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

The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

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Page 1: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

The Patterns of Genetic InheritanceBy Dr. Joann Boughman, PhD

• Autosomal Dominant• Autosomal Recessive• X-linked Recessive• X-linked Dominant• Y-linked

• Imprinting• Mitochondrial• Multifactorial• Sporadic• Contiguous gene syndromes

Mendelian Non-Mendelian

Page 2: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

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)?

Page 3: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

…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

Page 4: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

• 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

Autosomal Dominant

Page 5: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

• An individual who inherits the disease gene does not develop the disorder• The disorder appears to “skip” generations

Autosomal Dominant

Non-Penetrance

Page 6: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

3

3 2

2

• Gene expression limited to specific sex• Disorder/trait may appear to “skip” generations

Autosomal Dominant

Sex-Limited/Influenced

Page 7: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

23 3

• 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)

Autosomal Dominant

New Mutation

Page 8: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

4

Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

3 2

43

• An individual who inherits the disease gene but does not develop the condition until adulthood • Examples: Huntington disease, most hereditary cancer syndromes

Autosomal Dominant

Late-onset trait

dx 60

dx 45

dx 45

dx 50

Page 9: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

Lisch nodulescafé-au-lait spots

Neurofibromascafé-au-lait spotsLisch nodules

café-au-lait spotsscoliosis

Optic gliomalearning disabilityneurofibromascafé-au-lait spots

• Variability of severity of disorder among individuals with same genotype• Examples: Neurofibromatosis, Treacher-Collins syndrome

Autosomal Dominant

Variable Expressivity

Page 10: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting
Page 11: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting
Page 12: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

• 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.

Autosomal Recessive

Page 13: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

22

• 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

Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

Autosomal Recessive

Consanguinity

First cousins

Page 14: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

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”)

X-linked Recessive

Page 15: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

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

X-linked Recessive

Other characteristics

Page 16: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

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)

X-linked Dominant

Page 17: The Patterns of Genetic Inheritance By Dr. Joann Boughman, PhD Autosomal Dominant Autosomal Recessive X-linked Recessive X-linked Dominant Y-linked Imprinting

Adapted from The Pedigree: A Basic Guide, by Jorgenson, Yoder & Shapiro

4 4

• Only males are affected• Affected males pass the disease gene to all their sons and to none of their daughters

Y-linked (Holandric)