W1 - Inheritance Patterns

Question 1

How are males represented on a pedigree drawings?

Answer 1

Squares

Question 2

How are females represented in pedigree drawings?

Answer 2

Circles

Question 3

How are partners represented in pedigree drawings?

Answer 3

Has a line between them

Question 4

How are siblings represented in pedigree drawings?

Answer 4

Has a line above them

Question 5

How are children represented in pedigree drawings?

Answer 5

Line down

Question 6

How are affected people represented in pedigree drawings?

Answer 6

Affected = shaded
Carriers = dot

Question 7

How are unions of consanguineous (of the same blood) couples represented in pedigree drawings?

Answer 7

Double lines connecting the two

Question 8

How are still born babies of unknown sex represented in pedigree drawings?

Answer 8

Diamond with SB next to it

Question 9

How are spontaneous abortions represented in pedigree drawings?

Answer 9

Triangle

Question 10

How are therapeutic abortions represented in pedigree drawings?

Answer 10

Triangle with a diagonal line

Question 11

How are identical twins represented in pedigree drawings?

Answer 11

Has a line connecting the line coming from the parents to form a triangle at the top.

Question 12

How are non-identical twins represented in pedigree drawings?

Answer 12

Triangular stem without line joining them.

Question 13

How is pregnancy represented in pedigree drawings?

Answer 13

Diamond with a ‘p’ inside.

Question 14

How are no offsprings represented in pedigree drawings?

Answer 14

Upside down T underlined.

Question 15

How are unaffected people with unknown sex represented in pedigree drawings?

Answer 15

Diamond

Question 16

What are autosomal dominant conditions?

Answer 16

• Manifest in HETEROZYGOUS form
• Multiple generations affected
• Both sexes affected
• Male to female & female to male transmission
• Often an affected parent
• 50% risk to offspring

Question 17

What are the features of dominant inheritance to be aware of?

Answer 17

• Incomplete/reduced penetrance: some people have the mutation but do not have the disease
• Variable expressivity: variation in severity/symptoms of disorder between individuals with the same mutation
• De novo mutation rate: not all affected individuals have an affected parent; often depends on severity of disorder; varies greatly between conditions
• Mosaicism: mutation only present in a proportion of cells
• Anticipation: worsening of disease severity in successive generations, e.g. expansion disorders

Question 18

What is incomplete or reduced penetrance?

Answer 18

• Penetrance - Percentage of individuals who carry the mutation AND develop symptoms of the disorder
• many dominant disorders show age-dependant penetrance

Eg. if every one who has the disease has a parent with that same disorder it has high penetrance. But if not everyone that has that disorder has a parent with the same condition, it less penetrance.

Question 19

What is variable expressivity?

Answer 19

• Variation in severity/symptoms of disorder between individuals with same mut^n

Question 20

What is autosomal recessive inheritance?

Answer 20

• 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

Question 21

What are compound heterozygote or homozygote?

Answer 21

Compound heterozygous
* 2 mutns in same gene
* Mutns are different

Homozygote
* 2 mutns in same gene
* Identical mutns

Cystic fibrosis
* ∆F508
* ∆F508

May suggest consanguinity.

Question 22

What are features of autosomal recessive inheritance?

Answer 22

• 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.

Question 23

What is X-linked inheritance?

Answer 23

Females have two X chromosomes
* Two copies of X-linked genes
* Can be homozygous or heterozgous

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

Question 24

What are recessive and dominant X-linked inheritances?

Answer 24

Recessive
- Females are carriers + unaffected
* No male to male transmission
Dominant
* Females are affected
* Males more severely affected/lethal

Question 25

What are features of X-linked recessive inheritances?

Answer 25

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

Question 26

What are characteristics of Y-linked inheritances?

Answer 26

* Always and only passed from fathers to sons

Question 27

What are mutations and variants of these ?

Answer 27

* Mutation: a change in the genetic material * A pathogenic mutation (pathogenic variant) results in an alteration of the function of the gene product and can cause a disease phenotype * What types of mutations are there? * What happens when the amino acid sequence of a protein isn’t what it should be?

Question 28

What are the different types of mutations and where can they be found?

Answer 28

Types: * Substitutions (point mutations) * Deletions * Insertions Found in: * Coding DNA * Non-coding DNA (such as promoters and introns)

Question 29

What are synonymous substitutions?

Answer 29

These are silent mutations - basically there is a base change but it does not change the amino acid. This is usually the 3rd base that is alright to change. Changing the first or second base in a codon means the amino acid changes typically.

Question 30

What are non synonymous missense?

Answer 30

This is where a base change leads to a change in the amino acid sequence. It is difficult to predict their effect.

Question 31

What is the impact of amino acid substitution?

Answer 31

* Physicochemical similarity between the two amino acids * Functional role of the specific domain of the protein affected - is it going to effect it's ability to function? * Phylogenetic conservation of original aminoacid amongst diverse species

Question 32

What is non-synonymous nonsense?

Answer 32

If you have a premature stop codon, it is quite likely to cause a biological effect. It depends on where it is. They are not all damaging.

Question 33

What is insertion of a base?

Answer 33

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

Question 34

What is deletion of a base?

Answer 34

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

Question 35

What are De novo mutations?

Answer 35

Mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease.