By

Shveta Jaishankar and Swathi Jain

GCM III year
 INTRODUCTION
• Heredity refers to the passing on of characteristics
• DNA is deoxyribonucleic acid, our hereditary material
• DNA is made up of sugar, phosphate, and 4 nitrogenous
bases: Adenine, Thymine, Guanine and Cytosine
• DNA has to replicate before cell division, because DNA is
found in the nucleus
• Chromosomes are DNA molecules curled around histone
proteins
• Everyone has 46 chromosomes in each of their cells
• A gene is a sequence of DNA that contains instructions to
make proteins
 GENDER
• Humans have 23 pairs of
chromosomes
• Chromosome pairs 1-22
work on the function or
development of body
• Pair 23 determines sex
• Two X chromosomes
means it’s a girl
• A boy has X and Y
chromosomes
X and Y Chromosomes of humans
• Genes accomplish important tasks,
and if there is a malfunction while
DNA replication, a disorder will occur
in the baby developing in the womb
• During cell division, the chromosome
may fail to split and therefore, a
daughter cell will:
o Have an extra chromosome,
OR
o Have a missing chromosome
 Down’s Syndrome
• A disorder caused by an extra
chromosome 21 (trisomy 21)
• Causes severe mental retardation
• Prone to develop Leukemia and
Alzheimer's disese
• Occurs in every 1 out of 800 babies
• Almost half of DS pts will have a
congenital heart defect
• Many babies with DS are rejected
by the body and are therefore
miscarried
• About 92% of women who find out
they are carrying a DS baby will
abort
 SYMPTOMS
•Upward slant to eyes.
•Small ears that fold over at the top.
•Small, flattened nose.
•Small mouth, making tongue appear large.
•Short neck.
•Small hands with short fingers.
•Low muscle tone.
•Single deep crease across center of palm.
•Looseness of joints.
•Small skin folds at the inner corners of the eyes.
•Excessive space between first and second toe.
•.
Kleinfelter’s syndrome
• Disorder occurring due to
nondisjunction of the X chromosome.
• The Sperm containing both X and Y
combines with an egg containing the
X, results in a male child. (XXY)
• Males with some development of
breast tissue normally seen in females.
• Little body hair is present, and such
person are typically tall, have small
testes.
• Infertility results from absent sperm.
• Evidence of mental retardation may or
may not be present.
Klinefelters Syndrome – Trisomy Sex chromosome
(XXY)
 Turners Syndrome
• Monosomy of Sex
chromosome i.e only X is
presnt
• Turner syndrome is
associated with
underdeveloped ovaries,
short stature, webbed, and is
only in women.
• Bull neck, and broad chest.
Individuals are sterile, and
lack expected secondary
sexual characteristics.
• Mental retardation typically
not evident.
Turner’s Syndrome
Tay Sach’s Disease
• Monogenic, autosomal recessive
• Caused by a genetic mutation on the
HEXA gene on chromosome 15
• Harmful quantities of gangliosides
accumulate in the nerve cells of the
brain, eventually leading to the
premature death of those cells
• Central nervous system degrades,
ultimately causing death.
• Symptoms - relentless deterioration of
mental and physical disabilities occurs;
cognitive, motor, speech difficulties,
swallowing difficulties, hypotonia and
spasticity
• Most common among people of Jewish
(Ashkenazic Jews) – eastern Europe
descent.
• Occurs in about 1 for every 3600 births;
 Duchenne Muscular Dystrophy
(DMD)
• Sex linked recessive
• Cause – Mutation in DMD gene – the
longest gene.(Xp21). The DMD gene
codes for the protein dystrophin, an
important structural component
within muscle tissue. Dystrophin
provides structural stability to the
dystroglycan complex (DGC),
located on the cell membrane
• Progressive weakening of muscle
control ( due to lack of protein) ,
psuedohypertrophy, fibrotic tissue
development and loss of
coordination
• Occurs 1 in 3200 male births.
• Females are usually carriers
 Haemophilia
• Hemophilia is the oldest known hereditary
bleeding disorder.
• Caused by a recessive gene on the X
chromosome.
• Caused by the absence of one or more
proteins necessary for normal blood clotting.
