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Zebrafish orthologs of human muscular dystrophy genes.

Steffen LS, Guyon JR, Vogel ED, Beltre R, Pusack TJ, Zhou Y, Zon LI, Kunkel LM - BMC Genomics (2007)

Bottom Line: In addition, the genomic locations of all 29 genes have been found, allowing rapid candidate gene discovery during genetic mapping of zebrafish dystrophy mutants. 19 genes show conservation of syntenic relationships with humans and at least two genes appear to be duplicated in zebrafish.Significant sequence coverage on one or more BAC clone(s) was also identified for 24 of the genes to provide better local sequence information and easy updating of genomic locations as the zebrafish genome assembly continues to evolve.This resource supports zebrafish as a dystrophy model, suggesting maintenance of all known dystrophy-associated genes in the zebrafish genome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Children's Hospital, Program in Genomics, Boston, MA, USA. lsteffen@gmail.com <lsteffen@gmail.com>

ABSTRACT

Background: Human muscular dystrophies are a heterogeneous group of genetic disorders which cause decreased muscle strength and often result in premature death. There is no known cure for muscular dystrophy, nor have all causative genes been identified. Recent work in the small vertebrate zebrafish Danio rerio suggests that mutation or misregulation of zebrafish dystrophy orthologs can also cause muscular degeneration phenotypes in fish. To aid in the identification of new causative genes, this study identifies and maps zebrafish orthologs for all known human muscular dystrophy genes.

Results: Zebrafish sequence databases were queried for transcripts orthologous to human dystrophy-causing genes, identifying transcripts for 28 out of 29 genes of interest. In addition, the genomic locations of all 29 genes have been found, allowing rapid candidate gene discovery during genetic mapping of zebrafish dystrophy mutants. 19 genes show conservation of syntenic relationships with humans and at least two genes appear to be duplicated in zebrafish. Significant sequence coverage on one or more BAC clone(s) was also identified for 24 of the genes to provide better local sequence information and easy updating of genomic locations as the zebrafish genome assembly continues to evolve.

Conclusion: This resource supports zebrafish as a dystrophy model, suggesting maintenance of all known dystrophy-associated genes in the zebrafish genome. Coupled with the ability to conduct genetic screens and small molecule screens, zebrafish are thus an attractive model organism for isolating new dystrophy-causing genes/pathways and for use in high-throughput therapeutic discovery.

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Distribution of zebrafish muscular dystrophy orthologs. Orthologs of the 25 muscular dystrophy-associated genes and 4 additional myopathy-associated genes were identified on 20 of the 25 zebrafish chromosomes by computer searches of the Sanger Centre Zebrafish Genome. Duplicate loci were found for FLNC and TTN orthologs. TRIM32 is located on an orphan scaffold that has not yet been integrated within the genome.
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Figure 1: Distribution of zebrafish muscular dystrophy orthologs. Orthologs of the 25 muscular dystrophy-associated genes and 4 additional myopathy-associated genes were identified on 20 of the 25 zebrafish chromosomes by computer searches of the Sanger Centre Zebrafish Genome. Duplicate loci were found for FLNC and TTN orthologs. TRIM32 is located on an orphan scaffold that has not yet been integrated within the genome.

Mentions: All 29 genes could be placed in whole or in part on Version 6 of the Sanger Centre Zebrafish Genome. TRIM32, responsible for Limb Girdle Muscular Dystrophy 2H (LGMD 2H), resides on an orphan scaffold that has not yet been integrated into the chromosomal organization of the genome. The remaining 28 genes are scattered across 18 chromosomes with the majority of chromosomes having only one dystrophy ortholog (Fig. 1). Only Chr 9 (Collagen 6A3, desmin, and duplicate titin genes) and Chr 11 (ITGA7 and two syntenic collagen genes) contain more than two dystrophy orthologs. It is interesting to note that there is currently no identified sex chromosome in zebrafish. Indeed, dystrophin and emerin, genes that reside on the human X chromosome, are found on different chromosomes in zebrafish, and characterization of the zebrafish dystrophin mutant, sapje, has demonstrated an autosomal recessive inheritance pattern.


