9: Changes in Chromosome Number and Structure - Biology

9:  Changes in Chromosome Number and Structure - Biology

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Previous chapters described chromosomes as simple linear DNA molecules on which genes are located. For example, your largest chromosome, chromosome 1, has about 3536 genes. To ensure that each of your cells possesses these genes the chromosome has features that allow it to be passed on during cell division. Origins of replication found along its length provide places for DNA replication to start, telomeres protect each end of the chromosome, and a single centromere near the middle provides a place for microtubules to attach and move the chromosome during mitosis and meiosis. This chapter examines: (1) changes in the number of whole chromosomes and how they affect the phenotype of an organism and (2) changes in the structure of individual chromosomes and how they affect meiotic pairing. Human examples will be used to show the phenotypic consequences and methods for detection.

  • 9.1: Changes in Chromosome Number
    If something goes wrong during cell division, an entire chromosome may be lost and the cell will lack all of these genes. The causes behind these chromosome abnormalites and the consequences they have for the cell and the organism is the subject of this section.
  • 9.2: Changes in Chromosome Structure
    If the chromosome is altered, but still retains the three critical features of a chromosome (centromeres, telomeres, and origin of replication), it will continue to be inherited during subsequent cell divisions, however the daughter cell may not retain all the genes. For example, if a segment of the chromosome has been lost, the cell may be missing some genes. The causes of chromosome structural abnormalites, which involves breaks in the DNA that makes up the chromosome.
  • 9.3: Chromosome Abnormalities in Humans
    To better understand the consequences let's consider those that affect people. As you will recall humans are 2n=46. The convention when describing a person's karyotype (chromosome composition) is to list the total number of chromosomes, then the sex chromosomes, and then anything out of the ordinary. Most of us are 46,XX or 46,XY. What follows are some examples of chromosome number and chromosome structure abnormalities.
  • 9.4: Diagnosing Human Chromosome Abnormalities
    How can we confirm that a person has a specific chromosomal abnormality? The first method was simply to obtain a sample of their cells, stain the chromosomes with Giemsa dye, and examine the results with a light microscope. Each chromosome can be recognized by its length, the location of its centromere, and the characteristic pattern of purple bands produced by the Giemsa.
  • 9.E: Changes in Chromosome Number and Structure (Exercises)
  • 9.S: Changes in Chromosome Number and Structure (Summary)
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Each species of an organism has a specific number of chromosomes in its somatic cells.

These chromosomes are found in pairs. At the time of formation of gametes the chromosome number is reduced.

Hence, the gemetes carry haploid set of chromosomes.

Alterations in the number of chromosomes from the diploid set is called numerical chromosomal aberrations.

It is also known as ploidy. There are two types of ploidy they are euploidy and aneuploidy.


Euploidy is the variation in the chromosome number that occurs due to increase or decrease of full set of chromosomes.

Monoploidy, diploidy and polyploidy are the types in euploidy.


In most of the plants and animals, the somatic cells contain two sets of chromosome.

Diploidy is formed by the union of two gametes during fertilization.


Addition of one or more sets of chromosomes to the diploid set results in polyploidy.

It is commonly noticed in plants and rare in animals.

They are of two kinds – autopolyploidy and allopolyploidy.


Addition of one or more haploid set of its own genome in an organism results in autopolyploidy.

Watermelon, grapes and banana are autotriploids, whereas apple is an autotetraploid.


Increase in one or more haploid set of chromosomes from two different species result in allopolyploidy.

Triticale is the first man made cereal.

It is obtained by crossing a wheat Triticum durum (2n = 4x = 28) and a rye Secale cereale (2n = 2x = 14).

The Fl hybrid (2n = 3x = 21) is sterile.

Then the chromosome number is doubled using colchicine and it becomes an hexaploid.


Variation that involves one or two chromosomes within the diploid set of an organism results in aneuploidy.

It is of two types – hypoploidy and hyperploidy.


Decrease in one or two chromosomes from the diploid set is described as hypoploidy.

There are two types of hypoploidy – monosomy and nullisomy. Monosomy is due to loss of a chromosome from the diploid set

Nullisomy is the condition in which a pair of homologous chromosomes is lost from the diploid set i.e. 2n – 2.


Addition of one or two chromosomes to the diploid set of chromosome results in hyperploidy.

There are two types of hyperploidy – trisomy and tetrasomy.

Trisomy results due to the addition of one chromosome to diploid set of chromosomes.

It is represented by 2n + 1. Trisomics are observed in Datura stramonium.

Tetrasomy results due to the addition of two chromosomes to diploid set of chromosome.

Significance of ploidy

Polyploidy plays an important role in plant breeding and horticulture.

0 Polyploidy has more vigorous effect than the diploids and results in
the production of large sized flowers and fruits.

Hence, it has economical significance.

It plays significant role in the evolution of new species.

Polyploidy results in the changes in the season of flowering and fruiting.

Polyploids are vigorous invaders of new habitats.

It leads to the formation of new varieties which show high resistance to disease and increase in yield.

Tetraploid cabbages and tomatoes contain more ascorbic acid whereas tetraploid corn contains more vitamin A.

Both euploidy and aneuploidy in man cause congenital diseases.

Polyploidy varieties like apple, pear, grape and watermelons are cultivated because of their large size.

Mastering Biology Chapter 17

The central paradigm of biochemistry holds that information flows from DNA to RNA to protein. The process of making protein from the mRNA is called translation. Translation is carried out by the ribosome, which

binds to the mRNA and binds tRNA, which recognizes the codons on the mRNA and brings the appropriate

amino acid with it. The ribosome forms the peptide bond between the new amino acid and the growing peptide

The process of translation, or protein synthesis, is a crucial part of the maintenance of living organisms.

Proteins are constantly in use and will break down eventually, so new ones must always be available. If protein synthesis breaks down or stops, then the organism dies.

DNA polymerase is very accurate and rarely makes a mistake in DNA replication. Occasionally, however, an

error in replication, known as a point mutation, is introduced. There are two general categories of point

mutations—frameshift mutations (also called base-pair insertions or base-pair deletions) and base substitution

mutations (shown in the diagram).

Base substitution mutations and Frameshift mutations

If a segment of DNA were replicated without any errors, the replicated strand would have the following

Sort the following replicated DNA sequences by the type of point mutation each contains (frameshift, base

substitution, or neither), as compared to the correct sequence shown above.

A base substitution mutation can occur if the DNA polymerase inserts the wrong nucleotide base as it

synthesizes a new strand of DNA. A frameshift mutation can occur if the DNA polymerase leaves out a

nucleotide or adds an extra nucleotide to the sequence. Certain forms of cancer occur because of mutations

in DNA sequences that are located in so-called mutational hotspots. These hotspots are locations in the DNA

sequence where mutations occur more often than in other places.

Types of base substitution mutations

When a base substitution mutation occurs, one nucleotide in a replicating DNA sequence is substituted for

another, which results in the production of a mutant strand of DNA. The result of the mutation depends on how

the substituted nucleotide base alters the string of amino acids coded by the mutant DNA.

The three types of base substitution mutations are nonsense mutations, missense mutations, and silent

mutations. Each type is defined by how it affects protein synthesis.

Ribosomes provide the scaffolding on which tRNAs interact with mRNA during translation of an mRNA

sequence to a chain of amino acids. A ribosome has three binding sites, each of which has a distinct function in

the tRNA-mRNA interactions

During translation, new amino acids are added one at a time to the growing polypeptide chain. The addition of

each new amino acid involves three steps:

Binding of the charged tRNA to the A site. This step requires correct base-pairing between the codon on the

mRNA and the anticodon on the tRNA.

Formation of the new peptide bond. In the process, the polypeptide chain is transferred from the tRNA in the P site to the amino acid on the tRNA in the A site.

