A G-->A substitution in an HNF I binding site in the human alpha-fetoprotein gene is associated with hereditary persistence of alpha-fetoprotein (HPAFP).

McVey, JH, Michaelides, K, Hansen, LP, Ferguson-Smith, M, Tilghman, S, Krumlauf, R and Tuddenham, EG (1993) A G-->A substitution in an HNF I binding site in the human alpha-fetoprotein gene is associated with hereditary persistence of alpha-fetoprotein (HPAFP). Hum Mol Genet, 2 (4). pp. 379-384.

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Abstract

A family displaying hereditary persistence of alpha-fetoprotein (HPAFP) in adult life was detected in an antenatal screening programme for spina bifida. RFLP linkage analysis shows that the trait is linked with the albumin-AFP locus. The molecular mechanism responsible for the post-natal repression of the AFP gene is unknown. We wished to determine the molecular mechanism underlying HPAFP in this family. Sequence analysis of the 5'-flanking sequences of their gene revealed a GA substitution at position -119 associated with the trait. This substitution occurs in a potential HNF I binding site, and increases the similarity of the sequence to a consensus HNF I recognition site. In a competitive gel retardation assay the mutant sequence binds HNF I alpha more tightly than the wild type sequence. Furthermore, 5'-flanking sequences of the human AFP gene containing the G-->A substitution direct a higher level of CAT expression in transfected human hepatoma cells than the wild type sequences. We conclude that the G-->A substitution at position -119 of the AFP gene is the mutation causing HPAFP in this family. These results highlight the importance of this HNF I binding site in the developmental regulation of the AFP gene.

Item Type:	Article
Divisions :	Surrey research (other units)
Authors :	Name Email ORCID McVey, JH j.mcvey@surrey.ac.uk Michaelides, K Hansen, LP Ferguson-Smith, M Tilghman, S Krumlauf, R Tuddenham, EG
Date :	April 1993
Uncontrolled Keywords :	Adult, Alleles, Amino Acid Sequence, Base Sequence, Binding Sites, Chloramphenicol O-Acetyltransferase, DNA, DNA Mutational Analysis, Gene Expression, Humans, Molecular Sequence Data, Point Mutation, Promoter Regions, Genetic, alpha-Fetoproteins
Related URLs :	Author
Depositing User :	Symplectic Elements
Date Deposited :	17 May 2017 10:16
Last Modified :	24 Jan 2020 18:51
URI:	http://epubs.surrey.ac.uk/id/eprint/827096

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