Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Phân tích in silico về các biến thể đơn nucleotide không đồng nghĩa (nsSNPs) trong gen GJA3 ở người liên quan đến đục thủy tinh thể bẩm sinh
Tóm tắt
Protein liên kết khoảng trống alpha 3 (GJA3), một gen gây bệnh quan trọng của đục thủy tinh thể bẩm sinh, mã hóa protein xuyên màng connexin46, chức năng như một kênh tế bào liên tế bào để kiểm soát điện và hóa học bằng cách hình thành các dodecamer. Nghiên cứu này đã hệ thống thu thập thông tin về nsSNP của gen GJA3 từ các cơ sở dữ liệu SNP và tài liệu khoa học và sàng lọc các nsSNP có nguy cơ gây bệnh cao. Tổng số 379 nsSNP của GJA3 đã được xác định. Có tổng cộng 88 nsSNP GJA3 gây bệnh có nguy cơ cao đã được phát hiện, bao gồm 31 nsSNP đã được công bố liên quan đến đục thủy tinh thể bẩm sinh và 57 nsSNP mới được dự đoán bởi tất cả tám công cụ trực tuyến. 88 đột biến gây bệnh có nguy cơ cao, liên quan đến 67 axit amin trong các chuỗi loại hoang dã, gây ra sự giảm độ ổn định của protein theo I-Mutant 3.0, MUpro và INPS. G2 và R33 được dự đoán sẽ tham gia vào quá trình sửa đổi sau dịch mã và liên kết ligand thông qua ModPred, RaptorX Binding và COACH. Ngoài ra, các đột biến có nguy cơ cao có khả năng liên quan đến các vị trí bảo tồn cao, chuỗi ngẫu nhiên, alpha helix và vòng ngoài tế bào và đi kèm với sự thay đổi về kích thước axit amin, điện tích, độ kỵ nước và cấu trúc không gian. Tám mươi tám nsSNP GJA3 gây bệnh có nguy cơ cao đã được sàng lọc trong nghiên cứu, trong đó 57 nsSNP được báo cáo lần đầu. Sự kết hợp của nhiều công cụ in silico là rất hiệu quả trong việc nhắm mục tiêu các vị trí gây bệnh.
Từ khóa
#GJA3 #đục thủy tinh thể bẩm sinh #nsSNP #protein liên kết khoảng trống #phân tích in silicoTài liệu tham khảo
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