1. Chromosomal Mutations
Chapter 8

2. Chapter Overview 8.1 Specific Terminology
8.2 Variation in # of Chromosomes Results from Nondisjunction
8.3 Monosomy May Have Severe Phenotypic Effects
8.4 Trisomy Involves Addition of a Chromosome to a Diploid Genome
8.5 Polyploidy Is Prevalent in Plants
8.6 Variation Occurs in the Structure & Arrangement of Chromosomes
8.7 – 8.10 Deletions, Duplications, Inversions, & Translocations
8.11 Fragile Sites Are Susceptible to Chromosome Breakage

3. Terminology Chromosomal aberrations vs. mutations
Most diploid species normally contain precisely two haploid chromosome sets
Many known variations:
change in the total number of chromosomes
deletion or duplication of genes or segments of a chromosome
rearrangements of the genetic material either within or among chromosomes

4. Terminology Aneuploidy Euploidy
gain or loss of one or more chromosomes
has other than an exact multiple of the haploid set
Monosomy, Trisomy, etc.
Euploidy
Complete haploid sets are present
Polyploidy - more than two sets of chromosomes are present (common in plants)

5. Table 8-1 Copyright © 2006 Pearson Prentice Hall, Inc.
Table 8.1 Terminology for Variation in Chromosome Numbers
Table Copyright © 2006 Pearson Prentice Hall, Inc.

6. Nondisjunction Chromosomal variation can arise from nondisjunction
Chromosomes or chromatids fail to disjoin and move to opposite poles during meiosis I or II
Trisomy 21 (Down Syndrome) is an example of an aberration caused by nondisjunction

8. Figure 8-1 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 8-1 Nondisjunction during the first and second meiotic divisions. In both cases, some of the gametes formed either contain two members of a specific chromosome or lack that chromosome. Following fertilization by a gamete with a normal haploid content, monosomic, disomic (normal), or trisomic zygotes are produced.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

9. Monosomy
The loss of a single chromosome (monosomy) can have severe genotypic & phenotypic effects
What sex disorder is an example of a monosomy?
TURNER SYNDROME (XO)
Monosomies of autosomes usually lethal in animals/humans

10. Partial Monosomy Partial Monosomy (segmental deletion)
only a section of a chromosome is lost
Cri-du-chat syndrome
A small part of the short arm of chromosome 5 is lost
Mentally retardation (variable)
Small head w/ unusual facial features
Cry - mewing of a distressed cat

11. Figure 8-2 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 8-2 A representative karyotype and photograph of a child exhibiting cri-du-chat syndrome (46,5p). In the karyotype, the arrow identifies the absence of a small part of the short arm of one member of the chromosome 5 homologs.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

12. Cri-du-chat

13. Trisomy Trisomy – addition of a chromosome to a diploid genome
Trisomies in sex chromosomes
Less dramatic phenotype than trisomies for autosomes, which are often lethal
Examples?
XXX
XYY
Klinefelter’s (XXY)

14. Trisomy
3 copies of one chromosome are present, so pairing configurations are usually irregular
At any particular region along the chromosome length, only 2 of the 3 homologs may synapse, though different regions of the trio may be paired

15. Trivalents Trivalent - three copies of a chromosome are synapsed
In some cases, prior to the first meiotic division, one bivalent and one univalent may be present instead of a trivalent

16. Down Syndrome Down syndrome results from trisomy of chromosome 21
Down syndrome has 12 to 14 characteristics, and affected individuals express 6 to 8 on average
1 in 700 children in the U.S.
Mother’s age a factor
Familial DS - a translocation of chromosome 21 (rarer)

17. Figure 8-5 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 8-5 The karyotype and a photograph of a child with Down syndrome. In the karyotype, three members of the G-group chromosome 21 are present, creating the 47, condition.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

18. Maternal Age
Down syndrome is usually a result of nondisjunction of the maternal chromosome 21 during meiosis
Incidence as maternal age

