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Biology for AP® Courses

13.2 Chromosomal Basis of Inherited Disorders

Biology for AP® Courses13.2 Chromosomal Basis of Inherited Disorders
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  1. Preface
  2. Unit 1
    1. 1 The Study of Life
      1. Introduction
      2. 1.1 The Science of Biology
      3. 1.2 Themes and Concepts of Biology
      4. Key Terms
      5. Chapter Summary
      6. Review Questions
      7. Critical Thinking Questions
      8. Test Prep for AP® Courses
    2. 2 The Chemical Foundation of Life
      1. Introduction
      2. 2.1 Atoms, Isotopes, Ions, and Molecules: The Building Blocks
      3. 2.2 Water
      4. 2.3 Carbon
      5. Key Terms
      6. Chapter Summary
      7. Review Questions
      8. Critical Thinking Questions
      9. Test Prep for AP® Courses
      10. Science Practice Challenge Questions
    3. 3 Biological Macromolecules
      1. Introduction
      2. 3.1 Synthesis of Biological Macromolecules
      3. 3.2 Carbohydrates
      4. 3.3 Lipids
      5. 3.4 Proteins
      6. 3.5 Nucleic Acids
      7. Key Terms
      8. Chapter Summary
      9. Review Questions
      10. Critical Thinking Questions
      11. Test Prep for AP® Courses
      12. Science Practice Challenge Questions
  3. Unit 2
    1. 4 Cell Structure
      1. Introduction
      2. 4.1 Studying Cells
      3. 4.2 Prokaryotic Cells
      4. 4.3 Eukaryotic Cells
      5. 4.4 The Endomembrane System and Proteins
      6. 4.5 Cytoskeleton
      7. 4.6 Connections between Cells and Cellular Activities
      8. Key Terms
      9. Chapter Summary
      10. Review Questions
      11. Critical Thinking Questions
      12. Test Prep for AP® Courses
      13. Science Practice Challenge Questions
    2. 5 Structure and Function of Plasma Membranes
      1. Introduction
      2. 5.1 Components and Structure
      3. 5.2 Passive Transport
      4. 5.3 Active Transport
      5. 5.4 Bulk Transport
      6. Key Terms
      7. Chapter Summary
      8. Review Questions
      9. Critical Thinking Questions
      10. Test Prep for AP® Courses
      11. Science Practice Challenge Questions
    3. 6 Metabolism
      1. Introduction
      2. 6.1 Energy and Metabolism
      3. 6.2 Potential, Kinetic, Free, and Activation Energy
      4. 6.3 The Laws of Thermodynamics
      5. 6.4 ATP: Adenosine Triphosphate
      6. 6.5 Enzymes
      7. Key Terms
      8. Chapter Summary
      9. Review Questions
      10. Critical Thinking Questions
      11. Test Prep for AP® Courses
      12. Science Practice Challenge Questions
    4. 7 Cellular Respiration
      1. Introduction
      2. 7.1 Energy in Living Systems
      3. 7.2 Glycolysis
      4. 7.3 Oxidation of Pyruvate and the Citric Acid Cycle
      5. 7.4 Oxidative Phosphorylation
      6. 7.5 Metabolism without Oxygen
      7. 7.6 Connections of Carbohydrate, Protein, and Lipid Metabolic Pathways
      8. 7.7 Regulation of Cellular Respiration
      9. Key Terms
      10. Chapter Summary
      11. Review Questions
      12. Critical Thinking Questions
      13. Test Prep for AP® Courses
      14. Science Practice Challenge Questions
    5. 8 Photosynthesis
      1. Introduction
      2. 8.1 Overview of Photosynthesis
      3. 8.2 The Light-Dependent Reaction of Photosynthesis
      4. 8.3 Using Light to Make Organic Molecules
      5. Key Terms
      6. Chapter Summary
      7. Review Questions
      8. Critical Thinking Questions
      9. Test Prep for AP® Courses
      10. Science Practice Challenge Questions
    6. 9 Cell Communication
      1. Introduction
      2. 9.1 Signaling Molecules and Cellular Receptors
      3. 9.2 Propagation of the Signal
      4. 9.3 Response to the Signal
      5. 9.4 Signaling in Single-Celled Organisms
      6. Key Terms
      7. Chapter Summary
      8. Review Questions
      9. Critical Thinking Questions
      10. Test Prep for AP® Courses
      11. Science Practice Challenge Questions
    7. 10 Cell Reproduction
      1. Introduction
      2. 10.1 Cell Division
      3. 10.2 The Cell Cycle
      4. 10.3 Control of the Cell Cycle
      5. 10.4 Cancer and the Cell Cycle
      6. 10.5 Prokaryotic Cell Division
      7. Key Terms
      8. Chapter Summary
      9. Review Questions
      10. Critical Thinking Questions
      11. Test Prep for AP® Courses
      12. Science Practice Challenge Questions
  4. Unit 3
    1. 11 Meiosis and Sexual Reproduction
      1. Introduction
      2. 11.1 The Process of Meiosis
      3. 11.2 Sexual Reproduction
      4. Key Terms
      5. Chapter Summary
      6. Review Questions
      7. Critical Thinking Questions
      8. Test Prep for AP® Courses
      9. Science Practice Challenge Questions
    2. 12 Mendel's Experiments and Heredity
      1. Introduction
      2. 12.1 Mendel’s Experiments and the Laws of Probability
      3. 12.2 Characteristics and Traits
      4. 12.3 Laws of Inheritance
      5. Key Terms
      6. Chapter Summary
      7. Review Questions
      8. Critical Thinking Questions
      9. Test Prep for AP® Courses
      10. Science Practice Challenge Questions
    3. 13 Modern Understandings of Inheritance
      1. Introduction
      2. 13.1 Chromosomal Theory and Genetic Linkages
      3. 13.2 Chromosomal Basis of Inherited Disorders
      4. Key Terms
      5. Chapter Summary
      6. Review Questions
      7. Critical Thinking Questions
      8. Test Prep for AP® Courses
      9. Science Practice Challenge Questions
