Inheritance Patterns Flashcards

1
Q

Describe the characteristics of the autosomal dominant inheritance pattern.

A
  • most individuals have an affected parent (not everybody due to cases of new mutations or incomplete penetrance)
  • males and females are equally likely to inherit the allele and be affected
  • the risk for each child of an affected parent is 1/2
  • if an unaffected individual’s siblings/children are not affected, and they do not carry the mutation, then they cannot pass it on to their own offspring
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2
Q

What is penetrance?

A

Penetrance is the percentage of individuals who carry the mutation AND develop symptoms of the disorder - many dominant disorders show age-dependent penetrance.

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3
Q

List and describe some features of autosomal dominant inheritance patterns.

A

VARIABLE EXPRESSIVITY: It is the variation in the severity/symptoms of the disorder between individuals with the same mutation.

NEW MUTATION RATE: the de novo mutation rate varies considerably between AD conditions

SOMATIC MOSAICISM: new mutations arising at an early stage in embryogenesis - present in only some tissues/cells

GERM-LINE MOSAICISM (gonadal mosaicism): new mutation arises during oogenesis or spermatogenesis - mutation must be present in a variable proportion of gametes; can be transmitted to offspring

ANTICIPATION: the worsening of disease severity in successive generations - characteristically occurs in triplet repeat disorders

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4
Q

Describe the characteristics of autosomal recessive inheritance.

A
  • manifest in homozygous/compound heterozygous form
  • carriers (heterozygous) not affected
  • both sexes affected
  • male to female and female to male transmission
  • usually, one generation affected
  • may be consanguinity (eg. cousin marriages)
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5
Q

What is the difference between compound heterozygote and homozygote?

A

Compound Heterozygote:

  • two mutations are in the same gene
  • the mutations are different

Compound Homozygote:

  • two mutations are in the same gene
  • they are identical mutations
  • (may suggest consanguinity)
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6
Q

List some features of autosomal recessive inheritance.

A
  • the traits are often found in clusters of siblings, but not in parents and offspring
  • the recurrence risk is 1/4 for each sibling of an unaffected person
  • the carrier probability is 2/3 for unaffected siblings of the affected person
  • all offspring of the affected person are obligate carriers
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7
Q

Describe how the difference in sex chromosomes affects X-linked inheritance.

A

Women have 2 X chromosomes.

  • thus, they have two copies of X-linked genes, giving slight protection
  • they can be homozygous or heterozygous for these disorders

Men have one X and one Y chromosome.

  • thus, they only have a single copy of X-linked genes
  • they are said to be hemizygous
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8
Q

How is X-linked inheritance recessive or dominant?

A

X-linked inheritance can be:

RECESSIVE:

  • women are carriers + unaffected
  • no male to male transmission

DOMINANT:

  • women are affected
  • males more severely affected/lethal
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9
Q

Describe the characteristics of X-linked recessive inheritance.

A
  • X-linked genes are never passed from father to son
  • all daughters of affected males are obligate carriers
  • children of carrier females have a 50% chance of inheriting the mutant allele

Skewed X-Inactivation: normally, the majority of genes on one of a woman’s X-chromosomes are inactivated (it’s generally random, but ~10% of women have uneven or skewed X-inactivation)

Manifesting Carriers: some women have some symptoms in X-linked recessive conditions (eg. cardiomyopathy in DMD)

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10
Q

Define a pathogenic mutation.

A

A mutation is a change in genetic material.
A pathogenic mutation (pathogenic variant) results in an altercation of the function of the gene product and can cause a disease phenotype.

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11
Q

List the types of mutations and where they are found.

A

Types of mutations:

  • substitutions (point mutations)
  • deletions
  • insertions

Found in:

  • coding DNA
  • non-coding DNA (such as promoters and introns)
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12
Q

What is a silent/synonymous substitution?

A

It when there is a nucleotide change that doesn’t change the amino acid made.

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13
Q

How do we determine the impact of an amino acid substitution?

A
  • physicochemical similarity between the two amino acids
  • functional role of the specific domain of the protein
  • phylogenetic conservation of the original amino acid amongst a diverse species
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