Polygenic and Multifactorial Inheritance Chapter 10

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

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)

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

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

Variation in Height

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

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

Some Multifactorial Traits

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

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

Formation of Neural Tube

Types of Spina Bifida

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

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

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

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

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

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

Identical Twins and Fingerprints

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

Obesity in Mice Pedigree

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

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

Obesity Genes

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

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

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

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