    4. 14 DNA Structure and Function
      1. Introduction
      2. 14.1 Historical Basis of Modern Understanding
      3. 14.2 DNA Structure and Sequencing
      4. 14.3 Basics of DNA Replication
      5. 14.4 DNA Replication in Prokaryotes
      6. 14.5 DNA Replication in Eukaryotes
      7. 14.6 DNA Repair
      8. Key Terms
      9. Chapter Summary
      10. Review Questions
      11. Critical Thinking Questions
      12. Test Prep for AP® Courses
      13. Science Practice Challenge Questions
    5. 15 Genes and Proteins
      1. Introduction
      2. 15.1 The Genetic Code
      3. 15.2 Prokaryotic Transcription
      4. 15.3 Eukaryotic Transcription
      5. 15.4 RNA Processing in Eukaryotes
      6. 15.5 Ribosomes and Protein Synthesis
      7. Key Terms
      8. Chapter Summary
      9. Review Questions
      10. Critical Thinking Questions
      11. Test Prep for AP® Courses
      12. Science Practice Challenge Questions
    6. 16 Gene Regulation
      1. Introduction
      2. 16.1 Regulation of Gene Expression
      3. 16.2 Prokaryotic Gene Regulation
      4. 16.3 Eukaryotic Epigenetic Gene Regulation
      5. 16.4 Eukaryotic Transcriptional Gene Regulation
      6. 16.5 Eukaryotic Post-transcriptional Gene Regulation
      7. 16.6 Eukaryotic Translational and Post-translational Gene Regulation
      8. 16.7 Cancer and Gene Regulation
      9. Key Terms
      10. Chapter Summary
      11. Review Questions
      12. Critical Thinking Questions
      13. Test Prep for AP® Courses
      14. Science Practice Challenge Questions
    7. 17 Biotechnology and Genomics
      1. Introduction
      2. 17.1 Biotechnology
      3. 17.2 Mapping Genomes
      4. 17.3 Whole-Genome Sequencing
      5. 17.4 Applying Genomics
      6. 17.5 Genomics and Proteomics
      7. Key Terms
      8. Chapter Summary
      9. Review Questions
      10. Critical Thinking Questions
      11. Test Prep for AP® Courses
      12. Science Practice Challenge Questions
  5. Unit 4
    1. 18 Evolution and Origin of Species
      1. Introduction
      2. 18.1 Understanding Evolution
      3. 18.2 Formation of New Species
      4. 18.3 Reconnection and Rates of Speciation
      5. Key Terms
      6. Chapter Summary
      7. Review Questions
      8. Critical Thinking Questions
      9. Test Prep for AP® Courses
      10. Science Practice Challenge Questions
    2. 19 The Evolution of Populations
      1. Introduction
      2. 19.1 Population Evolution
      3. 19.2 Population Genetics
      4. 19.3 Adaptive Evolution
      5. Key Terms
      6. Chapter Summary
      7. Review Questions
      8. Critical Thinking Questions
      9. Test Prep for AP® Courses
      10. Science Practice Challenge Questions
    3. 20 Phylogenies and the History of Life
      1. Introduction
      2. 20.1 Organizing Life on Earth
      3. 20.2 Determining Evolutionary Relationships
      4. 20.3 Perspectives on the Phylogenetic Tree
      5. Key Terms
      6. Chapter Summary
      7. Review Questions
      8. Critical Thinking Questions
      9. Test Prep for AP® Courses
      10. Science Practice Challenge Questions
  6. Unit 5
    1. 21 Viruses
      1. Introduction
      2. 21.1 Viral Evolution, Morphology, and Classification
      3. 21.2 Virus Infection and Hosts
      4. 21.3 Prevention and Treatment of Viral Infections
      5. 21.4 Other Acellular Entities: Prions and Viroids
      6. Key Terms
      7. Chapter Summary
      8. Review Questions
      9. Critical Thinking Questions
      10. Test Prep for AP® Courses
      11. Science Practice Challenge Questions
    2. 22 Prokaryotes: Bacteria and Archaea
      1. Introduction
      2. 22.1 Prokaryotic Diversity
      3. 22.2 Structure of Prokaryotes
      4. 22.3 Prokaryotic Metabolism
      5. 22.4 Bacterial Diseases in Humans
      6. 22.5 Beneficial Prokaryotes
      7. Key Terms
      8. Chapter Summary
      9. Review Questions
      10. Critical Thinking Questions
      11. Test Prep for AP® Courses
      12. Science Practice Challenge Questions
  7. Unit 6
    1. 23 Plant Form and Physiology
      1. Introduction
      2. 23.1 The Plant Body
      3. 23.2 Stems
      4. 23.3 Roots
      5. 23.4 Leaves
      6. 23.5 Transport of Water and Solutes in Plants
      7. 23.6 Plant Sensory Systems and Responses
      8. Key Terms
      9. Chapter Summary
      10. Review Questions
      11. Critical Thinking Questions
      12. Test Prep for AP® Courses
      13. Science Practice Challenge Questions
  8. Unit 7
    1. 24 The Animal Body: Basic Form and Function
      1. Introduction
      2. 24.1 Animal Form and Function
      3. 24.2 Animal Primary Tissues
      4. 24.3 Homeostasis
      5. Key Terms
      6. Chapter Summary
      7. Review Questions
      8. Critical Thinking Questions
      9. Test Prep for AP® Courses
    2. 25 Animal Nutrition and the Digestive System
      1. Introduction
      2. 25.1 Digestive Systems
      3. 25.2 Nutrition and Energy Production
      4. 25.3 Digestive System Processes
      5. 25.4 Digestive System Regulation
      6. Key Terms
      7. Chapter Summary
      8. Review Questions
      9. Critical Thinking Questions
      10. Test Prep for AP® Courses
      11. Science Practice Challenge Questions
    3. 26 The Nervous System
      1. Introduction
      2. 26.1 Neurons and Glial Cells
      3. 26.2 How Neurons Communicate
      4. 26.3 The Central Nervous System
      5. 26.4 The Peripheral Nervous System
      6. 26.5 Nervous System Disorders
      7. Key Terms
