The Genes for Mouse Salivary Androgen-Binding Protein (Abp) Subunits Alpha and Gamma Are Located on Chromosome 7

We demonstrate that the previously described gene Androgen binding protein (Abp; Dlouhy and Karn, 1984) codes for the Alpha subunit of ABP and rename the locus Androgen binding protein alpha (Abpa). A study of recombinant inbred strains demonstrates that Abpa is located on chromosome 7 near Glucose phosphate isomerase-1 (Gpi-1). Biochemical and genetic evidence indicates the existence of another ABP subunit, Gamma, and its locus, Androgen binding protein gamma (Abpg), that is closely linked to Abpa. Although no polymorphism has yet been found for the previously described Beta subunit of ABP (Dlouhy and Karn, 1983; 1984), we suggest that it represents a third locus. Androgen binding protein beta (Abpb). ABP subunits appear to dimerize randomly and a model is presented demonstrating the origin of six ABP dimers in the salivas of AbpaaAbpga/AbpabAbpgb heterozygous mice. The results of cell-free translation studies in which the pre-ABP subunits are identified specifically by immunoprecipitation with anti-ABP antibody supports the idea that independent mRNAs code for the Alpha, Beta and Gamma subunits.     

Genes Responsible for Size Reduction of Marine Vibrios during Starvation Are Located on the Chromosome

In a survey of 21 marine Vibrio spp., all responded to nutrient deprivation by undergoing a reduction in size (dwarfing). However, only 43% of these strains possessed one or more plasmids, suggesting that the genes responsible for dwarfing were located on the chromosome rather than on the plasmids. This conclusion was confirmed by the observation that fragmentation and subsequent size reduction occurred in three strains from which the plasmids had been removed by curing. The cured strains lost certain characteristics, such as resistance to some heavy metals and antibiotics, that were restored when the plasmids were reintroduced by either transformation or electroporation.     

Mapping of theKHSRPGene to a Region of Conserved Synteny on Human Chromosome 19p13.3 and Mouse Chromosome 17

The K homology-type splicing regulatory protein, KSRP, activates splicing through intronic splicing enhancer sequences. It is highly expressed in neural cells and is required for the neural-specific splicing of the c-src N1 exon. In this study, we mapped the gene (gene symbolsKHSRPandKhsrp) to human chromosome 19 by using radiation hybrid panels and to mouse chromosome 17 by studying an interspecific backcross panel. HumanKHSRPis a positional candidate gene for familial febrile convulsion and Cayman type cerebellar ataxia. Comparative analysis of the human and mouse genomes indicates that theKHSRPgene is located in regions of conserved synteny between the two species.     

Rearrangement of Genes Located on Homologous Chromosomal Segments in Mouse and Man: The Location of Genes for Alpha-and Beta-Interferon, Alpha-1 Acid Glycoprotein-1 and -2, and Aminolevulinate Dehydratase on Mouse Chromosome 4

Gene mapping studies to determine the order of alpha- and beta-interferon (Ifa, Ifb), aminolevulinate dehydratase (Lv), and alpha-1 acid glycoprotein-1 and -2 (Orm-1, Orm-2) relative to each other and to the reference genes brown (b), B-cell maturation factor responsiveness (Bmfr-1), and major urinary protein-1 (Mup-1) are reported. The most likely order was Mup-1--Lv--b--Orm-1, Orm-2--Ifa, Ifb--Bmfr-1. This order suggested that two chromosomal segments located on chromosome 4 in the mouse and chromosome 9 in man have been conserved since divergence of lineages leading to man and mouse; these segments are marked by soluble aconitase-1 (Aco-1) and galactose-1 phosphate uridyl transferase (Galt) and by Lv and Orm-1. This order also demonstrated that, although genes located on opposite arms of chromosome 9 in man remain syntenic in the mouse, gene order has not been conserved; Ifa and Ifb are not located in their expected locations near Aco-1 and Galt. The position of Ifa and Ifb between Orm-1 and Bmfr-1 could not be determined with certainty because of apparent heterogeneity in recombination frequencies between crosses involving conventional laboratory strains of mice and crosses involving interspecific matings between laboratory mice and Mus spretus. This result suggests that caution must be exercised when using M. spretus in linkage crosses.     

