3 - Chromosome Variation

In the first half of Chapter 3, we will consider changes in chromosome structure. These changes in chromosome structure refer to altering the total amount of genetic information on a chromosome (deletions, duplications), rearranging the order of genes on a chromosome (inversions), or moving genes from one chromosome to a nonhomologous chromosome (translocations). In the second half of Chapter 3, we will consider situations in which the number of chromosomes within an individual varies (variations in euploidy and aneuploidy). 

A. Changes in Chromosome Structure

Overview

We learned in Chapter 1 that most structural genes are unique DNA sequences, found as a single copy on a particular chromosome.  However, since we have two copies of each chromosome (one copy of the homologous chromosome pair is inherited from dad; the other member of the pair is inherited from mom), each structural gene is actually present in two copies per genome. Changes to this general rule include the following (see Figure 3.1):

• Deletions. A deletion occurs when a portion of a chromosome is missing. A deletion can be as small as a single base pair or can include the loss of several structural genes. The portion of the chromosome that is missing is called a deficiency.  Instead of two copies of a structural gene, a person who suffers a deletion often has a single copy of one or several structural genes per genome.
• Duplications. A duplication occurs when a portion of the chromosome is repeated. In a duplication, a single chromosome can have two copies of the same structural gene. As a result, the genome now contains three copies of of one or several structural genes.

Mutations can also move structural genes from their normal location to a new location in the genome.  The mutations that alter the location of a gene include:

• Inversions. Inversions involve changing the direction of structural genes within a single chromosome.  Even though an inversion changes the location of a structural gene within an individual chromosome, the genome still contains two copies of the structural gene.
• Translocations. A translocation occurs when a portion of a chromosome becomes attached to a nonhomologous chromosome. For example, a portion of chromosome 1 can be translocated to chromosome 5. Like inversions, the genome still contains two copies of a particular structural gene; however, one copy of the gene is now located on a nonhomologous chromosome.  There are three types of translocations:
  • Simple (nonreciprocal) translocation. A simple translocation occurs when a segment of one chromosome becomes attached to a nonhomologous chromosome. The chromosome receiving the DNA segment remains intact.
  • Reciprocal translocation. Reciprocal translocations involve nonhomologous chromosomes exchanging pieces.  For example, one copy of chromosome 1 and one copy of chromosome 5 could exchange the majority of the p arm. 
  • Robertsonian translocation. Robertsonian translocations involve the fusion of the long (q) arms of two acrocentric chromosomes.  For example, the q arm of chromosome 14 could fuse with the q arm of chromosome 21.  The p arms of chromosomes 14 and 21 are lost (see below).

Deletions

Deletions occur when one or more DNA breaks lead to the loss of a portion of a chromosome (see Figure 3.2).  For example, a single break in a chromosome results in a DNA fragment that contains a centromere and a DNA fragment that lacks a centromere. The centromere fragment is retained by the cell, while the DNA fragment that lacks the centromere is lost during cell division. This type of event is a terminal deletion. Terminal deletions are usually generated by endonuclease damage or by environmental factors, such as ionizing radiation, that break the DNA backbone.  Alternatively, an interstitial deletion occurs within the interior of the chromosome and does not involve the telomere.  Interstitial deletions are typically generated by defects in meiosis, specifically defects in homologous chromosome alignment during meiosis I (i.e., synapsis), followed by crossing over (see below).

Cri-du-chat

In general, the larger the deletion (i.e., the more structural genes involved), the more negative the phenotypic consequences. Moreover, a detrimental phenotype often occurs even though the individual has a normal copy of the homologous chromosome, indicating that most deletions behave as dominant mutations.

