Week 8 Random Flashcards
Multifactorial/Polygenic Inheritance
Charactersitics
interaction of genes and environment
recurrence risk varies and is determined empirically
Heritabillity
H = 2(cmz- cdz)
cmz or cdz =concordance mz or dz.
Type I diabetes (Juvenile Onset or IDDM)
Autoimmunity disease in which the insulin-producing b-cells of the pancreas are destroyed.
Requires administration of insulin to prevent death (wasting due to inability to utilize glucose, acidosis, and ketosis).
Chronic, lifelong condition.
Although treatable, difficult to manage. blindness, limb amputations, kidney failure
Major goals in treatment of type 1 diabetes
1) Use genetic screens/tests to identify at risk individuals.
2) Prevent the destruction of the b-cells by modifying environment (eliminate triggers).
DPT Diabetes Prevention Trial
Large, multicenter, multiyear study of individuals at high risk of developing type I diabetes (children, twins, and siblings of diabetics).
Examining the influence of specific environmental factors on the risk these individuals will develop diabetes.
IDDM-1 locus: HLA class II DR gene. 95% of Caucasians with type I diabetes have DR3 and/or DR4 alleles, these occur in only 50% of the general population.
IDDM-2 locus: A VNTR in the 5’ region of the insulin gene itself, accounts for about 10% of the heritability.
HLA DQ alleles confer resistance to diabetes.
Polygenic/multifactorial disorders:
Recurrence and transmission patterns
Recurrence risk will change from population to population, and from family to family! Due to differences in genetic load.
Although clearly genetic, risk cannot be calculated based on degree of relationship (probability of shared genes).
Recurrence risks are determined from empirical data (risk based on direct observation of the population data).
Attributes of Polygenic/Multifactorial Inheritance:
- Recurrence risk decreases rapidly for more distantly related relatives. Risk is less than would be predicted from coefficient of relationship
- Recurrence risk varies from family to family (genetic load).
- Recurrence risk increases if more than one family member affected (indicates higher genetic load)
- The more severe the expression, the higher the _risk _(indicates higher genetic load)
- Recurrence risk higher if proband is of the less commonly affected sex
Relationship between risk and relativeness
If disease is multifactorial, risk decreases more rapidly than predicted from coefficient of relationship.
Polygenetic vs. Multifactorial
Polygenic- involves multiple genes.
Multifactorial- environmental trigger as well as genetic causes.
Quantitative trait-
phenotype distributes across a more or less Gaussian (normal) distribution across a population.
Threshold of liability
disease does not have a normal distribution, but is the result of a continuous underlying liability. If threshold is exceeded, then disease results
Membrane Lipid Composition
Phospholipid
Cholesterol
Glycolipids
Lipid Rafts
Lipid rafts has specific proteins. Thus, there are biochemical activities associated with lipid rafts.
Immune mechanisms
Signaling mechanisms
Five Major Phospholipids
Which one is negative?
What groups are attached?
Which are found in lipid rafts?
Phosphatidyl-ethanolamine (enamine)
Phosphatidyl-serine (serine) (-)
Phosphatidyl-choline (choline)
Sphingomyelin (choline)&OH
Sphingosine OH/NH3/OH
Function of Ca2+ in activation of PKC
PKC is a soluble protein in the cytoplasm. After Ca2+ binds to it, PKC moves to the membrane where it binds to phosphatidylserine.
No phosphatidylserine -> no binding -> no function.
Phosphatidylserine exposed on the cell surface serves as a signal to induce neighboring cells (macrophage) to phagocytose the dead cell and digest it.
Types of membrane proteins
Integral
Peripheral