Movement of the mRNA through the ribosome. In this step, the discharged tRNA shifts to the E site (where

it is released) and the tRNA carrying the growing polypeptide shifts to the P site.

Predicting the effect of a point mutation

The diagram below shows an mRNA molecule that encodes a protein with 202 amino acids. The start and stop

codons are highlighted, and a portion of the nucleotide sequence in the early part of the molecule is shown in

detail. At position 35, a single base-pair substitution in the DNA has changed what would have been a uracil

(U) in the mRNA to an adenine (A).

  1. Based on the genetic code chart above, which of the following would be the result of this single base- pair substitution?
    • a nonsense mutation resulting in early termination of translation
    • The effect of a single base substitution depends on the new codon formed by the substitution. To identify the new codon, it is first necessary to determine the reading frame for the amino acid sequence. The first codon starts with base 1, the second codon with base 4, the third with base 7, and so on.
    • In this problem, the codon that contains the single base substitution begins with base 34. The original codon (UUA, which encodes the amino acid leucine) is converted by the single base substitution to UAA, which is a stop codon. This will cause premature termination of translation, also called a nonsense mutation.

Protein targeting pathways The DNA in a cell’s nucleus encodes proteins that are eventually targeted to every membrane and compartment in the cell, as well as proteins that are targeted for secretion from the cell. For example, consider these two proteins:

 Phosphofructokinase (PFK) is an enzyme that functions in the cytoplasm during glycolysis.  Insulin, a protein that regulates blood sugar levels, is secreted from specialized pancreatic cells.

Assume that you can track the cellular locations of these two proteins from the time that translation is complete until the proteins reach their final destinations. For each protein, identify its targeting pathway: the sequence of cellular locations in which the protein is found from when translation is complete until it reaches its final (functional) destination. (Note that if an organelle is listed in a pathway, not in the membrane that surrounds the organelle.)

Once RNA polymerase II is bound to the promoter region of a gene, transcription of the template strand begins.

 Soon after transcription begins, the 5' end of the RNA transcript is capped by addition of a modified guanine nucleotide.  As transcription continues, introns are spliced out of the RNA transcript.  After transcription ends, a poly-A tail (chain of adenine nucleotides) is added to the 3' end of the RNA transcript.

Only after all these steps have taken place is the mRNA complete and capable of exiting the nucleus. Once in the cytoplasm, the mRNA can participate in translation.

You labeled 5 of 6 targets incorrectly. For target (a), consider that before any modification of the RNA transcript can occur, there must be at least a partially completed RNA transcript to modify.

  1. Which statement is correct concerning the function(s) of the 5’ cap and the 3’ poly(A) tail of eukaryotic mRNAs?
    • Both structures serve as recognition signals for the translational machinery and extend the life span of the mRNA.
    • Experiments have shown that mRNAs with a cap and a tail last longer and produce more proteins when introduced into cells.

 During elongation, the RNA strand is extended in a 5' to 3' direction.

  1. At which site do new aminoacyl tRNAs enter the ribosome during elongation?
    • A-Site
    • This is the site at which new aminoacyl tRNAs that are complementary to the mRNA codon enter the ribosome.
  2. What is meant by translocation?
    • The ribosome slides one codon down the mRNA.
    • Translocation is the process by which the ribosome slides down the mRNA so a new cycle of elongation can begin.
  3. True or false. A tRNA with an anticodon complementary to the stop codon catalyzes the reaction by which translation is terminated.
    • False
    • There are no tRNAs complementary to the three stop codons termination occurs when release factors recognize the stop codon in the A-site and catalyze the release of the polypeptide from the tRNA in the P-site
  1. There should be a strong positive correlation between the rate of protein synthesis and _____.
    • the number of ribosomes
  1. The direction of synthesis of an RNA transcript is _____.
    • 5’  3’
    • Nucleotides are added to the 3' end of RNA.
  1. The wobble hypothesis explains the _____.
  • ability of some tRNAs to read more than one codon Item 11

Chromosomal mutations are changes in the normal structure or number of chromosomes.

 Changes in chromosome structure can result from errors in meiosis or from exposure to radiation or other damaging agents.  Certain changes in chromosome number can result from nondisjunction during either meiosis or mitosis.

If one chromosome pair undergoes nondisjunction in meiosis I, half the gametes will have an extra chromosome (n +1), and half will be missing a chromosome (n – 1). If all chromosome pairs undergo nondisjunction in meiosis I, half the gametes will have twice the normal haploid number of chromosomes (2n), and half will have no chromosomes. If one chromosome undergoes nondisjunction in meiosis II, half the gametes will have the normal haploid number of chromosomes (n), one-quarter will have an extra chromosome (n +1), and one-quarter will be missing a chromosome (n – 1).

If all chromosomes undergo nondisjunction in meiosis II, half the gametes will have the normal haploid number of chromosomes (n), one-quarter will have twice the haploid number (2n), and one-quarter will have no chromosomes.

Trisomy 21 Down syndrome is caused by trisomy 21, the presence of three copies of chromosome 21. The extra copy usually results from nondisjunction during meiosis. In some cases, however, the extra copy results from a translocation of most of chromosome 21 onto chromosome 14. A person who has had such a translocation in his or her gamete-producing cells is a carrier of familial Down syndrome. The carrier is normal because he or she still has two copies of all the essential genes on chromosome 21, despite the translocation. However, the same may not be true for the carrier’s offspring. The diagram shows the six possible gametes that a carrier of familial Down syndrome could produce.

A carrier of familial Down syndrome has two copies of chromosome 21 and a normal phenotype. However, one of those copies has been translocated to another chromosome, often chromosome 14.

Some of the carrier’s gametes will contain both the normal and the translocated chromosome 21. If one of those gametes fuses with a gamete from a person with a normal karyotype, a zygote with trisomy 21 will result.

  1. What is the process called that converts the genetic information stored in DNA to an RNA copy?
    • Transcription
    • DNA is transcribed to give an RNA copy.
  2. Transcription begins at a promoter. What is a promoter?
    • A site in DNA that recruits the RNA Polymerase in order to begin transcription.
    • This is the site where the RNA polymerase must bind to initiate transcription.
  3. What determines which base is to be added to an RNA strand during transcription?
    • Base pairing between the DNA template strand and the RNA nucleotides
    • Transcription involves the formation of an RNA strand that is complementary to the DNA template strand.
  4. Which of the following terms best describes the relationship between the newly synthesized RNA molecule and the DNA template strand?
    • Complementary
    • Because the template strand determines the nucleotides to be added to the RNA strand, using the same complementarity rules of the DNA, they will be complementary to each other.
  5. What happens to RNA polymerase II after it has completed transcription of a gene?
    • It is free to bind to another promoter and begin transcription.
    • The enzyme is free to transcribe other genes in the cell.

We can divide translation, the process of building a polypeptide, into three stages— initiation,

elongation, and termination. Translation is initiated when the small ribosomal subunit binds to the leader at the 5' end of the mRNA molecule. The anticodon of the initiator tRNA binds to the start codon,

AUG. The initiator tRNA always bears the amino acid methionine. Proteins called initiation factors help bring the mRNA, the initiator tRNA, and the small ribosomal subunit together with the large ribosomal

subunit to form an initiation complex. The initiator tRNA sits in the P site on the ribosome.

Elongation of the polypeptide now occurs, with amino acids being added one by one. The codon in the A site of the ribosome pairs with the anticodon of the appropriate tRNA molecule. Part of the ribosome

catalyzes the formation of a peptide bond between the amino acid extending from the P site and the amino acid extending from the A site. The tRNA in the A site now translocates to the P site. The tRNA that was in the P site moves to the E site and exits from the ribosome. Meanwhile, a new tRNA brings its

amino acid to the A site and the process is repeated.

