CYTOGENETICS

MODULE 5: Matters of Sex

○ If a gene on the Y
chromosome called SRY (for
Lesson 1: Our Sexual Selves
“sex-determining region of
Maleness or femaleness is the Y”) is activated,
determined at conception, when he hormones steer
inherits an X and a Y chromosome, or development along a male
she inherits two X chromosomes. route.
○ In the absence of SRY
Another level of sexual identity activation, a female
comes from the control that hormones develops. Femaleness was
exert over the development of long considered a “default”
reproductive structures. Finally, both option in human
biological factors and social cues development, defined as
influence sexual feelings, including the the absence of maleness.
strong sense of whether we are male or
female.

Sexual Development

● During the fifth week, all embryos

develop two unspecialized
gonads, which are organs that
will develop as either testes or
ovaries. Each such “indifferent”
gonad forms near two sets of
ducts that offer two
developmental options:
○ If one set of tubes, called
the Müllerian ducts,
continues to develop, they
eventually form the sexual
structures characteristic of
a female.
○ If the other set, the Wolffian
ducts, persist, male sexual
structures form.
● The choice to follow a male or
female developmental pathway
occurs during the sixth week,
depending upon the sex
chromosome constitution and
actions of certain genes.
CYTOGENETICS
MODULE 5: Matters of Sex
Sex Chromosomes
● Human males and females have
equal numbers of autosomes (44
or 22 pairs), but males have one X
chromosome and one
chromosome, and females have
two X chromosomes. The sex with
two different sex chromosomes is
called the heterogametic sex, and
the other, with two of the same
sex chromosome, is the
homogametic sex. In humans,
males are heterogametic and
females are homogametic.
● The sex chromosomes differ both
in size and in gene content. The X
chromosome in humans has
more than 1,500 genes and is
much larger than the
chromosome, which has 231
protein-encoding genes. In
meiosis in a male, the X and Y
chromosomes act as if they are a
pair of homologs.
● Identifying genes on the human Y
chromosome has been difficult. It
was not possible to create linkage
maps for the Y, as it was for the
other chromosomes, because the
Y does not cross over along all of
its length.
● Analysis of the genome sequence
Y revealed why mapping the Y
chromosome was so hard: It has a
very unusual organization. In the
95 percent of the chromosome
that harbors male-specific genes,
many DNA segments are
palindromes i.e. sequences of
letters that read the same in both
directions.
● This symmetry in a DNA
sequence, described by
researchers as “a hall of mirrors,”
destabilizes DNA replication. As a
result, during meiosis, sections of
Y a Y chromosome attract each
other. This can loop out parts in
between, which may account for
many cases of male infertility
caused by missing parts of the Y.
Yet this “hall of mirrors”
organization may also provide a
way for the chromosome to
recombine with itself, essentially
sustaining its structure.
CYTOGENETICS
MODULE 5: Matters of Sex

● The Y chromosome has a ancient autosome that long

distinctive overall structure with a ago gave rise to the X
short arm and a long arm. At chromosome.
both tips of the Y chromosome ○ The remainder of the MSY
are pseudoautosomal regions, includes palindrome-ridden
termed PAR1 and PAR2. They regions, called amplicons.
comprise only 5 percent of the ● The genes in the MSY include
chromosome and include 63 many repeats and specify protein
pseudoautosomal genes. The segments that combine in
term “pseudoautosomal” means different ways, which is one
that the DNA sequences have reason why counting the number
counterparts on the X of protein-encoding genes on the
chromosome and can cross over Y chromosome has been difficult.
with them. Many of the genes in the MSY are
● The pseudoautosomal genes essential to fertility, including SRY.
encode a variety of proteins that
function in both sexes,
participating in or controlling The Phenotype Forms
bone growth, cell division,
immunity, signal transduction, ● The SRY gene encodes a very
the synthesis of hormones and important type of protein called a
receptors, fertility, and energy transcription factor, which
metabolism. controls the expression of other
● Most of the Y chromosome is the genes. The SRY transcription
male-specific region, or MSY, that factor stimulates male
lies between the two development by sending signals
pseudoautosomal regions. It to the indifferent gonads.
consists of three classes of DNA ● In response, sustentacular
sequences. (Sertoli) cells in the developing
○ About 10 to 15 percent of testis secrete anti-Müllerian
the MSY is X-transposed hormone, which destroys
sequences that are 99 potential female structures
percent identical to (uterus, uterine tubes, and upper
counterparts on the X vagina). At the same time,
chromosome. interstitial (Leydig) cells in the
Protein-encoding genes are testis secrete testosterone, which
scarce here. stimulates the development of
○ Another 20 percent of the male structures (the
MSY consists of epididymides, ductus deferentia,
X-degenerate DNA seminal vesicles, and ejaculatory
sequences, which are ducts). Some testosterone is also
somewhat similar to X converted to dihydrotestosterone
chromosome sequences (DHT), which directs the
and may be remnants of an development of the urethra,
CYTOGENETICS
MODULE 5: Matters of Sex

