Genomes, Inheritance/Genetics, & Phenotypes€¦ · Inheritance/Genetics Genetic and Phenotypic...
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Genomes, Inheritance/Genetics, & Phenotypes Gregor Gorjanc & John Hickey @GregorGorjanc @HickeyJohn www.AlphaGenes.Roslin.ed.ac.uk
Transcript of Genomes, Inheritance/Genetics, & Phenotypes€¦ · Inheritance/Genetics Genetic and Phenotypic...
Genomes, Inheritance/Genetics, & Phenotypes
Gregor Gorjanc & John Hickey
@GregorGorjanc @HickeyJohnwww.AlphaGenes.Roslin.ed.ac.uk
Roadmap
Genome
Inheritance/Genetics
Genetic and Phenotypic values
Some numbers …
• N pairs of chromosomes(1 chrom. = 1 DNA molecule)
• Chromosome ~108 base pairs
• Genome ~x109 base pairs
• #SNP– human ~50-100x106
– livestock ~10- 20x106
Allele coding
• C-G base pair present in most samplesà major allele, named as A, coded as 0
• T-Aà minor allele, named as a, coded as 1
• Genotype & Allele dosages– AA = 0 + 0 = 0– Aa = 0 + 1 = 1– aA = 1 + 0 = 1– aa = 1 + 1 = 2
Chromosome painting
… in a conceptual breeding program
Generations
..
1
2
..
n
..
Paint founder chromosomes
Roadmap
Genome
Inheritance/Genetics
Genetic and Phenotypic values
Meiosis
• Recombination• Segregation• Linkage & Linkage disequilibrium
Inheritance
Daddy Mammy
Children
1 1 0 1 0 0
0 1 1 0 1 0
1 1 1 1 0 0 1 1 0 1 0 0
1 1 0 1 1 1
0 0 1 0 1 0
1 0 1 0 1 1 1 1 0 1 1 1
1 2 1 1 1 0 1 1 1 1 2 1
2 1 2 1 1 1 2 2 0 2 1 1
Some numbers …
• ~1 recombination per chromosome– recombination rate ~1x10-8
– 1 Morgan (=100 cM) chromosome– r ~ Poisson(l = 1)
• ~2 mutations per chromosome– mutation rate ~2x10-8
– 23x2x2 = ~100 new mutations – ~100 new + 2x50 old + … + 4x25 old-old +– ~1 new mutation has an effect?
Other processes
Daddy Mammy
Children
1 1 0 1 0 0
0 1 1 0 1 0
1 1 1 0 0 1 1 0 1 0 0
1 1 0 1 1 1
0 0 1 0 1 0
1 0 1 0 1 1 1 1 1 1 1 1 1
1 2 1 1 1 0 1 1 1 1 2 1
2 1 ? 1 1 1 ? 2 2 0 2 1 1
Roadmap
Genome
Inheritance/Genetics
Genetic and Phenotypic values
From genomes to phenotypes?
Phenotype = Function(Genomes, Environment)
But what is The Function?
Assume an additive function
• Simple 1st order approximation of The Function• With additive effects and no environment interaction
Phenotype = Dosage1 * Effect1 +Phenotype = Dosage2 * Effect2 +
Phenotype = … +Phenotype = Dosagen * Effectn +
Phenotype Noise
Effect size?
• Empirical data suggest only few large effects• Let’s assume a standard normal distribution
Freq
uenc
y
Effect
QTN Effect1 -2.702 +0.013 +1.504 -0.635 +0.346 -0.02
Haploid and Diploid genetic values(chromosomal/haplotype & Individual)
• What are min & max haploid/diploid values?
Daddy
1 1 0 1 0 0
0 1 1 0 1 0
1 2 1 1 1 0
QTN Effect Gen1 Gen2 Ind1 -2.70 -2.70 0 -2.702 +0.01 +0.01 +0.01 +0.023 +1.50 0 +1.50 +1.504 -0.63 -0.63 0 -0.635 +0.34 0 +0.34 +0.346 -0.02 0 0 0
Total -3.32 1.85 -1.47
Genome and individual genetic values
Daddy Mammy
Children
1 1 0 1 0 0
0 1 1 0 1 0
1 1 1 1 0 0 1 1 0 1 0 0
1 1 0 1 1 1
0 0 1 0 1 0
1 0 1 0 1 1 1 1 0 1 1 1
1 2 1 1 1 0 1 1 1 1 2 1
2 1 2 1 1 1 2 2 0 2 1 1
-3.32
+1.85
-1.47
-0.36
-2.22
-1.82
+1.84
-1.16
-3.00
-3.00
-5.35
-2.35
Hypoth. architecture for cattle coat color
Most phenotypes are polygenic
-5.35
-1.16
-1.47
Thousands of QTN
Polygenic Model
Population version
Most traits are polygenic
• 23andMe & UKBB, n ~ 300,000• 124 hits, explain ~25-35% hair color heritability
Roadmap
Genome
Inheritance/Genetics
Genetic and Phenotypic values
Genomes, Inheritance/Genetics, & Phenotypes
Gregor Gorjanc & John Hickey
@GregorGorjanc @HickeyJohnwww.AlphaGenes.Roslin.ed.ac.uk
