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Human Genetics. Multifactorial Traits. Genes and the Environment. Genes and the environment interact to mold many of our traits. Mendelian trait due to a single gene. Polygenic trait due to multiple genes. Multifactorial trait results from action of

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Human genetics

Human Genetics

Multifactorial Traits

Genes and the environment interact to mold many of our traits
Genes and the environment interact to mold many of our traits.

Mendelian trait due to a single gene

Polygenic trait due to multiple genes

Multifactorial trait results from action of

genes and the environment

Discontinuous variation
Discontinuous Variation traits.

  • Phenotypesfall into two or more distinct non-overlapping classes

    • Example - short and tall phenotypes in pea plants

    • no in betweens

Continuous variation
Continuous Variation traits.

  • Phenotypes distribute from one extreme to another in an overlapping (continuous) fashion.

  • Examples - height, skin color, eye color, intelligence

Polygenic traits
Polygenic Traits traits.

  • Polygenic Traits are produced by the action of multiple genes.

  • Variation is continuous, not discrete

  • Effect of genes is additive or synergistic

  • Also called quantitative trait loci (QTL)

  • Genes can have major or minor impacts

Qtl takes time and lots of chromosomal markers
QTL takes time and lots of chromosomal Markers. traits.

Nature Genetics31, 235 - 236 (2002) doi:10.1038/ng0702-235

Diseases can be polygenic

Congenital malformations traits.

Cleft palate

Congenital dislocation of the hip

Congenital heart defects

Neural tube defects (spina bifida etc.)

Pyloric stenosis

Club Foot (Talipes)

Adult onset diseases


Diabetes Mellitus





Ischaemic heart disease

Manic depression


Diseases can be Polygenic

Osteoporosis traits.

  • Osteoporosis is defined as low bone mineral density (BMD) and associated fractures.

  • Osteoporosis causes morbidity and mortality in the elderly.

  • It has a significant genetic components that are largely unknown.

  • In Iceland, a linkage analysis in a large number of extended osteoporosis families in Iceland, (using a phenotype that combines osteoporotic fractures and BMD measurements) showed linkage to Chromosome 20p12.3.

Qtl on chromosome 20 for osteoporosis
QTL on Chromosome 20 for Osteoporosis traits.

  • Styrkarsdottir U, Cazier JB, Kong A, Rolfsson O, Larsen H, et al. (2003) Linkage of Osteoporosis to Chromosome 20p12 and Association to BMP2. PLoS Biol 1(3): e69

Osteoporosis qtl gene identification
Osteoporosis QTL Gene Identification traits.

  • Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients.

Eye color a polygenic trait
Eye color: A polygenic trait? traits.

Five eye colors can be produced by the interaction of just two genes.

Polygenic inheritance
Polygenic Inheritance phenotypes

  • Each allele for all the genes involved contributes to the expression of the trait

  • Not necessarily the same for each gene

  • Some alleles will make no contribution

  • Expressed trait is the sum of all the small contributions.

Polygenic inheritance challenge
Polygenic Inheritance Challenge phenotypes

  • Phenotypic expression can vary over a wide range

  • Traits are often quantified by measurement rather than by counting.

    • Height- relatively easy

    • Eye Color- need instrumentation

    • Skin Color- Environmental component like tanning- use unexposed skin

  • Needs to analyzed populations rather than individuals.

Multifactorial traits
Multifactorial Traits phenotypes

  • Traits produced through gene-gene interactions and gene interactions with environment factors.

  • What are “environmental factors”?

    Non-genetic factors

    • physical – pregnancy, obesity, diet

    • chemical - diet, smoking, alcohol , medicine

    • social - illness, stress

    • Age

  • How much of a given phenotype is genetic (inherited) and how much is environment?

Multifactorial traits1
Multifactorial Traits phenotypes

- are influenced by genes and by the environment

Many genes +

Trait environment

fingerprints prenatal touch

height nutrition

skin color sun exposure

Height is influenced by genes and environment during growth
Height is influenced by genes and environment during growth phenotypes


Maximum 6’5”

Improved nutrition can impact height.

Empiric risk
Empiric Risk phenotypes

  • Based on incidence in a specific population.

