GENETICS A Conceptual Approach Benjamin A. Pierce GENETICS A Conceptual Approach SIXTH EDITION CHAPTER 8 Chromosome Variation © 2017 W. H. Freeman and Company

Bananas have multiple sets of chromosomes.

Chromosome morphology (position of the centromere on the chromosome): 8.1 Chromosome Mutations Include Rearrangements, Aneuploids, and Polyploids Chromosome morphology (position of the centromere on the chromosome): Metacentric Submetacentric Acrocentric Telocentric

8.1 Chromosome Mutations Include Rearrangements, Aneuploids, and Polyploids Karyotyping Chromosomes prepared from actively dividing cells Halted in metaphase Chromosomes arranged according to size Banding G bands: Giemsa stain Q bands: quinacrine mustard C bands: centromeric heterochromatin R bands: rich in cytosine-guanine base pairs

8. 1 A human karyotype consists of 46 chromosomes 8.1 A human karyotype consists of 46 chromosomes. A karyotype for a male is shown here; a karyotype for a female would have two X chromosomes. [© pr philippe Vago © ISM/Phototake.]

8. 2 Chromosome banding is revealed by special staining techniques 8.2 Chromosome banding is revealed by special staining techniques. (a) G banding. (b) Q banding. (c) C banding. (d) R banding. [part a: Leonard Lessin/Science Source. parts b and c: University of Washington Pathology Department. http://pathology.washington.edu. part d: © Dr. Ram Verma/Phototake.]

8.1 Chromosome Mutations Include Rearrangements, Aneuploids, and Polyploids Types of chromosome mutations: Rearrangements: Aneuploidy Polyploidy

8.3 Chromosome mutations consist of chromosome rearrangements, aneuploids, and polyploids. Duplications, trisomy, and autotriploids are examples of each category of mutation.

8.2 Chromosome Rearrangements Alter Chromosome Structure Four types of chromosomal rearrangements: Fig. 8.4 Duplication: Fig. 8.5, Fig. 8.6, Fig. 8.7 Unbalanced gene dosage: Fig. 8.8

8.4 The four basic types of chromosome rearrangements areduplications, deletions, inversions, and translocations.

8.5 In an individual heterozygous for a duplication, the duplicated chromosome loops out during pairing in prophase I.

8.6 The Bar phenotype in Drosophila melanogaster results from an X-linked duplication. (a) Wild-type fruit flies have normal-size eyes. (b) Flies heterozygous and (c) homozygous for the bar mutation have smaller, bar-shaped eyes. (d) Flies with double Bar have three copies of the duplication and much smaller bar-shaped eyes.

8.7 Unequal crossing over produces duplications and deletions.

8.8 Unbalanced gene dosage leads to developmental abnormalities.

8.2 Chromosome Rearrangements Alter Chromosome Structure Deletions: loss of a chromosomal segment Large deletions easily detected; during pairing, normal chromosome loops out (Fig. 8.9) Effects of deletions Imbalances in gene product Expression of a normally recessive gene (pseudodominance) Haploinsufficiency

8.9 In an individual heterozygous for a deletion, the normal chromosome loops out during chromosome pairing in prophase I.

8.10 The Notch phenotype is produced by a chromosome deletion that includes the Notch gene. (Left) Normal wing veination. (right) Wing veination produced by a Notch mutation. [Spyros Artavanis-Tsakonas, Kenji Matsuno, and Mark E. Fortini.]

Effects of some human chromosome rearrangements TABLE 8.1 Effects of some human chromosome rearrangements Type of Rearrangement Chromosome Disorder Symptoms Duplication 4, short arm — Small head, short neck, low hairline, reduced growth, and intellectual disability 4, long arm Small head, sloping forehead, hand abnormalities 7, long arm Delayed development, asymmetry of the head, fuzzy scalp, small nose, low-set ears 9, short arm Characteristic facial features, variable intellectual disability, high and broad forehead, hand abnormalities Deletion 5, short arm Cri-du-chat syndrome Small head, distinctive cry, widely spaced eyes, round face, intellectual disability Wolf–Hirschhorn syndrome Small head with high forehead, wide nose, cleft lip and palate, severe intellectual disability Small head, mild to moderate intellectual disability, cleft lip and palate, hand and foot abnormalities Williams–Beuren syndrome Distinctive facial features, heart defects, cognitive impairment 15, long arm Prader–Willi syndrome Feeding difficulty at early age but becoming obese after 1 year of age, mild to moderate intellectual disability 18, short arm Round face, large and low-set ears, mild to moderate intellectual disability 18, long arm Distinctive mouth shape, small hands, small head, intellectual disability

8.2 Chromosome Rearrangements Alter Chromosome Structure Inversion (depends on the involvement of the centromere in the inversion): Paracentric inversion Pericentric inversion

8.2 Chromosome Rearrangements Alter Chromosome Structure Inversions in meiosis: Individuals homozygous: no problems arise during meiosis Individuals heterozygous: Homologous sequences align only if the two chromosomes form an inversion loop Demonstrate reduced recombination in a paracentric inversion, as gametes formed result in nonviable offspring Have abnormal gametes formed in a pericentric inversion

8.11 Chromosome 4 differs in humans and chimpanzees by a pericentric inversion. 21

8.12 In an individual heterozygous for a paracentric inversion, the chromosomes form an inversion loop during pairing in prophase I.