Isolation of the Mouse Homologue of BRCA1 and Genetic Mapping to Mouse Chromosome 11

The BRCA1 gene is in large part responsible for hereditary human breast and ovarian cancer. Here we report the isolation of the murineBrca1homologue cDNA clones. In addition, we identified genomic P1 clones that contain most, if not all, of the mouseBrca1locus. DNA sequence analysis revealed that the mouse and human coding regions are 75% identical at the nucleotide level while the predicted amino acid identity is only 58%. A DNA sequence variant in theBrca1locus was identified and used to map this gene on a (Mus m. musculusCzech II × C57BL/KsJ)F1 × C57BL/KsJ intersubspecific backcross to distal mouse chromosome 11. The mapping of this gene to a region highly syntenic with human chromosome 17, coupled with Southern and Northern analyses, confirms that we isolated the murineBrca1homologue rather than a related RING finger gene. The isolation of the mouseBrca1homologue will facilitate the creation of mouse models for germline BRCA1 defects.     

Touch-Inducible Genes for Calmodulin and a Calmodulin-Related Protein Are Located in Tandem on a Chromosome of Arabidopsis thaliana

Genes for calmodulin and calmodulin-related proteins in Arabidopsisare up-regulated by a variety of physical stimuli, which includerain, wind and touch [Braam and Davis (1990) Cell 60: 357].We have isolated five genes for calmodulin (AtCALl, 2, 3, 5,6) and one gene for a calmodulin-related protein (AtCAL4) froman Arabidopsis genomic library. Touch stimulus of Arabidopsisplants induces the accumulation of mRNA transcribed from AtCAL4andAtCAL5, but not from the other isolated genes. The two touch-induciblegenes are arrayed in tandem with a short intergenic region of700 bp but they show different organ-specific patterns of expression. (Received April 27, 1995; Accepted July 20, 1995)     

Isolation and Characterization of Conditional Alleles of Bacteriophage T4 Genes uvsX and uvsY

The bacteriophage T4 uvsW, uvsX and uvsY gene functions are required for wild-type levels of recombination and for normal survival and mutagenesis after treatments with ultraviolet (UV) and ionizing radiations. The ability of uvsX and uvsY mutations to suppress the lethality of gene 49 mutations was used to select temperature-sensitive and amber alleles of these two genes. (uvsW mutations do not suppress gene 49 mutations.) A simple and powerful complementation test was developed to assist in assigning uvs mutations to genes. The amber alleles of uvsX and uvsY behave as simple null alleles, fully suppressing a gene 49 defect, enhancing UV killing and abolishing UV mutagenesis. However, the properties of the ts alleles of uvsX and uvsY demonstrated that suppression of a gene 49 defect, sensitivity to UV-induced inactivation and UV mutability can be partially uncoupled. These results prompt the hypothesis that radiation mutagenesis occurs during DNA chain elongation past template damage within a recombinational intermediate rather than within a conventional replication fork.     

人体基因组随机单拷贝顺序的分离及其在染色体上的定位

本文从构建杂种细胞14-7-1的基因组文库出发,用种特异的探针分离出含有人体基因组顺序的重组子,并进一步分析了其中13个克隆,得到8个单拷贝顺序。通过与已建立的杂种细胞克隆分布板杂交以及染色体的原位杂交方法,将1个单拷贝顺序FD11-1定位在11p11-q11上。由于已经报道在11号染色体上具有3个连锁群,它们分别位于11p15、11p13和11q13上,因此,FD11-1有可能为11号染色体连锁基因图的建立提供1个有意义的座位。     

P-Element Insertion Alleles of Essential Genes on the Third Chromosome of Drosophila Melanogaster: Correlation of Physical and Cytogenetic Maps in Chromosomal Region 86e-87f

