Điều chỉnh mục tiêu phụ thuộc vào miRNA: đặc trưng chức năng của các đa hình nucleotide đơn được xác định trong các nghiên cứu liên kết toàn bộ gen về bệnh Alzheimer
Tóm tắt
Một lượng ngày càng tăng bằng chứng cho thấy rằng microRNA (miRNA) có liên quan đến bệnh Alzheimer (AD) và một số biến thể gen liên quan đến bệnh được xác định nằm trong các điểm gắn kết miRNA. Trong nghiên cứu hiện tại, chúng tôi đã cố gắng đặc trưng hóa các đa hình chức năng trong các điểm mục tiêu miRNA trong các loci được xác định trong các nghiên cứu liên kết toàn bộ gen trước đó (GWAS). Các mục tiêu chính của nghiên cứu này là (1) hỗ trợ việc xác định gene hoặc các gene chịu trách nhiệm cho tín hiệu GWAS trong một locus quan tâm và (2) xác định cách mà các đa hình chức năng có thể tham gia vào quá trình bệnh AD (ví dụ: bằng cách ảnh hưởng đến sự biến thiên trong biểu hiện gen qua trung gian miRNA).
Các phân tích in silico nghiêm ngặt đã được phát triển để lựa chọn các đa hình tiềm năng dễ bị tổn thương trong việc ức chế do miRNA trung gian, và các xét nghiệm chức năng tiếp theo được thực hiện trên tế bào HeLa và HEK293.
Hai đa hình đã được xác định và phân tích thêm trong vitro. Allele rs7143400-T liên quan đến AD (nằm trong vùng không phiên mã 3′ [3′-UTR] của
Khi được xem xét cùng với các phát hiện của các nghiên cứu liên kết trước đó, kết quả của chúng tôi gợi ý rằng sự giảm biểu hiện của
Từ khóa
Tài liệu tham khảo
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