Prediksi Struktur 3 Dimensi dan Analisis In Silico Protein Akibat Delesi Alfa 4,2 pada Gen Alfa-Globin

NURUL FITRI T TAGUNU, Dr. Niken Satuti Nur Handayani, M.Sc.

2019 | Tesis | MAGISTER BIOLOGI

Thalassemia merupakan kelainan genetik diakibatkan oleh mutasi pada gen globin. Mutasi delesi α4,2 merupakan mutasi silent trait, namun pada penelitian ini nilai hematologis MHC dan MCV lebih rendah dibandingkan dengan kisaran normal serta terdapat abnormalitas morfologi eritrosit. Tujuan penelitian ini adalah menentukan titik potong delesi α4,2, memprediksi dan menganalisis efek mutasi delesi α4,2 terhadap protein hemoglobin dikaitkan dengan gangguan fisiologi penderita. DNA sampel darah disekuensing menggunakan metode Sanger. Proses alignment dilakukan dengan Clustal Omega, prediksi dan analisis struktur hemoglobin dilakukan dengan CHIMERA dan Discovery Studio. Titik potong delesi α4,2 berada diantara basa nomor 26 sekuens box X2 dan basa nomor 347 sekuens box X1. Delesi α4,2 memiliki struktur protein yang sama dengan protein normal baik residu ataupun seluruh ikatan penstabil protein. Nilai MCH dan MCV yang rendah serta abnormalitas morfologi eritrosit merupakan konsekuensi kurangnya produksi subunit α yang diakibatkan mutasi. Hasil analisis menyimpulkan delesi 1 gen yakni α4,2 tetap menghasilkan struktur hemoglobin yang normal dengan fungsi yang normal.

Thalassemia is a genetic disorder caused by mutations in the globin gene. The α4.2 deletion mutation is a silent trait mutation, but in this study the hematological value of MHC and MCV is lower than the normal range and there are morphological abnormalities of erythrocytes. The aim of this study is to determine the breakpoint of α4.2 deletion, predict and analyze the effect of the α4.2 deletion mutation on the hemoglobin protein associated with physiological disorders of the patient. DNA of blood sample was sequenced by using the Sanger method. The alignment process was carried out with Clustal Omega, prediction and analysis of the structure of hemoglobin is done by CHIMERA and Discovery Studio. The breakpoint for deletion α4.2 was found in base number 26 of box X2 sequence and base number 347 of box X1 sequence. The α4.2 deletion showed the same protein structure as a normal protein either residue or all protein stabilizing bonds. Low MCH and MCV values and morphological abnormalities of erythrocytes were a consequence of the lack of α subunit production caused by mutations. The results of the analysis concluded that deletion of 1 gene, α4.2, produces a normal hemoglobin structure with normal function.

Kata Kunci : eritrosit, hemoglobin, delesi α4,2, struktur protein, patologi thalassemia