19. Maternal Age
How could the age of a mother relate to rate of nondisjunction?
Possible Theory:
Human females undergo primary oogenesis (Meiosis I) as fetuses
Oocyte development is stopped at that stage until puberty
Each primary oocyte undergoes Meiosis II during monthly ovulation throughout life
Therefore, an older woman has ova that have been arrested for 10 – 20 years longer than her earlier ova
Currently, no DIRECT evidence to support
Genetic counseling, amniocentesis, CVS (chorionic villus sampling)

20. Other trisomies Patau syndrome (trisomy 13)
Edwards syndrome (trisomy 18)

21. Patau Syndrome
Fatal (2-3 months or at birth)
1/19,000 live births

22. Edwards Syndrome
Fatal (2-3 months)
1/8000 live births
80% females

23. Trisomy vs. Monosomy
Trisomies are found in aborted fetuses at a much higher rate than monosomies (monosomies generally never found)
Why do trisomies show a higher rate of survival?
Monosomy of a chromosome may reveal a recessive (lethal)
Early development a delicate process – may require equal amts of gene products

24. Polyploidy
Polyploidy – more than 2 haploid sets of chromosomes (prevalent in plants)
Naming of polyploids is based on the number of sets of chromosomes found:
Triploid - 3n
Tetraploid - 4n
Pentaploid - 5n, etc.

25. Animals Lower order animals
Flatworms, leeches, brine shrimp (parthogenesis)
Goldfish, salmon, salamanders
Argentian rodent
(tetraploid)
Polyploids more normal
(pheno) than aneuploids
WHY?

26. Plants Triploid crops: banana, apple, ginger
Tetraploid crops: durum or macaroni wheat, maize, cotton, potato, cabbage, leek, tobacco, peanut
Hexaploid crops: chrysanthemum, bread wheat, oat
Octaploid crops: strawberry, dahlia, pansies, sugar cane

27. Polyploidy – how? Two scenarios can give rise to polyploid organisms
Autopolyploidy
Allopolyploidy
Autopolyploidy - the addition of one or more sets of chromosomes identical to the haploid complement of the same species (nondisjunction, double fert., no div after replication)
Allopolyploidy - the combination of chromosome sets from different species as a consequence of interspecific matings

28. Figure 8-9 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 8-9 Contrasting chromosome origins of an autopolyploid with an allopolyploid karyotype.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

29. Endopolyploidy
Endopolyploidy - only certain cells in an otherwise diploid organism are polyploid.
In these cells, replication and segregation of chromosomes occur without nuclear division

30. Chromosomal Variation
Variations in a chromosome can occur in one (or more) of the following ways:
Deletions
Duplications
Inversions
Nonreciprocal translocations
Reciprocal translocations

31. Figure 8-14 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 8-14 Overview of the five different types of rearrangement of chromosome segments.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

32. Deletions Deletion: missing region of a chromosome
When a chromosome breaks in one or more places and a portion of it is lost, the missing piece is referred to as a deletion (or a deficiency)
Terminal deletion – deletion occurs near one end of the chromosome
Intercalary deletion – deletion occurs in the interior of the chromosome

33. Figure 8-14a Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 8-14a Overview of the five different types of rearrangement of chromosome segments.
Figure 8-14a Copyright © 2006 Pearson Prentice Hall, Inc.

34. Pairing (Synapsis) of ID
When one chromosome undergoes an intercalary deletion, this presents problems for synapsis with its homolog
The unpaired region of the normal homolog must loop out of the linear structure into a deletion or compensation loop

35. Figure 8-15 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 8-15 Origins of (a) a terminal and (b) intercalary deletion. In part (c), pairing occurs between a normal chromosome and one with an intercalary deletion by looping out the undeleted portion to form a deletion (or a compensation) loop.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

36. Prader – Willi & Angelman
Deletion of specific segment of chromosome 15
Prader-Willi syndrome - mental retardation, obesity, short stature, unusually small hands & feet
Inherited from father
Angelman syndrome - spontaneous laughter, jerky movements, & other motor/mental symptoms
Inherited from mother

37. Duplications
Duplication - fragment becomes attached as an extra segment to a sister chromatid
Arise as the result of unequal crossing over during meiosis or through a replication error prior to meiosis

38. Figure 8-14b Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 8-14b Overview of the five different types of rearrangement of chromosome segments.
Figure 8-14b Copyright © 2006 Pearson Prentice Hall, Inc.

