Autosomal Dominant Inheritance

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Autosomal Dominant Inheritance
Human Genetics

• Autosomal dominant inheritance occurs when one
  copy of an allele is sufficient for expression of
  a trait and the gene is located on one of the 22
  autosomes.

Genetics, Disease, and Dentistry
Each affected person has at least one affected
parent. An affected person has a 50 chance of
passing the trait to a child. Males and females
are equally likely to be affected. Two affected
people can have an unaffected child.
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Autosomal Dominant Disorders

• Progeria characterized by an appearance of
  accelerated aging in children, affects 1 in 8
  million newborns
• Huntingtons Disease degenerative brain
  disorder, slowly diminishes the affected
  individuals ability to walk, think, talk and
  reason ? dementia

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Autosomal Recessive Inheritance

• Autosomal recessive inheritance occurs when two
  copies of an altered gene located on one of the
  autosomes must be present for an individual to be
  affected with the trait or condition determined
  by that gene.

• An affected individual (homozygote) has two
  parents who are unaffected but each parent
  carries the altered gene (heterozygote).
• Males and females are at equal risk for being
  affected.
• Two affected individuals usually produce children
  all of whom are affected as well.

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Autosomal Recessive Disorders

• Tay-Sachs Disease individuals lack an enzyme in
  the lysosomes of their brain cells needed to
  break down lipids. The undigested lipids enlarge
  and eventually destroy the brain cells that house
  them.
• Phenylketonuria (PKU) individuals lack an enzyme
  that converts Phe to Tyr. Failure of the
  conversion to take place results in a buildup of
  Phe. Through a mechanism that is not well
  understood, the excess Phe is toxic to the
  central nervous system. This results in mental
  retardation and other neurological problems if
  not detected early.
• Albinism

Sickle Cell Anemia
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X-Linked Inheritance

• Most individuals who are affected with the trait
  or condition in questions are males.
• Mothers of the affected males are carriers and
  the sisters of affected males may be either
  carriers or not carry the gene al all. The basis
  for X-linked inheritance is that females have two
  X chromosomes and males have only one X
  chromosome.

• Affected males are hemizygous (their one X
  chromosome has the mutant allele)
• Affected females are homozygous (both X
  chromosomes have the mutant allele)
• Affected males transmit the gene to all
  daughters, but not to any of their sons
• The daughters of an affected male will usually be
  a carrier (heterozygote) and thus not show the
  trait (masked)
• Sons of heterozygous females have a 50 chance of
  receiving the gene and thus expressing the trait
  or condition

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X-linked Disorders

• Colour Blindness
• In red-green colour vision deficiency, the
• visible spectrum is divided into two parts
• a red segment and a blue segment, separated
• by grey or indistinct areas. The amount of grey
• or indistinct areas varies according to the
  severity of the deficiency.
• Men are mainly affected
• For a woman to be colour deficient, her father
  must be colour-blind and her mother must be a
  carrier
• A defective male always inherits his deficiency
  from his mother who usually has normal colour
  vision is therefore a carrier of the defect.

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• Duchenne Muscular Dystrophy
• Involves the wasting away of muscle tissue
• Muscle cells become engorged with fat and they
  eventually waste away most individuals suffer
  from respiratory failure in their early twenties.

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Human Pedigrees Working out Inheritance Patterns

• Pedigrees are a convention for keeping track of
  human genetic traits used to infer genotype.
• Pedigrees are the human equivalent of test
  crosses.
• In a visualization of a pedigree
• males are designated with square symbols.
• females with round symbols
• lines are drawn to indicated matings,
  parent-offspring relationships, and relationships
  between siblings.

Factors to Consider in Pedigrees
Is the trait located on a sex chromosome or an
autosome? Autosomal not on a sex chromosome Sex
Linkage located on one of the sex
chromosomes Y-linked - only males carry the
trait. X-linked (recessive) - sons inherit the
disease from normal parents How is the trait
expressed? Dominant - the trait is expressed in
every generation. Recessive - expression of the
trait may skip generations.
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Pedigree Diagrams I
Pedigree Diagrams II

• Basic Symbols

Basic Symbols for offspring and the expression of
a trait. The offspring are depicted below the
parents. Filling the symbol with black indicates
the expression of the studied trait.
Pedigree analysis
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Note that the symbols for non-identical twins and
for identical twins differ by whether they
descend from a common vertical before bifurcating
Media Showcase
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Pedigrees

• Generations are numbered from the top of the
  pedigree in uppercase Roman numerals, I, II, III
  etc. Individuals in each generation are numbered
  from the left in arab numberals as subscripts,
  III1 , III2, III3 etc. For example, here is a
  typical autosomal dominant pedigree with numbered
  generations and individuals.

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Marfans Syndrome An Example

• Expressed in both sexes.
• Thus, autosomal.
• Expressed in every generation.
• Thus, dominant.

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Marfans Genotype the Normal Individuals

• Assign codes for the alleles.
• Code m for the recessive normal allele.
• Code M for the dominant allele for Marfans
  syndrome.
• Normal individuals must be mm.

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Marfans Genotype the Affected Individuals

• Affected individuals must have at least one M.