Three special base triplets— UAA, UAG, and UGA— do not code for amino acids, but instead act as stop

codons, which terminate the process of translation. A protein called a release factor binds to the stop codon in the A site. It acts to free the completed polypeptide from the tRNA that is in the P site, and the

translation assembly comes apart. The polypeptide becomes folded, modified, or combined with other polypeptides to form a functional protein.

What enzyme catalyzes the attachment of an amino acid to tRNA?

This enzyme matches a particular tRNA with a particular amino acid.

The tRNA anticodon, GAC, is complementary to the mRNA codon with the sequence _____.

Telomere-to-Telomere Chromosome Assemblies: New Insights Into Genome Biology and Structure

We are entering into an exciting era of genomics where truly complete, high-quality assemblies of human chromosomes are available end-to-end, or from &lsquotelomere-to-telomere&rsquo (T2T). Recently, the Telomere-to-Telomere (T2T) consortium announced our v1.0 assembly that includes more than 150 Mbp of novel sequence compared to GRCh38, achieves near-perfect sequence accuracy, and unlocks the most complex regions of the genome to functional study. This technological advance, crediting the confluence of new assembly methods with long read sequencing technologies, offers a new opportunity to comprehensively the genomic structure and epigenetic organization in the most repeat-dense regions of our chromosomes. In particular, I will focus on the release of initial genetic and epigenetic reference of all human centromeric regions. High-resolution study of the pericentromeric sequence content and organization reveals new satellite families, sites of transposable element insertion, segmental duplications, and pericentromeric gene predictions. Using unique markers (marker-assisted method) to anchor ultra-long nanopore reads to human centromeric regions regions we report hypomethylated dips at every centromeric region, as previously described for the T2TX centromere. These sites are shown to coincide with regions enriched in centromere protein A (CENP-A) and may provide a signature of sites of kinetochore assembly genome-wide.

1. Understand the incomplete nature of the human reference genome, which sequences are missing and how that impacts our understanding for basic/translational research

#136 Summary of Inherited change

1 Meiosis consists of two divisions. The first division, meiosis I , separates the homologous chromosomes, so that each cell now has only one of each pair. The second division, meiosis II, separates the chromatids of each chromosome. Meiotic division therefore produces four cells, each with one complete set of chromosomes.

2 Diploid organisms contain two copies of each gene in each of their cells. In sexual reproduction, gametes are formed containing one copy of each gene. Each off spring receives two copies of each gene, one from each of its parents.

3 The cells produced by meiosis are genetically different from each other and from their parent
cell. This results from independent assortment of the chromosomes as the bivalents line up on the
equator during metaphase I, and also from crossing over between the chromatids of homologous
chromosomes during prophase I.

4 Genetic variation also results from random fertilisation, as gametes containing diff erent varieties
of genes fuse together to form a zygote.

5 An organism’s genetic constitution is its genotype. The observable expression of its genes is its phenotype.

6 Different varieties of a gene are called alleles. Alleles may show dominance, codominance or recessiveness. An organism possessing two identical alleles of a gene is homozygous an organism possessing two different alleles of a gene is heterozygous. If a gene has several diff erent alleles, such as the gene for human blood groups, these are known as multiple alleles.

7 The position of a gene on a particular chromosome is its locus.

8 A gene found on the X chromosome but not on the Y chromosome is known as a sex-linked gene.

9 The genotype of an organism showing dominant characteristics can be determined by looking at the off spring produced when it is crossed with an organism showing recessive characteristics. This is called a test cross.

10 Monohybrid crosses consider the inheritance of one gene. Dihybrid crosses consider the inheritance of two diff erent genes.

11 The χ2 test can be used to find out whether any diff erences between expected results and observed results of a genetic cross are due to chance, or whether the difference is significant.

12 The genotype of an organism gives it the potential to show a particular characteristic. In many cases, the degree to which this characteristic is shown is also affected by the organism’s environment.

13 Mutation can be defined as an unpredictable change in the base sequence in a DNA molecule (gene mutation) or in the structure or number of chromosomes (chromosome mutation). New alleles arise by gene mutation. Gene mutations include base substitutions, deletions or additions. The HbS (sickle cell) allele arose by base substitution. Such mutations may affect the organism’s phenotype.

1. End-of-chapter questions

1. A cell in the process of meiosis was seen to have a spindle with sister chromatids being drawn towards opposite poles of the cell. In what stage of meiosis was the cell? .
A anaphase I
B anaphase II
C metaphase I
D metaphase II

2 All the offspring of a cross between pure-bred red-flowered and pure-bred white-flowered snapdragons were pink.

Two of these pink-flowered plants were interbred. What proportion of the offspring were pink?
A 25%
B 33%
C 50%
D 100%

3 A man has haemophilia. Which statement correctly describes the inheritance of the gene causing his condition?

A He inherited the recessive allele from his mother.
B He inherited the dominant allele from his father.
C He can pass the recessive allele to a son.
D He can pass the dominant allele to a daughter.


Cell culture and drug treatments

Human HeLa cells were maintained in DMEM (Corning) with 10% fetal bovine serum (FBS HyClone) and 1% 100× penicillin/streptomycin (Corning). The cells were incubated at 37°C and 5% CO2 for no more than 30 generations, and were passaged every 2–4 d. Experiments on captured chromosomes used cells that were allowed to recover 1–3 d before capture. Cells were freely cycling and not treated with drugs designed to affect or synchronize the cell cycle.

For epigenetic drug treatments, the cells were plated as above in drug-free DMEM and allowed to recover for ∼8 h, and then treated with 2 mM VPA (Sigma), 50 nM TSA (Sigma), or 2 µM MS (Cayman Chemicals), all dissolved in DMEM. Chromosomes were then captured from the cells (see below) 16–24 h after treatment for VPA and TSA, or 40–48 h for MS treatments.

Fixed IF

Cells were grown in small wells built on coverslips (Fisher) and treated as above. All solutions were diluted with and wash steps performed with PBS (Lonza) at room temperature, unless noted otherwise. Slides were washed, fixed in 4% paraformaldehyde (EMS), washed, permeabilized with 0.10–0.20% Triton X-100 (USBio), incubated in 0.06% Tween 20 (Fisher), washed, and blocked in 10% goat serum (Sigma). The slides were incubated with a primary solution overnight at 4°C. The slides were then washed, incubated in a secondary solution, incubated in Hoechst (Life Tech), washed, and mounted.

Primary and secondary solutions were diluted in 10% goat serum. HDACi treatments were assayed using a 1:400 rabbit anti-H3K9ac (Cell Signaling 9649) primary solution and a 1:500 488-nm anti-rabbit immunoglobulin G (IgG) (Invitrogen A11034) secondary solution. HDMi treatments used 1:100 mouse anti-H3K9me 2,3 (Cell Signaling 5327) with1:1600 rabbit anti-H3K27me 3 (Cell Signaling 9733) primary solution and 1:500 of 488-nm anti-mouse IgG (Invitrogen A11001) with 1:500 of 594-nm anti-rabbit IgG (Invitrogen A11037) secondary solution. Mitotic cells were identified by finding cells that showed compact mitotic chromosomes in the Hoechst channel. The final IF values reported are given by the fluorescence signal to background ratio of the antibody of interest over the Hoechst signal to background ratio. Averages and standard errors are divided by the average untreated values in normalized graphs.

Single chromosome capture: setup and microscopy

Single chromosome capture experiments used an inverted microscope (IX-70 Olympus) with a 60× 1.42 NA oil immersion objective with a 1.5× magnification pullout at room temperature and atmospheric CO2 levels. Experiments were performed in less than 3 h after removal from the incubator to ensure minimum damage to the cells being analyzed.

Prometaphase cells were identified by eye and lysed with 0.05% Triton X-100 in PBS. All other pipettes were filled with PBS. After lysis, the bundle of chromosomes was held with a pipette. One end of a random, loose chromosome was grabbed by the force pipette (WPI TW100F-6), moved from the bundle, and grabbed with the pulling pipette on the other end. The bundle was then removed to isolate the tracked and unbroken chromosome (Figure 1A and Supplemental Figure S1).