Cri-du-chat (46, 5p-) is an example genetic disease caused by a deletion in the p arm of chromosome 5.  Cri-du-chat occurs in 1 in 25,000–50,000 live births and is not usually inherited.  Instead, the disease is caused by the loss of the p arm of chromosome 5 during meiosis (see Figure 3.3). A cri-du-chat individual usually has one normal copy of chromosome 5 and a terminal deletion copy of the same chromosome. The deletion in chromosome 5 can be quite small or can encompass much of the p arm; however, it is thought that the absence of a specific structural gene causes cri-du-chat.  This missing structural gene encodes a portion of the telomerase protein called TERT; we will learn about the function of TERT in Chapter 6.  The cri-du-chat individual displays mental deficiencies, facial abnormalities, gastrointestinal defects, and cardiac complications. Those afflicted also tend to vocalize using a catlike cry, due to defects in the formation of the glottis and larynx.

Duplications

A duplication produces two copies of the same structural gene on a single chromosome.  Since the homologous chromosome contributes another copy of the same structural gene, a person with a duplication has three copies of a particular structural gene, instead of two copies. As the region of the chromosome that is duplicated gets larger, the phenotypic effect on the individual becomes increasingly severe. One example disease caused by a duplication is the neuropathic disease Charcot-Marie-Tooth disease type 1A (CMT type 1A), produced by a duplication on chromosome 17.

Duplications and interstitial deletions (see above) are often produced simultaneously by the misalignment of synapsed homologous chromosomes during meiosis, followed by unequal crossing over (see figure 3.4). Unequal crossing over produces four gametes; one gamete contains an interstitial deletion chromosome; a second gamete contains a chromosome with a duplication.  The final two gametes contain contain chromosomes with the normal gene arrangement.   

Duplications Produce Gene Families

Small duplications can sometimes be beneficial and are important in the formation of gene families.  Gene families are closely related genes that have similar DNA sequences and similar but not identical functions. For example, the globin gene family in humans is thought to have been formed by multiple duplications from a single ancestral globin gene (see figure 3.5). To form the globin gene family, the ancestral globin gene was duplicated to produce two identical structural genes on the same chromosome. These two structural genes then accumulated mutations independently over the course of thousands of generations to become specialized; one gene became the hemoglobin gene, the other became the myoglobin gene. Later, the hemoglobin gene duplicated additional times followed by divergence through the continued accumulation of mutations. The current globin gene family, consisting of fourteen structural genes, includes genes that encode the protein subunits of hemoglobin, which is specialized to carry oxygen in the bloodstream, and the protein subunits of myoglobin, which carries oxygen within muscles. The globin gene family is a good example of how gene duplication can produce the genetic variability needed to drive evolutionary change.

Types of Inversions

Inversions involve the rearrangement of structural genes along a single chromosome.  An inversion can be thought of as breaking the chromosome in two places, flipping the DNA between the break points, and resealing the DNA breaks. The total amount of genetic material (i.e., the number of structural genes) along the chromosome is unchanged. Interestingly, inversions are quite common; about 2% of the human population carry detectable inversions.

There are two types of inversions (see Figure 3.6):

• Pericentric inversion. In a pericentric inversion, one chromosome break occurs in the p arm, while a second break occurs in q arm of the same chromosome.  The central region of the chromosome, including the centromere, is then inverted. Note that a pericentric inversion has the potential to change the position of the centromere within the chromosome.
• Paracentric inversion. In a paracentric inversion, two chromosome breaks occur within the same arm of the chromosome.  The chromosome region between the two breaks is inverted, with the centromere of the chromosome lying outside of the inverted region. As a result, a paracentric inversion does not change the position of the centromere within the chromosome.

Most inversions have no phenotypic consequences; however, if one of the chromosome breaks occurs within a structural gene, then a change in phenotype can occur. For example, in type A hemophilia, the breakpoint of an inversion within the X chromosome occurs in the factor VIII gene. Since the encoded Factor VIII protein is required for proper blood clotting, this inversion leads to a deficiency in blood clotting (i.e., hemophilia).  

