Lecture 5: Patterns of Inheritance

Question 1

What is a pedigree chart?

Answer 1

A pedigree chart is a diagram that shows the occurrence and appearance or phenotypes of a particular gene or organism and its ancestors from one generation to the next.

Question 2

What is important to consider about the inheritance of a mutation and the inheritance of a disease?

Answer 2

Inheritance of a mutation is not always the same as the inheritance of a disease as genes are not always expressed, or are expressed in varying degrees, so a mutation may not automatically lead to its associated disease.

Question 3

Who is the ‘proband’?

Answer 3

The ‘proband’ is the individual that is the focus of the pedigree chart.

Question 4

What is a consanguineous relationship?

Answer 4

Relationship between individuals who are closely related. Though it may involve incest, it implies more than the sexual nature of incest. In a clinical sense, marriage between two family members who are second cousins or closer qualify as having a consanguineous marriage.

Question 5

What is the nature of recessive mutations?

Answer 5

If the mutation causes the gene to not be expressed, or it is non-functional, the mutation is said to recessive

Question 6

What is the nature of dominant mutations?

Answer 6

If the mutation causes a change in the function of a protein, and leads to a change in the phenotype expressed, the mutation is said to be dominant.

Question 7

What happens when 1 dominant allele is inherited?

Answer 7

The presence of one dominant allele will mean the allele will be expressed in the phenotype.

Question 8

What is an example of an autosomal dominant disorder?

Answer 8

Achondroplasia

Question 9

What is the likelihood of transferring the autosomal dominant mutant allele?

Answer 9

A couple with one affected individual will have a 50% chance of producing offspring with the disorder.

Question 10

What is achondroplasia and how is it caused?

Answer 10

Achondroplasia results in dwarfism. Achondroplasia is caused by a mutation to the fibroblast growth factor receptor 3 (FGFR3) and results in abnormalities in cartilage formation. 7/8 of all cases are caused by new mutations.

Question 11

What is reduced penetrance?

Answer 11

Penetrance refers to the proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder. If some people with the mutation do not develop features of the disorder, the condition is said to have reduced (or incomplete) penetrance.

Question 12

What is the likely cause of reduced penetrance?

Answer 12

Gene could be inherited but not expressed due to gene interactions (epistasis) or the environment.

Question 13

What is an example of a disorder with reduced penetrance?

Answer 13

Retinoblastoma has a penetrance of 90%, meaning 10% of individuals that inherit the genes do not exhibit the disorder.

Question 14

What is age-dependent penetrance?

Answer 14

The older a person is, the more likely he or she is to develop the condition if carrying a susceptible genotype.

Question 15

What is an example of a disorder with age-dependent penetrance?

Answer 15

Huntington’s Disease

Question 16

What causes Huntington’s Disease?

Answer 16

Triplet repeat expansion of CAG codon on chromosome 4; number of repeats increases with age, and the more repeats present, the more likely an individual is to develop the disorder. CAG codes for glutathione amino acid.

Question 17

Who is most likely to be affected by Huntington’s Disease?

Answer 17

Individuals with more than 40 CAG codon repeats, are expected to develop Huntington’s Disease as the high level of proteins with glutathione causes the formation of plaque in the nervous system.

Question 18

What causes the Huntington’s Disease gene mutation?

Answer 18

Mutation of genes leading to Huntington’s Disease during gametogenesis. Males are at greater risk of inheriting and passing on disease as sperm is constantly being produced and disease has the opportunity to progress.

Question 19

How are females at less risk of developing and passing on Huntington’s Disease?

Answer 19

Females tend to have a set number of CAG codons in their eggs, which may or may not lead to Huntington’s Disease, as females are born with all possible eggs, and do not continuously produce gametes; however, ‘fragile egg’ genetic disorder means that female eggs can continue to mutate even though they do not undergo continuous gametogenesis.

Question 20

What is variable expression?

