Chapter 17 Chromosome Changes - Lecture Slides PDF

Anthony J.F. Griffiths, John Doebley, Catherine Peichel, David A. Wassarman An Introduction to Genetic t Analysis TWELFTH EDITION Lecture Slides CHAPTER SEVENTEEN Copyright © 2020, W.H. Freeman and  KEY QUESTIONS 1. How do polyploids (3n, 4n, and so forth)...

Anthony J.F. Griffiths, John Doebley, Catherine Peichel, David A. Wassarman An Introduction to Genetic t Analysis TWELFTH EDITION Lecture Slides CHAPTER SEVENTEEN Copyright © 2020, W.H. Freeman and  KEY QUESTIONS 1. How do polyploids (3n, 4n, and so forth) arise, and what are their properties? 2. How do aneuploids (2n − 1, 2n + 1, and so forth) arise, and what are their properties? 3. How do duplications and deletions arise, and what are their properties? 4. How do inversions and translocations arise, and what are their properties? 5. What is the relevance of such changes to human beings?  INTRODUCTION (1 of 2) Chapter objective: to distinguish between major types of chromosomal mutations and to predict the effects of chromosomal mutations on organismal phenotypes. Concepts to note: Chromosome mutations Down syndrome  INTRODUCTION (2 of 2) Key concepts: Type of chromosome mutations Chromosome mutation and gene mutation  17.1 CHANGES IN CHROMOSOME NUMBER (1 of 19) TABLE 17-1 Chromosome Constitutions in a Normally Aberrant euploidy Diploid Organism with Three Chromosomes (Identified as A, B, and C) in the Basic Set* Aneuploidy Name Designation Constitution Number of chromosomes Key concepts: Normal Euploid Diploid 2n AA BB CC 6 Euploid: haploid (n) and Aberrant Euploids diploid (2n) Monoploid n ABC 3 Triploid 3n AAA BBB CCC 9 Polyploids: Tetraploid 4n AAAA BBBB CCCC 12 Aneuploids Haploid chromosome number Monosomic 2n-1 A BB CC 5 Monoploid (n) AA B CC 5 AA BB C 5 3n (triploid), 4n (tetraploid), Trisomic 2n+1 AAA BB CC 7 AA BBB CC 7 5n (pentaploid), 6n AA BB CCC 7 (hexaploid)... *In the case shown, the number of chromosomes in the basic set (the haploid chromosome number) is three.  17.1 CHANGES IN CHROMOSOME NUMBER (2 of 19) Monoploids and polyploids Key concepts: Monoploids (Male bees, wasps, and ants bypass meiosis; gametes are produced by mitosis.) Parthenogenesis Genetic load Polyploids are often larger and have larger component parts than their diploid relatives.  17.1 CHANGES IN CHROMOSOME NUMBER (3 of 19) Autopolyploids, meiotic pairing in triploids Key concepts: Polyploids with odd numbers of chromosome sets, such as triploids, are sterile or highly infertile. Unpaired chromosomes at meiosis, and their gametes and offspring are aneuploid. Bivalents (paired homologs), unpaired homologs (univalents) The paired homologs (bivalent) and the unpaired one (univalent) = (trivalents)  17.1 CHANGES IN CHROMOSOME NUMBER (4 of 19) Colchicine induces polyploidy Key concepts: All alleles in the genotype are doubled. Plants are much more tolerant of polyploidy. Natural and induced autotetraploid plants have increased sizes. Tetraploid grapes are larger than diploid grapes Meiotic nondisjunction generates aneuploid products Meiotic nondisjunction generates aneuploid products Meiotic nondisjunction generates aneuploid products Meiotic nondisjunction generates aneuploid products Meiotic nondisjunction generates aneuploid products 17.1 CHANGES IN CHROMOSOME NUMBER (5 of 19) Natural and induced autotetraploid plants have increased sizes. 17.1 CHANGES IN CHROMOSOME NUMBER (6 of 19) Autotetraploids can mostly have regular meiosis. Key concepts: If trivalents form, segregation leads to nonfunctional aneuploid gametes.  17.1 CHANGES IN CHROMOSOME NUMBER (7 of 19) Allopolyploids Key concepts: Amphidiploid The origin of the amphidiploid  17.1 CHANGES IN CHROMOSOME NUMBER (8 of 19) Origin of three allopolyploid species of Brassica Key concepts: Nearly 50 percent of all angiosperm plants are polyploids, resulting from auto- or allopolyploidy. New World cotton and wheat are natural allopolyploids that arose spontaneously.  17.1 CHANGES IN CHROMOSOME NUMBER (9 of 19) Polyploid animals 1. Polyploidy is less common in animals. 2. Some naturally occurring polyploid animals: species of flatworms, leeches, and brine shrimps reproduce by parthenogenesis. 3. Naturally occurring polyploid amphibians and reptiles are surprisingly common. The Salmonidae (the family of fishes that includes salmon and trout) appear to have originated through ancestral polyploidy. 4. Triploid oysters have been developed because they have a commercial advantage over their diploid relatives. The sterile triploids do not spawn and are palatable year-round.  