Estimating risk of inherited disease and genetic predisposition to cancer

Question 1

What is anticipation?

Answer 1

Anticipation is the phenomenon whereby a disease presents earlier and with increasing severity in successive generations. It is a feature of triplet repeat diseases, and in each generation more triplet repeats are present

Question 2

What is fitness?

Answer 2

affected by alleles, its the relative ability of organisms to survive and pass on genes.

Question 3

What factors can increase or decrease fitness?

Answer 3

Advantageous alleles can increase fitness, deleterious alleles can decrease it, neutral alleles don’t affect fitness

Question 4

What is the equation used to estimate allele frequencies?

Answer 4

Hardy Weinberg equation - p2+|2pq|+q2=1

Question 5

What does the hardy weinburg equation rely on?

Answer 5

large population, random mating, no migration, mutations ignored, no selective pressures,

Question 6

What is genetic drift?

Answer 6

random fluctuation of alleles transmitted to a large population of offspring by chance

Question 7

What is founder effect and what does it lead to?

Answer 7

Small group migrates and allele frequency decreases a lot. Leads to bottleneck effect - less individuals and less diversity

Question 8

What is the cause of the majority of cancers?

Answer 8

Environmental factors or by chance. only a few are genetic predispositions

Question 9

Which genes lead to a cancer mutation?

Answer 9

Non heritable somatic - not germline

Question 10

What are the three main genetic process that lead to cancer?

Answer 10

Oncogenes, tumour supressor genes (RB), DNA damage response genes (p53)

Question 11

How can oncogenes lead to cancer?

Answer 11

Proto-oncogene is normal gene that codes for proteins. If this is mutated, it changed to oncogene, which changed cells mechanism for division, usually accelerating it

Question 12

How can tumour suppressor genes lead to cancer?

Answer 12

They are the cell’s brakes for cell division. It tells a cell when to die, slow growth or repair DNA. Retinoblastoma is an example, and if its mutated, it can lead to cells multiplying uncontrollably

Question 13

How can DNA damage repair genes lead to cancer?

Answer 13

Mutations in P53 or MLH1 leads to mismatch repair failure at G2-M phase of cell cycle, so mutated genes can exist and multiply.

Question 14

How can we tell if a cell has an abnormal mismatch repair mechanism?

Answer 14

It will present with errors in the form of microsatellites

Question 15

What are 2 examples of a tumour suppressor gene mutation?

Answer 15

BRCA 1/2 mutations lead to breast and ovarian cancers.
Retinoblastoma Mutations result in retinoblastoma cancer

Question 16

What is a de-novo mutation and which cancers does it commonly cause?

Answer 16

One which occurs as a result of a germ cell, so has no family history. Leads to 50% of all RB and MEN (multiple endocrine neoplasia) cancers

Question 17

What are risk factors for breast/ovarian cancer?

Answer 17

inherited variants of BRCA 1/2 can lead to this. Also DNA mismatch repair - TP53. poor diet, exercise, age, family history, late menopause, early period. all increase breast cancer risk

Question 18

What are the risk factors for colorectal cancer?

Answer 18

Mainly due to mismatch repair failure. Family history and diet important. MLH1 protein expression fails.

Question 19

What is penetrance?

Answer 19

The probability that a person carrying a gene will manifest the trait. E.g. if 4/12 people carrying a recessive gene develop symptoms, penetrance is 33%

Question 20

What is non-mendelian inheritance?

Answer 20

The inheritance of traits that have a more complex genetic basis than dimple dominant/ recessive inheritance of alleles leading to definite expression

Question 21

Who can do genetic counselling?

Answer 21

Clinical geneticist, GPs, hospital doctors, nurse specialists

Question 22

What are examples of imprinting disorders, and what they’re an example of?

Answer 22

Angleman syndrome and Prader-Willi syndrome. These are imprinting disorders

Question 23

What are characteristics of colorectal cancer?

Answer 23

Polyposis in the colon - usually become cancerous (small bumps)