8.13 In a heterozygous individual, a single crossover within a paracentric inversion leads to abnormal gametes.

8.14 In a heterozygous individual, a single crossover within a pericentric inversion leads to abnormal gametes.

Concept Check 1 A dicentric chromosome is produced when crossing over takes place in an individual heterozygous for which type of chromosome rearrangement? Duplication Deletion Paracentric inversion Pericentric inversion

Concept Check 1 A dicentric chromosome is produced when crossing over takes place in an individual heterozygous for which type of chromosome rearrangement? Duplication Deletion Paracentric inversion Pericentric inversion

Translocations Nonreciprocal translocation Reciprocal translocation Robertsonian translocation

8.15 In a Robertsonian translocation, the short arm of one acrocentric chromosome is exchanged with the long arm of another.

Translocations in Meiosis 8.16 In an individual heterozygous for a reciprocal translocation, crosslike structures form in homologous pairing.

8.17 Fragile sites are chromosomal regions susceptible to breakage under certain conditions. Shown here is a fragile site on the human X chromosome. [Courtesy of Dr. Christine Harrison.]

Translocations in Evolution

Concept Check 2 What is the outcome of a Robertsonian translocation? Two acrocentric chromosomes One metacentric chromosome and one chromosome with two very short arms One metacentric chromosome and one acrocentric chromosome Two metacentric chromosomes

Concept Check 2 What is the outcome of a Robertsonian translocation? Two acrocentric chromosomes One metacentric chromosome and one chromosome with two very short arms One metacentric chromosome and one acrocentric chromosome Two metacentric chromosomes

Variations in copy number: aneuploidy and polyploidy 8.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes Variations in copy number: aneuploidy and polyploidy Causes of aneuploidy: Deletion of centromere during mitosis and meiosis Robertsonian translocation Nondisjunction during meiosis and mitosis

8.18 Aneuploids can be produced through nondisjunction in meiosis I, meiosis II, and mitosis. The gametes that result from meiosis with nondisjunction combine with a gamete (with blue chromosome) that results from normal meiosis to produce the zygotes.

Types of Aneuploidy Nullisomy: loss of both members of a homologous pair of chromosomes; 2n − 2 Monosomy: loss of a single chromosome; 2n − 1 Trisomy: gain of a single chromosome; 2n + 1 Tetrasomy: gain of two homologous chromosomes; 2n + 2

Concept Check 3 A diploid organism has 2n = 36 chromosomes. How many chromosomes will be found in a trisomic member of this species?

Concept Check 3 A diploid organism has 2n = 36 chromosomes. How many chromosomes will be found in a trisomic member of this species? 2n + 1 = 36 + 1 = 37

8.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes Effects of aneuploidy: In plants: Fig. 8.19. In humans: Sex-chromosome aneuploids: Turner syndrome; XO Klinefelter syndrome; XXY

8.19 Mutant capsules in Jimson weed (Datural stramonium) result from different trisomies. Each type of capsule is a phenotype that is trisomic for a different chromosome.

8.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes Effects of aneuploidy: In plants: mutants could actually be trisomics (Fig. 8.19) In humans: Autosomal aneuploids: Trisomy 21: Down syndrome Primary Down syndrome, 75% random nondisjunction in egg formation (Fig. 8.20) Familial Down syndrome, Robertsonian translocation between chromosomes 14 and 21 (Figs. 8.21 and 8.22)

8.20 Primary Down syndrome is caused by the presence of three copies of chromosome 21. Karyotype of a person who has primary Down syndrome.

8.21 The translocation of chromosome 21 onto another chromosome results in familial Down syndrome. Here, the long arm of chromosome 21 is attached to chromosome 15. This karyotype is from a translocation carrier, who is phenotypically normal but is at increased risk for producing children with Down syndrome.

8.22 Translocation carriers are at increased risk for producing children with Down syndrome.

8.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes Effects of aneuploidy: In humans: Autosomal aneuploids: Trisomy 18: Edward syndrome, 1/8000 live births Trisomy 13: Patau syndrome, 1/15,000 live births Trisomy 8: 1/25,000 ~ 1/50,000 live births Why is there a drastic decrease in frequency of this trisomic syndrome from chromosome 18 to chromosome 8?

