Inheritance Patterns

Question 1

Male shape

Answer 1

Square

Question 2

Female shape

Answer 2

Circles

Question 3

Partners shape

Answer 3

Line between the shapes

Question 4

Siblings shape

Answer 4

Line above them

Question 5

Children shape

Answer 5

Line down

Question 6

Affected people

Answer 6

Shaded

Question 7

Carriers

Answer 7

Dots

Question 8

Double line represents…

Answer 8

Union of consanguineous couple

Question 9

Stillborn baby

Answer 9

Diamond with SB

Question 10

Spontaenous abortion

Answer 10

Triangle

Question 11

Therapeutic abortion

Answer 11

Triangle with line

Question 12

Non-identical Twins

Answer 12

Diamond line

Question 13

Identical twins

Answer 13

Line closing diamond

Question 14

Unknown shape

Answer 14

Diamond shape

Question 15

No offspring

Answer 15

Double line

Question 16

Define autosomal dominant

Answer 16

• Mainfest in Heterozygous form
• Homozygous is lethal
• Multiple generations affected
• Both sexes affected (not sex-linked)
• Male to female and female to male transmission
• Affected parent -> dominant conditions are heterzoygous, only need one allele copy
• May rely on transmissions
• May rely on de novo mutations
• 50% risk to offspring

Question 17

Characteristics of autosomal dominant

Answer 17

• Most individuals have an affected patient
• Males and females are equally likely to inherit the allele and be affected.
• Risk for each child of an affected parent is 1/2.
• 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.

Question 18

What is penetrance?

Answer 18

Percentage of individuals who carry the mutation and develop symptoms of the disorder. (May have the genotype but not expressed phenotypically)

Question 19

Age-dependent penetrance

Answer 19

Individuals may develop the conditions later in life.

Question 20

Incomplete penetrance

Answer 20

Mutant allele but not having the disease can be due to the interaction of the environment or hormonal protection from conditions.

Question 21

How is penetrance calculated?

Answer 21

By the number of individuals and divide by the number of people with the genotype. There are very few diseases that are 100% penetrant.

Question 22

Features of autosomal dominant inheritance

Answer 22

• Penetrance
• Variable expressivity
• New mutation rate
• Somatic mosaicism
• Germ-line mosaicism
• Anticipation

Question 23

What is variable expressivity?

Answer 23

Variation in severity/symptions of disorder between individuals with the same mutation e.g. neurofibromatosis type 1

Question 24

What is new mutation rate feature in ADI?

Answer 24

De novo mutation rate varies considerably between AD conditions

Question 25

What is somatic mosaicism feature in ADI?

Answer 25

New mutation arising at early stage in embryogenesis | - Present in only some tissues/cells

Question 26

What is germ-line mosaicism feature in ADI?

Answer 26

New mutation arises during oogenesis or spermatogenesis

Question 27

What is anticipation in ADI?

Answer 27

worsening of disease severity in successive generations | - Occurs in triplet repeat disorders/expansion disorders

Question 28

Define autosomal recessive inheritance

Answer 28

- Both copies of the gene are affected for the condition to be present - 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 29

What is compound heterozygote in ARI?

Answer 29

2 mutations in the same gene and the mutations are different

Question 30

What is homozygote in ARI?

Answer 30

2 mutations in the same gene and the mutations are identical which may suggest consanguinity

Question 31

Example of compound heterozygote

Answer 31

Deletion at position 508 on the cystic fibrosis gene. Two different mutations can cause cystic fibrosis

Question 32

atures of ARI

Answer 32

- Trait often found in clusters of siblings but not in parents and offspring (unlike dominant inheritance which is seen in multiple generations) - 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 - 25% affected, 50% carriers, 25% unaffected

Question 33

Define X-linked inheritance

Answer 33

In women, can be homozygous or heterozygous as two copies of X-linked genes In men, hemizygous because only one single copy of X-linked genes.

Question 34

Where does recessive X-linked inheritance occur?

Answer 34

Women are carriers + unaffected | No male to male transmission - men will give their Y chromosome to son

Question 35

Where does dominant X-linked inheritance occur?

Answer 35

Women are affected | Males more severly affected/lethal.

Question 36

What are some important aspecfts of X-linked recessive inheritance?

Answer 36

- 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 mutant allele.

Question 37

What is skewed X-inactivation?

Answer 37

The healthy X-chromosome is switched off. A smaller proportion of cells will have less of the healthy X chromosome and more will have the unhealthy X chromosome even if the condition is homozygous. This leads to manifesting carriers.

Question 38

What are manifesting carriers?

Answer 38

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

Question 39

What is Y-linked inheritance?

Answer 39

Always and only passed from fathers to sons

Question 40

Mutation

Answer 40

A change in the genetic material

Question 41

Pathogenic mutation

Answer 41

An alteration of the function of the gene product and can cause a disease phenotype.

Question 42

What types of mutations are there?

Answer 42

Substitutions (point mutations) Deletions Insertions

Question 43

Where are mutations found?

Answer 43

In coding DNA | Non-coding DNA (such as promoters and introns)

Question 44

What is a silent or synonymous base substitutions?

Answer 44

Nucleotide change without amino acid change; synonymous substitution

Question 45

What is a point mutation - missense?

Answer 45

Base substitution and the amino acid result is a missense change. A change in the bases results in the change of the amino acids.

Question 46

What is a nonsense point mutation?

Answer 46

- Introduction of a stop codon resulting in a truncated protein. - Can cause removal of functional parts of protein - However, mRNA strand can sometiems be degraded via nonsense mediated decay.

Question 47

Two types of indels

Answer 47

In Frame (multiple of three) or Frameshift (not multiple of three)

Question 48

What type of mutation is a frameshift?

Answer 48

Can be pathogenic