Lecture 12

Question 1

Why are some alleles more common in certain populations?

Answer 1

The founder effect and the heterozygote advantage

Question 2

What is the Founder Effect?

Answer 2

The loss of genetic variation that occurs when a new population is established by a very small number of individuals from a larger population

Question 3

What is a Heterozygote Advantage?

Answer 3

A single copy of a disease allele confers an advantage. E.g. sickle cell anemia

Question 4

What can’t physicians use to diagnose genetic crosses of their patients?

Answer 4

Mendelian Crosses

Question 5

What do Physicians use to predict heredity of rare disease?

Answer 5

Family histories or pedigrees

Question 6

What did Polygamy lead to?

Answer 6

Rare alleles from small groups to be widely spread

Question 7

What is the Propositus?

Answer 7

The first case of a disease that comes to the attention of a doctor

Question 8

What are the characteristics of an Autosomal recessive disorder in a pedigree?

Answer 8

The parents are unaffected (usually)
It can affect both males and females
Entire generations can be unaffected
More frequency when there is inbreeding

Question 9

What is the inheritance of PKU?

Answer 9

Autosomal Recessive

Question 10

What occurs in PKU?

Answer 10

There is a defect in Phenylalanine hydroxylase, a liver enzyme
Causes buildup of phenylalanine & phenylpyruvic acid in the body which affects the development of neurons

Question 11

What can manage PKU?

Answer 11

Low protein diet

Question 12

What are the characteristics of pedigrees with autosomal Dominant disorders?

Answer 12

Generally the disease appears in the parental generation
Tends to appear in every generation
Affected progeny includes males and females

Question 13

What causes Pseudoachondroplasia?

Answer 13

Mutation in the COMP gene that affects the structural integrity of Cartilage. It is a dominant allele and the allele that causes it is homozygous lethal

Question 14

What causes Achondroplasia?

Answer 14

Mutation in the FGFR3 that is a regulator of bone development. Also homozygous lethal

Question 15

What is the inheritance of Piebald spotting?

Answer 15

Autosomal Dominant

Question 16

What occurs in Piebald spotting?

Answer 16

It affects the migration of melanocytes from dorsal to ventral

Question 17

What is Penetrance?

Answer 17

The proportion of percentage of individuals with a specific allele or allele combination (genotype) that display the corresponding phenotype

Question 18

When can we say something is fully penetrant?

Answer 18

When all individuals with this genotype manifest the phenotype

Question 19

When can we say incomplete penetrance?

Answer 19

An allele for which a phenotype manifests is less than 100%

Question 20

Why would the same genotype not always give rise to the same phenotype?

Answer 20

Environment factors e.g. nutrients, exposure to UV light, altitude
Influence of other alleles/genes
Stochastic events e.g. X inactivation

Question 21

What is Expressivity?

Answer 21

The degree to which a given allele influences the phenotype in an individual. It describes the intensity of the phenotype

Question 22

What is the dominance of Polydactyly?

Answer 22

Autosomal dominant

Question 23

What are the characteristics of X linked disorders?

Answer 23

Males are more common than females
No transmission from father to son
Daughters of affected males are carriers
Affected females have affected fathers and carrier mothers

Question 24

What does is Pseudodominant?

Answer 24

In X-linked genes, disease causing recessive alleles in a hemizygous organism/cell

Question 25

What is Hemophilia?

Answer 25

The inability to make fibrin which is used in clotting

Question 26

What is the difference between Hemophilia A and B?

Answer 26

Hemophilia A patients have a mutation in the F8 gene | Hemophilia B patients have a mutation in the F9 gene

Question 27

What is another way that females can have an X-linked disease?

Answer 27

If the X chromosome carrying the wild type allele become deactivated early on in embryogenesis functional mosaicism can occur where the whole organism is mostly the mutated X-chromosome

Question 28

What are the characteristics of X-linked dominant mutations?

Answer 28

A female heterozygote transmits to 1/2 of their children Affected male will transmit to all daughters but not to sons Affected females may be more common than males No transmission from father to son

Question 29

What is the inheritance of Fragile X syndrome?

Answer 29

X-linked dominant

Question 30

What causes fragile X syndrome?

Answer 30

The non-coding region of the FMR1 gene has an increased number of CGG repeats which cause the gene to be turned off (via methylation)

Question 31

What is the Dominance of fragile X syndrome due to?

Answer 31

Haploinsufficiency if the wild type allele

Question 32

What are the 3 types of Mosaicism?

Answer 32

Repeat Length Mosaicism Repeat Methylation Mosaicism X-chromosome inactivation Mosaicism

Question 33

What is Repeat Length Mosaicism?

Answer 33

Because full mutations are mitotically unstable some patients have a mixture of cells with repeat lengths ranging from permutation to full mutation

Question 34

What is Repeat Methylation Mosaicism?

Answer 34

Some patients have a mixture of cells with and without methylation of CGG repeat

Question 35

What causes repeat sequences in DNA?

Answer 35

Strand slippage of the newly synthesized strand which causes the replication machine to believe that it missed nucleotides so it goes back and synthesizes them

Question 36

How do Trinucleotide expansions occur?

Answer 36

CAG next to CAG tend to attract to each other which cause the slippage

Question 37

How does Fragile X syndrome occur?

Answer 37

There is an increased number of CGG nucleotides in the untranslated region which causes a loss of function of the gene because RNA binding is impaired

Question 38

What is the cause of Huntington disease?

Answer 38

Increased CAG produces polyglutamine which give the gene new function through increased transcriptions

Question 39

What is methylation?

Answer 39

When a Methyl group is added to a cytosine nucleotide and signals for the associated gene to be transcripted less

Question 40

How does DNA methylation cause gene repression?

Answer 40

The methylation marks DNA for repression and this attracts proteins like MeCP2 which recruits other repression proteins that make DNA inaccessible

Question 41

What occurs in Rett Syndrome?

Answer 41

In the X-linked dominant disease there is a mutation in the MeCP2 a DNA binding protein that regulates many genes which is critical for brain function and development. Only occurs in females because males die