ANHB1102 Lecture Notes - Lecture 31: Copy-Number Variation, 1000 Genomes Project, Single-Nucleotide Polymorphism
25 May 2018
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Evolutionary Genetics:
What is evolutionary genetics?
-Genetics of evolution (microevolution)
-Darwin - descent with modification
-Today - genetic change over time
-Genetics of variation
-Within and between organisms
What is population genetics?
-Study of the patters and causes of genetic variation
Genetic Variation:
Biological variation within species:
-Many intra-species differences = genetic variation (+/- environment)
-Other species also exhibit intra-species variation
Genetic variation os the catalyst for evolution:
-Genetic terms: source of variation is MUTATION = change in the DNA, producing an altered
gene (allele)
-Evolution is a change in allele (variation) frequency over time
Forms of Variation:
a) Sequence polymorphism (SNPs - Single Nucleotide Polymorphism)
b) Length polymorphism (insertion/deletion)
c) Copy number variation (CNV)
d) Chromosome inversion/genome duplication
Central Dogma of Information Transfer:
Redundancy in the Genetic Code:
Types of Mutations:
-Synonymous/Silent (neutral - No amino acid change)
-E.g TTT (Phe) to TTC (Phe)
-Non-synonymous:
-Missense (amino acid change)
-E.g CCT (Pro) to CAT (His)
-Nonsense (change to termination)
-E.g TGC (Cys) to TGA (Stop)
Haemoglobin Varient Example:
-A and S differ at the 6th codon (β mRNA)
-A = GAG
-S = GUG
-A and S differ at the 6th amino acid (β polypeptide)
-A = glu
-S = val
-Suggests a selective advantage to being heterozygote (protection
against malaria)
Polymorphism and Monomorphism:
-Polymorphism:
-A locus is polymorphic in a population if there are at least two alleles each with frequencies
greater than 1%
-e.g β locus in Ghana
-Monomorphism:
-One allele has a frequency greater than 99%
-E.g β locus in Europe
-Polytypism:
-Differences between populations
-E.g β locus in humans
-Why? prevalence of malaria
How much genetic variation?
-Humans differ on average by 0.1% - this implies that each person is a heterozygote at about 1 in
1000 nucleotide pairs
-= nucleotide diversity (= heterozygosity)
-If the human genome contains ~ 3x 10^9, there are about 3x 10^6 differences between each
person’s maternal DNA and paternal DNA
Summary:
-Genetic variation exists within and between organisms and is the catalyst for evolution
-Humans on average differ by 0.1-0.3%
-Different types of genetic variations
-Human Hapmap and 1000 genomes project increasing our
knowledge of genetic variation in different human
populations
Allele Frequencies:
-Genotype: genetic constitution of an individual
-Phenotype: trait determined by genotype (+/- environment)
-Locus: area on a chromosome
-BB or bb = homozygote
-Bb = heterozygote
Genetic Constitutions:
-An individual (2 allele system - A and a at a single locus)
-Genotype: AA, Aa, aa
-Population
-Allele frequency: - = f(A) and q= f(a)
-Total no. chromosomes with allele/2n
Haemoglobin Variation:
-‘Incomplete’ dominance (AS)
-Heterozygote advantage
Calculating Genotype Frequencies:
-2 allele system - 3 genotypes (frequency always
add to 1)
Document Summary
Study of the patters and causes of genetic variation. Many intra-species differences = genetic variation (+/- environment) Genetic terms: source of variation is mutation = change in the dna, producing an altered gene (allele) Evolution is a change in allele (variation) frequency over time. Forms of variation: sequence polymorphism (snps - single nucleotide polymorphism, length polymorphism (insertion/deletion, copy number variation (cnv, chromosome inversion/genome duplication. Synonymous/silent (neutral - no amino acid change) A and s differ at the 6th codon ( mrna) A and s differ at the 6th amino acid ( polypeptide) Suggests a selective advantage to being heterozygote (protection against malaria) A locus is polymorphic in a population if there are at least two alleles each with frequencies greater than 1% One allele has a frequency greater than 99% Humans differ on average by 0. 1% - this implies that each person is a heterozygote at about 1 in.