      8. Chapter Summary
      9. Review Questions
      10. Critical Thinking Questions
      11. Test Prep for AP® Courses
      12. Science Practice Challenge Questions
    4. 27 Sensory Systems
      1. Introduction
      2. 27.1 Sensory Processes
      3. 27.2 Somatosensation
      4. 27.3 Taste and Smell
      5. 27.4 Hearing and Vestibular Sensation
      6. 27.5 Vision
      7. Key Terms
      8. Chapter Summary
      9. Review Questions
      10. Critical Thinking Questions
      11. Science Practice Challenge Questions
    5. 28 The Endocrine System
      1. Introduction
      2. 28.1 Types of Hormones
      3. 28.2 How Hormones Work
      4. 28.3 Regulation of Body Processes
      5. 28.4 Regulation of Hormone Production
      6. 28.5 Endocrine Glands
      7. Key Terms
      8. Chapter Summary
      9. Review Questions
      10. Critical Thinking Questions
      11. Test Prep for AP® Courses
      12. Science Practice Challenge Questions
    6. 29 The Musculoskeletal System
      1. Introduction
      2. 29.1 Types of Skeletal Systems
      3. 29.2 Bone
      4. 29.3 Joints and Skeletal Movement
      5. 29.4 Muscle Contraction and Locomotion
      6. Key Terms
      7. Chapter Summary
      8. Review Questions
      9. Critical Thinking Questions
      10. Science Practice Challenge Questions
    7. 30 The Respiratory System
      1. Introduction
      2. 30.1 Systems of Gas Exchange
      3. 30.2 Gas Exchange across Respiratory Surfaces
      4. 30.3 Breathing
      5. 30.4 Transport of Gases in Human Bodily Fluids
      6. Key Terms
      7. Chapter Summary
      8. Review Questions
      9. Critical Thinking Questions
      10. Test Prep for AP® Courses
      11. Science Practice Challenge Questions
    8. 31 The Circulatory System
      1. Introduction
      2. 31.1 Overview of the Circulatory System
      3. 31.2 Components of the Blood
      4. 31.3 Mammalian Heart and Blood Vessels
      5. 31.4 Blood Flow and Blood Pressure Regulation
      6. Key Terms
      7. Chapter Summary
      8. Review Questions
      9. Critical Thinking Questions
      10. Test Prep for AP® Courses
      11. Science Practice Challenge Questions
    9. 32 Osmotic Regulation and Excretion
      1. Introduction
      2. 32.1 Osmoregulation and Osmotic Balance
      3. 32.2 The Kidneys and Osmoregulatory Organs
      4. 32.3 Excretion Systems
      5. 32.4 Nitrogenous Wastes
      6. 32.5 Hormonal Control of Osmoregulatory Functions
      7. Key Terms
      8. Chapter Summary
      9. Review Questions
      10. Critical Thinking Questions
      11. Test Prep for AP® Courses
    10. 33 The Immune System
      1. Introduction
      2. 33.1 Innate Immune Response
      3. 33.2 Adaptive Immune Response
      4. 33.3 Antibodies
      5. 33.4 Disruptions in the Immune System
      6. Key Terms
      7. Chapter Summary
      8. Review Questions
      9. Critical Thinking Questions
      10. Test Prep for AP® Courses
      11. Science Practice Challenge Questions
    11. 34 Animal Reproduction and Development
      1. Introduction
      2. 34.1 Reproduction Methods
      3. 34.2 Fertilization
      4. 34.3 Human Reproductive Anatomy and Gametogenesis
      5. 34.4 Hormonal Control of Human Reproduction
      6. 34.5 Fertilization and Early Embryonic Development
      7. 34.6 Organogenesis and Vertebrate Formation
      8. 34.7 Human Pregnancy and Birth
      9. Key Terms
      10. Chapter Summary
      11. Review Questions
      12. Critical Thinking Questions
      13. Test Prep for AP® Courses
      14. Science Practice Challenge Questions
  9. Unit 8
    1. 35 Ecology and the Biosphere
      1. Introduction
      2. 35.1 The Scope of Ecology
      3. 35.2 Biogeography
      4. 35.3 Terrestrial Biomes
      5. 35.4 Aquatic Biomes
      6. 35.5 Climate and the Effects of Global Climate Change
      7. Key Terms
      8. Chapter Summary
      9. Review Questions
      10. Critical Thinking Questions
      11. Test Prep for AP® Courses
      12. Science Practice Challenge Questions
    2. 36 Population and Community Ecology
      1. Introduction
      2. 36.1 Population Demography
      3. 36.2 Life Histories and Natural Selection
      4. 36.3 Environmental Limits to Population Growth
      5. 36.4 Population Dynamics and Regulation
      6. 36.5 Human Population Growth
      7. 36.6 Community Ecology
      8. 36.7 Behavioral Biology: Proximate and Ultimate Causes of Behavior
      9. Key Terms
      10. Chapter Summary
      11. Review Questions
      12. Critical Thinking Questions
      13. Test Prep for AP® Courses
      14. Science Practice Challenge Questions
    3. 37 Ecosystems
      1. Introduction
      2. 37.1 Ecology for Ecosystems
      3. 37.2 Energy Flow through Ecosystems
      4. 37.3 Biogeochemical Cycles
      5. Key Terms
      6. Chapter Summary
      7. Review Questions
      8. Critical Thinking Questions
      9. Test Prep for AP® Courses
      10. Science Practice Challenge Questions
    4. 38 Conservation Biology and Biodiversity
      1. Introduction
      2. 38.1 The Biodiversity Crisis
      3. 38.2 The Importance of Biodiversity to Human Life
      4. 38.3 Threats to Biodiversity
      5. 38.4 Preserving Biodiversity
      6. Key Terms
      7. Chapter Summary
      8. Review Questions
      9. Critical Thinking Questions
      10. Test Prep for AP® Courses
  10. A | The Periodic Table of Elements
  11. B | Geological Time
  12. C | Measurements and the Metric System
  13. Index

