CHAPTER 8 part 2

VARIATION IN CHROMOSOME STRUCTURE AND NUMBER

8-18Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Like deletions, the phenotypic consequences of duplications tend to be correlated to size Duplications are more likely to have phenotypic effects if

they involve a large piece of the chromosome

However, duplications tend to have less harmful effects than deletions of comparable size

In humans, relatively few well-defined syndromes are caused by small chromosomal duplications

Duplications

Bar eyes is a trait in which flies have a reduced number of facets

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 incomplete dominance

8-19Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Bridges’ Experiment Investigating the Bar-Eye Phenotype in Drosophila

Figure 8.6

Calvin Bridges in the 1930s investigated the bar/ultra-bar phenomenon at the cytological level

The cells of the salivary gland of Drosophila have gigantic chromosomes, termed polytene chromosomes The banding patterns on these chromosomes is easily

seen It is thus possible to detect the duplication or deletion of single

genes

8-20Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Bridges’ Experiment Investigating the Bar-Eye Phenotype in Drosophila

The Hypothesis Information concerning the nature of the bar and

ultra-bar phenotypes may be revealed by a cytological examination of polytene chromosomes

8-21Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Testing the Hypothesis

Refer to Figure 8.7

8-22Figure 8.7

The Data

8-23Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

This is a drawing of a short segment of a polytene chromosome that corresponds to the region of the X chromosome where the bar allele is located. This bar allele is found within the region designated 16A

Interpreting the Data

8-24Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Bar phenotype is caused by a duplication in region 16A of the X chromosome

The 16A region duplication returned to the wild-type banding pattern

Ultra-bar phenotype is caused by three copies in the 16A region

8-25Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

The mechanism of formation of the bar allele can be explained by a misaligned crossover

Likewise for the formation of ultra-bar and bar-revertant alleles

Interpreting the Data

Figure 8.8

8-26Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

The bar and ultra-bar alleles are also associated with the phenomenon of position effect

Interpreting the Data

A female that is homozygous for the bar allele has four copies of region 16A

And 70 facets A female that is heterozygous for the ultra-bar and normal alleles also has four copies of region 16A

But only 45 facets

The positioning of three copies next to each other on the X chromosome increases the severity of the defect

Figure 8.6

8-27Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

The majority of small chromosomal duplications have no phenotypic effect

However, they are vital because they provide raw material for additional genes

This can ultimately lead to the formation of gene families A gene family consists of two or more genes that are

similar to each other

Duplications and Gene Families

8-28Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Figure 8.9

Genes derived from a single ancestral gene

8-29Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

A well-studied example is the globin gene family The genes encode polypeptides which function in

proteins that bind oxygen Hemoglobin

The globin gene family is composed of 14 homologous genes on three different chromosomes All 14 genes are derived from a single ancestral gene

Accumulation of different mutations in the members of the gene family created

1. Globin genes that are expressed during different stages of human development

2. Globin proteins that are more specialized in their function

8-30Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

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

8-31Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

A chromosomal inversion is a segment that has been flipped to the opposite orientation

Inversions

Figure 8.11

Centromere lies within inverted

region

Centromere lies outside inverted

region

8-32Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

In an inversion, the total amount of genetic information stays the same

Therefore, the great majority of inversions have no phenotypic consequences

In rare cases, inversions can alter the phenotype of an individual

Break point effect The breaks leading to the inversion occur in a vital gene

Position effect A gene is repositioned in a way that alters its gene expression

About 2% of the human population carries inversions that are detectable with a light microscope

Most of these individuals are phenotypically normal However, a few an produce offspring with genetic abnormalities

8-33Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

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

Inversion Heterozygotes

Such individuals may be phenotypically normal They also may have a high probability of producing gametes that are

abnormal in their genetic content The abnormality is due to crossing-over in the inverted segment

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

Figure 8.128-34

8-35Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

A chromosomal translocation occurs when a segment of one chromosome becomes attached to another

In reciprocal translocations two non-homologous chromosomes exchange genetic material Reciprocal translocations arise from two different

mechanisms 1. Chromosomal breakage and DNA repair 2. Abnormal crossovers

Translocations

8-36Figure 8.13

Telomeres prevent chromosomal DNA from sticking to each other

8-37Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Reciprocal translocations lead to a rearrangement of the genetic material, not a change in the total amount Thus, they are also called balanced translocations

Reciprocal translocations, like inversions, are usually without phenotypic consequences In a few cases, they can result in position effect

Translocations

8-38Copyright ©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) The individual would have three copies of genes found

on a large segment of chromosome 21 Therefore, they exhibit the characteristics of Down syndrome Refer to Figure 8.14b

