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Developmental Genetics and Health Risks of Smoking During Pregnancy

Explore gene regulation in development, microRNA control, protein targeting, and smoking effects on fetal development influencing adult health. Understand genetic impacts on obesity, heart disease, and more.

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Developmental Genetics and Health Risks of Smoking During Pregnancy

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  1. Homework #2 is due 10/18 • Bonus #1 is due 10/25 • Weekly quiz online each Thursday, due each Tuesday Fig 8.19

  2. Gene Expression is controlled at all of these steps: • DNA packaging • Transcription • RNA processing and transport • RNA degradation • Translation • Post-translational Fig 16.1

  3. C. elegans is commonly used to study development

  4. C. elegans development

  5. C. elegans mutants with cells that do not develop properly. Fig 12.25 and

  6. C. elegans mutants with cells that do not develop properly. The product of these genes was found to be RNA?

  7. MicroRNAs (miRNA) are ~22nt RNAs that play important regulatory roles Cell vol. 116, 281-297 2004

  8. miRNA expressed How do microRNAs control gene expression? miRNA processed to ~22nt RNA Mature miRNA

  9. A processed mRNA ready for translation: microRNAs inhibit translation by binding to the 3’ end of mRNA microRNA bind to 3’-UTR 5’-UTR 3’-UTR

  10. miRNA expressed the 3’ end with attached microRNA interacts with the 5’ end, blocking translation miRNA processed to ~22nt RNA Mature miRNA

  11. miRNAs can lead to methylation of DNA that leads to inhibition of transcription

  12. microRNAs primarily target gene products that function during development Tbl 1

  13. tissue specific expression of mouse microRNA PNAS vol. 101 #1 pg 360-365, 2004

  14. Silencing RNAs (siRNA) are artificially induced dsRNA Fig 8.22

  15. siRNA with exact matches to the target mRNA causes degradation of the mRNA Fig 8.21

  16. microRNA siRNA mRNA degraded Translation inhibited

  17. Gene Expression is controlled at all of these steps: • DNA packaging • Transcription • RNA processing and transport • RNA degradation • Translation • Post-translational Fig 16.1

  18. Phosphorylation and dephosphorylation of proteins can change activity Fig 9.21

  19. Ubiquitinization targets proteins for degradation Fig 9.23

  20. All protein interactions in an organism compose the interactome

  21. Some proteins function in the cytoplasm; others need to be transported to various organelles.

  22. How can proteins be delivered to their appropriate destinations?

  23. Protein Destinations: secretion or membrane

  24. Signal sequences target proteins for secretion Fig 9.24

  25. Translation of secreted proteins

  26. Translation of membrane bound proteins

  27. Translation of secreted or membrane bound proteins This step determines secretion or membrane bound.

  28. Protein Destinations: nucleus Signal anywhere in protein, Translation in cytoplasm, Signal not removed

  29. Protein Destinations: mitochondria or chloroplast Signal translated first, Translation in cytoplasm, Signal removed

  30. Protein Destinations: signals in protein determine destination

  31. Development: differentiating cells to become an organism

  32. Cells function differently because they express differentgenes.

  33. The proper control of gene expression is critical for proper development.

  34. So development in animals is one way.

  35. Inverse relationship between smoking and weight: more smoking : less weight

  36. Effect of smoking on fetal development and how that can affect adults

  37. Adults exposed to smoke as fetuses have higher risk of obesity and heart disease

  38. What is the connection?

  39. Obesity, Diabetes, Heart Disease, High Blood Pressure, Some Cancers all may have some origins during fetal development.

  40. Adults metabolism may react to poor nutrition as fetuses… Adaptation of Thriftiness or Catch Up Growth.

  41. Adults metabolism may react to poor nutrition as fetuses…Adaptation of Thriftiness or Catch Up Growth. Study of babies born during Dutch famine of 1944-45…

  42. Adults metabolism may react to poor nutrition as fetuses…Adaptation of Thriftiness or Catch Up Growth. Study of babies born during Dutch famine of 1944-45… 20 years later found that these babies had higher rates of obesity.

  43. Adults metabolism may react to poor nutrition as fetuses…Adaptation of Thriftiness or Catch Up Growth. Study of babies born during Dutch famine of 1944-45… 20 years later found that these babies had higher rates of obesity. Precise mechanism is not known

  44. What about smoking? 17,000 births studied and checked at age 16 and 33. Fetuses exposed to smoking had increased rate of obesity.

  45. What about smoking? 17,000 births studied and checked at age 16 and 33. Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity.

  46. What about smoking? 17,000 births studied and checked at age 16 and 33. Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity. For Mom’s who abstained during pregnancy, no effect on fetus or as adult.

  47. What about smoking? 17,000 births studied and checked at age 16 and 33. Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity. Smoking during first trimester had same effect as during whole pregnancy.

  48. What about smoking? For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes.

  49. What about smoking? Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy

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