In this section, you will explore the following question:

  • What are the genetic consequences that result from nondisjunction and errors in chromosome structure through inversions and translocations?

Connection for AP® Courses

The number, size, shape, and banding patterns of chromosomes make them easily identifiable in a karyogram and allows for the assessment of many chromosomal abnormalities. Although the cell cycle, mitosis, and meiosis are highly regulated to prevent errors, the processes are not perfect. One example is the failure of homologous chromosomes or sister chromatids to separate properly during meiosis I or meiosis II (a phenomenon referred to as nondisjunction). This results in gametes with too many or too few chromosomes. Disorders in chromosome number (aneuploidy) are typically lethal to the embryo, although a few trisomic genotypes are viable (e.g., Down syndrome). Because of X inactivation, aberrations in sex chromosomes typically have milder phenotypic effects (e.g., Turner syndrome) than aneuploidy. Sometimes segments of chromosome are duplicated, deleted, or rearranged by inversion or translocation. These aberrations can result in problematic phenotypic effects. Diagnostic testing can detect many of these chromosomal disorders in individuals well before birth, resulting in medical, ethical, and civic issues, such as the right to privacy.

A condition in which an organism has more than the normal number of chromosome sets (two for diploid species) is called polyploidy. Polyploidy resulting in odd numbers of chromosomes is rare because it results in sterile organisms. One set of chromosomes has no pair so meiosis cannot proceed normally. In contrast, polyploidy resulting in even chromosome numbers is very common in the plant kingdom. Polyploid plants tend to be larger and more robust than individuals with the normal number of chromosomes.

Information presented and the examples highlighted in the section support concepts outlined in Big Idea 3 of the AP® Biology Curriculum Framework. The Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP® Biology course, an inquiry-based laboratory experience, instructional activities, and AP® exam questions. A Learning Objective merges required content with one or more of the seven Science Practices.

