genetics week 8 Flashcards
what is fitness
the relative ability of organsims to survive long enough to pass on their genes
what are de novo mutations
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
where are de novo mutations common
common in dominant disorders
especially where disease reduces reproductive fitness
what is the ideal population in HWE
- 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
what is gene flow
introduction of new alleles as a result of migration or intermarriage leads to new frequency in hybrid population
what is non-random mating
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
what is the founder effect
the reduction in genetic variation that results when a small subset of a large population is used to establish a new colony
what does negative natural selection do
- reduces reproductive fitness
- decreases the prevalence of traits
- leads to gradual reduction of mutant allele
what does positive natural selection do
- increases reproductive fitness
- increases the prevalence of adaptive traits
- heterozygous advantage
what is genetic drift
change in gene frequencies due to a random chance event
what are the two type of mutations cancer arises from
somatic mutations
- non heritable
germline mutations
- heritable
what are photo-oncogenes
normal gene that codes for proteins to regulate cell growth and differentiation
how many mutations for photo-oncogene to lead to cancer
just one
in tumour suppressor genes how many mutations required for cancer development
2 mutations
- first mutation in germline makes susceptible carrier
- second mutation of loss leads to cancer
what are DNA damage-response genes
the repair mechanisms for DNA
when does cancer arise in DNA damage-response genes
when both genes fail, speeding the accumulation of mutations in other critical genes
what does HNPCC result from
failure of mismatch repair genes
what happens in failure of mismatch repair genes
- 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
what are some dominantly inherited cancer syndromes as a result of oncogenes
- MEN2 (multiple endocrine neoplasia)
- familial medullary thyroid cancer
- e.g. RET gene
what are some dominantly inherited cancer syndromes as a result of tumour suppressor genes
- breast/ovarian cancer
- FAP
- retinoblastoma
- li-fraumeni syndrome
- e.g. p53, BRCA
what are some dominantly inherited cancer syndromes as a result of DNA repair (mis match repair)
- HNPCC/Lynch syndrome
- e.g. MLH1
what are risk factors for colorectal cancer
- ageing
- personal history of CRC or adenomas
- high fat low fibre diet
- IBS
- family history
what is the adenoma to carcinoma sequence
- normal epithelium (APC mutations occur) - hyper proliferative epithelium (k ras mutations) - adenoma (p53 mutations) - carcinoma
what are the different hereditary colorectal cancer (CRC) syndromes
- non polyposis (few to no adenomas) = HNPCC
- polyposis (mulitple adenomas) = FAP (severe), AFAP (less severe) and MAP (varying degrees of polyposis)
what do multiple modifier genes of lower genetic risk explain
- why families with history of cancer have no identified mutation
- differences in cancer penetrance in families with same mutation
what are the classification of variants in a lab
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
what are the challenges in increasing testing
- 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
what is standard genetic testing
- number of chromosomes and pieces of chromosomes
- targeted to one to a few hundred genes
- aimed at particular conditions considered likely
how do you decide the classification of genes
compare them to publications and registers
what is talking to families about their genetics
genetic counselling
