VARIATION IN CHROMOSOME STRUCTURE AND NUMBER Duplications n

VARIATION IN CHROMOSOME STRUCTURE AND NUMBER

Duplications n Like deletions, the phenotypic consequences of duplications tend to be correlated to size n n n 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 Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -18

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

Bridges’ Experiment Investigating the Bar-Eye Phenotype in Drosophila n n Calvin Bridges in the 1930 s investigated the bar/ultra-bar phenomenon at the cytological level The cells of the salivary gland of Drosophila have gigantic chromosomes, termed polytene chromosomes n The banding patterns on these chromosomes is easily seen n It is thus possible to detect the duplication or deletion of single genes Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -20

The Hypothesis n Information concerning the nature of the bar and ultra-bar phenotypes may be revealed by a cytological examination of polytene chromosomes Testing the Hypothesis n Refer to Figure 8. 7 Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -21

Figure 8. 7 8 -22

The Data n 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 16 A Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -23

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

Interpreting the Data n n 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 Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -25

Interpreting the Data The bar and ultra-bar alleles are also associated with the phenomenon of position effect n n n A female that is homozygous for the bar allele has four copies of region 16 A n And 70 facets A female that is heterozygous for the ultra-bar and normal alleles also has four copies of region 16 A n But only 45 facets Figure 8. 6 n The positioning of three copies next to each other on the X chromosome increases the severity of the defect Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -26

Duplications and Gene Families n n n 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 n A gene family consists of two or more genes that are similar to each other Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -27

Genes derived from a single ancestral gene Figure 8. 9 Copyright ©The Mc. Graw-Hill

n A well-studied example is the globin gene family n The genes encode polypeptides which function in proteins that bind oxygen n n Hemoglobin The globin gene family is composed of 14 homologous genes on three different chromosomes n n All 14 genes are derived from a single ancestral gene Accumulation of different mutations in the members of the gene family created n n 1. Globin genes that are expressed during different stages of human development 2. Globin proteins that are more specialized in their function Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -29

Expressed very early in embryonic life Expressed maximally during the second and third trimesters Better at binding and storing oxygen in muscle cells Duplication Expressed after birth Better at binding and transporting oxygen via red blood cells Figure 8. 10 Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -30

Inversions n A chromosomal inversion is a segment that has been flipped to the opposite orientation Centromere lies within inverted region Figure 8. 11 Centromere lies outside inverted region Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -31

n In an inversion, the total amount of genetic information stays the same n n Therefore, the great majority of inversions have no phenotypic consequences In rare cases, inversions can alter the phenotype of an individual n Break point effect n n Position effect n n The breaks leading to the inversion occur in a vital gene 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 n n Most of these individuals are phenotypically normal However, a few an produce offspring with genetic abnormalities Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -32

Inversion Heterozygotes n n Individuals with one copy of a normal chromosome and one copy of an inverted chromosome Such individuals may be phenotypically normal n They also may have a high probability of producing gametes that are abnormal in their genetic content n n The abnormality is due to crossing-over in the inverted segment During meiosis I, homologous chromosomes synapse with each other n n 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 Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -33

Figure 8. 12 8 -34

Translocations n n A chromosomal translocation occurs when a segment of one chromosome becomes attached to another In reciprocal translocations two non-homologous chromosomes exchange genetic material n Reciprocal translocations arise from two different mechanisms n n 1. Chromosomal breakage and DNA repair 2. Abnormal crossovers Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -35

Telomeres prevent chromosomal DNA from sticking to each other Figure 8. 13 8 -36

Translocations n Reciprocal translocations lead to a rearrangement of the genetic material, not a change in the total amount n n Thus, they are also called balanced translocations Reciprocal translocations, like inversions, are usually without phenotypic consequences n In a few cases, they can result in position effect Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -37

n In simple translocations the transfer of genetic material occurs in only one direction n These are also called unbalanced translocations Unbalanced translocations are associated with phenotypic abnormalities or even lethality Example: Familial Down Syndrome n n In this condition, the majority of chromosome 21 is attached to chromosome 14 (Figure 8. 14 a) The individual would have three copies of genes found on a large segment of chromosome 21 n n Therefore, they exhibit the characteristics of Down syndrome Refer to Figure 8. 14 b Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -38

n n Familial Down Syndrome is an example of Robertsonian translocation This translocation occurs as such n n 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 Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -39

