Genetics 6-Complex Genetic Diseases IGNORE FOR NOW Flashcards
What is leptin
It is a hormone/cytokine
It is a protein signalling molecule that is produced by ADIPOSE TISSUE
It moves through the circulator system to the brain and tells the brain how much fat is in storage in the adipose tissue.
More Fat = More Leptin
High leptin tells the brain that you do not need to eat more food - it controls the fat in your body
Leptin also stimulates the onset of puberty
Before puberty there is a build up of fat which sends a permissive signal via leptin to the brain to tell it that puberty can begin.
What is leptin deficiency
Uncontrollable appetite
People with leptin deficiency don’t go through puberty
They have low thyroid function and immune problems.
This child had leptin deficiency
The photo on the right is him after having 6 months of treatment with recombinant leptin.
If the boy was starving to death, his brain wouldn’t know that he had plenty of fat stores so he would eat even more.
Most fat people have a lot of leptin.
Generally, a higher BMI means a higher leptin concentration.
Fat people may have lots of leptin but may not respond to it.
Leptin Deficiency is very rare
Fat people have an insensitivity to leptin (sort of like type 2 diabetes).
It is possible that the leptin receptor in the brain is deficient, causing the insensitivity.
Families were found with a genetic deficiency of the leptin receptor.
What is common obesity
Common Obesity - Obesity in the General Population
Genome-Wide Association Study - you can take someone’s genome and look for 6 million markers across the genome. If you have two groups of people, one with obesity and the other without, you can identify natural variations among the two groups and see if any of the markers are more common in obese people or normal people.
The approach is hypothesis-free - you do not need to know what causes obesity.
GWA isn’t used to search for mutations - you just look at sequence variations.
Common diseases can be caused by the accumulation of slightly disadvantageous components in your genome.
Many genetic markers were found which are associated with obesity, the strongest marker is FTO.
GWAS-identified single nucleotide polymorphisms explain only a small proportion of common obesity risk.
GWAS has identified associations that are statistically strong and reproducible but their contribution to the genetic component of BMI is estimated to be low (<5%).
