Download If there are errors in the gene (bases are missing or out of order

Birth Defects
Resulting From
Single Gene
Defects
Categories of Factors Responsible
for
Birth Defects
Abnormalities of Individual Genes
(Single Gene Defects)
Chromosomal Abnormalities
Intrauterine Injury
Multifactorial Circumstances
How Genetic Errors Cause
Disease
 If there are errors in the gene (bases are
missing or out of order) then the protein
synthesis becomes confused.
 This confusion can result in defective protein
construction.
 The function that was supposed to occur is
halted creating pathology.
Single Gene Disorders
 Over 4,000 have been identified
 Most are recessive
 Examples:
 Recessive-- Sickle Cell Anemia, PKU, Tay
Sachs, Cystic Fibrosis
 Dominant-- Huntington’s Chorea, Marfan’s
Syndrome
 Sex-linked-- Hemophilia, Color Blindness
Recessive Inheritance
Parent Status
Possible Outcomes
One
Heterozygous
n
n
n
nn
nn
d
dn
dn
d
n
n
dn
nn
d
dd
dn
n
n
Both
Heterozygous
One
Homozygous
One Free
d
dn
dn
d
dn
dn
50% Carrier
0 Expression
50% Carrier
25% Expression
100% Carrier
Dominant Inheritance
Parent Status
Possible Outcomes/Dominant
Inheritance
Either Homozygous
n
n
D Dn
Dn All
D Dn
Dn Offspring
One Heterozygous
n
n
n
nn
nn 50% chance
D Dn
Both Heterozygous
n
Dn
n
D
nn
Dn 75% chance
D Dn
DD
Sex Linked Inheritance
Male
Parent
X
Y
Female
Parent
Xn
Xd
XXn
XXd
Female Free
Female
Carrier
XnY
XdY
Male Free
Male Expresses
Categories of Factors Responsible
for
Birth Defects
1.Abnormalities of Individual Genes
(Single Gene Defects)
2.Chromosomal Abnormalities
3.Intrauterine Injury
4.Multifactorial Circumstances
Sickle Cell Anemia
 Occurs when the gene that codes for glutamic
acid codes wrong and instead codes for valine
which doesn’t bind well with O2.
 This causes cells to become sickle shaped
 Sickle shaped cells do not circulate well and
clog capillaries easily
Sickle Cell Anemia
 Epidemiology:
 8% or 1/12 of African Americans carry the gene
 1/400 have sickle cell
 A blood test is available to determine if one carries
the gene
 In utero determination is also available
 An example of co-dominance:
 both alleles are fully expressed in the heterozygous
state
Sickle Cell Anemia Syndrome
1. Anemia- red cells live only 10-20 days as opposed to
120
2. Clotting- loss of blood flow to tissue = pain
3. Infection- due to poor delivery of blood
4. Dactylitis- swelling of hands and feet
5. Physical development- Stunted
6. Lower life expectancy- Males: 42 Females: 48
Sickle Cell Anemia Treatment
 Rest
 Hydration
 Analgesia
 Transfusion therapy
 Prophylactic antibiotics
 Oxygen therapy
Cystic Fibrosis
 Epidemiology:
 Most common lethal genetic disorder in the
Caucasian population.
 Estimates are that 1/25 people may be carriers
 Syndrome:
 Defect alters the way epithelial calls transport
sodium and chloride ions
 Disease targets the lungs and pancreas
Cystic fibrosis Syndrome
 Respiratory insufficiency
 Poor growth
 Malnutrition
 Life expectancy varies from a few years
to the 30’s
Inborn Errors of Metabolism
ENZYMOPATHIES
Precursors
Enzyme
Alternate Route
Product A
Product B
lack of end product
precursor accumulation
secondary product
accumulation
loss of feedback inhibition
PKU (Phenylketonuria)
Secondary Product Accumulation
 Syndrome:
 The body cannot breakdown the protein phenylanine.
 The infant appears healthy the first year then
gradually develops retardation as a result of nervous
system damage caused by excess acid in cells.
 Epidemiology:
 1/14,000 white babies
 1/300,000 black babies
PKU
• Treatment:
 Special diet is available in which foods containing
phenylalanine are removed thus eliminating
secondary product accumulation.
• Prevention:
 A screening test at birth is routine.
 This test has proven to be very cost effective.
 Special diet is available in which foods containing
phenylalanine are removed thus eliminating
secondary product accumulation.
Tay Sachs Disease
 Syndrome:
 Hexosaminidase, the enzyme responsible for lipid
metabolism is absent
 The cells are unable to break down fat
 The build up of lipids (ganglioside) occurs in the
nerve cells
 The child will begin to lose developmental skills at
about six months and deteriorate until death by age
four.
 Prevention:
 Screening for carriers of the gene and screening of
the fetus.
Other In-Born Errors of
Metabolism
1. Albinism- enzyme is missing to produce melanin
2. Familial Hypothyroidism- loss of feedback
inhibition
3. Sex-linked / x-linked inheritancea. Color blindness
b. Hemophilia
Categories of Factors Responsible for
Birth Defects
Abnormalities of Individual Genes
(Single Gene Defects)
Sickle Cell Anemia
Cystic Fibrosis
Phenylketonuria
Tay Sachs Disease
Albinism
Familial Hypothyroidism
Hemophilia