prostate gland, penis, and develop as male. The

scrotum. person looks female, but is
○ XX embryos don't have SRY, XY.
so they develop as female. ● Several terms are used to
○ XY embryos do have SRY, so describe individuals whose
they develop as male. genetic/chromosomal sex and
physical structures, both
internal and external, are not
consistent with one gender.
○ Hermaphroditism is an
older and more general
term for an individual with
both male and female
sexual structures.
○ o Intersex refers to
individuals whose internal
structures are inconsistent
with external structures, or
whose genitalia are
ambiguous. It is the
preferred term outside of
medical circles.
○ o Pseudohermaphroditism
● Prenatal sexual development is a
refers to the presence of
multistep process, genetic
both types of structures but
abnormalities can intervene at
at different stages of life.
several different points during
prenatal sexual development (Fig ● In 5-alpha reductase deficiency
3). The result may be an XY (MIM 264600), which is autosomal
individual with a block in the recessive. Affected individuals
gene- and hormone-controlled have a normal Y chromosome, a
elaboration of male structures so wild type SRY gene, and testes.
that the phenotype is female. Testosterone stimulates the
○ For example, in androgen Wolffian duct system to develop
into the internal male
insensitivity syndrome (MIM
reproductive tract, while
300068), caused by a
antiMüllerian hormone eliminates
mutation in a gene on the X
the female precursor structures,
chromosome, the absence
so the male anatomy makes
of receptors for androgens
sense on the inside. The outside
(the male sex hormones
is a different story. When 5-alpha
testosterone and DHT)
reductase, which normally
stops cells in early
catalyzes the reaction of
reproductive structures
testosterone to form DHT, is
from receiving the signal to
deficient, lack of DHT causes the
CYTOGENETICS
MODULE 5: Matters of Sex

fetus to develop externally as facial hair grows, and

female—that is, without DHT, a menstruation does not occur.
penis cannot form. Changes
begin to be noticed at puberty,
when the adrenal glands, which Is Homosexuality Inherited
sit atop the kidneys, start to
produce testosterone. This now In homosexuality, a person’s
leads to masculinization. In this phenotype & genotype are consistent,
XY individual who thought she and physical attraction is toward
was female, the voice deepens, members of the same sex. Evidence
facial hair grows, and muscles suggests that homosexuality reflects
begin to build an undeniably complex input from both genes & the
masculine physique. Instead of environment. The genetic influence has
experiencing the expected breast been suspected for a long time based
development and menstruation, on the strong feelings that homosexual
the clitoris enlarges into a penis. individuals have as young children, well
Usually sperm production is before they know of the existence or
normal. XX individuals with meaning of the term. Other evidence
5-alpha reductase deficiency look comes from identical twins, who are
female. more likely to both be homosexual than
● In a more common form of are both members of fraternal twin
pseudohermaphroditism, pairs, suggesting a genetic component.
congenital adrenal hyperplasia Table 1 summarizes the several
(CAH) due to 21-hydroxylase components of sexual identity.
deficiency (MIM 201910), an
enzyme block causes
testosterone and DHT to
accumulate. It is autosomal
recessive, and both males
and females are affected.
The higher levels of
androgens cause
precocious puberty in
males or male secondary
sex characteristics to
develop in females. Boys
may enter puberty as early as 3
years old, with well-developed Sex Ratio
musculature, small testes, and an
● Mendel’s law of segregation
enlarged penis. At birth, girls may
predicts that populations should
have a swollen clitoris that
have approximately equal
appears to be a small penis. They
numbers of male and female
are female internally, but as they
newborns. That is, male meiosis
reach puberty, the voice deepens,
CYTOGENETICS
MODULE 5: Matters of Sex

