Michael R. Cummings

David Reisman • University of South Carolina

The Inheritance of Complex Traits

Chapter 5

5.1 Polygenic Traits

Discontinuous variation• Phenotypes that fall into two or more distinct,

nonoverlapping classes or varieties• Mendels’ peas

Continuous variation• A distribution of phenotypes from one extreme to

another in an overlapping fashion (like height in tobacco plants and humans)

• The phenotypes together represent a bell-shaped curve

Comparison of Discontinuous and Continuous Phenotypes

Example of a Continuous phenotype

Fig. 5-2, p. 96

Polygenic Inheritance

The distribution of polygenic traits through the population follows a bell-shaped (normal) curve

Types of Traits

Polygenic traits• Traits controlled by two or more genes

Multifactorial traits• Polygenic traits resulting from interactions of two or

more genes and one or more environmental factors

Polygenic Inheritance

Two or more genes contribute to the phenotype

Phenotypic expression varies across a wide range so a large population must be analyzed when studying a trait

Interactions with the environment often participate in creating the phenotype.

Height, weight, skin color, eye color, and intelligence

5.3 The Additive Model of Polygenic Inheritance The number of phenotypic classes increases as the

number of genes controlling a trait increases

The Additive Model of Polygenic Inheritance

Regression to the Mean

Averaging out the phenotype is called regression to the mean• In a polygenic system, parents who have extreme

differences in phenotype tend to have offspring that exhibit a phenotype that is the average of the two parental phenotypes

A Polygenic Trait: Eye Color

Five basic eye colors fit a model with two genes, each with two alleles

Fig. 5-6, p. 99

The Threshold Model

Explains the discontinuous distribution of some multifactorial traits (clubfoot, cleft lip, congenital hip dislocation in females, pyloric stenosis in males)

5.5 Heritability Measures the Genetic Contribution to Phenotypic Variation Phenotypic variation is derived from two sources:

Genetic variance• The phenotypic variance of a trait in a population that

is attributed to genotypic differences

Environmental variance• The phenotypic variance of a trait in a population that

is attributed to differences in the environment

Heritability of a Trait

HeritabilityThe proportion of a phenotype that is dependent upon

genotype.

Measuring heritability involves study of twins and adopted children.

Heritability Estimates

Heritability is estimated by observing the amount of variation among relatives who have a known fraction of genes in common (known as genetic relatedness)

Heritability can be estimated only for the population under study and the environmental condition in effect at the time of the study

Correlation

Correlation coefficient• The fraction of genes shared by two relatives

Identical twins have 100% of their genes in common (correlation coefficient = 1.0)• When raised in separate environments identical twins

provide an estimate of the degree of environmental influence on gene expression

5.6 Twin Studies and Multifactorial Traits

Monozygotic (MZ)• Genetically identical twins derived from a single

fertilization involving one egg and one sperm

Dizygotic (DZ)• Twins derived from two separate and nearly

simultaneous fertilizations, each involving one egg and one sperm

• DZ twins share about 50% of their genes

Fig. 5-11, p. 105

Concordance

• Agreement between traits exhibited by both twins

In twin studies, the degree of concordance for a trait is compared in MZ and DZ twins reared together or apart • The greater the difference, the greater the heritability

Concordance, Heritability, and Obesity

Concordance can be converted to heritability by statistical methods

Twin studies of obesity show a strong heritability component (about 70%)

Table 5-3, p. 106

Genetic Clues to Obesity: The ob Gene

The ob gene encodes the weight-controlling hormone leptin in mice; receptors in the hypothalamus are controlled by the db gene

The ob gene encodes the hormone Leptin• produced by fat cells that signals the brain and ovary• As fat levels become depleted, secretion of leptin slows

and eventually stops

Fig. 5-13, p. 108

Fig. 5-13, p. 108

Human Obesity Genes

In humans, mutations in the gene for Leptin (LP) of the Leptin receptor (LEPR) account for about 5% of all cases of obesity; other factors cause the recent explosive increase in obesity

Scanning the Human Genome for Additional Obesity Genes

5.7 More on the Genetics of Height

The development of new technologies allows researchers to survey the genome to detect associations with phenotypes such as height, weight, etc.

The use of single nucleotide polymorphisms (SNPs) allows the association between haplotypes and phenotypes.

• Haplotype: specific combinations of SNPs located close to gather on a chromosome that are very likely inherited as a group.

Fig. 5-16, p. 110

DNA source

SNP SNP SNP SNP

Reference standard

Original haplotype

10,000 nucleotides

Person 1 Haplotype 1

Person 2 Haplotype 2

Person 3 Haplotype 3

Person 4 Haplotype 4

5.8 Skin Color and IQ are Complex Traits

Skin color is a polygenic trait It is controlled by 3 or 4 genes, plus environmental

factors (most obvious—sun exposure)

Can intelligence be measured quantitatively?• Psychological measurements and the ability to

perform specific tasks at a specific age led to the development of the intelligent quotient (IQ) test.

• There is no evidence that intelligence can be measured objectively (like height or weight)

• Interestingly, IQ measurements do have a significant heritable components

Are Intelligence and IQ Related?

Can intelligence be measured quantitatively?• Early studies believed that physical dimensions of

regions of the brain were a measure of intelligence.

Fig. 5-19, p. 112

More meaningful measures of intelligence and the search for genes that control intelligence

IQ test scores can’t be equated with intelligence• Relative contributions of genetics, environment, social and

cultural influences can’t be measured

General cognitive ability• Characteristics include verbal and spatial abilities,

memory and speed of perception, and reasoning• Genes associated with reading disability (dyslexia)

and cognitive ability have been discovered by comparing haplotypes

• Both genetic and environmental factors make important contributions to intelligence

Fig. 5-20, p. 113

Pairs studiedExpected

value

Nonbiological sibling pairs (adopted/natural pairings) (5) 0.0Nonbiological sibling pairs (adopted/adopted pairings) (6) 0.0Foster-parent child (12) 0.0Single-parent offspring reared together (32) 0.5

Single-parent offspring reared apart (4) 0.5Siblings reared apart (2) 0.5Siblings reared together (69) 0.5Dizygotic twins, opposite sex (18) 0.5Dizygotic twins, same sex (29) 0.5Monozygotic twins reared apart (3) 1.0Monozygotic twins reared together (34) 1.0

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0Correlation coefficient

Correlation coefficients of IQ measurements