quantitative genetics. continuous phenotypic variation within populations- not discrete characters...

Quantitative Genetics

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 thedifferent 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 withany 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 = 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.

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 alleles50% 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