Further, altering the position of a structural gene along a chromosome can alter the function of nearby genes. This alteration of gene function by an inversion is called a position effect. In some cases, the position effect results in the overexpression of genes that regulate the cell cycle, resulting in cancer.

Crossing Over in Inversion Heterozygotes

An inversion heterozygote is an individual who has a chromosome with a normal structural gene arrangement, while the homologous chromosome contains an inversion. Even though an inversion heterozygote individual has a normal phenotype, they produce unusual gametes during meiosis. Recall that prior to meiosis, the two chromosomes within a homologous chromosome pair are copied by DNA replication, producing four sister chromatids (see Figure 3.7).  DNA replication is followed by synapsis (alignment) of the homologous chromosome pair during meiosis I. For the normal chromosome and the inversion chromosome to synapse properly, one of the two chromosomes twists to form an inversion loop. After the inversion loop is formed, crossing over occurs between the homologous chromosome pair to exchange genetic material. Once crossing over is concluded, abnormal chromosomes are distributed to gamete cells.

• Pericentric inversion.  In a pericentric inversion, the centromere lies within the inverted region of the chromosome (see above). When crossing over occurs between the homologous chromosomes and after meiosis is completed, the following gametes are produced:
  • A gamete that contains a chromosome with the normal structural gene arrangement. This gamete produces offspring with the normal gene arrangement and phenotype.
  • A gamete that contains an inversion chromosome. Thus, inversion chromosomes are passed from parents to offspring. The resulting offspring will not suffer negative phenotypic effects.
  • Two gametes contain abnormal chromosomes. Each gamete contains a chromosome with a duplication of some structural genes and a deletion of other structural genes. The embryo produced from either of these two gametes is not generally viable.

• Paracentric inversion. In a paracentric inversion, the centromere lies outside of the inverted region of the chromosome. After crossing over between the homologous chromosomes occurs and meiosis is completed, the following gametes are produced (see Figure 3.8):
  • A gamete that contains a chromosome with the normal structural gene arrangement. This gamete will produce offspring with a normal phenotype.
  • A gamete that contains an inversion chromosome. The inversion chromosome is inherited, passed from parents to offspring. The resulting offspring will suffer no negative phenotypic consequences.
  • Two gametes that contain highly unusual chromosomes. One gamete contains an abnormal chromosome containing duplications and deletions, but more importantly, the chromosome lacks a centromere. This acentric fragment will be lost during cell division. The other gamete will contain an abnormal chromosome that has two centromeres (dicentric chromosome) along with duplications and deletions. Between the two centromeres of this dicentric chromosome is a DNA region called a dicentric bridge. When a dicentric chromosome, attached to opposite spindle poles, tries to separate during anaphase of meiosis, it is torn apart. Breakage produces chromosome fragments that are missing structural genes.  These two gametes do not typically produce viable embryos after fertilization.

Importantly, 50% of the gametes produced by either pericentric or paracentric inversion heterozygotes fail to produce viable offspring. Thus, even though the inversion does not affect the individual's phenotype directly, the inversion causes a 50% reduction in fertility.

Reciprocal Translocations

A translocation occurs when a chromosome fragment becomes attached to a nonhomologous chromosome. As mentioned earlier, there are three types of translocations: simple, reciprocal, and Robertsonian.  We will focus primarily on reciprocal and Robertsonian translocations in this chapter.  Reciprocal translocations involve nonhomologous chromosomes exchanging pieces.  Reciprocal translocations are formed by two general mechanisms (see Figure 3.9):

• Chromosome breakage and defective DNA repair. Some chemicals or environmental agents cause chromosomes to break at internal sites, forming chromosome ends not protected by telomeres. Recall that telomeres are the structures found on the ends of linear eukaryotic chromosomes that are designed to prevent chromosome ends from sticking together (see Chapter 1). Cells contain repair enzymes to handle these situations, and in most cases, quickly repair these breaks. However, when nonhomologous chromosomes are broken simultaneously, the repair enzymes can sometimes inadvertently join nonhomologous chromosomes together, resulting in a reciprocal translocation.
• Nonhomologous chromosomes experience crossing over. If two nonhomologous chromosomes accidently synapse and undergo crossing over during meiosis I, a reciprocal translocation occurs.