17.1 CHANGES IN CHROMOSOME NUMBER (10 of 19) Meiotic nondisjunction generates aneuploid products Key concepts: Aneuploidy Meiotic nondisjunction Mitotic nondisjunction Monosomic 2n − 1 Trisomic 2n + 1 Nullisomic 2n − 2 Disomic n+1  17.1 CHANGES IN CHROMOSOME NUMBER (11 of 19) Monosomics (2n − 1) Key concepts: Turner syndrome, represented as XO. About 1 in 5000 female births show Turner syndrome.  17.1 CHANGES IN CHROMOSOME NUMBER (12 of 19) Three equally likely segregations may take place in the meiosis of an A/a/a trisomic, yielding the gametes with genotypes: Aa and a, aa, and A.  17.1 CHANGES IN CHROMOSOME NUMBER (13 of 19) Klinefelter syndrome XXY Key concepts: Persons with this syndrome are males who have lanky builds and a mildly impaired IQ and are sterile. A few genes scattered throughout an “inactive X” are still transcriptionally active in XXY.  17.1 CHANGES IN CHROMOSOME NUMBER (14 of 19) Down syndrome Key concepts: The frequency of Down syndrome is about 0.15 percent of all live births. An extra copy of chromosome 21 caused by nondisjunction of chromosome 21 in a parent who is chromosomally normal. Rarer types of Down syndrome arise from chromosome translocations. The average life expectancy is now 60 years. Metacentric Chromosomes Metacentric chromosomes have the centromere in the center, such that both sections are of equal length. Human chromosome 1 and 3 are metacentric. Submetacentric Chromosomes Submetacentric chromosomes have the centromere slightly offset from the center leading to a slight asymmetry in the length of the two sections. Human chromosomes 4 through 12 are submetacentric. Acrocentric Chromosomes Acrocentric chromosomes have a centromere which is severely offset from the center leading to one very long and one very short section. Human chromosomes 13,15, 21, and 22 are acrocentric. Telocentric Chromosomes Telocentric chromosomes have the centromere at the very end of the chromosome. Humans do not possess telocentric chromosomes but they are found in other species such as mice.  Edwards Syndrome Edwards syndrome also Chromosome known as Trisomy 18, is a 18 genetic disorder that is caused when there is all or part of an extra 18th chromosome. A person with Edwards Syndrome has three copies of chromosome 18 instead of the normal two copies Common Characteristics Edwards syndrome severely affects all organ systems of the body Mental retardations, delayed development High muscle tone Seizures Physical malformations Heart defects Small head, small eyes, wide set eyes, small lower jaw  Patau Syndrome Patau Syndrome also known as trisomy 13 and trisomy D is a syndrome where there is an extra chromosome 13. A person with Patau Syndrome has three copies of chromosome 13 instead of the normal two copies  17.1 CHANGES IN CHROMOSOME NUMBER (15 of 19) The incidence of Down syndrome is related to maternal age. Key concepts: Older mothers run a greatly elevated risk of having a child with Down syndrome. Most nondisjunction related to the effect of maternal age is due to nondisjunction at anaphase I. Trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome)  17.1 CHANGES IN CHROMOSOME NUMBER (16 of 19) Plants tend to be more tolerant of aneuploidy than are animals. Key concepts: Jimsonweed (Datura stramonium) The 12 different trisomies lead to 12 different an characteristic shape changes in the capsule.  17.1 CHANGES IN CHROMOSOME NUMBER (17 of 19) Aneuploidy affects the balance of gene dosage in a cell Key concepts: Gene balance Monosomics are more severely affected than are the corresponding trisomics. Aneuploids are much more abnormal than polyploids.  17.1 CHANGES IN CHROMOSOME NUMBER (18 of 19) Sex chromosome gene balance Key concepts: Dosage compensation In fruit flies, the male’s X chromosome appears to be hyperactivated. Only one transcriptionally active X chromosome in each somatic cell in mammals. 17.1 CHANGES IN CHROMOSOME NUMBER (19 of 19) Gene balance and aneuploidy 1. Autosomal aneuploidy alters the organism’s shape and proportions in characteristic ways. Plants tend to be somewhat more tolerant of aneuploidy than are animals. 2. Gene-dosage effect is the relation between the number of copies of a gene and the amount of the gene’s product made. Haplo-abnormal and triplo-abnormal phenotype. 3. The phenotypes of any deleterious recessive alleles present on a monosomic autosome will be automatically observed due to the absence of the wild-type allele. 4. Aneuploidy is deleterious because of gene imbalance: the ratio of gene products is different from that in euploids, and this difference interferes with the normal function of the genome.  