1. Multifactoral Traits
Genetics
Spring 2016

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

3. 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

4. 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.

6. 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. 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

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

9. What patterns are your fingerprints?

10. 7.1 Height How can our environment affect our height?
The following pictures show students from and 1997 lined up according to their height

13. 7.1 Height What differences did you notice?
Note that the tallest students in were only 5'9" while the tallest in were 6'5"
Environmental factors such as improved diet and better overall health attributed to this difference

14. 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

15. 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

16. 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

17. 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

18. Study of Twins
Twins Study

19. 7.2 Investigating Multifactorial Traits
Empiric Risk
Heritability
Twins
Association Studies

20. 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

21. 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

22. 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%

23. 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!

24. 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

25. 7.2 Heritability Heritability changes as the environment changes
ex. skin color
This can also cause heritability to be different among different populations

26. 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

27. 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

28. Activity Break!
Connecting Cousins

29. 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)

30. 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

31. 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

33. 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?

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

35. 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

36. 7.3 A study of two multifactorial traits
Heart Health
Weight

37. 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

38. 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

39. 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

40. 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

41. 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

42. 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

44. 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

45. 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

46. 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

47. 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

48. 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