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) 8-2 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

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, XXY45, X Klinefelter syndromeTurner 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

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 (2 9 = 512) Produces bundle of chromosome strands Euploidy Variations

L R 4 32 L R Repeated chromosome replication produces polytene chromosome. A polytene chromosome. Composition of polytene chromosome from regular Drosophila chromosomes. Chromocenter Each polytene arm is composed of hundreds of chomosomes aligned 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 desirable agricultural 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

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 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 8-78

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 Duplication Better 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

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

Fig. 8.13b(TE Art) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nonhomologous chromosomes Reciprocal translocation 1177 Nonhomologous crossover 17 Crossover between nonhomologous chromosomes

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 DNA repair enzymes recognize broken ends and connect them. Chromosomal breakage and DNA repair

8-38 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 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)

8-39 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 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

8-40 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 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

8-41 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 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

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 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 8-71 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