3. 13.1 Counseling for
chromosomal disorders
• Genetic counseling – potential parents are
advised on their risk of inherited disorders.
• Counselor helps couple understand the mode
of inheritance, medical consequences of
disorder and decisions they might wish to
make.
• Karyotyping – visual display of chromosomes
arranged by size, shape and banding pattern
• Can be from white blood cells or fetal cells by
amniocentesis or chorionic villus sampling
7. •Chorionic villus sampling
Chorionic cells from where placenta will develop
As early as 5th week of pregnancy
Greater risk (0.8%) but earlier results
9. • Chromosomal mutations
Karyotype reveals changes in chromosome
number and differences in structure.
In humans only a few variations in number are
typically seen.
• Down syndrome, Turner syndrome, Klinefelter
syndrome
Changes in chromosome structure more
common
• Due to breakage and failure to reunite properly
• Results in deletion, duplication, translocation or
inversion
10. • Deletion
When a single break causes a chromosome to lose
an end or 2 breaks result in the loss of an internal
segment
Williams syndrome – chromosome 17 loses a tiny end
piece.
Cri du chat – chromosome 5 loses an end piece.
13. • Duplication
Chromosome segment repeated
Individual has more than 2 alleles for certain
traits.
Inv dup 15 syndrome – inverted duplication of
chromosome 15
• Inversion – segment joins in direction opposite
from normal.
15. • Translocation
Exchange of chromosome segments between
nonhomologous chromosomes
A person with both the involved chromosomes
has a normal amount of genetic material and
is healthy unless the exchange disrupts a
gene.
5% of Down syndrome cases caused by a
translocation in previous generation between
chromosome 21 and 14
• Not related to parental age but is inherited
16. • Alagille syndrome
Translocation between chromosome 2 and 20
Normal amount of genetic material but distinctive
face, some abnormalities and severe itching
Translocation disrupted allele on chromosome
20
Father did not realize he had the syndrome until
he had this child.
18. • Inversion
Segment of a chromosome is turned 180°
Reverse sequence of alleles can lead to
altered gene activity if it disrupts control of
gene expression.
Usually do not cause problems
During meiosis, crossing-over can lead to
recombinant chromosomes.
• Alignment only possible when inverted
chromosome forms a loop
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21. 13.2 Counseling for
Genetic Disorders
• Even if no chromosomal abnormality is
likely, amniocentesis might still be done to
perform biochemical tests for over 400
different disorders caused by specific
genes.
• Counselor needs to know medical history
of family to construct a pedigree
• Determines what tests are warranted
22. • Pedigree
Chart of a family’s history with regard to a
particular genetic trait
• Males are squares
• Females are circles
• Shading represents individuals expressing
disorder.
• Horizontal line between circle and square is a
union.
• Vertical line down represents children of that
union.
Counselor may already know pattern of
inheritance and then can predict chance that
child born to a couple would have the
abnormal phenotype.
23. • Pedigrees for autosomal disorders
Autosomal recessive disorder
• Child can be affected when neither parent is
affected
• Heterozygous parents are carriers
• Parents can be tested before having children
25. Autosomal dominant disorder
•Child can be unaffected even when parents
are heterozygous and therefore affected.
•When both parents are unaffected, none of
their children will have the condition.
No dominant gene to pass on
27. • Pedigree for sex-linked disorder
X-linked recessive disorder
• Sons inherit trait from mother – son’s X comes from
mother.
• More males than females have disorder – allele on X is
always expressed in males.
• Females who have the condition inherited the mutant
allele from both their mother and their father.
• Conditions appear to pass from grandfather to
grandson.
29. X-linked dominant
• Only a few traits
• Daughters of affected males have the condition.
• Affected females can pass condition to daughters
and sons.
Depends on which X inherited from a carrier mother if
father is normal
Y chromosome
• Only a few disorders
• Present only in males and are passed to all sons
but not daughters
35. X-linked recessive disorders
• Color blindness
About 8% of Caucasian men have red-green color
blindness.
• Duchenne muscular dystrophy
Absence of protein dystrophin causes wasting away of
muscles.
Therapy – immature muscle cells injected into muscles
37. • Testing for genetic disorders
Testing for a protein
• Some disorders caused by a missing enzyme
Test for quantity of enzyme produced
Testing the DNA
• Genetic marker – relies on an abnormality in the
DNA sequence due to presence of abnormal allele.
Fragments from restriction digest will differ from a normal
person’s results.
39. • Genetic profiling
Individual’s complete genotype
DNA sample applied to DNA chip
DNA chip contains probes – single-stranded
DNA that binds to complementary DNA from
patient
Binding shows patient has particular
mutated genes
43. Testing the embryo and egg
• Testing egg – meiosis results in single egg and 2
polar bodies.
• Polar bodies can be used in genetic testing.
• If a woman is a heterozygote, when the polar body
has the defective allele, the egg must be normal.
45. 13.3 Gene Therapy
• Insertion of genetic material into human
cells for treatment of a disorder
• 2 methods
Ex vivo – outside the body
In vivo – inside the body
46. • Ex vivo
Treatment of SCIDS
• Severe combined immunodeficiency
• Lack enzyme involved in maturation of cells
producing antibodies
• Bone marrow are stem cells removed and infected
with RNA retrovirus carrying gene for normal
enzyme.
• Cells are then retuned to patient.
Treatment of familial hypercholesterolemia
• High levels of cholesterol lead to early fatal heart
attacks.
• Small portion of liver is removed and infected with
retrovirus containing normal cholesterol receptor.
• Tissue is returned to patient.
51. • In vivo
Cystic fibrosis treatment
• Gene needed is sprayed into the nose or delivered
to lower respiratory tract.
• Use adenoviruses or liposomes to carry gene
Poor coronary circulation treatment
• Vascular endothelial growth factor can cause
growth of new blood vessels.
• Genes coding for growth factor can be injected
alone, or within a virus, into the heart to stimulate
branching of coronary arteries.
Rheumatoid arthritis
• Immune system destroys person’s own body.
• Inject adenoviruses that contain anti-inflammatory
genes into the affected joint
