Chromosome Aberrations

Types of Genetic variation

Allelic variations

mutations in particular genes (loci) substantial changes in chromosome structure Typically affect multiple genes (loci)

Chromosomal aberrations

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Cytogenetics

Microscopic examination of chromosomes Karyotype Main features to identify and classify chromosomes 1. Size 2. Location of the centromere 3. Banding patterns

G-Banded Metaphase Chromosomes

Figure 8.1

Categories of Chromosomal Aberrations

Aneuploidies A change from euploid number

Inversions Pericentric inversion about the centromere Paracentric inversion not involving the centromere Deletions Loss of a region of a chromosome Duplications Translocations Exchange or joining of regions of two nonhomologous chromosomes

Variation In Chromosome Number

Euploidy

Normal variations of the number of complete sets of chromosomes Haploid, Diploid, Triploid, Tetraploid, etc Variation in the number of particular chromosomes within a set Monosomy, trisomy, polysomy

Aneuploidy

Aneuploidies of the Sex Chromosomes

47, XXY Klinefelter syndrome

45, X Turner syndrome

Trisomy 13 Karyotype: 47, 13+

Karyotype of t(14;21) Familial Down Syndrome

Polyploidy v Aneuploidy

Figure 8.16

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Relationship Between Age and Aneuploidy

Older mothers more likely to produce aneuploid eggs

Trisomy 21 Due to meiotic non-disjunction in during oocyte maturation

Figure 8.19

Meiotic Nondisjunction Generates Aneuploidies

abnormal gametes

Zygotic Ploidy

Zygotic Ploidy

Euploid Number can Naturally Vary

Most animal species are diploid Polyploidy in animals is generally lethal Some naturally occurring euploidy variations

bees - females are diploid; drones are monoploid (ie haploid) some amphibian & fish polyploids are known

Euploidy Variations

Certain body tissues can display euploidy variations

endopolyploidy

Polytene chromosomes of dipteran salivary glands Chromosomes undergo repeated rounds of replication

In Drosophila, 9 rounds of replication (29 = 512)

Produces bundle of chromosome strands

Drosophila Polytene Chromosomes

Repeated chromosome replication produces polytene chromosome. L 2 R 4 3 L R

Chromocenter

Each polytene arm is composed of hundreds of chomosomes aligned side by side.

A polytene chromosome.

Composition of polytene chromosome from regular Drosophila chromosomes.

Euploidy Variations

Plants commonly exhibit polyploidy

30-35% of ferns and flowering plants are polyploid Many of the fruits & grain are polyploid plants

Polyploid strains often display desirable agricultural characteristics

wheat cotton strawberries bananas large blossom flowers

Polyploidy

Polyploids with odd #d chromosome sets are usually sterile

produce mostly aneuploid gametes rare a diploid & haploid gamete are produced

Each cell receives one copy of some chromosomes and two copies of other chromosomes

Figure 8.23

Benefit of Odd Ploidy-Induced Sterility

Seedless fruit

watermelons and bananas asexually propagated by human via cuttings

Seedless flowers

Marigold flowering plants

Prevention of cross pollination of transgenic plants

Generation of Polyploids

Autopolyploidy

Complete nondisjunction of both gametes can produce an individual with one or more sets of chromosomes

Figure 8.27

Interspecies Crosses can Generate Alloploids

Alloploidy Offspring generally sterile

Figure 8.27

Alloploid Antelope Karyotype

Hippotragus equinus x H. niger

Only slight differences between chromosomes allow for synapsis Pairs of chromosomes refered to as homeologous Questionable if these are in fact different species Homologous regions of homeologous chromosomes called synteny

Interspecies Crosses Result in Alloploids

Allodiploid

one set of chromosomes from two different species combination of both autopolyploidy and alloploidy

Allopolyploid

An allotetraploid: Contains two complete sets of chromosomes from two different species

Figure 8.27

Experimental Treatments Can Promote Polyploidy

Polyploid and allopolyploid plants often exhibit desirable traits Colchicine is used to promote polyploidy Colchicine binds to tubulin, disrupting microtubule formation and blocks chromosome segregation

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Variation In Chromosome Structure

Amount of genetic information in the chromosome can change

Deficiencies/Deletions Duplications

The genetic material remains the same, but is rearranged

Inversions Translocations

Deficiencies (aka Deletions)

A chromosomal deficiency occurs when a chromosome breaks and a fragment is lost

Figure 8.3

Deficiencies

Phenotypic consequences of deficiency depends on

Size of the deletion Functions of the genes deleted

Phenotypic effect of deletions usually detrimental

Cri-du-chat Syndrome

Duplications

A chromosomal duplication is usually caused by abnormal events during recombination

Figure 8.5

Duplications

Phenotypic consequences of duplications correlated to size & genes involved Duplications tend to be less detrimental

Bar-Eye Phenotype in Drosophila

Phenotype: reduced number of ommatidia Ultra-bar (or double-bar) is a trait in which flies have even fewer facets than the bar homozygote Both traits are X-linked and show intermediate dominance

Bar-eye Phenotype due to Duplication

Duplications and Gene Families

Majority of small duplications have no phenotypic effect However, they provide raw material for evolutionary change Lead to the formation of gene families

A gene family consists of two or more genes that are similar to each other derived from a common gene ancestor

Duplications Generate Gene Families

Genes derived from a single ancestral gene

Figure 8.9

Gene Families

Well-studied example is the globin gene family

Genes encode proteins that bind oxygen

Globin gene family

14 homologous genes derived from a single ancestral gene Accumulation of mutations in the members of generated

Globin genes expressed during different stages of development Globin proteins specialized in their function

Mammalian Globin Genes

Expressed very early in embryonic life Expressed maximally during the second and third trimesters Expressed after birth

Better at binding and storing oxygen in muscle cells

Duplication

Better at binding and transporting oxygen via red blood cells

Figure 8.10

Inversions

A segment of chromosome that is flipped relative to that in the homologue

Centromere lies within inverted region

Centromere lies outside inverted region

Figure 8.11

Inversions

No loss of genetic information

Many inversions have no phenotypic consequences Inversion break point is within regulatory or structural portion of a gene Gene is repositioned in a way that alters its gene expression separated from regulatory sequences, placed next to constitutive heterochromatin

Break point effect

Position effect

~ 2% of the human population carries karyotypically detectable inversions

Inversion Heterozygotes

Individuals with one copy of a normal chromosome and one copy of an inverted chromosome Usually phenotypically normal

Have a high probability of producing gametes that are abnormal in genetic content Abnormality due to crossing-over within the inversion interval

During meiosis I, homologous chromosomes synapse with each other

For the normal and inversion chromosome to synapse properly, an inversion loop must form If a cross-over occurs within the inversion loop, highly abnormal chromosomes are produced

Crossing Over Within Inversion Interval Generates Unequal Sets of Chromatids

Crossing Over Within Inversion Interval Generates Unequal Sets of Chromatids

Inversions Prevent Generation of Recombinant Offspring Genotypes

Only parental chromosomes (nonrecombinants) will produce normal progeny after fertilization

Translocations

When a segment of one chromosome becomes attached to another In reciprocal translocations two non-homologous chromosomes exchange genetic material

Usually generate so-called balanced translocations Although can result in position effect

Usually without phenotypic consequences

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Nonhomologous chromosomes Fig. 8.13b(TE Art)

1 1

7 7

Crossover between nonhomologous chromosomes

Reciprocal translocation Nonhomologous crossover

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Fig. 8.13a(TE Art)

22 Environmental agent 2 causes 2 chromosomes to break. 22 2

DNA repair enzymes recognize broken ends and connect them.

Reactive ends

Chromosomal breakage and DNA repair

In simple translocations the transfer of genetic material occurs in only one direction

These are also called unbalanced translocations

Unbalanced translocations are associated with phenotypic abnormalities or even lethality Example: Familial Down Syndrome

In this condition, the majority of chromosome 21 is attached to chromosome 14 (Figure 8.14a)

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Familial Down Syndrome is an example of Robertsonian translocation This translocation occurs as such

Breaks occur at the extreme ends of the short arms of two non-homologous acrocentric chromosomes The small acentric fragments are lost The larger fragments fuse at their centromeic regions to form a single chromosome

This type of translocation is the most common type of chromosomal rearrangement in humans
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Balanced Translocations and Gamete Production

Individuals carrying balanced translocations have a greater risk of producing gametes with unbalanced combinations of chromosomes

This depends on the segregation pattern during meiosis I

During meiosis I, homologous chromosomes synapse with each other

For the translocated chromosome to synapse properly, a translocation cross must form
Refer to Figure 8.15
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Figure 8.15

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Meiotic segregation can occur in one of three ways

1. Alternate segregation

Chromosomes on opposite sides of the translocation cross segregate into the same cell Leads to balanced gametes

Both contain a complete set of genes and are thus viable

2. Adjacent-1 segregation

Adjacent non-homologous chromosomes segregate into the same cell Leads to unbalanced gametes

Both have duplications and deletions and are thus inviable

3. Adjacent-2 segregation

Adjacent homologous chromosomes segregate into the same cell Leads to unbalanced gametes

Both have duplications and deletions and are thus inviable

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Consider a fertilized Drosophila egg that is XX

One of the Xs is lost during the first mitotic division This produces an XX cell and an X0 cell

The XX cell is the precursor for this side of the fly, which developed as a female

The X0 cell is the precursor for this side of the fly, which developed as a male

Figure 8.26

This peculiar and rare individual is termed a bilateral gynandromorph

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