VARIATION IN CHROMOSOME STRUCTURE AND NUMBER CHAPTER 8 part 2 VARIATION IN CHROMOSOME STRUCTURE AND NUMBER

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

Bridges’ Experiment Investigating the Bar-Eye Phenotype in Drosophila 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 Figure 8.6 8-19 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Bridges’ Experiment Investigating the Bar-Eye Phenotype in Drosophila 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 8-20 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Testing the Hypothesis Information concerning the nature of the bar and ultra-bar phenotypes may be revealed by a cytological examination of polytene chromosomes Testing the Hypothesis Refer to Figure 8.7 8-21 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Figure 8.7 8-22

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

Interpreting the Data 8-24 The 16A region duplication returned to the wild-type banding pattern Interpreting the Data Bar phenotype is caused by a duplication in region 16A of the X chromosome Ultra-bar phenotype is caused by three copies in the 16A region 8-24 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Interpreting the Data 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 Figure 8.8 8-25 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Interpreting the Data The bar and ultra-bar alleles are also associated with the phenomenon of position effect 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 Figure 8.6 The positioning of three copies next to each other on the X chromosome increases the severity of the defect 8-26 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

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

8-28 Figure 8.9 Genes derived from a single ancestral gene Copyright ©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 8-29 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

8-30 Figure 8.10 Expressed very early in embryonic life Expressed maximally during the second and third trimesters Expressed after birth Duplication Better at binding and storing oxygen in muscle cells Better at binding and transporting oxygen via red blood cells Figure 8.10 8-30 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Inversions A chromosomal inversion is a segment that has been flipped to the opposite orientation Centromere lies within inverted region Centromere lies outside inverted region Figure 8.11 8-31 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

In rare cases, inversions can alter the phenotype of an individual 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 8-32 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Inversion Heterozygotes Individuals with one copy of a normal chromosome and one copy of an inverted chromosome 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 8-33 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Figure 8.12 8-34

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

Telomeres prevent chromosomal DNA from sticking to each other Figure 8.13 8-36

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

Example: Familial Down Syndrome 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 8-38 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 8-39 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

8.2 VARIATION IN CHROMOSOME NUMBER 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

Figure 8.16 Polyploid organisms have three or more sets of chromosomes Individual is said to be trisomic Individual is said to be monosomic Figure 8.16 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

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

In most cases, these effects are detrimental They produce individuals that are less likely to survive than a euploid individual Figure 8.17 8-47 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

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

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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 8-52 Copyright ©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 8-53 Copyright ©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 8-54 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

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

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

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

Each chromosome attaches to the chromoventer near its centromere Central point where chromosomes aggregate Figure 8.21 8-58 Copyright ©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 8-59 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

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

and two copies of other chromosomes one copy of some chromosomes 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 and two copies of other chromosomes Each cell receives one copy of some chromosomes Figure 8.23 8-61 Copyright ©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 Developed by Burpee (Seed producers) 8-62 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

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