Chapter 6: Mosaicism

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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

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Chapter 6: Mosaicism
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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

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Chapter 6: Mosaicism
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(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)
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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
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Chapter 6: Mosaicism
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(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

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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
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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)

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Chapter 6: Mosaicism
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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
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Chapter 6: Mosaicism
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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.

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Chapter 6: Mosaicism
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Kenner/Lewis, Instructor’s Resource Manual for Genetics and Genomics for Nursing, 1st Edition
Another random document with
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 Cooler for a Developing Tray

Water-Jacketed Tray for Use in Cooling a Developing Tray with a Flow of

Water

Regardless of the fact that tank development for photography is

the better method under most conditions, there are many who take
special delight in tray development, because they enjoy seeing the
picture as it develops on the plate or film.
There are many of this class of photographers both among
amateurs and professionals, and they universally experience much
trouble in keeping the solutions cool enough for good work in hot
weather or a warm dark room. Many schemes have been used, but
there is none simpler than that shown in the illustration. It is certainly
better than letting the developing tray float in the bathtub, a common
practice among amateurs who are compelled to use the bathroom as
a dark room.
Any tinsmith can make a water-jacketed tray of zinc at a nominal
price. If one expects to use it for developing films by hand, it should
be made relatively deep, or at least shaped so that whatever method
is used in manipulating the film will be suited to the size and shape
of the tray. I had one made of zinc to accommodate an 8 by 10-in.
plate and providing about ¹⁄₄-in. space all around the sides and
bottom of the inner tray for the circulation of the water.
Two brass gas tips were soldered into the ends of the tray and a
rubber tube was attached to one of them, as shown. By connecting
this tray to the bathroom hydrant the developing solution can be kept
as cool as desired without slopping water where it is not wanted.—
Contributed by T. B. Lambert, Chicago, Ill.
Doorbell Push Button on Screen Door
 Method of Connecting a Push Button for a Doorbell on a Screen Door

Push buttons are frequently put in hallways, or other places, not

accessible when the screen doors are hooked shut. By connecting
an extra button on the screen door with the regular doorbell line, the
service can be made to go on uninterrupted whether the screen be
locked or open.
To do this, one wire, carefully insulated, from the outside button is
laid under the upper molding strip of the screen, as shown, coming
out through the hinge and passing down to the battery line, being
concealed in any suitable manner, by molding or within the door
frame. The button circuit is completed by connecting it to the screen
with a short wire, the screen then acting as a conductor. If preferred,
the line may be run down under the screen-door molding, and out
through the bottom hinge same as with the other wire at the top. If
the screen is used as conductor, a piece of wire should be
connected to it near the bottom, and led through the hinge as before.
In either case, after leaving the hinge, the wire must be led and
connected to the battery line, to complete the circuit. It is then
possible to operate the bell either from outside of the screen door or
at the regular place within.—Contributed by E. M. Davis,
Philadelphia, Pa.
 Working Wood by the Application of Heat
It is often desirable to fit a piece of wood into a piece of metal by
means of cutting a thread in the metal and screwing the wood
therein. This can be accomplished by heating the metal to a little
over the boiling point of water and screwing the wood piece into the
metal while hot; or, if this is impractical on account of size, to heat
the metal, make a screw plate by cutting a thread in a small piece of
metal, the size and thread corresponding to the hole into which the
wood piece is to be inserted, and heating it to the required
temperature, then running the wood with some pressure through the
thread. The wood then can be screwed into the larger piece, where it
will hold firmly.
The process of heating wood without the aid of steam can be used
to advantage in a number of ways; for instance, a hammer handle
that is crooked can be straightened by careful heating without
burning; also billiard cues, or almost anything of hard wood. It is
surprising how easily it is done and how permanent the repair will be.
The Indians at one time made their arrows from small hardwood
twigs which were almost always crooked to start with, but after being
dried they were warmed over a fire and straightened.
Another use for the application of heat is as follows: When it is
desired to place a screw in a fragile piece of wood that is likely to
split, if the screw is heated to a blue color and turned into the wood
while hot, there will be scarcely any danger of splitting. In this case
do not try to use oil or a lubricant of any kind, as the screw is sure to
set before it is in place.—Contributed by James H. Beebee,
Rochester, N. Y.
 A Parlor Table

Detail of the Parlor Table, Together with Dimensions of the Pieces

The material required for the parlor table illustrated is as follows:

