1. Concepts and Connections
Benjamin A. Pierce
GENETICS ESSENTIALS
Concepts and Connections
SECOND EDITION
CHAPTER 6
Chromosome Variation
© 2013 W. H. Freeman and Company

2. The case of down syndrome
Chromosome 21 and the Down Syndrome Critical Region:
5 million base pair region
33 genes
Still not clear
Indicates complex gene
Interactions at chromosome 21
Down syndrome is caused by the presence of three copies of one or more genes located on chromosome 21.

3. Chapter 6 Outline
6.1 Chromosome Mutations Include Rearrangements, Aneuploids, and Polyploids, 148
6.2 Chromosome Rearrangements Alter Chromosome Structure, 150
6.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes, 159
6.4 Polyploidy Is the Presence of More Than Two Sets of Chromosomes, 163
6.5 Chromosome Variation Plays an Important Role in Evolution, 168

4. 6.1 Chromosome Mutations Include Rearrangements, Aneuploids, and Polyploids
Chromosome Morphology: (position of the centromere on the chromosome)
Metacentric
Submetacentric
Acrocentric
Telocentric
Karyotype
Complete set of chromosomes

5. 6.1 Chromosome Mutations Include Rearrangements, Aneuploids, and Polyploids
Types of Chromosome Mutations:
Rearrangements:
Aneuploidy
Polyploidy

6. 6.2 Chromosome Rearrangements Alter Chromosome Structure
Duplication:
Tandem
ABoCDEFEFG
Displaced
ABoCDEFGEF
Or to other chromosome
Reverse
ABoCDEFFEG
What are the consequences?

7. The bar mutation and duplication in Drosophila
Bar mutation reduces the number of facets in the eye
Heterozygous females and hemizygous males carrying the mutation have smaller eyes.

8. How does the duplication affect phenotype?
Not well understood but gene dosage is main suspect
Interactions of many gene products influence development
Or novel functions
Human globin genes
Segmental duplications on one chromosome (intrachromosmal) or on different chromosomes (interchromosomal)

9. 6.2 Chromosome Rearrangements Alter Chromosome Structure
Deletions
ABoCDEFG becomes ABoCD/G
Observable on metaphase chromosomes similar to duplications have looping.
Consequences:
Homozygous lethal
Heterozygous:
Imbalance
Pseudodominance
Haploinsufficient gene

11. 6.2 Chromosome Rearrangements Alter Chromosome Structure
Inversions (depending on the involvement of centromere):
ABoCDEFG becomes ABoCFEDG (paracentric)
ABoCDEFG becomes ADCoBEFG (pericentric)
Consequences (even no genetic material is delted or gained):
Gene break
Position effect

12. Translocation Nonreciprocal translocation Reciprocal translocation
ABoCDEFG and MNoOPQRS leads to ABoCDG and MNoOPEFQRS
Reciprocal translocation
ABoCDEFG and MNoOPQRS leads to ABoCDQRG and MNoOPEFS
Consequences:
Fused genes leading to fusion
proteins
Position effect
Break within a gene
Robertsonian translocation

13. 6.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes
Causes of Aneuploidy:
Deletion of centromere during mitosis and meiosis
Robertsonian translocation
Nondisjunction during meiosis and mitosis

14. Types of Aneuploidy
Nullisomy: loss of both members of a homologous pair of chromosomes. 2n − 2
Monosomy: loss of a single chromosome n − 1
Trisomy: gain of a single chromosome. 2n + 1
Tetrasomy: gain of two homologous chromosomes. 2n + 2
More example
2n+1+1 (double trisomy)
2n-1-1 (double monosomy)
2n+2+2 (double tetrasomy)

15. Effects of Aneuploidy:
6.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes
Effects of Aneuploidy:
Mostly drastic effects
Gene dosage
Aneuploidy in humans:
Sex-chromosome:
Turner syndrome. XO
Klinefelter sydrome. XXY

16. Effects of Aneuploidy:
9.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes
Effects of Aneuploidy:
In humans:
Autosomal aneuploids:
Trisomy 21 – Down sydrome
Primary Down syndrome,
75% random nondisjunction in egg formation.
Familial Down syndrome,
Robertsonian translocation between chromosomes 14 and 21.

17. Carriers of translocations: increased risk for child with down syndrome
Figure Translocation carriers are at increased risk for producing children with Down syndrome.

18. Effects of Aneuploidy:
6.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes
Effects of Aneuploidy:
In humans:
Autosomal aneuploids:
Trisomy 18 – Edward syndrome, 1/8000 live births
Trisomy 13 – Patau syndrome, 1/15,000 live births
Trisomy /25,000 ~ 1/50,000 live births
Why is there a drastic decrease in frequency of these trisomic syndromes from Chromosome 18 to Chromosome 8?

19. Effects of Aneuploidy:
6.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes
Effects of Aneuploidy:
In humans:
Autosomal aneuploids:
Aneuploidy and maternal age.
Possible interpretation?

20. 6.4 Polyploidy is the Presence of More Than Two Sets of Chromosomes
Failure of whole sets of chromosomes to separate
Tripolids (3n); tertaploids (4n), pentaploidsn (5n)
Common in plants; less so in animals
Autopolyploidy:
From a single species

21. Unbalanced chromosomes after meiosis of a triploid cell

22. 6.4 Polyploidy is the Presence of More Than Two Sets of Chromosomes
Allopolyploidy
From two species
Creation of amphidiploid

23. 6.4 Polyploidy is the Presence of More Than Two Sets of Chromosomes
The significance of polyploidy:
Nuclear volume increases-cell volume increases
Selection of plants with bigger leaves, flowers,
fruits, seeds.

24. 6.5 Chromosome Variation Plays an Important Role in Evolution
New and extra copies of genes give rise to new functions.
New and extra sets of genes may give rise to new species.