Meiosis in Cells with Reciprocal Translocations

How do nonhomologous chromosomes that have experienced a reciprocal translocation synapse and then segregate into gametes during meiosis?  During synapsis, the two pairs of homologous chromosomes (four chromosomes total), including the two individual chromosomes that have suffered a reciprocal translocation, attempt to synapse.  Because of the reciprocal translocation, the four chromosomes synapse to form a translocation cross (see Figure 3.10).  For example, suppose a translocation cross is produced from a normal copy of chromosome 5, a normal copy of chromosome 13, and copies of chromosomes 5 and 13 that have suffered a reciprocal translocation. Prior to meiosis, these four chromosomes are copied by DNA replication to produce eight sister chromatids. In order to synapse properly, the normal copy of chromosomes 5 and 13 end up diagonal from each other in the translocation cross, while the two translocation chromosomes are diagonal from each other (see Figure 3.10). The chromosomes in the translocation cross then segregate during anaphase I in three possible ways:

• Alternate segregation (common). The chromosomes diagonal from each other segregate into the same cells at the conclusion of meiosis I. For example, the normal copies of chromosomes 5 and 13 segregate with each other into the same daughter cell while the two translocation chromosomes segregate with each other into the same daughter cell. After meiosis II, there are two normal gametes and two gametes that carry translocations. Because none of these gametes are missing structural genes, all four gametes produced by alternate segregation are capable of producing viable offspring.
• Adjacent-1 segregation (common). The two chromosomes on the bottom half of the translocation cross (normal chromosome 13 and translocation chromosome 5) segregate with each other into the same daughter cell. The two chromosomes on the top half of the cross (normal chromosome 5 and translocation chromosome 13) also segregate with each other into the same daughter cell at the conclusion of meiosis I. After meiosis II, all four gametes carry duplications and deletions and therefore do not produce viable offspring.
• Adjacent-2 segregation (rare). The two chromosomes on the left half of the translocation cross (normal chromosome 5 and translocation chromosome 5) segregate with each other into the same daughter cell, while the two chromosomes on the right half of the translocation cross (normal chromosome 13 and translocation chromosome 13) segregate into the same daughter cell at the conclusion of meiosis I. One daughter cell receives, in essence, both copies of chromosome 5; the other daughter cell receives both copies of chromosome 13. Since both copies of chromosome 5 end up in the same cell and both copies of chromosome 13 end up in the same cell, adjacent-2 segregation is considered a nondisjunction event (see below). After meiosis II, all four gametes carry duplications and deletions and do not produce viable offspring.

Robertsonian Translocations

A rare form of Down syndrome called familial Down syndrome is inherited (see Figure 3.11). In familial Down syndrome, a phenotypically normal parent carries a translocation chromosome. This carrier parent has normal copies of chromosomes 14 and 21 and a chromosome that contains a fusion between the long (q) arms of chromosome 14 and 21. In this balanced carrier person, the short (p) arms of chromosome 14 and 21 have been lost, but since these regions carry repetitive DNA sequences that are found on other acrocentric chromosomes (see Chapter 1), the individual can tolerate the loss of the two p arms. This type of translocation, involving the fusion of the long arms of two acrocentric chromosomes, is a Robertsonian translocation. The Robertsonian translocation, which involves only human chromosomes 13, 14, 15, 21, and 22 (i.e., the five acrocentric chromosomes), is the most common chromosome abnormality in humans.