Answer 20

Describes the phenomenon of differing clinical features or phenotype among individuals carrying the same gene allele or genotype.

Question 21

How does variable expressivity differ from reduced penetrance?

Answer 21

Expressivity differs from penetrance, which describes the probability that a genetic variation (or allele) will yield the phenotype at all. Variable expression means individuals will experience different severities of the disease, despite inheriting the same genes.

Question 22

What is an example of a disorder with variable expressivity?

Answer 22

: Neurofibromatosis is a common disorder of the nervous system, eyes and skin and often leads to patches of skin pigmentation on the skin.

Question 23

What is the likely cause of variable expressivity?

Answer 23

Possible environment cue may affect the expression of the gene.

Question 24

What happens when 1 recessive allele is inherited?

Answer 24

Individual becomes a carrier of the autosomal recessive mutation. Due to the possibility of a functioning gene in the other chromosome, it is possible that the faulty gene is compensated for.

Question 25

How are autosomal recessive mutations caused?

Answer 25

Disorders are caused by mutations that result in the loss of a functional gene product due to insertions, selections, premature stop codons, and frame shift mutations. The majority of new mutations are deleterious and recessive.

Question 26

What is an example of an autosomal recessive disorder?

Answer 26

Cystic Fibrosis (CF)

Question 27

What causes Cystic Fibrosis (CF)?

Answer 27

Cystic Fibrosis (CF) is caused by deletion mutation (of CTT) to gene 508 on chromosome 7; loss of phenylalanine amino acid leading to the formation of a non-functional protein that would otherwise result in the formation of the cystic fibrosis transmembrane conductance regulator (CFTR) protein.

Question 28

What is needed for a autosomal recessive disorder to be expressed?

Answer 28

Individual needs to be heterozygous recessive for the gene in order to express the phenotype and the disorder. Carriers do not express the phenotype of the condition.

Question 29

What is the inbreeding coefficient (f)?

Answer 29

The probability that two genes at any locus in an individual are IDENTICAL BY DESCENT from the common ancestor of the two parents.

Question 30

What does inbreeding do?

Answer 30

Inbreeding increases likelihood of homozygosity which is bad for recessive mutations. Inbreeding increases the risk of inheriting recessive mutations.

Question 31

What is assumed for the inbreeding coefficient to work?

Answer 31

The technique assumes that there are 2 forms of a gene and that each form has an equal chance to be passed on to the next generation.

Question 32

What is compound heterozygosity?

Answer 32

The presence of two different mutant alleles at a particular gene locus, one on each chromosome of a pair. The human genome contains two copies of each gene, a paternal and a maternal allele. A mutation affecting only one allele is called heterozygous.

Question 33

What are sex-lined mutations?

Answer 33

Diseases that are passed down through families through one of the X or Y chromosomes. X and Y are sex chromosomes.

Question 34

Where are sex-linked mutations most common?

Answer 34

Sex-linked disorders are most common in males, due to the presence of only one X chromosome which always appears dominant for males. The presence of 2 X chromosomes in females, means that there is a possibility that the other X chromosome does not contain a mutation and so the mutated gene is expressed as a recessive mutation.

Question 35

What happens to the second X chromosome in females during early embryogenesis?

Answer 35

One of the females X chromosomes in inactivated (lyonisation) during early embryogenesis as only 1 X chromosome is needed; if this was not the case, males would not be able to function.

Question 36

How can you distinguish between X-linked recessive and X-linked dominant inheritance?

Answer 36

X-linked recessive genes are expressed in females only if there are two copies of the gene (one on each X chromosome). However, for males, there needs to be only one copy of an X-linked recessive gene in order for the trait or disorder to be expressed. Families with an X-linked recessive disorder often have affected males, but rarely affected females, in each generation.

For X-linked dominant diseases, however, a mutation in one copy of an X-linked gene will result in disease for both males and females. Families with an X-linked dominant disorder often have both affected males and affected females in each generation.