Molecular disease(分子病) a disease in which there is an abnormality in or a deficiency of a particular molecule, such as hemoglobin in sickle cell anemia 酶蛋白病( enzymopathy): Any of a group of congenital disorders caused by an inherited defect in a single specific enzyme that results in a disruption or abnormality in a specific metabolic pathway
Molecular Disease（分子病） A disease in which there is an abnormality in or a deficiency of a particular molecule, such as hemoglobin in sickle cell anemia 酶蛋白病（enzymopathy）：Any of a group of congenital disorders caused by an inherited defect in a single specific enzyme that results in a disruption or abnormality in a specific metabolic pathway
Hemoglobinopathies血红蛋白病 Disorders of the human hemoglobins The most common single gene disorders in the world WHO: 5% of the worlds population are carriers for clinically significant hemoglobinopathies Well understood at biochemical and molecular levels
Hemoglobinopathies血红蛋白病 • Disorders of the human hemoglobins • The most common single gene disorders in the world – WHO: 5% of the world’s population are carriers for clinically significant hemoglobinopatihies • Well understood at biochemical and molecular levels
HbA: a2B2/HbF: a2Y2 Globular tetramer MW645KD a-Chain 16pl33 Polypeptide length of 141 amino acids 阝 Chain 11p15.4 Polypeptide length of 146 amino acids
HbA: α2β2 / HbF: α2 γ2 • Globular tetramer • MW 64.5 kD • α-Chain – 16p13.3 – Polypeptide length of 141 amino acids • β-Chain – 11p15.4 – Polypeptide length of 146 amino acids
Globin Tertiary structure Myoglobin One O2 binding site 阝 Hemoglobin A Four O2 binding sites
Globin Tertiary Structure
BLCR YG YA YB1 8 B TH IHm Chromosome 11: B-globin genes Hs-40 yC2 vC1 yo2 vol a2 a1 01 I IH HH HIHI Pseudogene 0 10 20 30 50 60 kb Chromosome 16: a-globin genes Gene cluster基因簇: a group of adjacent genes that are identical or related Pseudogene假基因: DNA Sequence homologous with a known gene but is non-functional
Gene cluster基因簇: A group of adjacent genes that are identical or related Pseudogene假基因: DNA sequence homologous with a known gene but is non-functional