Goosecoid-like sequences and the smallest region of deletion overlap in DiGeorge and velocardiofacial syndromes.
Goosecoid-like sequences and the smallest region of deletion overlap in DiGeorge and velocardiofacial syndromes.
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DiGeorge 和腭心面综合征中的 Goosecoid 样序列和最小的缺失区域重叠。
DOI：
10.1086/301652
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发表时间：
1997
影响因子：
9.8
通讯作者：
Baldini,A
中科院分区：
文献类型：
--
作者：
Pragliola,A;Jurecic,V;Chau,CK;Philip,N;Baldini,A
在1997年5月的期刊上，Gottlieb et al.等（1997）报道了从22 q11中鉴定出名为“GSCL”（Goosecoid-like）的同源框编码基因。DiGeorge综合征（DGS）和腭心面综合征（VCFS）的2区缺失。该基因位于由林赛等人定义的所谓的最小DiGeorge临界区（MDGCR）内。（1993）和Gong et al.（1996年）。该文章（Gottlieb et al. 1997，p.1199）的图3显示GSCL基因位于缺失重叠的最小区域（SRDO，MDGCR的一个亚片段），因为GSCL被假定在患者G中缺失。患者G受DGS影响，存在间质缺失，其近端断点定义了SRDO的近端边界（Levy等人，1995）。然而，来自患者G的染色体未用GSCL序列进行测试。我们决定自己进行实验以测试患者G是否实际上缺失了GSCL。从我们覆盖同源小鼠区域的细菌人工染色体重叠群（Botta等人，我们亚克隆了一个3.7-kb的SmaI DNA片段，该片段对应于基因组序列MMU 70231（Galili等，1997）的nt 27970-31642，并含有鼠Gsc 1的三个编码外显子。我们已经用该片段筛选了人DGS关键区的重叠群（林赛等，1996）。从fosmid 39 g9中鉴定并亚克隆了一个12.2 kb的HindIII DNA片段（pHgscl）。部分测序证实，该片段含有GSCL序列，对应于基因组序列HSU 30597的nt 129598-141800（Gottlieb et al.1997）;因此，它包括整个GSCL基因，如Gottlieb et al.（1997），但需要注意的是，该基因的转录起始尚未通过实验确定，而仅基于序列特征推断。对患者G染色体的FISH实验表明，pHgscl没有缺失（图1A）;两条染色体中的杂交信号强度没有观察到可检测的差异。NotI-HindIII 3.7-kb片段（含有大部分编码序列）与来自患者G的限制性消化的基因组DNA杂交，
In the May 1997 issue of the Journal, Gottlieb et al.(1997) reported the identification of a homeobox-coding gene named “GSCL”(Goosecoid-like) from a 22q11. 2 region deleted in DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). The gene is located within the so-called minimal DiGeorge critical region (MDGCR), as defined by Lindsay et al.(1993) and Gong et al.(1996). Figure 3 of that article (Gottlieb et al. 1997, p. 1199) shows the GSCL gene as localized in the smallest region of deletion overlap (SRDO, a subsegment of the MDGCR), because GSCL was presumed to be deleted in patient G. Patient G is affected by DGS and has an interstitial deletion the proximal breakpoint of which defines the proximal boundary of the SRDO (Levy et al. 1995). However, chromosomes from patient G were not tested with GSCL sequences. We decided to perform experiments ourselves to test whether patient G is in fact deleted for GSCL.From our bacterial-artificial-chromosome contig covering the homologous mouse region (Botta et al., in press), we have subcloned a 3.7-kb SmaI DNA fragment corresponding to nt 27970–31642 of the genomic sequence MMU70231 (Galili et al. 1997) and containing the three coding exons of the murine Gscl. We have used this fragment to screen our contig of the human DGS critical region (Lindsay et al. 1996). A 12.2-kb HindIII DNA fragment (pHgscl) was identified and subcloned from fosmid 39g9. Partial sequencing confirmed that this fragment contains GSCL sequences and corresponds to nt 129598–141800 of the genomic sequence HSU30597 (Gottlieb et al. 1997); thus it includes the entire GSCL gene, as characterized by Gottlieb et al.(1997), with the caveat that the transcription initiation of this gene has not yet been experimentally determined but has only been deduced on the basis of sequence features. FISH experiments on patient G’s chromosomes showed that pHgscl is not deleted (fig. 1A); no detectable difference was seen in the hybridization-signal intensities in the two chromosomes. The NotI-HindIII 3.7-kb fragment (containing most of the coding sequences) was hybridized to restriction-digested genomic DNA from patient G and