Big Idea 3 Living systems store, retrieve, transmit and respond to information essential to life processes.
Enduring Understanding 3.A Heritable information provides for continuity of life.
Essential Knowledge 3.A.2 In eukaryotes, heritable information is passed to the next generation via processes that include the cell cycle and mitosis or meiosis plus fertilization.
Science Practice 6.2 The student can construct explanations of phenomena based on evidence produced through scientific practices.
Learning Objective 3.9 The student is able to construct an explanation, using visual representations or narratives, as to how DNA in chromosomes is transmitted to the next generation via mitosis, or meiosis followed by fertilization.
Essential Knowledge 3.A.3 The chromosomal basis of inheritance provides an understanding of the pattern of passage (transmission) of genes from parent to offspring.
Science Practice 3.1 The student can pose scientific questions.
Learning Objective 3.13 The student is able to pose questions about ethical, social or medical issues surrounding human genetic disorders.
Big Idea 3 Living systems store, retrieve, transmit and respond to information essential to life processes.
Enduring Understanding 3.C The processing of genetic information is imperfect and is a source of genetic variation.
Essential Knowledge 3.A.3 Changes in genotype can result in changes in phenotype.
Science Practice 6.4 The student can make claims and predictions about natural phenomena based on scientific theories and models.
Science Practice 7.2 The student can connect concepts in and across domain(s) to generalize or extrapolate in and/or across enduring understandings and/or big ideas.
Learning Objective 3.24 The student is able to predict how a change in genotype, when expressed as a phenotype, provides a variation that can be subject to natural selection.

Teacher Support

Introduce karyotyping using this activity, which has students create a karyotype by matching chromosomes, this activity or this activity.

Background information on karyotyping is available at this site.

Some students have difficulties connecting the idea of chromosome structure with inheritance, as discussed in this paper.

Students may therefore have trouble understanding the role of chromosomal abnormalities in inherited disorders. It may help students to review meiosis, using videos such as this.

Inherited disorders can arise when chromosomes behave abnormally during meiosis. Chromosome disorders can be divided into two categories: abnormalities in chromosome number and chromosomal structural rearrangements. Because even small segments of chromosomes can span many genes, chromosomal disorders are characteristically dramatic and often fatal.

Identification of Chromosomes

The isolation and microscopic observation of chromosomes forms the basis of cytogenetics and is the primary method by which clinicians detect chromosomal abnormalities in humans. A karyotype is the number and appearance of chromosomes, and includes their length, banding pattern, and centromere position. To obtain a view of an individual’s karyotype, cytologists photograph the chromosomes and then cut and paste each chromosome into a chart, or karyogram, also known as an ideogram (Figure 13.5).

This is a karyotype of a human female. There are 22 homologous pairs of chromosomes and an X chromosome.
Figure 13.5 This karyotype is of a female human. Notice that homologous chromosomes are the same size, and have the same centromere positions and banding patterns. A human male would have an XY chromosome pair instead of the XX pair shown. (credit: Andreas Blozer et al)

In a given species, chromosomes can be identified by their number, size, centromere position, and banding pattern. In a human karyotype, autosomes or “body chromosomes” (all of the non–sex chromosomes) are generally organized in order of size from largest (chromosome 1) to smallest (chromosome 22). (The X and Y chromosomes, the 23rd pair, are not autosomes.) However, chromosome 21 is actually shorter than chromosome 22. This was discovered after the naming of Down syndrome as trisomy 21, reflecting how this disease results from possessing one extra chromosome 21 (three total). Not wanting to change the name of this disease, scientists retained the original numbering system. The chromosome “arms” projecting from either end of the centromere may be designated as short or long, depending on their relative lengths. The short arm is abbreviated p (for “petite”), whereas the long arm is abbreviated q (because it follows “p” alphabetically). Each arm is further subdivided and denoted by a number. For example, locus 3 on the short arm of chromosome 21 is denoted 21p3. Using this naming system, locations on chromosomes can be described consistently in the scientific literature.

Career Connection

Geneticists Use Karyograms to Identify Chromosomal Aberrations

Although Mendel is referred to as the “father of modern genetics,” he performed his experiments with none of the tools that the geneticists of today routinely employ. One such powerful cytological technique is karyotyping, a method in which traits characterized by chromosomal abnormalities can be identified from a single cell. To observe an individual’s karyotype, a person’s cells (like white blood cells) are first collected from a blood sample or other tissue. In the laboratory, the isolated cells are stimulated to begin actively dividing. A chemical called colchicine is then applied to cells to arrest condensed chromosomes in metaphase. Cells are then made to swell using a hypotonic solution so the chromosomes spread apart. Finally, the sample is preserved in a fixative and applied to a slide.

The geneticist then stains chromosomes with one of several dyes to better visualize the distinct and reproducible banding patterns of each chromosome pair. Following staining, the chromosomes are viewed using bright-field microscopy. A common stain choice is the Giemsa stain. Giemsa staining results in approximately 400–800 bands (of tightly coiled DNA and condensed proteins) arranged along all of the 23 chromosome pairs; an experienced geneticist can identify each band. In addition to the banding patterns, chromosomes are further identified on the basis of size and centromere location. To obtain the classic depiction of the karyotype in which homologous pairs of chromosomes are aligned in numerical order from longest to shortest, the geneticist obtains a digital image, identifies each chromosome, and manually arranges the chromosomes into this pattern (Figure 13.5).

At its most basic, the karyogram may reveal genetic abnormalities in which an individual has too many or too few chromosomes per cell. Examples of this are Down Syndrome, which is identified by a third copy of chromosome 21, and Turner Syndrome, which is characterized by the presence of only one X chromosome in women instead of the normal two. Geneticists can also identify large deletions or insertions of DNA. For instance, Jacobsen Syndrome—which involves distinctive facial features as well as heart and bleeding defects—is identified by a deletion on chromosome 11. Finally, the karyotype can pinpoint translocations, which occur when a segment of genetic material breaks from one chromosome and reattaches to another chromosome or to a different part of the same chromosome.