A problem occurs during meiosis in an individual that carries the Robertsonian translocation. In this balanced carrier, the normal chromosome 14, normal chromosome 21, and the Robertsonian translocation chromosome replicate to produce sister chromatids, synapse, and attempt to segregate into gametes during meiosis. There are six possible types of offspring that can be produced by the carrier individual:

• Normal.  The carrier parent can produce a gamete that contains normal copies of chromosomes 14 and 21.  When this normal gamete fuses with a normal gamete from the other parent during fertilization, an offspring is produced that contains two copies of chromosomes 14 and 21. This offspring is phenotypically normal.
• Balanced carrier. The carrier parent can produce a gamete containing the Robertsonian translocation chromosome.  When this gamete fuses with a normal gamete from the other parent during fertilization, a carrier offspring is produced containing one copy of chromosome 14, one copy of chromosome 21, and a Robertsonian translocation chromosome. The total chromosome number in this person is 45 (humans typically have 46 chromosomes) due to the loss of the short arms of chromosomes 14 and 21. This carrier is phenotypically normal but can produce familial Down syndrome offspring in the next generation.
• Familial Down syndrome. The carrier parent can produce a gamete that contains the Robertsonian translocation chromosome and a copy of chromosome 21.  When this gamete fuses with a normal gamete from the other parent during fertilization, the offspring contains two copies of chromosome 21, one copy of chromosome 14, and the Robertsonian translocation chromosome. Since there are three copies of the long arm of chromosome 21 (trisomy 21), Down syndrome results. Interestingly, a familial Down syndrome patient has 46 total chromosomes, like a normal individual.  Conversely, conventional Down syndrome patients (see below) have 47 total chromosomes.
• Unbalanced, lethal (three types of gametes). Fifty percent of the gametes produced by a balanced carrier parent will not produce viable offspring. The resulting offspring produced from these gametes are either missing chromosome 14 (monosomy 14), missing chromosome 21 (monosomy 21), or have three copies of the long arm of chromosome 14 (trisomy 14).

B. Changes in Chromosome Number

Euploidy and Aneuploidy

Sometimes the total number of chromosomes within individuals can vary. These variations in chromosome number are placed into two categories (see Figure 3.12):

• Variations in euploidy.  Variations in euploidy involve changes in the total number of chromosome sets in a cell or individual. Recall that a chromosome set is all of the chromosomes inherited from one parent (i.e. humans contain two chromosome sets total; each set contains 23 individual chromosomes).  Variations in euploidy involves organisms or cells that are:
  • Haploid (n; n = the number of chromosomes within a set). Haploid organisms or cells have one chromosome set (i.e., one copy of every chromosome). Haploid is the normal state for gamete cells and some eukaryotic organisms, such as yeast.
  • Diploid (2n). Diploid organisms or cells have two chromosome sets. One chromosome set is inherited from the paternal parent; one chromosome set is inherited from the maternal parent.  Diploid is the normal state for many eukaryotic organisms and for most of the cells in the human body.
  • Triploid (3n). Triploid organisms or cells have three chromosome sets. Triploid is an abnormal state for most organisms; however, there are examples of triploid plants.  For example, seedless watermelon and banana plants are triploid.
  • Polyploid. Polyploid organisms or cells have more than two chromosome sets.
• Aneuploidy. Aneuploidy involves changes to the number of chromosomes within a chromosome set. For example, aneuploidy occurs when an individual is missing or has an extra chromosome within a set. Interestingly, aneuploidy of the sex chromosomes is usually better tolerated than aneuploidy of the autosomes (non-sex chromosomes) in many organisms.  Aneuploid conditions include:
  • Trisomy (2n+1). A trisomic organism or cell has one more chromosome than normal. The conventional form of Down syndrome is an example trisomic human condition (see below).
  • Monosomy (2n-1). A monosomic organism or cell is missing a single chromosome.  Turner syndrome is an example monosomic human condition (see below).
  • Disomy (2n). Disomy is a normal state in which an organism or cell has two copies of a particular chromosome.
  • Nullisomy (2n-2). An organism or cell that is nullisomic is missing both copies of the chromosomes that constitute a homologous chromosome pair.

