Genes, Environment and Traits Few, if any, genes act alone Environmental factors and other genes may modify expression Traits can be described as - Mendelian = Caused by a single gene - Polygenic = Caused by multiple genes Both can be multifactorial or complex due to an interaction between genes and the environment

Genes, Environment and Traits Single-gene traits are discrete or qualitative - Often produce an “all-or-none” effect Polygenic traits produce a continuously varying phenotype - Also called quantitative traits - DNA sequences involved are termed quantitative trait loci (QTLs) 3

Genes, Environment and Traits Figure 7.1 4

Polygenic Traits Are influenced by interaction of genes and by the environment Examples: - Height - Skin color - Body weight - Fingerprint patterns - Behavioral traits 5

Polygenic Traits Individual genes follow Mendel’s laws, but their expression is hard to predict Effect of genes is additive or synergistic - However, input of genes is not necessarily identical The frequency of distribution of phenotypes forms a bell-shaped curve! 6

Fingerprint Patterns Dermatoglyphics is the study of fingerprints The number of ridges is largely determined by genes and prenatal contact The average total ridge count is 145 in a male and 126 in a female 7

Fingerprint Patterns Figure 7.2 8

Height Figure 7.3 9

Height The difference in height between the two sets of students is attributed to improved diet and better overall health Genome-wide association studies have identified dozens of genes that affect height - Also, certain SNPs patterns are seen in individuals with periods of rapid height increase 10

Skin Color Melanin protects against DNA damage from UV radiation, and exposure to the sun increases melanin synthesis We all have same number of melanocytes per unit area of skin - However, we differ in melanosome number, size and density distribution 11

Skin Color Figure 7.4 12

Skin Color The definition of race based largely on skin color is a social construct more than a biological concept Skin color is NOT a reliable indicator of ancestry - Overall, 93% of varying inherited traits are no more common in people of one skin color than any other 13

Investigating Multifactorial Traits Empiric risk measures the likelihood that a trait will recur based on incidence Incidence is the rate at which a certain event occurs Prevalence is the proportion or number of individuals who have a particular trait at a specific time 14

Investigating Multifactorial Traits Cleft lip is more likely in a person who has a relative with the condition Figure 7.5 15

Investigating Multifactorial Traits Table 7.2 16

Heritability (H) Estimates the proportion of the phenotypic variation in a population due to genetic differences Figure 7.6 17

Heritability (H) 18

Heritability (H) Researchers use several statistical methods to estimate heritability One way is to compare the proportion of people sharing a trait to the proportion predicted to share the trait The expected proportion is derived by knowing the blood relationships of the individuals 19

Coefficients of Relatedness The proportion of genes shared between two people related in a certain way Table 7.4 20

Tracing Relatives Figure 7.7 21

Adopted Individuals Similarities between adopted people and adopted parents reflect mostly environmental influences Similarities between adoptees and their biological parents reflect mostly genetic influences Therefore, information on both sets of parents can reveal how heredity and the environment both contribute to a trait 22

Twins Twin studies have largely replaced adoption methods Concordance measures the frequency of expression of a trait in both members of monozygotic (MZ) or dizygotic (DZ) twins - Twins who differ in a trait are said to be discordant for it For a trait largely determined by genes, concordance is higher for MZ than DZ twins 23

Twins Table 7.4 24

Separating Genetic and Environmental Influences 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 25

Twins Figure 7.8 26

Table 7.5

SNPs SNPs (single nucleotide polymorphisms) are sites in a genome where the DNA base varies in at least 1% of the population In these studies, SNPs span the genome, rather than define a single gene - A SNP can be anywhere among our roughly 3.2 billion base pairs 28

SNPs Figure 7.9 29

Genome-Wide Association Studies Older techniques search for known gene variants, typically in only a few people Sequencing of the human genome and the HapMap project (which identifies SNPs) have led to a new tool Genome-wide association studies seek correlations between SNP patterns and phenotypes in large groups of individuals 30

Genome-wide association studies seek SNPs that are shared with much greater frequency among individuals with the same trait than among others Figure 7.10 31

A Step-wise Approach to Gene Discovery Figure 7.11 32

Study Designs In a cohort study, researchers follow a large group of individuals over time and measure many aspects of their health In a case-control study, pairs of individuals are matched so that they share as many characteristics as possible - SNP differences are then associated with the presence or absence of the disorder 33

Study Designs The “affected sibling pair” strategy scans genomes of siblings for SNPs shared by those with the condition, but not by those who don’t have it Homozygosity mapping is performed on families that are consaguineous - The children in this case are more likely to inherit two copies of the mutation 34

Limitations of Genome-Wide Association Studies 1) They include so many data points and so are prone to error 2) They reveal associations between two types of information, not causes 3) Bias can be introduced in the way the patient population is selected 4) Their accuracy is affected by complicating factors, such as phenocopy and epistasis 5) They may miss extremely rare SNPs 35

Table 7.7 36

Body Weight Body weight is a multifactorial trait that reflects energy balance About 30% of all adults in the US are obese, and another 35% are overweight Scientific studies use a measurement called body mass index (BMI) = weight (kg)/height2 (m2) 37

Body Mass Index (BMI) Figure 7.12 38

Body Weight Studies on adopted individuals and twins indicate a heritability of 75% for obesity Lifestyle, including diet and exercise, are environmental components impacting weight Genes influence hunger and metabolism 39

Leptin and Associated Proteins Leptin is a protein hormone produced by fat cells - Acts on the brain to decrease appetite Ghrelin is a peptide hormone produced in the stomach - Responds to hunger by increasing appetite These and other hormones are important for general weight regulation 40

Leptin and Associated Proteins Table 7.8 41