The Inheritance of Complex Traits
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- Oswald Summers
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1 The Inheritance of Complex Traits
2 Differences Among Siblings Is due to both Genetic and Environmental Factors
3 VIDEO: Designer Babies
4 Traits 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
5 % of individuals % of individuals % of individuals Comparison of Discontinuous and Continuous Phenotypes Dwarf Tall P 1 parental generation Dwarf Tall F 1 generation (a) Pea plants Dwarf Tall F 2 generation
6 % of individuals % of individuals % of individuals Comparison of Discontinuous and Continuous Phenotypes Dwarf Tall P 1 parental generation Intermediate F 1 generation (b) Tobacco plants Dwarf Intermediate F 2 generation Tall
7 Traits Controlled by Two or More Genes (contd.) Discontinuous variation Phenotypes that fall into two or more distinct, nonoverlapping classes (e.g. Mendel s peas) Continuous variation Phenotypic characters that are distributed from one extreme to another in an overlapping fashion (e.g. height in humans)
8 Example of a Continuous phentoype
9 What are Complex Traits? These 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
10 What are Complex Traits? Multifactorial traits Polygenic traits resulting from interactions of two or more genes and one or more environmental factors
11 Keep In Mind Many human diseases are controlled by the action of several genes
12 Polygenic Traits 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 makes a small contribution) control a phenotype the result is continuous phenotypic variation
13 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
14 Percentage of men Polygenic Inheritance The distribution of polygenic traits through the population follows a bell-shaped (normal) curve Phenotype (height in inches)
15 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
16 Keep In Mind Environmental factors interact with genes to produce variations in phenotype
17 The Additive Model of Polygenic Inheritance As the number of genes involved increase, the number of phenotypic classes increases
18 % of individuals The Additive Model of Polygenic Inheritance 2 genes F 2 ratio: 1:4:6:4:1 Classes
19 % of individuals The Additive Model of Polygenic Inheritance 3 genes F 2 ratio: 1:6:15:20:15:6:1 Classes
20 % of individuals The Additive Model of Polygenic Inheritance 4 genes F 2 ratio: 1:8:28:56:70:56:28:8:1 Classes
21 The Additive Model of Polygenic Inheritance
22 The Additive Model of Polygenic Inheritance Gametes ABc Gametes ABC AABBCc 7 ft. AbC abc abc AABbCc 6 ft. 9 in. AaBBCc 6 ft. 9 in. AaBbCc 6 ft. 6 in. Abc AABbCc 6 ft. 9 in. AAbbCc 6 ft. 6 in. AaBbCc 6 ft. 6 in. AabbCc 6 ft. 3 in. abc AaBBCc 6 ft. 9 in. AaBbCc 6 ft. 6 in. aabbcc 6 ft. 6 in. aabbcc 6 ft. 3 in. (b) abc AaBbCc 6 ft. 6 in. AabbCc 6 ft. 3 in. aabbcc 6 ft. 3 in. aabbcc 6 ft.
23 A Polygenic Trait: Eye Color Five basic eye colors fit a model with two genes, each with two alleles
24 Regression to the Mean Averaging out the phenotype In a polygenic system, parents with extreme differences in phenotype, tend to have offspring that exhibit a phenotype that is the average of the two parental phenotypes
25 Percentage of offspring Regression to the Mean % 30 25% 25% % 6.25% 6 ft. 6 ft. 3 in. 6 ft. 6 in. 6 ft. 9 in. 7 ft.
26 5.5 Multifactorial Traits 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
27 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
28 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
29 The Genetic Revolution: Dissecting Genes and Environment 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
30 Frequency The Threshold Model Explains the discontinuous distribution of some multifactorial traits Unaffected Affected Threshold Genetic liability
31 Risk of Recurrence In multifactorial phenotypes the risk of recurrence is predicted to decline as the degree of relatedness of the individuals declines
32 Familial Risks for Multifactorial Traits
33 Keep In Mind The genetic contribution to phenotypic variation can be estimated
34 Heritability The degree of phenotypic variation produced by a genotype in a specific population can be estimated by calculating the heritability of a trait
35 Heritability 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
36 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
37 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) Only for the population under study and the environmental condition in effect at the time of the study
38 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
39 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
40 VIDEO: Obesity Genes
41 ANIMATION: Chronology of leptin research To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERE
42 Monozygotic (identical) Twins Share a Single Genotype
43 Monozygotic and Dizygotic Twins Monozygotic (MZ) twins Single fertilization event Mitosis (a) Two genetically identical embryos
44 Monozygotic and Dizygotic Twins Dizygotic (DZ) twins Two independent fertilization events Mitosis (b) Two embryos sharing about half their genes
45 Concordance The study of heritablity 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
46 Concordance in MZ and DZ Twins
47 Keep In Mind Twin studies provide an insight into the interaction of genotypes and environment
48 Concordance, Heritability, and Obesity Concordance can be converted to heritability by statistical methods Twin studies of obesity show a strong heritability component (about 70%)
49 Obesity: Now a National Health Problem
50 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
51 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
52 Leptin and Fat Storage Hypothalamus Leptin Conversion of food to energy Resolution of energy consumption Fat cells
53 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
54 Additional Obesity Genes X Y
55 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
56 Genetics of Height New technologies allow 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 together on a chromosome that are likely inherited as a group.
57 Haplotypes 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
58 Distribution of individuals Skin Color and IQ Skin color is characteristic of a polygenic trait P (a) Class
59 Distribution of individuals 5.9 Skin Color and IQ Skin color is characteristic of a polygenic trait F 1 (b) Class
60 Distribution of individuals Skin Color and IQ Skin color is characteristic of a polygenic trait F (c) Class
61 Multifactorial Traits: Skin Color Skin color is controlled by 3 or 4 genes, plus environmental factors KEY 1 gene 2 genes F 1 F 1 (F 2 ) 3 genes 4 genes Skin reflectance at 685 nm.
62 Are Intelligence and IQ Related? Early studies believed that physical dimensions of regions of the brain were a measure of intelligence
63 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
64 IQ Correlation Coefficients Pairs studied Expected value 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 Single-parent offspring reared apart (4) 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 Monozygotic twins reared apart (3) 1.0 Monozygotic twins reared together (34) Correlation coefficient 0.5
65 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
66 Controversy About IQ and Race Both genetic and environmental factors make important contributions to intelligence
67 Intelligence: meaningful measures and the search for genes General cognitive ability An expanded definition of intelligence e.g. 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
68 Keep In Mind Many multifactorial traits have environmental social and cultural impacts
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