Concept Check 4 Briefly explain why sex-chromosome aneuploids are more common than autosomal aneuploids in humans and mammals.

Concept Check 4 Briefly explain why sex-chromosome aneuploids are more common than autosomal aneuploids in humans and mammal. No mechanism of dosage compensation for autosomal chromatids. Autosomes carry more genes. Most autosomal aneuploids are spontaneously aborted.

8.3 Aneuploidy Is an Increase or Decrease in the Number of Individual Chromosomes Effects of aneuploidy: In humans: Autosomal aneuploids: Aneuploidy and maternal age; Fig. 8.23 Possible interpretation of this connection? Uniparental disomy: both chromosomes are inherited from the same parent. Mosaicism and nondisjunction in mitotic division; Fig 8.24

8.23 The incidence of primary Down syndrome and other aneuploids increases with maternal age.

8.24 Genetic mosaicism for the sex chromosomes produces a gynandromorph. This XX/XO gynandromorph fruit fly carries one wild-type X chromosome and one X chromosome with recessive alleles for white eyes and miniature wings. The left side of the fly has a normal female phenotype because the cells are XX and the recessive alleles on one X chromosome are masked by the presence of wild-type alleles on the other. The right side of the fly has a male phenotype with white eyes and miniature wing because the cells are missing the wild-type X chromosome (are XO), allowing the white and miniature alleles to be expressed.

8.4 Polyploidy Is the Presence of More Than Two Sets of Chromosomes Autopolyploidy: From single species Fig. 8.25 Allopolyploidy From two species Fig. 8.28

8.25 Autopolyploidy can arise through nondisjunction in mitosis or meiosis.

8.26 In meiosis in an autotriploid, homologous chromosomes can pair, or fail to pair, in three ways. This example illustrates the pairing and segregation of a single homologous set of chromosomes.

8.27 Most allopolyploids arise from hybridization between two species followed by chromosome doubling.

8.4 Polyploidy Is the Presence of More Than Two Sets of Chromosomes The significance of polyploidy: Increase in cell size Larger plant attributes Evolution: may give rise to new species

8.28 Modern bread wheat, Triticum aestivum, is a hexaploid with genes derived from three different species. Two diploid species, T. monococcum (n = 14) and probably T. searsii (n = 14), originally crossed to produce a diploid hybrid (2n = 14) that underwent chromosome doubling to create T. turgidum (4n = 28). A cross between T. trugidum and T. tauschi (2n – 14) produced a triploid hybrid (3n = 21) that then underwent chromosome doubling to produce T. aestivum, which is a hexaploid (6n = 42).

Examples of polyploid crop plants TABLE 8.2 Examples of polyploid crop plants Plant Type of Polyploidy Chromosome Sets Chromosome Number Potato Autopolyploid 4n 48 Banana 3n 33 Peanut 40 Sweet potato 6n 90 Tobacco Allopolyploid Cotton 52 Wheat 42 Oats Sugarcane 8n 80 Strawberry 56 Source: After F. C. Elliot, Plant Breeding and Cytogenetics (New York: McGraw-Hill, 1958).

Different types of chromosome mutations TABLE 8.3 Different types of chromosome mutations Chromosome Mutation Definition Chromosome rearrangement Change in chromosome structure Chromosome duplication Duplication of a chromosome segment Chromosome deletion Deletion of a chromosome segment Inversion Chromosome segment inverted 180 degrees Paracentric inversion Inversion that does not include the centromere in the inverted region Pericentric inversion Inversion that includes the centromere in the inverted region Translocation Movement of a chromosome segment to a nonhomologous chromosome or to another region of the same chromosome Nonreciprocal translocation Movement of a chromosome segment to a nonhomologous chromosome or to another region of the same chromosome without reciprocal exchange Reciprocal translocation Exchange between segments of nonhomologous chromosomes or between regions of the same chromosome Aneuploidy Change in number of individual chromosomes Nullisomy Loss of both members of a homologous pair Monosomy Loss of one member of a homologous pair Trisomy Gain of one chromosome, resulting in three homologous chromosomes Tetrasomy Gain of two homologous chromosomes, resulting in four homologous chromosomes Polyploidy Addition of entire chromosome sets Autopolyploidy Polyploidy in which extra chromosome sets are derived from the same species Allopolyploidy Polyploidy in which extra chromosome sets are derived from two or more species

Concept Check 5 Species A has 2n = 16 chromosomes and species B has 2n = 14. How many chromosomes would be found in an allotriploid of these two species? 21 or 24 42 or 48 22 or 23 45

Concept Check 5 Species A has 2n = 16 chromosomes and species B has 2n = 14. How many chromosomes would be found in an allotriploid of these two species? 21 or 24 42 or 48 22 or 23 45