should yield equal numbers of numbers of “missing females.” In

X-bearing and Y-bearing sperm. these societies, prenatal
After birth, societal and diagnostic techniques are used
environmental factors may favor to identify XX fetuses.
survival of one gender over the Termination of XX fetuses,
other. underreporting of female births,
● The proportion of males to and, rarely, selective infanticide
females in a human population is of girl babies all have
called the sex ratio. Sex ratio is contributed to a very unnaturally
calculated as the number of skewed sex ratio favoring males.
males divided by the number of
females multiplied by 1,000, for
people of a particular age. (Some Traits Inherited on Sex Chromosomes
organizations describe sex ratio
based on 1.0.) A sex ratio of equal ● Genes carried on the Y
numbers of males and females chromosome are said to be
would be designated 1,000. The Y-linked, and those on the X
sex ratio at conception is called chromosome are X-linked. Genes
the primary sex ratio. Sex ratio at on the X chromosome have
birth is termed secondary and at different patterns of expression
maturity is called tertiary. in females and males, because a
● In the United States for the past female has two X chromosomes
six decades, newborn boys have and a male just one.
slightly outnumbered newborn ● In females, X-linked traits are
girls, with the primary sex ratio passed just like autosomal
averaging 1,050. The slight excess traits—that is, two copies are
of boys may reflect the fact that required for expression of a
Y-bearing sperm weigh slightly recessive allele, and one copy for
less than X-bearing sperm, and a dominant allele.
so they may reach the oocyte ● In males, a single copy of an
faster. X-linked allele causes expression
● Sex ratio can change markedly of the trait or illness because
with age, reflecting medical there is no copy of the gene on a
conditions that affect the sexes second X chromosome to mask
differently, as well as the effect.
environmental factors that affect
one sex more than the other, such
as participation in combat or
engaging in other dangerous
behaviors.
● A society can intentionally alter
the sex ratio. This has been done
in India and China, where
researchers have identified great
CYTOGENETICS
MODULE 5: Matters of Sex
● A male inherits his Y chromosome
from his father and his X
chromosome from his mother.
The human male is considered
hemizygous for X-linked traits,
because he has only one set of
X-linked genes.
● A female inherits one X
chromosome from each parent. If
a mother is heterozygous for a
particular X-linked gene, her son
or daughter has a 50 percent
chance of inheriting either allele
from her X-linked traits are always
passed on the X chromosome
from mother to son or from either
parent to daughter, but there is
no male-to male transmission of
X-linked traits.
● Females must inherit recessive
X-linked alleles from both of their
parents in order to express the
trait. When they inherit one
recessive X-linked mutant allele
and one dominant X-linked
wild-type allele, they are carriers
of the trait and are typically
unaffected (Figure7).
● Carrier females can manifest mild
forms of the trait due to the
inactivation of the dominant
allele located on one of the X
chromosomes.
X-Linked Genes
● When a gene is present on the X
chromosome, but not on the Y
chromosome, it is said to be
X-linked. Since a female has two X
chromosomes, she will have two
copies of each X-linked gene.
● For instance, in the fruit fly
Drosophila (which, like humans,
has XX females and XY males),
there is a eye color gene called
white that's found on the X
chromosome, and a female fly will
have two copies of this gene. If
the gene comes in two different
CYTOGENETICS
MODULE 5: Matters of Sex
alleles, such as XW (dominant,
normal red eyes) and Xw
(recessive, white eyes), the female
fly may have any of three
genotypes: XW XW (red eyes), XW
Xw (red eyes) and Xw Xw (white
eyes).
● In Figure 7, because the gene is
X-linked, and because it was the
female parent who had the
recessive phenotype (white eyes)
all the male offspring—who get
their only X from their
mother—have white eyes (Xw Y).
All the female offspring have red
eyes because they received two
Xs, with the XW from the father
concealing the recessive (Xw)
from the mother.
X-Linked Recessive Inheritance
Criteria for an X-Linked Recessive Trait:
1. Always expressed in the male.
2. Expressed in a female
homozygote but very rarely in a
heterozygote.
3. Passed from heterozygote or
homozygote mother to affected
son.
4. Affected female has an affected
father and a mother who is
affected or a heterozygote.
If an X-linked condition is not lethal, a
man may be healthy enough to
transmit it to offspring.
Examples:
● Ichthyosis, an enzyme deficiency
blocks removal of cholesterol
from skin cells, the upper skin
layer cannot peel off as it
normally does, appearing brown
and scaly. It is transmitted as an
X-linked recessive trait. In Fig. 7, a
grandfather and grandson were
affected in the family.
● Colorblindness is another
X-linked recessive trait that does
not hamper the ability of a man
to have children. About 8 percent
of males of European ancestry
are colorblind, as are 4 percent
of males of African descent. Only
0.4 percent of females in both
groups are colorblind.
CYTOGENETICS
MODULE 5: Matters of Sex

parents have normal blood

clotting, but the mother is a
carrier.

How colorblindness arises (Fig. 9):

The sequence similarities among

the opsin genes responsible for
color vision may cause
chromosomes to misalign during
meiosis in the female. Offspring ○ Since the mother is a
may inherit too many, or too few, carrier, she will pass on the
opsin genes. A son inheriting an hemophilia allele (Xh) on to
X chromosome missing an opsin half of her children, both
gene would be colorblind. A boys and girls.
daughter, unless her father is ○ None of the daughters will
colorblind, would be a carrier. have hemophilia (zero
A missing gene causes X-linked chance of the disorder).
colorblindness. That's because, in order to
have the disorder, they must
get (Xh) from both their
mother and their father.
● Hemophilia A, blood-clotting
There is 0 chance of the
disorder. This X-linked recessive
daughters getting an
disease usually passes from a
(Xh))allele from their father,
heterozygous woman (designated
so their overall chance of
XHXh, where h is the
having hemophilia is zero.
hemophilia-causing allele) to
○ The sons get a Y from their
heterozygous daughters or
father instead of an X, so
hemizygous sons.
their only copy of the blood
○ A woman who is
clotting gene comes from
heterozygous for normal
their mother. The mother is
and hemophilia alleles
heterozygous, so half of the
(XHXh) has children with a
sons, on average, will get an
man who is hemizygous for
(Xh) and have hemophilia
the normal form(XHY). Both
(1/2 chance of the disorder).
 CYTOGENETICS
MODULE 5: Matters of Sex
X-Linked Dominant Inheritance
Criteria for an X-Linked Dominant Trait:
1. Expressed in female in one copy.
2. Much more severe effects in
males.
3. High rates of miscarriage due to
early lethality in males.
4. Passed from male to all
daughters but to no sons.
● A female who inherits a dominant
X-linked allele has the associated trait
or illness, but a male who inherits the
allele is usually more severely affected
because he has no other allele to
mask its effect. A female who has an
X-linked dominant trait has a 1 in 2
probability of passing it to her
offspring, male or female.
Example of an X-linked dominant
conditions:
1. Incontinentia pigmenti, in
affected females, swirls of skin
pigment arise when melanin
penetrates the deeper skin layers.
A newborn girl with IP has yellow,
pus filled vesicles on her limbs
that come and go over the first
few weeks. Then the lesions
become warty & eventually give
way to brown splotches that may
remain for life, although they
fade with time. Males with the
condition are severely affected
that they do not survive to be
born.
2. Congenital generalized
hypertrichosis, this condition
produces many extra hair
follicles, and hence denser and
more abundant upper body hair.
Hair growth is milder and
patchier in females because of
hormonal differences and the
presence of a second X
chromosome. Figure 13b shows
part of a pedigree of a large
Mexican family with 19 members
who have this X-linked dominant
condition. In this partial pedigree
of a large Mexican family, the
affected male in the second
generation passed the condition
to all of his daughters and none
of his sons. This is because he
transmits his X chromosome only
to females.
Lesson 2: Sex-Limited & Sex-Influenced
Traits
An X-linked recessive trait
generally is more prevalent in males
than females. Other situations, however,
can affect gene expression in the sexes
differently.
Sex-Limited Traits
● A sex-limited trait affects a
structure or function of the body
CYTOGENETICS
MODULE 5: Matters of Sex

that is present in only males or which is why more men than

only females. Such a gene may be women are bald. A heterozygous
X-linked or autosomal. male is bald, but a heterozygous
● In humans, beard growth is female is not. A bald woman is
sex-limited. A woman does not homozygous recessive.
grow a beard because she does
not manufacture the hormones
required for facial hair growth. X Inactivation
She can, however, pass to her
sons the genes specifying heavy ● Females have two alleles for every
beard growth. gene on the X chromosomes,
● An inherited medical condition whereas males have only one. In
that arises during pregnancy is mammals, a mechanism called X
obviously sex-limited, but the inactivation balances this
male genome contributes to the apparent inequality in the
development of supportive expression of genes on the X
structures, such as the placenta. chromosome.
This is the case for preeclampsia, ● X-inactivation is a random
a sudden rise in blood pressure process that happens separately
late in pregnancy. It kills 50,000 in individual cells during
women worldwide each year. embryonic development. By the
Perhaps a gene from the father time a female embryo consists of
affects the placenta in a way that 8 cells, about 75 percent of the
elevates the pregnant woman’s genes on one X chromosome in
blood pressure. each cell are inactivated, and the
remaining 25 percent are
expressed to different degrees in
Sex-Influenced Traits different women. As a result, a
female mammal expresses the X
● In a sex-influenced trait, an allele chromosome genes inherited
is dominant in one sex but from her father in some cells and
recessive in the other. Such a those from her mother in others.
gene may be X-linked or ● A female is a mosaic for
autosomal. The difference in expression of genes on the X
expression can be caused by chromosome because of the
hormonal differences between random inactivation of either the
the sexes. maternal or paternal X in each
● For example, an autosomal gene cell early in prenatal
for hair growth pattern has two development.
alleles, one that produces hair all
over the head and another that
causes pattern baldness. The
baldness allele is dominant in
males but recessive in females,
CYTOGENETICS
MODULE 5: Matters of Sex
In anhidrotic ectodermal
dysplasia, a woman has patches of skin
that lack sweat glands and hair. (Colors
distinguish cells with the inactivated X,
not to depict skin color.)
● A gene called XIST controls X
inactivation. It encodes an RNA
that binds to a specific site on
the same (inactivated) X during interphase, has one
chromosome. From this point out
to the chromosome tip, the X
chromosome is inactivated.
● Once an X chromosome is
inactivated in one cell, all its
daughter cells have the same X
chromosome inactivated.
Because the inactivation occurs
early in development, the adult
female has patches of tissue that
differ in their expression of
X-linked genes. With each cell in
her body having only one active
X chromosome, she is roughly
equivalent to the male in terms of
gene expression.
● X inactivation can alter the
phenotype (gene expression), but
not the genotype. It is not
permanent, and is reversed in
germline cells destined to
become oocytes. Therefore, a
fertilized ovum does not have an
inactivated X chromosome.
● X inactivation is an example of an
epigenetic change i.e. one that is
passed from one cell generation
to the next but that does not
alter the DNA base sequence. We
can observe X inactivation at the
cellular level because the
turned-off X chromosome
absorbs a stain much faster than
the active X. This differential
staining occurs because
inactivated DNA has chemical
methyl (CH 3 ) groups that
prevent it from being transcribed
into RNA and also enable it to
absorb stain.
● X inactivation can be used to
check the sex of an individual.
The nucleus of a cell of a female,
dark-staining X chromosome
called a Barr body (a small, dense
structure). Most of the genes on
the Barr body are inactive,
meaning that they are not
transcribed. A cell from a male
has no Barr body because his
one X chromosome remains
active.
Effect on the Phenotype
● For homozygous X-linked
genotypes, X inactivation has no
effect. No matter which X
chromosome is turned off, the
same allele is left to be expressed.
For heterozygotes, however, X
inactivation leads to expression
of one allele or the other. This
CYTOGENETICS
MODULE 5: Matters of Sex

doesn’t affect health if enough damage, and enlarged liver

cells express the functional gene and spleen.
product. However, some traits ○ o In contrast, in Fabry
reveal the X inactivation. disease
● A female who is heterozygous for (alpha-galactosidase A
an X-linked recessive gene can deficiency), the enzyme is
express the associated condition not easily released from
if the normal allele is inactivated cells, so a female who is a
in the tissues that the illness heterozygote may have
affects. Consider a carrier of cells in the affected organs
hemophilia A. If the X that lack the enzyme. She
chromosome carrying the normal may develop mild
allele for the clotting factor is symptoms of this disorder
turned off in the liver, then the that causes skin lesions,
woman’s blood will clot slowly abdominal pain, and kidney
enough to cause mild hemophilia. failure in boys.
A carrier of an X-linked trait who
expresses the phenotype is called
a manifesting heterozygote. Calico Cat
● Whether or not a manifesting
heterozygote results from X ● A familiar example of X
inactivation depends upon how inactivation is the coat colors of
adept cells are at sharing. tortoiseshell and calico cats. An
Consider two lysosomal storage X-linked gene confers
disorders, which are deficiencies brownish-black (dominant) or
of specific enzymes that normally yellowish-orange (recessive) color.
dismantle cellular debris in A female cat heterozygous for
lysosomes. this gene has patches of each
○ In Hunter syndrome color, forming a tortoiseshell
(mucopolysaccharidosis II), pattern that reflects different
cells that make the enzyme cells expressing either of the two
readily send it to alleles.
neighboring cells that do ○ If a female cat is
not, essentially correcting heterozygous for black and
the defect in cells that can’t tan alleles of a coat color
make the enzyme. Carriers gene found on the X, she
of Hunter syndrome do not will inactivate her two Xs
have symptoms because (and thus, the two alleles of
cells get enough enzyme. the coat color gene) at
Affected boys are deaf, random in different cells
mentally retarded, have during development.
dwarfism and abnormal ○ The result of is a
facial features, heart tortoiseshell coat pattern,
made up of alternating
CYTOGENETICS
MODULE 5: Matters of Sex
patches of black and tan
fur. The black patches come
from groups of cells in
which the X with the black
allele is active, while the tan
patches come from cells in
which the X with the tan
allele is active.
Subtle Effects of X Inactivation
● Theoretically, X inactivation
evens out the sexes for
expression of X-linked genes. In
actuality, however, a female may
not be equivalent, in gene
expression, to a male because
she has two cell populations,
whereas a male has only one.
One of a female’s two cell
populations has the X she
inherited from her father active,
and the other has the X
chromosome she inherited from
her mother active. For
heterozygous X-linked genes, she
would have some cells that
manufacture the protein
encoded by one allele, and some
cells that produce the protein
encoded by the other allele.
● Although most heterozygous
genes have the alleles about
equally represented, sometimes X
inactivation can be skewed. That
is, most cells express the X
inherited from the same parent.
This can happen if one of the X
chromosomes includes an
expressed allele that confers a
greater rate of cell division than
the different allele from the other
parent, giving certain cells a
survival advantage.
● Another way that X inactivation
makes a female different from a
male is seen when the proteins
encoded by different alleles
interact. This can be beneficial or
harmful. A beneficial example of
dual expression of alleles occurs
in certain types of monkeys in
which an X-linked visual pigment
gene has two alleles. Females who
are homozygous for this gene
and males have 2-color vision,
but lucky female monkeys who
are heterozygous for this gene
enjoy 3-color vision.
● A situation in which being a
heterozygote for an X-linked gene
is harmful is craniofrontonasal
syndrome. Males and
homozygous females have
asymmetrical facial features.
However, heterozygous females
have a much more severe
phenotype, with very abnormal
faces resulting from abnormal
fusing of the skull bones. An
explanation is that the encoded
protein is part of a signal
transduction pathway that
controls the bone fusion, and
when two forms of that protein
CYTOGENETICS
MODULE 5: Matters of Sex
are made in the female
heterozygote, the signal is
disrupted in a way that blocks the
cells that form the sutures of the
skull from joining cleanly.
Genomic Imprinting
● In Mendel’s pea experiments, it
didn’t matter whether a trait
came from the male or female
parent. For certain genes in
mammals, however, parental
origin does influence the
phenotype. These genes are said
to be imprinted. In genomic
imprinting, methyl (CH 3) groups
cover a gene or several linked
genes and prevent them from
being accessed to synthesize
protein.
Methyl (CH3) groups (red) “silence” certain
genes
● For a particular imprinted gene,
the copy inherited from either the
father or the mother is always
covered with methyls, even in
different individuals. The result of
this gene cloaking is that a
disease may be more severe, or
different, depending upon which
parent transmitted the mutant
allele. That is, a particular gene
might function if it came from the
father, but not if it came from the
mother, or vice versa.
Silencing the Contribution from One
Parent
● Imprinting is an epigenetic
alteration. It is a layer of meaning
stamped upon a gene without
changing its DNA sequence. The
imprinting pattern is passed from
cell to cell in mitosis, but not from
individual to individual through
meiosis. When silenced DNA is
replicated during mitosis, the
pattern of blocked genes is
exactly placed, or imprinted, on
the new DNA, covering the same
genes as in the parental DNA In
this way, the “imprint” of
inactivation is perpetuated, as if
each such gene “remembers”
which parent it came from.
CYTOGENETICS
MODULE 5: Matters of Sex

embryo and placenta. In the early

1980s, researchers created
fertilized mouse ova that
contained two male pronuclei or
two female pronuclei, instead of
one from each.
● When the fertilized ovum had two
male genomes, a normal
placenta developed, but the
embryo was tiny and quickly
stopped developing. A zygote
with two female pronuclei, on the
other hand, developed into an
embryo, but the placenta was
grossly abnormal. Therefore, the
male genome controls placenta
development, and the female
genome, embryo development.
● The mouse results were
consistent with abnormalities of
human development. When two
sperm fertilize an oocyte and the
female pronucleus degenerates,
an abnormal growth of
placenta-like tissue called a
hydatidiform mole forms. If a
fertilized ovum contains only two
● In meiosis, imprints are removed female genomes but no male
and reset. As oocyte and sperm genome, a mass of random
form, the CH 3 groups shielding differentiated tissue, called a
their imprinted genes are teratoma, grows.
stripped away, and new patterns
are set down, depending upon
whether the fertilized ovum Imprinting Disorders in Humans
chromosomally is male (XY) or
female (XX). In this way, women ● The effects of genomic imprinting
can have sons and men can have are revealed only when an
daughters without passing on individual has one copy of a
their sex specific parental normally imprinted allele and the
imprints. other, active allele is inactivated
● Genomic imprinting suggests or deleted. The effects of
that for mammals, two genomic imprinting gone awry
opposite-sex parents are can be dramatic, such as two
necessary to produce a healthy different syndromes that arise
CYTOGENETICS
MODULE 5: Matters of Sex

from small deletions in the same

region of chromosome 15.

a. Two distinct syndromes

result from missing genetic
material in the same region
of chromosome 15.
b. Prader-Willi syndrome, due
to a deletion in the copy of
the chromosome he
inherited from his father.
Note his small hands.
c. Angelman syndrome,
caused by a deletion in the
chromosome 15 that he
inherited from his mother.
He is mentally retarded.