Genetic diseases

Presenter –
Mrs.Shruthi s
MSc MLT-III sem
 Genetic disease
• An abnormal condition that a person inherits through gene
or chromosomes.
 classification
• 1. Chromosomal disorders
• 2. Single gene disorders:
• 3. Multifactorial inheritance
• 4. mitochondrial disorders
• 5. acquired somatic genetic diseases
 classification
1. Chromosomal disorders:
• abnormality in the number or structure of chromosomes

2. Single gene disorders:

• due to a single mutant gene. # Mendelian disorders

3. Multifactorial inheritance:
• result of interaction of gene and environmental factors
• such as infectious agents, drugs or ionizing radiations, etc.
 SINGLE GENE DISORDERS
Follow one of four patterns of inheritance:
1. Autosomal dominant inheritance.
2. Autosomal recessive inheritance.
3. Sex/X-linked dominant inheritance
4 . X-linked recessive inheritance
Single gene disorders
Autosomal dominant inheritance. – •Achondroplasia
• huntingtons disease
•tuberous sclerosis
•treacher collin’s syndrome
Autosomal recessive inheritance.- cystic fibrosis
Sickle cell disease
Sex/X-linked dominant inheritance - Rare-fragile x syndrome

X-linked recessive inheritance- •Hemophilia

•duchene muscular dystrophy
•colour blindness
• 2.Multifactorial inheritance:

• Alternative term- polygenic inheritance

• Combination of genetic factor and nongenetic

• Ex. congenital malformations

• show multifactorial inheritance Nongenetic factors-
• Ex. cleft lip drugs (anticancer)
• cleft palate, infections(rubella virus),
• club foot, ionizing radiations (X rays)
• congenital dislocation of hip joint,
• CHD
 3.Chromosomal disorders

• structural chromosomal abnormality (change in strucure)

• Numerical chromosomal abnormality ( change in number )

 structural chromosomal abnormality

• The change in structure is called structural chromosomal

abnormality (or aberration)

• Factors responsible mainly –

• Ionizing radiation
• chemical agents,
• viruses
• Structural chromosomal abnormalities

1. Deletion- terminal deletion, interstitial deletion

2. Duplication
Stable
3. Inversion- pricentric, paracentric
4. Translocation- robertsonian T, reciprocal T
5. Insertion
6. Isochromosome
7. Ring chromosome Unstable
 Structural chromosomal abnormalities
• 1. Deletion— In deletion, loss of part of chromosome

• 2 types-
• terminal deletion
• interstitial deletion

EX, retinoblastoma is caused due to deletion of a portion of

chromosome 13.
# Sometimes when two ends of a chromosome are deleted,
they can reattach to form a ring chromosome.
• terminal deletion -involves single break
• and terminal part of xme is lost.
• Ex-cri du chat syndrome

• interstitial deletion -involves 2 break and the intervening

portion of xme is lost
• Also called-prader will syndrome
• wilms tumour with aniridia.
 cri du chat syndrome/5p
• Results from the deletion of short arm of xme 5
• Name- cry of affected baby mimics mewing of a cat.
• Symptoms-
• typical facial appearance,
• microcephaly,
• hypertelorism
• antimangoloid slant of palpebral
• fissures
• Low set ears, microganthia
 Microdeletion syndromes
• In prader will syndrome →There is deletion of 3-4 million base
pairs of xme when this deletion is inherited from father

• Short stature Examples-

• Hypotonia ✓angleman
• Obesity ✓Prader - will
• Small hands and feets ✓Miller- dieker
• hypogonadism
✓Langer -giedion
• Mild-moderate mental retardation
Microdeletion syndromes
• 2. Duplication—

segment of the chromosome gets repeated resulting in a longer

chromosome
• e.g., Charcot-Marie-Tooth disease caused due to duplication of genes
on chromosome 17.
• 3. Inversion—

• In inversion, a segment of the chromosome breaks away, completely

reverses itself and reattaches with the chromosome.
• overall length of the chromosome remains same but the orientation
of genes is reversed by 180 degrees
• For ex-
• RCAD syndrome caused by inversion of a segment of chromosome 17.
Inversion

2 types:
❖pericentric inversion - both the arms p and q are involved
❖paracentric inversion -only one arm either p or q is involved

•
• 4. Translocation—
• In translocation, a segment of a chromosome breaks away
and reattaches itself with another chromosome.

Types-
• reciprocal translocation
• Robertsonian translocation
 translocation-

Robertsonian translocation –
reciprocal translocation-
• If a segment of a chromosome
• mutual exchange of segments breaks away and attaches with
between two chromosomes, it another chromosome, without
is called reciprocal mutual exchange, it is called
translocation. Robertsonian translocation.
• Example: Burkitt’s lymphoma, • This may result in decrease of
chromosome number of the cell
 insertion
• It is a rare non-reciprocal type of
translocation which involves the breaks.
• A fragment is transferred from a
chromosome to a nonhomologous
chromosome.
• Two breaks release the fragment from
one chromosome and one break occurs
in another chromosome to admit this
fragment
 Isochromosome
This involves an abnormal split
along the centromere leading
to a separation of arms.

It is found in some of the Turner

syndrome patients
 Ring chromosome

• It involves two breaks at the

terminal portions of the
chromosome followed by fusion
of the cut ends
• This is found in about one fifth of
the cases of Turner's syndrome
Deletion Duplication Inversion Translocation
 Factors playing role in chromosomal aberration

• 1. Maternal age
• 2. Nondisjunction gene
• 3. Radiation
• 4. Chromosomal abnormality
• 5. Autoimmune disorders
 Factors playing role in chromosomal aberration
• 1. Maternal age:
• Advanced maternal age (>35 years) is one of the significant
factors associated with Down's syndrome.
• It is believed nondisjunction during meiosis this results in trisomy
21 (Down's syndrome).
• # late paternal age in the aetiology of Down's syndrome.

• 2. Nondisjunction gene:
• Nondisjunction gene- occurs in other organisms.
• It may be responsible for nondisjunction in man too.
 3. Radiation:
• studies have indicated that radiation certainly increases
frequency of Down's syndrome
4. Chromosomal abnormality:
• A balanced translocation in Parents may result in an
offspring with chromosomal aberration.
5. Autoimmune disorders:
• believed that there exists a correlation between them.
• An association of high titre of thyroid autoantibody in
mothers and Down's syndrome in their children indicates the
role of autoimmune disease in nondisjunction
 Numerical chromosome aberration
• the change in number chromosome is called numerical
chromosomal abnormalities

• #due to environmental radiation, food intake or internal

genetic conditions →damage or may change in numbers.

• Ploidy- change in no. of xme

• Euploidy→ exact no. of haploid xme (23 pairs)
I. Diplody→ 2n
II. Polyploidy→ >2sets of xme
(triploidy/tetraploidy/pntaploidy/hexaploids)
aneuploidy → loss or + of or more xme to complete set of
xme
1.Hypoploidy→ fewer
ex.monosomy– loss of xme from whole set of xme
Nullisomy- loss of xmepair from whole set of xme (2n-2)
2.hyperploidy→1 or more greater no. of xme than normal
Euploidy→condition xme Aneuploidy → loss or + of 1 or more xme
number is an exact multiple to complete set of xme
of haploid number
a)Diplody- 2n a).Hypoploidy→ fewer
b)Polyploidy→ >2sets of xme ex.1)monosomy– loss of 1 xme from
•triploidy whole set of xme
•Tetraploidy
•Pentaploidy 2)Nullisomy- loss of xme pair from whole
•hexaploids set of xme (2n-2)

b.hyperploidy→1 or more greater no. of

xme than normal
Trisomy-gain of 1 chromosome
 Aneuploidy
Autosomal abnormality Sex chromosome abnormality

• Ex.
• Ex
• Turners
• downs – trisomy 21
• Klinefelters
• Edward- trisomy 18 • Polysomy x
• patau – trisomy 13
 1. Down's Syndrome
• Incidence: Occurs in approx.1 per 800 live births.
• It was first identified by Langdon Down in 1866.
• Risk group- increases with the maternal age.
• >85% Down syndrome babies are born in mothers over 35
years of age, at the time of pregnancy
• Chromosomal basis:
• Down syndrome is a genetic condition that arises due to
presence of an extra chromosome 21.('G' group.)
• Here, chromosome 21 is repeated thrice (trisomy 21),
• (twice in a normal individual)
• It was designed as chromosome 21, a small acrocentric
chromosome.
• The karyotype of Down syndrome is represented as
• 47, XX,+21 (females)
• 47, XY, +21 (males)
Downs syndrome
Clinical symptoms:
• Predominant feature- mental
retardation
• flat face, slanting eye
• small mouth, protruding tongue,
flattened nose, short neck,
• short arms and legs,
• single deep crease across the palm,
• low IQ, stunted growth,
• muscular hypotonia,
• under developed gonads.
 single deep crease across palm

#Down's syndrome babies also show

breathing, heart or hearing problems.
• Mosaic down-
• 2%, mixture of cells /Combination
Milder phenotype
• They have some of their cells have 3
copies of xme 21,but other cells
• have typical 2copies of xme.

• Partial trisomy-
• very rare
• Part of long arm fragment of xme 21 is present in triplicate.
 Diagnosis and Treatment:
• diagnosed →an extra chromosome 21 in the karyotype.
• treatment - There is no single standard treatment protocol
for Down syndrome.
• Treatments are tailored on specific set of conditions presented
by these individuals.
• At early age, children – benefit--speech therapy,
physiotherapy and taking nutritional supplements.
• # earlier used to live until age 9.
# advances in diagnostic and treatment technologies,
• increased up to 60 and even longer
 Klinefelter's syndrome
Incidence: Occurs in approximately 1 out of 1000 new born
males.
• Chromosomal basis:
• Genotype: 47, XXY.
• Affects males.

• The extra chromosome is not transmitted genetically

• (i.e a Klinefelter newborn cannot have a Klinefelter father)
• .
but arises from inability of X
chromosome to detach itself
from the pair during meiosis
(at the time of gamete
formation).

Fertilisation of an XX ova with a

Y sperm produces an XXY zygote
 Klinefelter's syndrome
• Clinical Symptoms:
• unusually tall for their age
• reduced facial and body hair
• smaller testes
• enlarged breasts and
• coarse voice
 Diagnosis
• One of the most frequent methods to diagnose Klinefelter
syndrome is→through Barrbody test of buccal smear.

• Normaly→ no Barr body appears in the male buccal smear.

• in Klinefelter→ one Barr body shows up
• indicating the presence of an extra X chromosome.
 Treatment- klinefelter syndrome
• At the time of birth, babies with Klinefelter differ a little with
other normal babies.
• differences become noticeable, especially at the time
of puberty.
• People with Klinefelter's syndromes are often treated with
testosterone to look masculine.
• They also need to be psychologically counselled to control
depression
 Turner's Syndrome - 45, X.
• Incidence: Occurs in 1 in 2,500 newborn girls, frequently
• observed in miscarriages and still births.
• Chromosomal basis:
• Affects females
• arises due to the missing X xme.
• This is called monosomy X
• karyotype : 45, X
A cell division error during
meiosis of an ovum →
ovum with no X chrme
with two X chromosomes.
turner

(ovum) no X xme + (sperm) one X

xme → 45, X condition
klinefelter
Mothers →cannot pass the condition to their daughters i.e., this
condition is not inherited.
 Turner syndrome
• Clinical symptoms:
• short stature
• webbed neck (i.e., the neck skin is unusually loose and can be pulled several centimetres of the neck)
• small breasts, low set ears (i.e., ears are placed below the normal position),
• swollen hands and feet
• ovaries are under developed
• menstrual periods are usually absent
Diagnosis and treatment: -turners syndrome
• Prenatal chromosomal
• → amniocentesis or chorionic villus sampling.
• →Barr body of buccal smear.
• The absence of Barr body is the first indicator to follow up the
condition with a detailed investigation.
• Treatment→no permanent cure.
• growth and ovarian functions can be strengthened by the
controlled administration of hormones androgen and estrogen.
 Trisomy18 - edward syndrome

• It was described by Edwards in 1960.

• It is also called E-trisomy.
• It is the second most common
autosomal trisomy
• 1 in 6000 live births.
• About 95% of the fetuses abort, only
5% of trisomy 18 conceptions survive
to term.
 Trisomy 18-Cytogenetics
About 95% of babies with Edward syndrome →trisomy 18.
A small percentage show mosaicism.
 Symptoms- edward
syndrome
• Patients present with hypertonia
• prominent occiput, receding jaw
• low set malformed ears.
• Ears may be small
• with unraveled helices
• mouth is small.
• short sternum, clenched fists
• and rocker-bottom feet.
• Congenital heart defects
 Patau
syndrome/trisomy 13
Trisomy 13 / D trisomy / Patau syndrome
• first identified by Patau
• The life span = trisomy 18.
• About 95% of the live born babies die
during infancy.
• Those who survive childhood show
significant growth retardation
severe mental retardation.
• Cytogenetics
• Nearly 80% of the trisomy 13
patients show an extra
chromosome 13
• The risk -- increases with the
advanced maternal age
• About 95% of the trisomy 13
conceptions end up in
spontaneous abortions
 Patau syndrome-Clinical features
• sloping forehead
• hypertelorism, microphthalmia,
• coloboma iridis and postaxial
polydactyly.
• Cleft lip, cleft palate , Facial cleft
• Congenital malformations --
cardiovascular system and urogenital
system
• central nervous system malformation
• Cutis aplasia ( a scalp defect)
 Polysomy X
• It may be in the form XXX, XXXX or XXXXX karyotype.
• Trisomy X presents with a female phenotype which is almost
a normal one.
• detected on examination/investigation for infertility and
mental retardation
• Somatic cells show two chromatin bodies.
• Among other polysomies, ie. patients with four or five X
chromosomes, patients develop severe mental retardation
and have multiple physical defects
 Diagnosis of genetic disorders
• Amniocentesis
• Amniotic fluid is collected
• Fluid containing cells analysed in karyotype
• Karotypes
• A picture of all chromosome in a cell
• Chromsomes arranged in pairs
• Look for correct number and shape
• Genetic councelling
• If they have a history of genetic disorders in their family
• Genetic councellor use karyotype,
• pedigree charts
• ,punnet squares
• to determine a couples chances of having a child with certain
genetic disorders
• FISH
• Markers
• Protein truncation test
• linkage testing
• Non DNA based
• Protein analysis
• enzyme assay
• Reference
• Thompson and thompson
• S D Gangane
• internet