genetics week 8

Question 1

what is fitness

Answer 1

the relative ability of organsims to survive long enough to pass on their genes

Question 2

what are de novo mutations

Answer 2

a genetic alteration that is present for the first time in one family member as a result of a mutation
- so mutation seen in individual despite no being seen in their parents

Question 3

where are de novo mutations common

Answer 3

common in dominant disorders

especially where disease reduces reproductive fitness

Question 4

what is the ideal population in HWE

Answer 4

• mutation can be ignored
• migration is negligible (no gene flow)
• mating is random
• no selective pressure
• population size is large
• allele frequencies are equal in the sexes

Question 5

what is gene flow

Answer 5

introduction of new alleles as a result of migration or intermarriage leads to new frequency in hybrid population

Question 6

what is non-random mating

Answer 6

non random mating leads to increase in mutant alleles thereby increasing the proportion of affected homozygotes
assortive mating
- choosing of partners due to shared characteristics e.g. deaf
consanguinity
- marriage between close blood relatives

Question 7

what is the founder effect

Answer 7

the reduction in genetic variation that results when a small subset of a large population is used to establish a new colony

Question 8

what does negative natural selection do

Answer 8

• reduces reproductive fitness
• decreases the prevalence of traits
• leads to gradual reduction of mutant allele

Question 9

what does positive natural selection do

Answer 9

• increases reproductive fitness
• increases the prevalence of adaptive traits
• heterozygous advantage

Question 10

what is genetic drift

Answer 10

change in gene frequencies due to a random chance event

Question 11

what are the two type of mutations cancer arises from

Answer 11

somatic mutations
- non heritable
germline mutations
- heritable

Question 12

what are photo-oncogenes

Answer 12

normal gene that codes for proteins to regulate cell growth and differentiation

Question 13

how many mutations for photo-oncogene to lead to cancer

Answer 13

just one

Question 14

in tumour suppressor genes how many mutations required for cancer development

Answer 14

2 mutations

• first mutation in germline makes susceptible carrier
• second mutation of loss leads to cancer

Question 15

what are DNA damage-response genes

Answer 15

the repair mechanisms for DNA

Question 16

when does cancer arise in DNA damage-response genes

Answer 16

when both genes fail, speeding the accumulation of mutations in other critical genes

Question 17

what does HNPCC result from

Answer 17

failure of mismatch repair genes

Question 18

what happens in failure of mismatch repair genes

Answer 18

• well normally if there was an extra nucleotide with no partner it would be taken out but in failure it remains in sequence and its partner is added in
• this results in micro satellite instability (MSI) which is the addition of nucleotide repeats making areas of the helix longer

Question 19

what are some dominantly inherited cancer syndromes as a result of oncogenes

Answer 19

• MEN2 (multiple endocrine neoplasia)
• familial medullary thyroid cancer
• e.g. RET gene

Question 20

what are some dominantly inherited cancer syndromes as a result of tumour suppressor genes

Answer 20

• breast/ovarian cancer
• FAP
• retinoblastoma
• li-fraumeni syndrome
• e.g. p53, BRCA

Question 21

what are some dominantly inherited cancer syndromes as a result of DNA repair (mis match repair)

Answer 21

• HNPCC/Lynch syndrome

- e.g. MLH1

Question 22

what are risk factors for colorectal cancer

Answer 22

• ageing
• personal history of CRC or adenomas
• high fat low fibre diet
• IBS
• family history

Question 23

what is the adenoma to carcinoma sequence

Answer 23

- normal epithelium 
  (APC mutations occur)
- hyper proliferative epithelium 
  (k ras mutations)
- adenoma 
  (p53 mutations)
- carcinoma

Question 24

what are the different hereditary colorectal cancer (CRC) syndromes

Answer 24

• non polyposis (few to no adenomas) = HNPCC

- polyposis (mulitple adenomas) = FAP (severe), AFAP (less severe) and MAP (varying degrees of polyposis)

Question 25

what do multiple modifier genes of lower genetic risk explain

Answer 25

• why families with history of cancer have no identified mutation
• differences in cancer penetrance in families with same mutation

Question 26

what are the classification of variants in a lab

Answer 26

class 1 = clearly not pathogenic 
class 2 = unlikely to be pathogenic 
class 3 = unknown significance (VUS)
class 4 = likely to be pathogenic 
class 5 = clearly pathogenic

Question 27

what are the challenges in increasing testing

Answer 27

• variant interpretation
• separating pathogenic from benign
• sole cause rather than risk factor (rn looking at only gene causing issue)
• each genome has >500,000 variants

Question 28

what is standard genetic testing

Answer 28

• number of chromosomes and pieces of chromosomes
• targeted to one to a few hundred genes
• aimed at particular conditions considered likely

Question 29

how do you decide the classification of genes

Answer 29

compare them to publications and registers

Question 30

what is talking to families about their genetics

Answer 30

genetic counselling