1. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-1 Chapter 7 Multifactorial Traits

2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-2 Cleft Lip and Palate Symptoms- –Hole between nose and upper lip –Difficulty feeding- lack of suction Variability in severity Genetic and environmental factors –Prenatal exposure to drugs- seizures, anziety, elev. Cholesterol –Pesticides –Cigarette smoke –Infections 4% risk if in a sibling. Tests to detect haplotypes assoc. with elevated risk.- series of known DNA sequences linked on a chromosome or SNPs.

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-3 Contribution of Genes or Environment Genes rarely act completely alone Environmental factors and other genes may modify expression Traits can be described as – Mendelian or primarily due to a single gene – Polygenic or primarily due to multiple genes – Multifactorial or complex due to an interaction between genes and the environment

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-4 Polygenic Traits Variation is continuous, not discrete( normal vs affected) Individual genes follow Mendel’s laws Effect of genes is additive or synergistic – together they do not produce a single gene phenotype, they all contribute DNA sequences that contribute are called quantitative trait loci (QTL) Genes can have major or minor impacts Examples: –Height –Hair color –Body weight –Cholesterol levels

5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-5 Fingerprint Patterns Based on skin folds- dermal ridges. Dermatoglyphics- skin writing. –Compares number of ridges to identify individuals. Total ridge count = # ridges on all fingers. –Determined by genes –Responds to environment- wk 6-13 of prenatal development Fetus in contact with amniotic sac. Identical twins can have different fingerprints. Plot of total ridge count – bell curve of continuously varying trait.

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-6 Inheritance of Height (1920s) Figure 7.2a

7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-7 Inheritance of Height (1997) Figure 7.2b

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-8 Height- multifactorial Effect of environment- poor nutrition and diet- results in individuals not reaching their full genetic potential. Difference in height- tallest of 1920s= 5’9’’; tallest 1997- 6’5’’. Hard to determine how many genes are responsible formultifactorial traits that are also polygenic

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-9 An Example of Variations in Eye Color The number of human eye color genes is unknown Analysis will probably reveal many genes Mice have more than 60 eye color genes Figure 7.3

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-10 Eye color Probably a pure polygenic trait.

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-11 Multifactorial Traits Are influenced by interaction of genes and by the environment Examples: – Fingerprint, many genes and prenatal contact – Height, many genes and nutrition – Skin color, many genes and UV exposure

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-12 Fingerprints Figure 7.1

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-13 Model for Variation in Skin Color Figure 7.4

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-14 Skin Color Melanin production - skin pigmentation and protects skin from UV radiation Skin color is a phenotype interaction between pigment genes + environment In a genetic sense, race based on skin color has little meaning Medical treatment differences/difficulties

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-15 Some Drug Responses vary Between Populations Table 7.1

16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-16 Analyzing Multifactorial Traits Difficult, requires multiple techniques Use human genome sequences, population, and family studies. Empiric risk –incidence or rate an event occurs in a population. Prevalence- proportion of the population that has a disorder at a specific time. Empiric Risk –increases with the severity, more family members affected and the closer the relationship to an affected individual. –The closer the relationship; increased probability, since increase in genes in common. –Based on observations so it can be used even in difficult transmission patterns. Heritability- Measurement of genetic. –Blood relationship and the coefficient of relatedness ( genes 2 related people share. –Designate 1 0, 2 0,3 0 –Pedigrees –50 % chance of inheriting genes from parents and between siblings.

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-17 Heritability (H) Estimates the proportion of the phenotypic variation in a population due to genetic differences Figure 7.5

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-18 Empiric Risk of Cleft Palate Table 7.2

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-19 Heritability High Heritability- high influence of genes. Heritability= observed phenotypic variation / expected. –Example Height- 0.4/0.5 = 80% Some traits- epistasis influence- LDL Polygenic traits- use additive effects of recessive alleles of different genes because dominant traits may influence the phenotype but are very rare and may not contribute to Heritability.

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-20 PTC – Bitter taste- taster or nontaster phenotypes. SNPs –3 polymorphic sites –2 haplotypes-form two alleles. –Taster- G,T, A; non tasters C,C,G substituted DNA bases. –multifactorial Largely determined by 1 gene on chromosome #7 Influenced by other genes-lesser extent but addittive.

21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-21 Heritability Values Heritability is estimated from the proportion of people sharing a trait compared to the proportion predicted to share the trait May vary between populations and time period Table 7.3

22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-22 Coefficients of Relatedness for Pairs of Relatives Table 7.4 Figure 7.6

23. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-23 Importance of Multifactorial Inheritance in Agriculture Breeders –Birth weight, milk yield, eggs hatched, fiber length, –Genetics- additive or epistatic –Envirnoment can be controlled –Matings can be selected.

24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-24 Analyzing Multifactorial Traits Comparisons between and within families –Twins dizygotic and monozygotic –Twins raised apart –Adopted children Association studies – compare SNP patterns between affected and unaffected groups, identify important DNA regions

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-25 Separating Genes and Environment Dizygotic twins:Shared environment and 50% of genes Monozygotic twins:Identical genotype, and shared environment Twins raised apart:Shared genotype but not environment Adopted individuals: Shared environment but not genes

26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-26 Concordance Concordance - the percentage of pairs in which both twins express the trait Used to determine heritability Has limitations, assumes both type of twins share similar environments MZ twins often share more similar environments

27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-27 Table 7.5

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-28 Single Nucleotide Polymorphism SNP Nucleotide site with more than one allele is a polymorphism Site is considered polymorphic if allele is present in >1% of the population On average, between two random individuals, there is one SNP every 1,200 bases or about 10 million differences! Linkage disequilibrium

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-29 Association Studies Studies compare a group of interest (cases) to a control group for the presence of a gene or SNP Controls are matched to cases for characteristics that may confound results: age, ethnicity, gender, environment If the SNP is present more often in cases than controls, it is associated with the trait and implies that the SNP may be near a gene impacting the trait

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-30 Two Examples of Multifactorial Traits Heart Health Body Weight Both are controlled by many genes and interaction with a complex environment

31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-31 Risk Factors for Cardiovascular Disease Table 7.7

32. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-32 Body Weight Reflects energy balance 30% of US adults are obese Twin studies suggest obesity has 75% heritability Lifestyle, including diet and exercise, are environmental components impacting weight Genes influence hunger and metabolism

33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-33 The Leptin Pathway Impacts Weight Leptin is a protein hormone produced by fat It signals sufficient calorie intake Travels in bloodstream, is bound by leptin receptors in the brain and triggers a decrease in eating Mutations in the leptin gene can cause obesity in mice and rarely in humans Components of the leptin pathway may be important for general weight regulation

34. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-34 Table 7.8