1 table top, 1 by 26 by 41 in.
1 bottom shelf, 1 by 15 by 35 in.
2 side rails, ³⁄₄ by 4 by 33 in.
2 end rails, ³⁄₄ by 4 by 21 in.
2 top cross braces, 1 by 4 by 19¹⁄₂ in.
4 feet, 1³⁄₄ by 4 by 4 in.
2 posts, 6 by 6 by 26 in.
2 side corner strips, 1 by 1 by 31¹⁄₂ in.
 2 end corner strips, 1 by 1 by 17¹⁄₂ in.
The bottom shelf can be made of two pieces of 1-in. material, 8 in.
wide, carefully glued together, and reinforced on the under side with
two crosspieces, glued and screwed to it. The foot pieces are
secured to the bottom shelf so as to project 1 in. on the ends and
sides. In case a center support is deemed advisable, another foot
piece can be added, but unless the floor is very level, rocking may
result. The uprights, or posts, are made from solid 6 by 6-in. lumber,
26 in. long, carefully squared at the ends, and tapered to 4 in. square
at the upper end. If desired, the posts can be made of boards, cut
and fastened together to form a hollow tapered post. In either case,
they should be set in about 4 in. from each side of the bottom shelf
and fastened to it by means of screws.

Design of a Table That will Appear Well in the Different Oak Finishes as
Well as in Mahogany
 The rail pieces for the table top should be cut and fitted with
mitered joints at the corner to form a rectangular frame, 21 by 33 in.
This is glued to the top and may be toenailed to it; but to provide a
more secure bracing, a 1-in. square strip of material is fastened all
around the inside edge of the rails, flush with their upper edge. The
top is screwed to this. In order to prevent tipping when the top is
resting on the 4 by 4-in. ends of the posts, two cross braces are
provided. These should be screwed to the outer-end sides of the
posts, and beveled off on their upper edges to fit the table top. They
should be of such length as to have a tight fit between the side rails,
and are fastened to these by means of finishing nails driven from the
outside. Gluing and toenailing can also be used to secure the top
more firmly to the braces; care should be taken that no nails cut
through the table top. After thoroughly sandpapering and smoothing
off the table, it can be finished to suit.—Contributed by H. J.
Blacklidge, San Rafael, Cal.
 Homemade Fuses for Battery Circuits
To carry out the general arrangement of the regular electrical
equipment of a large power plant, the battery circuit should have
some sort of a fuse block. An excellent way to make such a block is
as follows: Procure a piece of glass tubing, about 1 in. long, and
make a mounting for it with four pieces of sheet brass, as shown in
the sketch. The brass pieces are shaped and fastened to a wood
base so that their upper ends form a clamp to hold the glass tube.

The Fuse is Well Insulated and Protected against Fire the Same as the
Large Fuse
 A very thin piece of tinfoil, about 1¹⁄₂ in. long, is cut ¹⁄₈ in., or less,
in width, the size depending on the amount of current used. This is
placed in the glass tube and the ends are bent over the edge. A
piece of tinfoil is then wrapped around each end, over the ends of
the inclosed piece, and pasted to the tube.
The fuse thus made is pushed into the spring clamps of the block
which are connected in the circuit.—Contributed by Charles W.
Meinberg, Somerville, Mass.
 Reproducing Flowers and Leaves in Colors
A very cheap, easy, and quick way to make reproductions of
flowers, leaves, insects, butterflies, etc., is the following: Purchase 1
oz. of bichromate of potash and dissolve it in water. Spread this fluid
over the surface of the paper upon which the picture is to be made,
using a soft brush, and place it in a dark room to dry. When dry it will
be a light lemon color.
The leaf, or part to be reproduced, is placed upon the yellow side
of the paper and the whole exposed to the sunlight. The uncovered
portions will gradually turn brown, while the part covered by the
object will remain a lemon color. When the desired shade of brown is
attained, remove the paper from the sunlight, and the image of the
object will be on the paper.
Go over the outline with crayons or colors, and fill in the print
according to the natural colors. Very beautiful pictures may be made
in this way, and a butterfly made up in natural colors on a dark-brown
ground is very pretty. These prints, uncolored, will keep for some
time, if they are not exposed to a strong light.
Washing as ordinary photographic prints are treated will improve
them a little. If the instructions are followed, many beautiful objects
can be preserved in color.—Contributed by J. B. Murphy, Plainfield,
N. J.
 Dishwasher and Drier
Where hot water is available the dishwasher illustrated is
especially suitable. It is easily constructed and inexpensive, the only
real expense being for the tank, which is 15 in. deep and 20 in. in
diameter. A washer of these dimensions will hold the dishes from a
table serving six to eight persons. The tank may be supported on
legs if desired.
 The Hot Water from the Faucet is Forced over the Dishes in a Fine Spray

