Chromosomal Aberrations

1. Chromosomal Aberrations • Changes in the numbers of chromosomes • Polyploidy • Extra complete sets of chromosomes • 3N, 4N, 5N, etc. • Aneuploidy • Extra or missing single chromosomes • 2N + 1, 2N -1, etc.

2. Chromosomal Aberrations • Changes in structure • Changes in the number of genes • deletions: genes missing • duplications: genes added

3. Chromosomal Aberrations • Changes in structure • Changes in the location of genes • inversions: 180o rotation • translocations: exchange • transpositions: gene “hopping” • Robertsonian changes: fissions or fusions

4. Polyploidy • Having extra sets • 3N, 4N, etc. • Suffix: “-ploid” or “-ploidy” • 3N = triploid • 4N = tetraploid

5. Polyploidy N = A B C: 2N = AA BB CC:

6. Polyploidy N = A B C: 3N = AAA BBB CCC

7. Polyploidy • Monoploidy (haploidy): rare in animals • exceptions: Bees: males are haploid - develop from unfertilized eggs; females are diploid • More common in plants • alternation of generations increases occurrence of haploidy

8. Haploidy in Plants • Occasionally, unfertilized gamete may develop into adult plant • usually small, with lowered viability • sterile

9. 3N or More in Animals • Most common form of polyploidy in animals is triploidy • arises from two sperm fertilizing the same egg • if the organism survives, it is sterile • pairing of homologues in meiosis is disrupted • Survival is extremely rare

10. 3N or More in Plants • Polyploidy generally improves viability in plants • Plants are larger, produce larger flowers, more seeds, hardier, etc. • Pairing at meiosis is still a problem, especially w/ odd ploidies: 3N, 5N, 7N, etc. • May reproduce asexually

11. Autopolypoidy Extra sets of chromosomes come from the same species Arise from double fertilization usually All chromosomes have homologues Allopolyploidy Extra sets of chromosomes come from different species Arise from hybridization New chromosomes have no homologues 3N or More

12. Allopolyploidy or hybridization Horse + donkey  mule haploid 32 31 N = 63 +

13. Instant Plant Speciation Through Allo- and Autopolyploidy • Possible for entirely new species of plant to be created almost instantly • Hybridization (allopolyploidy) followed by autopolyploidy --> plant w/ totally different chromosomal make up from either parent • Fertile only w/ itself; NEW SPECIES

14. Aneuploidy • Extra single chromosomes or missing single chromosomes • 2N + 1 • 2N - 1 • Suffix: “-somy” or “-somic” • 2N + 1 = trisomy • 2N - 1 = monosomy • 2N + 2 = tetrasomy

15. Aneuploidy • Generally arise through non-disjunction at meiosis • homologues or chromatids do not separate • gametes contain 2 or no copies of one chromosome

16. Aneuploidies in Humans • Most aneuploidies in humans lead to such drastic effects, the fetus is spontaneously aborted early in development • A few survive ‘til birth; some beyond

17. Trisomy 21; Down Syndrome • 47, +21 • 1/700 live births • over 60% of conceptions aborted spontaneously • 20% stillborn • incidence increases sharply w/ maternal age • 1/300 for 35 year olds • 1/22 for 45 year olds

18. Trisomy 21 • characteristic facial appearance • small nose, flat face, epicanthal fold • single palmar crease • mental retardation (avg. IQ < 50) • multiple complications • heart disease • leukemia • epilepsy • some fertility

19. Trisomy 18; Edward Syndrome • 47; +18 • 1/8000 live births; maternal age affect • low birth weight • multiple dysmorphic features • chin, ears, single palmar crease, clenched hands • malformations of the brain, heart, kidneys, and other organs • rarely survive beyond 1 year

20. Trisomy 13; Patau Syndrome • 47; + 13 • 1/20,000 live births; maternal age effect • multiple dysmorphic features • micropthalmia, cleft palate, clenched fists, polydactyly, ears and scalp abnormal… • heart defects; systemic defects…. • 50% die in first month; rarely survive beyond 1 year

21. 47, XXY; Klinefelter Syndrome • 1/500 live male births (?) • often asymptomatic except for sterility, learning disabilities • small testes; low testosterone levels • poorly developed male 2o sexual charact. • some female characteristics: • enlarged breasts, elongated limbs, increased incidence of “female” diseases: breast cancer, scoliosis, osteoporosis • hormone therapy improves symptoms

22. 47, XYY; Jacobs Syndrome • 1/1000 live male births? • formerly called “criminal chromosome” • 99% asymptomatic, though high incidence in penal institutions for the mentally subnormal (20/1000) • lower than average intelligence? (learning disabilities) above average height, tendency to severe acne

