Abstract：
Type IV collagen is an integral component of basement membranes. Mutations in COL4A1, one of the key genes encoding Type IV collagen, can result in a variety of diseases. It is clear that a significant proportion of mutations that affect splicing can cause disease directly or contribute to the susceptibility or severity of disease. Here, we analyzed exonic mutations and intronic mutations described in the COL4A1 gene using bioinformatics programs and identified candidate mutations that may alter the normal splicing pattern through a minigene system. We identified seven variants that induce splicing alterations by disrupting normal splice sites, creating new ones, or altering splice regulatory elements. These mutations are predicted to impact protein function. Our results help in the correct molecular characterization of variants in COL4A1 and may help develop more personalized treatment options.
摘要：
IV型胶原是基底膜的组成部分。COL4A1是编码IV型胶原蛋白的关键基因之一，会导致多种疾病。显然,影响剪接的显著比例的突变可直接引起疾病或促成疾病的易感性或严重性。这里,我们使用生物信息学程序分析了COL4A1基因中描述的外显子突变和内含子突变,并鉴定了可能通过小基因系统改变正常剪接模式的候选突变.我们鉴定了7种通过破坏正常剪接位点诱导剪接改变的变体，创造新的，或改变剪接调节元件。预计这些突变会影响蛋白质功能。我们的结果有助于COL4A1变体的正确分子表征，并可能有助于开发更个性化的治疗方案。