The supports for holding the dishes in a vertical position are made
of wire in a U-shape, the ends being fastened into two wood hoops
that snugly fit the inside of the tank, one near the bottom and the
other about 9 in. above the first one. The wires are set about 1¹⁄₂ in.
apart and radiate from the center like wire spokes in a wheel.
A funnel-shaped piece, having a hole 5 in. in diameter in the
center, is made of mesh wire and hung in place with several wires
running to the upper edge of the tank. Hooks are attached to the
edge of the hole on which cups and glasses are hung.
 The cover consists of a wood disk, with a hole bored in its center
for a ¹⁄₂-in. pipe. The piece of pipe used should be 3 or 4 in. longer
than the depth of the tank. A long thread is cut on the lower end of
the pipe, and two rectangular holes are cut in the pipe end through
the threaded part. These holes are made by cutting through the pipe
as if making a slot for a key. Two large nuts are run on the threads of
the pipe. These nuts should be thick enough to cover the slot in the
pipe. A pipe cap is then screwed on the end of the pipe. The upper
end of the pipe is attached to a hose connected to the hot-water
faucet. By separating the two nuts just a little, a fine spray of water
will be forced out of the holes.
When the dishes are in place the spray of hot water can be
directed over them by moving the pipe up and down through the hole
in the cover.
After the dishes are washed sufficiently the hose is removed and
the tank placed over a gas jet so that the heat will pass up through
the funnel-shaped attachment in the bottom of the tank. The dishes,
already heated by the hot water, soon dry in the heat from the gas
jet. If desired, the tank can be allowed to remain over the jet until the
next meal is ready to serve, using a very small flame.—Contributed
by W. K. Baxter, Massillon, O.

¶To empty a large sack filled with heavy material, turn or roll it over a
barrel.
 How to Make Pop-Corn Cakes

The Pop Corn When Formed into Cakes About One Inch Thick is Easily
Handled

It is very difficult to take a bite from a ball of pop corn, and it

becomes more difficult as the ball increases in size. As a large
number of balls were required for a church entertainment I decided
to make the pop corn into cakes. This was more easily accomplished
than first imagined with the use of a cake-forming device as shown in
the illustration. The body of the former was made of a baking-powder
can with the bottom removed. The cover of the can was nailed to the
top of an old table with its flange upward. A plunger of wood was
made to fit snugly inside of the can and a lever, about 3 ft. long,
attached to it and fulcrumed to the wall.
 After the pop corn has been prepared with the sirup, it is placed in
the can and compressed. The can is then lifted out of the cover and
the pop-corn cake removed. This method offers a much better way
to serve pop corn than in balls. In making the cakes, the can, cover,
and plunger must be kept well covered with butter.—Contributed by
Howard A. Hopkins, Youngstown, New York.
 Threading a Darning Needle
Having occasion to use a darning needle, the eye of which was
too small to insert the yarn in the usual manner, I tried the following
method with good results. A thread was doubled and passed through
the eye, and the loop thus formed was used to pull the yarn through.
—Contributed by Joe Henderson, Eldred, Ill.
 A Fish Scaler

Bottle Caps Nailed to a Wood Block for Removing Scales from a Fish

All kinds of devices, both simple and complex, have been made
and patented for use in scaling fish, but for a novelty I found the
following, which necessity compelled me to improvise on an outing
trip, to be as efficient as any of them. As usual, the commissary, in
making up the outfit, neglected to take the curry comb to clean the
fish, and at the same time remembered to take a plentiful supply of
bottled goods. Long before it became necessary to scale any fish
enough bottles had been opened to provide the basis of a tool for the
purpose, which I constructed by using the small tin bottle caps, a few
being nailed on a block of wood, about 3 in. wide by 4 in. long,
making a splendid fish scaler, as good and efficient at home as in the
camp, and both inexpensive and easily made. The sketch shows the
general appearance.— Contributed by T. B. Lambert, Chicago.