ANIRIDIA-ASSOCIATED CYTOGENETIC REARRANGEMENTS SUGGEST THAT A POSITION EFFECT MAY CAUSE THE MUTANT PHENOTYPE
ANIRIDIA-ASSOCIATED CYTOGENETIC REARRANGEMENTS SUGGEST THAT A POSITION EFFECT MAY CAUSE THE MUTANT PHENOTYPE
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DOI：
10.1093/hmg/4.3.415
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发表时间：
1995-03-01
影响因子：
3.5
通讯作者：
HANSON, I
中科院分区：
文献类型：
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作者：
FANTES, J;REDEKER, B;HANSON, I
目前的证据表明，无虹膜（虹膜缺失）是由PAX6基因的一个拷贝的功能丧失引起的，该基因定位于11p13。我们提出了两个无虹膜家系的进一步表征，其中疾病分离与染色体重排，涉及11p13，但不破坏PAX6基因。我们已经分离了三个包含PAX6基因座的人YAC克隆，并且我们已经使用这些克隆来显示在两种情况下染色体断裂点都在PAX6的3'末端的至少85kb远端。此外，PAX 6的开放阅读框显然没有突变。我们提出，PAX6基因重排的11号染色体是在一个不适当的染色质环境正常表达，因此，“位置效应”是在这些家庭的疾病的潜在机制。
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.