Unit 4: Developmental Genetics

1. Unit 4: Developmental Genetics 6 days

2. October 23:

3. Birth Defects • The medical impact of birth defects is considerable • More than 20% of infant deaths are from birth defects • An additional 20% may be caused by complications of pre-maturity

4. Birth Defects • In addition to mortality there is a high level of morbidity • Mental retardation and other dysfunctions that limit the productivity of affected individuals

5. Birth Defects • Developmental anomalies have a major impact on public health • Genetic counseling and prenatal diagnosis, with the option to terminate the pregnancy, are important for helping individuals faced with a risk of serious birth defects in their offspring

6. Birth Defects • Dysmorphy is the study of congenital birth defects that alter the shape or form of one or more parts of the body of a newborn • A dysmorphologist strives to understand how genes and environmental influences lead to birth defects

7. Birth Defects • They also suggest diagnostic evaluations • They develop a plan to manage expected complications • They provide the family with an understanding of the causation of the malformation

8. Birth Defects • Perhaps the most important job is to give recurrence risks to the parents and other relatives

9. Birth Defects • Three major categories: • Malformations • Deformations • Disruptions

10. Malformations • Result from intrinsic abnormalities in one or more genetic programs operating during development • Ex. Extra fingers in Greig Cephalopolysyndactyly

11. Greig Cephalopolysyndactyly

12. Polydactyly

13. Syndactyly

14. Deformations • Caused by extrinsic factors impinging physically on the fetus during development • Especially common during the second trimester when the fetus is constrained within the amniotic sac

15. Deformations • Ex. Contractions of the joints of the extremities called arthrogryposes • Occasionally accompany constraint of the fetus due to twin or triplet gestation

16. Congenital Arthrogryposes

17. Deformations • Most deformations apparent at birth can be treated by external fixation devices or resolve spontaneously

18. Disruptions • Result from destruction of irreplaceable normal fetal tissue • More difficult to treat than deformations because of the loss of actual tissue

19. Disruptions • May be caused by vascular insufficiency, trauma, or teratogens • Ex. Amnion disruption which is the partial amputation of a fetal limb, caused by strands of amniotic tissue • Often recognized by the presence of partial irregular digit amputation in conjunction with constriction rings

20. Amnion Disruption

21. Malformations • Malformations can have many causes • Chromosome imbalance (25%) • Trisomy 21, 18, 13 are most common • Single gene mutations (20%) • Achondroplasia • Complex inheritance (50%) • Cleft lip and cleft palate • Environmental teratogen (5%) • Fetal alcohol syndrome • Can be drugs, infections, chemicals, radiation, etc.

22. October 24:

23. Developmental Biology • A single cell is transformed into an adult human with • 1014 cells • Hundreds of different cell types • Dozens of tissues

24. Developmental Biology • Has roots in embryology • 19th and early 20th century studies showed that organisms develop from single cells • Used amphibian and avian embryos • Defined many of the fundamental processes

25. Developmental Biology • Evolution is critically important • Early in development embryos of many species look similar • As development progresses the features shared between species successively transform into more specialized features, that are in turn shared by successively fewer, but more closely related, species

26. October 31:

27. Developmental Biology

28. Homologous Structures • Evolved from a structure present in a common ancestor

29. Divergent Evolution

30. Analogous Structures • Appear to be similar, but arose independently

31. Convergent Evolution

32. November 4:

33. Developmental Genetics • Development results from genes interacting with cellular and environmental cues • However, the genome is not an architect’s blueprint, not a literal description of the final form of all structures

34. Developmental Genetics • Rather it specifies a set of interacting proteins that set in motion different processes like growth, migration, differentiation, and apoptosis • This ultimately results in the correct mature structures, with a high degree of accuracy

35. Developmental Genetics • For example: • It is not coded for the eye to be spherical • The shape is a consequence of developmental processes

36. Developmental Genetics • Probability also plays a huge role as well • A mutation being present does not ensure that the organism will have malformations

37. Developmental Genetics • Environmental factors can be a huge factor in development as well • Many cells use concentration gradients and cell to cell signaling to determine placement and function • Environmental substances can mimic or disrupt this (teratogens)

38. Developmental Genetics • Sometimes the pathways active in embryonic development are turned off in adulthood • Chemicals that disrupt embryos may cause little to no damage to adults

39. Developmental Genetics • Isoretinoid • Used to treat acne • Alcohol • Fetal alcohol syndrome • Thalidomide • Sedative used widely in the 1950’s

40. Fetal Retinoid Syndrome

41. Fetal Alcohol Syndrome

42. Thalidomide Syndrome

43. November 7:

44. Cellular Processes • Proliferation • Differentiation • Migration • Apoptosis

45. Human Embryogenesis • After fertilization, the human embryo undergoes a series of cleavages • After 3 days and 4 divisions, the 16 cell morula has been formed

46. Human Embryogenesis • At day 4 the mass transitions to a blastocyst • Cells that give rise to the placenta form a wall • Cells that will turn in to the embryo itself aggregate to one side (this is called the inner cell mass)

47. Human Embryogenesis • At this point the embryo acquires its first manifestations of polarity • The inner cell mass is bilaterally symmetrical

48. Human Embryogenesis • Then the inner cell mass separates again into the epiblast (which will form the embryo proper) and the hypoblast (which will for the amniotic membrane) • The embryo then implants in the endometrial wall between 7 and 12 days after fertilization

49. Human Embryogenesis

50. Human Embryogenesis • After implantation, gastrulation occurs • This is where the cells rearrange themselves into the 3 germ layers • Ectoderm • Mesoderm • Endoderm