Birth Defects Resulting From Single Gene Defects

Birth Defects Resulting From

Single Gene Defects

Categories of Factors Responsible for

Birth DefectsAbnormalities 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 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 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 InheritanceFemale Parent

Xn Xd

Male X XXnFemale Free

XXdFemaleCarrier

Parent Y XnYMale Free

XdYMale Expresses

Categories of Factors Responsible for

Birth Defects1.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

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 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 Product A

Alternate Route Product B

lack of end productprecursor 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.

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

Categories of Factors Responsible for

Birth DefectsAbnormalities of Individual Genes

(Single Gene Defects)

Sickle Cell AnemiaCystic FibrosisPhenylketonuria

Tay Sachs DiseaseAlbinism

Familial HypothyroidismHemophilia