Quantitative Genetics

Continuous phenotypic variation within populations- not discrete characters Phenotypic variation due to both genetic and environmental factors

Quantitative traits are described by a frequency distribution Figure 18-3b

The distribution of a trait is composed of the distributions of the different genotypes Figure 18-16

A norm of reaction is the relation between environment and phenotype Figure 18-6

Crosses are performed to test for heritability Figure 18-11

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.

Selection altered bristle number Figure 18-14

Selection increased egg production Figure 18-15

An experimental protocol for localizing genes Figure 18-17

Only a small percentage of character difference is associated with any one DNA marker Figure 18-18

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 = log 10 (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.

Crosses are performed to test for heritability Figure 18-11

Generating the Backcross Cast/EiJ x C57BL/6J F1 x Cast/EiJ BC1s Backcross progeny have on average: 75% CE, 25% B6 alleles 50% C/C, 50% C/B genotypes for all loci C57BL/6J (B6) Cast/EiJ (CE)

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.

Mice have 20 chromosomes

Generating the Backcross Cast/EiJ x C57BL/6J F1 x Cast/EiJ BC1s C57BL/6J (B6) Cast/EiJ (CE) # Scored: (21/20) (16) (224)

CE B6 CE/B6 F2 lines CE B6

Genetic Map of Markers used in Analysis