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Flashcards in Sources of variability in gene expression Deck (20):
1

What is penetrance?

The proportion of individuals with a mutation that develop the disease

2

What is expressivity?

If the disease is present, expressivity refers to the degree to which the disease is expressed i.e. number and severity of clinical features. This is probably affected by additional genetic and environmental factors

3

Give an example of a disease or syndrome that exhibits expressivity

Marfan syndrome - dominant inheritance, but has various types and severity of clinical features within and between generations

4

Give an example of a disease or syndrome that exhibits penetrance

BRCA1 gene mutation - this displays autosomal dominant inheritance, but the cancer may not develop even in generations with the mutation

5

What is "genotype-phenotype correlation"?

This basically means that the type of mutation predicts the type of features in the patient
It is not always true

6

What is a disease or syndrome that demonstrates genotype-phenotype correlation?

Duchenne muscular dystrophy, an X-linked disorder.
Most cases of DMD are caused by deletion, which results in a frameshift that produces unstable mRNA and no dystrophin protein. However,a milder form of the disease is Becker muscular dystrophy, which occurs when a mutation does not cause a frame shift

7

What is mosaicism?

When a post-zygotic mutation results in two or more genetically distinct cell lines, where one of the lines is disease/syndrome causing, which results in a mixed phenotype and (usually) a milder disease

8

What is an example of a disease/syndrome that displays mosaicism?

Monosomy X-turners syndrome

9

Explain the difference between mono-allelic and bi-allelic gene expression

Bi-allelic means that the allele on each chromosome for a gene is expressed i.e. they both produce proteins
Mono-allelic expression is when both alleles are present, but only one is protein producing

10

What are three examples of mono-allelism?

Imprinting, X-activation and autosomal mono-allelic gene expression, which is seen in 10--15% of autosomal genes, thought to be involved with fine-tuning levels of proteins or reactions in the body

11

Explain gene dosage

Genes in which 1 or 3+ functioning copies of a gene are not tolerated, are called dosage sensitive genes.
Gene functions that are dose sensitive include gene products that are the rate limiting factor in a biochemical pathway, gene products that compete with each other etc

12

What is haploinsufficiency?

This occurs when having only one functioning copy of a gene is not tolerated

13

Explain the dominant negative effect

When a protein loses normal function and interferes with normal function in other proteins. This explains why we see loss or protein function in autosomal dominant mutations

14

Give an example of a disease or syndrome that exhibits a dominant negative effect

Autosomal dominant Osteogenesis Imperfectica (OI)
This is a group of diseases characterised by susceptibility to bone fractures due to defects in collagen type 1 synthesis.
In the mild form of the disease, there is a nonsense mutation which does not produce an alpha chain for collagens so less collagen is produced.
In the moderate form, there's usually a missense mutation with glycine - this produces an abnormal form of collagen, which causes severe OI as these collagen clump together and interfere with other structures - this is the dominant negative effect

15

Describe imprinting

Imprinting is gene expression according to the parent of origin. It is the epigenetic silencing of a gene according to the parent it was inherited from , which is reset every generation

16

If a gene is paternally imprinted, is it turned off or on, if it is passed on from the father?

It is ALWAYS turned off, no matter the sex of the child

17

If a gene is paternally imprinted, is it turned off or on, if it is passed on from the mother?

It is ALWAYS turned on, no matter the sex of the child

18

If a gene is maternally imprinted, is it turned off or on, if it is passed on from the mother?

It is ALWAYS turned off, no matter the sex of the child

19

Give an example of an imprinting disorder

Prader-Willi

20

Describe X-inativation

The random, epigenetic inactivation of an X-chromosome, usually in women who are born with two copies. The one that is to be turned off is coated with a protein necessary for inactivation.
However, there is a region on both X chromosomes that escapes inactivation - these are called pseudoautosomal regions, found on the tips of the chromosomes.

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