医学遗传学Inborn error of metabolism and molecular disease.pptVIP

Molecular Disease and Inborn Errors of Metabolism ZHANG Xian-Ning, PhD zhangxianning@zju.edu.cn Tel Office: C303, Teaching Building 2014/10 Molecular Biochemical Genetics The study of structure and function of individual genes. 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. The Effect of Mutation on Pr. Function Loss of Pr. function (功能失去突变。the great majority): is seen in (1)recessive diseases; (2)diseases involving haploinsufficiency（单倍不足性）, in which 50% of the gene product is insufficient for normal function; and (3)dominant negative mutations（显性负效突变）, in which the abnormal protein product interferes with the normal protein product. The Effect of Mutation on Pr Function 2. Gain of function（功能获得突变）: are sometimes seen in dominant diseases. 3. Novel property (新特性。infrequent) 4. The expression of a gene at the wrong time (Heterochronic expression异时表达), or in the wrong place (Ectopic expression异位表达), or both. (uncommon, except in cancer) Hemoglobinopathies血红蛋白病: Disorders of human hemoglobins 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. Genetic disorders of Hb 1. Structural variants: alter the globin（珠蛋白） polypeptide without affecting its rate of synthesis. 2. Thalassemias: reduced rate of production of one or more globin chains. 3. Hereditary persistence of fetal hemoglobin (HPFH遗传性胎儿血红蛋白持续存在症) : a group of clinically benign conditions, impairing the perinatal switch from γ- toβ-globin synthesis. There are 400 structural variants of normal hemoglobin. The 4 most common structural variants are: Hb S (Sickle cell anemia):βchain: Glu6Val Hb C: β chain: Glu6Lys Hb E: β chain: Glu26Lys Hb M (Methemoglobin高铁血红蛋白): An oxidizing form of Hb containing ferric iron that is produced by the action of oxidizing po