Refinement of the Van der Woude gene location and construction of a 3.5-Mb YAC contig and STS map spanning the critical region in 1q32-q41.
Refinement of the Van der Woude gene location and construction of a 3.5-Mb YAC contig and STS map spanning the critical region in 1q32-q41.
复制标题
完善 Van der Woude 基因定位并构建跨越 1q32-q41 关键区域的 3.5-Mb YAC 重叠群和 STS 图谱。
DOI：
10.1006/geno.1996.0496
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Murray,JC
中科院分区：
文献类型：
--
作者：
Schutte,BC;Sander,A;Malik,M;Murray,JC
货车德沃德综合征（VWS）是最常见的综合征性裂。连锁分析将该基因定位在D1S245和D1S414之间，间隔4.1cM，位点顺序为：着丝粒-D1S245/D1S471-D1S491-D1S205-D1S414-端粒。D1S205周围的微缺失有助于通过杂合性测试将关键区域缩小到D1S491-D1S414。在这项研究中，通过检测一个新家族中的D1S205重组体来精确定位，表明VWS位于D1S491和D1S205之间，间隔为1.6 cM。从D1S245到D1S414构建了大约3.5-Mb的YAC重叠群，包括1级或2级路径中的间隔D1S491-D1S205。利用上述5个多态性标记、4个从YAC末端鉴定的新的STS和一个来自探针CRI-L461（D1S70）的新的STS，通过序列标记位点（STS）含量组装克隆。D1S70被指定为关键区域。一个单一的YAC，yCEPH785B2，含有两个侧翼STS（D1S491，D1S205）。STS内容图谱表明，既不是嵌合体，也没有删除yCEPH 785 B2，但确实表明，关键区域的最大大小约为850 kb。测试所有STS在含有微缺失的1号染色体作为唯一的人1号染色体组分的体细胞杂交体上的存在。微缺失的近端和远端均定位于850-kb YAC，yCEPH 785 B2。因此，微缺失与关键区域重叠，证实了遗传重组数据。
Van der Woude syndrome (VWS) is the most frequent form of syndromic clefting. Linkage analysis has localized the gene between D1S245 and D1S414, an interval of 4.1 cM with the following order of loci: centromere–D1S245/D1S471–D1S491–D1S205–D1S414–telomere. A microdeletion around D1S205 aided in narrowing the critical region to D1S491–D1S414 by heterozygosity testing. In this study, the location was refined by detection of a recombinant with D1S205 in a new family, indicating that VWS lies between D1S491 and D1S205, a 1.6-cM interval. A roughly 3.5-Mb YAC contig was built from D1S245 through D1S414, encompassing the interval D1S491–D1S205 in level 1 or level 2 paths. Clones were assembled by sequence tagged site (STS) content using the five polymorphic markers from above, four novel STSs identified from YAC ends, and a new STS derived from probe CRI-L461 (D1S70). D1S70 was assigned to the critical region. One single YAC, yCEPH785B2, contains both flanking STSs (D1S491, D1S205). STS content mapping suggests neither chimerism nor deletion of yCEPH785B2 but does suggest that the maximum size of the critical region is approximately 850 kb. All STSs were tested for their presence on a somatic cell hybrid containing the microdeleted chromosome 1 as the sole human chromosome 1 component. Both the proximal and distal ends of the microdeletion mapped to the 850-kb YAC, yCEPH785B2. Therefore, the microdeletion overlapped the critical region, confirming the genetic recombinant data.