Chapter 6 - Genetic And Congenital Disorders

Front 1

Genes Are Found on Chromosomes

Back 1

- DNA: person’s blueprint
- 46 chromosomes (genes) (alleles)
- 44 autosomes
- 2 sex chromosomes: X and Y
- Karyotype: complete chromosomal composition of
the nucleus

Front 2

Normal Human Karyotype

Back 2

2 sex chromosomes, 44 autosomes

Front 3

DNA

Back 3

Each cell nucleus throughout the body contains
the genes, DNA, and chromosomes that make
DNA bases: adenine, guanine, thymine, cytosine
RNA bases: adenine, guanine, uracil, cytosine

Front 4

Genetic Inheritance

Back 4

Alleles: are copies of a gene
– Homozygous: pair of alleles is similar (hh, HH)
– Heterozygous: pair of alleles is different (Hh)
• If you are heterozygous for a recessive trait and
do not show it, you are a carrier
– Dominant: always produce trait when inherited
– Recessive: manifest themselves when person is
homozygous for trait

Front 5

Achondroplasia

Back 5

Short limb dwarfism

AUTOSOMAL DOMINANT

Front 6

Adult polycystic kidney disease

Back 6

Chronic kidney disease

AUTOSOMAL DOMINANT

Front 7

Huntington chorea

Back 7

Neurodegenerative disorder

AUTOSOMAL DOMINANT

Front 8

Familial hypercholesterolemia

Back 8

Premature atherosclerosis

AUTOSOMAL DOMINANT

Front 9

Marfan syndrome

Back 9

Connective tissue disorder with abnormalities in the skeletal, ocular, and cardiovascular systems

AUTOSOMAL DOMINANT

Front 10

Neurofibromatosis

Back 10

Neurogenic tumors, fibromatious skin tumors, pigmented skin lesions, and ocular nodules in NF-1, bilateral acoustic neuromas in NF-2

AUTOSOMAL DOMINANT

Front 11

Osteogenesis imperfecta

Back 11

Brittle bone disease due to defects in collagen synthesis

AUTOSOMAL DOMINANT

Front 12

Spherocytosis

Back 12

Disorder of the RBCs

AUTOSOMAL DOMINANT

Front 13

von Willebrand disease

Back 13

Bleeding disorder

AUTOSOMAL DOMINANT

Front 14

Cystic Fibrosis

Back 14

Disorder of membrane transport of chloride ions in exocrine glands causing lung and pancreatic disease

AUTOSOMAL RECESSIVE

Front 15

Glycogen storage diseases

Back 15

Excess accumulation of glycogen in the liver and hypoglycemia; glycogen accumulation in striated muscle in myopathic forms

AUTOSOMAL RECESSIVE

Front 16

Oculocutaneous albinism

Back 16

Hypopigmentation of skin, hair, and eyes as a result of inability to synthesize melanin

AUTOSOMAL RECESSIVE

Front 17

Phenylketonuria (PKU)

Back 17

Lack of phenylalanine hydroxylase with hyperphenylalaninemia and impaired brain developement

AUTOSOMAL RECESSIVE

Front 18

Sickle cell disease

Back 18

Red blood cell defect

AUTOSOMAL RECESSIVE

Front 19

Tay-Sachs disease

Back 19

Deficiency of hexosaminidase A; severe mental and physical deterioration beginning in infancy

AUTOSOMAL RECESSIVE

Front 20

Bruton-type hypogammaglobulinemia

Back 20

Immunodeficiency

X LINKED RECESSIVE

Front 21

Hemophilia A

Back 21

Bleeding disorder

X LINKED RECESSIVE

Front 22

Duchenne dystrophy

Back 22

Muscular dystrophy

X LINKED RECESSIVE

Front 23

Fragile X syndrome

Back 23

Mental retardation

X LINKED RECESSIVE

Front 24

Autosomal Dominant Diseases

Back 24

- Single mutant allele (dominant) from affected
parent is transmitted to an offspring
- 50% chance of being affected
- Disease appears in every generation
- Both males and females can be affected

- Gene products of autosomal dominant diseases are usually regulatory proteins involved in rate-limiting components of complex metabolic pathways OR key components of structural proteins i.e. collagen

- Some cases are due to new mutations involving ovum and sperm from which they were derived

It could be expressed at step one, at the level of the trait, or at the level of the eggs and sperm.

