Genetics: Study Unit 7 - 2024 PDF

STUDY UNIT 7 GENETICS A Conceptual Approach Benjamin A Pierce SEVENTH EDITION CHAPTER 8 Chromosome Variation p 223 – 256  STUDY UNIT 7 Chapter 8 Outline Chromosomal mutations Chromosome...

STUDY UNIT 7 GENETICS A Conceptual Approach Benjamin A Pierce SEVENTH EDITION CHAPTER 8 Chromosome Variation p 223 – 256  STUDY UNIT 7 Chapter 8 Outline Chromosomal mutations Chromosome Polyploidy rearrangements Aneuploidy  EXAM: What to know from this study unit? The nature of the different types of chromosomal mutations. - Chromosomal rearrangements Duplications, deletions, inversions and translocations. - Aneuploidy - Polyploidy How they pair during prophase I of meiosis. What effect the structural mutation or change in chromosome number has on the chromosome composition of the gametes, and the fertility of the organism. (Ignore all sections, figures and details from Chapter 8 not included in these notes.) Open PointSolutions app, join session GTS161 STUDY UNIT 7 CHAPTER 8 Chromosome Variation LECTURE 7.1 Ch 8 p 224 - 235 Chromosome rearrangements  LECTURE 7.1 Ch 8 p 224 - 235 Chromosome rearrangements LEARNING OBJECTIVES At the end of this lecture, you should be able to: Define the major types of chromosome mutations Describe the major types of chromosome rearrangements and their effects on chromosome structure. Explain how duplications and deletions alter phenotypes. Outline the results of crossing over within paracentric and pericentric inversions in individuals heterozygous for the inversion. Explain how translocations alter phenotypes. Outline the results of chromosome segregation in individuals heterozygous for a reciprocal translocation. 8.1 Chromosome Mutations Include Rearrangements, Aneuploidy, and Polyploidy Revision: Chromosome Morphology (based on position of centromere on chromosome) – Metacentric – Submetacentric – Acrocentric – Telocentric Karyotype: complete set of chromosomes possessed by an organism. Usually presented as a picture of metaphase chromosomes arranged according to their size. Human male karyotype NB: Revise normal meiosis SU 1 - chromosome pairing (synapsis) - chromosome segregation - chromatid segregation - gamete formation 8.2 Chromosome Rearrangements Alter Chromosome Structure  Duplications A chromosome duplication is a mutation where part of the chromosome has been doubled (duplicated). ABCDEFG ABCDEFEFG ABCDEFGEF ABCDEFFEG tandem displaced reverse duplication duplication duplication  Effects of chromosome duplications Duplications often have major effect on the phenotype. Phenotypic effect likely due to imbalances in the amounts of gene products present (gene dosage). Duplicated gene will result in higher than normal levels of its protein product, this imbalance can e.g. affect developmental processes.  Effects of duplications on meiosis Prophase I pairing in an individual heterozygous for a duplication requires one chromosome to loop out to allow pairing of homologous regions.  Deletions A chromosome deletion is a mutation where part of the chromosome has been lost (deleted). ABCDEFG ABCDG  Effects of chromosome deletions Phenotypic consequences depend on which genes were located on the deleted region. Homozygotes are usually lethal. Heterozygotes may produce imbalanced levels of gene products. Pseudodominance = expression of a normally recessive mutation on one homolog, due to deletion of the dominant allele on the other homolog.  Effects of deletions on meiosis Prophase I pairing in an individual heterozygous for a deletion requires the normal chromosome to loop out to allow pairing of homologous regions. For interest only:  Inversions A chromosome inversion occurs when a chromosome segment is inverted – turned 180. ABCDEFG ABCFEDG ADCBEFG Paracentric inversion Pericentric inversion (does not include centromere) (includes centromere)  Effects of inversions DNA neither lost nor gained, just rearranged. Often significant phenotypic effects. E.g. gene may be broken into two parts, destroying its function. Position effect – if gene is in new position due to an inversion, the regulation of its expression may be altered.  Effects of inversions on meiosis In prophase I pairing in an individual heterozygous for inversion, the homologous sequences can only pair if an inversion loop is formed. Paracentric inversions in meiosis ABCDEFG → ABCFEDG In an individual heterozygous for a paracentric inversion (does not include centromere): Inversion loop forms. If crossing over occurs within loop: - Two chromatids are not involved in crossover. - One dicentric chromatid (two centromeres) and one acentric fragment (no centromere) form. - Dicentric bridge breaks during anaphase I, acentric fragment is lost. Of the four gametes, two contain non-recombinant chromosomes (one normal and one with inversion), the other two contain recombinant chromosomes missing some genes, these gametes are not viable. In Achieve – SU 7 Ch 8 – Resources: Do Ch 8 Interactive Video Assignment: Crossing Over in an Individual Heterozygous for a Paracentric Inversion Pericentric inversions in meiosis ABCDEFG → ADCBEFG In an individual heterozygous for a pericentric inversion (includes centromere): Inversion loop forms. If crossing over occurs within loop: - Two chromatids are not involved in crossover. - No dicentric bridge or acentric fragment formed. - Two chromatids involved in crossover have multiple copies of some genes and no copies of other genes. Of the four gametes, two contain non-recombinant chromosomes (one normal and one with inversion), the other two contain recombinant chromosomes (with two copies of some genes and other genes missing), these gametes are not viable.  