1. The Patterns of Genetic Inheritance
By Dr. Joann Boughman, PhD
Mendelian
Non-Mendelian
Autosomal Dominant
Autosomal Recessive
X-linked Recessive
X-linked Dominant
Y-linked
Imprinting
Mitochondrial
Multifactorial
Sporadic
Contiguous gene syndromes

2. How to evaluate a pedigree...
1) Transmission: Are there affected family members in every generation
(vertical pattern) or in only a single generation (horizontal pattern)?
2) Sex Differences: What is the ratio of affected males to females?
3) Segregation: Is disease/gene being passed through unaffected females?
Is there male to male transmission? What % of children are affected
(e.g. all of sons but none of daughters)?

3. …but don’t forget the complicating factors!
Non-penetrance
New mutation
Adult-onset conditions
Consanguinity
Interaction
Sex-limited/sex influenced
Germline mosaicism
Anticipation
Heterogeniety
Pleiotropy

4. Autosomal Dominant Vertical pattern: multiple generations affected
Males and females equally likely to be affected
See male to male transmission
Each child of an affected individual has a 50% chance to be affected
Unaffected individuals do pass on the gene
Every affected child has an affected parent
Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

5. Autosomal Dominant Non-Penetrance
An individual who inherits the disease gene does not develop
the disorder
The disorder appears to “skip” generations
Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

6. Autosomal Dominant Sex-Limited/Influenced 3 2 3 2
Gene expression limited to specific sex
Disorder/trait may appear to “skip” generations
Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

7. Autosomal Dominant New Mutation 3 3 2
An alteration occurs in the egg or sperm that made the affected individual (may be first family member to be affected)
Recurrence risk for unaffected parents is considered to be low
Risk of new mutation is associated with advanced paternal age in some disorders (e.g. Achondroplasia)
Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

8. Autosomal Dominant Late-onset trait 4 3 4 3 2
dx 60
dx 50
dx 45 4 3 4
dx 45 3 2
An individual who inherits the disease gene but does not develop
the condition until adulthood
Examples: Huntington disease, most hereditary cancer syndromes
Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

9. Autosomal Dominant Variable Expressivity Variability of severity of
Lisch nodules
café-au-lait spots
Neurofibromas
café-au-lait spots
Lisch nodules
café-au-lait spots
scoliosis
Variability of severity of
disorder among individuals
with same genotype
Examples: Neurofibromatosis,
Treacher-Collins syndrome
Optic glioma
learning disability
neurofibromas
café-au-lait spots

12. Autosomal Recessive Horizontal pattern: single generation affected.
Males and females equally likely to be affected
Parents of affected child are unaffected gene carriers and have
a 1 in 4 or 25% recurrence risk
Unaffected siblings have a 2/3 or 67% chance to be carriers.
Children of affected individuals are obligate carriers.
Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

13. Autosomal Recessive Consanguinity
First cousins
Autosomal Recessive
Consanguinity
Increased consanguinity (over general
population) is often found between parents
of a child with a rare autosomal recessive disorder
Condition may appear to be dominant in a consanguineous family 2 2
Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

14. X-linked Recessive 2 3 4 2 3 2
Males are more often affected than females
Affected males pass the gene to all of their daughters and none of
their sons (NO male-to-male transmission)
Daughters of carrier females have a 50% chance to be unaffected
carriers. Sons of carrier females have 50% chance to be affected.
Affected males in the family are related to each other through carrier
females (“Knight’s move”)

15. X-linked Recessive Other characteristics 2 3 4 2 3
For genetically lethal X-linked conditions, 1/3 of isolated cases
(i.e. no family history) are new mutations.
In 2/3 of cases, the mother is an unaffected carrier
Female gene carriers are usually not affected
Exceptions: Turner syndrome, skewed X-inactivation,
X;autosome translocation carriers

16. X-linked Dominant 2 2
For rare conditions, females are about 2x as likely to be affected than
males. May be lethal in males and usually milder, but variable,
in females.
Affected males pass the gene to all of their daughters, who will be
affected, and to none of their sons (NO male-to-male transmission)
Sons and daughters of affected females have 50% chance of being
affected (similar to autosomal dominant)

17. Y-linked (Holandric) 4 4 Only males are affected
Affected males pass the disease gene to all their sons and to
none of their daughters
Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro