The tau mutation is a semidominant autosomal allele that dramatically shortens period length of circadian rhythms in Syrian hamsters. We report the molecular identification of the tau locus using genetically directed representational difference analysis to define a region of conserved synteny in hamsters with both the mouse and human genomes. The tau locus is encoded by casein kinase I epsilon (CKIɛ), a homolog of the Drosophila circadian gene double-time . In vitro expression and functional studies of wild-type and tau mutant CKIɛ enzyme reveal that the mutant enzyme has a markedly reduced maximal velocity and autophosphorylation state. In addition, in vitro CKIɛ can interact with mammalian PERIOD proteins, and the mutant enzyme is deficient in its ability to phosphorylate PERIOD. We conclude that tau is an allele of hamster CKIɛ and propose a mechanism by which the mutation leads to the observed aberrant circadian phenotype in mutant animals.

/pdf/positional-syntenic-cloning-and-functional-characterization-4h4a5jqkj8.pdf

Positional Syntenic Cloning and Functional Characterization of the Mammalian Circadian Mutation tau

Genome-wide analysis techniques such as chromosome painting, comparative genomic hybridization, representational difference analysis, restriction landmark genome scanning and high-throughput analysis of LOH are now accelerating high-resolution genome aberration localization in human tumors. These techniques are complemented by procedures for detection of differentially expressed genes such as differential display, nucleic acid subtraction, serial analysis of gene expression and expression microarray analysis. These efforts are enabled by work from the human genome program in physical map development, cDNA library production/sequencing and in genome sequencing. This review covers several commonly used large-scale genome and gene expression analysis techniques, outlines genomic approaches to gene discovery and summarizes information that has come from large-scale analyses of human solid tumors.

/pdf/genome-changes-and-gene-expression-in-human-solid-tumors-4bas0g1nvg.pdf

Genome changes and gene expression in human solid tumors.

The gray, short-tailed opossum, Monodelphis domestica, is the most extensively used, laboratory-bred marsupial resource for basic biologic and biomedical research worldwide. To enhance the research utility of this species, we are building a linkage map, using both anonymous markers and functional gene loci, that will enable the localization of quantitative trait loci (QTL) and provide comparative information regarding the evolution of mammalian and other vertebrate genomes. The current map is composed of 83 loci distributed among eight autosomal linkage groups and the X chromosome. The autosomal linkage groups appear to encompass a very large portion of the genome, yet span a sex-average distance of only 633.0 cM, making this the most compact linkage map known among vertebrates. Most surprising, the male map is much larger than the female map (884.6 cM vs. 443.1 cM), a pattern contrary to that in eutherian mammals and other vertebrates. The finding of genome-wide reduction in female recombination in M. domestica, coupled with recombination data from two other, distantly related marsupial species, suggests that reduced female recombination might be a widespread metatherian attribute. We discuss possible explanations for reduced female recombination in marsupials as a consequence of the metatherian characteristic of determinate paternal X chromosome inactivation.

https://www.genetics.org/content/genetics/166/1/307.full.pdf

First-Generation Linkage Map of the Gray, Short-Tailed Opossum, Monodelphis domestica, Reveals Genome-Wide Reduction in Female Recombination Rates

The prairie vole (Microtus ochrogaster) is an emerging rodent model for investigating the genetics, evolution and molecular mechanisms of social behavior. Though a karyotype for the prairie vole has been reported and low-resolution comparative cytogenetic analyses have been done in this species, other basic genetic resources for this species, such as a genetic linkage map, are lacking. Here we report the construction of a genome-wide linkage map of the prairie vole. The linkage map consists of 406 markers that are spaced on average every 7 Mb and span an estimated ~90% of the genome. The sex average length of the linkage map is 1707 cM, which, like other Muroid rodent linkage maps, is on the lower end of the length distribution of linkage maps reported to date for placental mammals. Linkage groups were assigned to 19 out of the 26 prairie vole autosomes as well as the X chromosome. Comparative analyses of the prairie vole linkage map based on the location of 387 Type I markers identified 61 large blocks of synteny with the mouse genome. In addition, the results of the comparative analyses revealed a potential elevated rate of inversions in the prairie vole lineage compared to the laboratory mouse and rat. A genetic linkage map of the prairie vole has been constructed and represents the fourth genome-wide high-resolution linkage map reported for Muroid rodents and the first for a member of the Arvicolinae sub-family. This resource will advance studies designed to dissect the genetic basis of a variety of social behaviors and other traits in the prairie vole as well as our understanding of genome evolution in the genus Microtus.

/pdf/a-genetic-linkage-map-and-comparative-mapping-of-the-prairie-1k3b5lvcat.pdf

A genetic linkage map and comparative mapping of the prairie vole (Microtus ochrogaster) genome

Variation in intake of sweet and bitter solutions by inbred strains of laboratory mice has helped identify genes related to taste behaviors; but similar information is not available for golden hamsters (Mesocricetus auratus ), a species used much in taste research. Thus, 6-hour, 1-bottle intake by water-replete hamsters of 7 inbred strains was measured for water and 2 concentrations of sucrose, maltose, D-phenylalanine (D-Phe), and sodium saccharin, which are sweet; and quinine.HCl, L-phenylalanine (L-Phe), caffeine, and sucrose octaacetate (SOA), which are bitter to humans. Difference scores (DIF), calculated as solution intake minus mean baseline water intake (mL) for each animal, were evaluated by analysis of variance. Compared to ACN, CN, APA, APG, and CBN, five strains with similar DIF for all compounds, GN, an ancestral strain of ACNT, and ACNT preferred sucrose, caffeine, and SOA more strongly; ACNT also preferred saccharin and maltose more strongly and rejected quinine more strongly. Narrow sense heritabilities for the 6 compounds for which strain differences were revealed ranged from 0.31 to 0.57. Genetic correlations indicated the strain variations in intake of sucrose, saccharin, SOA, and caffeine were coupled; a statistical association with several possible interpretations. Intakes of the two amino acids, preferred D-Phe and aversive L-Phe, did not reveal strain differences, and heritability ranged from 0.13 to 0.23 for the two optical isomers. Thus, although, compared to mice, genetic variation in laboratory hamsters may be small, genetic differences that influence taste behaviors in existing strains may help identify relevant genes.

Variation in intake of sweet and bitter solutions by inbred strains of golden hamsters.

We have constructed the linkage map with precise genetic analysis of the Syrian hamster, Mesocricetus auratus, according to the restriction landmark genomic scanning (RLGS) spot mapping method. Although only 3.2–6.6% of the total RLGS spots between the two strains, ACN and BIO 14.6, showed genetic variance, 572 loci were found to be polymorphic. Out of 569 RLGS loci and 3 other loci, 531 were mapped with the backcross (ACN x BIO 14.6) F1 x BIO 14.6. The cumulative map was 1111.6 cM, indicating that the spots/loci are located throughout the genome at 1.94 cM intervals on average. Thus, RLGS provides us with a rapid tool to construct the genetic map of any species, even if it has less genetic variation.

Linkage map of Syrian hamster with restriction landmark genomic scanning

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Linkage map of Syrian hamster with restriction landmark genomic scanning