Autosomal Dominant 

(AD)
• Only one copy of the defective gene is required to express the disease phenotype
• Genders affected - male and female at equal frequency
• Generations affected - does not skip generations
• If two parents without the AD disease have child with an AD disease
– possibility is reduced penetrance
– germline mutation
• Homozygote dominant parent has a 100% of having an affected child
• If condition is nonviable with homozygotes then percentages of
penetrance changes! (Achondroplasia)
• two heterotyzgote parents with the AD disease condition have a 75%
chance of having a child with the disease phenotype 
• Often pleiotropic
• Examples  -  von Willebrand disease, Huntington's disease,
osteogenesis imperfecta, achondroplasia, Marfan syndrome,
neurofibromatosis type I, Porphyrias
 Autosomal Recessive
• Genders affected - male and female
• Generations affected   
– 1/4 of offspring affected when both parents are carriers
– usually 1 generation
• Pathology - defects in enzymes
• Presentation timing - infancy to childhood
• Other notes
– most often more severe than AD
– must have 2 defective copies of the gene
– chances greatly increased with consanguinity
• Examples - cystic fibrosis, PKU, von Gierke's, Pompe's, glycogen
storage diseases, sphingolipidoses (except Fabry's), and
mucopolysaccharidoses (except Hunter's), sickle cell anemia,
thalassemias, albinism, ARPKD, hemochromatosis
 X-linked Recessive (XR)
• Genders affected - males must receive defective gene from carrier mother
• carrier mother's sons have 50% of having disease 
• affected males give copy to all of their daughters
• Generations affected - skips generations
– male-to-male transmission not allowed
– diseases passes through carrier daughters
• Other notes
– only one defective copy necessary for disease in males
• because males are hemizygous for X chromosome
– two defective copies necessary for disease in females
– can be affected with just one defective copy if normal X chromosome is
inactivated to Barr body
• Examples -  hemophilia A and B, Menke's disease , Duchenne muscular
dystrophy , Lesch-Nyhan syndrome, Ornithine transcarbamoylase
deficiency, red-green color blindness, Fabry disease, Hunter’s Disease
 X-linked Dominant (XD)
• The allele responsible for the disease is located on
the X chromosome
• Both men and women are affected
• Affected mothers have a 50% risk of passing the
altered allele on to their offspring (regardless of
gender).
• Affected fathers pass the altered allele to all
daughters and no sons.
• Examples: Rett syndrome, Fragile x
syndrome, hypophosphatemic rickets
 Mitochondrial inheritance
• Genders affected - male and females at equal frequency
• Generations affected - does not skip generations
• only transmitted from affected female  - gives to all offspring
– due to the fact that the sperm do not contribute mitochondria to the
zygote
• variable expression due to heteroplasmy
– a small percentage of mitochondria within a cell are affected leading
to variable severity
• Examples
– myoclonic epilepsy with ragged red muscle fibers  
– Leber hereditary optic neuropathy 
– MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-
like episodes)
 Inheritance Algorithm for USMLE
• Does offspring with disease have a parent with disease? (Y/N)
– if YES
• dominant (does not skip generations)
– is there male-to-male transmission of disease? (Y/N)
» if YES
• autosomal dominant
» if NO
• do daughters of affected male have disease? (Y/N)
• if YES
• X-linked dominant
• if NO
• mitochondrial
– if NO
• recessive (can skip generations)
– predominantly males with disease? (Y/N)
» if YES
• X-linked recessive
» if NO
• autosomal recessive
• A 1-year-old boy with blonde hair, blue eyes, and fair skin is found to
have mental retardation, eczema, and vomiting. A mousy body odor is
apparent. Which of the following pedigrees best resembles the
inheritance pattern of this disease?
• The incidence of red-green color blindness in
males in a certain population is 1/100. Which
of the following is closest to the probability of
a female and a male with normal vision having
a daughter with red-green color blindness?
• A. 1/100
• B. 99/100
• C. 1/50
• D. 98/100
• E. 0
• A pregnant mother presents to your office with concerns
regarding the risk that her fetus will suffer from an inherited
disease. She reports a family history of hemophilia A in several of
her relatives. Figure A shows a pedigree created after a thorough
review of her family history (the mother in this scenario is
represented by the arrow). This is her first child, and the father
does not report any family history of blood disorders or other
diseases. Which of the following is the probability that this
patient's male offspring will have hemophilia A? 
• A. 0%
• B. 25%
• C. 50%
• D. 67%
• E. 75%
• A 5-year-old boy with a history of seizures presents to the pediatrician for
several seizures occurring over the past month. The mother states that her
son typically avoids recess, as he exhausts quite easily with any physical
activity. He has also had headaches and vomits after he eats. A family history
reveals that a maternal uncle and grandmother both had similar symptoms
and both lost their vision and hearing by the age of 40. The mother explains
that she also tires easily. With consent of the mother, a muscle biopsy was
taken and a Gömöri trichrome stain was performed. A blood analysis also
revealed significantly elevated lactate levels. Which of the following
statement best describes the mode of inheritance of the boy's disease? 

• A. Females of affected fathers are always affected

• A. 0%
• B. 25%
• C. 50%
• D. 75%
• E. 100%
• A 27-year-old G1P0 at 12 weeks gestation presents to her
obstetrician for her first prenatal visit. She and her husband both
have achondroplasia, and she is curious what are the chances that
they will have a child of average height. What percent of
pregnancies between two individuals with achondroplasia that
result in a live birth will be expected to be offspring that are
unaffected by this condition?
• A. 25%
• B. 33%
• C. 50%
• D. 75%
• E. 0%