title: Hutchinson-Gilford progeria: faithful DNA maintenance, inheritance and allelic transcription of beta(1-4) galactosyltransferase.
abstract: Hutchinson-Gilford progeria syndrome (HGPS) is a fatal segmental aging disorder affecting children. There is a paucity of prior data at the nucleotide level on DNA maintenance in HGPS. We have examined the specific nucleotide sequences and production of allelic transcripts from the locus GGTB2 encoding beta(1-4) galactosyltransferase. Quantitative Northern blots of mRNA from HGPS and control fibroblasts indicated identical mature beta(1-4) galactosyltransferase transcript sizes and amounts, regardless of their altered glycosylation status. DNA sequencing of cDNA derived from HGPS beta(1-4) galactosyltransferase mRNA populations confirmed the encoded amino acid sequence was unaffected. Population studies of 41 unrelated individuals provided allelic frequency estimates for a novel FokI polymorphism, which was identified in two of six progeria cell strains. The polymorphism was faithfully inherited in a progeria pedigree in a Mendelian manner. Furthermore, the polymorphism provided direct evidence through sequencing of reverse transcription polymerase chain reaction products that both alleles were transcribed and generated mature mRNA. Any defects in transcripts were below detectable levels over the lengths of coding sequences examined, despite multiple replication events from conception leading to the production and maintenance of patient-derived cells. These results indicate faithful transcription in HGPS.
authors.affiliation: Department of Biochemistry, University of Sydney, NSW, Australia.
authors.forename: M E
authors.initials: ME
authors.lastname: O'Brien
authors.forename: S
authors.initials: S
authors.lastname: Jensen
authors.forename: A S
authors.initials: AS
authors.lastname: Weiss
mesh_terms: D000483:Alleles; D015152:Blotting, Northern; D004247:DNA; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009237:N-Acetyllactosamine Synthase / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011371:Progeria / Q000201:enzymology* / Q000235:genetics*; D013577:Syndrome; D014158:Transcription, Genetic
chemical_list: D004247:DNA; D009237:N-Acetyllactosamine Synthase; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific