Chromosomal disorders

Prof Vandana Rai

Department of Biotechnology
VBS Purvanchal University
Jaunpur
• Chromosomal disorders include all conditions associated with visible
changes of the chromosomes .

• About 20% of all conceptions have a chromosomal disorders ,but most of

these are spontaneously aborted so that birth frequency is 0.6%.

• Amongst early spontaneous abortions the frequency of chromosomal

disorders is 60%,whereas in late spontaneous abortions and still births the
frequency is 5%.

Triploid fetuses may survive to term, but the majority aborts/still birth.
The commonest chromosomal disorders seen in newborns are balanced and
unbalanced translocations, deletions, duplications, trisomies 21, 18 and 13, sex
trisomies and monosomy etc.

Not all of these chromosomal changes are associated with disease ,but in
general autosoaml abnormalities tend to be more severe than sex chromosomal
abnormalities, and deletions tends to be more severe than duplications.

The failure of chromosome to segregate properly during meiosis I and meiosis II

can result in gametes with an extra chromosome or the loss of a whole single
chromosome .

Usually result from nondisjunction, chromosomes line pair up properly but fail
to segregate.

Less common causes are premature separation of paired chromosomes and

normal meiotic segregation in a trisomy parent.
In meiosis, the parent cell is meant to split, and give one of each chromosome to
each reproductive cell, when non-disjunction occurs, both copies of a chromosome
end up in the same reproductive cell, which then combines with the single
chromosome of the other parents cell during fertilization, leading to a trisomy.
 Down syndrome
• Trisomy 21, have 3 copies of chromosome 21

• Can be male or female

• Physically and intellectually challenged

• Incidence is 1 in 800-1000 births

• Most common non-lethal trisomy

• 95% due to maternal nondisjunction

• Remaining 5% result from mosaicism or translocation

• In the majority of cases, the egg passes on the extra chromosome. But
there are some cases where the sperm passes on the extra chromosome.

• Affected children have marked hypotonia, tongue protrusion, small head,

flattened occiput, flat nasal bridge, epicanthal folds with up-slanting,
palpebral fissures, loose skin around neck, short, stubby fingers, single
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 Down syndrome
• Narrow eye openings

• Up-slanting eyes

• Arched eyebrows

• Arched palate (cleft)

• Flat nose bridge

• Bow shaped mouth

• Small, low set ears

• Short neck

• Sloping shoulders

• Associated defects include heart defects (endocardial cushion), GI atresias,

leukemia and thyroid disease
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 Patau Syndrome
Trisomy 13
• Cleft lip and palate
• Extra fingers & toes
– polydactylism
• Defects
– Heart
– Brain
– Kidneys [Link]
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• Most abort
• Live span < 1 month

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 Patau Syndrome

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 Edward Syndrome
Trisomy 18

• Heart defects
• Displaced liver
• Low-set ears
• Abnormal hands
• Severe retardation
• 98% abort
• Lifespan < 1 year
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 Turner syndrome
Also called XO, because people with Turner’s have only 1 X chromosome: 45,
X.

No Y means Turner’s people are female. However, no ovaries develop, so

they don’t undergo the body changes of puberty and they are sterile.

Hormone treatment cures all but the sterility.

Other symptoms: short stature, webbed skin and low hairline at the neck,
some oddities of spatial perception. Not retarded.

Hypogonandism with female phenotype, short body, webbing of neck, heart

anomalies, infertility, amenorrhea, pigmented nevi, peripheral
lymphedema at birth.
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 Klinefelter Syndrome

Non-disjunction can also result in a person with 2 X’s and a Y: 47,XXY. This is
called Klinefelter Syndrome.

The Y chromosome makes a person withKlinefelter’s male: possessing

testes.

Often not diagnosed, or diagnosed only accidentally.

Most symptoms are helped by testosterone treatment.

Symptoms: female body hair pattern, breast development, sterile, can be

some developmental delay or retardation, especially for verbal skills.

Breast development

Small testes
 Other Sex Chromosome Number Variations

Triplo-X, having 3 X chromosomes. No Y chromosome means female. Many

with this syndrome are undiagnosed because they have no symptoms. Some
have slight social and developmental problems, especially language-related.
Occasional fertility problems, but many have normal fertility. Not well
studied.

Typically, females have two XX chromosomes that define sex. in trisomy X, the
additional X chromosome brings the total number of chromosomes to 47.
This chromosomal abnormality is rare, occurring in approximately 1 in every
1,000 female births.

Other concurring minor conditions displayed by females with trisomy X include

congenital heart disease, clinodactyly, and epicanthal folds. Facial
dysmorphism, strabismus, genitourinary malformation, and minor hand and
 Disorders from changes in chromosomal structure

(i)Deletion

(ii)Duplication

(iii)Translocation

(iv)Inversion

Even though there is no gain or loss of genetic material in translocation

and inversion, the change in location of a segment may alter the
regulation of a gene in the segment.
 Deletion
Deletion was the first structural aberration detected by Bridges in 1917 from
his genetic studies on X chromosome of Drosophila.

An event in which a piece of chromosome is missed or deleted.

Can remove one or more genes from chromosome.

Mostly occur during meiosis due to misalignment or mismatching during

paring of homologous chromosomes

Deletions can occur in autosomes or sex chromosomes

Deletion may occurs due to

(a) Losses from translocation

Types of deletion
deletion--
Terminal Deletion In this case loss of a terminal segment occurs, with a
single break in the chromosomes

Intercalary Deletion In this case, internal part of a chromosome is

missing.

In human genome deletion mutation cause:

Granulocytic leukemia

Cri-du-chat syndrome
 Cri du chat syndrome
Cri du chat syndrome is the deletion of 5p (short arm).

Features include high pitched cat like cry, sever mental retardation,
hypotonia, and growth restriction
 Duplication

• Duplication is the doubling or repetition of chromosome segment during

chromosome duplication.
• As a result of it, a set of genes gets doubled or repeated.
• The extra set of genes is generally called “repeat”.
• Duplication was first detected by Bridges in 1919 from his genetic studies
on X chromosome of Drosophila.
 Translocation

Two pieces of different chromosomes are interchanged.

A portion of one chromosome is transferred to another chromosome

Types of Translocation
(i) Intrachromosomal translocation

Change in position of a segment within a chromosome, either from one arm

to the other or from one location to another in the same arm.

a. Intraradial

Translocationfrom one location to another in the same arm

b. Extraradial

Translocationfrom one arm to the other

(ii) Interchromosomal Translocation

Translocation Transferof a segment from one chromosome to other

a. Transpositional translocation
Effects of translocation
Cause diseases in human such as cancer and infertility.
It may causes changes in chromosomes & also in gene combinations,
promoting variation, speciation, & evolution.
A good example is the translocation between chromosomes 9 and 22,
creating the“Philadelphia chromosome”.
This causes about 90% of the cases of chronic myelogenous leukemia.
Burkitt’s lymphoma is another example of a cancer which is usually (90%)
caused by a translocation (8 and 14)
 Inversion
Occurs when two breaks happen in the same chromosome.

No genetic material is lost but the rearrangement may alter gene function.

Paracentric inversions occur when the break is in one arm and the centromere is
not included.

The carrier can either have a normal gamete or gametes that are extremely
abnormal and fertilization can not occur.

Paracentric inversion carriers have a high risk of infertility but a low risk of
abnormal off spring

Segment is turned 180 degrees

Leads to altered gene activity

Effects of inversion
• Helps to retain the original gene combination by reducing the crossing
over frequency.

• Inversion enhances the position effect & there by produces phenotypic

changes.

• Inversion causes chromosome polymorphism with in a population leading

to karyotype evolution.

• Inversion produces balanced gene complexes(super genes) through

reduction of crossing over, which in turn confers greater biological fitness
and adaptability & increases the evolutionary potentiality