23. 45, XO; Turner Syndrome • 1/2500 live female births • generally asymptomatic ‘til puberty • lack of 2o sexual characteristics; amenorrhoea • short stature; low hair line; • heart disease, renal malformations, ovaries generally underdeveloped, sterile • hormone therapy helpful

24. 47; XXX • 1/700 live female births (?) • generally asymptomatic • 15 - 25% mildly mentally retarded • some sterility

25. Changes in Chromosome Structure • Changes in the numbers of genes • deletions • duplications • Changes in the location of genes • inversions • translocations • transpositions • Robertsonian changes

26. Deletions • Loss of a (generally small) segment of chromosome A B D E F G A B C D E F G C

27. Deletions • Arise through spontaneous breakage • some chromosomes have fragile spots • radiation, UV, chemicals, viruses may increase breakage

28. A B C D E F G x A B C D E F G A B C D E G A B C D E F F G Deletion Duplication Deletions • May arise through unequal crossing over

29. Deletions • Large deletions will most probably be lethal • Smaller deletions may allow survival • E. coli: deletions of up to 1% have been observed in living cells • D. melanogaster : deletions of up to 0.1% observed

30. Deletions in Humans • Cri-du-chat syndrome • Micro deletion of chromosome 5 • DiGeorge syndrome • Micro deletion of chromosome 22 • Schizophrenia & Obsessive Compulsive Disorder • Micro deletion of chromosome 22 associated

31. Deletions in Humans • Angelman syndrome • Micro deletion of chromosome 15 • Prader-Willi syndrome • Micro deletion of chromosome 15

32. lack of muscle tone in newborn poor swallowing reflex as adult - gross obesity mean I.Q. ~ 50 microdeletion of 15 developmentally delayed jerky movements stiff, fixed smile uncontrolled laughter abnormal E.E.G., epilepsy microdeletion of 15 Prader-Willi and Angelman Syndromes Prader-Willi Angelman

33. Duplications • Redundant segment of a chromosome A B C D E F F G A B C D E F G

34. Effects of Duplications on Phenotype • Some duplications have a direct effect on phenotype • “Bar” in Drosophila • Acts as an incompletely dominant allele • BB = reduced eye size • Bb = slightly reduced • bb = normal eye

35. Evolutionary Effects of Duplications • Allows development of new, related genes • duplicated gene may mutate and produce a new form of the gene • function may differ slightly, or time of action may differ, etc. • human hemoglobins

36. Human Hemoglobins • Hemoglobin is a tetramer • several different polypeptides which may be involved in forming functional hemoglobin • adults: a(1 & 2) and b polypeptides • embryonic and fetal development: d, e, g(A and G) polypeptides

37. Globin gene clusters a – like cluster (chr. 16): x yx ya1 a2 a1 5’ 3’ 2 Kb b – like cluster (chr. 11): yb2 eGg Ag yb1d b 5’ 3’ 4 Kb

38. Human Hemoglobins • a-1 and a-2: both on chr. 16; both 141 amino acids • g-A and g-G: chr. 11; 146 amino acids; differ by only one amino acid • b and d: chr. 11; 146 amino acids; differ by 10 amino acids

39. Human Hemoglobins Possible phylogeny: myoglobin a-1 a-2 g-A g-G bd 500 million years ago ancestral gene

40. normal Down Syndrome Duplication of NOR and Down Syndrome • NOR = nucleolar organizer region

41. Changes in the Location of Genes • Inversions • Translocations • Transpositions • Robertsonian changes No gain or loss of information; just rearrangement of genome.

42. 180O A B C H G F E D I J K Inversions • 180o reversal of chromosome segment A B C D E F G H I J K

43. Inversions • Produced through breakage and reassociation of chromosome D E C B A F G

44. Inversions • Produced through breakage and reassociation of chromosome D E C B A F G

45. Inversions • May change phenotype through “position effects” • move active genes to sites generally inactive; lose gene function • move inactive genes to sites generally active; gain gene function • May act to preserve blocks of genes (specific alleles) which function well together

46. Inversions and Crossing-Over • Inversions cause complicated synapsis at meiosis for heterozygotes • Chromatids involved in crossing over do not allow development of functional gametes • Only parental type chromosomes passed on

47. E D F C A B G A B F E D C G A B C D E F G Paracentric

48. E D F C A B G 1 2 3 4 1 2 3 4 A B F E D C G A B C D E F G Pericentric

49. Inversions and Crossing-Over • Only parental type chromosomes passed on • Recombination leads to large duplications and deletions in the chromosomes • gametes do not function or zygote does not survive

50. Translocations • Exchange of segments between non-homologous chromosomes F E L D M N O P C B Q A