A comparative transcription map of the murine bare patches (Bpa) and striated (Str) critical regions and human Xq28.
A comparative transcription map of the murine bare patches (Bpa) and striated (Str) critical regions and human Xq28.
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DOI：
10.1101/gr.6.6.465
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发表时间：
1996-06
期刊：
影响因子：
7
通讯作者：
Michael L. Levin;Aurobindo Chatterjee;Antonella Pragliola;Kim C. Worley;Manfred Wehnert;Olga Zhuchenko-Olga-Zhuc
中科院分区：
文献类型：
--
作者：
Michael L. Levin;Aurobindo Chatterjee;Antonella Pragliola;Kim C. Worley;Manfred Wehnert;Olga Zhuchenko-Olga-Zhuc
基于遗传定位和临床表型，x连锁发育小鼠突变裸斑（Bpa）和条纹（Str）可能分别与人类x连锁显性点状软骨发育不良（CDPX2）和色素失禁（IP2）同源。Bpa和Str定位于一个600 kb的重叠关键区域，该区域与人类Xq28中的DXS1104和DXS52之间的基因顺序保守。作为分离与这些疾病有关的基因的努力的一部分，我们已经开始在两个物种中开发跨越该区域的比较转录图谱。利用跨物种保护和杂交、外显子捕获和cDNA选择技术，我们已经确定了四个已知基因或基因家族成员-caltractin， γ -氨基丁酸（GABAA）受体基因家族成员，黑色素瘤抗原基因（MAGE）家族成员，以及小鼠特异性x连锁淋巴细胞调节基因（Xlr3）家族的几个成员。捕获的外显子，在某些情况下，更长的cdna已经被分离出潜在的7-9个额外的基因。其中一个cDNA与锌指转录因子kr<e:1> ppel家族成员具有高度同源性。第二个新的cDNA在预测的氨基酸序列的3'端与LIM结构域一致。基因顺序似乎在那些确定存在于人类和小鼠中的cdna中是保守的。三种小鼠转录本似乎在Bpa/Str关键区域内存在多个副本，可能与基因组重排的易感性有关。逆转录酶PCR （RT-PCR）和Northern分析表明，其中一些转录本在妊娠中期的小鼠胚胎和新生儿皮肤中表达，使它们成为Bpa和Str突变及其相应的人类疾病的候选基因。
The X-linked developmental mouse mutations bare patches (Bpa) and striated (Str) may be homologous to human X-linked dominant chondrodysplasia punctata (CDPX2) and incontinentia pigmenti (IP2), respectively, based on their genetic mapping and clinical phenotypes. Bpa and Str have been localized to an overlapping critical region of 600 kb that demonstrates conserved gene order with loci in human Xq28 between DXS1104 and DXS52. As part of efforts to isolate the genes involved in these disorders, we have begun to develop a comparative transcription map spanning this region in both species. Using techniques of cross-species conservation and hybridization, exon trapping, and cDNA selection we have identified four known genes or members of gene families--caltractin, a member of the gamma-aminobutyric acid (GABAA) receptor gene family, a member of the melanoma antigen gene (MAGE) family, and several members of the murine-specific, X-linked lymphocyte regulated gene (Xlr3) family. Trapped exons and, in some cases, longer cDNAs have been isolated for potentially 7-9 additional genes. One cDNA demonstrates highly significant homology with members of the Krüppel family of zinc finger transcription factors. A second novel cDNA demonstrates homology at the 3' end of the predicted amino acid sequence to a LIM domain consensus. Gene order appears conserved among those cDNAs determined to be present in both human and mouse. Three of the murine transcripts appear to be present in multiple copies within the Bpa/Str critical region and could be associated with a predisposition to genomic rearrangements. Reverse transcriptase PCR (RT-PCR) and Northern analysis demonstrate that several of the transcripts are expressed in mid-gestation murine embryos and neonatal skin, making them candidates for the Bpa and Str mutations and their respective homologous human disorders.