A radiation hybrid map of the zebrafish genome

Geisler, Robert; Rauch, Gerd-Jörg; Baier, Herwig; Bebber, Frauke van; Bross, Linda; Dekens, Marcus P. S.; Finger, K; Fricke, Cornelia; Gates, Michael A.; Geiger, Horst; Geiger-Rudolph, Silke; Gilmour, Darren; Glaser, Stefanie; Gnügge, Lara; Habeck, Hinrich; Hingst, K; Holley, Scott A.; Keenan, Jessica L.; Kirn, Annette; Knaut, Holger; Lashkari, Deval; Maderspacher, Florian; Martyn, Ulrike; Neuhauss, Stephan C.F.; Neumann, Carl J.; Nicolson, Teresa; Pelegri, Francisco; Ray, Russell; Rick, Jens M.; Roehl, Henry; Roeser, Tobias; Schauerte, Heike E.; Schier, Alexander F.; Schönberger, Ulrike; Schönthaler, Helia B.; Schulte‐Merker, Stefan; Seydler, C; Talbot, William S.; Weiler, Christian; Nüsslein‐Volhard, Christiane; Haffter, P.

doi:10.1038/12692

Cited by 253 publications

(151 citation statements)

References 22 publications

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“…We mapped the noa mutation near the centromere of linkage group 21 by generating amplified fragment length polymorphisms (19) and screening two RH panels (20,21) with these markers (Fig. 2A).…”

Section: Resultsmentioning

confidence: 99%

“…Carriers of the a13 allele in the F 1 generation were identified and crossed to produce a mapping panel of 2,000 mutants. Amplified fragment length polymorphism markers were generated as described (19) and mapped on two radiation hybrid (RH) panels (20,21). Simple sequence-length polymorphism markers, Z20205 and Z7609, were used for recombination analysis by PCR and agarose gel electrophoresis.…”

Section: Methodsmentioning

confidence: 99%

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A zebrafish model for pyruvate dehydrogenase deficiency: Rescue of neurological dysfunction and embryonic lethality using a ketogenic diet

Taylor

Hurley

Epps

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Defects in the pyruvate dehydrogenase (PDH) complex result in severe neurological dysfunction, congenital lactic acidosis, growth retardation, and early death. Current treatments for PDH deficiency are administered postnatally and are generally unsuccessful. Because many patients with this disease are born with irreversible defects, a model system for the development of effective pre-and postnatal therapies would be of great value. In a behavioral genetic screen aimed to identify zebrafish with visual function defects, we previously isolated two alleles of the recessive lethal mutant no optokinetic response a (noa). Here we report that noa is deficient for dihydrolipoamide S-acetyltransferase (Dlat), the PDH E2 subunit, and exhibits phenotypes similar to human patients with PDH deficiency. To rescue the deficiency, we added ketogenic substrates to the water in which the embryos develop. This treatment successfully restored vision, promoted feeding behavior, reduced lactic acidosis, and increased survival. Our study demonstrates an approach for establishing effective therapies for PDH deficiency and other congenital diseases that affect early embryonic development.H uman diseases that affect tissues with high-energy requirements are often caused by defects in mitochondrial function (1). Pyruvate dehydrogenase (PDH) deficiency is a rare metabolic disorder that severely affects the central nervous system due to the high-energy demand of neurons and often results in developmental delay, feeding difficulties, lethargy, ataxia, blindness, and early death (2-4). PDH is a nuclear-encoded mitochondrial matrix multienzyme complex that provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle by catalyzing the irreversible conversion of pyruvate into acetyl-CoA (5). Defects in PDH result in decreased acetyl-CoA synthesis and the accumulation of pyruvate and lactate, causing reduced energy production and metabolic acidosis, respectively.Current treatments for PDH deficiency, which include the activation of residual PDH with dichloroacetate (6), the administration of cofactors (lipoic acid and thiamine) (7,8), and the provision of ketogenic diets (9, 10), have yielded only limited or variable success (see Fig. 1). The technical challenges of working with small numbers of human patients has made it difficult to include all of the necessary controls and to systematically evaluate therapeutic agents and diets with varying proportions of calories from fat, carbohydrate, and protein (9, 11). Furthermore, preexisting neurological disorders compound the difficulty of evaluating treatments. A therapy that bypasses the entire complex would potentially be of greatest benefit, because it could be used to treat patients with defects in any of the PDH subunits and varying degrees of deficiency.An animal model for PDH deficiency would be of great value to improve current treatments and to allow the development of novel therapies. This model should exhibit phenotypic characteristics similar to those seen in human ...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A zebrafish model for pyruvate dehydrogenase deficiency: Rescue of neurological dysfunction and embryonic lethality using a ketogenic diet

