Fantes J, Redeker B, Breen M, Boyle S, Brown J, Fletcher J, Jones S, Bickmore W, Fukushima Y, Mannens M
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
Hum Mol Genet. 1995 Mar;4(3):415-22. doi: 10.1093/hmg/4.3.415.
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.
目前的证据表明，无虹膜症（虹膜缺失）是由PAX6基因的一个拷贝功能丧失引起的，该基因定位于11p13。我们进一步描述了两个无虹膜症家系，在这些家系中，疾病与涉及11p13但不破坏PAX6基因的染色体重排相关。我们分离出了三个包含PAX6基因座的人类酵母人工染色体（YAC）克隆，并利用它们证明在这两种情况下，染色体断点位于PAX6 3'端至少85 kb远的位置。此外，PAX6的开放阅读框显然没有突变。我们提出，重排的11号染色体上的PAX6基因处于不利于正常表达的染色质环境中，因此“位置效应”是这些家族中疾病的潜在机制。
