inheritance pattern

Question 1

What are pedigree drawing symbols?

Answer 1

=> square = male
=> circle = female 
=> line between = partners
=> line above = siblings
=> 2 branch = twins 
=> line down = children 
=> shaded = affected 
=> dots = carriers 
=> crossed shape = dead
=> diamond = still birth(SB), pregnant (p), => empty diamond = unknown sex of baby
=>triangle = miscarriage 
=> triangle with cross = abortion. 

consanguineous couple:
double line joins partners
=> first cousins couple.

Question 2

What are characteristics of inheritance patterns of autosomal dominant?

Answer 2

• manifest in heterozygous form
• multiple generations affected (but if individual’s siblings or children not affected then can not pass it to their offspring).
• both sexes affected
• male to female and female to male transmission
• most will have an affected parent (but sometimes it can be a random mutation)
• 50% risk of offspring

Question 3

Define penetrance.

Answer 3

• percentage of individuals who carry the mutation AND develop symptoms of the disorder
  => many dominant disorders show age- dependent penetrance

Question 4

What are features of autosomal dominant inheritance?

Answer 4

=>VARIABLE EXPRESSIVITY
variation in severity/symptoms of disorder between individuals with same mutation
=> NEW MUTATION RATE.
de novo mutation rate varies between autosomal dominant conditions.
=> SOMATIC MOSAICISM
new mutation arising at early stage in embryogenesis - present in only tissues/ cells
=> GERM LINE MOSAICISM (GONADAL)
new mutation arises during oogenesis or spermatogenesis - mutation present in gametes can be transmitted to offspring
=> ANTICIPATION
worsening or disease severity in successive generations, characteristically occurs in triplet repeat disorder

Question 5

What are characteristics of autosomal recessive inheritance?

Answer 5

-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
- could be consanguinity

Question 6

What are features of autosomal recessive inheritance?

Answer 6

• trait often found in clusters of siblings but not in parents and offsprings
• reoccurrence risk = 1/4 for each siblings of affected person
• carriers probability = 2/3 for unaffected siblings of affected person
• all offspring of affected person are OBLIGATE CARRRIERS

Question 7

what are features of X - linked inheritance?

Answer 7

• recessive : women are carriers + unaffected

- dominant : women are affected , males are more severely affected bc they dont have a back up X

Question 8

What are aspects of X - linked recessive inheritance?

Answer 8

• x linked genes never passed from father to son
• all daughters of affected males are obligate carriers
• children of carriers females have 50% chance of inheriting mutant allele

Question 9

Define skewed X - inactivation.

Answer 9

generally random but ~ 10% of women have uneven or skewed X - inactivation

Question 10

Define manifesting carriers.

Answer 10

some women have some symptoms in X -linked recessive conditions e.g. cardiomyopathy in DMD

Question 11

What the 3 main types of mutations?

Answer 11

1. substitutions (point mutations)
2. deletions
3. insertions

Question 12

What is synonymous (silent) base substitution?

Answer 12

• mutation makes no difference because both codon codes for the same amino acid.
  => degeneracy

Question 13

What is point (missense) mutation?

Answer 13

• replacement of a single base leads to incorrect amino acid being codes => malfunctioning protein.

Question 14

Why does missense mutation not always lead to malfunctional protein?

Answer 14

• depends where the mutation is , if at the end of sequence doesn’t make much difference
• depends what protein is being coded (functional role) if the two proteins are similar then function isnt that affected.
• is it conserved bc if it is then it is important as it has been selected through evolution so it is important.

Question 15

What is in frame insertion/deletion?

Answer 15

• multiple of 3 so 3, 6, 9 etc

- not damaging bc it doesn’t change reading frame, codons are read in 3s.

Question 16

What is frameshift insertion/deletion?

Answer 16

• not a multiple of 3

- so changes the reading frame, downstream = leads to pathogenic protein.