A Cis-acting locus determines the polymorphic parental imprinting of the human IGF2R gene

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133860

Xu, Y; Polychronakos, C ^[1]

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1. McGill Univ., Montreal, Quebec (Canada)

The murine gene encoding the insulin-like growth factor receptor (IGF2R) is parentally imprinted in the mouse with exclusive maternal expression, but most humans express both gene copies. We have reported preferential expression of the maternal copy in approximately 17% of normal human pre-term placenta samples and in 50% of the kidneys of Wilms` tumor patients. Thus, IGF2R imprinting appears to be a polymorphic trait that may predispose to cancer. We explored the possibility that imprinting is associated with sequence variations of the imprinted domain itself (cis-acting locus). We studied 9 subjects with imprinted IGF2R expression that were informative for parental origin. These subjects were heterozygous for a transcribed CA repeat at the 3{prime}UTR of the gene, used for the study of the parental origin of mRNA transcripts. The two most common alleles, A162 and A164 (names refer to size in bp), were analyzed. In all cases the preferentially transcribed allele was maternal (p=0.002). In all 8 cases in which A164 was present, it was of paternal origin and was repressed (p=0.008), while A162 was maternal and preferentially expressed in 8/9 cases. Parental origin of A162 and A164 was random in individuals with biallelic expression. PCR amplification of genomic DNA after digestion with the methylation-sensitive enzyme HpaII revealed biallelic methylation at the 3{prime}UTR in both imprinting and non-imprinting individuals, making it unlikely that the imprint-controlling element (ICE) is located there. Polymorphic IGF2R imprinting depends on a cis-acting locus, at linkage disequilibrium with, but probably distinct from, our 3{prime}UTR marker. Biallelic expression in many subjects with a paternal A164 suggests that the frequency of the imprintable ICE is much lower than that of A164. Alternatively, the cis-locus is necessary but not sufficient and input in trans is additionally required for paternal-germline specific IGF2R repression.

• OSTI ID: 133860
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
DNA
DNA SEQUENCING
GENE REPRESSORS
GENES
GENETICS
GROWTH FACTORS
HUMAN POPULATIONS
MESSENGER-RNA
METHYLATION
MICE
NEOPLASMS
POLYMERASE CHAIN REACTION
RECEPTORS
RISK ASSESSMENT
SIZE
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION