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© 2012 W. H. Freeman and Company

CHAPTER 8 (p 209 – 240)[CHAPTER 10 (p 259 – 288)]

Study Unit 7Chromosome Variation

Study Unit 7Chromosome Variation

Benjamin A. PierceGENETICS

A Conceptual Approach

FOURTH EDITION

© 2012 W. H. Freeman and Company

Chromosome Mutations Include

Rearrangements, Aneuploids, and Polyploids

What to know?• The different types of chromosomal

mutations.

i.e.

- Chromosomal rearrangements:

Duplications, Deletions, Inversions and Translocations.

- Aneuploidy

- Polyploidy

• How they pair during Prophase I of

Meiosis.

• What effect the mutation has on the fertility of the organism.

Chromosome Rearrangements Alter

Chromosome Structure

Duplication:

Deletion:

Inversion:

Translocation:

Duplications

• A chromosome duplication is a mutation where part of the chromosome has been doubled (duplicated).

AB�CDEFG

AB�CDEFEFG AB�CDEFGEF AB�CDEFFEG

tandem displaced reverse

duplication duplication duplication

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Duplications Effects of chromosome duplications

Deletions

• A chromosome deletion is a mutation where part of the chromosome has been lost (deleted).

AB�CDEFG

AB�CDG

Effects of chromosome deletions

Consequences of chromosome deletions

• Phenotypic consequences depend on which genes arelocated on the deleted region.

•Homozygotes are usually lethal.

•Heterozygotes may produce imbalanced gene products.

•Pseudodominance = expression of a normally recessive

mutation on one homolog due to deletion of the dominantallele on the other homolog.

• Some genes need two copies for normal function. When a

single copy is insufficient for the wild-type pt =haploinsufficient gene. (e.g. Notch phenotype in

Drosophila melanogaster.)

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Inversions

• A chromosome inversion occurs when a chromosome segment is inverted – turned 180°.

AB�CDEFG

AB�CFEDG ADC�BEFG

Paracentric inversion Pericentric inversion

(does not include centromere) (includes centromere)

Paracentric inversion(does not include centromere)

Pericentric inversion(includes centromere)

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Consequences of chromosome inversions

• DNA neither lost nor gained, just rearranged.

•Often significant phenotypic effects.

•E.g.•Gene may be broken into 2 parts

•Position effect

Translocations

• A chromosome translocation occurs when genetic material moves between nonhomologous chromosomes

(translocates).

AB����CDEFG MN����OPQRS AB����CDEFG MN����OPQRS

AB����CDG MN����OPEFQRS AB����CDQRG MN����OPEFS

Nonreciprocal translocation Reciprocal translocation

Effects of chromosome translocations

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Robertsonian translocation Consequences of chromosome translocations

E.g. Philadelphia translocation chromosome

Reciprocal translocation between human chromosomes 9 and 22. Associated

with chronic myelogenous leukaemia (CML). Produces an oncogenic gene fusion.

Fragile sites

Fragile sites are constrictions or gaps at particular places on chromosome that are prone to breakage.

Common fragile sites: found in all humans, normal feature of chromosomes.

Often location of chromosome breakage and

rearrangement in cancer cellsLead to deletions, translocations and other

chromosome mutations.

Rare fragile sites:

Found in few people, inherited as Mendelian trait.

Often associated with mental retardationMost often expanding nucleotide repeats

E.g. Fragile-X-Syndrome C D

C D

a compensation loop

Synapsis configurations of chromosome rearrangements

Deletion heterozygote

Duplication heterozygote

Paracentric inversion heterozygote

Pericentric inversion heterozygote

Translocation heterozygote

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Problems

3. The following diagram illustrates a homozygous chromosome inversion during meiosis:

a. Name this type of inversion.

b. Draw the daughter chromosomes and/or fragments that would be found after segregation of the chromatids in the diagram below.

