title: Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype.
abstract: Current evidence suggests that aniridia (absence of iris) is caused by loss of function of one copy of the PAX6 gene, which maps to 11p13. We present the further characterisation of two aniridia pedigrees in which the disease segregates with chromosomal rearrangements which involve 11p13 but do not disrupt the PAX6 gene. We have isolated three human YAC clones which encompass the PAX6 locus and we have used these to show that in both cases the chromosomal breakpoint is at least 85 kb distal of the 3' end of PAX6. In addition, the open reading frame of PAX6 is apparently free of mutations. We propose that the PAX6 gene on the rearranged chromosome 11 is in an inappropriate chromatin environment for normal expression and therefore that a 'position effect' is the underlying mechanism of disease in these families.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
authors.forename: J
authors.initials: J
authors.lastname: Fantes
authors.forename: B
authors.initials: B
authors.lastname: Redeker
authors.forename: M
authors.initials: M
authors.lastname: Breen
authors.forename: S
authors.initials: S
authors.lastname: Boyle
authors.forename: J
authors.initials: J
authors.lastname: Brown
authors.forename: J
authors.initials: J
authors.lastname: Fletcher
authors.forename: S
authors.initials: S
authors.lastname: Jones
authors.forename: W
authors.initials: W
authors.lastname: Bickmore
authors.forename: Y
authors.initials: Y
authors.lastname: Fukushima
authors.forename: M
authors.initials: M
authors.lastname: Mannens
mesh_terms: D015783:Aniridia / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D007446:Chromosome Inversion; D018244:Chromosomes, Artificial, Yeast; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D004268:DNA-Binding Proteins / Q000235:genetics*; D016521:Electrophoresis, Gel, Pulsed-Field; D005136:Eye Proteins; D005260:Female; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008969:Molecular Sequence Data; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins