A cattle genetic linkage map was constructed which covers more than 95 percent of the bovine genome at medium density. Seven hundred and forty six DNA polymorphisms were genotyped in cattle families which comprise 347 individuals in full sibling pedigrees. Seven hundred and three of the loci are linked to at least one other locus. All linkage groups are assigned to chromosomes, and all are orientated with regards to the centromere. There is little overall difference in the lengths of the bull and cow linkage maps although there are individual differences between maps of chromosomes. One hundred and sixty polymorphisms are in or near genes, and the resultant genome-wide comparative analyses indicate that while there is greater conservation of synteny between cattle and humans compared with mice, the conservation of gene order between cattle and humans is much less than would be expected from the conservation of synteny. This map provides a basis for high-resolution mapping of the bovine genome with physical resources such as Yeast and Bacterial Artificial Chromosomes as well as providing the underpinning for the interpolation of information from the Human Genome Project.

A cosmid containing the human sequence (HOX7) homologous to the mouse homeogene Hox-7 was isolated from a genomic cosmid library. There is only one highly conserved homologous gene in the human genome. The C-terminal two-thirds of the HOX7 homeobox DNA sequence has been determined; there are no predicted amino acid changes from the mouse sequence. Data from mouse/human hybrid cell lines show that HOX7 maps to human chromosome 4p16.1, a region that is syntenic with part of mouse chromosome 5, the site of the murine Hox-7 gene. Analysis of chromosomes from two patients with Wolf-Hirschhorn syndrome, which is characterised by profound dysmorphologies, indicates that the HOX7 locus is deleted. Although not all Wolf-Hirschhorn syndrome patients analysed were deleted for HOX7, the combination of positional data and functional correlation with mouse expression implicates HOX7 as a candidate gene for this syndrome.

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A new variant rat myogenic cell line, ts485, was isolated by subcloning the cell line ts3b2 (H. T. Nguyen, R. M. Medford, and B. Nadal-Ginard, Cell 34:281-293, 1983). Unlike the progenitor cell line, ts485 was thermosensitive for differentiation. Experiments with conditioned medium suggested that diffusible extracellular factors were not involved in dictating the differential phenotypes of ts485 cells cultured at the permissive and nonpermissive temperatures. Temperature shift experiments performed on cultures of ts485 cells indicated that the temperature-sensitive lesion was in a factor active during the growth phase and required to trigger a cascade of events leading to terminal differentiation.Our understanding of the molecular control of gene expression during cellular differentiation is still superficial despite efforts with multiple experimental approaches. At the genomic level, several types of cis-acting DNA sequences which regulate gene expression in a tissue-specific manner have been characterized (14,28,36). trans-Acting, tissue-specific regulatory factors which may interact with such elements have been identified by a combination of molecular (17), biochemical (41), and cell biological approaches (8,22). In most biological systems, complexities and incongruities in the tissue-specific regulation of gene expression suggest a hierarchy of control steps which to date remain unresolved (26,28,36,53).Muscle is an ideal system with which to study molecular differentiation in vitro. Mononucleate myoblasts from primary cultures or established cell lines can be propagated in the undifferentiated state under conditions of high serum and low cell density. After removal of mitogens from the medium, the cells will align, differentiate, and fuse to form multinucleate myotubes. The muscle-specific genes encoding contractile proteins, cell surface receptors, and energygenerating enzymes are coordinately activated during this process (10,23,48). By experimental manipulation, myogenesis has been dissected into sequential stages, beginning with withdrawal from the cell cycle at Gl. This is followed by muscle-specific gene activation, commitment to terminal differentiation, and cell fusion (37, 40). Each step can be studied independently with biological inhibitors of the various processes of myogenesis (3,15,31,39,46).Identification of conditional myoblast mutants temperature sensitive for various stages of myogenesis has allowed further characterization of the sequential events of myogenesis at the morphological and biochemical levels (30, 40). The rat myoblast line ts3b2, in particular, has been extensively studied with respect to its temperature-sensitive phenotype for commitment to terminal differentiation (39, 40). The availability of other temperature-sensitive cell lines defective for various stages of myogenesis would not only provide models to probe the mechanisms regulating differentiation but could also provide the potential to isolate specific regulatory genes by DNA complementation.Here we report the isolat...

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