Single chromosome capture: force measurement

An easily bendable force pipette and stiff pulling pipette were used for stretching chromosomes. Once captured, the pipettes were moved perpendicular to the chromosome, stretching the chromosome to roughly its native length. The stiff pipette was then moved 6 µm and returned to the starting position at a constant rate of 0.20 µm/s in 0.04 µm steps using a LabVIEW program, while tracking the stiff and force pipette. Figure 1B shows an example stretch-deflection experiment. Deflection of the force pipette multiplied by its calibrated spring constant and divided by the distance between the pipettes (the stretch) was used to obtain the chromosome spring constant. Each chromosome was stretched at least three times to provide an accurate and reproducible measurement of the chromosome spring constant. The chromosome spring constant multiplied by its initial length gave the doubling force. The initial length was given by measuring the distance between the centers of the pipettes in ImageJ and converting the pixels into microns while the chromosome was perpendicular to the pipettes. The chromosome cross-sectional area was estimated as 0.25πd 2 with the chromosome diameter d calculated as the full width at half maximum of an ImageJ line scan.

Single chromosome capture: immunofluorescence

After force measurements, the chromosome was lifted above the glass surface and microsprayed with a primary, secondary, and tertiary solution from a wide bore pipette, moving the chromosome between sprays. The solutions used 50 µl PBS, 36–38 µl USP sterile molecular biology grade water (Corning), 10 µl 5% casein (Sigma), and 2 µl of each antibody. HDACi experiments used a rabbit anti-H3K9ac primary solution and a 488-nm anti-rabbit secondary solution. HDMi experiments used a mouse anti-H3K9me 2,3 and a rabbit anti-H3K27me 3 primary solution and a 488-nm anti-mouse IgG with a 594-nm anti-rabbit IgG secondary solution. The tertiary spray used Hoechst instead of an antibody.

Western blots

Cells were grown in 100-mm dishes and treated as described in Cell culture and treatments. TSA treatments were done at 200 nM. Cells were then harvested in PBS, centrifuged into a pellet, and lysed with RIPA buffer. The solution was then pelleted and the supernatant saved. The solution was then mixed with 2× Laemmli buffer, run on a 4–20% gradient SDS–PAGE gel, transferred to a nitrocellulose sheet, incubated in a primary solution, washed, and incubated in a secondary solution, then imaged.


For fixed immunofluorescence, the reported N refers to the number of technical replicates, that is, the total number of cells analyzed. The N measurements are furthermore from a set of biological replicates, that is, separate cell colonies on separate slides. All interphase-staining results are from data taken from two biological replicates. Mitotic staining for H3K9ac and SMC2 was also obtained using two biological replicates. H3K9me 2,3 and H3K27me 3 data came from four biological replicates. For captured chromosomes, the reported N refers to each individual captured chromosome for both mechanical and immunofluorescence experiments these experiments were from different slides (colonies) of cells and thus are independent biological replicates. Outliers were identified and discarded by using a generalized Studentized deviate test at α = 0.05. All p values were calculated using a t test. All averaged values are reported as average ± SE.

4. The somatic cells of sexually-reproducing eukaryotic organisms are diploid, meaning that they have 2 sets of homologous chromosomes.

The somatic cells of the human body—that is, the cells that aren’t gametes, or sex cells—each have 46 chromosomes. They are diploid cells, which means that those 46 chromosomes are organized into 23 pairs. Diploid is sometimes abbreviated as 2n (where n is the number of different chromosomes).

In humans, 22 out of the 23 chromosome pairs are autosomes, or non-sex chromosomes. These are referred to as homologous pairs because the two chromosomes within the pair are the same size and shape and contain the same genes (with potentially different alleles, which are alternate versions of a gene). The 23rd pair is made up of the sex chromosomes. Typically, people who are biologically male have an XY genotype (an X chromosome and a Y chromosome), and people who are biologically female have an XX genotype (two X chromosomes). The XX pair, but not the XY pair, is considered to be a homologous pair.

The sex cells, or gametes, of sexually-reproducing eukaryotic organisms are haploid (1n), meaning they only have 23 unpaired chromosomes. When a sperm cell fertilizes an egg, the resulting zygote is diploid the combination of the two haploid sex cells is what results in the zygote having the full 46 chromosomes. One chromosome in each pair comes from the mother’s egg cell, and the other comes from the father’s sperm cell.

9: Changes in Chromosome Number and Structure - Biology

19. Chromosomes and Cell Division

In the previous few chapters, we considered reproduction and development. In this chapter, we examine the role of two types of cell division, mitosis and meiosis, in the human life cycle. We consider the physical basis of heredity—the chromosomes—and we consider how the chromosomes are parceled out during mitosis and meiosis. We finish the chapter by examining why it is important for each cell to have the correct number of chromosomes.

Two Types of Cell Division

We begin life as a single cell called a zygote, formed by the union of an egg and a sperm. By adulthood, our bodies consist of trillions of cells. What happened in the intervening years? How did we go from a single cell to the multitude of cells that make up the tissues of a fully functional adult? The answer is cell division, which happened over and over again as we grew. Even in adults, many cells continue to divide for growth and repair of body tissues. With very few exceptions, each of those cells carries the same genetic information as its ancestors. The type of nuclear division that results in identical body cells is called mitosis.

In Chapter 17 you learned that males and females produce specialized reproductive cells called gametes (eggs or sperm). You'll recall that meiosis is a special type of nuclear division that gives rise to gametes. In females, meiosis occurs in the ovaries and produces eggs. In males, meiosis occurs in the testes and produces sperm. Meiosis is important because through it the gametes end up with half the amount of genetic information (half the number of chromosomes) in the original cell. When the nuclei of an egg and sperm unite (fertilization), the chromosome number is restored to that of the original cell. As a result, the number of chromosomes in body cells remains constant from one generation to the next.

· Down syndrome, which results from an error in cell division, is the most frequent inherited cause of mild to moderate retardation.

The roles of mitosis (which produces new body cells) and meiosis (which forms gametes) are summarized in the diagram of the human life cycle in Figure 19.1. You will learn more about both mitosis and meiosis later in this chapter.

FIGURE 19.1. The human life cycle

A chromosome is a tightly coiled combination of a DNA molecule (which contains genetic information for the organism) and specialized proteins called histones. Chromosomes are found in the cell nucleus. The information contained in the DNA molecules in chromosomes directs the development and maintenance of the body. The histones combined with the DNA are for support and control of gene activity. A gene is a specific segment of the DNA that directs the synthesis of a protein, which in turn plays a structural or functional role within the cell. By coding for a specific protein, a gene determines the expression of a particular characteristic, or trait. Each chromosome in a human cell contains a specific assortment of genes. Like beads on a string, genes are arranged in a fixed sequence along the length of specific chromosomes.

In the human body, somatic cells—that is, all cells except for eggs or sperm—have 46 chromosomes. Those 46 chromosomes are actually 23 pairs of chromosomes. One member of each pair came from the mother's egg, and another member of each pair came from the father's sperm. Thus, each cell contains 23 homologous chromosome pairs, a pair being two chromosomes (one from the mother and one from the father) with genes for the same traits. Homologous pairs are called homologues for short. Any cell with two of each kind of chromosome is described as being diploid (annotated as 2n, with n representing the number of each kind of chromosome). In diploid cells, then, genes also occur in pairs. The members of each gene pair are located at the same position on homologous chromosomes.

One of the 23 pairs of chromosomes consists of the sex chromosomes that determine whether a person is male or female. There are two types of sex chromosomes, X and Y. A person who has two X chromosomes is described as XX and is genetically female a person who has an X and a Y chromosome is described as XY and is genetically male. The other 22 pairs of chromosomes are called the autosomes. The autosomes determine the expression of most of a person's inherited characteristics.

