short arm of human chromosome 1 (MYCL, glucose transporter, protein kinase LCK, and atrial natriuretic factor genes).     

Probable assignment of the serum cholinesterase (E1) and transferrin (Tf) loci to chromosome 1 in man.

Suggestions of linkage in males between the E1 and Rh loci (Z = + 1.849; THETA = 0.20) and between the Tf and Rh loci (Z = + 0.595; THETA = 0.35) are presented. The assignment of the E1 and Tf loci to chromosome 1 and the order Tf:E1:PGD:Rh:PGM1 are cautiously proposed.     

A glutaminase (gis) gene maps to mouse chromosome 1, rat chromosome 9, and human chromosome 2

A rat cDNA clone encoding a portion of phosphate-activated glutaminase was used to identify DNA restriction fragment length polymorphisms (RFLPs) in sets of somatic cell hybrids and between wild-derived and inbred strains of mice. Segregation of rat and mouse chromosomes among somatic cell hybrids indicated assignment to rat chromosome 9 and mouse chromosome 1. Analysis of chromosome 1 alleles for several genes in an interspecific cross between Mus spretus and C3H/HeJ-gld/gld mice indicates that glutaminase can be positioned within 5.5 +/- 2.0 cM proximal to Ctla-4. Similarly, human-hamster somatic cell hybrids were examined for RFLPs, and four human EcoRI restriction fragments were found to hybridize with the rat glutaminase probe. Two of these restriction fragments cosegregated and mapped to human chromosome 2 in a region that is syntenic with mouse chromosome 1 and rat chromosome 9.     

Nucleotide sequences of mouse genomic loci including a gene or pseudogene for U6 (4.8S) nuclear RNA.

We have isolated four clones which hybridize with U6 (4.8S) nuclear RNA, a mammalian small nuclear RNA(nRNA), from DNA of BALB/C mouse liver. Their restriction maps are totally different from each other, indicating that they derived from different loci in the mouse genome. The nucleotide sequences around the hybridizing region in the three clones have been determined. One clone gives a gene that is co-linear with the U6 RNA. There is a sequence TATAAAT beginning 31 nucleotides upstream of the gene, which may suggest that the U6 RNA is transcribed by RNA polymerase II. The other two clones contain a pseudogene for the U6 RNA which has 7 or 9 nucleotide changes from the RNA. The pseudogenes are surrounded by radically different sequences from those surrounding the gene, and they are closely linked to a pseudogene for another snRNA, 4.5S-I RNA, or a part of highly repetitive an interspersed sequence B1.