Chapter 21
Congenital and Genetic Disorders
Genetic Control
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Genetic information stored in chromosomes
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23 pairs in humans
22 pairs—autosomes
One pair of sex chromosomes—XX or XY
Karyotype
• Visual representation of chromosomes arranged in order
of size
• Used in diagnosis of chromosomal disorders
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Examples of Karyotypes
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Genetic Control (Cont.)
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Genotype
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Actual genetic information carried by the individual
All cells except the gametes of an individual have
the same genotype.
Not all genes are expressed in all cells.
Phenotype
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Expression of genes
Appearance of the individual’s characteristics
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Congenital Disorders
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Disorders present at birth
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Inherited disorders may be caused by
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Include inherited or developmental disorders
Single-gene expression
Chromosomal defect
Polygenic expression
Single-gene disorders
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Trait controlled by one set of alleles
Transmitted to subsequent generations
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Congenital Disorders (Cont.)
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Chromosomal anomalies
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Usually caused by an error during meiosis
• Nondisjunction
• Translocation
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Congenital Disorders (Cont.)
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Teratogenic agents
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Agents that cause damage during embryonic or
fetal development
Multifactorial disorders
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Large number of disorders are of this type
Often have pattern of familial inheritance
Environmental component
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Congenital Disorders (Cont.)
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Other congenital or developmental disorders
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Result from premature birth
Difficult labor and delivery
Cerebral palsy is an example.
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Single-Gene Disorders
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Classified by inheritance patterns
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Single gene controls a specific function
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Recessive
Dominant
X-linked recessive
Example: color blindness
May have systemic effects
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Examples: cystic fibrosis, Tay-Sachs disease,
phenylketonuria (PKU)
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Single-Gene Disorders
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Autosomal dominant disorders
Adult polycystic kidney disease
Huntington’s chorea
Familial hypercholesterolemia
Marfan’s syndrome
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Autosomal Recessive Disorders
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Both parents must pass on the allele for disorder.
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Parents may be heterozygous and unaffected; they are
termed carriers.
¾ Parents may be homozygous and affected.
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Male and female children are affected equally.
Homozygous recessive child has the disorder.
Heterozygous child
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No clinical signs of disease
Child is a carrier
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Autosomal Recessive Disorders
(Punnett Square) (Cont.)
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Autosomal Recessive Disorders
(Cont.)
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z
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Cystic fibrosis
PKU
Tay-Sachs disease
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Autosomal Dominant Disorders
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Inheritance of one allele causes disorder;
only one parent needs to carry allele
No carriers
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Unaffected persons do not transmit the disorder.
Some conditions become evident later in life.
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Allele for disorder may have been passed on to
next generation before diagnosis of disease in
parent.
Termed delayed lethal genotype
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Autosomal Dominant Disorders
(Punnett Square) (Cont.)
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Autosomal Dominant Disorders
(Cont.)
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z
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Adult polycystic kidney disease
Huntington’s disease
Familial hypercholesterolemia
Marfan’s syndrome
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X-Linked Disorders
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Recessive
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Allele carried on the X chromosome but not the Y
chromosome
Manifested in heterozygous males lacking the
matching unaffected gene on the Y chromosome
Heterozygous females are carriers.
Homozygous recessive females may be affected.
Inheritance may appear to skip generations.
Examples:
• Duchenne muscular dystrophy
• Classic hemophilia
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X-Linked Recessive Disorder
(Punnett Square)
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X-Linked Disorders (Cont.)
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Dominant disorder
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Heterozygous males and females affected
Reduced penetrance in females
Fragile X syndrome is an example.
• Most common genetic cause of cognitive deficits
• Effects are variable and related to the extent of mutation
of the allele.
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Single-Gene Disorders
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Autosomal recessive disorders
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X-linked dominant disorders
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Cystic fibrosis
Phenylketonuria
Sickle cell anemia
Tay-Sachs disease
Fragile X syndrome
X-linked recessive disorders
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Color blindness
Duchenne muscular dystrophy
Hemophilia A
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Chromosomal Disorders
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Down syndrome
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Turner syndrome XO
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Trisomy 21
May be caused by nondisjunction or translocation
Affects females
Short stature
Infertility
Klinefelter syndrome XXY
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Extra X chromosome is present
Infertility
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Down Syndrome
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Trisomy 21
Common chromosomal disorder
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Affects physical and mental development
Risk increases with maternal age
Triple or quad screening test and/or firsttrimester screening test (ultrasound +
maternal blood screening)
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May be used to screen for risk of Down syndrome
Amniocentesis or chorionic villi sampling used to
confirm the disorder prior to birth
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Characteristics of Down
Syndrome
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Small head, round face, flat facial profile
Slanted eyes and epicanthic fold
Large tongue, high-arched palate
Small hands, single palmar crease
Short stature
Muscles tend to be hypotonic; loose joints
Delayed developmental stages
Cognitive impairment ranges from mild to major
Delayed or incomplete sexual development
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¾
Males infertile
Females have lower rate of conception
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Down Syndrome (Cont.)
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Down Syndrome (Cont.)
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Multifactorial Disorders
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Genetic influences combined with
environmental factors
Examples:
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Cleft palate
Congenital hip dislocation
Congenital heart disease
Type 2 diabetes mellitus
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Developmental Disorders
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Exposure to drugs, chemicals, or radiation
during childbearing years
TORCH—acronym for maternal infections
that can result in anomalies
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Routine prenatal screening tests
Exposure to known teratogens in the first 2
months of development
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Impairs organogenesis
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Effects of Teratogens During
Pregnancy
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Diagnostic Tools
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Testing may be available.
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Prior to conception
During first trimester of pregnancy
In newborn
Testing recommended for:
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Family history of a specific disease
Previous birth to child with abnormality
Ethnic groups with high risk for specific disease
Pregnant women > 35 years of age
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Diagnostic Tools (Cont.)
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Blood tests of pregnant woman
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In utero testing
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Alpha-fetoprotein testing
Amniocentesis
Chorionic villi assay
Neonatal testing
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Excreted metabolites (e.g., PKU)
Blood testing
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Genetic Engineering
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Isolating, copying, and transplanting genes
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In microorganisms, plants, animals, humans
Used in agriculture to produce transgenic or
genetically modified foods
Ultimate goal
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Insert normally functioning allele to prevent
disease
Technically possible but clinical trials have not
been uniformly successful
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Gene Therapy
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Identifies gene and protein responsible for
condition
Determines how gene expression is
controlled
Produces drug that will inhibit gene
expression
Research focus on cancer growth promoters
has resulted in these types of drugs.
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Genetic Screening and DNA
Testing
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Screening at-risk populations for a specific allele
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Costly
Concerns regarding privacy and access to information
DNA testing to identify individuals for paternity or
forensic purposes
Legislation has been drafted in the United States to
protect the genetic rights of individuals.
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¾
Health care
Employment
Insurance
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Designer Drugs
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Proteomics research
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Gene expression
Characterization of proteins significant in the
metabolic pathway for expression of a particular
allele
Some designer drugs act differently in genetically
different individuals.
This research will help develop drugs tailored to an
individual’s genotype.
Reduce unwanted side effects of commonly used
medications
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