Taylor

Hurley

Epps

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…To examine the origin of the duplications, we mapped all of these genes by somatic cell radiation hybrid (RH) mapping (Geisler et al 1999). As shown in Figure 2, atp␣2 is on linkage group 2 (LG 2), whereas atp␣1A1 and atp␣1B1 both map to LG 1 in the z9394-z9382 interval.…”

Section: Map Positions Of the Zebrafish Catalytic Subunitsmentioning

confidence: 99%

Partitioning of Tissue Expression Accompanies Multiple Duplications of the Na+/K+ ATPase α Subunit Gene

Serluca

Sidow²,

Mably³

et al. 2001

Genome Res.

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Vertebrate genomes contain multiple copies of related genes that arose through gene duplication. In the past it has been proposed that these duplicated genes were retained because of acquisition of novel beneficial functions. A more recent model, the duplication-degeneration-complementation hypothesis (DDC), posits that the functions of a single gene may become separately allocated among the duplicated genes, rendering both duplicates essential. Thus far, empirical evidence for this model has been limited to theengrailed and sox family of developmental regulators, and it has been unclear whether it may also apply to ubiquitously expressed genes with essential functions for cell survival. Here we describe the cloning of three zebrafish α subunits of the Na(+),K(+)-ATPase and a comprehensive evolutionary analysis of this gene family. The predicted amino acid sequences are extremely well conserved among vertebrates. The evolutionary relationships and the map positions of these genes and of other α-like sequences indicate that both tandem and ploidy duplications contributed to the expansion of this gene family in the teleost lineage. The duplications are accompanied by acquisition of clear functional specialization, consistent with the DDC model of genome evolution.[The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AY028628, AY028629, and AY028630]

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“…Radiation hybrid (RH) mapping was performed on the Goodfellow zebrafish T51 RH panel, which was developed by fusing irradiated zebrafish fin AB9 cells to hamster Wg3H cells (37). In brief, primer pairs are designed from the 3Ј-untranslated regions of putative orthologous gene or EST sequences obtained from http:͞͞www.ncbi.nlm.nih.gov and http:͞͞zfish.wustl.edu͞.…”

Section: Mapping Of Zebrafish Orthologs With a Radiation Hybrid Panelmentioning

confidence: 99%

Evolutionary conservation of zebrafish linkage group 14 with frequently deleted regions of human chromosome 5 in myeloid malignancies

Liu

Zhou

Kanki

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Recurring interstitial loss of all or part of the long arm of chromosome 5, del(5q), is a hallmark of myelodysplastic syndrome and acute myeloid leukemia. Although the genes affected by these changes have not been identified, two critically deleted regions (CDRs) are well established. We have identified 76 zebrafish cDNAs orthologous to genes located in these 5q CDRs. Radiation hybrid mapping revealed that 33 of the 76 zebrafish orthologs are clustered in a genomic region on linkage group 14 (LG14). Fifteen others are located on LG21, and two on LG10. Although there are large blocks of conserved syntenies, the gene order between human and zebrafish is extensively inverted and transposed. Thus, intrachromosomal rearrangements and inversions appear to have occurred more frequently than translocations during evolution from a common chordate ancestor. Interestingly, of the 33 orthologs located on LG14, three have duplicates on LG21, suggesting that the duplication event occurred early in the evolution of teleosts. Murine orthologs of human 5q CDR genes are distributed among three chromosomes, 18, 11, and 13. The order of genes within the three syntenic mouse chromosomes appears to be more colinear with the human order, suggesting that translocations occurred more frequently than inversions during mammalian evolution. Our comparative map should enhance understanding of the evolution of the del(5q) chromosomal region. Mutant fish harboring deletions affecting the 5q CDR syntenic region may provide useful animal models for investigating the pathogenesis of myelodysplastic syndrome and acute myeloid leukemia.

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A radiation hybrid map of the zebrafish genome

Cited by 253 publications

References 22 publications

A zebrafish model for pyruvate dehydrogenase deficiency: Rescue of neurological dysfunction and embryonic lethality using a ketogenic diet

A zebrafish model for pyruvate dehydrogenase deficiency: Rescue of neurological dysfunction and embryonic lethality using a ketogenic diet

Partitioning of Tissue Expression Accompanies Multiple Duplications of the Na+/K+ ATPase α Subunit Gene

Evolutionary conservation of zebrafish linkage group 14 with frequently deleted regions of human chromosome 5 in myeloid malignancies

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