Chapter 6: Mosaicism

Page 1 of 10

Formatted: Centered, No bullets or numbering

Solution Manual for Genetics and Genomics for
Nursing 1st Edition by Kenner Lewis ISBN 0132174073
9780132174077
Formatted: Centered
Full download link at:
Solution manual: https://testbankpack.com/p/solution-manual-for-genetics-
and-genomics-for-nursing-1st-edition-by-kenner-lewis-isbn-0132174073-
9780132174077/
Test bank: https://testbankpack.com/p/test-bank-for-genetics-and-genomics-
for-nursing-1st-edition-by-kenner-lewis-isbn-0132174073-9780132174077/

Chapter 6
Mosaicism

Objectives:
1. Explore the basics of chromosomes to clarify the definition of mosaicism.

2. Discuss the theoretical concepts of the development of mosaicism.

3. Describe and define chromosomal mosaicism.

4. Explain the ways mosaicism can occur.

5. Review the implications of mosaicism in pregnancy.

I. CHROMOSOMAL BASICS
A. Definitions
1. Eukaryote cells – contain long strands of DNA that encode an individual’s genetic
information

©2013 by Pearson Education, Inc.

Kenner/Lewis, Instructor’s Resource Manual for Genetics and Genomics for Nursing, 1st Edition
Chapter 6: Mosaicism
Page 2 of 10

2. Nucleotides – contain alternating patterns of four bases: adenine, cytosine,

tyrosine, and guanine
3. Replication – process of linking structures to create DNA while RNA is created
through transcription
4. Genotype – determined at the gene level as long stretches of DNA
a) Repeatedly coiled in complex ways to facilitate packing into a chromosome
b) Nucleosomes – small spheres of histone proteins
(1) Resemble small beads
5. Histones – special class of protein contained within the nucleic acid mixture
a) Assist in making the chromosome more compact so it can properly fit in the
nucleus and provide structural support
b) Regulate the transcription of the DNA that makes up the chromosome by
virtue of their presence and absence
(1) When present areas of chromosome are transcribed
(2) When absent areas of chromosome are not transcribed
B. Structure
1. Chromosome contains a single long DNA molecule with only a portion
corresponding to a single gene
a) Gene – working subunit of DNA
2. Mitochondria – energy center of cells
a) Contains DNA but in one long string of genes, not arranged as chromosomes
3. Allele – alternative forms or versions of genes
a) One allele is inherited for each autosomal gene from each parent
b) Categorized as normal or wild alleles and abnormal or mutant alleles
4. Locus – where on a chromosome a specific gene is – physical location
C. RNA – single strand, ribose and a phosphate backbone
1. Structurally similar to DNA – same bases as DNA except uracil replaces tyrosine
2. Performs tasks via messenger RNA (mRNA) – nucleic acid information molecule
that transcribes codes from the genome into proteins by the process of translation
a) Codon – trinucleotide sequence of DNA or RNA that corresponds to a specific
amino acid

©2013 by Pearson Education, Inc.

Kenner/Lewis, Instructor’s Resource Manual for Genetics and Genomics for Nursing, 1st Edition
Chapter 6: Mosaicism
Page 3 of 10

(1) Describes the relationship between the sequence of DNA bases in a

gene and the corresponding protein sequence
(2) 64 different codons
(a) 61 specify amino acids
(b) Other 3 are stop signals
3. Transfer RNA (tRNA) – nonprotein-encoding molecule that physically carries
amino acids to the translation site and facilitates their assembly into proteins
4. Endoplasmic reticulum - network of membranes in the cell through which the
different forms of RNA act and is essentially the protein generating factory of the
cell
D. DNA replication
1. Molecule that can be almost perfectly copied with the use of enzymes called DNA
polymerases
2. 3 billion base pairs to be replicated
a) Replication of a single human cell can take several hours
(1)Flow of information goes DNA to RNA to proteins
E. Emerging Evidence
1. Cell-free fetal DNA in the plasma of pregnant women has led to a feasible way of
diagnosing fetal genetic disorders prenatally in a noninvasive way
2. Approximately 98%of invasive diagnostic procedures could be avoided if pooled
maternal plasma DNA sequencing analysis is used to rule out fetal trisomy 21
among high risk pregnancies
F. Changes in Chromosome Number
1. Diploid – have 23 pairs of chromosomes for a total of 46 in each cell
2. Haploid – human sex cells, contain a single set of chromosomes
3. Meosis – critical transition period that allows the reduction of chromosomes from
diploid to haploid
a) Creates eggs or sperm
b) Haploid cells have the duplicated identical nuclei of each parent; during
reproduction and fertilization
(1) Form a zygote – reconstituted diploid cell of newly combined
genetic material
4. Chromosomes are numbers 1–22 from largest to smallest – 2 sex chromosomes (X
and Y)
©2013 by Pearson Education, Inc.
Kenner/Lewis, Instructor’s Resource Manual for Genetics and Genomics for Nursing, 1st Edition
Chapter 6: Mosaicism
Page 4 of 10

