Mendelian Inheritance

Question 1

Mendel’s first law?

Answer 1

Law of segregation: At meiosis each allele (2) of a single gene separates into different gametes –> 50:50 ratio

Question 2

Mendel’s second law?

Answer 2

Law of independent assortment: At meiosis, the segregation of each pair of alleles in 2 more genes is independent –> each 50:50 ratio

Question 3

Two components of heredity that Mendel’s laws explain?

Answer 3

1. How alleles at a single locus segregate independently at meiosis
2. How separate loci (separate genes) also segregate independently

Question 4

Genotype

Answer 4

refers to the molecular sequence of an individual’s DNA

Question 5

Phenotype

Answer 5

refers to the observable expression of a genotype
- morphological 
- clinical 
- cellular 
- biochemical
(depends on your measurement method)

Question 6

Inheritance pattern: In classic Mendelian how many genes are we looking at

Answer 6

1

Question 7

In classic Mendelian disorders, what two features are we looking for to describe a disorder?

Answer 7

Whether it is dominant or recessive

Whether the chromosomal locus is on an autosome or a sex chromosome

Question 8

Are dominance and recessiveness intrinsic properties of a given allele?

Answer 8

No! Dominance and recessivity are not properties instrinsic to a particular allele, but refer to the relationship of one allele to the corresponding allele on the homologous chromosome

Question 9

What makes a trait dominant?

Answer 9

If it is expressed in the heterozygous state –> one mustant allele yields disease

Question 10

What makes a trait recessive?

Answer 10

If it is expressed ONLY in teh homozygous or compound heterozygous state (both alleles must be mutant to yield disease)

Question 11

What is compound heterozygous

Answer 11

Both alleles are mutant but not the same mutation (ie neither is WT)

Question 12

What are codominant traits?

Answer 12

Traits are codominant if both traits (Alleles) are expressed in the heterozygous state

Question 13

When the heterozygous phenotype is intermediate between the two homozygous pehnotypes, what do we call it?

Answer 13

The terms
Semi-dominant or
Incomplete dominant

Question 14

What about when the homozygote is more severe than the heterzygote of a dominant mutation?

Answer 14

In theory a truly dominant trait would be expressed equally in heterozygotes adn homozygotes; this is rarely the case as the homozygous (mutant) forms are typically more severe. However, the term “dominant” is still widely used to refer to most (if not all) cases where the disease is present in the heterozygote (irrespective of the severity of the homozygote)

Question 15

Inheritance Patterns: autosomal dominant

Does it skip generations?

Answer 15

No…phenotype sually appears in every generation, each affected person having an affected parent

Question 16

Inheritance Patterns: autosomal dominant

What is the risk of a child of an affected parent inheriting the trait?

Answer 16

50% risk (assuming other parent WT )

Question 17

Inheritance Patterns: autosomal dominant - what can we say about phenotypically normal parent?

Answer 17

Phenotypically normal parents do not transmit the phenotype to their children.

Question 18

Inheritance patterns: autosomal dominant

Sex?

Answer 18

Males adn females are equally likely to transmit phenotype to children of either sex - in particular, male to male transmission can occur, and males can have unaffected daughters

Question 19

Charateristics of X-linked recessive inheritance

Is the incidence different in sexes?

Answer 19

Yes, the incidence of the trait is much higher in males than in females

Question 20

X-linked recessive characteristics

Heterozygous females?

Answer 20

usually unaffected, but some may express the condition with variable severity as determined by the pattern of X inactivation

Question 21

Characteristics of X linked recessive

What happens to daughters of affected men?

Answer 21

The gene responsible for the condition is transmitted from an affected man to all his daughters. Any of his daughters sons has a 50% chance of inheriting it

Question 22

Characteristics of X linked recessive

Father to son transmission

Answer 22

Not possible!
The mutant allele is never transmitted directly from father to son, but is transmitted by an affected male to ALL is daughters

Question 23

Characteristics of X linked recessive

Mutant allele and female family

Answer 23

The mutant allele may be transmitted through a series of carrier females; if so, the affected males in a kindred are related through females

Question 24

Characteristic of X linked recessive

Isolated cases

Answer 24

A significant proprotion are due to due mutations

Question 25

Characteristics of X linked dominant inheritance | Affected male progeny?

