BSMDT 2: CYTOGENETICS
TOPIC 4: Matters of Sex
1st Semester | A.Y. 2023 - 2024
Sexual Development
• Gender differences become apparent around
the ninth week of prenatal 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, female sexual
structures form. If the other set, the Wolffian
ducts, persists, male sexual structures form.
Sex 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 (XY) and
females are homogametic (XX). Some other
species are different.
• The Y
chromosome
has a very short
arm and a long
arm. At both
tips are regions,
called PAR1
and PAR2,
which are termed “pseudoautosomal” because
they can cross over with counterparts on the X
chromosome.
• The pseudoautosomal regions comprise only 5 • Homosexuality reflects complex input from
percent of the Y chromosome and include 63
pseudoautosomal genes that encode proteins
that function in both sexes.
• These genes control bone growth, cell division,
immunity, signal transduction, the synthesis of
hormones and receptors, fertility, and energy
metabolism.
The Phenotype Forms
• The SRY gene encodes an important type of
protein called a transcription factor, which
controls the expression of other genes.
• The SRY transcription factor stimulates male
development by sending signals to the
indifferent gonads that destroy potential
female structures while stimulating
development of male structures.
• Hermaphroditism is an older and more
general term for an individual with male and
female sexual structures.
• 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.
• Pseudohermaphroditism refers to the presence
of both female and male structures but at
different life stages.
Is homosexuality inherited?
• No one really knows why we have feelings of
belonging to one gender or the other, or of
being attracted to the same or opposite
gender, but these feelings are intense. In
homosexuality, a person’s phenotype and
genotype are consistent, and physical
attraction is toward members of the same sex.
Homosexuality is seen in all human cultures
and has been observed for thousands of
years.
genes and the environment. The genetic
influence may be seen in the strong feelings
that homosexual individuals have as young
children, long before they know of the
existence or meaning of the term.
• Such a study done on all adult twins in
Sweden found that in males, genetics
contributes about 35 percent to
homosexuality, whereas among females the
 BSMDT 2: CYTOGENETICS

TOPIC 4: Matters of Sex

1st Semester | A.Y. 2023 - 2024

genetic contribution is about 18 percent. Genomic Imprinting

Homosexuality likely reflects the input of many • In genomic imprinting, methyl (CH3 ) groups
genes and environmental factors, and may cover a gene or several linked genes and
arise in a variety of ways prevent them from being accessed
(transcribed and translated) to synthesize
protein.
• For an imprinted gene, the copy inherited
from either the father or the mother is always
covered with methyls, even in different
individuals. That is, a particular gene might
function if it came from the father, but not if it
came from the mother, or vice versa. This
parental effect on gene expression is seen as
diseases that are always inherited from the
mother or father.
• In meiosis, imprints are removed and reset. As
oocyte and sperm form, the CH3 groups
shielding their imprinted genes are stripped
away, and new patterns are set down,
depending upon whether the fertilized ovum
is chromosomally male (XY) or female (XX).
• In this way, women can have sons and men
can have daughters without passing on sex-
specific parental imprints.
• Imprinting may be an important concern in
Sex-Limited and Sex-Influenced Traits
assisted reproductive technologies that
• A sex-limited trait affects a structure or
manipulate gametes to treat infertility.
function of the body that is present in only
• For example, the otherwise rare Beckwith-
males or only females. The gene for such a trait
Wiedemann syndrome is more prevalent
may be X-linked or autosomal.
among the offspring of people who used in
• With a sex-influenced trait, an allele is
vitro fertilization and intracytoplasmic sperm
dominant in one sex but recessive in the other.
injection to become pregnant.
Such a gene may be X-linked or autosomal.
The difference in expression can be caused by
Imprinting Diseases in Humans
hormonal differences between the sexes. For
• Imprinting diseases can be dramatic, such as
example, an autosomal gene for hair growth
two syndromes that arise from small deletions
pattern has two alleles, one that produces hair
in the same region of chromosome 15.
all over the head and another that causes
• A child with Prader-Willi syndrome is small at
pattern baldness. The baldness allele is
birth and in infancy has difficulty gaining
dominant in males but recessive in females,
weight. Between ages 1 and 3, the child
which is why more men than women are bald.
develops an obsession with eating and a very
slow metabolism. Parents lock kitchen
 BSMDT 2: CYTOGENETICS
TOPIC 4: Matters of Sex
1st Semester | A.Y. 2023 - 2024
cabinets and refrigerators to keep these
children from eating themselves to death by
bursting digestive organs.
• The other condition resulting from the small
deletion in chromosome 15, Angelman
syndrome, causes autism and intellectual
disability, an extended tongue, large jaw, poor
muscle coordination, and convulsions that
make the arms flap.
Multifactorial Traits
• A trait can be described as either single-gene
(Mendelian or monogenic) or polygenic. As its
name implies, a polygenic trait reflects the
activities of more than one gene. Both single
gene and polygenic traits can also be
multifactorial, which means they are influenced • Genes affect how the brain responds to
by the environment.
Fingerprint Patterns
• Skin on the fingertips is folded into raised
patterns called dermal ridges that align to form
loops, whorls, and arches.
• This pattern is a fingerprint. A technique called
dermatoglyphics (“skin writing”) compares the
number of ridges that comprise these patterns • Variants of hundreds of genes contribute in
to identify and distinguish individuals.
• Dermatoglyphics is part of genetics because
certain diseases (such as Down syndrome)
produce unusual ridge patterns. Forensic
fingerprint analysis is also an application of
dermatoglyphics.
• A fingerprint is quantified with a measurement
called a total ridge count, which tallies the
numbers of ridges in whorls, loops, or arches.
The average total ridge count in a male is 145,
and in a female, 126.
Methods to Investigate Multifactorial Traits
• Empiric risk measures the likelihood that a
multifactorial trait will recur based on
incidence. The risk rises with genetic closeness,
severity, and number of affected relatives.
• Heritability estimates the proportion of
variation in a multifactorial trait due to
genetics in a particular population at a
particular time.
• The coefficient of relatedness is the proportion
of genes that two people related in a certain
way share.
Genetics of Behavior
Genes and Behavior
environmental stimuli. Neurons and neuroglia
are the two major types of brain cells.
• Candidate genes for behavioral traits and
disorders affect neurotransmitters crossing
synapses (neurotransmission).
• Old and new genetic tools are being used to
describe the biological causes of various
behavioral disorders.
different degrees to behavioral disorders.
Sleep
• Twin studies and single-gene disorders that
affect the sleep-wake cycle reveal a large
inherited component to sleep-wake behavior.
• Clock genes such as period 2 enable a person
to respond to day and night environmental
cues.
Intelligence and Intellectual Disability
• The general intelligence ability (g) measures
the inherited portion of IQ that may underlie
population variance in IQ test performance.
• Studies indicate that general intelligence is
maintained throughout life. The fact that
 BSMDT 2: CYTOGENETICS
TOPIC 4: Matters of Sex
1st Semester | A.Y. 2023 - 2024
many syndromes that result from abnormal
chromosomes affect intelligence suggests
high heritability.
• Exome and genome sequencing are
identifying mutations that cause or contribute
to intellectual disability, which has many
causes.
Drug Addiction
• Drug addiction is a severe substance use
disorder that arises from developing tolerance
to and dependence on a drug. Addiction
produces stable changes in certain brain
parts.
• Proteins involved in drug addiction affect
neurotransmitter synthesis and neurotransmitter
removal from synapses, and receptor structure • Exposure to certain pathogens and chemicals
and function.
• Candidate genes for drug addiction encode
the dopamine D(2) receptor and nicotinic
receptor parts.
Mood Disorders
• Major depressive disorder is common and
associated with mutations in genes that
regulate circadian rhythms and deficits of
serotonin.
• Bipolar disorder includes depressive periods
and periods of mania or hypomania. Variants
of hundreds of genes may raise the risk of
developing bipolar disorder.
• Combinations of such predisposing gene
variants in the presence of certain
environmental influences can lead to the
disorder.
Schizophrenia
• Schizophrenia greatly disrupts the ability to
think and perceive the world. Onset is typically
in early adulthood, and the course is episodic
or it plateaus.
• Empiric risk values and a heritability of 0.9
indicate a large genetic component to
schizophrenia.
• An overactive or inappropriate immune
response during prenatal development or in
late adolescence may increase the risk of
developing schizophrenia.
• Inheriting a variant of a gene (C4A) that
encodes an immune system protein increases
schizophrenia risk by increasing the rate of
synaptic pruning during late adolescence or
young adulthood.
Autism
• Autism is a loss of communication and social
skills beginning in early childhood.
can increase the risk of autism.
• Autism is part of many genetic syndromes, but
these account for a small percentage of
autism cases.
• Three approaches are used to analyze exome
or genome sequences to identify gene
variants that contribute to developing autism.
The “multiple unrelated affected subjects”
approach seeks gene variants in individuals
with autism that are not in population
databases of unaffected children. “Trio
analysis” distinguishes carrier parents from de
novo mutations in the child. “Recessive
analysis” searches for gene variants that two
or more affected siblings share.
• Neurexins and neuroligins are proteins
embedded in the plasma membranes of the
presynaptic and postsynaptic neurons,
respectively, that cannot interact normally at
synapses in some cases of autism.