a) Centromere – single constriction point

(1) Separates the chromosome into the long (p) and short (q) arms
(2) Very tightly coiled DNA
(3) Used as a reference point in cytogenetics to distinguish the
appearance of the chromosome structure for genetic testing
5. Marker – DNA sequence with a known physical location on a chromosome
a) Comes from a variety of sources
b) Single Nucleotide Polymorphism – a single variation of DNA sequence
c) Insight into linking an inherited disease with the responsible genes
d) Track the inheritance of a nearby gene that has not yet been identified but
whose approximate location is known
(1) Haplotypes – sets of closely linked genes or DNA polymorphisms
inherited as a unit
6. Structural Changes
a) Translocation – Involves a break in one particular chromosome that then fuses
to a different chromosome to create a fusion product or gene fusion
(1) Balanced if no genetic material is gained or lost in the cell
(2) Unbalanced if there is a gain or loss of genetic material
(a) Inversion – Involves the same chromosome
(3) Percentric inversion – Involves the centromere
(4) Paracentric inversion – Occurs in the long or short arms of the
chromosome
b) Deletion – Loss of genetic material
(1) Involving a single missing DNA base pair, or involving part of a
gene, or even larger involving an entire chromosome
(2) Can affect behavior, looks, deformities
c) Duplication – more than one copy of a specific stretch of DNA or of a gene or
a region of a chromosome
(1) Important mechanism involved with evolution
(2) Isochromosome – two identical arms
(a) extra copies of some genes and are missing copies of others
(3) Dicentric chromosomes – contain two centromere
©2013 by Pearson Education, Inc.
Kenner/Lewis, Instructor’s Resource Manual for Genetics and Genomics for Nursing, 1st Edition
Chapter 6: Mosaicism
Page 5 of 10

(a) Unstable
(4) Ring chromosomes – chromosome breaks in two places and the
ends of the chromosome arms fuse together to form a circular structure
(a) genetic material near the ends of the chromosome is lost

II. ANEUPLOIDY FORMATIONS

A. Meiotic Stages
1. Reduction division stage
a) Division in which the chromosome number is reduced from diploid to haploid
b) Two strands of a chromosome pair may physically accomplish crossing over
(1) Crossing Over
(a) Strands may break apart at the crossover point and reconnect to the
other chromosome
(b) Recombination results in a new arrangement of maternal and paternal
alleles on the same chromosome
(c) Ensure variation in the gametes
(2) Nondisjunction
(a) Mistake that occurs during the sorting of chromosomes for the
production of a sperm or egg
(b) Meiosis I – error occurs when the homologous pairs both migrate into
the same daughter cell
(c) Meiosis II – error occurs when the sister chromatids will not separate
and thus migrate into the same daughter cell
(d) Cause is unknown
(e) Maternal age a factor
2. Trisomy zygote
a) Zygote receives three different chromosomes because the egg contributed both
a maternal copy and a paternal copy of homologous chromosomes

III. CHROMOSOMAL MOSAICISM

A. Anaphase lag
1. One chromosome simply fails to get incorporated into the nucleus of a daughter
cell

©2013 by Pearson Education, Inc.

Kenner/Lewis, Instructor’s Resource Manual for Genetics and Genomics for Nursing, 1st Edition
Chapter 6: Mosaicism
Page 6 of 10

2. Most common mechanism for trisomy mosaicism formation

B. Trisomy mosaicism
1. Somatic origin
a) Linked with lower levels of trisomy in the body
2. Meiotic origin
a) Higher levels of trisomy
C. Trisomic rescue
1. Occurs early in the post-zygotic divisions
2. Abnormal chromosomal content will be decreased
D. Mitoic nondisjunction and meiotic nondisjunction
1. Timing important
E. Mosaic – Factors
1. Number of cells present at the time of the nondisjunction mistake
a) Very early in either meiosis or mitosis
b) It will affect a greater quantity of cells in the developing embryo
2. Type of cells affected
a) Change in the number of chromosomes
(1) If the duplicated chromosome contains genetic instructions
3. Survival of trisomic cells
a) Trisomic cells usually divide less quickly and undergo cell death more
commonly than diploid cells
b) Particular chromosome involved plays a role in the survival of the cells so that
the abnormal trisomic cells are prevented from reproducing
c) Minimizes or eliminates the effect of the original nondisjunction error

IV. FACTORS AFFECTING CLINICAL PRESENTATION OF

CHROMOSOMAL MOSAICISM
A. Chorionic villus sampling (CVS)
1. Analyzing the chromosomes in the placenta
B. Amniocentesis
1. The analysis of fetal cells present in the amniotic fluid
©2013 by Pearson Education, Inc.
Kenner/Lewis, Instructor’s Resource Manual for Genetics and Genomics for Nursing, 1st Edition
Chapter 6: Mosaicism
Page 7 of 10

