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A roadmap of the mouse genome
News & Comment
TRENDS in Genetics Vol.18 No.11 November 2002
553
A roadmap of the mouse genome Complete sequencing of complex genomes is greatly facilitated by the availability of physical maps that assign ‘addresses’ to large genomic fragments to precise sites within the genome. Construction of a physical map provides the scaffolds upon which targeted sequencing strategies for partial or complete sequencing of genomes can be based. Additionally, the clones themselves are a valuable resource to the community for experimental studies. Gregory et al. [1] have generated a detailed physical map of the mouse genome containing 296 overlapping contigs and 16 992 unique markers. They were able to accomplish this by generating restriction fragment maps of bacterial artificial chromosomes (BACs), by aligning human and mouse genomes using sequences obtained from the ends of BAC clones, and by using thousands of previously mapped mouse markers. The human genome consists of
22 autosomes and two sex chromosomes, X and Y, whereas the mouse genome consists of 19 autosomes and two sex chromosomes. Overall, the coverage for all individual human chromosomes by corresponding mouse contigs was >80%, excepting chromosome 19, where it was 61%, and the Y chromosome, where it was 0%. The non-alignment of the Y chromosome was because of the high fraction of repetitive sequences on the human Y chromosome and the fact that <40% of the sequenced BAC ends were from a male mouse. Interestingly, as has been reported earlier, significant homology between human and mouse genomes was noted in regions other than those coding for genes. For instance, only about 20% of the representative mouse sequences corresponding to human chromosome 20 matched coding regions whereas 32% matched introns and 49% were in intergenic regions. The reason for such
conservation outside of gene-coding segments is not currently understood and warrants detailed analyses. The continuity of the mouse clone map described by Gregory et al. is the same as the current human map. Because the gaps in the two genomes are generally not at corresponding locations, this allows for design of probes to finish both human and mouse genomes at an accelerated pace. Comparative genomic analyses of whole genome sequences that are rapidly becoming available will not only assist in identification of genes and their regulatory sequences but also provide insights into structural and evolutionary relationships between genomes. 1 Gregory, S.G. et al. (2002) A physical map of the mouse genome. Nature 418,743–750
Babylakshmi Muthusamy [email protected] Akhilesh Pandey [email protected]
In Brief
PufferFISH: comparison of human and Tetraodon genes Because of its compactness, the genome of Tetraodon nigroviridis (freshwater pufferfish) has been described as an ideal reference to identify and validate vertebrate genes. Using fluorescence in situ hybridization (FISH), scientists under the leadership of Thomas Haaf have mapped genes from human chromosome X to those in the pufferfish. The results demonstrate that the human X chromosome is a mosaic of three pufferfish chromosomes. More than 350 million years ago, an ancestral vertebrate shared orthologous Xp and Xq genes with Tetraodon chromosomes 1 and 7; the third chromosomal addition appears to be more recent. The authors propose that before its conversion into a mammalian sex chromosome, the X chromosome underwent a highly specialized evolutionary selection procedure to generate the highly conserved gene arrays, followed by the recruitment of genes for reproduction and/or the development of cognitive abilities. (Grutzner, F. et al. [2002] Genome Res. 12, 1316–1322) SG http://tig.trends.com
Genome size Ever wanted to know the genome size of a particular organism? Check out www.genomesize.com. T. Ryan Gregory’s site is the most comprehensive reference for genome size information with genome sizes (C-values) listed for approximately 950 species of invertebrates (mostly insects) and 2150 species and subspecies of vertebrates. References to the original studies are listed along with the species and its C-value. Such a compendium will be a valuable reference for comparative studies involving correlates to genome size. NJ
A major step for microarray analysis The use of microarrays for studying gene expression has generated hundreds of papers, none of which contain sufficient information for them to be reproduced by anybody else. This is the opinion of a large collaboration involving both US and European bioinformatics and microarrays teams, which has prompted the search for a more standardized means of reporting
information. Their latest contribution is a suite of open-source software that can run in Java, Perl or C, based on MAGE-OM (Microarray Analysis of Gene Expression Object Model). The idea is that individuals other than the original authors will be able to analyze gene expression data derived from various microarray experiments, and this will ultimately result in the generation of new public and private databases to hold the experimental results. (Spellman, P.T. et al. [2002] Genome Biol. 3, research0046.1–0046.9) CH
Lhx4 and Prop1 in pituitary development Mutations in the Lhx4 and Prop1 genes are frequently responsible for the congenital failure of pituitary gland development in humans, and a recent study in mice has helped to explain how these genes function. Intriguingly, mutation of either of these genes results in severe hypoplasia of the anterior pituitary, and yet the two genes seem to be required for two distinct developmental processes. Lhx4, a lim homeodomain transcription factor, is
0168-9525/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved.
