The putative imprinted locus D15S9 within the common deletion region for the Prader-Willi and Angelman syndromes encodes two overlapping mRNAs transcribed from opposite strands
- Univ. of Florida, Gainesville, FL (United States)
- Case Western Reserve Univ., Cleveland, OH (United States); and others
Prader-Willi syndrome is typically caused by a deletion of paternal 15q11-q13, or maternal uniparental disomy (UPD) of chromosome 15, while Angelman syndrome is caused by a maternal deletion or paternal UPD of the same region. Therefore, these two clinically distinct neurobehavioral syndromes result from differential expression of imprinted genes within 15q11-q13. A 3.1 kb cDNA, DN34, from the D15S9 locus within 15q11-q13 was isolated from a human fetal brain library. We showed previously that DN34 probe detects a DNA methylation imprint and therefore may represent a candidate imprinted gene. Isolation of genomic clones and DNA sequencing demonstrated that the gene segment encoding the partial cDNA DN34 was split by a 2 kb intron, but did not encode a substantial open reading frame (ORF). Preliminary analysis of expression by RT-PCR suggests that this gene is expressed in fetal but not in tested tissue types from the adult, and thus its imprinting status has not been possible to assess at present. Surprisingly, we found an ORF on the antisense strand of the DN34 cDNA. This ORF encodes a putative polypeptide of 505 amino acid residues containing a RING C{sub 3}HC{sub 4} zinc-finger motif and other features of nuclear proteins. Subsequent characterization of this gene, ZNF127, and a mouse homolog, demonstrated expression of 3.2 kb transcript from all tested fetal and adult tissues. Transcripts initiate from within a CpG-island, shown to be differentially methylated on parental alleles in the human. Interestingly, functional imprinting of the mouse homolog was subsequently demonstrated in an F{sub 1} cross by analyzing a VNTR polymorphism in the mRNA. The ZNF127 gene is intronless, has significant overlap with the DN34 gene on the antisense strand, and a 1 kb 3{prime} end within the 2 kb DN34 intron.
- OSTI ID:
- 133380
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0108
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
Gene structure, DNA methylation, and imprinted expression of the human SNRPN gene
Identification and uniparental expression of a novel gene from the Prader-Willi region of chromosome 15
Related Subjects
BASIC STUDIES
GENES
DNA-CLONING
DNA SEQUENCING
TRANSCRIPTION
HUMAN CHROMOSOME 15
CHROMOSOMAL ABERRATIONS
PATIENTS
HEREDITARY DISEASES
NERVOUS SYSTEM DISEASES
BEHAVIOR
NUCLEOTIDES
METHYLATION
GENETICS
PROBES
BIOLOGICAL MARKERS
INTRONS
POLYMERASE CHAIN REACTION
AMINO ACIDS
POLYPEPTIDES
MICE