Front 25

Marfan syndrome (Autosomal Dominant Diseases)

Back 25

- Prevalence: 1/20,000
- Dysfunction of gene that
codes for fibrillin, component
of microfibrils found in
extracellular matrix
- Affects several organs:
skeletal, ocular, cardiovascular
- No cure

The top part of the body is pushed up and the rest of the torso just sags down

Expansion of the aorta (aneurysm) and floppy valves in the heart - unfavourable cardiovascular adaptations

Front 26

Achondroplasia (Autosomal Dominant Diseases)

Back 26

(Note the disproportion of the limbs to the
trunk, the curvature of the spine, and the prominent buttocks.)

Disproportion of the limbs to the trunk, prominent glutes, curvature of the spine

Front 27

Autosomal Recessive

Back 27

- Disease manifests when individual is homozygous for the
defective allele
- Parents are carriers; they do not have the disease
- Affects both sexes
- Child has a 25% chance of being affected
- Recessive allele appears more frequently in close
intermarriages
- Includes most inborn errors of metabolism

Hypermobile joints and long arm span

Front 28

Phenylketonuria (Autosomal Recessive)

Back 28

You can't break down phenylalanine (essential amino acid)

Reduced tyrosine results in loss of pigmentation. In order to prevent brain damage a special diet of low protein is required for the individual.

Front 29

Tay-Sachs disease (Autosomal Recessive)

Back 29

- Lysosomal storage disease
- Absence of enzyme Hexosaminodase A (Hex-A)
- Lipid (GM2 ganglioside) accumulates in lysosomes
- Predominant disorder of Eastern European Jews
- Progressive destruction of neurons in brain
- Mental retardation, physical regression, visual
impairment > blindness

Fats accumulate in the lysosomes leading to the destruction of neurons in the brain --> mental retardation, physical regression, etc.

- Albinism
Albinism is also a recessive homozygous disease

Front 30

Which of the following statements is true about
an individual who is a carrier for the cystic
fibrosis (CF) gene (autosomal recessive)?
a. Homozygous; suffers from CF
b. Homozygous; does not suffer from CF
c. Heterozygous; suffers from CF
d. Heterozygous; does not suffer from CF

Back 30

d. Heterozygous; does not suffer from CF

If an individual is a carrier, they are
heterozygous for the recessive trait (in this
case, CF), but they do not display the trait
(because the trait is recessive).

Front 31

Sex-Linked Inheritance

Back 31

- Defective gene on X chromosome
- Inheritance pattern is usually recessive
- Males: defective X on male is unmasked and
the trait is expressed
- transmit the defective allele to their daughter(s)
- Females (heterozygotes): carriers for the
disease

Front 32

Sex-Linked Inheritance - Examples

Back 32

Color blindness
- Inability to distinguish colors (red-green)
- Defect in cones

Hemophilia
- Bleed for longer period of time
- Factor VIII, intrinsic clotting factor is inactive
- “Royal Disease”

Front 33

Fragile X syndrome (Sex-linked)

Back 33

- Mutation of FMR-1 gene (gene mapped to fragile site on X
chromosome)
- A break or weakness in the long arm of X chromosome

Mental retardation is typically associated with X-linked disease
- Mothers are carriers
- Sons at risk of being affected, daughters at risk of being
carriers and sometimes affected
- Most common inherited cause of mental retardation
- Others: large face, mandible, everted ears, testes; learning
disability; hyper extendible joints
- No cure

Front 34

Familial Disease

Back 34

• Diseases run in families but means of inheritance are not
understood
• Most likely the effects of several genes working together
• Examples: diabetes, allergies, familial polyposis

Front 35

Abnormal Chromosome Diseases

Back 35

• Altered number or structure
• Failure of chromosome to separate during cell
division
• Loss of autosome is usually incompatiblewith
life

Ex. Down Syndrome

Front 36

Abnormal Chromosome Diseases - Down Syndrome

Back 36

• Most common chromosomal disorder
• Caused by the presence of an extra autosome, chromosome 21 is inherited in triplicate
• Results in mental retardation and shorter life expectancy
• Characteristic appearance: slanted eyes, extra fold of skin at upper medial corner of the eye, protrusion of the tongue, short nose, short stature, underdeveloped sex organs

Typical characteristics:
- Malformed ears
- Acute lymphoblastic leukemia
- Big, protruding wrinkled tongue
- Intestinal malformations
etc.

