Multifactoral Traits Genetics Spring 2016

Think about it.... What determines your traits? What does the phrase "Nature vs. Nurture" mean?

7.1 Genes and the Environment Traits can either be Mendelian or polygenic Mendelian- controlled by a single gene Polygenic- controlled by multiple genes Both types of traits can also be multifactorial influenced by the environment too

7.1 Polygenic Traits are continuously varying Since polygenic traits are controlled by multiple genes, the phenotypes continuously vary. The individual genes in a polygenic trait follow Mendel's laws but together they do not produce Mendelian phenotypic ratios They are not dominant or recessive to each other.

7.1 Fingerprint Patterns The skin on fingertips folds into patterns of raised skin called dermal ridges form loops, whorls or arches The number of ridges is largely determined by genes also responds to the environment

7.1 Fingerprint Patterns During weeks 6-13 of development, the ridges can be altered when the fetus touches fingers and toes to the wall of the amniotic sac This is an example of how identical twins can share the same genetic code but not always the same exact traits

Activity Break You will need: Pencil Tape Scratch sheet of paper Blank sheet of paper

What patterns are your fingerprints?

7.1 Height How can our environment affect our height? The following pictures show students from 1920 and 1997 lined up according to their height

7.1 Height What differences did you notice? Note that the tallest students in 1920 were only 5'9" while the tallest in 1997 were 6'5" Environmental factors such as improved diet and better overall health attributed to this difference

7.1 Eye Color Eye color is a polygenic trait but is probably NOT a multifactoral trait It is unknown exactly how many genes code for eye color (more than 60 in mice!) However, there is more to eye color than just green, brown, blue or hazel Our eyes also have: specks and flecks steaks and rings regions of dark vs light

7.1 Eye Color Lipochromes- greenish-blue pigments determined by two genes Melanins- brownish pigments determined by two or more (separate) genes Pure Blue is a spectral color results from light scattering not from pigment

7.1 Skin Color Melanin- the pigment that colors our skin Protects against UV damage Sunlight increases melanin synthesis Genetically speaking, are there different races? Races based on skin color don't really exist However, racial groups do appear to have different incidences of certain diseases

7.1 Skin Color Study of 100 students from Penn State demonstrated that skin color does not reflect ancestery Had their DNA tested, no student was pure anything A student who considered herself black was actually 58% White European

Study of Twins Twins Study

7.2 Investigating Multifactorial Traits Empiric Risk Heritability Twins Association Studies

7.2 Empiric Risk Used to predict the chance that a multifactorial trait will occur in a specific individual These risks are based on incidence in a specific population incidence- the rate at which a certain event occurs these are statistics, not specific calculations

7.2 Empiric Risk The population might be broad or more narrow ex. an ethnic group or entire community vs a specific family Risk increases with: severity of disorder # of affected family members how closely related a person is to affected individuals

7.2 Empiric Risk These observations can help us better predict the risk of disorders with transmission patterns that we don't yet understand Ex. Pyloric Stenosis More common among males risk of recurrence for the brother of an affected brother is 3.8% risk for the brother of an affected sister is 9.2%

Activity Break! I will give you some instruction shortly, here is some info you'll need Neural Tube Defect In the U.S. Empiric Risk is about 1 in 1,000 People of English, Irish or Scottish ancestry,risk is about 3 in 1,000 If a sibling has NTD, recurrence increases to 3% (that would be 30 out of 1,000) ethnicity doesn't matter in these cases even higher for a third child with two affected siblings!

7.2 Heritability Heritability (H) estimates the proportion of the phenotypic variation that is due to genetic differences this measurement is taken from a certain population at a certain time H=1.0 for a trait whose variability is completely the result of genetics

7.2 Heritability Heritability changes as the environment changes ex. skin color This can also cause heritability to be different among different populations

7.2 Heritability To estimate heritability determine the expected proportion of pairs of related people who would share a trait if it were inherited in a Mendelian fashion determine the actual proportion of those same pairs To determine the expected proportion find out the blood relationships of the individuals Use the coefficient of relatedness - the proportion of genes that the two related people would share

7.2 Heritability Close relatives such as parents and children or siblings share about 50% of their genes with each other. The further away two individuals get in their relatedness, the less genes they share can calculate by multiplying by 1/2 for example a person shares 25% of their genes with their grandparents Next, you calculate the percentage of phenotypes that are actually seen for a specific trait

Activity Break! Connecting Cousins

7.2 Adopted Individuals and Twins Adopted individuals- can be used to study both environmental and genetic influences on traits individuals in these families share their environment but not many genes (if any) also share many genes but not their environment with biological relatives Twins also great for studying both environmental and genetic influences has replaced studying adopted individuals (for the most part)

7.2 Twins By studying twins, we can determine the concordance values of traits concordance value- percentage of twins that both express a certain trait Traits caused by a single gene with no environmental influence identical twins- 100% concordance fraternal twins 50% concordance for dominant traits 25% concordance for recessive traits These follow the typical Mendelian laws

7.2 Twins Polygenic traits with little to no environmental influence Identical twins have a much higher concordance that fraternal twins Traits with a lot of environmental influence Identical and fraternal twins have similar concordances

Activity Break! Concordance for the eating disorder anorexia nervosa for identical twins is 55% and for fraternal twins it is 7% Maggie and Ashley are fraternal twins Maggie has anorexia nervosa Should Ashley be concerned about developing the condition? Why or why not? What if they were identical twins? What do these concordances tell you about the trait?

Exit Slip 2 things you learned/found interesting 2 questions you still have

7.2 Association Studies a method of studying multifactoral traits by looking directly at the DNA sequence compares SNP patterns between a group of individuals with a particular disorder to a group of individuals without the disorder SNP- single nucleotide polymorphism

7.3 A study of two multifactorial traits Heart Health Weight

7.3 Heart Health Genes control how well our body handles lipids in the blood Lipids can only move when bound to proteins (called lipoproteins) these types of proteins are apolipoproteins the allele for apolipoprotein E, called E4, increases the risk of a heart attack threefold in people who smoke shows that genes and environmental factors can interact in negative ways

7.3 Heart Health A healthy cardiovascular system requires balance cells require enough lipids inside but cannot allow accumulation outside many different genes control lipid levels by specifying enzymes that process lipids Our knowledge of the role of genetics in cardiovascular health comes from studying rare inherited conditions Ex. hypercholesterolemia- the liver cells lack receptors that take up the LDL form of cholesterol from the bloodstream

7.3 Heart Health At least 50 genes regulate blood pressure One gene codes angiotensinogen this protein is elevated in the blood of people with hypertension Lipoprotein lipase breaks down lipids released from the small intestine and liver activated by HDL (high density lipoproteins) breaks down LDL (low density lipoproteins) high HDL levels and low LDL levels are associated with a healthy cardiovascular system

7.3 Heart Health There are many other genetic factors that contribute to heart health We study these factors to determine who is more at risk for certain cardiovascular diseases We can also use these studies to develop the most effective medications with the fewest side effects risks can sometimes also be controlled by lifestyle changes such as exercising, not smoking and maintaining a healthy weight

Research Activity 1. ACE Inhibitors 2. Aldosterone Inhibitors 3. Angiotensin II Receptor Blocker (ARBs) 4. Beta-Blockers 5. Calcium Channel Blockers 6. Choleserol-Lowering Drugs 7. Diuretics 8. Vasodilators

7.3 Weight being overweight or obese increases the risk of developing hypertension, diabetes, stroke, gallstones, sleep apnea and some cancers Studies of body weight use a measurement called BMI Body Mass Index BMI between 25 and 30 = overweight BMU of 30+ = obese Heritability for BMI is 0.55 this means there is room for environmental influenceson weight

7.3 Weight Leptin is a protein hormone produced by the body eating stimulates our fat cells (adipocytes) to secrete leptin Leptin travels to the hypothalamus and binds to the arcuate nucleus cells then produce melanocyte stimulating hormone (MSH) MSH travels elsewhere in the Hypothalamus and binds to specific receptors This binding suppresses appetite and increases metabolism to digest food

7.3 Weight when mice were given extra leptin, they are less and lost weight biotech company began giving it to obese individuals to help them lose weight only worked in about 15% of people other 85% actually had a leptin resistance, not a deficiency

7.3 Weight Lipodystrophy at puberty the fat pads beneath the skin shrink away this leaves the person extremely skinny and constantly hungry fats are laid down beneath the skin in painful lesions triglycerides must be cleansed from the blood often Leptin injections have helped some gain weight and feel less hungry not sure what the connection is

7.3 Weight most people who are heterozygous for a mutation in the gene for melanocortin-4 receptor are obese people who have the mutation in both alleles are morbidly obese mutation accounts for about 6% of very obese children most common single-gene cause of obesity

7.3 Weight Twins studies suggest that obesity has a heritablilty of .75 (75%) remember the heritability for BMI was only .55 this suggests that genes play a larger role in those who gain weight easily The Pima Indians separated during the middle ages one group in the Sierra Madre mountains of Mexico one group in southern Arizona 1970's Arizona Indians no longer farmed and ate high fat diets half the group had diabetes by age 35 weighed, on average, 57 pounds more than their relatives in Mexico