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Phân tích di truyền các gen ứng cử viên làm biến đổi tuổi khởi phát bệnh Huntington
Tóm tắt
Sự mở rộng của sự lặp lại CAG đa hình trong gen HD mã hóa protein huntingtin đã được xác định là nguyên nhân chính gây ra bệnh Huntington (HD) và quyết định 42–73% sự khác biệt về độ tuổi khởi phát bệnh. Các đột biến đa hình ở huntingtin và các gen liên quan được cho là có khả năng làm biến đổi diễn biến của bệnh. Để xác định các yếu tố di truyền làm ảnh hưởng đến tuổi khởi phát bệnh, chúng tôi đã tìm kiếm các dấu hiệu đa hình trong các gen GRIK2, TBP, BDNF, HIP1 và ZDHHC17 và phân tích bảy gen trong số này thông qua các nghiên cứu liên kết trên 980 bệnh nhân HD Châu Âu độc lập. Trong quá trình sàng lọc các biến thể trình tự chưa biết, bên cạnh một số biến thể im lặng, chúng tôi đã phát hiện ba đột biến đa hình trong gen ZDHHC17. Các đột biến này cùng với các đa hình trong gen GRIK2, TBP và BDNF đã được phân tích liên quan đến tuổi khởi phát bệnh HD. Mặc dù một số yếu tố đã được xác định là các yếu tố di truyền điều chỉnh trong các nghiên cứu trước đây, không có gen mã hóa GRIK2, TBP, BDNF và ZDHHC17 nào được xác định là yếu tố điều chỉnh di truyền cho bệnh HD.
Từ khóa
#bệnh Huntington #gen HD #đa hình #tuổi khởi phát #nghiên cứu di truyềnTài liệu tham khảo
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