In mitosis, one nucleus divides into two daughter nuclei containing the same number and kinds of chromosomes. But mitosis is only one phase during the life of a dividing cell. The entire sequence of events that a cell goes through from its origin in the division of its parent cell through its own division into two daughter cells is called the cell cycle (Figure 19.2). The cell cycle consists of two major phases: interphase and cell division.

FIGURE 19.2. The cell cycle

Interphase is the period of the cell cycle between cell divisions. It accounts for most of the time that elapses during a cell cycle. During active growth and divisions (depending on the type of cell), an entire cell cycle might take about 16 to 24 hours to complete, and only 1 to 2 hours are spent in division. Interphase is not a "resting period," as once thought. Instead, interphase is a time when the cell carries out its functions and grows. If the cell is going to divide, interphase is a time of intense preparation for cell division. During interphase, the DNA and organelles are duplicated. These preparations ensure that when the cell divides, each of its resulting cells, called daughter cells, will receive the essentials for survival.

Interphase consists of three parts: G1 (first "gap"), S (DNA synthesis), and G2 (second "gap"). All three parts of interphase are times of cell growth, characterized by the production of organelles and the synthesis of proteins and other macromolecules. There are, however, some events specific to certain parts of interphase:

• G1: A time of major growth before DNA synthesis begins.

• S: The time during which DNA is synthesized (replicated).

• G2: A time of growth after DNA is synthesized and before mitosis begins.

The details of DNA synthesis (replication) are described in Chapter 21. Our discussion in this chapter introduces some basic terminology pertaining to the cell cycle.

Throughout interphase, the genetic material is in the form of long, thin threads that are often called chromatin (Figure 19.3). They twist randomly around one another like tangled strands of yarn. In this state, DNA can be synthesized (replicated) and genes can be active. At the start of interphase, during G1, each chromosome consists of a DNA molecule and proteins. When the chromosomes are being replicated during the S phase, the chromosome copies remain attached. The two copies, each an exact replicate of the original chromosome, stay attached to one another at a region called the centromere. As long as the replicate copies remain attached, each copy is called a chromatid. The two attached chromatids are genetically identical and are called sister chromatids.

FIGURE 19.3. Changes in chromosome structure because of DNA replication during interphase and preparation for nuclear division in mitosis

Describe the difference in the structure of a chromosome between the start of interphase and at the end of interphase.

At the start of interphase, a chromosome is a single strand of DNA. At the end of interphase, a chromosome consists of two sister chromatids that are replicate copies of the original strand of DNA.

Division of the Nucleus and the Cytoplasm

Body cells divide continually in the developing embryo and fetus. Such division also plays an important role in the growth and repair of body tissues in children. In the adult, specialized cells, such as most nerve cells, lose their ability to divide. Late in G1 of interphase, these cells enter what is called the G0 stage they are carrying out their normal cellular activities but do not divide. Other adult cells, such as liver cells, stop dividing but retain the ability to undergo cell division should the need for tissue repair and replacement arise. Still other cells actively divide throughout life. For example, the ongoing cell division in skin cells in adults serves to replace the enormous numbers of cells worn off each day.

We see, then, that the cell cycle requires precise timing and accuracy. Proteins monitor the environment within the cell to ensure that it is appropriate for cell division and that the DNA has been accurately replicated. Healthy cells will not divide unless these two conditions are met. However, as we will see in Chapter 21a, cancer cells escape this regulation and divide uncontrollably.

The division of body cells (after interphase) consists of two processes that overlap somewhat in time. The first process, division of the nucleus, is called mitosis. The second process is cytokinesis, which is the division of the cytoplasm that occurs toward the end of mitosis (Figure 19.4).

FIGURE 19.4. An overview of mitosis

Mitosis: Creation of Genetically Identical Diploid Body Cells

For the purpose of discussion, mitosis is usually divided into four stages: prophase, metaphase, anaphase, and telophase. The major events of each stage are depicted in Figure 19.5 (pp. 396-397).

• Prophase Mitosis begins with prophase, a time when changes occur in the nucleus as well as the cytoplasm. In the nucleus, the chromatin condenses and forms chromosomes as DNA wraps around histones. The DNA then loops and twists to form a tightly compacted structure (see Figure 19.3). When DNA is in this condensed state, it cannot be replicated, and gene activity is shut down. In this condensed state, the sister chromatids are easier to separate without breaking. At about this time, the nuclear membrane also begins to break down.

FIGURE 19.5. The stages of cell division (mitosis and cytokinesis) captured In light micrographs and depicted in schematic drawings

Outside the nucleus, in the cytoplasm, the mitotic spindle forms. The mitotic spindle is made of microtubules associated with the centrioles (see Chapter 3). During prophase, the centrioles, duplicated during interphase, move away from each other toward opposite ends of the cell.

• Metaphase During the next stage of mitosis, metaphase, the chromosomes attach to the mitotic spindles, forming a line at what is called the equator (center) of the mitotic spindles. This alignment ensures each daughter cell receives one chromatid from each of the 46 chromosomes when the chromosomes separate at the centromere. Thus each daughter cell is a diploid cell that is genetically identical to the parent cell.

• Anaphase Anaphase begins when the sister chromatids of each chromosome begin to separate, splitting at the centromere. Now separate entities, the sister chromatids are considered chromosomes in their own right. The spindle fibers pull the chromosomes toward opposite poles of the cell. By the end of anaphase, equivalent collections of chromosomes are located at the two poles of the cell.

• Telophase During telophase, a nuclear envelope forms around each group of chromosomes at each pole, and the mitotic spindle disassembles. The chromosomes also become more threadlike in appearance.

Cancer cells divide rapidly and without end. One type of drug used in cancer chemotherapy inhibits the formation of spindle fibers. Why can this be an effective anticancer treatment?

Cytokinesis—division of the cytoplasm—begins toward the end of mitosis, sometime during telophase. During this period, a band of microfilaments in the area where the chromosomes originally aligned contracts and forms a furrow, as shown in Figure 19.6. The furrow deepens, eventually pinching the cell in two.

FIGURE 19.6. Cytokinesis is the division of the cytoplasm to form two daughter cells.

What would happen if a cell completed mitosis but did not complete cytokinesis?

As we have seen, a major feature of cell division is the shortening and thickening of the chromosomes. In this state, the chromosomes are visible with a light microscope and can be used for diagnostic purposes, such as when potential parents want to check their own chromosomal makeup for defects. One often-used method takes white blood cells from a blood sample and grows them for a while in a nourishing medium. The culture then is treated with a drug that destroys the mitotic spindle, thus preventing separation of the chromosomes and halting cell division at metaphase. Next the cells are fixed, stained, and photographed so that the images of the chromosomes can be arranged in pairs based on physical characteristics such as location of the centromere and overall length. The chromosomes are numbered from largest to smallest, in an arrangement called a karyotype (Figure 19.7). Karyotypes can be checked for irregularities in number or structure of chromosomes.

FIGURE 19.7. Chromosomes in dividing cells can be examined for defects in number or structure. A karyotype is constructed by arranging the chromosomes from photographs based on size and centromere location.

Meiosis: Creation of Haploid Gametes

We have seen that the somatic cells contain a homologous pair of each type of chromosome, one member of each pair from the father and one member of each pair from the mother. Recall that a cell with homologous pairs of chromosomes is described as being diploid, 2n. The gametes—eggs or sperm—differ from somatic cells in that they are haploid, indicated by n, meaning that they have only one member of each homologous pair of chromosomes. As you read earlier in the chapter, gametes are produced by a type of cell division called meiosis, which is actually two divisions that result in up to four haploid daughter cells. When a sperm fertilizes an egg, a new cell—the zygote—is created. Because the egg and sperm both contribute a set of chromosomes to the zygote, it is diploid. After many mitotic cell divisions, a zygote can eventually develop into a new individual.

