Chapter 7 Multifactorial Traits

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Chapter 7

Multifactorial Traits


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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.


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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


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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 impactsExamples:

– Height– Hair color– Body weight – Cholesterol levels


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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

developmentFetus in contact with amniotic sac.Identical twins can have different fingerprints.

• Plot of total ridge count – bell curve of continuously varying trait.


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Inheritance of Height (1920s)

Figure 7.2a


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Inheritance of Height (1997)

Figure 7.2b


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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


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An Example of Variations in Eye Color

• The number of human eye color genes is unknown

• Analysis will probably reveal many genes

• Mice have more than 60 eye color genes

Figure 7.3


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Eye color

• Probably a pure polygenic trait.


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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


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Fingerprints

Figure 7.1


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Model for Variation in Skin Color

Figure 7.4


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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


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Some Drug Responses vary Between Populations

Table 7.1


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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.


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Heritability (H)Estimates the proportion of the phenotypic

variation in a population due to genetic differences

Figure 7.5


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Empiric Risk of Cleft Palate

Table 7.2


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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.


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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.


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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


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Coefficients of Relatedness for Pairs of Relatives

Table 7.4

Figure 7.6


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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.


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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


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Separating Genes and Environment

• Dizygotic twins: Shared environment

and 50% of genes• Monozygotic twins: Identical genotype, and

shared environment• Twins raised apart: Shared genotype but

not environment• Adopted individuals: Shared environment

but not genes


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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


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Table 7.5


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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


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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


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Two Examples of Multifactorial Traits

• Heart Health

• Body Weight

• Both are controlled by many genes and interaction with a complex environment


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Risk Factors for Cardiovascular Disease

Table 7.7


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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


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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


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Table 7.8

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Chapter 7 Multifactorial Traits