Genomic organization of the human fibroblast growth factor receptor 2 (FGFR2) gene and comparative analysis of the human FGFR gene family.
Genomic organization of the human fibroblast growth factor receptor 2 (FGFR2) gene and comparative analysis of the human FGFR gene family.
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人成纤维细胞生长因子受体 2 (FGFR2) 基因的基因组组织和人 FGFR 基因家族的比较分析。
DOI：
10.1016/s0378-1119(99)00047-5
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发表时间：
1999
期刊：
影响因子：
3.5
通讯作者：
Ehrlich,GD
中科院分区：
文献类型：
--
作者：
Zhang,Y;Gorry,MC;Post,JC;Ehrlich,GD
人成纤维细胞生长因子受体(FGFR)基因在脊椎动物正常发育过程中发挥着重要作用。人类FGFR2基因突变与许多颅脑融合综合征和畸形有关，包括Crouzon、Pfeiffer、Apert、Jackson-Weiss、Beare-Stevenson cutis gyrata和Antley-Bixler综合征，以及Kleeblaatschadel(三叶草颅骨)畸形。到目前为止，已发现的突变集中在FGFR2先前描述的区域，该区域编码受体蛋白的细胞外IgIII结构域。然而，由于缺乏对基因组结构的了解，在该基因其他区域寻找突变的工作一直受到阻碍。利用基因组文库筛选、长距离聚合酶链式反应和基因组行走相结合的方法，我们已经描述了几乎整个人类FGFR2基因的基因组结构，包括描绘了所有内含子和外显子的组织和大小，并确定了内含子/外显子边界的DNA序列。对人类FGFR基因家族的比较分析表明，FGFR的基因组结构相对保守。此外，氨基酸序列的比对表明，四个相应的蛋白质总体上有46%的同源性，个别FGFR蛋白对之间的同源性高达70%。然而，FGFR2基因包含一个在该家族其他成员中没有的额外外显子，而且它在整个基因中也有更大的内含子序列。人类和小鼠FGFR2基因在基因组结构、内含子/外显子边界和内含子大小方面有显著的相似之处。从这项关于人类FGFR2基因结构的研究中获得的知识可能被证明在未来的筛查研究中被证明是有用的，该研究旨在发现与颅缝融合综合征相关的其他突变，并有助于了解该受体家族的分子和细胞生物学。
The human fibroblast growth factor receptor (FGFR) genes play important roles in normal vertebrate development. Mutations in the human FGFR2 gene have been associated with many craniosynostotic syndromes and malformations, including Crouzon, Pfeiffer, Apert, Jackson–Weiss, Beare–Stevenson cutis gyrata, and Antley–Bixler syndromes, and Kleeblaatschadel (cloverleaf skull) deformity. The mutations identified to date are concentrated in the previously characterized region of FGFR2 that codes for the extracellular IgIII domain of the receptor protein. The search for mutations in other regions of the gene, however, has been hindered by lack of knowledge of the genomic structure. Using a combination of genomic library screening, long-range PCR, and genomic walking, we have characterized the genomic structure of nearly the entire human FGFR2 gene, including a delineation of the organization and size of all introns and exons and determination of the DNA sequences at the intron/exon boundaries. Comparative analysis of the human FGFR gene family reveals that the genomic organization of the FGFRs is relatively conserved. Moreover, alignment of the amino acid sequences shows that the four corresponding proteins share 46% identity overall, with up to 70% identity between individual pairs of FGFR proteins. However, the FGFR2 gene contains an additional exon not found in other members of the family, and it also has much larger intronic sequences throughout the gene. Remarkable similarities in genomic organization, intron/exon boundaries, and intron sizes are found between the human and mouse FGFR2 genes. Knowledge gained from this study of the human FGFR2 gene structure may prove useful in future screening studies designed to find additional mutations associated with craniosynostotic syndromes, and in understanding the molecular and cell biology of this receptor family.
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