Translocations A chromosome translocation occurs when genetic material moves (translocates) between nonhomologous chromosomes or within the same chromosome. ABCDEFG MNOPQRS ABCDEFG MNOPQRS ABCDG MNOPEFQRS ABCDQRS MNOPEFG Nonreciprocal translocation Reciprocal translocation  Effects of translocations Following translocation, genes are physically linked that were previously in different chromosomes, this may affect gene expression (position effect). Chromosomal breaks may affect gene function. Deletions frequently accompany translocations. In a Robertsonian translocation the long arms of two acrocentric chromosomes join. The smaller chromosome is often lost.  Effects of translocations on meiosis An individual heterozygous for a translocation possess one normal copy of each chromosome, and one translocated copy. Pairing results in crosslike configuration consisting of all four chromosomes. Depending on which combinations of centromeres segregate to the same pole at anaphase I, gametes can be viable (with normal and translocation chromosomes) or nonviable (some genes present in two copies, other missing). Note: difference between crossing over and translocation Crossing over: Translocation: Exchange of genetic material Exchange of genetic material between homologous between non-homologous chromosomes. chromosomes. Normal part of meiosis. Structural abnormality. In Achieve – SU 7 Ch 8 – Resources: Do Ch 8 Interactive Video Assignment: Segregation in Individuals Heterozygous for Reciprocal Translocations Summary of synapsis (pairing) configurations of chromosome rearrangements: Deletion Paracentric inversion Translocation heterozygote heterozygote heterozygote Duplication Pericentric inversion heterozygote heterozygote C D C D Question: The following diagram illustrates a heterozygous chromosome inversion during meiosis: a. Name this type of inversion. b. Draw the daughter chromosomes and/or fragments that would be found after segregation of the chromatids. c. Give the allele composition of the resulting gametes. E crossover e D d centromeres A B G chromatids a b g Question: In a certain species, the normal chromosome 1 carries loci a bcdefg and chromosome 2 carries t uvwxyz. Following reciprocal translocation, the translocated chromosomes are a bcdxyz and t uvwefg. a) Diagram the chromosome synapsis during meiosis of the translocation heterozygote. b) Which chromosome segregation pattern following synapsis will result in the highest frequency of viable gametes? In conclusion Chromosomal rearrangements which alter chromosome structure are deletions, duplications, inversions (para- or pericentric) and translocations. Individuals heterozygous for a structural rearrangement will show a specific characteristic chromosome pairing configuration during meiosis. Structural rearrangements impact on % gamete viability of carriers. Open PointSolutions app, join session GTS161 STUDY UNIT 7 CHAPTER 8 Chromosome Variation LECTURE 7.2 Ch 8 p 236 - 241 Aneuploidy  STUDY UNIT 7 Chapter 8 Outline Chromosomal mutations Chromosome Polyploidy rearrangements Aneuploidy  LECTURE 7.2 Ch 8 p 236 - 241 Aneuploidy LEARNING OBJECTIVES At the end of this lecture, you should be able to: Describe the different types of aneuploidy. Understand the role of nondisjunction in the origin of aneuploids. Explain the consequences of aneuploidy. 8.3 Aneuploidy is an Increase or Decrease in the Number of Individual Chromosomes Causes of Aneuploidy: Chromosome is lost during mitosis or meiosis, e.g. if its centromere is deleted. Small chromosome generated by a Robertsonian translocation is lost in mitosis or meiosis. Nondisjunction, i.e. failure of homologous chromosomes or sister chromatids to separate normally during meiosis or mitosis. Nondisjunction in Meiosis I Nondisjunction in Meiosis II Nondisjunction in Mitosis  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  Double trisomic: extra copy of each of two nonhomologous chromosomes. 2n + 1 + 1 Double monosomic: loss of two nonhomologous chromosomes. 2n - 1 - 1 Double tetrasomic: gain of two extra pairs of homologous chromosomes. 2n + 2 + 2 Effects of Aneuploidy: In most animals and many plants aneuploid mutations are lethal. If viable, aneuploidy usually alters the phenotype drastically. As a results of abnormal gene dosage (3x copies rather than 2) for some genes the relative concentration of gene products are disrupted, this often interferes with normal development. Exception is human X-chromosome, where inactivation of all X’s more than one prevents gene dosage problems. Aneuploidy in plants E.g. Jimson weed (2n = 24) 12 different mutant phenotypes. Each is trisomic (2n+1 = 25) for a different chromosome pair. Aneuploidy in humans Very high percentage of all human embryos that are conceived possess chromosome abnormalities. >30% of all conceptions abort spontaneously, of which at least 50% have chromosome defects - usually aneuploidies. Sex-chromosome aneuploids: Most common aneuploidies in living humans involve sex chromosomes. Sex chromosome aneuploidies better tolerated than autosomal aneuploidies. Turner syndrome XO Klinefelter sydrome XXY. Autosomal aneuploids: Down syndrome (trisomy 21) Most common human autosomal aneuploidy, 1/700 births. Primary Down Syndrome: Individuals with three full copies of chromosome 21. 