Genetic disorders 4

1,268 views

Published on

Genetic Disorders (No 4)

Published in: Health & Medicine, Technology
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,268
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
23
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Genetic disorders 4

  1. 2. Genetic Disorders Biochemical and Molecular Basis of Single Gene (Mendelian) Disorders Dr. Shahab Riaz
  2. 3. Biochemical and Molecular Basis of Single Gene (Mendelian) Disorders <ul><li>Protein or gene product synthesis affected by: </li></ul><ul><li>Affecting transcription </li></ul><ul><li>Affecting mRNA processing </li></ul><ul><li>Affecting translation </li></ul><ul><li>Phenotypic Effects of Altered Protein: </li></ul><ul><li>Direct influence by abnormal protein on structure </li></ul><ul><li>Indirect influence by interaction of abnormal with normal protein </li></ul><ul><li>Example: </li></ul><ul><li>Ehlers Danlos Syndrome (abnormal collagen) </li></ul><ul><li>Vascular Type EDS  mutation in one of the collagen genes </li></ul><ul><li>Kyphoscoliosis Type EDS  Collagen genes normal  mutant lysyl hydroxylase enzyme gene  abnormal collagen cross-linking </li></ul>
  3. 4. Biochemical and Molecular Basis of Single Gene (Mendelian) Disorders <ul><li>Mechanisms: </li></ul><ul><li>Enzyme defects and their consequences </li></ul><ul><li>Defects in membrane receptors and transport systems </li></ul><ul><li>Alterations in the structure, function or quantity of non-enzyme proteins </li></ul><ul><li>Mutations resulting in unusual reactions to drugs </li></ul>
  4. 5. Biochemical and Molecular Basis of Single Gene (Mendelian) Disorders <ul><li>Enzyme defects and their consequences: </li></ul><ul><li>Defective enzyme  reduced activity OR reduced amount </li></ul><ul><li>As a consequence  metabolic block </li></ul><ul><li>Accumulation of Substrate (galactosemia, phenylketonuria, LSD) </li></ul><ul><li>Metabolic block, end product (melanin lack, tyrosinase) </li></ul><ul><li>Failure to inactivate toxic substrate ( α 1-AT deficiency) </li></ul>
  5. 6. Biochemical and Molecular Basis of Single Gene (Mendelian) Disorders <ul><li>Defects in membrane receptors and transport systems: </li></ul><ul><li>Active transport across CM  receptor mediated endocytosis OR Transport protein </li></ul><ul><li>E.g., Familial Hypercholesterolemia  LDL receptors  LDL accumulates outside cell  intermediary mechanisms  cholesterol </li></ul>
  6. 7. Biochemical and Molecular Basis of Single Gene (Mendelian) Disorders <ul><li>Alterations in the structure, function or quantity of non-enzyme proteins: </li></ul><ul><li>Quality compromised  sickle cell anemia  structure of globin molecule abnormal </li></ul><ul><li>Quantity compromised  thalassemia  α or β globin chains </li></ul>
  7. 8. Biochemical and Molecular Basis of Single Gene (Mendelian) Disorders <ul><li>Genetically Determined Adverse Reactions to Drugs: </li></ul><ul><li>Some genetic enzyme deficiencies unmasked only after exposure to certain drugs </li></ul><ul><li>Pharmacogenetics </li></ul><ul><li>E.g., G6PD deficiency  under normal conditions no disease  but if given some drug like antimalarials  severe hemolysis </li></ul>
  8. 9. Disorders Associated with Defects in Structural Proteins <ul><li>Example: Marfan Syndrome </li></ul><ul><li>Disorder of connective tissues  skeleton, eyes and CVS </li></ul><ul><li>1 in 5000, 70 – 85% cases familial, Autosomal Dominant </li></ul><ul><li>Mostly mis-sense mutations  abnormal fibrillin-1 , dominant negative effect </li></ul><ul><li>Mutation in FBN1 gene  EC glycoprotein fibrillin-1 defect </li></ul><ul><li>Defective microfibrils  def. scaffolding and tropoelastin deposition and elastic fiber production </li></ul><ul><li>MFs abundant in aorta, ligaments and ciliary zonules of eye </li></ul><ul><li>Patients tall and thin, abnormally long legs and arms, spider-like fingers ( arachnodactyly ), hyperextensible joints </li></ul><ul><li>Dislocation of ocular lens ( ectopia lentis ) </li></ul><ul><li>Weakness of adventitia and media leads to aortic dilatation, aneurysm of proximal aorta, aortic valvular insufficiency, and aortic dissection, mitral valve prolapse </li></ul>
  9. 10. <ul><li>READ OTHER EXAMPLES AND DISEASES FROM THE BOOK YOURSELF </li></ul>

×