Chromosomes are the structures that
hold our genes
 Genes are the individual instructions
that tell our bodies how to develop
and function
They govern our physical and medical
characteristics, such as hair color,
blood type and susceptability to
disease.
 Each chromosome has a p and q arm;
p is the shorter arm and q is the
longer arm.
 The arms are separated by a pinched
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The typical number of
chromosomes in a human cell is
46 - two pairs of 22 + XX/XY
Holding an estimated 30,000 to
35,000 genes.
One set of 23 chromosomes is
inherited from the biological
mother (from the egg), and the
other set is inherited from the
biological father (from the
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with a microscope , then Stainning
The chromosomes look like strings
with light and dark "bands"
A picture, or chromosome map, of
all 46 chromosomes is called a
karyotype
The karyotype can help identify
chromosome abnormalities that are
evident in either the structure or
the number of chromosomes.
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The pairs have been numbered from 1 to 22,
with the 23rd pair labeled "X" and "Y."
In addition, each chromosome arm is defined
further by numbering the bands that appear
after staining
The higher the number, the further that area
is from the centromere.
The first 22 pairs of chromosomes are called
"autosomes"
Final pair is called the "sex chromosomes."
The sex chromosomes an individual has
determines that person's gender; females
have two X chromosomes (XX), and males
have an X and a Y chromosome (XY).
Karyotype 46), Xy)
Meiosis
Mitosis
Maternal Age
Environment
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Chromosome abnormalities :
happen as a result of an error in cell
division. “Meiosis” is the name used to
describe the cell division that the egg and
sperm go through when they are
developing.
Normally, meiosis causes a halving of
chromosome material, so that each parent
gives 23 chromosomes to a pregnancy
Meiosis
Meiosis
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Abnormality of
chromosome number or
structure:
◦Numerical Abnormalities
◦Structural Abnormalities
When an individual is missing
either a chromosome from a
pair (monosomy) or has more
than two chromosomes of a
pair (trisomy).
 An example: Down Syndrome,
also known as Trisomy 21 (an
individual with Down Syndrome
has three copies of
chromosome 21, rather than
two).
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 Kleinfelter
Syndrome is an
example of trisomy the
individual is born with
three sex chromosome,
XXY.
 Turner Syndrome is an
example of monosomy the
individual is born with only
one sex chromosome, an X.
Down
Syndrome
(Trisomy 21(
Down Syndrome (Trisomy 21(
Trisomy 2(
critical region:
A
region on the long (q) arm of
chromosome 21
 Down syndrome causes mental
retardation
 a characteristic facial
appearance
 multiple malformations
 Associated
with a major risk for
heart malformations
 a small but still significant risk
of acute leukemia
 3 copies of chromosome number
21
 incidence
of 1 in 660 and is by far
the most common chromosomal
abnormality Slight flattening of
the face
 A low bridge of the nose (lower
than the usually flat nasal bridge
of the normal newborn)
 An epicanthal fold (a fold of skin
over top of the inner corner of
the eye, which can also be seen
less frequently in normal babies)
 A ring of tiny harmless white
spots around the iris
 mental retardation
 The
risk of trisomy 21 is
directly related to maternal age
 Patients who will be 35 years or
older on their due date should
be offered chorionic villus
sampling or second-trimester
amniocentesis
 Women
younger than 35 years
should be offered maternal serum
screening at 16 to 18 weeks of
gestation
 The maternal serum markers used
to screen for trisomy 21 are
alpha-fetoprotein, unconjugated
estriol and human chorionic
gonadotropin
 The
use of ultrasound to
estimate gestational age
improves the sensitivity
and specificity of maternal
serum screening. (Am Fam
Physician
2000;62:825-32,837-8.)
 Trisomy
21 is present in 95
percent of persons with Down
syndrome.
 Mosaicism, a mixture of normal
diploid and trisomy 21 cells,
occurs in 2 percent.
 The
remaining 3 percent
have a Robertsonian
translocation in which all or
part of an extra chromosome
21 is fused with another
chromosome.
 The
reciprocal transfer of
the long arms of two of the
acrocentric chromosomes:
13, 14, 15, 21 or 22
 On rare occasions, other
non-acrocentric
chromosomes undergo
Robertsonian translocation
a
reciprocal transfer of the whole
long or short arms close to the
centromere
 A relatively common
Robertsonian translocation is
between chromosome 14 and
chromosome 21
 In meiosis, a trivalent is formed .
Robertsonian
translocation
TRANSLOCATIONS
Balanced reciprocal
translocation
Balanced reciprocal translocation
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Dysmorphic sign
(%)
Frequency
Flat facial profile
Poor Moro reflex
Hypotonia
Hyperflexibility of large joints
Loose skin on back of neck
Slanted palpebral fissures
90
85
80
80
80
80
Dysmorphic sign
Frequency (%)
Dysmorphic pelvis on radiograph 70
Small round ears
60
Hypoplasia of small finger,
middle phalanx
60
Single palmar crease
45
 Persons
with Down syndrome
usually have mild to moderate
mental retardation
 School-aged children with Down
syndrome often have difficulty
with language, communication
 Adults with Down syndrome
have a high prevalence of early
Alzheimer's disease
Mental retardation
>95
Growth retardation
>95
Early Alzheimer's disease
75%
by age 60
Congenital heart defects
(atrioventricular canal defect,
ventricular septal defect, atrial septal
defect
40
Hearing loss
40 to 75
Ophthalmic disorders
(congenital cataracts,
glaucoma(
60
Epilepsy
5 to 10
Gastrointestinal malformations
(duodenal atresia,
Hirschsprung disease)
5
Hypothyroidism
5
Leukemia
5
Increased susceptibility to
infection (pneumonia, otitis
media, sinusitis, pharyngitis(
1-6
Infertility
>99% in men
anovulation in
30% of women
Estimated risk of Down
syndrome according to maternal
age
 1/1,300
for a 25-year-old
woman;
 at age 35, the risk increases
to 1/365
 At age 45, the risk of a
having a child with Down
syndrome increases to 1/30
 If
all pregnant women 35 years or
older chose to have amniocentesis
 about
30 percent of trisomy 21
pregnancies would be detected
 Women
younger than 35 years give
birth to about 70 percent of infants
with Down syndrome
 Maternal
serum screening
(multiple-marker screening)
can allow the detection of
trisomy 21 pregnancies in
women in this younger age
group.
 Alpha-fetoprotein
(AFP)
 unconjugated estriol
 human chorionic gonadotropin
(hCG)
 the serum markers most widely
used to screen for Down syndrome
 AFP
is produced in the yolk sac and
fetal liver.
 Unconjugated estriol and hCG are
produced by the placenta.
 The maternal serum levels of each of
these proteins and of steroid
hormones vary with the gestational
age of the pregnancy.
 With
trisomy 21,
second-trimester maternal
serum levels of AFP and
unconjugated estriol are about
25 percent lower than normal
levels
 maternal serum hCG is
approximately two times higher
than the normal hCG level
 The
triple test can detect
approximately 60 percent of the
pregnancies affected by trisomy
21, with a false-positive rate of
about 5 percent.
 In
women older than 35
years, the triple test fails to
detect 10 to 15 percent of
pregnancies affected by
trisomy 21.
If a patient has had a trisomy 21
pregnancy in the past, the risk
of recurrence in a subsequent
pregnancy increases to
approximately 1-3
percent above the baseline risk
determined by maternal age
 Diagnosis
of a
chromosome-21
translocation in the fetus or
newborn is an indication for
karyotype analysis of both
parents
 If both parents have normal
karyotypes, the recurrence
risk is 2 to 3 percent
Chorionic villus sampling
10 to 12 weeks
0.5 to 1.5
%
Early amniocentesis
12 to 15 weeks 1.0 to 2.0 %
Second-trimester amniocentesis
15 to 20 weeks 0.5 to 1.0 %
 Women
who will be 35 years or
older on their due date should
be offered chorionic villus
sampling or second-trimester
amniocentesis.
 Women younger than 35 years
should be offered maternal
serum screening at 15 to 18
weeks' gestation.
 During
the first trimester of the
majority of pregnancies, it is
possible to measure the size of
the fluid area at the back of the
fetus’s neck, known as the
nuchal translucency or NT The
increasing size of the NT
indicates a greater risk of the
fetus having Down’s syndrome.
Ultrasound
Fluorescent In Situ Hybridisation
techniques
•
chromosomes
13 (green),
and 21 (red)

chromosomes 18
(aqua), X
(green), and Y
(red).
2:1 ratio (Down's
Syndrome)
1:1 ratio (normal fetus)
Trisomy 18, 47 Ch.
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incidence of about 1 in 3,000
There is a 3:1 preponderance of females
to males
Thirty percent of affected newborns die
within the first month
50% by two months
and 90% by one year.
severe mental retardation
microcephaly
overlapping fingers, and rocker bottom
feet
Neurologically they are hypertonic
Other common malformations include
congenital heart, kidney, ....
abnormalities.
Trisomy 18, 47 Ch.
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has an incidence of 1 in 5,000
Forty-four percent of affected newborns
succumb in the first month of life
and 69% by six months
Only 18% of the babies born with trisomy
13 survive the first year
microcephaly
microophthalmia (small eyes)
cleft lip or cleft palate
polydactyly (extra fingers)
congenital heart defects
urogenital defects
brain malformations
severe to profound mental retardation.
Turner Syndrome ( 45,
X)
45, X
Turner
Syndrome (45,
X)
• Only females
• One X chromosome
• Or has two X chromosomes but
one is damaged
• Short stature
• Delayed growth of the skeleton
• Sometimes heart abnormalities
• Usually infertile due to ovarian
failure
• Diagnosis is by blood test
(karyotype)
• 1 out of every 2,500 female live
births worldwide
Kleinefelter
XXY
Kleinefelter/47XXY