8-39Copyright ©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

Chromosome numbers can vary in two main ways Euploidy

Variation in the number of complete sets of chromosome

Aneuploidy Variation in the number of particular chromosomes within a set

Euploid variations occur occasionally in animals and frequently in plants

Aneuploid variations, on the other hand, are regarded as abnormal conditions

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

8.2 VARIATION IN CHROMOSOME NUMBER

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or displayFigure 8.16

Polyploid organisms have three or more sets of chromosomes

Individual is said to be trisomic

Individual is said to be monosomic

8-46Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

The phenotype of every eukaryotic species is influenced by thousands of different genes The expression of these genes has to be intricately

coordinated to produce a phenotypically normal individual

Aneuploidy commonly causes an abnormal phenotype It leads to an imbalance in the amount of gene products

Refer to Figure 8.17

Aneuploidy

8-47Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or displayFigure 8.17

In most cases, these effects are

detrimentalThey produce

individuals that are less likely to survive

than a euploid individual

8-50Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Alterations in chromosome number occur frequently during gamete formation About 5-10% of embryos have an abnormal chromosome

number Indeed, ~ 50% of spontaneous abortions are due to such

abnormalities

In some cases, an abnormality in chromosome number produces an offspring that can survive Refer to Table 8.1

Aneuploidy

8-51

8-52Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

The autosomal aneuploidies compatible with survival are trisomies 13, 18 and 21 These involve chromosomes that are relatively small

Aneuploidies involving sex chromosomes generally have less severe effects than those of autosomes This is explained by X inactivation

All additional X chromosomes are converted into Barr bodies

The phenotypic effects listed in Table 8.1 may be due to 1. The expression of X-linked genes prior to embryonic X-

inactivation 2. An imbalance in the expression of pseudoautosomal genes

8-53Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Some human aneuploidies are influenced by the age of the parents Older parents more likely to produce abnormal offspring Example: Down syndrome (Trisomy 21)

Incidence rises with the age of either parent, especially mothers

Figure 8.19

8-54Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Down syndrome is caused by the failure of chromosome 21 to segregate properly This nondisjunction most commonly occurs during

meiosis I in the oocyte

The correlation between maternal age and Down symdrome could be due to the age of oocytes Human primary oocytes are produced in the ovary of the

female fetus prior to birth They are however arrested in prophase I until the time of ovulation

As a woman ages, her primary oocytes have been arrested in prophase I for a progressively longer period of time

This added length of time may contribute to an increased frequency of nondisjunction

8-55Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Most species of animals are diploid In many cases, changes in euploidy are not tolerated

Polyploidy in animals is generally a lethal condition Some euploidy variations are naturally occurring

Female bees are diploid Male bees (drones) are monoploid

Contain a single set of chromosomes

A few examples of vertebrate polyploid animals have been discovered Rat - Argentinean

Euploidy

8-56Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

In many animals, certain body tissues display normal variations in the number of sets of chromosomes

Diploid animals sometimes produce tissues that are polyploid This phenomenon is termed endopolyploidy

Liver cells, for example, can be triploid, tetraploid or even octaploid (8n)

Polytene chromosomes of insects provide an unusual example of natural variation in ploidy

Euploidy

8-57Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Occur mainly in the salivary glands of Drosophila and a few other insects

Chromosomes undergo repeated rounds of chromosome replication without cellular division In Drosophila, pairs of chromosomes double approximately

nine times (29 = 512) These doublings produce a bundle of chromosomes

that lie together in a parallel fashion This bundle is termed a polytene chromosome

Polytene Chromosomes

8-58Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Figure 8.21

Each chromosome attaches to the chromoventer near its centromere

Central point where chromosomes aggregate

8-59Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Because of their size, polytene chromosomes lend themselves to an easy microscopic examination They are so large, they can be even seen in interphase

Polytene chromosomes exhibit a characteristic banding pattern (Figure 8.21b) Each dark band is known as a chromomere

The DNA within the dark band is more compact than that in the interband region

Cytogeneticists have identified about 5,000 bands

Polytene chromosomes have facilitated the study of the organization and functioning of interphase chromosomes

8-60Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

In contrast to animals, plants commonly exhibit polyploidy 30-35% of ferns and flowering plants are polyploid Many of the fruits and grain we eat come from polyploid

plants Refer to Figure 8.22a

In many instances, polyploid strains of plants display outstanding agricultural characteristics They are often larger in size and more robust

Refer to Figure 8.22b

Euploidy

8-61Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Polyploids having an odd number of chromosome sets are usually sterile These plants produce highly aneuploid gametes

Example: In a triploid organism there is an unequal separation of homologous chromosomes (three each) during anaphase I

Figure 8.23

Each cell receives one copy of some

chromosomes

and two copies of other chromosomes

8-62Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Sterility is generally a detrimental trait However, it can be agriculturally desirable because it

may result in 1. Seedless fruit

Seedless watermelons and bananas Triploid varieties

Asexually propagated by human via cuttings

2. Seedless flowers Marigold flowering plants

Triploid varieties Developed by Burpee (Seed producers)

UGA UAG UAA