Polygenic and Multifactorial Inheritance

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 • Encodesweight-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 • Drosophilaand 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