During Mendel’s lifetime, inheritance was an abstract concept that could only be inferred by performing crosses and observing the traits expressed by offspring. By observing a karyogram, today’s geneticists can actually visualize the chromosomal composition of an individual to confirm or predict genetic abnormalities in offspring, even before birth.

Disorders in Chromosome Number

Of all of the chromosomal disorders, abnormalities in chromosome number are the most obviously identifiable from a karyogram. Disorders of chromosome number include the duplication or loss of entire chromosomes, as well as changes in the number of complete sets of chromosomes. They are caused by nondisjunction, which occurs when pairs of homologous chromosomes or sister chromatids fail to separate during meiosis. Misaligned or incomplete synapsis, or a dysfunction of the spindle apparatus that facilitates chromosome migration, can cause nondisjunction. The risk of nondisjunction occurring increases with the age of the parents.

Nondisjunction can occur during either meiosis I or II, with differing results (Figure 13.6). If homologous chromosomes fail to separate during meiosis I, the result is two gametes that lack that particular chromosome and two gametes with two copies of the chromosome. If sister chromatids fail to separate during meiosis II, the result is one gamete that lacks that chromosome, two normal gametes with one copy of the chromosome, and one gamete with two copies of the chromosome.

Visual Connection

This illustration shows nondisjunction that occurs during meiosis I. Nondisjunction during meiosis I occurs when a homologous pair fails to separate, and results in two gametes with n + 1 chromosomes, and two gametes with n − 1 chromosomes. Nondisjunction during meiosis II would occur when sister chromatids fail to separate, and results in one gamete with n + 1 chromosomes, one gamete with n − 1 chromosomes, and two normal gametes.
Figure 13.6 Nondisjunction occurs when homologous chromosomes or sister chromatids fail to separate during meiosis, resulting in an abnormal chromosome number. Nondisjunction may occur during meiosis I or meiosis II.
Which of the following statements about nondisjunction is true?
  1. Nondisjunction only results in gametes with n+1 or n-1 chromosomes.
  2. Nondisjunction occurring during meiosis II results in 50 % normal gametes.
  3. Nondisjunction during meiosis I results in 50 % normal gametes.
  4. Nondisjunction always results in four different kinds of gametes.

Aneuploidy

An individual with the appropriate number of chromosomes for their species is called euploid; in humans, euploidy corresponds to 22 pairs of autosomes and one pair of sex chromosomes. An individual with an error in chromosome number is described as aneuploid, a term that includes monosomy (loss of one chromosome) or trisomy (gain of an extraneous chromosome). Monosomic human zygotes missing any one copy of an autosome invariably fail to develop to birth because they lack essential genes. This underscores the importance of “gene dosage” in humans. Most autosomal trisomies also fail to develop to birth; however, duplications of some of the smaller chromosomes (13, 15, 18, 21, or 22) can result in offspring that survive for several weeks to many years. Trisomic individuals suffer from a different type of genetic imbalance: an excess in gene dose. Individuals with an extra chromosome may synthesize an abundance of the gene products encoded by that chromosome. This extra dose (150 percent) of specific genes can lead to a number of functional challenges and often precludes development. The most common trisomy among viable births is that of chromosome 21, which corresponds to Down Syndrome. Individuals with this inherited disorder are characterized by short stature and stunted digits, facial distinctions that include a broad skull and large tongue, and significant developmental delays. The incidence of Down syndrome is correlated with maternal age; older women are more likely to become pregnant with fetuses carrying the trisomy 21 genotype (Figure 13.7).

 This graph shows the risk of Down syndrome in the fetus with increasing maternal age. Risk dramatically increases past a maternal age of 35.
Figure 13.7 The incidence of having a fetus with trisomy 21 increases dramatically with maternal age.

Link to Learning

Visualize the addition of a chromosome that leads to Down syndrome in this video simulation.

With increasing age, women are at increased risk of having a baby with a chromosomal abnormality such as Down syndrome. Why is age a risk factor?
  1. Cells are more likely to make mistakes as we age due to an increase in the nondisjunction of cells during cell division, which is the reason for the occurrence of Down syndrome.
  2. The chance of this disorder increases with age due to increased mistakes in the mitotic cells with age.
  3. There are increased risks of translocation mutations with age, even though other mutation rates are constant, and this increases the risk.
  4. The risk of having a child with Down syndrome is associated primarily with lifestyle factors that change with age.

Polyploidy

An individual with more than the correct number of chromosome sets (two for diploid species) is called polyploid. For instance, fertilization of an abnormal diploid egg with a normal haploid sperm would yield a triploid zygote. Polyploid animals are extremely rare, with only a few examples among the flatworms, crustaceans, amphibians, fish, and lizards. Polyploid animals are sterile because meiosis cannot proceed normally and instead produces mostly aneuploid daughter cells that cannot yield viable zygotes. Rarely, polyploid animals can reproduce asexually by haplodiploidy, in which an unfertilized egg divides mitotically to produce offspring. In contrast, polyploidy is very common in the plant kingdom, and polyploid plants tend to be larger and more robust than euploids of their species (Figure 13.8).