We have established a collection of 2460 lethal or semi-lethal mutant lines using a procedure thought to insert single P elements into vital genes on the third chromosome of Drosophila melanogaster. More than 1200 randomly selected lines were examined by in situ hybridization and 90% found to contain single insertions at sites that mark 89% of all lettered subdivisions of the Bridges' map. A set of chromosomal deficiencies that collectively uncover ~25% of the euchromatin of chromosome 3 reveal lethal mutations in 468 lines corresponding to 145 complementation groups. We undertook a detailed analysis of the cytogenetic interval 86E-87F and identified 87 P-element-induced mutations falling into 38 complementation groups, 16 of which correspond to previously known genes. Twenty-one of these 38 complementation groups have at least one allele that has a P-element insertion at a position consistent with the cytogenetics of the locus. We have rescued P elements and flanking chromosomal sequences from the 86E-87F region in 35 lines with either lethal or genetically silent P insertions, and used these as probes to identify cosmids and P1 clones from the Drosophila genome projects. This has tied together the physical and genetic maps and has linked 44 previously identified cosmid contigs into seven ``supercontigs' that span the interval. STS data for sequences flanking one side of the P-element insertions in 49 lines has identified insertions in the αγ element at 87C, two known transposable elements, and the open reading frames of seven putative single copy genes. These correspond to five known genes in this interval, and two genes identified by the homology of their predicted products to known proteins from other organisms.     

Essential Genes in the Hdf6 Region of Chromosome I in Caenorhabditis Elegans

In this paper we describe the analysis of essential genes in the hDf6 region of chromosome I of Caenorhabditis elegans. Nineteen complementation groups have been identified which are required for the growth, survival or fertility of the organism (essential genes). Since ten of these genes were represented by more than one allele, a Poisson calculation predicts a minimum estimate of 25 essential genes in hDf6. The most mutable gene in this region was let-354 with seventeen alleles. An average mutation rate of 5 x 10(-5) mutations/gene/chromosome screened was calculated for an ethyl methanesulfonate dose of 15 mM. Mutations were recovered by screening for lethal mutations using the duplication sDp2 for recovery. Our analysis shows that duplications are very effective for maintenance and mapping of large numbers of lethal mutations. Approximately 600 lethal mutations were mapped in order to identify the 54 that are in the deficiency hDf6. The hDf6 region appears to have a lower proportion of early arresting mutations than other comparably sized regions of the genome.     

Conserved Linkage within a 4-Cm Region of Mouse Chromosome 9 and Human Chromosome 11

A six-point cross was carried out to determine the gene order and distances among loci on mouse chromosome 9. Our results are consistent with the following arrangement: centromere – Lap-1 – (1.2 ± 0.8) – Es-17 – (3.0 ± 1.0) – Ups – (1.3 ± 0.7) – Alp-1 – (23.1 ± 3.4) – Mod-1 – (10.9 ± 2.6) – Acy-1 . This study provides the first estimate of the distances between Es-17, Ups and Alp-1. Exceptions to the preferred association of alleles of Es-17 and Ups have been found in three feral populations and one inbred strain. Evidence is presented for the homology of this chromosome region with the ESA4 – UPS – APO-AI region on the long arm of human chromosome 11.     

The Polar-Lethal Ovum Mutant Gene Maps to the Distal Portion of Mouse Chromosome 11

Genome imprinting is the process by which identical alleles at a particular locus may be rendered functionally different depending on the sex of the parent contributing the allele. While several mutations in imprinted genes have been defined, no variants in the regulatory system that gives rise to imprinting have been described. Here we report our genetic analysis of the behavior of the interstrain, polar, embryonic-lethal phenotype known as the "DDK syndrome." We have mapped the interstrain, polar-lethal region of the genome to the distal portion of mouse chromosome 11, near the Xmv-42 locus. We propose that the lethal phenotype is not caused by a standard mutation, but by aberrant imprinting of a gene within this region.     

Normal Testis Determination in the Mouse Depends on Genetic Interaction of a Locus on Chromosome 17 and the Y Chromosome

We previously described a locus on chromosome (Chr) 17 of the mouse that is critical for normal testis development. This locus was designated "T-associated sex reversal" (Tas) because it segregated with the dominant brachyury allele hairpin tail (Thp) and caused gonads of C57BL/6J XY, Thp/+ individuals to develop as ovaries or ovotestes rather than as testes. To clarify the inheritance of Tas, we investigated the effects of T-Orleans (TOrl), another brachyury mutation, on gonad development. We found that gonads of C57BL/6J XY, Thp/+ and TOrl/+ mice develop ovarian tissue if the Y chromosome is derived from the AKR/J inbred strain, whereas normal testicular development occurs in the presence of a Y chromosome derived from the C57BL/6J inbred strain. From these observations we conclude that: (1) Tas is located in a region on Chr 17 common to the deletions associated with Thp, and TOrl, and (2) the Y-linked testis determining gene, Tdy, carried by the AKR/J inbred strain differs from that of the C57BL/6J inbred strain. We suggest that in mammals Tdy is not the sole testis determinant because autosomal loci must be genetically compatible with Tdy for normal testicular development.     