Main problems = shorter life expectancy (which depends on the person and the treatments that are available for them)

Front 37

Turner Syndrome (Sex Anomalies)

Back 37

Turner syndrome
- Missing all or part of X
chromosome
- Person appears female
- Ovaries do not develop, what
happens?
- Diagnosis often delayed until late
childhood/early adolescence
- Treatment options: GH and
estrogen therapy

One sex chromosome is seen on the karyotype.
X0 = 1X and missing an X (0)

There is no Y therefore they appear to be a female, however they lack fundamental anatomy such as ovaries (no estrogen or eggs, etc. - lack of estrogen = lack of secondary sex characteristics). We give GH and estrogen therapy to provide those essential hormones.

Front 38

Turner Syndrome (Sex Anomalies) - Characteristics

Back 38

3 consecutive months without a period = amenorrhea

Secondary amenorrhea = absence for 3 months (ex.

Female athlete triad. - leads to an energy deficit in the body, therefore the reproductive system is the first system starved of energy)

Primary amenorrhea = periods never start within the body for females

Front 39

Klinefelter Syndrome (Sex Anomalies)

Back 39

Klinefelter syndrome
- Extra X chromosome
- Person appears male
- Small testes, fail to mature and
produce no sperm
- Breasts enlarge, female distribution
of hair
- Little facial hair
- Tall, slender, sterile
- Intellect is normal, some language
impairment

Pay attention to the Klinefelter karyotype = 47, XXY

Front 40

Genetic Counseling

Back 40

• A genetic counselor usually begins with a complete family history of both prospective parents, a pedigree.

• Pedigrees are used to determine the pattern of inheritance of a genetic disease within a family.

• Genetic counselor can inform prospective parents of the possibility of having genetically abnormal offspring, and they can make an informed decision

This is a way to determine if your future child is susceptible to any diseases

Front 41

Diagnosis of Genetic Diseases

Back 41

• Early diagnosis is critical to prevention and treatment of genetic diseases.
• During amniocentesis, a small amount of amniotic fluid is withdrawn after the 14th week of pregnancy.
• Can detect approximately 200 genetic diseases before birth.
• Chorionic villi - projections of the membrane that surrounds the embryo
• Chorionic villus sampling involves removing cells from the villi through the cervix.
• Chorionic villus sampling gives embryonic or fetal results (gender and chromosomal information) earlier in the pregnancy.

Front 42

Gene Therapy

Back 42

• A procedure that involves identification, manipulation, and transference of genetic segments into a host to replace defective genes and to perform desired genetic activities.

You have the ability to manipulate the genes

Front 43

Congenital Diseases

Back 43

• Appear at birth or shortly after, but they are not caused by genetic or chromosomal abnormalities.
• Congenital defects usually result from some failure in development during the embryonic stage, or in the first 2 months of pregnancy. Therefore, congenital diseases cannot be transmitted to offspring.

No genetics or chromosomes related therefore no genetic cause but rather failure during the embryonic development stage

Front 44

Congenital Diseases - Examples

Back 44

• Examples include spina bifida (incomplete closing of
embryonic neural tube), syphilis, cleft lip and cleft palate, andpyloric stenosis.

Front 45

If an unaffected mother carries one normal and
onemutant allele on her X chromosome,
what are the chances that she will transmit
the defective gene to her sons?
a. 25%
b. 50%
c. 75%
d. 100%

Back 45

b. 50%
Because a son receives the X sex chromosome
from his mother (who has one normal and
one mutant allele), there is a 50% chance that
the mutant allele will be inherited.