Meiosis serves two important functions in sexual reproduction:

• Meiosis keeps the number of chromosomes in a body cell constant from generation to generation.

• Meiosis increases genetic variability in the population.

Meiosis keeps the number of chromosomes in a body cell constant over generations because it creates haploid gametes (sperm and eggs) with only one member of each homologous pair of chromosomes. If gametes were produced by mitosis, they would be diploid each sperm and egg would contain 46 chromosomes instead of 23. Then, if a sperm containing 46 chromosomes fertilized an egg with 46 chromosomes, the zygote would have 92 chromosomes. The zygote of the next generation would have 184 chromosomes, having been formed by an egg and sperm each containing 92 chromosomes. The next generation would have 368 chromosomes in each cell, and the next one 736—and so on. You can see that the chromosome number would quickly become unwieldy and, what is more important, alter the amount of genetic information in each cell. As we will see toward the chapter's end, even one extra copy of a single chromosome usually causes an embryo to die.

Meiosis also increases genetic variability in the population. Later in this chapter we consider the mechanisms by which it accomplishes this increase. Genetic variability is important because it provides the raw material through which natural selection can act, leading to the changes described collectively as evolution. The relationship between genetic variability and evolution is discussed in Chapter 22.

Two Meiotic Cell Divisions: Preparation for Sexual Reproduction

First, let's consider how meiosis keeps the chromosome number constant. The stages in meiosis are summarized in Figure 19.8. Meiosis and mitosis begin the same way. Both are preceded by the same event—the replication of chromosomes. Unlike mitosis, however, meiosis involves two divisions. In the first division, the chromosome number is reduced, because the two homologues of each pair of chromosomes (each replicated into two chromatids attached by a centromere) are separated into two cells so that each cell has one member of each homologous pair of chromosomes. In the second division, the replicated chromatids of each chromosome are separated. We see, then, that meiosis begins with one diploid cell and, two divisions later, produces four haploid cells. The orderly movements of chromosomes during meiosis ensure that each haploid gamete produced contains one member of each homologous pair of chromosomes. Although not shown in the summary figure, each of the two meiotic divisions has four stages similar to those in mitosis: prophase, metaphase, anaphase, and telophase.

FIGURE 19.8. Overview of meiosis. Meiosis reduces the chromosome number from the diploid number to the haploid number. Meiosis involves two cell divisions.

Meiosis I . The first meiotic division—meiosis I—produces two cells, each with 23 chromosomes. Note that the daughter cells do not contain a random assortment of any 23 chromosomes. Instead, each daughter cell contains one member of each homologous pair, with each chromosome consisting of two sister chromatids.

It is important that each daughter cell receive one of each kind of chromosome during meiosis I. If one of the daughter cells had two of chromosome 3 and no chromosome 6, it would not survive. Although there would still be 23 chromosomes present, part of the instructions for the structure and function of the body (chromosome 6) would be missing. The separation of homologous chromosomes occurs reliably during meiosis I because, during prophase I (the I indicates this phase takes place during meiosis I), members of homologous pairs line up next to one another by a phenomenon called synapsis ("bringing together"). For example, the chromosome 1 that was originally from your father would line up with the chromosome 1 originally from your mother. Paternal chromosome 2 would pair with maternal chromosome 2, and so on. During metaphase I, matched homologous pairs become positioned at the midline of the cell and attach to spindle fibers. The pairing of homologous chromosomes helps ensure that the daughter cells will receive one member of each homologous pair. Consider the following analogy. By pairing your socks before putting them in a drawer, you are more likely to put matching socks on your feet than if you randomly pulled out two socks.

Next, during anaphase I, the members of each homologous pair of chromosomes separate, and each homologue moves to opposite ends of the cell. During telophase I, cytokinesis begins, resulting in two daughter cells, each with one member of each chromosome pair. Each chromosome in each daughter cell still consists of two replicated sister chromatids. Telophase I is followed by interkinesis, a brief interphase-like period. Interkinesis differs from mitotic interphase in that there is no replication of DNA during interkinesis.

Meiosis II During the second meiotic division—meiosis II— each chromosome lines up in the center of the cell independently (as occurs in mitosis), and the sister chromatids (attached replicates) making up each chromosome separate. Separation of the sister chromatids occurs in both daughter cells that were produced in meiosis I. This event results in four cells, each containing one of each kind of chromosome. The events of meiosis II are similar to those of mitosis, except that only 23 chromosomes are lining up independently in meiosis II compared with the 46 chromosomes aligning independently in mitosis. Figure 19.9 depicts the events of meiosis. Table 19.1 and Figure 19.10 compare mitosis and meiosis.

FIGURE 19.9. Stages of meiosis

TABLE 19.1. Mitosis and Meiosis Compared

Involves one cell division

Involves two cell divisions

Produces two diploid cells

Produces up to four haploid cells

Occurs only in ovaries and testes during the formation of gametes (egg and sperm)

Results in growth and repair

Results in gamete (egg and sperm) production

No exchange of genetic material

Parts of chromosomes are exchanged in crossing over

Daughter cells are genetically similar

Daughter cells are genetically dissimilar

FIGURE 19.11. Comparison of spermatogenesis and oogenesis. Meiosis results in haploid cells that differentiate into mature gametes. Spermatogenesis produces four sperm cells that are specialized to transport the male’s genetic information to the egg. Oogenesis produces up to three polar bodies and one ovum that is packed with nutrients to nourish the early embryo.

Genetic Variability: Crossing Over and Independent Assortment

At the moment of fertilization, when the nuclei of an egg and a sperm fuse, a new, unique individual is formed. Although certain family characteristics may be passed along, each child bears its own assortment of genetic characteristics (Figure 19.12).

FIGURE 19.12. Each child inherits a unique combination of maternal and paternal genetic characteristics due to the shuffling of chromosomes that occurs during meiosis. This photograph shows Eric and Mary Goodenough with their four sons: Derick, Stephen, David, and John.

Genetic variation arises largely because of the shuffling of maternal and paternal forms of genes during meiosis. One way this mixing occurs is through a process called crossing over, in which corresponding pieces of chromatids of maternal and paternal homologues (nonsister chromatids) are exchanged during synapsis when the homologues are aligned side by side. After crossing over, the affected chromatids have a mixture of DNA from the two parents. Because the homologues align gene by gene during synapsis, the exchanged segments contain genetic information for the same traits. However, because the genes of the mother and those of the father may direct different expressions of the trait—attached or unattached earlobes, for instance—the chromatids affected by crossing over have a new, novel combination of genes. Thus, crossing over increases the genetic variability of gametes (Figure 19.13).

FIGURE 19.13. Crossing over. During synapsis, when the homologous chromosomes of the mother and the father are closely aligned, corresponding segments of nonsister chromatids are exchanged. Each of the affected chromatids has a mixture of maternal and paternal genetic information.

Independent assortment is a second way that meiosis provides for the shuffling of genes between generations (Figure 19.14). Recall that the homologous pairs of chromosomes line up at the equator (midpoint) of the mitotic spindles during metaphase I. However, the orientation of the members of the pair is random with respect to which member is closer to which pole. Thus, like the odds that a flipped coin will come up heads, there is a fifty-fifty chance that a given daughter cell will receive the maternal chromosome from a particular pair. Each of the 23 pairs of chromosomes orients independently during metaphase I. The orientations of all 23 pairs will determine the assortments of maternal and paternal chromosomes in the daughter cells. Thus, each child (other than identical siblings) of the same parents has a unique genetic makeup.

FIGURE 19.14. Independent assortment. The relative positioning of homologous maternal and paternal chromosomes with respect to the poles of the cell is random. The members of each homologous pair orient independently of the other pairs. Notice that with only two homologous pairs, there are four possible combinations of chromosomes in the resulting gametes.