 Photo shows an orange daylily
Figure 13.8 As with many polyploid plants, this triploid orange daylily (Hemerocallis fulva) is particularly large and robust, and grows flowers with triple the number of petals of its diploid counterparts. (credit: Steve Karg)

Sex Chromosome Nondisjunction in Humans

Humans display dramatic deleterious effects with autosomal trisomies and monosomies. Therefore, it may seem counterintuitive that human females and males can function normally, despite carrying different numbers of the X chromosome. Rather than a gain or loss of autosomes, variations in the number of sex chromosomes are associated with relatively mild effects. In part, this occurs because of a molecular process called X inactivation. Early in development, when female mammalian embryos consist of just a few thousand cells (relative to trillions in the newborn), one X chromosome in each cell inactivates by tightly condensing into a quiescent (dormant) structure called a Barr body. The chance that an X chromosome (maternally or paternally derived) is inactivated in each cell is random, but once the inactivation occurs, all cells derived from that one will have the same inactive X chromosome or Barr body. By this process, females compensate for their double genetic dose of X chromosome. In so-called “tortoiseshell” cats, embryonic X inactivation is observed as color variegation (Figure 13.9). Females that are heterozygous for an X-linked coat color gene will express one of two different coat colors over different regions of their body, corresponding to whichever X chromosome is inactivated in the embryonic cell progenitor of that region.

 Photo shows a tortoiseshell cat with orange and black fur.
Figure 13.9 In cats, the gene for coat color is located on the X chromosome. In the embryonic development of female cats, one of the two X chromosomes is randomly inactivated in each cell, resulting in a tortoiseshell pattern if the cat has two different alleles for coat color. Male cats, having only one X chromosome, never exhibit a tortoiseshell coat color. (credit: Michael Bodega)

An individual carrying an abnormal number of X chromosomes will inactivate all but one X chromosome in each of her cells. However, even inactivated X chromosomes continue to express a few genes, and X chromosomes must reactivate for the proper maturation of female ovaries. As a result, X-chromosomal abnormalities are typically associated with mild mental and physical defects, as well as sterility. If the X chromosome is absent altogether, the individual will not develop in utero.

Several errors in sex chromosome number have been characterized. Individuals with three X chromosomes, called triplo-X, are phenotypically female but express developmental delays and reduced fertility. The XXY genotype, corresponding to one type of Klinefelter syndrome, corresponds to phenotypically male individuals with small testes, enlarged breasts, and reduced body hair. More complex types of Klinefelter syndrome exist in which the individual has as many as five X chromosomes. In all types, every X chromosome except one undergoes inactivation to compensate for the excess genetic dosage. This can be seen as several Barr bodies in each cell nucleus. Turner syndrome, characterized as an X0 genotype (i.e., only a single sex chromosome), corresponds to a phenotypically female individual with short stature, webbed skin in the neck region, hearing and cardiac impairments, and sterility.

Duplications and Deletions

In addition to the loss or gain of an entire chromosome, a chromosomal segment may be duplicated or lost. Duplications and deletions often produce offspring that survive but exhibit physical and mental abnormalities. Duplicated chromosomal segments may fuse to existing chromosomes or may be free in the nucleus. Cri-du-chat (from the French for “cry of the cat”) is a syndrome associated with nervous system abnormalities and identifiable physical features that result from a deletion of most of 5p (the small arm of chromosome 5) (Figure 13.10). Infants with this genotype emit a characteristic high-pitched cry on which the disorder’s name is based.

 Photos show a boy with cri-du-chat syndrome. In parts a, b, c, and d of the image, he is two, four, nine, and 12 years of age, respectively.
Figure 13.10 This individual with cri-du-chat syndrome is shown at two, four, nine, and 12 years of age. (credit: Paola Cerruti Mainardi)

Chromosomal Structural Rearrangements

Cytologists have characterized numerous structural rearrangements in chromosomes, but chromosome inversions and translocations are the most common. Both are identified during meiosis by the adaptive pairing of rearranged chromosomes with their former homologs to maintain appropriate gene alignment. If the genes carried on two homologs are not oriented correctly, a recombination event could result in the loss of genes from one chromosome and the gain of genes on the other. This would produce aneuploid gametes.

Chromosome Inversions

A chromosome inversion is the detachment, 180° rotation, and reinsertion of part of a chromosome. Inversions may occur in nature as a result of mechanical shear, or from the action of transposable elements (special DNA sequences capable of facilitating the rearrangement of chromosome segments with the help of enzymes that cut and paste DNA sequences). Unless they disrupt a gene sequence, inversions only change the orientation of genes and are likely to have more mild effects than aneuploid errors. However, altered gene orientation can result in functional changes because regulators of gene expression could be moved out of position with respect to their targets, causing aberrant levels of gene products.

An inversion can be pericentric and include the centromere, or paracentric and occur outside of the centromere (Figure 13.11). A pericentric inversion that is asymmetric about the centromere can change the relative lengths of the chromosome arms, making these inversions easily identifiable.

 Illustration shows pericentric and paracentric inversions. In this example, the order of genes in the normal chromosome is ABCDEF, with the centromere between genes C and D. In the pericentric inversion the order is ABDCEF. In the paracentric inversion example, the resulting gene order is ABCDFE.
Figure 13.11 Pericentric inversions include the centromere, and paracentric inversions do not. A pericentric inversion can change the relative lengths of the chromosome arms; a paracentric inversion cannot.

