《医学遗传学》课程PPT教学课件（留学生 Medical Genetics）09 Chapter Molecular Disease

Medical Genetics Molecular Disease

Molecular Disease Medical Genetics

Emphasis Molecular Disease Pathogenesis of Abnormal Hemoglobin Pathogenesis of Thalassemia 10

Emphasis ❖ Molecular Disease ❖ Pathogenesis of Abnormal Hemoglobin ❖ Pathogenesis of Thalassemia

*1902,Garrod AE the incidence of alkaptonuria: a study in clinical individuality *1948,Horlein H,Weber G g 1949,PaulingL Sickle cell anemia,a molecular disease. Science.110:543-548,1949

❖ 1902, Garrod AE the incidence of alkaptonuria: a study in clinical individuality ❖ 1949, Pauling L Sickle cell anemia, a molecular disease. Science. 110: 543-548, 1949. ❖ 1948, Hörlein H, Weber G

Molecular Disease A disease in which the manifestations are due to alterations in protein structure and quantity

Molecular Disease A disease in which the manifestations are due to alterations in protein structure and quantity

Structure of Hemoglobin

Structure of Hemoglobin

B-globin Ancestral globin gene Duplication a-globin Heme Mutation HEMOGLOBIN Transposition BI Duplications and mutations B扇 A Fetus Fetus Adult and adult Embryo Pseudogenes Embryo Pseudogene a-globin gene family B-globin gene family (chromosome 16) (chromosome 11) 1999 Addison Wesley Longman,Inc

Hemoglobin Alpha Chain 16pter-p13.3 w%yC2必 1 313299100 141

  1 2 1 5‘ 3’ 16pter-p13.3 1 31 32 99 100 141 Hemoglobin Alpha Chain

Hemoglobin Beta Chain 11p15.5 Cy Ay Bδ 3 10 13031104105 146

11p15.5 ε G A ψ1 δ β 5’ 3’ Hemoglobin Beta Chain 1 30 31 104 105 146

Development of Hemoglobin 100 (%)sIS uAs uqoT3 80 60 40 : 2 ◆ 0 6 8 Birth 2 Months

0 2 4 6 8 Birth 2 4 6 8 Months 100 80 60 40 Percentage of 20 globin synthesis(%) Development of Hemoglobin δ ζ ε α γ β α

Development of Hemoglobin Developmental Hemoglobin Hemoglobin Stage Composition Embryo Hb Gower1 S22 Hb Gower2 02E2 Hb Portland 52SY2 52AY2 Fetus Hb F O2GY2 Q2AY2 Adult Hb A a2β2 Hb A2 0a2⊙2

Developmental Stage Hemoglobin Hemoglobin Composition Embryo Hb Gower1 2 2 Hb Gower2 2 2 Hb Portland 2 G 2 2 A 2 Fetus Hb F 2 G 2 2 A 2 Adult Hb A 2 2 Hb A2 2 2 Development of Hemoglobin