Genetic Analysis of Mouse T Haplotypes Using Mutations Induced by Ethylnitrosourea Mutagenesis: The Order of T and Qk Is Inverted in T Mutants

The t region of mouse chromosome 17 exhibits recombination suppression with wild-type chromatin. However, the region has resisted classical genetic dissection because of a lack of defined variants. Mutations induced by N-ethyl-N-nitrosourea (ENU) at the Brachyury (T), quaking (qk), and tufted (tf) loci of the mouse tw5 haplotype have now allowed the analysis of crossovers between two complete t haplotypes. A classical breeding analysis of the complete t haplotypes, tw5 and t12, utilizing the newly induced markers, reveals two inversions in t chromatin: one involving T and qk, and one involving tf and the H-2 complex. Moreover, the recombination frequency between the loci of T and qk is reduced compared to the frequency reported in normal chromatin. These two inversions are a sufficient explanation for the recombination inhibition with normal chromatin exhibited by t haplotypes isolated from the wild. Furthermore, the reduced recombination frequency between T and qk may indicate that the proximal gene rearrangement is not a simple inversion.     

Isolation and Sequencing of a Genomic Clone for Mouse Brain Specific Small RNA

We isolated a mouse genomic clone that hybridized with small RNA present in the cytoplasm of the brain. The RNA was about 150 nucleotides long. This RNA seemed to be specific to the brain, since it was not found in the liver or kidney. The clone DNA contained a sequence homologous to 82-nucleotide "identifier" core sequence of cDNA clones of rat. The sequence contained a split promoter for RNA polymerase III and was flanked by a 12-nucleotide direct repeat (ATAAATAATTTA).     

A Cluster of Keratin-Associated Proteins on Mouse Chromosome 10 in the Region of Conserved Linkage with Human Chromosome 21

A gene cluster of three to five high-cysteine keratin-associated proteins (KAPs) has been identified on mouse Chromosome 10 (MMU10) in the region of conserved linkage with human chromosome 21 (HSA21). One of these genes,Krtap12-1,has been sequenced in its entirety and shown to be an intronless gene encoding a predicted 130-amino-acid protein.Krtap12-1is most closely related to two previously identified KAP4 genes, but variation in sequence and cysteine content suggests that it represents a new KAP family.Krtap12-1is expressed in the skin of a 3-day-old mouse. The corresponding region of HSA21, betweenITGB2(integrin β2) andPFKL(the liver isoform of phosphofructokinase), has proven refractory to cloning, and thus mapping of this region at high resolution has been problematic. Based on the KAP gene cluster position in mouse, evidence has been found for an orthologous human KAP cluster on HSA21q22.3, reinforcing the observation that comparative genomics can play an essential and practical role in determining mammalian genome organization.     

Genomic Structure and Precise Mapping of a Thymic Regulatory Region on Mouse Chromosome 17 Revealed by a c-mycTransgene Insertion

In one transgenic strain harboring a human c-mycproto-oncogene construct, the transgene was actively and exclusively expressed in the thymus, where it contributed to the development of lymphoma that corresponded to CD4⁺CD8⁺cells. Here, we have pursued the analysis of transgene expression in healthy transgenic mice and show that transgene activation occurs in the thymus 3 days before birth, at a time when CD4⁺CD8⁺lymphocytes emerge. In the adult, its expression is restricted to the CD4⁺CD8⁺cells. The region flanking the transgene insertion site was isolated and made it possible to map the preintegration locus, hereafter calledTsil(for thymus-specific integration locus) on chromosome 17 betweenD17Rp11eandRas12-3.A YAC that contains bothTsiland thePim2locus, previously shown to be involved in progression of T-cell lymphoma, was isolated. Analysis ofTsiloffers a unique opportunity to identify a regulatory region or a gene that might play an important role in T-cell maturation.