Type A is caused by a mutation in the F8
gene which causes a protein called
coagulant factor VIII(8)Type B is caused a
mutation in the F9 gene which causes
another protein called coagulant factor IX(9)
• One can bleed to death with small cuts.
• The severity of hemophilia is related to the
amount of the clotting factor in the blood.
About 70% of hemophilia patients have less
than one percent of the normal amount and,
thus, have severe hemophilia.
• Hemophilia A occurs in about 1 in 5,000–
10,000 male births, while Hemophilia B
occurs at about 1 in about 20,000–34,000
X-linked Inheritance pedigree chart
Huntington’s Disease
• Autosomal Dominant Disease
• An inherited, degenerative brain
disorder which results in an
eventual loss of both mental and
physical control.
• The disease is also known as
Huntington's chorea. Chorea
means "dance-like movements"
• Symptoms - uncoordinated, jerky
body movements and a decline in
some mental abilities;
deterioration of nervous system
• Occurs 1 in 10,000 people
 Phenylketonuria or PKU
• Autosomal recessive disorder
• Caused by a deficiency of an
enzyme which is necessary for
proper metabolism of an amino
acid called phenylalanine.
• Phenylalanine is an essential
amino acid and is found in nearly
all foods which contain protein,
dairy products, nuts, beans, tofu…
etc.
• Requires elimination of
phenylalanine from diet
• Brain damage can result if the diet
is not followed causing mental
retardation and mousy body odor
(phenylacetic acid is in sweat).
• Occurs one in 25000 people
 Cystic Fibrosis
• An Autosomal recessive disorder
• The gene responsible resides on the long
arm of chromosome 7. It encodes a protein
termed cystic fibrosis transmembrane
conductance regulator, CFTR, which acts as
a gate in the cell membrane and regulates
the movement of chloride ions into and out of
the cell. Patients with cystic fibrosis have a
mutated, dysfunctional form of CFTR that
causes the channel to stay closed, and so
chloride ions build up in the cell.
• Excessive mucus production causes lung
infections, and affects other organs; poor
nutrient absorption; chronic bronchitis; foul
stools;bacterial infections
• 1 out of every 2500 people of European
descent; rare in other groups
 Genetic testing and genetic
counseling
• I Prenatal screening /
testing
• II Newborn screening
• III Carrier and other
adult testing
• IV Genetic Counseling
 Prenatal screening/testing

• 1. Ultrasound
• 2. Maternal serum alpha-fetoprotein or
multiple marker screening
• 3. Amniocentesis
• 4. Chorionic villus sampling (cvs)
• 5. Nuchal translucency
 UltraSound
• Obstetric sonography
(ultrasonography) is the
application of medical
ultrasonography to
obstetrics, in which
sonography is used to
visualize the embryo or
foetus in its mother's uterus
(womb). The procedure is
often a standard part of
prenatal care, as it yields a
variety of information
regarding the health of the
Obstetric sonogram of a fetus at 16 weeks. The mother and of the fetus, as
bright white circle center-right is the head, which
faces to the left. Features include the forehead at
well as regarding the
10 o'clock, the left ear toward the center at 7 progress of the pregnancy.
o'clock and the right hand covering the eyes at
9:00.
Maternal serum alpha-fetoprotein
• MSAFP is a screening test that examines
the level of alpha-fetoprotein in the mother's
blood during pregnancy.
• MSAFP may be performed during the 16th
to 18th week
• Alpha- fetoprotein(AFP) is found in both
fetal serum and also amniotic fluid.
• The AFP test is measures high and low
levels of alpha-fetoprotein. The results are
combined with the mother’s age and
ethnicity in order to assess probabilities of
potential genetic disorders.
• High levels of AFP suggestS neural tube
defect such as spina bifida or anencephaly,
defects with the esophagus or a failure of
your baby's abdomen to close.
• Low levels of AFP and abnormal levels of
hCG and estriol may indicate that the
developing baby has Trisomy 21( Down
syndrome), Trisomy 18 (Edwards
Syndrome) or another type of chromosome
abnormality.
