1. Polygenic and Multifactorial Inheritance
Chapter 10

2. Central Points Polygenic traits controlled by two or more genes
Multifactorial traits are polygenic with an environmental component
Spina bifida is a multifactorial trait
Many other multifactorial traits

3. 10.1 Polygenic Traits Determined by two or more gene pairs
Examples: immune system, color of skin, hair, and eyes
Cause slight and often variable range of differences throughout population
Trait value: measurable aspect of the phenotype (height, skin color, and sizes of body parts)

4. Typical Polygenic Trait in a Population
Bell curve
Most individuals are clustered at ~average
Few individuals at extremes of the phenotype

5. 10.2 What Is a Multifactorial Trait?
Controlled by two or more genes and affected by environmental factors
Example: Height
Genes inherited in Mendelian fashion
Interaction of genes with environment produce many different phenotypes

6. Variation in Height

7. Characteristics of Multifactorial Traits
Several genes control trait
Not inherited as dominant or recessive
Genes controlling trait contribute a small amount to phenotype
Environmental factors interact with genes to produce phenotype
Many phenotypic differences in trait
Distributions of phenotypes form a bell-shaped curve

8. Multifactorial Diseases
Diabetes
Spina bifida
Club foot
Cancer
Hypertension and cardiovascular disease

9. Some Multifactorial Traits

10. 10.3 Spina Bifida Birth defect involving nervous system
Occurs first month of embryonic development
Type of neural tube defect
Problems in development of spinal cord and related parts of nervous system

11. Neural Tube Gives rise to: Brain Spinal cord
Meninges: membranes that cover and protect brain and spinal cord

12. Formation of Neural Tube

13. Types of Spina Bifida

14. Anencephaly
Extreme form of a neural tube defect, head end of neural tube does not close
Major portions of brain and skull do not form, remaining portions may not be enclosed in skull
Can survive only within mother, most stillborn
If survive, die within a few hours or days from heart and breathing problems

15. Spina Bifida
Opening and damage can be surgically repaired, damage to nervous system permanent
Varying degrees of paralysis
Learning disabilities
Bowel and bladder problems
No cure for SB but most live into adulthood

16. Is Spina Bifida a Multifactorial Trait?
Yes
Tends to cluster in families
Risk of second child with SB or another neural tube defect increases significantly
Environmental factors include dietary deficiencies in folic acid

17. VANGL1: Gene on Chromosome 1
In mice, gene acts early in development of neural tube
Mutations in gene cause conditions similar to SB
V239I, may cause a partial loss of function in VANGL1 protein

18. Environmental Risk Factor for SB
Diets deficient in folic acid, a B vitamin
Need 0.4 mg/day for at least three months before pregnancy, and until week 12
Reduces risk of SB and related conditions by ~70%
How folic acid interacts with genes in formation of neural tube unknown

19. 10.4 Other Multifactorial Traits
Fingerprints: a polygenic trait
Influenced by prenatal environment
Nutrition of the mother
Rate of finger formation and growth
Even identical twins have unique fingerprints

20. Identical Twins and Fingerprints

21. Obesity: A Multifactorial Trait?
Twin studies used to estimate how much of obesity is genetic
Identical twins, monozygotic (MZ) twins, genetically identical, form from same zygote
Occurs in both MZ twins ~70% of the time: 70% concordance

22. Obesity in Mice Pedigree

23. Mouse ob Gene
Encodes weight-controlling hormone leptin, produced in fat cells
Along with cell receptors in brain, controls how energy used
Human gene for leptin, equivalent to mouse ob gene, is on chromosome 7
Mutations result in obesity

24. Obesity
Complex disorder involving action and interaction of multiple genes and environment
Important genes for obesity located on chromosomes 2, 3, 5, 6, 7, 10, 11, 17, and 20
Further work to ID additional genes and how these genes interact with environmental factors

25. Obesity Genes

26. Is Intelligence a Multifactorial Trait?
Head size was used to determine intelligence
Early 20th century, psychological rather than physical methods
Intelligence quotient (IQ) assumes that intelligence is a biological property
Concordance in MZ twins raised together and apart indicates genetic and environmental factors

27. Genes that Control Intelligence
Searching for single genes that control aspects of learning, memory, and spatial perception
Drosophila and the mouse models
Drosophila has many biochemical pathways identical to those in humans
Pathways play important roles in learning and memory

28. Quantitative Trait Loci (QTLs)
Use information from Human Genome Project
Associated with reading disability (developmental dyslexia)
Genes on chromosomes 6, 15, and 4 for cognitive ability
Accumulated results indicate intelligence is polygenic and multifactorial trait

30. Cleft Lip/Palate Occurs as part of syndromic cases and sporadic
Genetics of syndromic cases
- Van der Woude Syndrome – variation in IRF6 gene
- Siderious X-linked mental retardation – caused by mutation in PHF8 gene
Genetics of non-syndromic cases – variations in IRF6, PVRL1, MSX1 and others
Environmental Factors – lack of oxygen