Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A.

Calhoun, David H.; Bishop, David F.; Bernstein, Harold S.; Quinn, Merrigene; Hantzopoulos, Petros; Desnick, Robert J.

doi:10.1073/pnas.82.21.7364

Cited by 54 publications

(38 citation statements)

References 37 publications

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“…Lanes 4^6 are three lots of enzyme ¢nished with separate chromatography conditions. The highest speci¢c enzyme activity reported previously for Gal-A was 5.0 Â 10 6 units mg 71 (Calhoun et al 1985) for enzyme isolated from human lung tissue. Gal-A puri¢ed from transfected leaves routinely has a speci¢c activity of over 5.5 Â 10 6 units mg À1 protein.…”

Section: Tmv Biotechnology T H Turpen 669mentioning

confidence: 88%

Tobacco mosaic virus and the virescence of biotechnology

Turpen¹

1999

Phil. Trans. R. Soc. Lond. B

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There is a growing realization that a modern combination of molecular biology and agriculture will provide a photosynthetic basis for the biosynthesis of an increasing variety of complex and valuable molecules. This`greening' of biotechnology may impact on the global environment in many bene¢cial ways, but will perhaps have its most signi¢cant impact on human health. In the past decade, the capacity to use plants as an expanded source of therapeutics has grown through the accelerated development of e¡ective viral transfection vectors for gene transfer to cultivated crops. Recombinant vectors based on tobacco mosaic virus (TMV) and other members of the Tobamovirus genus are now used to transfect commercially meaningful quantities of plant biomass cultivated in enclosed greenhouses and multiacre ¢elds. Viral RNA promoters are e¡ectively manipulated for the synthesis of recombinant messenger RNAs in whole plants. Chimeric plant virus and virus-like particles are designed for peptide production and display from recombinant structural protein^gene fusions. Gene functions are assessed and modi¢ed by either virus-mediated expression or cytosolic inhibition of expression at the RNA level. Recombinant virus populations, propagated by inoculating plants with infectious RNA transcripts or recombinant virions, have proved to be genetically stable over product-manufacturing cycles. Large volumes of highly puri¢ed protein products isolated from transfected foliage conform reproducibly to the speci¢cations required for well-characterized biologics. In some cases, they exceed the speci¢c activities of molecules puri¢ed from alternative recombinant and native sources. The resulting products are then formulated according to the developing national regulatory guidelines appropriate for agriculture-based manufacturing. Each of these innovations was ¢rst realized by researchers using clones of tobamovirus genes and recombinant genomes. This progress is founded on the heritage of a century of fundamental TMV research.

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Section: Tmv Biotechnology T H Turpen 669mentioning

confidence: 88%

Tobacco mosaic virus and the virescence of biotechnology

Turpen¹

1999

Phil. Trans. R. Soc. Lond. B

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“…Since cDNA of a-GalA was cloned and characterized (Calhoun et aL, 1985;Bishop et aL, 1986), molecular abnormalities in more than one hundred families with Fabry disease have been studied. Bernstein et al (1989) reported that partial gene deletions were seen only seven families out of 130 families by Southern blotting analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the full-length cDNA encoding human a-GalA has been isolated and characterized (Calhoun et al, 1985;Bishop et al, 1986Bishop et al, , 1988Kornreich et al, 1989). Since then molecular analysis of this disease has been reported.…”

Section: Introductionmentioning

confidence: 99%

A 3′ splice site consensus sequence mutation in the intron 3 of the α-galactosidase a gene in a patient with Fabry disease

et al. 1991

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“…Recently, we reported the cloning and nucleotide sequence of a cDNA (AAG18) encoding the entire mature lysosomal form of human a-Gal A (15,16). The AAG18 cDNA did not contain the entire 5' sequence and encoded only five residues of the a-Gal A signal peptide.…”

mentioning

confidence: 99%

Structural organization of the human alpha-galactosidase A gene: further evidence for the absence of a 3' untranslated region.

Bishop

Kornreich

Desnick

1988

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

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145

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Human a-galactosidase A (a-D-galactoside galactohydrolase; EC 3.2.1.22) is a lysosomal hydrolase encoded by a gene localized to the chromosomal region Xq22. The deficient activity of this enzyme results in Fabry disease, an X chromosome-hnked recessive disorder that leads to premature death in affected males. For studies of the structure and function of a-galactosidase A and for characterization of the genetic lesions in families with Fabry disease, the full-length cDNA was isolated, sequenced, and used to screen human genomic libraries. The 1393-base-pair full-length cDNA had a 60-nucleotide 5' untranslated region and encoded a precursor peptide of 429 amino acids including a signal peptide of 31 residues. Three overlapping A clones spanning 32 kilobases were identified that contained the entire ,12-kilobase chromosomal gene as well as -9 and -11 kilobases of 5' and 3' flanking sequence, respectively. The gene had seven exons. The genomic exonic and full-length cDNA sequences were identical. All intron-exon splice junctions conformed to the GT/AT consensus sequence. The 5' flanking region of this lysosomal housekeeping gene contained Spl and CCAAT box promoter elements as well as sequences corresponding to the activator protein 1 (AP1), octanucleotide ("OCTA"), and "core" enhancer elements. There was an upstream "HTF" island (Hpa I tiny fragments) followed by four direct repeats of the "chorion box" enhancer. The unique lack of a 3' untranslated sequence in the a-galactosidase A cDNA was confirmed by sequencing additional cDNA clones and the genomic 3' region.Human a-galactosidase A (a-D-galactoside galactohydrolase; EC 3.2

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Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A.

Cited by 54 publications

References 37 publications

Tobacco mosaic virus and the virescence of biotechnology

Tobacco mosaic virus and the virescence of biotechnology

A 3′ splice site consensus sequence mutation in the intron 3 of the α-galactosidase a gene in a patient with Fabry disease

Structural organization of the human alpha-galactosidase A gene: further evidence for the absence of a 3' untranslated region.

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