Chapter 7 Multifactorial Traits

1. Chapter 7Multifactorial Traits

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. 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. 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. 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. Inheritance of Height (1920s) Figure 7.2a

7. Inheritance of Height (1997) Figure 7.2b

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. An Example of Variations in Eye Color Figure 7.3 • The number of human eye color genes is unknown • Analysis will probably reveal many genes • Mice have more than 60 eye color genes

10. Eye color • Probably a pure polygenic trait.

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. Fingerprints Figure 7.1

13. Model for Variation in Skin Color Figure 7.4

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. Some Drug Responses vary Between Populations Table 7.1

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 10, 20,30 • Pedigrees • 50 % chance of inheriting genes from parents and between siblings.

17. Heritability (H) Estimates the proportion of the phenotypic variation in a population due to genetic differences Figure 7.5

18. Empiric Risk of Cleft Palate Table 7.2

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. 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. 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. Coefficients of Relatedness for Pairs of Relatives Table 7.4 Figure 7.6

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. 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. 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 Separating Genes and Environment

26. Concordance • Concordance - the percentageof pairs in which both twins express the trait • Used to determine heritability • Haslimitations, assumes both type of twins share similar environments • MZ twins often share more similar environments

27. Table 7.5

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. 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. Two Examples of Multifactorial Traits • Heart Health • Body Weight • Both are controlled by many genes and interaction with a complex environment

31. Risk Factors for Cardiovascular Disease Table 7.7

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. 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. Table 7.8