Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters mediate the recurrent t(4;8)(p16;p23) translocation
Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters mediate the recurrent t(4;8)(p16;p23) translocation
复制标题
DOI：
10.1086/341610
复制
发表时间：
2002-08-01
影响因子：
9.8
通讯作者：
Zuffardi, O
中科院分区：
文献类型：
--
作者：
Giglio, S;Calvari, V;Zuffardi, O
t(4;8)（p16; p23）易位，以平衡形式或不平衡形式，已被多次报道。考虑到这种易位在常规细胞遗传学中可能未被检测到，我们发现它可能是t（11q;22q）之后最常见的易位，这是人类中最常见的反向易位。患有der(4)的病例受试者具有狼-赫施霍恩综合征，而患有der(8)的病例受试者表现出较轻微的畸形特征。两对嗅觉受体（OR）基因簇彼此靠近，分别位于4p16和8p23上。先前，我们证明了8p23 OR区域的反转多态性在通过不寻常的减数分裂交换产生染色体失衡中起着至关重要的作用。这些发现促使我们研究4p16和8p23的or相关倒置多态性是否也可能参与t(4;8)（p16;p23）易位的起源。在7例受试者中（其中5例均为新生病例，且均为母系），包括易位不平衡和平衡的个体，我们证明了断点落在4p和8p or基因簇内。用适当的细菌-人工染色体探针进行FISH实验，在所有五个新生病例的母亲中检测到4p和8p区域的杂合亚显微镜反转。在对照组中，分别有12.5%和26%的人检测到4p16和8p23的杂合反转，其中2.5%的人被标记为双杂合。这些新数据强调了区段重复和大规模基因组多态性在人类基因组进化和病理中的重要性。
The t(4;8)(p16; p23) translocation, in either the balanced form or the unbalanced form, has been reported several times. Taking into consideration the fact that this translocation may be undetected in routine cytogenetics, we find that it may be the most frequent translocation after t(11q;22q), which is the most common reciprocal translocation in humans. Case subjects with der(4) have the Wolf-Hirschhorn syndrome, whereas case subjects with der( 8) show a milder spectrum of dysmorphic features. Two pairs of the many olfactory receptor (OR)-gene clusters are located close to each other, on both 4p16 and 8p23. Previously, we demonstrated that an inversion polymorphism of the OR region at 8p23 plays a crucial role in the generation of chromosomal imbalances through unusual meiotic exchanges. These findings prompted us to investigate whether OR-related inversion polymorphisms at 4p16 and 8p23 might also be involved in the origin of the t(4;8)(p16;p23) translocation. In seven case subjects (five of whom both represented de novo cases and were of maternal origin), including individuals with unbalanced and balanced translocations, we demonstrated that the breakpoints fell within the 4p and 8p OR-gene clusters. FISH experiments with appropriate bacterial-artificial-chromosome probes detected heterozygous submicroscopic inversions of both 4p and 8p regions in all the five mothers of the de novo case subjects. Heterozygous inversions on 4p16 and 8p23 were detected in 12.5% and 26% of control subjects, respectively, whereas 2.5% of them were scored as doubly heterozygous. These novel data emphasize the importance of segmental duplications and large-scale genomic polymorphisms in the evolution and pathology of the human genome.