8. 2 VARIATION IN CHROMOSOME NUMBER n Chromosome numbers can vary in two main ways n Euploidy n n Aneuploidy n n n Variation in the number of complete sets of chromosome 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 Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display

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 Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display

Aneuploidy n The phenotype of every eukaryotic species is influenced by thousands of different genes n n Aneuploidy commonly causes an abnormal phenotype n n The expression of these genes has to be intricately coordinated to produce a phenotypically normal individual It leads to an imbalance in the amount of gene products Refer to Figure 8. 17 Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -46

In most cases, these effects are detrimental They produce individuals that are less likely to survive than a euploid individual Figure 8. 17 Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -47

Aneuploidy n Alterations in chromosome number occur frequently during gamete formation n 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 n Refer to Table 8. 1 Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -50

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n The autosomal aneuploidies compatible with survival are trisomies 13, 18 and 21 n n These involve chromosomes that are relatively small Aneuploidies involving sex chromosomes generally have less severe effects than those of autosomes n This is explained by X inactivation n n All additional X chromosomes are converted into Barr bodies The phenotypic effects listed in Table 8. 1 may be due to n n 1. The expression of X-linked genes prior to embryonic Xinactivation 2. An imbalance in the expression of pseudoautosomal genes Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -52

n Some human aneuploidies are influenced by the age of the parents n n Older parents more likely to produce abnormal offspring Example: Down syndrome (Trisomy 21) n Incidence rises with the age of either parent, especially mothers Figure 8. 19 Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -53

n Down syndrome is caused by the failure of chromosome 21 to segregate properly n n 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 n Human primary oocytes are produced in the ovary of the female fetus prior to birth n n 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 n This added length of time may contribute to an increased frequency of nondisjunction Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -54

Euploidy n n Most species of animals are diploid In many cases, changes in euploidy are not tolerated n n Polyploidy in animals is generally a lethal condition Some euploidy variations are naturally occurring n n Female bees are diploid Male bees (drones) are monoploid n n Contain a single set of chromosomes A few examples of vertebrate polyploid animals have been discovered n Rat - Argentinean Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -55

Euploidy n n In many animals, certain body tissues display normal variations in the number of sets of chromosomes Diploid animals sometimes produce tissues that are polyploid n This phenomenon is termed endopolyploidy n n Liver cells, for example, can be triploid, tetraploid or even octaploid (8 n) Polytene chromosomes of insects provide an unusual example of natural variation in ploidy Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -56

Polytene Chromosomes n n Occur mainly in the salivary glands of Drosophila and a few other insects Chromosomes undergo repeated rounds of chromosome replication without cellular division n n 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 n This bundle is termed a polytene chromosome Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -57

Each chromosome attaches to the chromoventer near its centromere Figure 8. 21 Central point where chromosomes aggregate Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -58

n Because of their size, polytene chromosomes lend themselves to an easy microscopic examination n n They are so large, they can be even seen in interphase Polytene chromosomes exhibit a characteristic banding pattern (Figure 8. 21 b) n Each dark band is known as a chromomere n n n 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 Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -59

Euploidy n In contrast to animals, plants commonly exhibit polyploidy n n 30 -35% of ferns and flowering plants are polyploid Many of the fruits and grain we eat come from polyploid plants n n Refer to Figure 8. 22 a In many instances, polyploid strains of plants display outstanding agricultural characteristics n They are often larger in size and more robust n Refer to Figure 8. 22 b Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -60

n Polyploids having an odd number of chromosome sets are usually sterile n These plants produce highly aneuploid gametes n Example: In a triploid organism there is an unequal separation of homologous chromosomes (three each) during anaphase I Each cell receives one copy of some chromosomes and two copies of other chromosomes Figure 8. 23 Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -61

n n Sterility is generally a detrimental trait However, it can be agriculturally desirable because it may result in n 1. Seedless fruit n Seedless watermelons and bananas n n n Triploid varieties Asexually propagated by human via cuttings 2. Seedless flowers n Marigold flowering plants n n Triploid varieties Developed by Burpee (Seed producers) Copyright ©The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display 8 -62