Genetics in Clinical Practice Flashcards

1
Q

Definition of mutation

A

Pathogenic alteration in the gene affecting the structure or function of a protein

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2
Q

Definition of hemizygous

A

Presence of only 1 copy of chromosome or gene (X chromosome in males)

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3
Q

Definition of phenotypic heterogeneity

A

Many phenotypes arise from 1 variant

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4
Q

Definition of genetic heterogeneity

A

Many variants => 1 phenotype

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5
Q

Definition of variable (reduced) penetrance

A

Proportion of carriers who show within and between families

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6
Q

Definition of variable expression

A

Extent of clinical manifestation can vary within and between families

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7
Q

Definition of germline mosaicism

A

Parent carries a small proportion of gametes that harbour the same mutation

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8
Q

Definition of compound heterozygosity

A

Different mutant recessive alleles in same gene at same locus => disease

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9
Q

What are Mendel’s 2 laws of inheritance

A

Law of segregation
-everyone has 2 alleles of each characteristic but only 1 is passed on

Law of independent assortment

  • genes at different loci segregate independently
  • does not apply if 2 loci are closely linked
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10
Q

What are the 3 main types of Mendelian disorder

A

Autosomal dominant
Autosomal recessive
Sex linked

MUTATION IS IN 1 GENE

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11
Q

Describe

  • phenotypic heterogeneity
  • genetic heterogeneity
A

Phenotypic heterogeneity
-many phenotypes arise from 1 variant

Genetic heterogeneity
-many variants => 1 phenotype

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12
Q

Describe the pedigree symbols for

  • male and female
  • marriage (consanguinous, many, unrelated)
  • deceased
  • affected with disorder/carrier
  • couple with children/pregnant with unknown gender
A
πŸ”²πŸ”˜
πŸ”²-πŸ”˜  πŸ”²=πŸ”˜  πŸ”²/πŸ”˜-πŸ”²
πŸ”²with a line through it
⬛️  ⏺
child has P inπŸ”·
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13
Q

What are the 2 types of phenotypic expression possible in autosomal dominant conditions

A

Variable (reduced) penetrance

  • proportion of carriers who show phenotypic signs of condition
  • Not all individuals who inherit a dominant mutation express it

Variable expression
-extent of clinical manifestation can vary within and between families

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14
Q

Describe the 2 ways in which autosomal dominant conditions can arise

How can you test for one of these methods

A

Can be inherited or de novo

Parent carries a small proportion of gametes that harbour the same mutation => inherited

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15
Q

What are the risks associated with cosanguinity

A

Increased risk of recessive diseases in offspring

Probability of an unaffected child being a carrier => 2 in 3 (not limited to consanguinity)

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16
Q

Describe compound heterozygosity

A

Different mutant recessive alleles in same gene at same locus => disease

17
Q

Describe how X inactivation affects the expression of X linked dominant and recessive disorders

A

Non random inactivation leading to chance expression in certain tissues

Affected females show mosaic pattern of involvement

18
Q

What is involved in the 2 branches of a genetic diagnosis

  • clinical
  • genetic tests
A

Clinical
-clinical dysmorphic features

Genetic tests

  • chromosome analysis
  • FISH
  • Array CGH
  • Single gene testing
  • NGS
  • Methylation analysis
19
Q

What is the function of a genetic diagnosis

A

Confirms diagnosis
Decreases need for other tests
Aids prognostication and recurrence risk, not predicitve
Reproductive choices/prenatal diagnosis

20
Q

What is the function of single gene testing

A

For diagnosis/confirmation of genetic disorders

  • prenatal diagnosis
  • preimplantation genetic diagnosis
  • carrier/presymptomatic at risk relatives
21
Q

What are the 2 equations used in the Hardy Weinburg Principle

A

Allele frequencies p+q=1

Genotype frequencies p^2 + 2pq + q^2 =1

22
Q

How would you calculate the risk of expressing an autosomal dominant phenotype in a child

A

Probability of inheriting mutant allele x penetrance

23
Q

How would you calculate the risk of having a child affected by an X linked recessive disease

A

Carrier risk of mother x probability risk of passing on gene (0.5) x gender of child

24
Q

How would you calculate the risk of passing on an autosomal recessive disease

A

Carrier risk in 1 parent x carrier risk in unaffected other parent x probability of offspring being homozygous recessive