Chromosome Aberrations

Types of Genetic variation

Allelic variations mutations in particular genes (loci)

Chromosomal aberrations substantial changes in chromosome structure Typically affect multiple genes (loci)

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Microscopic examination of chromosomes Karyotype

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

Cytogenetics

Figure 8.1

G-Banded Metaphase Chromosomes

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 non-homologous chromosomes

Variation In Chromosome Number

Euploidy Normal variations of the number of complete sets

of chromosomes Haploid, Diploid, Triploid, Tetraploid, etc…

Aneuploidy Variation in the number of particular

chromosomes within a set Monosomy, trisomy, polysomy

Aneuploidies of the Sex Chromosomes

47, XXY 45, XKlinefelter syndrome Turner syndrome

Trisomy 13 Karyotype: 47, 13+

Karyotype of t(14;21) Familial Down Syndrome

Figure 8.16

Polyploidy v Aneuploidy

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Figure 8.19

Relationship Between Age and Aneuploidy Older mothers more likely to produce aneuploid

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

maturation

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

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

Euploidy Variations

L

R4 32 L

R

Repeated chromosome replication produces polytene chromosome.

A polytene chromosome. Composition of polytene chromosome from regular Drosophila chromosomes.

Chromocenter

Each polytenearm is composed of hundreds ofchomosomesaligned side by side.

Drosophila Polytene Chromosomes

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 desirableagricultural characteristics wheat cotton strawberries bananas large blossom flowers

Euploidy Variations

Figure 8.23

Each cell receives one copy of some

chromosomes

and two copies of other chromosomes

Polyploidy Polyploids with odd #’d chromosome sets are

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

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

Figure 8.27

An allotetraploid: Contains two

complete sets of chromosomes

from two different species

Interspecies Crosses Result in Alloploids Allodiploid

one set of chromosomes from two different species Allopolyploid

combination of both autopolyploidy and alloploidy

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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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Amount of genetic information in the chromosome can change Deficiencies/Deletions Duplications

The genetic material remains the same, but is rearranged Inversions Translocations

Variation In Chromosome Structure

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

Deficiencies (aka Deletions)

Figure 8.3

Phenotypic consequences of deficiency depends on Size of the deletion Functions of the genes deleted

Phenotypic effect of deletions usually detrimental

Deficiencies

Cri-du-chat Syndrome

A chromosomal duplication is usually caused by abnormal events during recombination

Duplications

Figure 8.5

Phenotypic consequences of duplications correlated to size & genes involved

Duplications tend to be less detrimental

Duplications

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

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 and Gene Families

Genes derived from a single ancestral gene

Duplications Generate Gene Families

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

Figure 8.10

DuplicationBetter at binding

and storing oxygen in muscle

cells

Better at binding and transporting oxygen via red

blood cells

Expressed very early in embryonic life

Expressed maximally during the second and third trimesters

Expressed after birth

Mammalian Globin Genes

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

Inversions

Figure 8.11

Centromere lies within inverted

region

Centromere lies outside inverted

region

Inversions No loss of genetic information

Many inversions have no phenotypic consequences Break point effect

Inversion break point is within regulatory or structural portion of a gene

Position effect Gene is repositioned in a way that alters its gene expression separated from regulatory sequences, placed next to constitutive

heterochromatin ~ 2% of the human population carries karyotypically

detectable inversions

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

Inversion Heterozygotes

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 (non-recombinants) will produce normal progeny after fertilization

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

Usually without phenotypic consequences Although can result in position effect

Translocations

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Nonhomologous chromosomes

Reciprocaltranslocation

1 1 7 7

Nonhomologous crossover

1 7

Crossover betweennonhomologouschromosomes

Fig. 8.13a(TE Art)Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

22

Environmental agent causes 2 chromosomes to break.

Reactive ends

22

2 2

DNA repair enzymesrecognize broken ends and connect them.

Chromosomal breakage and DNA repair

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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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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

Balanced Translocations and Gamete Production

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 X’s is lost during the first mitotic division

This produces an XX cell and an X0 cell

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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

This peculiar and rare individual is termed a bilateral gynandromorph

Figure 8.26