Answer 25

Affected males with normal mates have no affected sons and no normal daughters

Question 26

Characteristics of X linked dominant inheritance | Female carrier progeny?

Answer 26

Both male and female offspring of female carriers have a 50% risk for inheriting the phenotype. The pedigree pattern is similar to that seen with autosomal dominant inheritance

Question 27

Characteristics of X linked dominant inheritance | frequency in females vs males?

Answer 27

Affected females are approximately twice as common as affected males, but affected females typically have milder (although variable) expression of the phenotype

Question 28

Characteristics of autosomal recessive | Where is it usually seen in family tree?

Answer 28

An autosomal recessive phenotype, if not isolated, is usually only seen in the sibship of the proband, and not in parents, offspring, or other relatives

Question 29

Characteristics of autosomal recessive | males vs females?

Answer 29

For most autosomal recessive diseases, males and females are equally likely to be affected

Question 30

Characteristics of autosomal recessive | parents of affected child?

Answer 30

The parents of an affected child are asymptomatic carriers of mutant alleles

Question 31

Characteristics of autosomal recessive | what makes more likely?

Answer 31

if the parents are consanguineous -

Question 32

Characteristics of autosomal recessive | recurrence risk

Answer 32

1/4

Question 33

Metabolic disorders are frequently ________________ (mode of inheritance)

Answer 33

Recessive

Question 34

Metabolic disorders are due to (most common cause)

Answer 34

due to deficiencies of protein (often enzyme) in biochemical pathways.

Question 35

Wilson's disease

Answer 35

example of autosomal recessive metabolic disorder - copper metabolism

Question 36

Wilson's disease - clinical

Answer 36

``` liver disease (cirrhosis) neurological problems ```

Question 37

Wilson's disease clinical give away?

Answer 37

Kayser Fleischer rings - copper around cornea

Question 38

Semi-dominant?

Answer 38

When the heterozygous phenotype is intermediate between the two homozygous phenotypes

Question 39

Mitochondrial inheritance

Answer 39

Non-mendelian inheritance - matrilineal mom has it --> all offspring dad has it --> no offspring

Question 40

Penetrance

Answer 40

The fraction of individuals with a trait (disease) genotype who show ANY manifestation of the disease

Question 41

Age dependent penetrance

Answer 41

The likelihood of manifesting the disease in mutation carriers is dependent on age. Observed in many adult onset conditions

Question 42

Expressivity

Answer 42

The degree to which a trait is expressed in an individual (severity)

Question 43

What helps explain variable expressivity?

Answer 43

sex influence genetic modifiers environment stochastic effects

Question 44

Stochastic effects

Answer 44

random effects - can influence the expression of phenotypes

Question 45

Sex Influence

Answer 45

Phenotypic expression is dependent on individuals sex (e.g. gout is more common in males than premenopausal females)

Question 46

Sex limitation

Answer 46

Occurs if only one sex can express phenotype (e.g. unicornuate uterus)

Question 47

Environmental factors

Answer 47

Some environmental factors can affect the expression of Mendelian genes - disease may only manifest in individuals if particular environmental factors are present

Question 48

In acute intermittent porphyria, episodes of abdominal pain and psychiatric illness are dependent on exposures (alcohol, medications) this is an example of what?

Answer 48

``` Environmental factors (threats to mendel) ```

Question 49

Modifier genes

Answer 49

Genetic factors outside of teh genetic locus causing a disease can be important for the expression of Mendelian diseases

Question 50

Phenocopies

Answer 50

Diseases (Traits) that are due to non-genetic factors. Example: A thyroid cancer due to radiation exposure cannot always be distinguished from a thyroid cancer due to mutations in RET gene

Question 51

Pleiotropy

Answer 51

Used to describe multiple different phenotypic effects due to mutations in a single gene. Often used, when the phenotypes are seemingly unrelated and/or in multiple different tissues.

Question 52

NF type I leads to cafe au lait, neurofibromas, hammartomas, abnormal freckling, and learnign difficulties - this is an example of?

Answer 52

Pleiotropy

Question 53

Threat to Mendelian Inheritance (10)

Answer 53

``` Penetrance Age dependent penetrance Expressivity Sex Influence Sex Limitation Environmental factors Stochastic effects Modifier genes Phenocopies Pleiotropy ```