Complex Inheritance

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

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?

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

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...)

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

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

Multiallele variation

Polygenic Phenotypes

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

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

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”

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

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

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

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

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

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

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

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

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

Heritability of IQ

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

See you Thursday!