Nucleotide, cytogenetic and expression impact of the human chromosome 8p23.1 inversion polymorphism.
Nucleotide, cytogenetic and expression impact of the human chromosome 8p23.1 inversion polymorphism.
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人类8p23.1反演多态性的核苷酸，细胞遗传学和表达影响。
DOI：
10.1371/journal.pone.0008269
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发表时间：
2009-12-14
期刊：
影响因子：
3.7
通讯作者：
Estivill X
中科院分区：
文献类型：
--
作者：
Bosch N;Morell M;Ponsa I;Mercader JM;Armengol L;Estivill X
人类染色体 8p23.1 区域包含一个 3.8–4.5 Mb 的片段，可以在个体之间以不同的方向（定义为基因组倒置）找到该片段。与给定区域的基因组方向紧密相关的单核苷酸多态性（SNP）的鉴定应该有助于间接评估个体中大基因组方向的基因型。我们已经鉴定出 16 个 SNP，通过荧光原位杂交 (FISH) 检测，这些 SNP 与 8p23.1 倒位处于连锁不平衡 (LD) 状态。使用这组 SNP 预测了 150 个 HapMap 样本中 8p23.1 方向的变异性，并通过 FISH 在样本子集中进行了验证。根据 8p23.1 区域的方向，发现四个基因（NEIL2、MSRA、CTSB 和 BLK）存在差异表达（p<0.0005）。最后，我们发现通过 FISH 确定的 8p23.1 方向存在不同程度的嵌合。通过该区域的密集SNP基因分型、基于单倍型的计算分析和FISH实验，我们可以通过检测倒转区域两端的两个短单倍型延伸来推断和验证8p23.1区域等位基因的方向状态，这很可能是发生原始倒转的染色体的遗迹。此外，不能排除 8p23.1 倒位对基因表达水平的影响，因为该区域的四个基因根据倒位状态具有统计学上显着的不同表达水平。类淋巴母细胞系中的 FISH 结果表明存在关于 8p23.1 倒位的嵌合现象。
The human chromosome 8p23.1 region contains a 3.8–4.5 Mb segment which can be found in different orientations (defined as genomic inversion) among individuals. The identification of single nucleotide polymorphisms (SNPs) tightly linked to the genomic orientation of a given region should be useful to indirectly evaluate the genotypes of large genomic orientations in the individuals. We have identified 16 SNPs, which are in linkage disequilibrium (LD) with the 8p23.1 inversion as detected by fluorescent in situ hybridization (FISH). The variability of the 8p23.1 orientation in 150 HapMap samples was predicted using this set of SNPs and was verified by FISH in a subset of samples. Four genes (NEIL2, MSRA, CTSB and BLK) were found differentially expressed (p<0.0005) according to the orientation of the 8p23.1 region. Finally, we have found variable levels of mosaicism for the orientation of the 8p23.1 as determined by FISH. By means of dense SNP genotyping of the region, haplotype-based computational analyses and FISH experiments we could infer and verify the orientation status of alleles in the 8p23.1 region by detecting two short haplotype stretches at both ends of the inverted region, which are likely the relic of the chromosome in which the original inversion occurred. Moreover, an impact of 8p23.1 inversion on gene expression levels cannot be ruled out, since four genes from this region have statistically significant different expression levels depending on the inversion status. FISH results in lymphoblastoid cell lines suggest the presence of mosaicism regarding the 8p23.1 inversion.
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影响因子：
30.8
作者：
Alkan, Can;Kidd, Jeffrey M.;Marques-Bonet, Tomas;Aksay, Gozde;Antonacci, Francesca;Hormozdiari, Fereydoun;Kitzman, Jacob O.;Baker, Carl;Malig, Maika;Mutlu, Onur;Sahinalp, S. Cenk;Gibbs, Richard A.;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
影响因子：
64.8
作者：
Eichler, Evan E.;Nickerson, Deborah A.;Altshuler, David;Bowcock, Anne M.;Brooks, Lisa D.;Carter, Nigel P.;Church, Deanna M.;Felsenfeld, Adam;Guyer, Mark;Lee, Charles;Lupski, James R.;Mullikin, James C.;Pritchard, Jonathan K.;Sebat, Jonathan;Sherry, Stephen T.;Smith, Douglas;Valle, David;Waterston, Robert H.
通讯作者：
Waterston, Robert H.
影响因子：
5.8
作者：
Gonzalez, Juan R.;Armengol, Lluis;Moreno, Victor
通讯作者：
Moreno, Victor
影响因子：
9.8
作者：
Fellermann, Klaus;Stange, Daniel E.;Stange, Eduard F.
通讯作者：
Stange, Eduard F.
影响因子：
5.3
作者：
Iida, A;Emi, M;Nakamura, Y
通讯作者：
Nakamura, Y