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)

Bell curve Most individuals are clustered at ~average

Few individuals at extremes of the phenotype

Typical Polygenic Trait in a Population

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