1. Complex Inheritance

2. Learning Objectives By the end of this class you should understand:
The difference between continuous and discontinuous traits
The different factors that produce a complex trait
The expected proportions of inheritance from polygenic traits
The threshold model of polygenic genetic disorders
The factors increasing risk of multifactorial disorders
The purpose of studying twins
The genetics of obesity, height, and intelligence

3. The Convenience of Mendel
Pea plant color and missing enzyme disorders are discontinuous traits
Obvious difference between phenotypes
Most important traits are continuous
A range of possible outcomes
What are some continuous traits in humans?

4. Continuous Traits Major examples today:
Height
Weight
Skin Color
Intelligence
Most traits in humans are continuous
Multiple loci
Multiple alleles per locus
Environmental effects

5. Polygenic Traits
Some traits are controlled solely by genetics but at multiple loci
Referred to as polygenic traits
Best examples are eye color and hair color
Wide range of traits but not influenced by environment
(Not counting cosmetics...)

6. Why So Much Variation?
The various hair proteins have many different genes
Recall what monohybrid and dihybrid cross ratios looks like
1:2:1
1:4:6:4:1
With three and four alleles the possibilities stack up quickly

7. Thought Experiment
The additive model for polygenic inheritance suggests certain codominant alleles increase a certain trait
AaBbCc, where A B C increase height +3 inches
A dihybrid cross between AaBbCc x AaBbCc will produce a normal (bell) curve

8. Multiallele variation

9. Polygenic Phenotypes

10. Bell Curve in Offspring
Due to heterozygosity, offspring rarely match parents in unusual traits
This phenomenon of a bell curve of offspring is called regression to the mean
Even a dominant allele will only be expressed in 50% of offspring
A result of the rare-allele phenomenon

11. What About Environment?
Eye and hair color are independent of environment
Height can be influenced by diet, endocrine function, and disease
Nature vs. Nurture
Even monozygotic twins are different heights if they are raised differently

12. Multifactorial Trait
Height is a multifactorial trait which means it is influenced by genetic and nongenetic factors
The best way to study whether a trait is multifactorial is to examine monozygotic twins
“Identical twins”

13. Why Monozygotic Twins?
Monozygotic twins have essentially identical DNA except for stray mutations
All genetic factors are the same, so any difference is solely due to environment
Adopted monozygotic twins tell us a lot about how much influence the environment has

14. Dizygotic Twins
Dizygotic twins come from two different sperm- egg fertilizations
Identical nurture in the womb but are otherwise only 50% identical (siblings)
Still a secondary valuable source of information on heredity

15. Percent DNA-related
When a trait is shared by twins it is referred to as concordance
When the trait is different between the two it is called discordance

16. Heritability
The more genetic in origin a condition is, the more heritable it is said to be
A multifactorial disorder such as diabetes or cleft lip has a genetic component but may also be partially triggered by the environment
Diabetes trigger: eating lots of refined sugars

17. Threshold Model
Some disorders (such as cleft palate) appear discontinuous but are polygenic and multifactorial
A combination of genes puts the child at risk

18. Risk Factors for Discontinuous Multifactorial Disease
A threshold model disease has the following risk factors:
Consanguinity
Previous affected child
Severity of defect
Higher frequency in one sex

19. Risk Factors Consanguinity: related parents (first cousins)
Previous Affected Child: parents most likely carry many markers
Severity of Defect: the more severe the defect, the more extreme the genetic markers are
Higher Frequency in One Sex: most likely there are markers on the X or Y chromosome

20. Heritability of Multifactorial Traits
Obesity can be studied as a disorder
Has many genetic factors but also heavily dependent on environment/behavior

21. Heritability of Other Traits
Skin color is also a complex trait
Intelligence (indirectly measured through IQ) is also highly heritable
“IQ” is a very poor estimate for complexity of cognitive function

22. Heritability of IQ

23. The Return of Bioethics
Many people believed that race and IQ are strongly correlated
Some people still believe this
This is not true
IQ has also been rising
Score of 100 (“average”) is a higher performance than it was 50 years ago
This is still a sticky topic for many people

24. See you Thursday!