Extra or Missing Chromosomes

Most of the time, meiosis is a precise process that results in the chromosomes being distributed evenly to gametes. But meiosis is not foolproof. A pair of chromosomes or sister chromatids may adhere so tightly to one another that they do not separate during anaphase. As a result, both go to the same daughter cell, and the other daughter cell receives none of this type of chromosome (Figure 19.15). The failure of homologous chromosomes to separate during meiosis I or of sister chromatids to separate during meiosis II is called nondisjunction.

FIGURE 19.15. Nondisjunction is a mistake that occurs during cell division in which homologous chromosomes or sister chromatids fail to separate during anaphase. One of the resulting daughter cells will have three of one type of chromosome, and the other daughter cell will be missing that type of chromosome.

One in every 700 infants is born with three copies of chromosome 21 (trisomy 21), a condition known as Down syndrome. Symptoms of Down syndrome include moderate to severe mental retardation, short stature or shortened body parts due to poor skeletal growth, and characteristic facial features (Figure 19.A). Individuals with Down syndrome typically have a flattened nose, a forward-protruding tongue that forces the mouth open, upward-slanting eyes, and a fold of skin at the inner corner of each eye. Approximately 50% of all infants with Down syndrome have heart defects, and many of them die as a result of this defect. Blockage in the digestive system, especially in the esophagus or small intestine, is also common and may require surgery shortly after birth.

FIGURE 19.A. A person with Down syndrome is moderately to severely mentally retarded and has a characteristic appearance.

The risk of having a baby with Down syndrome increases with the mother's age. A 30-year-old woman is twice as likely to give birth to a child with Down syndrome as is a 20-year-old woman. After age 30, the risk rises dramatically. At age 45, a mother is 45 times as likely to give birth to a Down syndrome infant as is a 20-year-old woman.

Today, people with Down syndrome live longer and with a higher quality life than they did in the past. These improvements are due to better healthcare, more effective teaching approaches, and a greater range of opportunities. Life expectancy is now approaching 60 years in many countries.

Prenatal screening for Down syndrome is common and usually recommended for pregnant women aged over 30 years. Approximately 95% of the “positive” screening tests are wrong. Nonetheless, allwomen who initially test positive for carrying a fetus with Down syndrome are encouraged to undergo more invasive tests and 1% to 2% of the pregnancies tested by these procedures result in miscarriage. As a result, prenatal screening for Down syndrome poses a risk to 700,000 pregnancies each year.

Questions to Consider

Down Syndrome International is encouraging reviews of screening policies and public debate about the acceptance of genetic screening for mental and physical disabilities.

• If you or a loved one were pregnant, would you advocate for prenatal screening for Down syndrome? Why or why not?

• Who should pay for prenatal screening? The person? Health insurer? The government?

• Do you agree that genetic screening for mental and physical disabilities should be recommended?

What happens if nondisjunction creates a gamete with an extra or a missing chromosome and that gamete is then united with a normal gamete during fertilization? The resulting zygote will have an excess or deficit of chromosomes. For instance, if the abnormal gamete has an extra chromosome, the resulting zygote will have three of one type of chromosome and two of the rest. This condition, in which there are three representatives of one chromosome, is called trisomy. If, on the other hand, a gamete that is missing a representative of one type of chromosome joins with a normal gamete during fertilization, the resulting zygote will have only one of that type of chromosome, rather than the normal two chromosomes. The condition in which there is only one representative of a particular chromosome in a cell is called monosomy. The imbalance of chromosome numbers usually causes abnormalities in development. Most of the time, the resulting malformations are severe enough to cause the death of the fetus, which will result in a miscarriage. Indeed, in about 70% of miscarriages, the fetus has an abnormal number of chromosomes.

When a fetus inherits an abnormal number of certain chromosomes—for instance, chromosome 21 or the sex chromosomes—the resulting condition is usually not fatal (see Ethical Issue essay, Trisomy 21). The upset in chromosome balance does, however, cause a specific syndrome. (A syndrome is a group of symptoms that generally occur together.)

Like autosomes, sex chromosomes may fail to separate during anaphase. This error can occur during either egg or sperm formation. A male is chromosomally XY, so when the X and Y separate during anaphase, equal numbers of X-bearing and Y-bearing sperm are produced. However, if nondisjunction of the sex chromosomes occurs during sperm formation, half of the resulting sperm will carry both X and Y chromosomes, whereas the other resulting sperm will not contain any sex chromosome. A female is chromosomally XX, so each of the eggs she produces should contain a single X chromosome. When nondisjunction of sex chromosomes occurs, however, an egg may contain two X chromosomes or none at all. When a gamete with an abnormal number of sex chromosomes is joined with a normal gamete during fertilization, the resulting zygote has an abnormal number of sex chromosomes (Figure 19.16).

FIGURE 19.16. The sex chromosomes may fail to separate during formation of a gamete. Here an egg with an abnormal number of sex chromosomes joins a normal sperm in fertilization the resulting zygote has an abnormal number of sex chromosomes. Imbalances of sex chromosomes upset normal development of reproductive structures.

Turner syndrome occurs in individuals who have only a single X chromosome (XO). Approximately 1 in 5000 female infants is born with Turner syndrome, but this represents only a small percentage of the XO zygotes that are formed. Most of these XO zygotes are lost as miscarriages. A person with Turner syndrome has the external appearance of a female. The only hint of Turner syndrome may be a thick fold of skin on the neck. As she ages, however, she generally is noticeably shorter than her peers. Her chest is wide, and her breasts underdeveloped. In 90% of the women with Turner syndrome, the ovaries are also poorly developed, leading to infertility. Pregnancy may be possible through in vitro fertilization (see Chapter 18), in which a fertilized egg from a donor is implanted in her uterus.

Klinefelter syndrome is observed in males who are XXY. Although the extra X chromosome can be inherited as a result of nondisjunction during either egg or sperm formation, it is twice as likely to come from the egg. Increased maternal age may increase the risk slightly.

Klinefelter syndrome is fairly common. Approximately 1 in 500 to 1 in 1000 of all newborn males is XXY. However, not all XXY males display the symptoms of having an extra X chromosome. In fact, some of them live their lives without ever suspecting that they are XXY. When there are signs that a male has Klinefelter syndrome, they do not usually show up until puberty. During the teenage years, the testes of an XY male gradually increase in size. In contrast, the testes of many XXY males remain small and do not produce an adequate amount of the male sex hormone, testosterone. As a result of the testosterone insufficiency, these males may grow taller than average but remain less muscular. Secondary sex characteristics, such as facial and body hair, may fail to develop fully. The breasts may also develop slightly. The penis is usually of normal size, but the testes may not produce sperm so men with Klinefelter syndrome may be sterile.

Nondisjunction can also result in a female with three X chromosomes (XXX, triple-X syndrome) or a male with two Y chromosomes (XYY, Jacob syndrome, produced when the chromatids of a replicated Y chromosome fail to separate). Most women with triple-X syndrome (XXX) have normal sexual development and are able to conceive children. Some triple-X females have learning disabilities and delayed language skills. Males with two Y chromosomes (XYY) are often taller than normal, and some have slightly lower than normal intelligence.

If you had a son with Klinefelter syndrome, would you want him to have testosterone treatments after puberty?

In this chapter we considered cell division: mitosis, which gives rise to new body cells for growth and repair, and meiosis, which gives rise to the gametes (eggs and sperm). In the next chapter, we consider mitosis further and explore stem cells, which are unspecialized cells that can divide continuously and develop into different tissue types.

Highlighting the Concepts

Two Types of Cell Division (p. 392)

• The human life cycle requires two types of nuclear division— mitosis and meiosis. Mitosis creates cells that are exact copies of the original cell. Mitosis occurs in growth and repair. Meiosis creates cells with half the number of chromosomes as were in the original cell. Gamete production requires meiosis.

