Genetics I Flashcards
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Why study genetics?
(evolutionary genetics and complex traits)
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Decreased cost per genome has changed the landscape in GENETICS and MEDICINE
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From 1000 genomes to the pangenome: efforts to capture human diversity
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Evolutionary Genetic lectures - themes
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- Genetic variation
- Genetic constitution of an individual and population
- Allele and genotype frequencies
- Evolutionary forces
- Relationship between allele and genotype frequencies in the absence of evolutionary forces (Hardy-Weinberg Equilibrium)
- Reconstructing Evolutionary History
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What is Evolutionary Genetics?
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- Study of how genetic variation leads to evolutionary change
- Genetics of evolution (microevolution)
- Darwin - descent with modification
- Today - genetic change over time
- Genetics of variation
- Within & between organisms
You don’t have any content yet. - Population genetics
- Study of the patterns of genetic variation within and between populations.
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Biological variation within species
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Intra-species differences = genetic
variation (+/- environment)
Other species also exhibit intra-species variation
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Genetic variation is the catalyst for evolution
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- In genetic terms
- source of variation is Mutation
= change in the DNA, producing an altered form (allele) - Evolution is a change in allele (variation) frequency over time
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Biological blueprint - DNA
Sugar-phosphate backbone with paired bases forms the double helix structure
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Types of point mutations
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8
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Genetic transfer of information
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9
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Forms of genetic variation
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Redundancy in the Ge
Side tode means not all SNPs
within exons change the amino acid
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A single SNP can have a major impact on
phenotype
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14
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Coding material (exons) only makes up a small proportion of our genome
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14
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Non-coding variation san affect phenotype
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15
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Gene structure more complex than just coding sequence (exons)
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16
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How much human genetic variation exists?
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17
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We will explore later in the unit how to use genetic variation data to predict susceptibility to specific diseases, ancestry, and the best medication for you (personalised medicine).
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Genetic constitutions
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18
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Genotype frequencies
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19
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How to calculate allele frequency?
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The allele frequency is the basic measure of the genetic constitution of a population
The allele frequency is also the basic measure of evolutionary change
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Terms to remember
* Allele - alternative form (variant at a locus)
* Genotype - genetic constitution of an individual (homozygote/heterozygote)
* Phenotype - trait determined by genotype (+/- environment)
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Summary
* Genetic variation exists within & between organisms and is
the catalyst for evolution
* Evolution is a change in the allele frequency over time
* Allele frequency is the basic measure of the genetic constitution of a population and evolutionary change
NEXT SESSION
Changes in allele frequency can occur due to evolutionary
forces
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Evolution is a 2-step process
Evolution is a change in allele frequency between
generations
- Allele frequency is the genetic constitution of a population
1. Create variation
2. Change allele frequencies
- evolutionary forces
You don't have any content yet.
An understanding of these processes provides the basis for personalised medicine/medical genetics, genetic counselling, forensics, biological anthropology
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* Principles of mutation
- Creates variation
- Makes small changes in allele frequencies
- Is a weak evolutionary force
* Some mutations can have a large impact on phenotype
- e.g. hemoglobin variant and sickle cell disease
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Random genetic drift
Allele frequencies change due to chance
- Sampling variation
* Variation lost
- One allele lost (p=0)
- One allele "fixed" (p=1)
* Affects all populations
Makes isolated populations genetically
different
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*Magnitude is inversely
proportional to N
*Direction is unpredictable
*Allele can be lost (freq. = 0) or
fixed (freq. = 1)
N = population size
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Founder effect - special case of drift
* Only a few founders
* Sampling error
* Results in different allele freq. between parent and founder population
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Example - Founder effect
Ellis van-Greveld syndrome
in Amish
* Autosomal recessive
* Worldwide p < 0.001
* All cases trace to 1 couple
* In founders p = 0.01
* Now p ~ 0.07
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Gene flow (migration)
* Keeps population similar
- Counteracts genetic drift
- Increases genetic variability
- Increases effective population size
Increases genetic variability
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Significant drift outcom Sic es ever evolutionary time
* Reduces genetic variability within populations
* Makes populations different from one another
- e.g. for two isolated populations allele A could be lost in population 1 and become fixed in population 2
* Very important in human evolution
Ne = 10,000 (for species)
Populations much smaller and likely to have been several founder events via migration to new lands - examine this later
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Gene Flow/Migration
Effects of gene flow over time. The two populations
exchange 10 percent of their genes with each generation.
Over time, gene flow acts to make the two populations
more similar genetically.
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Gene Flow/Migration
Has occurred throughout our history including with archaic
hominids - discuss in next
session
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Gene Flow/Migration
QUESTION: The outcome from gene flow counteracts the effect
of what other evolutionary force?
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Natural selection
* Process
- Some genotypes leave more offspring than others
so the frequency of alleles change
* Measure
- Fitness (reproductive success)
* Result
- alleles with higher fitness increase in frequency
* The only adaptive force
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Measure of NS
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Selection can affect the frequency in a population over time
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NS and adaptation
Natural selection acts in different
ways
a. Directional
b. Disruptive
c. Stabilising
d. Balancing selection
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Directional selection
* Consider brain size (MYH16), speech
(FOXP2), pigmentation
* The speed of the change is dependent on mode of expression and starting allele
frequency
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Recent example of selection
Sherpas (and similar
populations) and their ability to
survive at high altitude
- Genes likely to be under selection include EPAS1, EGLN1, PPARA involved in the hypoxia-inducible factor
and other metabolic pathways
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example: Brain evolution
Similar size brain but is neuron production the same?
Variation in the Transketolase-like 1 gene observed between modern human (arginine) and Neanderthal genomes (lysine) associated with differences in neurogenesis.
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Mutation - Selection balance
Mutation continually
produces new alleles
- Usually deleterious
Load of mutations
Selection tries to remove
"bad" alleles
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Evolution is a 2 step process
Evolution is a change in allele frequency between
generations
1. Create variation - mutation
2. Change allele frequencies (evolutionary forces)
- evolutionary forces
* Mutation - Makes variation
* Gene flow (migration) - Mixes variation
* Random genetic drift - Deletes variation
* Natural selection - Selects variation
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A useful corollary
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In the absence of the evolutionary forces
1. Allele frequencies remain constant from generation to
generation in the absence of the evolutionary forces
- Hardy-Weinberg Law (principle)
- Deviations from this relationship indicate evolutionary
forces are at play
- Can be used to estimate genotype frequency in a
population
* Determine carriers of disease gene
* Calculate the likelihood ratio for a match in forensics
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Using H-W
What is the probability of a person carrying a recessive disease gene given PKU occurs in 1 per 10,000 individuals?
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Assortative mating (e.g
consanguineous matings) can
affect genotype frequency
Assortative mating can have biological consequences
increase homozygote and decrease
heterozygote frequency
e.g. rare deleterious
recessive conditions
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Summary
* Genetic variation exists within & between organisms and is the catalyst for
evolution
* Evolution is a change in the allele frequency over time
* Allele frequency is the basic measure of the genetic constitution of a population and evolutionary change
* Changes in allele frequency can occur due to evolutionary forces
* In the absence of these forces, allele frequency remains constant from generation to generation according to the H-W principle
- (p+q)? =1 or p2 + 2pq + q? = 1
- Based on set of assumptions (includes random mating)
* Non-random mating can affect genotype frequencies
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Evolutionary forces have been, and continue to be, important in our
evolutionary history
