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Quantitative Genetics
Quantitative traits are described by a frequency distribution
Figure 18-3b
Variation in quantitative traits increases in progeny
Mendelian Behavior
Quantitative Behavior
A norm of reaction is the relation between environment and phenotype
Figure 18-6
Crosses are performed to test for heritability
Figure 18-11
Selection altered bristle number
Figure 18-14
Heritability
h2 = genetic variation phenotypic variation
Measured using resemblance between relatives
Genetic + environmental + interaction
Quantitative Trait Loci (QTL):the specific loci whose allelic differences are
responsible for the genetic variation in a quantitative trait (e.g. total sleep time)
Note: QTL does not refer to the sum total of all loci that influence a particular trait, only those
loci that are functionally polymorphic (with respect to the trait of interest in a given
environment) between the parental strains or within the population. In mice, Mutagenesis and engineered KOs can artificially alter any gene, however, “natural” polymorphisms can
represent more subtle variations.
QTL Mapping• QTL mapping: identification of chromosomal regions containing
gene(s) that correlate with measured phenotypes
• Different methods– Single-marker analysis: compares phenotypic means of different
marker genotypes – Interval mapping: estimates position of QTL between two markers using
maximum likelihood (compares null hypothesis of no QTL vs. a QTL between the markers).
– Composite Interval mapping: IM and multiple regression– Multiple QTL models
• QTL present when LOD score exceeds critical threshold– LOD = Log of the Odds = log10 (H1/H0) – often for single locus analysis, 3.0 is significant and 2.0 is
suggestive depending on sample size, number of markers, and other variables.
Crossing over produces new allelic combinations
An experimental protocol for localizing genes
Figure 18-17
Quantitative traits are described by a frequency distribution
Figure 18-3b
Only a small percentage of character difference is associated withany one DNA marker
Figure 18-18
Mapping by Backcrossing
Generating the Backcross
Cast/EiJ x C57BL/6J
F1 x Cast/EiJ
BC1s
Backcross progeny have on average:
75% CE, 25% B6 alleles50% C/C, 50% C/B genotypes for all loci
C57BL/6J (B6)
Cast/EiJ (CE)
Mice have 20 chromosomes
Some types of detectable variation
• RFLPs (Restriction fragment length polymorphisms)
• VNTRs (Variable nucleotide tandem repeats) = minisatellites
• Microsatellites• SNPs (Single nucleotide polymorphisms)
LOD Scores
• Null hypothesis: assume no linkage.• Alternative hypothesis: assume the
disease (or phenotype) and the marker locus are linked.