© 1995 Oxford University Press
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Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype
MRC Human Genetics Unit, Western General Hospital Crewe Road, Edinburgh EH4 2XU, UK 1Institute of Human Genetics, University Hospital Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands 2Division of Medical Genetics, Saitama Children's Medical Centre 2100 Magome, Iwatsuki, Saitama, 399 Japan
*To whom correspondence should be addressed
Received October 4, 1994; Revised December 19, 1994; Accepted December 19, 1994
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.
+Present address: Australian Equine Blood Typing Research Laboratory, University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia
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