Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes
Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes
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DOI：
10.1038/ng.2007.56
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发表时间：
2008-02-01
期刊：
影响因子：
30.8
通讯作者：
Ogata, Tsutomu
中科院分区：
文献类型：
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作者：
Kagami, Masayo;Sekita, Yoichi;Ogata, Tsutomu
人类染色体14q32.2携带一组印记基因，包括DLK1和RTL1等父系表达基因(Peg)和MEG3(也称为GTL2)、RTL1as(RTL1反义)和MEG8等母系表达基因(Meg)。1，2)，以及基因间差异甲基化区域(IG-DMR)和MEG3-DMR3-5。与此一致，14号染色体的父系和母系单亲二体(UPD(14)PAT和UPD(14)MAT)导致不同的表型(6，7)。我们研究了8个具有UPD(14)PAT样表型的个体(例1-8)和3个在没有UPD(14)的情况下具有UPD(14)MAT样表型的个体(例9-11)，并确定了影响印迹区域的各种缺失和表位突变。结合最近的小鼠数据(4，8-10)，这些结果表明IG-DMR在母系遗传的染色体上具有重要的顺式调节功能，RTL1的过度表达和DLK1和RTL1的表达降低分别与UPD(14)PAT样和UPD(14)MAT样的表型有关。
Human chromosome 14q32.2 carries a cluster of imprinted genes including paternally expressed genes (PEGs) such as DLK1 and RTL1 and maternally expressed genes (MEGs) such as MEG3 (also known as GTL2), RTL1as (RTL1 antisense) and MEG8 (refs. 1,2), together with the intergenic differentially methylated region (IG-DMR) and the MEG3-DMR3-5. Consistent with this, paternal and maternal uniparental disomy for chromosome 14 (upd(14) pat and upd(14) mat) cause distinct phenotypes(6,7). We studied eight individuals (cases 1-8) with a upd(14) pat-like phenotype and three individuals (cases 9-11) with a upd(14) mat-like phenotype in the absence of upd(14) and identified various deletions and epimutations affecting the imprinted region. The results, together with recent mouse data(4,8-10), imply that the IG-DMR has an important cis-acting regulatory function on the maternally inherited chromosome and that excessive RTL1 expression and decreased DLK1 and RTL1 expression are relevant to upd(14) pat-like and upd(14) mat-like phenotypes, respectively.