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Flashcards in Patterns of inheritance Deck (24)
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1
Q

Have a look at pedigree drawings and the signs

A

On first page of notes

2
Q

What is autosomal dominance?

A
  • Multiple generations affected
  • Both sexes affected
  • Male to female & female to male transmission
  • Most will have an affected parent
3
Q

What are the charactertistics of autosomal dominance? (4 marks)

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.
  • Risk for each child of an affected parent is ½.
  • If an affected individual’s siblings/children are not affected, and they do not carry the mutation they cannot pass it on to their own offspring.
4
Q

Define Penetrance

A

Percentage of individuals who carry the mutation AND develop symptoms of the disorder

– many dominant disorders show age-dependant penetrance
– some people can have reduce penetrance
– e.g Huntington’s disease

5
Q

What are obligate carriers?

A

Obligate carriers are people who are heterozygous but have not got the disease, they can pass this mutation on.

6
Q

How do we calculate Penetrance?

A

Number of individuals with disease/ number of people with genotype of disease x 100

7
Q

Explain the terms: Variable Expressivity, New mutation rate, Somatic mosaicism, Germ-line mosaicism (gonadal mosaicism and Anticipation which are all features of autosomal dominance

A
  • Variable Expressivity: variation in severity/symptoms of disorder between individuals with same mutn . Can occur within the same family
  • New mutation rate: de novo mutation rate varies considerably between AD conditions

• Somatic mosaicism: new mutn arising at early stage in embryogenesis
o Present in only some tissues/cells

• Germ-line mosaicism (gonadal mosaicism): new mutn arises during oogenesis or spermatogenesis
o mutn present in variable proportion of gametes; can be transmitted to offspring
• Anticipation: worsening of disease severity in successive generations
o characteristically occurs in triplet repeat disorders

8
Q

What are the features of Autosomal Recessive Inheritance

A
•	Manifest in HOMOZYGOUS/ COMPOUND HETEROZYGOUS form
•	Carriers (heterozygote) not affected
•	Both sexes affected
•	Male to female and female to male transmission
•	Usually one generation affected
•	May be consanguinity
 	e.g. cousin marriages
Refer to image as well
9
Q

How can cystic fibrosis cause a compound heterozygous?

How can cystic fibrosis cause compound homozygous?

A

Hetrozygous:
– 2 mutns in same gene
– Mutns are different

• Cystic fibrosis
– ∆F508
– G542X

Homozygote:
–	2 mutns in same gene
–	Identical mutns
•	Cystic fibrosis
–	∆F508
–	∆F508
•	May suggest consanguinity
10
Q

What are the features of Autosomal Recessive Inheritance? (4)

A
  • Trait often found in clusters of siblings but not in parents & offspring.
  • Recurrence risk = 1/4 for each sibling of affected person.
  • Carrier probability =2/3 for unaffected siblings of affected person.
  • All offspring of affected person are obligate carriers.
11
Q

What is X linked inheritance?

A

Women have two X chromosomes
Two copies of X-linked genes
Can be homozygous or heterozygous

Men have one X and a Y
Only a single copy of X-linked genes
Hemizygous

12
Q

How can X linked heriatnce be recessive or dominant?

A
•	Recessive
 	Women are carriers + unaffected
 	No male to male transmission
•	Dominant
 	Women are affected
 	Males more severely affected/lethal
13
Q

Give 3 aspects of X-linked Recessive Inheritance

A
  • X-linked genes never passed from father to son.
  • All daughters of affected males are obligate carriers.
  • Children of carrier females have a 50% chance of inheriting mutant allele.
14
Q

What is Skewed X-inactivation and Manifesting carriers

A
  • Skewed X-inactivation: generally random but ~10% of women have uneven or skewed X-inactivation.
  • Manifesting carriers: some women have some symptoms in X-linked recessive conditions e.g. cardiomyopathy in DMD.
15
Q

What is Y linked inheritance

A

Always and only passed from fathers to sons

16
Q

Define mutation

A

Mutation: a change in the genetic material

17
Q

What does a pathogenic mutation cause?

A

• A pathogenic mutation (pathogenic variant) results in an alteration of the function of the gene product and can cause a disease phenotype

18
Q

What type of mutations are there?

A
  • Substitutions (point mutations)
  • Deletions
  • Insertions
19
Q

Where are mutations found?

A
  • Coding DNA

* Non-coding DNA (such as promoters and introns)

20
Q

What is a silent or synonymous base substitutions?

A

Nucleotide change which causes an amino acid change

21
Q

What is a missense mutation (point)

A

Replacement of a single nucleotide

This leads to a different amino acid being incorporated.

Causes a change in DNA sequence

22
Q

What are the impacts of amino acid substitution?

A
  • Physicochemical similarity between the two amino acids
  • Functional role of the specific domain of the protein
  • Phylogenetic conservation of original aminoacid amongst diverse species
23
Q

What is a nonsense (point) mutation?

A

Replacement of a single nucleotide codes for a stop codon - shortening the protein

24
Q

What is an insertion of a base (or more)?

A

In-frame (multiple of three) or frameshift (not multiple of three)