4. Diagram the chromosome synapsis during meiosis of thefollowing translocation heterozygote. The normal chromosome

1 carries loci abcdefg and chromosome 2 carries tuvwxyz.Following reciprocal translocation, the resulting translocated

chromosomes are abcdvwxyz and tuefg. Assume thecentromere is at the left end of all the chromosomes.

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

• Fig. 10.19

Types of Aneuploidy

• Nullisomy: loss of both members of a

homologous pair of chromosomes. 2n − 2

• Monosomy: loss of a single chromosome.

2n − 1

• Trisomy: gain of a single chromosome. 2n + 1

• Tetrasomy: gain of two homologous

chromosomes. 2n + 2

Aneuploidy Is an Increase or Decrease in the

Number of Individual Chromosomes

• Effects of Aneuploidy:

– In plants: Fig. 10.20.

– In humans:

• Sex-chromosome aneuploids:

– Turner syndrome. XO

– Klinefelter sydrome. XXY

(Stine, 1989)

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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. Fig. 10.21

» Familial Down Syndrome. Robertsonian translocation between Chromosome 14 and 21. Fig. 10.22 and

23.

9.3 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 8 1/25,000 ~ 1/50, 000 live births

– Why there is a drastic decrease in frequency of these

trisomic syndrome from Chromosome 18 to chromosome 8?

Gynandromorph

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9.3 Aneuploidy Is an Increase or Decrease in

the Number of Individual Chromosomes

• Effects of Aneuploidy:– In humans:

• Autosomal aneuploids:

– Aneuploidy and maternal age. Fig. 9.24

– Possible interpretation of this connection?

• Uniparental disomy: both chromosomes are inherited from

the same parent.

– Mosaicism and nondisjunction in mitotic division.

9.4 Polyploidy is the Presence of More Than

Two Sets of Chromosomes

• Autopolyploidy:

– From single species.

• Fig. 10.26

• Allopolyploidy

– From two species

• Fig. 10.28

Autotriploids (3n) arise in several ways:

1. 1st or 2nd division nondisjunction →→→→ 2n gamete

2n + n = 3n

2. n + n + n = 3n zygote

3. 2n x 4n = 3n

Triploids often produce genetically unbalanced

gametes with odd numbers of chromosomes

• infertile

Autopolyploids generally larger than diploid relatives

•Due to larger cells as opposed to larger number of cells

•Increased size → → → → increased commercial value

Triploids (3n):

Tetraploids (4n)

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Octoploids (8n)Allopolyploidy

The significance of polyploidy

• Polyploidy is less common in animals than plants.

• Allopolyploidy requires interspecific hybridization – less

frequent in animals – behaviour & complex development renders most hybrids nonviable.

• Parthenogenesis – greater opportunities for non-disjunction.

• Few human polyploid babies, die within days of birth.

• Polyploidy (usually 3n) found in 10% of all spontaneously

aborted human foetuses.

• Bread wheat = hexaploid = 6n = 42 (derived 3 different

species) (Fig. 10.29)

Polyploidy is the Presence of

More Than Two Sets of

Chromosomes

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Allopolyploidy

• Polyploidy can result from hybridization of two closely related species

• AA X BB

• A B

• AB

• Where A has a1; a2; a3; …an chromosomes, and

• B has b1; b2; b3; …bn chromosomes

Hybrid plant may be sterile – unable to form viable gametes

Some or all of a and b chromosomes not homologous – cannot synapse during meiosis ~ unbalanced genetic conditions

AB undergoes chromosome doubling → → → → fertile AABB tetraploid

Called an allotetraploid

When both original species are known = amphidiploid

If amphidiploids are formed from closely related species, some homology will exist between a and b chromosomes.

Called homeologous chromosomes

During synapsis:

Multivalents may form, produces unbalanced gametes

9.5 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.

Problems

1. For a species with a diploid number of 20, how many chromosomes will be present in the somatic cells of

individuals who are:a. triploid

b. tetraploidc. monosomicd. Trisomic