17.2 CHANGES IN CHROMOSOME STRUCTURE (1 of 20) Chromosomal rearrangements Key concepts: DNA breakage or crossing over between repetitive DNA can produce chromosomal rearrangements. 17.2 CHANGES IN CHROMOSOME STRUCTURE (2 of 20) DNA breakage and chromosomal rearrangements: 1. Both DNA strands must break at two different locations, followed by a rejoining of the broken ends to produce a new chromosomal arrangement. 2. Double-stranded breaks are potentially lethal, unless they are repaired. 3. Repair systems in the cell correct the double-stranded breaks by joining broken ends back together. 4. If the two ends of the same break are rejoined, the original DNA order is restored. If the ends of two different breaks are joined, the result is some type of chromosomal rearrangement. 17.2 CHANGES IN CHROMOSOME STRUCTURE (3 of 20) Crossing over between repetitive (duplicated) DNA segments and chromosomal rearrangements: Unequal crossing over (nonallelic homologous recombination (NAHR)), i.e., sequences pair up that are not in the same relative positions on the homologs, crossing over can produce aberrant chromosomes with: deletions duplications inversions translocations  17.2 CHANGES IN CHROMOSOME STRUCTURE (4 of 20) Two general types of rearrangements: unbalanced and balanced. Unbalanced rearrangements: 1. Unbalanced rearrangements change the gene dosage of a chromosome segment. 2. Deletions, lost C–D segment. 3. The loss of a segment on one homolog unmasks recessive alleles present on the other homolog, leading to the appearance of phenotypes associated with those mutations.  17.2 CHANGES IN CHROMOSOME STRUCTURE (5 of 20) Chromosomal rearrangements Key concepts: Deletion (the loss of a part of one chromosome arm) Deletion loop Polytene chromosomes The lethality of large heterozygous deletions can be explained by gene imbalance and the expression of deleterious recessive alleles. 17.2 CHANGES IN CHROMOSOME STRUCTURE (6 of 20) Chromosomal rearrangements Key concepts: Deletion Pseudodominance Mapping mutant alleles by pseudodominance  17.2 CHANGES IN CHROMOSOME STRUCTURE (7 of 20) Chromosomal rearrangements Key concepts: Deletion Cri du chat syndrome, caused by a heterozygous deletion of the tip of the short arm of chromosome 5.  17.2 CHANGES IN CHROMOSOME STRUCTURE (8 of 20) Two general types of rearrangements: unbalanced and balanced. Unbalanced rearrangements: 1. Unbalanced rearrangements change the gene dosage of a chromosome segment. 2. Duplication is the repetition of a segment of a chromosome  17.2 CHANGES IN CHROMOSOME STRUCTURE (9 of 20) Chromosomal rearrangements Key concepts: Duplications The duplicate regions can be located adjacent to each other; or the extra copy can be located elsewhere in the genome. Williams syndrome deletion, and the 7q11.23 duplication syndrome.  5p-Syndrome 5P syndrome is a chromosomal condition where a piece of chromosome 5 is missing 5p syndrome develops in result of chromosomal deletion that occurs during reproductive cells during early fetal development Common Characteristics Cat like cry Failure to thrive Microcephaly Mental retardations Spastic quadriparesis Micro and retrognathia Glossoptosis Bilateral epicanthus Hypertelorism Time external genitalia  Prader-Willi Syndrome Prader Willi Syndrome is a condition where seven genes on chromosome 15 are deleted  Common Characteristics Hypotonia Hypogonadism Failure to thrive Scoliosis Speech delay Poor physical coordination sleep disorders Delayed puberty Obesity Short stature  17.2 CHANGES IN CHROMOSOME STRUCTURE (10 of 20) Chromosomal rearrangements Key concepts: Duplications Map of segmental duplications on human chromosome 7. The tandem segmental duplications overlaps are associated with Williams syndrome. Segmental duplications have an important role as substrates for nonallelic homologous recombination (NAHR). Key differences between human and ape sequences may come from NAHR mediated by segmental duplications. NAHR is responsible for rearrangements that cause some human diseases, including neurofibromatosis, hemophilia A, and red–green color blindness.  17.2 CHANGES IN CHROMOSOME STRUCTURE (11 of 20) Two general types of rearrangements: unbalanced and balanced. Balanced rearrangements: 1. Balanced rearrangements change the chromosomal gene order but do not remove or duplicate any DNA. 2. An inversion is a rearrangement in which an internal segment of a chromosome has been broken twice, flipped 180 degrees, and rejoined. 