Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Chapter 7
Multifactorial Traits
7-1
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Cleft Lip and Palate
• Symptoms– Hole between nose and upper lip
– Difficulty feeding- lack of suction
• Variability in severity
• Genetic and environmental factors
– Prenatal exposure to drugs- seizures, anziety, elev.
Cholesterol
– Pesticides
– Cigarette smoke
– Infections
• 4% risk if in a sibling.
• Tests to detect haplotypes assoc. with elevated
risk.- series of known DNA sequences linked on a
chromosome or SNPs.
7-2
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Contribution of Genes or Environment
• Genes rarely act completely alone
• Environmental factors and other genes may
modify expression
• Traits can be described as
– Mendelian or primarily due to a single gene
– Polygenic or primarily due to multiple genes
– Multifactorial or complex due to an interaction
between genes and the environment
7-3
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Polygenic Traits
• Variation is continuous, not discrete( normal vs
affected)
• Individual genes follow Mendel’s laws
• Effect of genes is additive or synergistic –
together they do not produce a single gene
phenotype, they all contribute
• DNA sequences that contribute are called
quantitative trait loci (QTL)
• Genes can have major or minor impacts
Examples:
– Height
– Hair color
– Body weight
7-4
– Cholesterol levels
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Fingerprint Patterns
• Based on skin folds- dermal ridges.
• Dermatoglyphics- skin writing.
– Compares number of ridges to identify
individuals. Total ridge count = # ridges on all
fingers.
– Determined by genes
– Responds to environment- wk 6-13 of prenatal
development
Fetus in contact with amniotic sac.
Identical twins can have different fingerprints.
• Plot of total ridge count – bell curve of
continuously varying trait.
7-5
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Inheritance of Height (1920s)
Figure 7.2a
7-6
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Inheritance of Height (1997)
Figure 7.2b
7-7
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Height- multifactorial
• Effect of environment- poor nutrition
and diet- results in individuals not
reaching their full genetic potential.
• Difference in height- tallest of 1920s=
5’9’’; tallest 1997- 6’5’’.
• Hard to determine how many genes
are responsible formultifactorial
traits that are also polygenic
7-8
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
An Example of
Variations in Eye Color
Figure 7.3
• The number of human eye color genes is unknown
• Analysis will probably reveal many genes
• Mice have more than 60 eye color genes
7-9
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Eye color
• Probably a pure polygenic trait.
7-10
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Multifactorial Traits
• Are influenced by interaction of genes
and by the environment
• Examples:
– Fingerprint, many genes and
prenatal contact
– Height, many genes and nutrition
– Skin color, many genes and UV
exposure
7-11
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Fingerprints
Figure 7.1
7-12
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Model for Variation in Skin Color
Figure 7.4
7-13
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Skin Color
• Melanin production - skin pigmentation
and protects skin from UV radiation
• Skin color is a phenotype interaction
between pigment genes + environment
• In a genetic sense, race based on skin
color has little meaning
• Medical treatment differences/difficulties
7-14
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Some Drug Responses vary Between
Populations
Table 7.1
7-15
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Analyzing Multifactorial Traits
•
•
Difficult, requires multiple techniques
Use human genome sequences, population, and family studies.
•
•
•
Empiric risk –incidence or rate an event occurs in a population.
Prevalence- proportion of the population that has a disorder at a specific time.
Empiric Risk –increases with the severity, more family members affected and
the closer the relationship to an affected individual.
– The closer the relationship; increased probability, since increase in genes in
common.
– Based on observations so it can be used even in difficult transmission patterns.
•
Heritability- Measurement of genetic.
–
–
–
–
Blood relationship and the coefficient of relatedness ( genes 2 related people share.
Designate 10, 20,30
Pedigrees
50 % chance of inheriting genes from parents and between siblings.
7-16
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Heritability (H)
Estimates the proportion of the phenotypic
variation in a population due to genetic
differences
Figure 7.5
7-17
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Empiric Risk of Cleft Palate
Table 7.2
7-18
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Heritability
• High Heritability- high influence of genes.
• Heritability= observed phenotypic variation /
expected.
– Example Height- 0.4/0.5 = 80%
• Some traits- epistasis influence- LDL
• Polygenic traits- use additive effects of
recessive alleles of different genes because
dominant traits may influence the phenotype
but are very rare and may not contribute to
Heritability.
7-19
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
PTC –
• Bitter taste• taster or nontaster phenotypes.
• SNPs
–
–
–
–
3 polymorphic sites
2 haplotypes-form two alleles.
Taster- G,T, A; non tasters C,C,G substituted DNA bases.
multifactorial
• Largely determined by 1 gene on chromosome #7
• Influenced by other genes-lesser extent but
addittive.
7-20
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Heritability Values
• Heritability is estimated from
the proportion of people
sharing a trait compared to
the proportion predicted to
share the trait
• May vary between populations
and time period
Table 7.3
7-21
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Coefficients of Relatedness
for Pairs of Relatives
Table 7.4
Figure 7.6
7-22
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Importance of Multifactorial
Inheritance in Agriculture
• Breeders
– Birth weight, milk yield, eggs hatched,
fiber length,
– Genetics- additive or epistatic
– Envirnoment can be controlled
– Matings can be selected.
7-23
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Analyzing Multifactorial Traits
• Comparisons between and within
families
– Twins dizygotic and monozygotic
– Twins raised apart
– Adopted children
• Association studies – compare SNP
patterns between affected and
unaffected groups, identify important
DNA regions
7-24
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Separating Genes and Environment
• Dizygotic twins:
• Monozygotic twins:
• Twins raised apart:
• Adopted individuals:
Shared environment
and 50% of genes
Identical genotype, and
shared environment
Shared genotype but
not environment
Shared environment
but not genes
7-25
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Concordance
• Concordance - the percentage of pairs
in which both twins express the trait
• Used to determine heritability
• Has limitations, assumes both type of
twins share similar environments
• MZ twins often share more similar
environments
7-26
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Table 7.5
7-27
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Single Nucleotide Polymorphism
SNP
• Nucleotide site with more than one allele is a
polymorphism
• Site is considered polymorphic if allele is
present in >1% of the population
• On average, between two random individuals,
there is one SNP every 1,200 bases or about 10
million differences!
• Linkage disequilibrium
7-28
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Association Studies
• Studies compare a group of interest (cases) to a
control group for the presence of a gene or SNP
• Controls are matched to cases for characteristics
that may confound results: age, ethnicity, gender,
environment
• If the SNP is present more often in cases than
controls, it is associated with the trait and implies
that the SNP may be near a gene impacting the
trait
7-29
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Two Examples of Multifactorial Traits
• Heart Health
• Body Weight
• Both are controlled by many genes and
interaction with a complex environment
7-30
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Risk Factors for Cardiovascular
Disease
Table 7.7
7-31
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Body Weight
• Reflects energy balance
• 30% of US adults are obese
• Twin studies suggest obesity has 75%
heritability
• Lifestyle, including diet and exercise, are
environmental components impacting weight
• Genes influence hunger and metabolism
7-32
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
The Leptin Pathway Impacts Weight
• Leptin is a protein hormone produced by fat
• It signals sufficient calorie intake
• Travels in bloodstream, is bound by leptin
receptors in the brain and triggers a
decrease in eating
• Mutations in the leptin gene can cause
obesity in mice and rarely in humans
• Components of the leptin pathway may be
important for general weight regulation
7-33
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Table 7.8
7-34