Estimating Risk of Inherited Genetic Disease Flashcards
fitness
relative ability of organisms to survive (long enough) to pass on their genes
effect of different allels on fitness
- Not at all (neutral)
- Sometimes decrease (deleterious)
- Rarely increase (advantageous)
what may change the importance of certain allales or cause some to become more common in population
selective pressure —> favours those with a selective advantage
effect of mutation in recessive genes
rarely affects carriers
notable common recessive diseases
- sickle cell disease
- thalassaemia
what is uncommon as a cause of disease
De novo recessive mutation
what can mutation in dominant and X-linked genes be from
inherited or de novo
where are de novo mutation common in
dominant disorders (especially where disease reduces reproductive fitness)
what is up to 1/3 due to de novo mutation
lethal X-linked cases
Hardy-Weinberg equations
p + q = 1.0
1.0 = p2 + 2pq +q2 (AA:Aa:aa)
ratio of p to q always works out the same
Briefly descripe genotype and allele frequencies of offspring
- relative frequencies remain constant
- Dominant conditions (alleles) do not become more common at the expense of recessive ones
hardy-weinberg equilibrium
- allele frequencies remain constant generation to generation
- Relative proportion of genotype frequencies remain constant from generation to generation
assumptions made in hardy weinberg equilibrium
6
Only works in an ideal population:
* no mutation (it is ignored)
* not gene flow/migration
* random mating
* no selective pressure
* lare population size
* allele frequencies are equal in all sexes
what does mutation do
increase the proportion of new alleles
what does introduction of new alleles as a result of migration or intermarriage lead to
new gene frequency in hybrid population
what does non-ramdon mating lead to and what types are there (2)
increase mutant alleles, therby increasing proportion of affected homozygotes
Assortative mating: choosing of partners due to shared characteristics (deafness and sign language)
Consanguinity: marriage between close blood relatives
what can founder effects be from
physical or cultural isolation
natural selection
gradual process where traits become more or les common in a population - inc in favourable alleles
What is negative selection
- reduces reproductive fitness (don’t survive to reproduce and pass on “bad” alleles)
- dec the prevalence of traits
- leads to gradual reduction of mutant allele
positive selection
- Inc reproductive fitness
- inc the prevalence of adaptive traits
- heterozygote advantage
what are heterozygote advantages
higher relative fitness than either the homozygous dominant or homozygous recessive genotype -despite carrying a disease-causing allele because their dominant allele protects them from the genetic disease, while their recessive allele protects them from an infectious disease
bad thing about small populations
can exhibit genetic drift and cause founder effect
genetic drift
random fluctuation of one allele transmitted to high proportion of offspring by chance
founder effect
reduction in genetic variation that results when a small subset of a large population is used to establish a new colony
explain how genetic drift arises
statistical drift of gene frequencies due to chance or random events
bottleneck effect
extreme example of genetic drift that happens when the size of a population is severely reduced. Events like natural disasters (earthquakes, floods, fires) can decimate a population, killing most individuals and leaving behind a small, random assortment of survivors.
founder effect
the reduction in genomic variability that occurs when a small group of individuals becomes separated from a larger population
what are the applications of hardy weinberg equilibrium
- useful for calculating risk in genetic counselling
- useful for planning population based carrier screeing programmes
what is important to remember (risk) in some circumstances
weird but in LO somewhere
ethnicity
examples…
weird but in LO
- sickle cell anaemia
- cystic fibrosis
- BRAC1/2
