Human Genetics Research Centre, Division of Biomedical Sciences (BMS), Saint George's University of London (SGUL), London, UK ; Princess Al-Jawhara Al-Ibrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
Princess Al-Jawhara Al-Ibrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
Comput Math Methods Med. 2014;2014:904052. doi: 10.1155/2014/904052. Epub 2014 Mar 4.
GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified in GalNAc-T1 by using FastSNP tool. Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases.
GalNAc-T1 是参与粘蛋白型 O-糖基化途径的 GalNac 转移酶基因家族的关键候选物，在大多数生物组织和细胞类型中表达。尽管已经报道 GalNAc-T1 基因突变与人类疾病易感性有关，但编码、非编码和调控 SNPs 及其对蛋白质水平的功能影响的综合计算分析仍然未知。因此，我们使用基于序列和结构的计算工具来筛选 GalNAc-T1 基因的所有列出的编码 SNP，以识别和表征它们。我们通过 SIFT、PolyPhen-2、PANTHER-cSNP 和 SNPeffect 工具进行的一致的计算机分析，从 GalNAc-T1 的 18 个非编码 SNP 中鉴定出潜在的 nsSNP（S143P、G258V 和 Y414D 变体）。此外，我们还使用 FastSNP 工具在 GalNAc-T1 中鉴定出 2 个调控 SNP（rs72964406 和 rs34304568）。通过多种计算方法，我们系统地对调节和编码区域的功能突变进行了分类，这些突变可以改变 GalNAc-T1 酶的表达和功能。这些遗传变异可以进一步帮助更好地理解与粘蛋白为基础的细胞信号和致病结合相关的广泛疾病易感性，并可能有助于为相关疾病开发新的治疗元素。
