Physical and transcriptional mapping of the X-linked cleft palate and ankyloglossia (CPX) critical region
Physical and transcriptional mapping of the X-linked cleft palate and ankyloglossia (CPX) critical region
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DOI：
10.1007/s004390100518
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发表时间：
2001-06-01
期刊：
影响因子：
5.3
通讯作者：
Stanier, P
中科院分区：
文献类型：
--
作者：
Braybrook, C;Warry, G;Stanier, P
腭裂最常见的是一种散发性的多因素疾病，具有明确但难以定义的遗传成分。作为一种半显性遗传疾病，X连锁腭裂（CPX）为研究一种受非遗传因素影响较小的先天性缺陷提供了一个有用的模型。通过使用冰岛的亲属，CPX已被定位在DXS 1196和DXS 1217之间，并映射在一个3-Mb的酵母人工染色体重叠群中，在Xq21.3。从该物理图谱产生的标记现在已用于构建PI的重叠群和细菌人工染色体克隆，用于基因组DNA测序。基因组DNA序列分析揭示了Cen-KLHL 4-LAMRL 5-CAPZA 1 P-CPXCR 1-Tel顺序的两个新表达基因和两个假基因。KLHL 4和CPXCR 1在胎儿组织中广泛表达，包括舌、下颌骨和腭。CPXCR 1的DNA突变筛查揭示了所有受影响的CPX染色体上存在的几种序列变体。然而，在未受影响的染色体上也以较低的频率检测到这些变体，表明它们是不太可能导致CPX表型的多态性。
Cleft palate most commonly occurs as a sporadic multifactorial disorder with a clear but difficult to define genetic component. As a semi-dominant disorder, X-linked cleft palate (CPX) provides a useful model to investigate a congenital defect that is little influenced by non-genetic factors. By using an Icelandic kindred, CPX has been localised between DXS1196 and DXS1217 and mapped, in a 3-Mb yeast artificial chromosome contig, at Xq21.3. Markers generated from this physical map have now been used to construct a contig of PI and bacterial artificial chromosome clones for genomic DNA sequencing. Genomic DNA sequence analysis has revealed two novel expressed genes and two pseudogenes in the order Cen-KLHL4-LAMRL5-CAPZA1P-CPXCR1-Tel. KLHL4 and CPXCR1 are widely expressed in fetal tissues, including the tongue, mandible and palate. DNA mutation screening of CPXCR1 has revealed several sequence variants present on all affected CPX chromosomes. However, these variants have also been detected at a lower frequency on unaffected chromosomes, indicating that they are polymorphisms that are unlikely to cause the CPX phenotype.