2. Unlikely an outcome can be predicted with either

C. Confined Placental Mosaicism
1. Placenta will be mosaic (i.e., contain two distinct cell lines) despite an entirely
euploid fetal karyotype
2. 1–2% of pregnancies
3. Occurs via two mechanisms
a) Mitotic nondisjunction occurring in the early development of the zygote
b) Meiotic error occurs during gametogenesis resulting in a trisomic zygote
(1) Usually results in a miscarriage

D. Clinical Outcomes
1. Dependent on the specific chromosome and the number of trisomic cells in the
fetus and the placenta
2. Inconstant
a) Individual who is mosaic for trisomy 21 may have the chromosomal change in
60% of skin cells and in only 5% of blood cells
b) Accurate determination of the proportion of trisomic cells present is virtually
impossible to determine in a living person
E. High resolution ultrasounds
1. Used to determine fetal morphology, nuchal translucency, and growth and
development
F. Uniparental disomy (UPD)
1. An individual inherits two copies of a chromosome pair from one parent and no
copy from the other parent
a) Mechanisms
(1) The loss of a chromosome from a trisomic zygote
(2) Possible duplication of a chromosome from a monosomic zygote
(3) Fertilization of a gamete with two copies of a chromosome by a
gamete with no copies of the same chromosome
(a) Gamete complementation
2. Associated with the type of confined placental mosaicism, the chromosome
involved, and the origin of the trisomy (mitotic or meiotic)

©2013 by Pearson Education, Inc.

Kenner/Lewis, Instructor’s Resource Manual for Genetics and Genomics for Nursing, 1st Edition
Chapter 6: Mosaicism
Page 8 of 10

G. Imprinting
1. Some genes are only expressed when inherited from the father while others are
only expressed when inherited from the mother

V. IMPLICATIONS OF MOSAICISM IN PREGNANCY

A. Statistics on percentage of pregnancy losses or stillbirths are
continuously changing
1. Estimated that genetic changes are responsible for 50% to 70% of spontaneous
abortions
a) Most Common abnormalities
(1) Autosomal trisomies (60%)
(2) Monosomy X (20%)
(3) Polyploidy (20%)
2. Rate of anomalies does decrease with increasing gestational age
a) Chromosomal abnormalities do exist in at least 6% to 12% of stillbirths at or
beyond 20 weeks
b) Anembryonic specimens
(1) 90% with approximately 50% at 8 to 11 weeks’ gestation, and
around 30% at 16 to 19 weeks’ gestation
3. Two-thirds of malformed embryos and one-third of malformed fetuses have
abnormal chromosomes
B. Factors that influence the rate of chromosomal abnormalities
1. Gestational age
2. Presence of malformations
3. Fetus that is small for the gestational age
4. Maternal age
C. Pregnancy Implications
1. Determination of a more precise recurrent risk assessment for a couple
2. No increased risk of recurrence with a 45X karyotype

VI. SUMMARY
A. Essential to having an understanding of the formation of trisomies
and trisomy mosaicism
©2013 by Pearson Education, Inc.
Kenner/Lewis, Instructor’s Resource Manual for Genetics and Genomics for Nursing, 1st Edition
Chapter 6: Mosaicism
Page 9 of 10

B. Essential that a health care provider possesses insight into

understanding the formation of trisomies in order to provide
appropriate counseling for the pregnant woman
C. Trisomic mosaicism can be confined to the placenta without affecting
the fetus and is believed to occur in approximately 1% to 2% of
pregnancies
D. Uniparental disomy is related to trisomy by virtue of two consecutive
mistakes involving either meiotic or mitotic nondisjunctions and is
significant for the potential expression of autosomal recessive genes

ACTIVITIES
Classroom
As a class explore the differences between somatic mosaicism and gonodal mosaicism.
Discuss how genetic mosaics may be useful to study biological systems.

Small Group
Assign each group a mosaicism disorder and create a plan of care if the patient becomes
hospitalized.

Individual
Direct the students to the Medical New Today (MNT) website at
http://www.medicalnewstoday.com/articles/245326.php. Have each student read the article
“Genetic Mosaicism Linked to Aging and Cancer” by Catharine Paddock. Rate the article for
Patients/Public and Health Professionals found at the end of the article.

©2013 by Pearson Education, Inc.

Kenner/Lewis, Instructor’s Resource Manual for Genetics and Genomics for Nursing, 1st Edition
Chapter 6: Mosaicism
Page 10 of 10

©2013 by Pearson Education, Inc.

Kenner/Lewis, Instructor’s Resource Manual for Genetics and Genomics for Nursing, 1st Edition