Zebrafish orthologs of human muscular dystrophy genes.

Steffen LS, Guyon JR, Vogel ED, Beltre R, Pusack TJ, Zhou Y, Zon LI, Kunkel LM - BMC Genomics (2007)

Distribution of zebrafish muscular dystrophy orthologs. Orthologs of the 25 muscular dystrophy-associated genes and 4 additional myopathy-associated genes were identified on 20 of the 25 zebrafish chromosomes by computer searches of the Sanger Centre Zebrafish Genome. Duplicate loci were found for FLNC and TTN orthologs. TRIM32 is located on an orphan scaffold that has not yet been integrated within the genome.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851013&req=5

Figure 1: Distribution of zebrafish muscular dystrophy orthologs. Orthologs of the 25 muscular dystrophy-associated genes and 4 additional myopathy-associated genes were identified on 20 of the 25 zebrafish chromosomes by computer searches of the Sanger Centre Zebrafish Genome. Duplicate loci were found for FLNC and TTN orthologs. TRIM32 is located on an orphan scaffold that has not yet been integrated within the genome.
Mentions: All 29 genes could be placed in whole or in part on Version 6 of the Sanger Centre Zebrafish Genome. TRIM32, responsible for Limb Girdle Muscular Dystrophy 2H (LGMD 2H), resides on an orphan scaffold that has not yet been integrated into the chromosomal organization of the genome. The remaining 28 genes are scattered across 18 chromosomes with the majority of chromosomes having only one dystrophy ortholog (Fig. 1). Only Chr 9 (Collagen 6A3, desmin, and duplicate titin genes) and Chr 11 (ITGA7 and two syntenic collagen genes) contain more than two dystrophy orthologs. It is interesting to note that there is currently no identified sex chromosome in zebrafish. Indeed, dystrophin and emerin, genes that reside on the human X chromosome, are found on different chromosomes in zebrafish, and characterization of the zebrafish dystrophin mutant, sapje, has demonstrated an autosomal recessive inheritance pattern.

Bottom Line: In addition, the genomic locations of all 29 genes have been found, allowing rapid candidate gene discovery during genetic mapping of zebrafish dystrophy mutants. 19 genes show conservation of syntenic relationships with humans and at least two genes appear to be duplicated in zebrafish.Significant sequence coverage on one or more BAC clone(s) was also identified for 24 of the genes to provide better local sequence information and easy updating of genomic locations as the zebrafish genome assembly continues to evolve.This resource supports zebrafish as a dystrophy model, suggesting maintenance of all known dystrophy-associated genes in the zebrafish genome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Children's Hospital, Program in Genomics, Boston, MA, USA. lsteffen@gmail.com <lsteffen@gmail.com>

ABSTRACT

Background: Human muscular dystrophies are a heterogeneous group of genetic disorders which cause decreased muscle strength and often result in premature death. There is no known cure for muscular dystrophy, nor have all causative genes been identified. Recent work in the small vertebrate zebrafish Danio rerio suggests that mutation or misregulation of zebrafish dystrophy orthologs can also cause muscular degeneration phenotypes in fish. To aid in the identification of new causative genes, this study identifies and maps zebrafish orthologs for all known human muscular dystrophy genes.

Results: Zebrafish sequence databases were queried for transcripts orthologous to human dystrophy-causing genes, identifying transcripts for 28 out of 29 genes of interest. In addition, the genomic locations of all 29 genes have been found, allowing rapid candidate gene discovery during genetic mapping of zebrafish dystrophy mutants. 19 genes show conservation of syntenic relationships with humans and at least two genes appear to be duplicated in zebrafish. Significant sequence coverage on one or more BAC clone(s) was also identified for 24 of the genes to provide better local sequence information and easy updating of genomic locations as the zebrafish genome assembly continues to evolve.

Conclusion: This resource supports zebrafish as a dystrophy model, suggesting maintenance of all known dystrophy-associated genes in the zebrafish genome. Coupled with the ability to conduct genetic screens and small molecule screens, zebrafish are thus an attractive model organism for isolating new dystrophy-causing genes/pathways and for use in high-throughput therapeutic discovery.

Show MeSH
Related in: MedlinePlus