39. Figure 8-17 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 8-17 The origin of duplicated and deficient regions of chromosomes as a result of unequal crossing over. The tetrad at the left is mispaired during synapsis. A single crossover between chromatids 2 and 3 results in deficient and duplicated chromosomal regions. (See chromosomes 2 and 3, respectively, on the right.) The two chromosomes uninvolved in the crossover event remain normal in their gene sequence and content.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

40. RNA Genes
Many organisms have multiple copies of the ribosomal RNA genes (rDNA).
This is an example of gene redundancy
Why might organisms have lots of RNA genes?
RNA codes for proteins – proteins are vital for all life functions
CENTRAL DOGMA
DNA → RNA → PROTEIN

41. Inversions
Inversion - chromosomal fragment reattaches to original chromosome, but in reverse orientation
In an inversion, a segment of a chromosome is turned around 180° within the chromosome

42. Inversions
An inversion requires two breaks in the chromosome and subsequent reinsertion of the inverted segment.
An inversion may arise from chromosomal looping

43. Pericentric inversion does change the relative lengths of the arms
Paracentric inversion - does not change the relative lengths of the two arms of a chromosome
Pericentric inversion does change the relative lengths of the arms
Figure 8-19 One possible origin of a pericentric inversion.

44. Synapsis of inverted chromosomes requires an inversion loop

45. Translocations
Translocation - chromosomal fragment joins a nonhomologous chromosome
Translocations are either reciprocal or non-reciprocal
Reciprocal: the exchange of segments between two nonhomologous chromosomes and has an unusual synapsis configuration during meiosis
Non-reciprocal: the movement of a segment to another nonhomologous chromosome

46. Figure 8-14e Copyright © 2006 Pearson Prentice Hall, Inc.
Place 08_14e.jpg here
Figure 8-14e Overview of the five different types of rearrangement of chromosome segments.
Figure 8-14e Copyright © 2006 Pearson Prentice Hall, Inc.

48. Robertsonian Translocation
Robertsonian translocation (centric fusion) -involves breaks at the extreme ends of the short arms of two nonhomologous acrocentric chromosomes
Familial Down syndrome is an example of this

49. Figure 8-24 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 8-24 The possible origin of a Robertsonian translocation. Two independent breaks occur within the centromeric region on two nonhomologous chromosomes. Centric fusion of the long arms of the two acrocentric chromosomes creates the unique chromosome. Two acentric fragments remain.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

50. Figure 8-251 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure Chromosomal involvement in familial Down syndrome. The photograph illustrates the relevant chromosomes from a trisomy 21 offspring produced by a translocation carrier parent.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

51. Translocation disorders
Implicated in certain cancers, including chronic myelogenous leukemia (CML)
Fragment of chrom 22 swaps with a small fragment from tip of chrom 9
Familial Down Syndrome
Normal # of chrom, but have all/part of 3 chrom 21 attached by translocation

52. Fragile Sites
Fragile sites are more susceptible to chromosome breakage when cells are cultured in the absence of certain chemicals such as folic acid.

53. Fragile X Syndrome
Fragile X syndrome - various degrees of mental retardation
Abnormal X chromosome - tip hangs on by a thin thread of DNA
1/4000 males & 1/8000 females
Complex inheritance, but syndrome more common when abnormal chrom inherited from mom
Consistent with higher freq in males
Imprinting by mom somehow causes it

54. Figure 8-26 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 8-26 A normal human X chromosome (left) contrasted with a fragile X chromosome (right). The [[p]]gap[[p]] region (near the bottom of the chromosome) is associated with the fragile X syndrome.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.