birth defects resulting from single gene defects
TRANSCRIPT
Birth Defects Resulting From
Single Gene Defects
Birth Defects Resulting From
Single Gene Defects
Categories of Factors Responsible for
Birth 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
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.
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 FibrosisDominant-- Huntington’s Chorea,
Marfan’s SyndromeSex-linked-- Hemophilia, Color Blindness
Over 4,000 have been identified Most are recessive
Examples:Recessive-- Sickle Cell Anemia, PKU, Tay
Sachs, Cystic FibrosisDominant-- Huntington’s Chorea,
Marfan’s SyndromeSex-linked-- Hemophilia, Color Blindness
Parent StatusParent Status Possible OutcomesPossible Outcomes
Recessive InheritanceRecessive Inheritance
One Heterozygous
n n
n nn nn
d dn dn
50% Carrier
0 Expression
Both Heterozygous
d n
n dn nn
d dd dn
50% Carrier
25% Expression
One Homozygous
One Free
n n
d dn dn
d dn dn
100% Carrier
Dominant InheritanceDominant InheritanceParent 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 Dn
Both Heterozygous n D
n nn Dn 75% chance
D Dn DD
Sex Linked InheritanceSex Linked InheritanceFemale Parent
Xn Xd
Male X XXnFemale Free
XXdFemaleCarrier
Parent Y XnYMale Free
XdYMale Expresses
Categories of Factors Responsible for
Birth Defects
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 AnemiaSickle 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
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
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
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 Syndrome
Sickle Cell Anemia Syndrome
Sickle Cell Anemia Treatment
Sickle Cell Anemia Treatment
Rest Hydration Analgesia Transfusion therapy Prophylactic antibiotics Oxygen therapy
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
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 SyndromeCystic fibrosis Syndrome
Respiratory insufficiency Poor growth Malnutrition Life expectancy varies from a few
years to the 30’s
Respiratory insufficiency Poor growth Malnutrition Life expectancy varies from a few
years to the 30’s
Inborn Errors of Metabolism
ENZYMOPATHIES
Precursors Enzyme Product A
Alternate Route 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
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.
• 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.
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.
1. Albinism- enzyme is missing to produce melanin
2. Familial Hypothyroidism- loss of feedback
inhibition
3. Sex-linked / x-linked inheritance-
a. Color blindness
b. Hemophilia
Other In-Born Errors of Metabolism
Other In-Born Errors of Metabolism
Categories of Factors Responsible for
Birth Defects
Categories of Factors Responsible for
Birth DefectsAbnormalities of Individual Genes
(Single Gene Defects)
Sickle Cell AnemiaCystic FibrosisPhenylketonuria
Tay Sachs DiseaseAlbinism
Familial HypothyroidismHemophilia