Aneuploidy and Gene Expression

A phenotypically normal cell has two copies of most structural genes. When the number of structural genes is out of balance, the phenotype of the cell is often affected in a negative way.  For example, in trisomic cells with three copies of a particular chromosome, the amount of protein produced from structural genes is 150% of the normal expression level. These cells produce too much protein product, so the phenotype is negatively affected (see Figure 3.12).  In the case of monosomy, the single copy of the chromosome can only produce protein products at 50% of the normal level. Since these cells produce lower amounts of protein product, the phenotype is negatively affected. Monosomic cells also have a second problem. In monosomic cells, recessive lethal alleles cannot be “masked” by the normal, dominant allele from the homologous chromosome. In a trisomic or monosomic animal, the overproduction or underproduction of protein product decreases viability.  However, it is worth noting that there are many natural varieties of plants that tolerate higher variations in euploidy.  For example, wheat plants are hexaploid, some potato varieties are tetraploid, and wild strawberry plants can be octaploid.  

Aneuploidy in Humans

About 30% of all fertilization events in humans produces an embryo that is aneuploid. In most cases, the embryo does not survive to birth. That being said, there are some aneuploid human conditions that result in live births.  These aneuploid conditions in humans include:

• Trisomy 13 (47,13+). Trisomy 13 produces Patau syndrome, which occurs in 1 in 19,000 births. Patau syndrome causes mental and motor deficiencies, cleft palate, polydactyly (extra digits), microcephaly (a small head), defects in several organs, and an early death (usually by 3 months of age).
• Trisomy 18 (47, 18+). Trisomy 18 produces Edwards syndrome, which occurs in 1 in 8,000 births. Edwards syndrome causes skeletal abnormalities such as elongated skulls, deformed hips, and facial deformities. Most infants with this syndrome are females, and death usually occurs within 4 months after birth.
• Trisomy 21 (47, 21+). Trisomy 21 causes the conventional form of Down syndrome, which occurs in 1 in 800 births. Down syndrome results in mental deficiencies, almond-shaped eyes, flattened faces, round heads, and a short stature. As described earlier, there is another type of Down syndrome called familial (inherited) Down syndrome. Familial Down syndrome is caused by a Robertsonian translocation (described above).
• XXY (47, XXY). An individual with XXY sex chromosomes has Klinefelter syndrome, which occurs in 1 in 1000 male offspring. Klinefelter syndrome results in infertility (no sperm production) and the formation of breast tissue.  Klinefelter syndrome patients produce a single Barr body per cell.
• XYY (47, XYY). An individual with XYY sex chromosomes has Jacobs syndrome, which occurs in 1 in 1000 male offspring. Jacobs syndrome produces mild phenotypic effects.
• XXX (47, XXX). An individual with XXX sex chromosomes has Triplo-X syndrome, which occurs in 1 in 1500 female offspring. Triplo-X syndrome produces mild phenotypic effects.  Triplo-X syndrome patients have two Barr bodies in each cell.
• XO (45, X). An individual with a single X chromosome has Turner syndrome, which occurs in 1 in 5000 female offspring. Turner syndrome females are short, have a webbed neck, and have reduced fertility.  Turner syndrome patients do not produce Barr bodies.

The aneuploid conditions described above are the result of chromosome nondisjunction, a defect in chromosome segregation during meiosis (see below) in one of the two parents.

Endopolyploidy

Some tissues contain cells that have more than two chromosome sets, whereas the other somatic cells are diploid. This situation is called endopolyploidy. For example, human liver cells can vary in euploidy (some cells are tetraploid or octaploid). Endopolyploidy allows liver cells to increase the production of protein products to meet the unique metabolic demands placed on liver cells.  Moreover, the fruit fly Drosophila is a diploid organism containing four pairs of homologous chromosomes. However, the salivary glands of the fruit fly contain higher variations in euploidy. Endopolyploidy results when the homologous chromosomes pair with each other and then undergo several rounds of DNA replication without cell division. In fruit flies, DNA replication in this way produces polytene chromosomes, a thick bundle of identical DNA molecules, lying parallel to each other.

