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.