Estimating risk of inherited genetic disease Flashcards
Fitness =
relative ability of organisms to survive (long enough) to pass on their genes.
what can affect fitness
alleles:
- not at all in most cases (neutral allele)
- sometimes decrease (deleterious allele)
- rarely increase (advantageous allele)
Few notable common recessive diseases
- Sickle cell disease
- Thalassaemia
Mutation in recessive genes rarely affects
carriers
Mutation in dominant and X-linked genes can be
inherited or de novo
De novo mutation common in
dominant disorders esp. where disease reduces reproductive fitness
- Recently recognised as a common cause of many severe learning disability syndromes
Up to 1/3 of lethal X-Linked cases are due to
a de novo mutation
Dominant conditions (alleles) do not
become more common at the expense of recessive ones!
Relative frequencies remain
constant
Allele frequencies remain
constant generation to generation.
Relative proportion of genotype frequencies remain
constant generation to generation.
Hardy-Weinberg equilibrium (HWE) calculates
expected genotypes
Assumptions underlying HWE
Ideal Population
- 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
60% of men in northwest Scotland have
Norwegian DNA
Introduction of new alleles as a result of
migration or intermarriage leads to new gene frequency in hybrid population.
Mutations increase the
proportion of new alleles.
Non-random mating leads to
increase mutant alleles, thereby increasing proportion of affected homozygotes.
Assortative mating =
Choosing of partners due to shared characteristics
- Deafness & sign language
Consanguinity =
- Marriage between close blood relatives.
Founder effects is caused by
physical or cultural isolation
Natural selection =
A gradual process by which biological traits become either more or less common in a population.
Negative selection
- Reduces reproductive fitness.
- decreases the prevalence of traits.
- leads to gradual reduction of mutant allele
Positive selection
- Increases reproductive fitness.
- Increases the prevalence of adaptive traits.
- Heterozygote advantage.
what recessive disorders lead to resistance to malaria
- sickle cell anaemia
- Thalassaemia
- glucose 6 phosphate dehydrogenase deficiency
what recessive disorders lead to resistance of cholera/typhoid
cystic fibrosis
what recessive disorder leads to resistance of influenza B
congenital adrenal hyperplasia
what recessive disorder leads to resistance of TB
GM2 gangliosidosis (Tay-Sachs)
Large populations can balance out fluctuations, but 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 =
The reduction in genetic variation that results when a small subset of a large population is used to establish a new colony.
- a new colony is started by a few members of the original population
Genetic drift:
Mutations (alleles) are
widespread and neutral
Genetic drift:
Statistical drift of gene frequencies due to
chance or random events rather than natural selection in the formation of successive generations.
Bottleneck effect:
Reduce genetic diversity.
genetic drift causes
bottleneck effect which leads to repopulation and founder effect.
Ellis-van Creveld syndrome
common in amish of Pennsylvania as they marry within their own community.
- natal teeth
- polydacyly - extra fingers
Applications of HWE
- Useful for calculating risk in genetic counselling
- Useful for planning population based carrier screening programmes
