The Inheritance of Complex Traits

 

Differences Among Brothers and Sisters is Due to both Genetic and Environmental Factors

5.1 Some Traits Are Controlled
by Two or More Genes

§     Many phenotypes are influenced by many gene pairs as well as the environment

§     Phenotypes can be discontinuous or continuous

 

§     Discontinuous variation

•     Phenotypes that fall into two or more distinct, nonoverlapping classes (like Mendels’ peas)

§     Continuous variation

•     Phenotypic characters that are distributed from one extreme to another in an overlapping fashion (like height in humans)

Comparison of  Discontinuous and Continuous Phenotypes

 

Example of a Continuous phenotype

 

Genotype + Environment

Produce the Phenotype

What are Complex Traits?

§     Complex traits are determined by the cumulative effects of genes and the influence of environment

 

§     Polygenic traits

•     Traits controlled by two or more genes

•     Patterns of inheritance that can be measured quantitatively

 

§     Multifactorial traits

•     Polygenic traits resulting from interactions of two or more genes and one or more environmental factors

 

§     Many human diseases are controlled by the action of several genes

5.2 Polygenic Traits
and Variation in Phenotype

 

§     Assessing interactions of genes, environment, and phenotype can be difficult

 

§     In some cases, only a specific gene and a specific environmental factor causes an effect

 

§     Polygenic: when several genes each make a small contribution to phenotype. The result is continuous phenotypic variation

 

Polygenic Inheritance

§     Traits are usually quantified by measurement

§     Two or more genes contribute to the phenotype

§     Phenotypic variation varies across a wide range

§     Better analyzed in populations than inindividuals

§     Example: human eye color

Polygenic Inheritance

 

§      Traits are usually quantified by measurement rather than counting

 

§      Two or more genes contribute to the phenotype

 

§      Phenotypic expression varies across a wide range

 

§      Interactions with the environment often participate in creating the phenotype.

 

Polygenic Inheritance

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

 

A Multifactorial Polygenic Trait:
Skin Color

§     Skin color is controlled by 3 or 4 genes and environmental factors leading to a wide range of phenotypes

 

§     Environmental factors interact with genes to produce variations in phenotype

Animation: Comb shape in chickens

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

§     As the number of genes involved increase, the number of phenotypic classes increases

 

The Additive Model of Polygenic Inheritance

 

A Polygenic Trait: Eye Color

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

 

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

 

5.4 Multifactorial Traits: Polygenic Inheritance and Environmental Effects

 

§     Variations in expression of polygenic traits often are due to the action of environmental factors

 

§     Multifactorial or complex traits are polygenic traits with a strong environmental component

 

Multifactorial Traits

 

§     Characteristics

•     Traits are polygenic

•     Each gene controlling the trait contributes a small amount to the phenotype

•     Environmental factors interact with the genotype to produce the phenotype

 

Environmental Effects and Phenotype

 

 

§     The impact of environment on genotype can cause genetically susceptible individuals to exhibit a trait discontinuously, even though there is an underlying continuous distribution of genotypes for the trait

The Genetic Revolution:
Dissecting Genes and Enviroment in Spina Bifida

 

 

§     Spina Bifida is a common birth defect involving the nervous system

 

§     Twin studies show a significant genetic component

 

§     Nutrition (especially folate) has a significant impact on the frequency of occurrence

 

 

The Threshold Model

§     Explains the discontinuous distribution of some multifactorial traits

 

Risk of Recurrence

 

§     In multifactorial phenotypes, the risk of recurrence is predicted to decline as the degree of relatedness of the individuals declines

 

 

§     The genetic contribution to phenotypic variation can be estimated

ANIMATION: Temperature effect

5.5 Heritability Measures the Genetic Contribution to Phenotypic Variation

 

§     The degree of phenotypic variation produced by a genotype in a specific population can be estimated by calculating the heritability of a trait

 

 

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

 

 

The degree of phenotypic variation produced by a genotype in a specific population can be estimated by calculating the heritability of a trait

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

Heritability of Fingerprints

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

 

Monozygotic (identical) Twins Share a Single Genotype

Monozygotic and Dizygotic Twins

 

Concordance

§      The study of heritability in twins assumes that MZ twins share all of their genes; DZ twins share half of their genes.

 

§      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 in MZ and DZ Twins

 

 

§     Twin studies provide an insight into the interaction of genotypes and environment

Concordance, Heritability, and Obesity

§     Concordance can be converted to heritability by statistical methods

 

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

 

Obesity is Now a National Health Problem

 

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

 

Leptin and Fat Storage

§     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

 

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

 

–  Heredity

–  Male

–  Hypertension

–  High LDL or low HDL

–  Smoking

–  Obesity

–  Lack of exercise

–  Stress

 

 

Genetic Disorders Associated with Cardiovascular Disease

 

•      Angiotensinogen gene

•      Familial hypercholesterolemia

   Autosomal dominant defective or absent LDL receptors

•      Numerous others

ANIMATION: Chronology of leptin research

Exploring Genetics
Twins, Quintuplets, and Armadillos

 

§     Some armadillos produce litters of two to six genetically identical, same-sex offspring by embryo splitting, the same way identical multiple births can occur in humans

 

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.

 

§     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 likely inherited as a group.

Haplotypes

 

5.8 Skin Color and IQ are Complex Traits

§     Skin color is characteristic of a polygenic trait

 

Skin color is Controlled by Three or Four Genes Plus Environment

§     Skin color is characteristic of a polygenic trait

 

Multifactorial Traits: Skin Color

§     Skin color is actually controlled by 3 or 4 genes, plus environmental factors

 

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.

 

Are Intelligence and IQ Related?

 

§     Can intelligence be measured quantitatively?

•     Psychological measurements and the ability to perform specific tasks as a function of 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

IQ Correlation Coefficients

 

Controversy About IQ and Race

 

§      IQ test scores can’t be equated with intelligence

•     Relative contributions of genetics, environment, social and cultural influences can’t be measured

§      Heritability can’t be used to estimate genetic variation between populations

•     Heritability measures only variation within a population at the time of measurement

•     Genetic variability within a population is greater than the variability between any two populations

§      Both genetic and environmental factors make important contributions to intelligence

 

 

 

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

 

 

§     General cognitive ability

•     An expanded definition of intelligence

•     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

 

§     Many multifactorial traits have, environmental  social and cultural impacts