75% are from maternal origin, arising from spontaneous nondisjunction during egg formation. Familial Down Syndrome: Individuals with 46 chromosomes including two normal copies of chromosome 21, but an extra copy of part of chromosome 21 is attached to another chromosome through a translocation. Usually originates from Robertsonian translocation between chromosomes 14 and 21. Translocation carrier has 45 chromosomes and is phenotypically normal, but has an increased chance of producing Down syndrome children. Other human trisomies: 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 these trisomic syndromes from chromosome 18 to chromosome 8? Aneuploidy and maternal age: Frequency of meiotic nondisjunction increase with maternal age. Possibly due to long arrest in meiosis during oocyte development (from birth until ovulation), breakdown of cellular structures required for chromosome segregation.  Uniparental Disomy Uniparental disomy: both chromosomes of a homologous pair are inherited from the same parent  Genetic Mosaicism Genetic mosaicism: regions of tissue in one individual with different chromosome constitutions. Often results from mitotic nondisjunction during embryonic development. XX/XO gynandromorph in Drosophila In conclusion Different types of aneuploidy. The role of nondisjunction in the origin of aneuploids. Consequences of aneuploidy. Open PointSolutions app, join session GTS161 STUDY UNIT 7 CHAPTER 8 Chromosome Variation LECTURE 7.3 Ch 8 p 242 - 250 Polyploidy  STUDY UNIT 7 Chapter 8 Outline Chromosomal mutations Chromosome Polyploidy rearrangements Aneuploidy  LECTURE 7.3 Ch 8 p 242 - 250 Polyploidy LEARNING OBJECTIVES At the end of this lecture, you should be able to: Describe how autopolyploidy arises and why autopolyploids are usually sterile. Describe how allopolyploidy arises and why these are sometimes fertile. 8.4 Polyploidy is the Presence of More Than Two Sets of Chromosomes Most eukaryotic organisms are diploid (2n), possessing two sets of chromosomes. Occasionally whole sets of chromosomes fail to separate in mitosis or meiosis. Polyploidy = organisms with more than two genomic sets of chromosomes. triploids (3n) tetraploids (4n) pentaploids (5n) etc. Polyploids are generally larger than diploid relatives. Larger cells rather than more cells. Increased size → increased commercial value. Triploids (3n) Tetraploids (4n) Octoploids (8n)  Autopolyploidy Extra sets of chromosomes are all derived from a single species. Autotetraploid (4n) can arise through nondisjunction of all chromosomes in mitosis in an early 2n embryo. Autotriploid (3n) can arise through: Nondisjunction in meiosis produces 2n gamete, this fuses with normal haploid n gamete → 3n. Cross between autotetraploid (produces 2n gamete) and diploid (produces n gamete) → 3n. During meiosis in autotriploids (3n) there are three homologs present for every chromosome. This results in abnormal pairing and segregation, producing unbalanced gametes with various numbers of chromosomes. Triploids usually do not produce viable offspring. Autopolyploid crops: bananas, potatoes, peanuts, sweet potatoes. Potential segregation of homologous chromosomes in an autotriploid:  Allopolyploidy Arises from hybridization between related species, followed by chromosome doubling. Original diploid hybrid may be sterile – unable to form viable gametes as some or all of its chromosomes cannot synapse. Chromosome doubling results in fertile allotetraploid, where homologous chromosomes can pair and segregate normally during meiosis, producing balanced gametes and fertile offspring. Allopolyploids carry chromosome sets derived from two or more different species. Allotetraploids are also called amphidiploids. (See Worked Problem on p 245.) Allopolyploidy can result from hybridization between two closely related species, followed by chromosome doubling. E.g. Species 1 x Species 2 Diploid AA BB Gametes A B Diploid (sterile) AB chromosome doubling Allotetraploid (fertile) AABB NB: In this example, A represents genome A with one copy of each type of “a” chromosome B represents genome B with one copy of each type of “b” chromosome Where A has a1; a2; a3; …an chromosomes, and B has b1; b2; b3; …bn chromosomes. The significance of polyploidy: Many polyploids are physically larger than diploids. Used extensively in plant breeding. Asexual reproduction may facilitate development of polyploids. Polyploidy is less common in animals than plants. Allopolyploidy requires interspecific hybridization, less frequent in animals due to animal behaviour & complex development that renders most hybrids nonviable. Polyploidy (usually 3n) found in 10% of all spontaneously aborted human foetuses. Very few human polyploid babies ever reported, die within days of birth. In Achieve – SU 7 Ch 8 – Resources: View Ch 8 Problem-Solving Video: Chromosome Number Variation in Aneuploids and Polyploids Summary SU 7: In conclusion: - Review the Chapter Summary, Pierce p 247-248. - Master the Important Terms, Pierce p 248. - Check the Concept Checks, answers on Pierce p 248. - Go through the Worked Problems, Pierce p 249-250. - Test yourself using the SU 7 Learning Outcomes and Self-Study Activities from the GTS 161 Study Guide.