  • Empiric Risk is a Statistic

  • Incidence is the rate a trait occurs- like number of new diagnoses

  • Prevalence is how common the trait is in the population a a particular time.

  • If a trait is inherited, the closer the relationship, the greater the risk.

Empiric risk1
Empiric Risk phenotypes

  • Empiric risk for an individual increases with

    •  severity of the disorder

    • number of affected family members

    • relatedness of the individual to the affected individual

  • We have to use the frequency of occurrence of the trait in a specific population to predict its reoccurrence.

Empiric risk of cleft lip

Relationship phenotypes

Identical Twin




First Cousin

General Population (no affected relatives)

Empiric Risk







Empiric Risk of Cleft Lip

Heritability h
Heritability: H phenotypes

  • Portion of the phenotypic differences due to genetic inheritance at any particular point in time.

  • Highly related trait, in a large group of siblings, 50% will share the trait.

  • Heritability =1 when a trait is completely genetic

  • Heritability= 0 (0%) when a trait is completely envoronmental

Multifactorial phenotypes

Polygenic Trait

Genetic Variation



Additive Effects of

Recessive Alleles


Dominant Alleles



Check out reading 7 1 in the text
Check out Reading 7.1 in the Text phenotypes

  • Each direct degree of relationship shares 50% of genes (1/2)

  • You and first cousin once removed

    • You to mom 1/2

    • Your mom to her mom (grandmother) 1/2

    • Your grandmother to her brother 1/2

    • Your great uncle to his daughter (your first cousin) 1/2

    • ½ X ½ X ½ X ½ = 1/16

How do we advised people on relative risks with poorly understood inheritance patterns
How do we advised people on relative risks with poorly understood inheritance patterns? 

  • We need to understand the components of phenotypic variation

  • genetic variance

    • number of different genotypes within the population

  • environmental variance

    • number of different environments in which all the genotypes have been expressed

Calculating heritabilty
Calculating Heritabilty understood inheritance patterns? 

Useful to study

- Relatives in pedigrees

- Adopted children

- Twins

- Twins raised apart

Heritability calculation

Relation understood inheritance patterns? %concordance % expected

MZ twins 0.81 1.00

DZ twins 0.42 0.5

Heritability Calculation

Estimated from the proportion of people sharing a trait compared to the proportion predicted to share the trait.

Concordance - % of pairs of individuals that share the trait

(both affected or both unaffected)

Language skills (measured by vocabulary at age 2)

How do we isolate environmental and genetic components to determine heritability

Adopted individuals understood inheritance patterns? 

- Share environment, but not genes

Dizygotic twins

- Share environment and 50% of genes

Monozygotic twins

- Identical genotype, shared environment

- Twins raised apart

- Share genotype, but not environment

How do we isolate environmental and genetic components to determine heritability?

Adoption studies
Adoption Studies

  • Danish Adoption Register 1924-1947

  • One study looked at causes of death

    • If a biological parent died of infection before age 50, then the Adoptive child was 5 times more likely to die of infection at a young age relative to the general population.

    • Suggests a strong genetic component

Adoption studies1
Adoption Studies

  • Danish Adoption Register 1924-1947

  • Regarding cardiovascular disease

    • Adoptive parents who died of cardiovascular disease before age 50, their adoptive children were 3 times more likely to die of cardiovascular disease than a person in the general population.

    • suggests a strong environmental component

Twin studies
Twin Studies

  • Powerful genetic tool

  • Identical twins (experiment)

    • Genotype is identical

    • Same environment at the same age

  • Fraternal twins (controls)

    • Different Genotypes (50%)

    • Same environment at the same age

What do we measure in twin studies?


- the expression of a trait in both twins

 - measured as a percentage of pairs in which both twins express the trait.

  - if both twins don’t share the trait - discordant

Bottom line: concordance values

A trait observed to be present more often in both members of a MZ twin pair than in both members of a DZ twin pair is presumed to have a significant inherited component.

Snp single nucleotide polymorphism
SNP (single nucleotide polymorphism twins.)

Nucleotide site with more than one allele is a polymorphism.

  • On average between two random individuals, there is one SNP every 1000 bases => 3 million differences!