Multifactorial inheritance in humans Flashcards
Outline Mendelian Inheritance
- It explains how certain patterns of how traits are passed from parents to offspring
- ‘either/or’ phenotype, you either have the disorder or you don’t
- Recessive and dominant genes involved
- While Mendelian traits tend to be influenced by a single gene, the vast majority of human phenotypes are actually polygenic traits
Outline Polygenic inheritance
- A phenotype determined by two or more genes are different loci
- Each gene exerts an additive effect
What are polygenes?
A gene whose individual effect on a phenotype is too small to be observed, but which can act together with others to produce observable variation. As a result, it can become difficult to predict a phenotype.
What is multifactorial inheritance?
- This involves environmental factors interacting with many genes to generate normal distributed susceptibility
- Differ from polygenic inheritance - which refers to traits that result from the additive effects of multiple genes
What factors are involved in multifactorial inheritance?
- A combination of inherited, environmental, and stochastic (chance) factors.
What are some examples of multifactorial inheritance?
- Normal human traits: height, intelligence, blood pressure, etc
- Congenital malformations: cleft lip/palate, neural tube defects, etc
- Acquired childhood and adult-onset examples: asthma, diabetes mellitus, epilepsy, etc
What is discontinuous multifactorial(/polygenic) inheritance?
- Things such as eye colour or blood group, which have a limited number of possible values
- A person’s blood can be A, B, AB or O, but it can’t be anything in between
- Other examples include: diabetes mellitus, etc
What is continuous multifactorial(/polygenic) inheritance?
- A characteristic that changes gradually over a range of values shows continuous variation
- A broad range
- Examples of such characteristics are: height, arm span, weight, etc
State two example of multifactorial, common human traits
- Skin colour
- Intelligence
What else tends to be commonly multifactorial?
- Diseases
Why is type two diabetes multifactorial?
- Due to the inheritance of susceptibility genes (genes which make one susceptible to developing it)
- Plus, environmental factors, such as obesity
What would happen if height was inherited in a mendelian manner?
- You would only see three heights: tall, short, average
What curve does height follow?
- Gaussian distribution curve
Outline continuous multifactorial inheritance
- It gives a normal distribution of genetic predisposition
- Environmental factors interact with this distribution
- Symmetrical bell-shaped curve distributed evenly around the mean
Explain evidence for environmental influence
‘Regression to the mean’
- When tall parents have children shorter than the average parental value
- When short parents have children taller than the average parental value
- If height were only governed by polygenetic inheritance (no environmental influence) you would only observe measurements around the mean of the parental values
How do you account for a discontinuous phenotype where normal distribution exists?
- The liability model, proposed for multifactorial inheritance
- There is a liability towards the trait that consists of a combination of genetic and non-genetic factors and is normally distributed in the population
- The trait is expressed ONLY in individuals who exceed the threshold
Outline the inheritance of congenital malformations
- Cleft lip: a congenital malformation inherited as a multifactorial trait (mild and severe forms)
- Parents can be unaffected with no previous family history yet have an affected child
- Thus, parents must have had SOME underactive genes for lip and palate formation
- The balance between underactive and active genes is what determines whether the child gets the abnormality
What are the rates of developing cleft lip/cleft palate?
- Population incidence: 1/1000
- In a family with an affected person: 1st relatives: x40, 2nd relatives: x6, 3rd relatives: x3
Outline the support for the threshold model
- Incidence is greatest amongst relatives of the most severely affected
- For example, the risk of reoccurrence is 6% for a first degree relative of bilateral cleft lip compared to a 2% risk of unilateral cases (more mild)
What are twins with identical genotypes called?
- Monozygotic twins
How do we study multifactorial inheritance?
- Association studies: compare the incidence of a variant in patients with the disease to those without (‘case control’ study)
- Whole-genome association studies: microarray (can test thousands of variants simultaneously)
- Twin studies: monozygotic twins = identical genotypes. So, those separated at birth would be exposed to different environments. If both develop the disorder (creating concordance) then it is known that the genetic contribution is strong. For multifactorial traits however, concordance rates will be less than 100% but greater than that of those found in siblings
What are some problems of studying multifactorial disorders?
- Variable age of onset: status of unaffected family members
- Few family members with disorder makes linkage difficult
- Heterogeneity of disorders associated with different causes means subtypes not present at phenotypic level
Summarise multifactorial inheritance
- Most human diseases have both genetic and environmental components
- Many vary along a continuum in the population (i.e., height)
- It indicated polygenetic inheritance-phenotype results form an additive effect of two or more genes
Outline the key points of multifactorial inheritance
- There is a similar risk for first degree relatives (offspring, siblings or parents)
- The greater the number of affected relatives, the higher the recurrence risk
- Identical twins are not 100% concordant, showing non-genetic factors
- The severity of the disorder, and occasionally the sex of the affected individual, may modify the risk
