Genetic principles

Question 1

What is the difference between somatic cells and gametes?

Answer 1

• Somatic cells are diploid (most body cells)
• Gametes are haploid

Question 2

What are alleles?

Answer 2

Alternative forms of gene

Question 3

If a gene displays genetic polymorphism what does this mean?

Answer 3

Genes exist in multiple forms (alleles)

Question 4

What is the locus (plural loci)?

Answer 4

Location of allele on chromosome

Question 5

What is the wild type gene/allele?

Answer 5

Gene/allele that is common in most individuals (A in Aa)

Question 6

What is the difference between a germilne and a somatic mutation?

Answer 6

Germ line
- DNA of sperm/eggs
- Transmitted to offspring
- Found in every cell of the body

Somatic mutations
- Acquired during lifespan of cell
- Not transmitted to offspring

Question 7

What is codominance?

Answer 7

When both alleles contribute to phenotype

Question 8

Give a common example of codominance?

Answer 8

Blood groups ABO
AB individuals will express both A and B antigens

Question 9

What is penetrance?

Answer 9

Proportion with allele that express phenotype

Question 10

What is incomplete penetrance?

Answer 10

Not all those with disease mutation develop disease

Question 11

Give an example of a gene mutation which displays incomplete penetrance?

Answer 11

BRCA1 and 2
- Usually Aut dominant disease

Question 12

What is expressivity?

Answer 12

Variations in the phenotype of gene

Question 13

What is an example of a disease which displays expressivity?

Answer 13

Neurofibromatosis type 1 (NF1)
- Aut dom
- 100% penetrance
- Extremely variable severity

Question 14

What is pleiotropy?

Answer 14

One gene which can have multiple different phenotypic effects and traits
- e.g one gene affecting skin, eyes and brain

Question 15

Give some examples of pleitropy

Answer 15

• PKU - skin, body odor, brain
• Marfan - CV, limbs
• CF - pancreas, lungs
• Osteogenesis imperfecta - eyes, limbs, hearing

Question 16

What genes are involved in the 2-hit hypothesis?

Answer 16

Tumour suppressor genes

Question 17

What is the more colloquial term for loss of heterozygosity?

Answer 17

2 hits
- Cancer requiring mutation of both alleles

Question 18

What percentage of retinoblastoma cases are heriditary?

Answer 18

40%
- Have one gene mutated in all cells at birth (germline mutation)

Question 19

HNPCC (Lynch syndrome) has a germline mutation in what genes?

Answer 19

Mismatch repair genes
- Example of 2-hit hypothesis
- 1 inherited germline mutation
- 2nd ‘hit’/mutation/inactivation will occur during lifetime -> cancer

Question 20

What percentage of those with FAP develop colon cancer?

Answer 20

100%
- Prophylactic colectomy

Question 21

What cancers are those with Li-Fraumeni Syndrome most at risk of?

Answer 21

• Sarcoma
• Breast
• Leukemia
• Adrenal gland

Question 22

What gene is mutated in Li-Fraumeni syndrome?

Answer 22

TP53

Question 23

What is mosaicism?

Answer 23

Gene differences in cells of the same individual

Question 24

What can germline mosaicism appear like?

Answer 24

May appear like a sporadic disease in offspring as it is difficult to detect
- In reality it is germline mosaicism passed down from parent

Question 25

What is somatic mosaicism?

Answer 25

Gene differences in tissues/organs of an individual that do not involve the germline cells

Question 26

What diseases may have somatic mosaicism?

Answer 26

- Milder forms of Turner syndrome (45X/46XX) - Rare forms of Down syndrome (some cells have trisomy 21, others do not)

Question 27

What syndrome is often used as an example of mosaicism?

Answer 27

McCune-Albright syndrome

Question 28

What are the features of McCune-Albright syndrome?

Answer 28

- Effects endocrine organs - Precocious puberty - Fibrous growth in bones (fractures, deformity) - Skin pigmentation (Cafe au lait spots. irregular borders)

Question 29

How early can menstraution occur due to precocious puberty in cafe au lait syndrome?

Answer 29

2 years old

Question 30

When does the mutation occur in Mccune-Albright syndrome?

Answer 30

- Sporadic mutation in development, after fertilization - Only some tissues affected, varied presentation due to - Not inherited from parent

Question 31

What gene is somatically mutated in McCune Albright syndrome?

Answer 31

GNAS gene

Question 32

What does GNAS gene code for (McCune-Albright)?

Answer 32

- Alpha subunit of G3 protein - Activates for adenylyl cyclase - Continued stimulation of cAMP signaling

Question 33

Why are germline GNAS mutations never seen?

Answer 33

They are lethal as entire body is affected

Question 34

Explain genetic heterogeneity?

Answer 34

Same phenotype from different genes/mutations - Multiple gene mutations often causing the same disease, many diseases have multiple genotypes causing them

Question 35

What is allelic heterogeneity?

Answer 35

When multiple different alleles can cause the same disease - However mutation will be found at the same loci

Question 36

Give 2 examples of diseases which express allelic heterogeneity?

Answer 36

- Beta thalassemia - Cystic fibrosis

Question 37

What is locus heterogenity?

Answer 37

When mutations at different loci can cause the same disease

Question 38

Give an example of a disease which displays locus hetergeneity?

Answer 38

Retinitis Pigmentosum - X-linked, aut dom and AR forms - 43 different loci can cause disease

Question 39

How is retinitis pigmentosum inherited?

Answer 39

Aut dom