Ocular retardation (or) is a murine eye mutation causing microphthalmia, a thin hypocellular retina and optic nerve aplasia. Here we show that mice carrying the OrJ allele have a premature stop codon in the homeobox of the Chx10 gene, a gene expressed at high levels in uncommitted retinal progenitor cells and mature bipolar cells. No CHX10 protein was detectable in the retinal neuroepithelium of orJ homozygotes. The loss of CHX10 leads both to reduced proliferation of retinal progenitors and to a specific absence of differentiated bipolar cells. Other major retinal cell types were present and correctly positioned in the mutant retina, although rod outer segments were short and retinal lamination was incomplete. These results indicate that Chx10 is an essential component in the network of genes required for the development of the mammalian eye, with profound effects on retinal progenitor proliferation and bipolar cell specification or differentiation. off

Linkage relationships of homologous loci in man and mouse were used to estimate the mean length of autosomal segments conserved during evolution. Comparison of the locations of >83 homologous loci revealed 13 conserved segments. Map distances between the outermost markers of these 13 segments are known for the mouse and range from 1 to 24 centimorgans. Methods were developed for using this sample of conserved segments to estimate the mean length of all conserved autosomal segments in the genome. This mean length was estimated to be 8.1 ± 1.6 centimorgans. Evidence is presented suggesting that chromosomal rearrangements that determine the lengths of these segments are randomly distributed within the genome. The estimated mean length of conserved segments was used to predict the probability that certain loci, such as peptidase-3 and renin, are linked in man given that homologous loci are x centimorgans apart in the mouse. The mean length of conserved segments was also used to estimate the number of chromosomal rearrangements that have disrupted linkage since divergence of man and mouse. This estimate was shown to be 178 ± 39 rearrangements.Recent progress in mammalian genetics has permitted the chromosomal assignment of numerous biochemically defined loci and the development of linkage maps for a variety of species (1)(2)(3)(4). Analysis of these linkage maps provides a useful means for studying genomic organization and evolution. For example, linkage of homologous loci on the X chromosome has been rigorously conserved in mammals, suggesting that chromosomal rearrangements involving the X chromosome and autosomes have been rejected by natural selection (5, 6). By contrast, analyses of conserved and disrupted autosomal linkages show that closely linked loci in one species tend to be linked in other species and loci that are loosely linked in one species tend to be unlinked in other species (7). It is not known, however, whether conserved segments are protected from chromosome rearrangement and may therefore represent adaptive combinations of loci or whether conserved segments reflect a random distribution of chromosomal rearrangements within the genome.Linkage maps for man and mouse are now sufficiently complete to warrant more quantitative analyses of the extent of linkage conservation and evaluation of a number of arguments concerning genomic organization and evolution. Perhaps the most useful parameter in these analyses is the length of conserved segments. There are two problems in calculating the lengths of these segments, however. The first is that the lengths of identified conserved segments are not precisely known because the lengths are probably greater than the distance between the outermost markers defining the segments. The second problem is that such lengths are based on segments marked by two or more homologous markers; segments lacking identified markers and segments with a single identified marker are necessarily excluded from these analyses. Because large segments are more likely to contain ...

Mice that are homozygous for the autosomal recessive chondrodysplasia (cho) mutation die at birth with abnormalities in cartilage of limbs, ribs, mandible, and trachea. Limb bones of newborn cho/cho mice are wider at the metaphyses than normal bones and only about half the normal length. By linkage analysis, the cho gene and the gene encoding the alpha 1 (XI) chain of cartilage collagen XI were mapped to the same region of chromosome 3. Deletion of a cytidine residue about 570 nt downstream of the translation initiation codon in cho alpha 1 (XI) mRNA causes a reading frame shift and introduces a premature stop codon. The data demonstrate that collagen XI is essential for normal formation of cartilage collagen fibrils and the cohesive properties of cartilage. The results also suggest that the normal differentiation and spatial organization of growth plate chondrocytes is critially dependent on the presence of type XI collagen in cartilage extracellular matrix.

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at  https://github.com/dib-lab/khmer/.

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