When one homologous chromosome undergoes an inversion but the other does not, the individual is described as an inversion heterozygote. To maintain point-for-point synapsis during meiosis, one homolog must form a loop, and the other homolog must mold around it. Although this topology can ensure that the genes are correctly aligned, it also forces the homologs to stretch and can be associated with regions of imprecise synapsis (Figure 13.12).

 This illustration shows the inversion pairing that occurs when one chromosome undergoes inversion but the other does not. For chromosome alignment to occur during meiosis, one chromosome must form an inverted loop while the other conforms around it.
Figure 13.12 When one chromosome undergoes an inversion but the other does not, one chromosome must form an inverted loop to retain point-for-point interaction during synapsis. This inversion pairing is essential to maintaining gene alignment during meiosis and to allow for recombination.

Evolution Connection

The Chromosome 18 Inversion

Not all structural rearrangements of chromosomes produce nonviable, impaired, or infertile individuals. In rare instances, such a change can result in the evolution of a new species. In fact, a pericentric inversion in chromosome 18 appears to have contributed to the evolution of humans. This inversion is not present in our closest genetic relatives, the chimpanzees. Humans and chimpanzees differ cytogenetically by pericentric inversions on several chromosomes and by the fusion of two separate chromosomes in chimpanzees that correspond to chromosome two in humans.

The pericentric chromosome 18 inversion is believed to have occurred in early humans following their divergence from a common ancestor with chimpanzees approximately five million years ago. Researchers characterizing this inversion have suggested that approximately 19,000 nucleotide bases were duplicated on 18p, and the duplicated region inverted and reinserted on chromosome 18 of an ancestral human.

A comparison of human and chimpanzee genes in the region of this inversion indicates that two genes—ROCK1 and USP14—that are adjacent on chimpanzee chromosome 17 (which corresponds to human chromosome 18) are more distantly positioned on human chromosome 18. This suggests that one of the inversion breakpoints occurred between these two genes. Interestingly, humans and chimpanzees express USP14 at distinct levels in specific cell types, including cortical cells and fibroblasts. Perhaps the chromosome 18 inversion in an ancestral human repositioned specific genes and reset their expression levels in a useful way. Because both ROCK1 and USP14 encode cellular enzymes, a change in their expression could alter cellular function. It is not known how this inversion contributed to hominid evolution, but it appears to be a significant factor in the divergence of humans from other primates.1

According to the passage, which of the following events are believed to have occurred after humans diverged from their common ancestor with chimpanzees?
  1. Paracentric inversions occurred at several chromosomes, including human chromosome 18.
  2. Two separate chromosomes underwent a pericentric inversion, then fused to form chromosome 2 in humans.
  3. 19 , 000 nucleotide bases were duplicated, inverted, and reinserted at human chromosome 18.
  4. The ROCK1 and USP14 genes were duplicated in early humans, which increased expression of these genes.

Translocations

A translocation occurs when a segment of a chromosome dissociates and reattaches to a different, nonhomologous chromosome. Translocations can be benign or have devastating effects depending on how the positions of genes are altered with respect to regulatory sequences. Reciprocal translocations result from the exchange of chromosome segments between two nonhomologous chromosomes such that there is no gain or loss of genetic information (Figure 13.13).

 Illustration shows a reciprocal translocation in which DNA is transferred from one chromosome to another. No genetic information is gained or lost in the process.
Figure 13.13 A reciprocal translocation occurs when a segment of DNA is transferred from one chromosome to another, nonhomologous chromosome. (credit: modification of work by National Human Genome Research/USA)

Science Practice Connection for AP® Courses

Activity

A Day in the Life. Compose a short story, PowerPoint presentation, video, poem, or significant piece of art to describe a day in the life of a teenager afflicted with a single gene disorder or chromosomal abnormality. You need to include the causes and effects of the disorder and pose a question about a social, medical, or ethical issue(s) associated with human genetic disorders.

Think About It

Create a series of representations to show how nondisjunction can result in a trisomic zygote from a cell with 2n = 4.

Teacher Support

The activity is an application of Learning Objective 3.24 and Science Practices 6.4 and 7.2, and Learning Objective 3.13 and Science Practice 3.1 because students are asked to show how a change in a human genotype, either by a single gene mutation or a chromosomal abnormality, can produce a change in phenotype; then students pose a question about an ethical, social, or medical issue surrounding human genetic disorders in general.

The Think About It question is an application of Learning Objective 3.9 and Science Practice 6.2 because students are creating a diagram to explain how errors in meiosis can result in an abnormal zygote following fertilization.

Answer

Nondisjunction occurs when homologous chromosomes or sister chromatids fail to separate during meiosis, resulting in an abnormal chromosome number. Nondisjunction may occur during meiosis I or meiosis II.

Footnotes

  • 1 Violaine Goidts et al., “Segmental duplication associated with the human-specific inversion of chromosome 18: a further example of the impact of segmental duplications on karyotype and genome evolution in primates,” Human Genetics. 115 (2004):116-122
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