Form of Chromosomes (p. 393)

• A chromosome contains DNA and proteins called histones. A gene is a segment of DNA that codes for a protein that plays a structural or functional role in the cell. Genes are arranged along a chromosome in a specific order. Each of the 23 different kinds of chromosomes in human cells contains a specific sequence of genes.

• Somatic cells (all cells except for eggs and sperm) are diploid that is, they contain pairs of chromosomes, one member of each pair from each parent. Homologous chromosomes carry genes for the same traits. In humans, the diploid number of chromosomes is 46—or 23 homologous pairs. One pair of chromosomes, the sex chromosomes, determines gender. Males are XY, and females are XX. The other 22 pairs of chromosomes are called autosomes. Eggs and sperm are haploid they contain only one set of chromosomes.

• The cell cycle consists of two major phases: interphase and cell division. Interphase is the period between cell divisions.

• During interphase, DNA and organelles become replicated in preparation for the cell to divide and produce two identical daughter cells. Somatic cell division consists of mitosis (division of the nucleus) and cytokinesis (division of the cytoplasm).

Mitosis: Creation of Genetically Identical Diploid Body Cells (pp. 394-398)

• In mitosis, the original cell, having replicated its genetic material, distributes it equally between its two daughter cells. There are four stages of mitosis: prophase, metaphase, anaphase, and telophase.

• Cytokinesis, division of the cytoplasm, usually begins sometime during telophase. A band of microfilaments at the midline of the cell contracts and forms a furrow. The furrow deepens and eventually pinches the cell in two.

• A karyotype is an arrangement of chromosomes based on their physical characteristics, such as length and position of the centromere.

Meiosis: Creation of Haploid Gametes (pp. 398-407)

• Meiosis, a special type of nuclear division that occurs in the ovaries or testes, begins with a diploid cell and produces four haploid cells that will become gametes (eggs or sperm).

• Meiosis is important because it halves the number of chromosomes in gametes, thereby keeping the chromosome number constant between generations. When a sperm fertilizes an egg, a diploid cell called a zygote is created. After many successful mitotic divisions, the zygote may develop into a new individual.

• Before meiosis begins, the chromosomes are replicated, and the copies remain attached to one another by centromeres. The attached replicated copies are called sister chromatids.

• There are two cell divisions in meiosis. During the first meiotic division (meiosis I), members of homologous pairs are separated. Thus, the daughter cells contain only one member of each homologous pair (although each chromosome still consists of two replicated sister chromatids). During the second meiotic division (meiosis II), the sister chromatids are separated.

• Genetic recombination during meiosis results in variation among offspring from the same two parents. One cause of genetic recombination is crossing over, in which corresponding segments of DNA are exchanged between maternal and paternal homologues, creating new combinations of genes in the resulting chromatids.

• A second cause of genetic recombination is the independent assortment of maternal and paternal homologues into daughter cells during meiosis I. The orientation of the members of the pair relative to the poles of the cell determines whether a daughter cell will receive the maternal or the paternal chromosome from a given pair. Each pair aligns independently of the others.

• Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate during cell division. It results in an abnormal number of chromosomes in the resulting gametes, and in zygotes created by fertilization involving these gametes, which generally results in death of the fetus. Nondisjunction of chromosome 21 can result in Down syndrome.

1. Explain the relationship between genes and a chromosome. р. 393

2. Define mitosis and cytokinesis. pp. 394-398

3. Why is meiosis important? p. 398

4. Describe the alignment of chromosomes at the midline during meiosis I and meiosis II. Explain the importance of these alignments in creating haploid gametes from diploid cells. pp. 400-403

5. Explain how crossing over and independent assortment result in genetic recombination that causes variability among offspring (aside from identical twins) from the same two parents. pp. 403-404

6. Define nondisjunction. Explain how nondisjunction can result in abnormal numbers of chromosomes in a person. p. 405

7. What causes Down syndrome? What are the usual characteristics of the condition? p. 405

8. The process of mitosis results in

9. DNA is synthesized (replicated) during

10. Crossing over occurs during which stage of meiosis?

11. During meiosis, the processes of _____ and _____ increase genetic diversity.

12. _____ chromosomes carry genes for the same traits.

13. _____ is the pairing of chromosomes during meiosis.

14. The stage of mitosis during which sister chromatids separate is _____.

15. The stage of meiosis during which sister chromatids separate is _____.

Applying the Concepts

1. A cell biologist is studying the cell cycle. She is growing the cells in culture, and they are actively dividing mitotically. One particular cell has half as much DNA as most of the other cells. Which stage of mitosis is this cell in? How do you know?

2. What would happen if the spindle fibers failed to form during mitosis?

3. What condition is indicated by the following karyotype?

Becoming Information Literate

Several genetic disorders are caused by too many or too few chromosomes. Use at least three reliable sources (books, journals, websites) to describe at least one such disorder other than Down syndrome, Turner syndrome, and Klinefelter syndrome. Indicate which chromosomes are extra or missing in the disorder, and note the symptoms of the disorder. List each source you considered, and explain why you chose the three sources you used.

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Chromosome number

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Chromosome number, precise number of chromosomes typical for a given species. In any given asexually reproducing species, the chromosome number is always the same. In sexually reproducing organisms, the number of chromosomes in the body (somatic) cells typically is diploid (2n a pair of each chromosome), twice the haploid (1n) number found in the sex cells, or gametes. The haploid number is produced during meiosis. In some sexually reproducing organisms, individuals may be produced from unfertilized eggs and therefore are haploid an example is a drone (a male bee).

An organism with any multiple of the diploid number of chromosomes is said to be polyploid. Polyploidy is a normal evolutionary strategy among many plant groups but appears to be quite rare in animals. Examples of polyploid plants and animals are the potato (Solanum tuberosum), the African clawed frog (Xenopus laevis), and the plains viscacha rat (Tympanoctomys barrerae also called red vizcacha rat). In most animals, however, any change from the typical chromosome number for a species may be accompanied by changes—sometimes drastic—in the organism. For instance, in humans, fetuses affected by polyploidy often are spontaneously aborted early in pregnancy.

The number of chromosomes does not correlate with the apparent complexity of an animal or a plant: in humans, for example, the diploid number is 2n = 46 (that is, 23 pairs), compared with 2n = 78, or 39 pairs, in the dog and 2n = 36 (18) in the common earthworm. There is an equally great range of numbers among plants.

This article was most recently revised and updated by Kara Rogers, Senior Editor.

For more information about structural changes to chromosomes:

The National Human Genome Research Institute provides a list of questions and answers about chromosome abnormalities, including a glossary of related terms.

Chromosome Disorder Outreach offers a fact sheet on this topic titled Introduction to Chromosomes. This resource includes illustrated explanations of several chromosome abnormalities.

The Centre for Genetics Education provides a fact sheet about chromosome changes.

The University of Leicester's Virtual Genetics Education Center provides an explanation of structural chromosome aberrations.

Your Genome from the Wellcome Genome Campus discusses chromosome disorders, including types of structural abnormalities in chromosomes that are involved in genetic diseases.

For more information about chromosomal disorders:

MedlinePlus provides a medical encyclopedia article about chromosomal mosaicism.

A discussion of how chromosomal abnormalities happen is provided by the National Human Genome Research Institute.

The Centre for Genetics Education offers a fact sheet about changes in chromosome number or size.

Information about chromosomal changes, including changes in the number of chromosomes, is available from EuroGentest.

The University of Leicester's Virtual Genetics Education Center provides an explanation of numerical chromosome aberrations.

Your Genome from the Wellcome Genome Campus discusses chromosome disorders, including how changes in the number of chromosomes cause genetic disorders.

The National Organization for Rare Disorders offers an overview of triploidy.

Watch the video: ΝΟΥΚΛΕΪΚΑΟΞΕΑ1Β Λυκείουpart39 (September 2022).


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