The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene

Journal Article · Wed May 15 04:00:00 EDT 1996 · Genomics

DOI:https://doi.org/10.1006/geno.1996.0238· OSTI ID:478556

Phillips, M S; Fujii, Junichi; Khanna, V K ^[1]

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1. Univ. of Toronto, Ontario (Canada); and others

The RYR1 gene encoding the Ca{sup 2+} release channel of human skeletal muscle sarcoplasmic reticulum has been cloned and exon/intron boundaries have been determined, together with a minimum of 30 bp of intron sequence flanking each splice junction. The gene contains 106 exons, of which two are alternatively spliced. The length of the gene, determined by the alignment of 16 genomic phage clones, a cosmid clone, and several long polymerase chain reaction products, is approximately 160 kb. Exons range from 15 to 813 bp, while introns range from 85 to about 16,000 bp. Analysis of the gene has confirmed published errors in the human RYR1 cDNA and confirmed the structure of two alternatively spliced exons. The numbering of the nucleotides comprising the RYR1 cDNA and the numbering of amino acids encoded by them were corrected to account for these earlier errors and omissions. Analysis of 2.4 kb of the 5{prime} upstream sequence indicated the presence of a CCAAT box and several Sp1 binding sites between nucleotides -200 and -60 bp, flanking the proposed transcription factor binding sites were identified throughout the 5{prime} sequence. Knowledge of the structure of the RYR1 gene will provide an invaluable resource for the discovery of mutations in the gene that are casual of human malignant hyperthermia and central core disease. 58 refs., 4 figs., 3 tabs.

• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 478556
• Journal Information: Genomics, Journal Name: Genomics Journal Issue: 1 Vol. 34; ISSN 0888-7543; ISSN GNMCEP
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
AMINO ACIDS
ANESTHETICS
BIOLOGICAL EFFECTS
CALCIUM
COSMIDS
DNA SEQUENCING
DNA-CLONING
GENE MUTATIONS
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 19
HYPERTHERMIA
MUSCLES
NUCLEOTIDES
PATIENTS
POLYMERASE CHAIN REACTION
PORINS
RECEPTORS
SARCOPLASMIC RETICULUM
SKELETON
SPLICING
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION