SEX DETERMINATION

AND
SEX CHROMOSOMES
INTRODUCTION
• successful fertilization depends on some form of sexual
diff erentiation in the reproductive organisms.

• diff erentiation of the sexes is more evident as phenotypic

dysmorphism of males and females.

• ancient symbol for iron and for Mars, depicting a shield and
spear (male: ♂)

• ancient symbol for copper and for Venus, depicting a mirror

(female: ♀)
INTRODUCTION
• dissimilar, or
heteromorphic,
chromosomes, such as the
XY pair in mammals,
characterize one sex or the
other in a wide range of
species, resulting in their
label as sex chromosomes.
X AND Y CHROMOSOMES
• presence or absence of the X chromosome in male gametes
provides an effi cient mechanism for sex determination

• females have two X chromosomes

• males have a single X and a smaller heterochromosome

labeled as the Y chromosome.

• females produce only gametes of the (6A+X) constitution,

but males produce two types of gametes in equal
proportions, (6A+X) and (6A+Y).
X AND Y CHROMOSOMES
• In Protenor and Lygaeus insects, males produce unlike
gametes. and are described as the heterogametic sex,
and in eff ect, determine the sex of the progeny in those
species.

• Female, which has like sex chromosomes is called

homogametic sex, producing uniform gametes with regard
to chromosomes numbers and types.
 Y CHROMOSOME DETERMINES
MALENESS IN HUMANS
• Human female has two X chromosomes

• Human male has one X and one Y chromosomes

• presence of two x chromosomes could cause femaleness or

maleness could result from the lack of second X
chromosomes.

• Y chromosomes determine maleness in humans.

 KLINEFELTER AND TURNER SYNDROME

• 1940- two human abnormalities characterized by aberrant

sexual development.

• Klinefelter syndrome (47, XXY) are generally tall and have

long arms and legs and large hands and feet.

• (+) genitalia and internal ducts that are male, but their
testes are rudimentary and fail to produce sperm.

• feminine sexual development is not entirely suppressed

• slight enlargement of breasts (gynecomastia) is common

 KLINEFELTER AND TURNER SYNDROME

• Klinefelter syndrome

• hips are often rounded

• intelligence is often below the normal range

 KLINEFELTER AND TURNER SYNDROME

• Turner syndrome

• aff ected individual has female external genitalia and

internal ducts and ovaries are rudimentary

• short stature (usually under 5 feet)

• skin fl aps on the back of the neck

• underdeveloped breast

• broad, shieldlike chest are sometimes noted.

• intelligence is usually normal.

 KLINEFELTER AND TURNER SYNDROME

• In 1959- karyotypes of individuals with Klinefelter and

Turner syndromes were determined to be abnormal with
respect to the sex chromosomes.

• Klinefelter syndrome

• more than one x chromosome; most often they have an

XXY complement in addition to 44 autosomes which is
why people with this type of karyotype are designated
47, XXY
 KLINEFELTER AND TURNER SYNDROME

• Turner syndrome

• most often have only 45 chromosomes, including just a

single X chromosomes

• designated 45,X

• can also result from karyotypes other than 45,X,

including individuals called mosaics.

• observed in about 1 in 2000 female births

 47,XXX

• abnormal presence of three X chromosomes along with a

normal set of autosomes (47, XXX results in female
diff erentiation.

• highly variable syndrome that accompanies this genotype,

often called triple-X, occurs in about 1 of 1000 female
births.

• women are perfectly normal and may remain unaware of

their abnormality unless karyotype is done.
 48,XXXX AND 49, XXXXX

• 48,XXXX (tetra-X)

• 49,XXXXX(penta-X)

• syndromes are similar but more pronounced that with

47,XXX syndrome.

• additional X chromosomes appears to disrupt the delicate

balance of genetic information essential to normal female
development.
 47,XYY SYNDROME

• 1965- Patricia Jacobs discovered that 9 of 315 males in a

Scottish maximum security prison had a 47,XYY karytypes.

• males were signifi cantly above average in height and had

been incarcerated as a result of dangerous, violent, or
criminal propensities.

• High but not constant, correlation between the extra Y

chromosome and the predisposition of males to exhibit
behavioral problems.
SEXUAL DIFFENRENTIATION IN HUMANS

• undergoes a period when it is potentially hermaphroditic

• during 5th week of gestation, gonadal primordia (tissues

that will form the gonad) aris as a pair of gonadal
(genital) ridges associated with each embryonic kidney.

• embryo is potentially hermaphroditic because at this stage

its gonadal phenotype is sexually indiff erent—male or
female reproductive structures cannot be distinguished, and
the gonadal ridge tissue can develop to form male or female
gonads.
SEXUAL DIFFENRENTIATION IN HUMANS

• As development progresses, primordial germ cells migrate

to these ridges, where an outer cortex and inner medulla
form.

• cortex is capable of developing into an ovary

• medulla may develop into a testis.

SEXUAL DIFFENRENTIATION IN HUMANS

• two sets of undiff erentiated ducts called the Wolffi an and

Müllerian ducts exist in each embryo.

• Wolffi an ducts diff erentiate into other organs of the male

reproductive tract,

• Müllerian ducts diff erentiate into structures of the female

reproductive tract.
SEXUAL DIFFENRENTIATION IN HUMANS

• Because gonadal ridges can form either ovaries or testes,

they are commonly referred to as bipotential gonads.

• If cells of the ridge have an XY constitution, development of

the medulla into a testis is initiated around the seventh
week.

• in the absence of the Y chromosome, no male development

occurs, the cortex of the ridge subsequently forms ovarian
tissue, and the Müllerian duct forms oviducts (Fallopian
tubes), uterus, cervix, and portions of the vagina.
SEXUAL DIFFENRENTIATION IN HUMANS

• Depending on which pathway is initiated, parallel

development of the appropriate male or female duct system
then occurs, and the other duct system degenerates.

• If testes diff erentiation is initiated, the embryonic testicular

tissue secretes hormones that are essential for continued
male sexual diff erentiation.
SEXUAL DIFFENRENTIATION IN HUMANS

• In females, as the twelfth week of fetal development

approaches, the oogonia within the ovaries begin mitosis,
and primary oocytes can be detected.

• By the twenty-fi fth week of gestation, all oocytes become

arrested in mitosis and remain dormant until puberty is
reached some 10 to 15 years later.

• In males, on the other hand, primary spermatocytes are

not produced until puberty is reached.
 Y CHROMOSOME AND MALE
DEVELOPMENT
• Y chromosome contains far fewer genes than does the X.

• Y chromosome has at least 75 genes, compared to 900–

1400 genes on the X.

• present on both ends of the Y chromosome are so-called

pseudoautosomal regions (PARs) that share homology
with regions on the X chromosome and synapse and
recombine with it during meiosis.
 Y CHROMOSOME AND MALE
DEVELOPMENT (DISCUSSION)
• The remainder of the chromosome, about 95 percent of it,
does not synapse or recombine with the X chromosome.

• As a result, it was originally referred to as the

nonrecombining region of the Y (NRY).

• More recently, researchers have designated this region as

the male-specifi c region of the Y (MSY).

• Some portions of the MSY share homology with genes on the

X chromosome, and others do not.
Y CHROMOSOME AND MALE
DEVELOPMENT
 Y CHROMOSOME AND MALE
DEVELOPMENT
• MSY is divided about equally between euchromatic regions,
containing functional genes, and heterochromatic regions,
lacking genes.

• Within euchromatin, adjacent to the PAR of the short arm

of tof the Y chromosome, is a critical gene that controls
male sexual development, called the sex-determining
region Y (SRY).

• absence of a Y chromosome almost always leads to female

development; thus, this gene is absent from the X
 Y CHROMOSOME AND MALE
DEVELOPMENT
• Six to eight weeks of development, the SRY gene becomes
active in XY embryos.

• SRY encodes a protein (Testis-determining factor [TDF])

that causes the undiff erentiated gonadal tissue of the
embryo to form testes
C H R O M O S O M E M U TAT I O N S :
VA R I AT I O N I N N U M B E R
AND ARRANGEMENT
INTRODUCTION
• chromosome mutations or chromosome abberations -
modifi cations include a change in the total number of
chromosomes, deletion or duplication of genes or segments,
and rearrangements of the genetic material either within or
among chromosomes.

• chromosome aberrations are passed to off spring in a

predictable manner, resulting in many unique genetic
outcomes.
1. VARIATION IN CHROMOSOME
•NUMBER
Aneuploidy- organism gains or loses one or more
chromosomes but not a complete set.

• monosomy-loss of a single chromosome from an

otherwise diploid genome

• trisomy- gain of one chromosome

• Euploidy-complete haploid sets of chromosomes are

present.

• Polyploidy- more than two sets are present

VARIATION IN CHROMOSOME NUMBER
• Such chromosomal variation originates as a random error
during the production of gametes.

• Nondisjunction- a phenomenon whereby paired homogols

fail to disjoin during segragation.
• process disrupts the normal distribution of chromosomes into
gametes.

• abnormal gametes can form that contain either two

members of the aff ected chromosome or none at all.

• Nondisjunction leads to a variety of aneuploid conditions in

humans and other organisms.
A. MONOSOMY
• loss of one chromosome produces a 2n − 1 complement.

• Although monosomy for the X chromosome occurs in

humans, as we have seen in 45,X Turner syndrome,
monosomy for any of the autosomes is not usually tolerated
in humans or other animals.

• if just one of those genes is represented by a lethal allele,

monosomy unmasks the recessive lethal that is tolerated in
heterozygotes carrying the corresponding wild-type allele,
leading to the death of the organism.
A. MONOSOMY
• haploinsuffi ciency- a phenomenon where a single copy of
recessive gene to due monosomy is insuffi cient to provide
life-sustaining function for the organism.
B. TRISOMY
• an extra chromosome produces somewhat more viable
individuals in both animal and plant species than does the
loss of a chromosome.

• eff ects of trisomy (2n + 1) parallel those of monosomy.

DOWN SYNDROME: TRISOMY 21
• only human autosomal trisomy in which a signifi cant
number of individuals survive longer than a year past birth.

• discovered in 1866 by Langdon Down.

• condition is of the G group and is called Down syndrome or

simply trisomy 21 (designated 47,21+)

• found in approximately 1 infant in every 800 live births.

• approximately 4000–5000 such births annually in the United

States, and there are currently over 250,000 individuals
with Down syndrome.
DOWN SYNDROME: TRISOMY 21
• 12 to 14 such characteristics, with each individual, on
average, expressing 6 to 8 of them.

• outward appearance of these individuals is very similar, and

they bear a striking resemblance to one another.

• prominent epicanthic fold in each eye and the typically fl at

face and round head.

• short and may have a protruding, furrowed tongue (which

causes the mouth to remain partially open) and short, broad
handswith characteristic palm and fi ngerprint patterns
(simian crease).
DOWN SYNDROME: TRISOMY 21
• Physical, psychomotor, and mental development are
retarded, and poor muscle tone

• life expectancy is shortened to an average of about 50

years, individuals are known to survive into their 60s.

• prone to respiratory disease and heart malformations,

• incidence of leukemia approximately 20 times higher than

that of the normal population.

• striking observation is that death in older Down syndrome

adults is frequently due to Alzheimer disease.
DOWN SYNDROME: TRISOMY 21
• Down syndrome individuals have a decreased risk of
developing a number of cancers involving solid tumors,
including lung cancer and melanoma.

• presence of an extra copy of the DSCR1 gene, which

encodes a protein that suppresses vascular endothelial
growth factor (VEGF).

• suppression blocks the process of angiogenesis.

• overexpression of this gene inhibits tumors from forming

proper vascularization, diminishing their growth.
ORIGIN: DOWN SYNDROME
• condition occurs through nondisjunction of chromosome 21
during meiosis.

• Failure of paired homologs to disjoin during either anaphase

I or II may lead to gametes with the n + 1 chromosome
composition.

• About 75% of these errors leading to Down syndrome are

attributed to nondisjunction during the fi rst meiotic division.

• Subsequent fertilization with a normal gamete creates the

trisomic condition.
ORIGIN: DOWN SYNDROME
• ovum is the source in about 95% of 47,21+ trisomy cases.

• frequency is about 1 in 1000 at maternal age 30, a tenfold

increase to a frequency of 1 in 100 is noted at age 40.

• The frequency increases still further to about 1 in 30 at age

45.

• A very alarming statistic is that as the age of childbearing

women exceeds 45, the probability of a Down syndrome
birth continues to increase substantially.
ORIGIN: DOWN SYNDROME
ORIGIN: DOWN SYNDROME
• In spite of this high probability, substantially more than half
of Down syndrome births occur to women younger than 35
years, because the overwhelming proportion of pregnancies
in the general population involve women under that age.
ORIGIN: DOWN SYNDROME
• amniocentesis and chorionic villus sampling (CVS)-
two most familiar approaches in order to obtained amniotic
fl uid or chorion of the placenta.

• newer approach, fetal cells and DNA are derived directly

from the maternal circulation, a technique referred to as
noninvasive prenatal genetic diagnosis (NIPGD).

• karyotype can be determined by cytogenetic analysis. If

the fetus is diagnosed as being aff ected, a therapeutic
abortion is one option currently available to parents.
HUMAN ANEUPLOIDY
• Patau and Edwards
syndromes (47,13+ and
47,18+,)

• individuals manifest severe

malformations and early
lethality.
TRISOMY 18- EDWARDS SYNDROME

• 2nd most common trisomy

• 80% female
• Majority die before birth
• Low survival rate
• Symptoms: small head, malformed
ears, widely spaced eyes, clenched
hands
TRISOMY 13- PATAU SYNDROME
HUMAN ANEUPLOIDY
• aff ected fetuses do not survive to term.

• (1). Approximately 20 percent of all conceptions

terminate in spontaneous abortion (some estimates are
considerably higher)

• (2). about 30 percent of all spontaneously aborted

fetuses demonstrate some form of chromosomal
imbalance.
2. VARIATION OCCURS IN THE
COMPOSITION AND ARRANGEMENT OF
CHROMOSOMES
• Translocation- exchange
and transfers in which the
locations of genes are
altered within the genome.
2. VARIATION OCCURS IN THE
COMPOSITION AND ARRANGEMENT OF
CHROMOSOMES
• structural changes are due to one or more breaks along the
axis of a chromosome, followed by either the loss or
rearrangement of genetic material.

• Chromosomes can break spontaneously, but the rate of

breakage may increase in cells exposed to chemicals or
radiation.

• If the aberration is found in one homolog but not the other,

the individual is said to be heterozygous for the aberration.
3. DELETION IS A MISSING REGION OF A
CHROMOSOME

• Deletion- missing piece of chromosome

• deletion can occur either near one end (terminal) or within the
interior (intercalary) of the chromosome.

• portion of the chromosome that retains the centromere region is

usually maintained when the cell divides, whereas the segment
without the centromere is eventually lost in progeny cells
following mitosis or meiosis.
A. CRI DU CHAT SYNDROME

• results from the deletion of a small terminal portion of

chromosome 5.

• might be considered a case of partial monosomy, but since the

region that is missing is so small, it is better referred to as a
segmental deletion.

• fi rst reported by Jérôme LeJeune in 1963

• described the clinical symptoms, including an eerie cry

similar to the meowing of a cat, after which the syndrome is
named.

• associated with the loss of a small, variable part of the short arm
A. CRI DU CHAT SYNDROME

• incidence of 1 in 25,000–50,000 live births has been estimated.

• Most often, the condition is not inherited but instead results from
the sporadic loss of chromosomal material in gametes.

• portion of the chromosome that is missing contains the TERT

gene, which encodes telomerase reverse transcriptase, an
enzyme essential for the maintenance of telomeres during DNA
replication.
4. DUPLICATION IS A REPEATED SEGMENT OF A
CHROMOSOME
• Duplication- a single locus or a large piece of a chromosome is
present more than once in the genome.

• As in deletions, pairing in heterozygotes can produce a

compensation loop.

• Duplications may arise as the result of unequal crossing over

between synapsed chromosomes during meiosis or through a
replication error prior to meiosis.

• In the former case, both a duplication and a deletion are

produced.
5. TRANSLOCATION ALTER THE LOCATION

• Translocation- is the movement of a chromosomal segment to a

new location in the genome.

• Reciprocal translocation- involves the exchange of segments

between two nonhomologous chromosomes.

• two nonhomologous chromosome arms to come close to each

other so that an exchange is facilitated.
5. TRANSLOCATION ALTER THE LOCATION