Meiotic Nondisjunction

Nondisjunction occurs when chromosomes do not separate properly in either meiosis or mitosis.  Meiotic nondisjunction produces aneuploid gamete cells that either have an extra chromosome or lack a chromosome (see Figure 3.13). After fertilization, the resulting offspring will be either trisomic or monosomic. Meiotic nondisjunction can occur during anaphase of either meiosis I or meiosis II.

• Meiosis I nondisjunction. During meiosis I nondisjunction, the chromosomes within a homologous pair fail to separate from each other and instead segregate into the same daughter cell. All gamete cells produced from meiosis I nondisjunction are aneuploid. These aneuploid gametes will produce 50% trisomic offspring and 50% monosomic offspring.
• Meiosis II nondisjunction. In meiosis II nondisjunction, meiosis I proceeds normally; however, nondisjunction occurs in one of the two daughter cells. During meiosis II nondisjunction, the sister chromatids that constitute one duplicated chromosome fail to separate from each other. Two of the resulting haploid gametes are normal, while two of the gametes are aneuploid. Collectively, the four possible gametes will produce 50% normal offspring, 25% trisomic offspring, and 25% monosomic offspring.

The aneuploid human conditions described above (e.g., conventional Down syndrome, Klinefelter syndrome, Turner syndrome, etc.) are thought to be produced from either meiosis I or meiosis II nondisjunction.

Mitotic Nondisjunction

Nondisjunction can also occur during mitosis (mitotic nondisjunction). During mitotic nondisjunction, the sister chromatids that constitute one duplicated chromosome fail to separate from each other during anaphase. Mitotic nondisjunction produces one daughter cell with three copies of a particular chromosome (trisomic), while the other daughter cell has one copy of the chromosome (monosomic) (see Figure 3.14; left panel). All future daughter cells produced from the trisomic cell will also be trisomic, whereas all daughter cells produced from the monosomic cell will be monosomic. As a result, mitotic nondisjunction produces a mosaic phenotype with some trisomic cells in the body, while other cells are monosomic.

A mosaic phenotype can also occur when a chromosome loses attachment to the mitotic spindle during anaphase (see Figure 3.14; right panel).  A detached chromosome often fails to be retained in the nucleus when the nuclear membrane reforms after mitosis, and is degraded by nucleases in the cytoplasm. This event produces one daughter cell with two copies of a particular chromosome (disomic), while the other daughter cell has one copy of the chromosome (monosomic). All future daughter cells produced from the monosomic cell will be monosomic. 

Review Questions

Fill in the Blanks:

1. A _________________________ is a change in chromosome structure that produces an acentric fragment and a dicentric chromosome during meiosis.
2. The disease ______________________ is caused by an inversion within the X chromosome, while __________________________ is a disease produced by a duplication.
3. A(n) __________________ and a(n) _____________________ are two changes in chromosome structure that alter the amount of genetic information found on a chromosome.
4. ___________ % of the gametes produced by a meiosis II nondisjunction event produce trisomic offspring, while ____________  % of the gametes produced by a meiosis I nondisjunction event produce trisomic offspring.
5. A terminal deletion in chromosome _________ causes ___________________, a disease that results in a malformation of the glottis and larynx.
6. Nondisjunction in _____________ can produce trisomic and monosomic somatic cells.
7. The term _______________ describes a cell with 2n-2 chromosomes.
8. The globin gene family arose due to a __________________________ (name the chromosome mutation type).
9. A ____________________ translocation involves only the acrocentric chromosomes.
10. Reciprocal translocations that separate via the __________________ segregation pattern produces two normal gametes and two translocation gametes.  All offspring produced from this event are normal.