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Marfans Parent-Offspring Relationships

• Possibilities for 1 and 2 Heterozygote (Mm) or
  homozygous for M?
• If MM, all offspring from a normal mate should
  be affected.
• Therefore, both must be heterozygotes.

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Marfans Parental Genotypes Known

• M must have come from the mother.
• The father can contribute only m.
• Thus, the remaining genotypes are Mm.

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Albinism An Example

• Expressed in both sexes at approximately equal
  frequency.
• Thus, autosomal.
• Not expressed in every generation.
• Thus, recessive.

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Albinism Genotype the Affected Individuals

• Assign codes for the alleles.
• Code A for the dominant normal allele.
• Code a for the recessive allele for albinism.
• Affected individuals must be homozygous for a.
• First generation parents must be Aa because
  they have normal phenotypes, but affected
  offspring.

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Albinism Genotype the Normal Individuals

• Normal individuals must have at least one A.

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Albinism Parent-Offspring Relationships

• 1 must transmit a to each offspring.
• The A in the offspring must come from the
  father.
• Normal father could be either heterozygous or
  homozygous for an A.

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Albinism Parental Genotypes are Known

• Both parents are heterozygous.
• Normal offspring could have received an A from
  either parent, or from both.

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Albinism One Parental Genotype is Known

• Only the genotype of the offspring expressing
  albinism are known.
• Normal offspring must have received an a from
  their affected father.

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Hairy Ears An Example

• Only males are affected.
• All sons of an affected father have hairy ears.
• Thus, hairy ears is Y-linked.

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Hairy Ears Female Sex Determination

• All females are XX

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Hairy Ears Male Sex Determination

• All males are XY.

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Hairy Ears Gene on the Y Chromosome

• Code H indicates the allele on the Y chromosome
  for hairy ears

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Hairy Ears Wild-Type Allele for Normal Ears

• Code indicates the allele on the Y chromosome
  for normal ears.

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Hemophilia An Example

• In this pedigree, only males are affected, and
  sons do not share the phenotypes of their
  fathers.
• Thus, hemophilia is linked to a sex
  chromosomethe X.
• Expression of hemophilia skips generations.
• Thus, it is recessive.

Children resemble their parents. Animation
Extensive bruising of the left forearm and hand
in a patient with hemophilia.
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Hemophilia Expression of the Female Sex
Chromosomes

• All females are XX

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Hemophilia Expression of Male Sex Chromosomes

• All males are XY.

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Hemophilia Genotype the Affected Individuals

• Assign codes for the alleles.
• Code H for the recessive hemophilia allele.
• Code for the wild-type normal allele.
• Affected individuals must have an H on an X
  chromosome.

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Hemophilia Father-Daughter Relationship

• All daughters of an affected father receive an X
  chromosome with the H allele.

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Hemophilia Genotyping the Normal Individuals

• Normal individuals must have at least one X
  chromosome with the wild-type allele, .

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Hemophilia Homozygous or Heterozygous?

• Only males affected
• Not Y-linked
• Skips a generation recessive
• X-linked

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Try It!

• Let us begin by drawing the pedigree described
  below (which is not necessarily an autosomal
  dominant condition and which contains extraneous
  information).

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The Scenario

• Alice and Bob have a two year old son, Charles,
  who is showing mental retardation, short stature,
  micropenis, and cryptorchidism. Alice has two
  living, unaffected, brothers but her eldest
  brother died at age 9 and a second brother died
  aged 10 months. Both had similar problems to
  Charles. Alice's father, David, who was
  symptomless, has a sister, Ethel, who has an
  unaffected boy and girl, and a brother, Fred, who
  also has two unaffected children. Alice's mother,
  Gertrude, has two living sisters and had a
  brother who had died in childhood and who, she
  remembers, had been mentally retarded. Bob has
  two brothers, Henry and Ignatius, who are still
  unmarried. His parents, John and Kate, had tragic
  lives, both were adopted and never knew their
  biological parents and both died as the result of
  a road accident.

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Step 1

• Begin with Alice, Bob and Charles.
• Here are three possible drawings of this nuclear
  family.

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Correct Solution

• Alice and Bob are connected by a horizontal line
  to show that this is a mating. Charles is
  connected to that horizontal line to show that he
  is a product of that mating.

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Choose One

• Now add Alice's siblings and parents to the
  pedigree.

Step 2
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Correct Solution was Possiblilty 3
Alice and her four brothers are connected
vertically to a horizontal line which is, in
turn, connected to the line drawn between her
parents David and Gertrude. Her two dead brothers
(whom we presume died of the same genetic disease
- though this can sometimes be a foolish
assumption without medical evidence) are shaded
in (to show that they suffered from the disease)
and are crossed through (to show that they are
dead).
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Step 3

• Now add Gertrude's siblings to the pedigree.
• And David's siblings and his nephews and nieces
• Finally add Bob's side of the family
• Try Drawing it!!!

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Correct Drawing!
http//bio1151.nicerweb.net/med/Vid/Discover2e/ch1
3a04_Pedigree.swf
Children resemble their parents. Problem