Amniocentesis
• Prenatal diagnosis of chromosomal
abnormalities and fetal infections, in
which a small amount of amniotic
fluid, which contains fetal tissues, is
extracted from the amnion or
amniotic sac surrounding a
developing fetus, and the fetal DNA
is examined for genetic
abnormalities.
• Amniocentesis is performed between
the 16th-20th week of pregnancy;
• Possible complications include
infection of the amniotic sac from the
needle, and failure of the puncture to
heal properly, resulting I n leakage or
infection. Serious complications can
result in miscarriage, preterm labor
and delivery, respiratory distress,
postural deformities, fetal trauma and
alloimmunisation (rhesus disease).
risk of amniocentesis-related
miscarriage 1 in 1,600 (0.06)
• One simple drawback is that
administration may be painful.
 Chorionic villus sampling (cvs)
• prenatal diagnosis to determine
chromosomal or genetic disorders in the
fetus. It entails getting a sample of the
chorionic villus (placental tissue) and
testing it.
• CVS can be carried out 10-13 weeks after
the last period, earlier than amniocentesis
(which is carried out as early as 14-16
weeks).
• CVS carries a higher risk of harming the
fetus than amniocentesis (miscarriages
occur in around 1 in 100 to 1 in 200 cases
with CVS, versus around 1 in 1,600 with
amniocentesis).
• a risk of miscarriage, there is a risk of
infection and amniotic fluid leakage. The
resulting amniotic fluid leak can develop
into a condition known as oligohydramnios
which is low amniotic fluid level.
• Additionally, there is a risk of CVS causing
digit-reduction defects in the fetus if
performed before 11 weeks (0.07%-0.10%
 Newborn Screening
• Purpose to find newborns who
will benefit from early diagnosis
and treatment
• historically, the criteria for
inclusion in a newborn
screening program:
1. Preventable damage
2. Frequency in population
3. Appropriate test
4. Needed to recognize disorder
• Mandated by state law
exception allowed for religious
objection
 Screening done for
• Phenylketonuria
• Galactosemia
• Congenital hypothyroidism
• Biotinidase deficiency
• Hemoglobinopathies
• Congenital adrenal hyperplasia
• Hearing
• Disorders detected by tandem mass spectrometry
(example: MCAD)
• Cystic fibrosis
• five lysosomal storage disorders: Pompe, Krabbe,
Niemann-Pick, Gaucher, Fabry (to be implemented)
 Newborn screening--tandem mass
spectrometer tests
Amino acid disorders Organic acid disorders
• pku • 3-methylcrotonyl-CoA carboxylase
• maple syrup urine disease deficiency (3MCC)
• tyrosinemia, types I, II and III • 3-hydroxy-3-methylglutaric-CoA lysase
deficiency (HMG)
Urea cycle disorders • glutaric aciduria types I and II (GAI,
• citrullinemia GAII)
• argininosuccinic aciduria • proprionyl CoA carboxylase deficiency
(IVA)
Fatty acid oxidation disorders • isovaleryl CoA dehydrogenase
• carnitine palmitoyl transferase deficiency deficiency
type II (CPT II) • methylmalonic acidemia (MMA)
• long chain 3-hydroxy-coA dehydrogenase • mitochondrial acetoactyl-CoA thiolase
deficiency (LCHAD) deficiency (b-KT)
• medium chain acyl-CoA dehydrogenase • ethylmalonic adipic aciduria
deficiency (MCAD)
• short chain acyl-CoA dehydrogenase
deficiency (SCAD)
• trifunctional protein deficiency (TFPD)
• very long chain acyl-CoA dehydrogenase
deficiency (VLCAD)
 Carrier screening
for reproductive decisions
• family history: Tay Sachs, cystic
fibrosis, sickle cell disease,
phenylketonuria
population screening in ethnic groups
• Tay Sachs
• sickle cell disease
• cystic fibrosis, spinal muscular
atrophy
for late onset disorders
• Huntington disease
• breast cancer
• hemochromatosis
 Genetic counselling
• possible problem detected
during prenatal testing
• birth of an affected child
• family diagnosis/history of
genetic disorder
• repeated unexplained loss of
pregnancy
• exposure to mutagen
• traditionally nondirective
(contrast with most health care
situations)
• frequently can give estimates
of risk:
– calculated
– empiric data
– test results
Thank You