Threshold Traits And Multifactoral Inheritance Flashcards
Most chronic disease in humans are explained…
By multifactorial genetics
Give examples of diseases that are multifactorial
Most cancers, asthma, heart disease, diabetes, neurodegradation
Most of the non-infectious stuff that a physic8an are multifactorial disorders
What are multifactorial traits?
A trait that is controlled by many genes (polygenic) in combination with environmental exposure
-Tend to avoid the term “complex inheritance”
What are threshold traits?
The trait does not manifest unless some combination of genes sand environment is reached
Give an example of threshold traits
Example… non-syndrome can orofaciak clefting (cleft lip/palate)
Some individuals develop cleft lip and/or palate because of some known syndrome (we already have described some of these in this course )
However, some babies are born with cleft lip, and they have no known genetic cause… (non-syndromic) -this is thought to be a combination of genetics and environment
All humans are …
At some risk of forming a cleft lip and/or cleft palate during embryonic and fetal development
Two normal parents have a first child with cleft lip…
The second child born to the couple is at higher risk of having orofacial clefting compared to the general population. Increased risk is not 25%(ss would expect fkrcsutisomal recessive) nor is it 50% (as we would expect from autosomal dominant)
For the general population, a first child with no cleft lip , a second child will have less risk (less risk, but there is still some risk)
How can the threshold curve be manipulated manipulated to show how the threshold of a specific family changes after the first baby is born with the trait?
- The threshold line moves to the left, and the curve doesn’t move
- The curve moves to the right, and the threshold line doesn’t move
These describe the same thing, and the end result is that the area under the curve that describes the risk becomes increased
Aside from orofacial clefting, give an example of a multifactorial trait
Cancer is an example that develops as we age
Colon cancer as an example-we are all at risk of developing colon cancer
Of course crossing the threshold might be influenced by an environmental modifier
What factors can increase or decrease risk of developing colon cancer?
- lack of exercise
- physical inactivity
- obesity
- being overweight
- low dietary fiber
- smoking
- excessive alcohol
- advanced age etc
How much of colon cancer is due to single gene inheritance?
Less than 4%
What is significant about the 4% of colon cancer?
The 4% of colon cancer cases that are caused by a single highly penetrant gene are inherited as autosomal dominant
-So each child of an affected parent would have a 50% chance of inheriting the trait
Who are at risk of developing cancer?
All humans are at risk of developing cancer
- Some people have a lot of “good” alleles meaning they can be exposed to more environmental risk factors and not develop colon cancer
- Some people have less “good” alleles meaning that exposure to more environmental risk puts them at higher risk of developing colon cancer
- Some people have familial risk, meaning that colon cancer occurs as “clusters” in their family, but it is not Mendelian (the autosomal dominant form )
Good in quotes as genes are never good or bad
What evidence suggests cancer is genetically controlled?
- autosomal dominant forms
- tumor suppressor genes
- Protooncogenes and oncogenes
- Cancer driver genes, and signaling pathways
- Cancer predisposition syndromes
- Cancer clustering in families (multifactorial)
What is evidence cancer is influenced by the environment?
- sunlight, UV light
- excessive exposure to mutagens
- smoking cigarettes (tobacco products)
- unhealthy lifestyle
- sugar consumption