3. If the centromere is outside the inversion, the inversion is said to be paracentric inversion. Inversions spanning the centromere are pericentric inversions.  17.2 CHANGES IN CHROMOSOME STRUCTURE (12 of 20) Chromosomal rearrangements Key concepts: Inversions A segment of a chromosome is cut out, flipped, and reinserted. Inversions may cause different structural changes in the DNA but do not result in gene imbalance. They may have no effect on genes, may disrupt a gene, or may fuse parts of two genes, depending on the location of the break points.  17.2 CHANGES IN CHROMOSOME STRUCTURE (13 of 20) Chromosomal rearrangements Key concepts: Inversions Inversion loop: one chromosome twists once at the ends of the inversion to pair with its untwisted homolog in meiosis.  17.2 CHANGES IN CHROMOSOME STRUCTURE (14 of 20) Chromosomal rearrangements Key concepts: Inversions Paracentric inversion: crossing over within the inversion loop at meiosis connects homologous centromeres in a dicentric bridge while also producing an acentric fragment. Inviable meiotic product. Paracentric inversions can lead to deletion products  17.2 CHANGES IN CHROMOSOME STRUCTURE (15 of 20) Chromosomal rearrangements Key concepts: Inversions Pericentric inversion—if a gamete carrying a crossover chromosome, the zygote is not viable because of gene imbalance. Only noncrossover chromatids are present in viable progeny.  17.2 CHANGES IN CHROMOSOME STRUCTURE (16 of 20) Chromosomal rearrangements Key concepts: Inversions Human chromosomes 5, 6, and 7 and the corresponding chimpanzee chromosomes 4, 5, and 6. Crossing lines indicate the homologous sequences in an inverted orientation on the human and chimpanzee chromosomes.  17.2 CHANGES IN CHROMOSOME STRUCTURE (17 of 20) Chromosomal rearrangements Key concepts: Reciprocal translocations The segregating chromosomes of a reciprocal-translocation heterozygote form a cross-shaped pairing configuration. A 50% reduction in viable gametes or zygotes occurs for the presence of a translocation.  17.2 CHANGES IN CHROMOSOME STRUCTURE (18 of 20) Chromosomal rearrangements Key concepts: Reciprocal translocations Pollen of a semisterile corn plant. The clear pollen grains contain chromosomally unbalanced meiotic products of a reciprocal translocation heterozygote. The opaque pollen grains contain either the complete translocation genotype or normal chromosomes.  17.2 CHANGES IN CHROMOSOME STRUCTURE (19 of 20) Chromosomal rearrangements Key concepts: Reciprocal translocations A translocation heterozygote that has been established by crossing an a/a ; b/b individual with a translocation homozygote bearing the wild-type alleles. Recombinants are created but do not survive because they carry unbalanced genomes. The only viable progeny are those bearing the parental genotypes. A reciprocal translocation demonstrated by chromosome painting  17.2 CHANGES IN CHROMOSOME STRUCTURE (20 of 20) Chromosomal rearrangements Key concepts: Reciprocal translocations Robertsonian translocations: In Down syndrome, the translocation involves two copies each of chromosome 14 and chromosome 21. 17.3 PHENOTYPIC CONSEQUENCES OF CHROMOSOMAL CHANGES (1 of 4) Chromosome rearrangements and evolution Key concepts: Chromosome number can vary greatly between closely related species, due to chromosomal fusion events. 17.3 PHENOTYPIC CONSEQUENCES OF CHROMOSOMAL CHANGES (2 of 4) Chromosome rearrangements and evolution Key concept: Butterfly mimicry is facilitated by chromosome inversions.  Philadelphia Chromosome Philadelphia chromosome is an abnormality associated with chronic myelogenous leukemia It is the result of a reciprocal translocation between chromosome 9 and 22 Common Characteristics This abnormality involves the cells of bone marrow It takes only one cell for this abnormality to develop Once it begins to develop the cells replicate It eventually causes problems wit the production of myelogenous blood cells 17.3 PHENOTYPIC CONSEQUENCES OF CHROMOSOMAL CHANGES (3 of 4) Chromosome rearrangements and cancer Key concept: Translocation relocates a proto-oncogene next to a new regulatory element. The formation of a hybrid gene between the two proto-oncogenes BCR1 and ABL. 17.3 PHENOTYPIC CONSEQUENCES OF CHROMOSOMAL CHANGES (4 of 4) Overall incidence of human chromosome mutations Key concepts: The estimated distribution of chromosome mutations among human conceptions that develop sufficiently to implant in the uterus. The proportion of chromosomal mutations is much higher in spontaneous abortions. The fates of a million implanted human zygotes