TRENDS in Genetics Vol.18 No.11 November 2002
553
A roadmap of the mouse genome Complete sequencing of complex genomes is greatly facilitated by the availability of physical maps that assign ‘addresses’ to large genomic fragments to precise sites within the genome. Construction of a physical map provides the scaffolds upon which targeted sequencing strategies for partial or complete sequencing of genomes can be based. Additionally, the clones themselves are a valuable resource to the community for experimental studies. Gregory et al. [1] have generated a detailed physical map of the mouse genome containing 296 overlapping contigs and 16 992 unique markers. They were able to accomplish this by generating restriction fragment maps of bacterial artificial chromosomes (BACs), by aligning human and mouse genomes using sequences obtained from the ends of BAC clones, and by using thousands of previously mapped mouse markers. The human genome consists of
22 autosomes and two sex chromosomes, X and Y, whereas the mouse genome consists of 19 autosomes and two sex chromosomes. Overall, the coverage for all individual human chromosomes by corresponding mouse contigs was >80%, excepting chromosome 19, where it was 61%, and the Y chromosome, where it was 0%. The non-alignment of the Y chromosome was because of the high fraction of repetitive sequences on the human Y chromosome and the fact that <40% of the sequenced BAC ends were from a male mouse. Interestingly, as has been reported earlier, significant homology between human and mouse genomes was noted in regions other than those coding for genes. For instance, only about 20% of the representative mouse sequences corresponding to human chromosome 20 matched coding regions whereas 32% matched introns and 49% were in intergenic regions. The reason for such
conservation outside of gene-coding segments is not currently understood and warrants detailed analyses. The continuity of the mouse clone map described by Gregory et al. is the same as the current human map. Because the gaps in the two genomes are generally not at corresponding locations, this allows for design of probes to finish both human and mouse genomes at an accelerated pace. Comparative genomic analyses of whole genome sequences that are rapidly becoming available will not only assist in identification of genes and their regulatory sequences but also provide insights into structural and evolutionary relationships between genomes. 1 Gregory, S.G. et al. (2002) A physical map of the mouse genome. Nature 418,743–750
Babylakshmi Muthusamy [email protected] Akhilesh Pandey [email protected]
In Brief
PufferFISH: comparison of human and Tetraodon genes Because of its compactness, the genome of Tetraodon nigroviridis (freshwater pufferfish) has been described as an ideal reference to identify and validate vertebrate genes. Using fluorescence in situ hybridization (FISH), scientists under the leadership of Thomas Haaf have mapped genes from human chromosome X to those in the pufferfish. The results demonstrate that the human X chromosome is a mosaic of three pufferfish chromosomes. More than 350 million years ago, an ancestral vertebrate shared orthologous Xp and Xq genes with Tetraodon chromosomes 1 and 7; the third chromosomal addition appears to be more recent. The authors propose that before its conversion into a mammalian sex chromosome, the X chromosome underwent a highly specialized evolutionary selection procedure to generate the highly conserved gene arrays, followed by the recruitment of genes for reproduction and/or the development of cognitive abilities. (Grutzner, F. et al. [2002] Genome Res. 12, 1316–1322) SG http://tig.trends.com
Genome size Ever wanted to know the genome size of a particular organism? Check out www.genomesize.com. T. Ryan Gregory’s site is the most comprehensive reference for genome size information with genome sizes (C-values) listed for approximately 950 species of invertebrates (mostly insects) and 2150 species and subspecies of vertebrates. References to the original studies are listed along with the species and its C-value. Such a compendium will be a valuable reference for comparative studies involving correlates to genome size. NJ
A major step for microarray analysis The use of microarrays for studying gene expression has generated hundreds of papers, none of which contain sufficient information for them to be reproduced by anybody else. This is the opinion of a large collaboration involving both US and European bioinformatics and microarrays teams, which has prompted the search for a more standardized means of reporting
information. Their latest contribution is a suite of open-source software that can run in Java, Perl or C, based on MAGE-OM (Microarray Analysis of Gene Expression Object Model). The idea is that individuals other than the original authors will be able to analyze gene expression data derived from various microarray experiments, and this will ultimately result in the generation of new public and private databases to hold the experimental results. (Spellman, P.T. et al. [2002] Genome Biol. 3, research0046.1–0046.9) CH
Lhx4 and Prop1 in pituitary development Mutations in the Lhx4 and Prop1 genes are frequently responsible for the congenital failure of pituitary gland development in humans, and a recent study in mice has helped to explain how these genes function. Intriguingly, mutation of either of these genes results in severe hypoplasia of the anterior pituitary, and yet the two genes seem to be required for two distinct developmental processes. Lhx4, a lim homeodomain transcription factor, is
0168-9525/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved.