Transcript Is Spina Bifida a Multifactorial Trait?

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