1. Multifactorial traits
OUR GENES AND THE ENVIRONMENT THAT INFLUENCE THEM

2. Are Peyton Manning's born? Or made?
Is athletic ability, obesity, alcoholism or intelligence, etc.--inherited or learned?
Which plays the greatest role?
Nature or Nurture?
For characteristics like these and many others, not an ‘either/or’ mechanism
Result of input from many genes, as
well as, environmental influences
Even single gene disorders can be influenced and expression modified by other genes and environment

3. Polygenetic Traits
Polygenetic traits are those expressed by more than one gene.
Purely polygenetic traits are rare, eye color comes the closest
Different genes may contribute to different aspects of phenotype as in skin and hair color, migraines, or type 2 diabetes, However…..

4. Multifactorial Traits
Both single-gene and polygenetic traits can be influenced by the environment; these are referred to as multifactorial traits
Once called complex traits, but, this implied genes of mulitfactorial traits were more complicated; they are not.
They follow Mendel’s laws, however, are more difficult to predict due to combined actions of genes and environment.

5. Polygenetic Multifactorial Traits
Polygenetic multifactorial traits include:
Height
Skin color
Body weight
Behavioral conditions and tendencies like alcoholism and drug addiction
Illnesses like lung cancer, diabetes, heart disease, etc
Migraine headaches are a polygenetic multifactorial trait: Genes on CH 1 contribute to sensitivity to sound, CH 5 produces pulsating headache and light sensitivity, CH 8 associated with nausea and vomiting.
However, environmental influences like stress, fatigue, and diet can trigger the headaches

6. Genetic “Variability”
Combined action of many genes produces a continuously varying phenotype, also called a quantitative trait
DNA sequences that contribute to polygenetic traits are called QLT’s or
quantitative trait loci
A multifactorial trait is continuously varying if it is also polygenetic, the multi-gene component contributes to the continuing variation of phenotype, without being dominant or recessive to each other
A polygenetic trait phenotype
varies in populations, as some genes
contribute more than others, i.e. within
genes, alleles can have differing impacts
depending upon how they alter
encoded proteins
Even tough expression of a PGT is
continuous, it is possible to categorize
individuals into classes and calculate
the frequencies of the classes, when
graphed results always form a…
bell curve

7. Fingerprint Patterns
Basic pattern of whorl, loops or arches as well as
number of ridges determined by genes
Can be influenced during fetal development if fingers/toes touch lining of amniotic sac

8. HEIGHT Genetic environmental 50 genes influence height
Proper diet Improved overall health
Note: tallest person in 1914 is 5’9”, tallest in 1996 was 6’2”

9. SKIN COLOR Probably more than 100 genes affect pigmentation in skin
Exposure to sun can alter melanin production
Genes can an independently assort in interesting ways even though we all have about the same # of melanocytes per unit of area of skin
Varying hues = number of melanosomes, size, and density of distribution

10. Polygenetic Traits Lab
5)Table 2 Class Totals
Group
0 Tails
6 Heads
1 Tails
5 Heads
2 Tails
4 Heads
3 Tails
3 Heads
4 Tails
2 Heads
5 Tails
1 Heads
6 Tails
0 Heads 1 7 6 4 2 3 9 5 8 10 13 11
TOTAL 20 37 71 49

11. INVESTIGATING MULTIFACTORIAL TRAITS
For obvious reasons; predicting recurrence risks for negative polygenetic traits is much more difficult than single-gene traits.
Traditional Approaches include:
Determining the Empiric Risk
Heritability
Studying Adopted Individuals
Studying Twins
Newer Approaches include:
Genomic-Wide Association Studies

12. EMPIRIC RISK Is a population statistic
Based upon observation of incidence: rate at which event occurs and prevalence (number of individuals who have at specific time).
ER increases with severity, # of affected family members and how closely related a person is to affected individual
Because empiric risk is based solely on observation, we can use it to derive risks for disorders with poorly understood transmission patterns
EMPIRIC RISK
Cleft Lip and Palate
Empiric
Risk
Normal parents 1 affected child 4%
2.5% unilateral lip
5.6% bilateral lip/palate
1 affected parent risk for 1st child
3.2%
Identical Twin
31%
Male/Female
Ratio
2:1
Population
Incidence
1/1000

13. HERITABILITY
Heritability equals 1.0 for a trait whose variability is completely due to genes
Variability of most traits reflects a combination of differences among genes and environmental components
Variability changes as the environment changes
Example: H for skin color increases in winter. Why?
Darwin noted that some variations in populations are due to inborn differences and some to differences in the environment.
The degree of variation in a trait due only to genetics is heritability, or H. It estimates the genetic contribution to the variability of a trait.

14. Calculating Heritibility
Calculated using the coefficient of relatedness
H= observed phenotype variation
expected phenotype variation
(ie r value)
In a group of 100 parents 35 were shown to have HBP, what is the H for any of their children?

15. twins Adopted individuals
Provide more meaningful information, replaced most adoption studies Not perfect, MZ twins not “identical” DNA Traits that occur more frequently in both members of MZ twin pairs than in both members of DZ twin pairs is at least partly controlled by heredity Concordance: measures the frequency of expression of a trait in both members of MZ or DZ twins The higher the difference in concordance between MZ and DZ twins, the more influence genes exert over a trait Twins who differ in a trait are said to be discordant
Share environmental influences w/adopted family
Studies found genetics determine some traits like, however, the environment the child was raised in altered expression
Way to determine those traits that are due more to genetics than environment

16. Concordance Values

17. Separated at Birth
These twin boys were separated at birth, being adopted by different families. Unknown to each other, both families named the boys Jim. And here the coincidences just begun. Both James grew up not even knowing of the other, yet both sought law-enforcement training, both had abilities in mechanical drawing and carpentry, and each had married women named Linda. They both had sons whom one named James Alan and the other named James Allan. The twin brothers also divorced their wives and married other women – both named Betty. And they both owned dogs which they named Toy. Jim Lewis and Jim Springer finally met in February 9, 1979 after 39 years of being separated.
Provide natural experiments for
distinguishing nature vs nurture
Concordance is high even when
environments were very different
Though not an ideal approach, the
idiosyncrasies are striking….

18. GENOME-WIDE ASSOCIATION STUDIES
New tool to analyze multifactorial
traits and diseases
Look at ‘sign-posts’ throughout the entire genome in many individuals to identify common variants behind a particular phenotype
Genetic markers are used to follow variants that form patterns that can be compared between two groups of people-one with the trait/disease and one without
To be statistically significant study must include at least 100,000 markers
Have examined 100’s of conditions
and genes, have explained how they
arise, providing drug developers and
new therapy techniques to be
developed based upon the genetics
of the disorder

19. Markers used in GWAS

20. Types of GWAS
Cohort Study: following a large group over time, measuring many aspects of health
Case-control study: individuals from one group are matched to another group who share as many characteristics as possible, SNP differences are then associated to presence or absence of a disorder
Affected sibling pair: tracking linkage in families, shared sibling SNP’s= inherited trait
Homozygosity mapping: variation of affected sibling, genomes mapped for consanguine families

21. Limitations to GWAS
Prone to error because contain lot of variables(data points), however, large numbers of markers, measurements, people are necessary to pin point genes
Reveal associations between two types of info, but, not the cause
Often ID parts of genome that contribute only slightly to the risk of developing a disease
Selection criteria can introduce bias, selection of control populations, time of study, etc
Epistasis can cause misleading results, ie is it environment or genetic, are there masked genes, etc.
Can miss rare SNP’s or CNV’s that can cause or contribute to disease
Limitations are overcome by pooling data, combining studies/techniques, expanding data