The Inheritance of Complex Traits Chapter 5 The Inheritance of Complex Traits

5.1 Polygenic Traits Discontinuous variation Continuous 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 Figure 5.2 An example of continuous variation: biology students organized according to height. 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 Multifactorial 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 Figure 5.6 Samples from the range of continuous variation in human eye color. Different alleles of more than one gene interact to synthesize and deposit melanin in the iris. Combinations of alleles result in small differences in eye color, making the distribution for eye color appear to be continuous over the range from light blue to black. 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 The 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

Figure 5.11 (a) Monozygotic (MZ) twins result from the fertilization of a single egg by a single sperm. After one or more mitotic divisions, the embryo splits in two and forms two genetically identical individuals. (b) Dizygotic (DZ) twins result from the independent fertilization of two eggs by two sperm during the same ovulatory cycle. Although these two embryos simultaneously occupy the same uterine environment, they share only about half 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 Figure 5.13 The obese (ob) mouse mutant, shown on the left (a normal mouse is on the right), has provided many clues about how weight is controlled in humans. Fig. 5-13, p. 108

Figure 5.13 The obese (ob) mouse mutant, shown on the left (a normal mouse is on the right), has provided many clues about how weight is controlled in humans. 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 Figure 5.15 Some obesity genes in the human genome. The green triangles represent single genes in which obesity is the main phenotype with little environmental influence. The red triangles represent genes that are candidates for obesity genes. Mutations in these genes have an association with obesity. Red bars represent chromosome regions that may contain other genes associated with obesity. More than 70 genes associated with obesity have been identified.

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.

DNA source SNP SNP SNP SNP Reference standard Original haplotype 10,000 nucleotides Person 1 Haplotype 1 Person 2 Haplotype 2 Figure 5.16 Single nucleotide polymorphisms (SNPs) are organized into blocks that are inherited together. These blocks, called haplotypes, are used as markers for specific regions on chromosomes. If a trait and a haplotype are inherited together, it means that a gene for the trait is located on the same chromosome as the haplotype and that the gene may be near the haplotype block. Person 3 Haplotype 3 Person 4 Haplotype 4 Fig. 5-16, p. 110

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. Figure 5.19 Phrenology model showing areas of the head overlaying brain regions that control different traits. Intelligence was estimated by measuring the area of the skull overlaying the region of the brain thought to control this trait. Fig. 5-19, p. 112

General cognitive ability 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

Correlation coefficients of IQ measurements Expected value Pairs studied Nonbiological sibling pairs (adopted/natural pairings) (5) 0.0 Nonbiological sibling pairs (adopted/adopted pairings) (6) 0.0 Foster-parent child (12) 0.0 Single-parent offspring reared together (32) 0.5 (4) Single-parent offspring reared apart 0.5 Siblings reared apart (2) 0.5 Siblings reared together (69) 0.5 Dizygotic twins, opposite sex (18) 0.5 Dizygotic twins, same sex (29) 0.5 Figure 5.20 A graphical representation of correlations in IQ measurements in different sets of individuals. The expected correlation coefficients are determined by the degree of genetic relatedness in each set of individuals. The vertical line represents the median correlation coefficient in each case. Monozygotic twins reared apart (3) 1.0 Monozygotic twins reared together (34) 1.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Correlation coefficient Fig. 5-20, p. 113