Module 1 SNPs Flashcards
What is a SNP?
Ex.
Single nucleotide polymorphism (base sub) leading to amino acid substitutions in encoded polypeptides
Synonymous - SNP encodes for the same AA
Non-synonymous - SNP encodes for a different AA and can alter function of protein
Ex. non-synonymous SNP in taste receptor protein leads to altered taste preference due to increased/decreased taste sensitivity and thus also altered food intake
Explain lactose persistence
LCT gene encodes lactase enzyme in humans
Expression of LCT normally winds down after weaning
SNP in LCT gene has led to lactase persistence (LCT expression continues)
It is a change in temporal pattern of gene expression leading to increased use of nutrient
Why does gas and bloating occur without lactase persistence
More lactose passes into the colon undigested
E coli in the colon have b-galactosidase which allows lactase to be digested in the colon, producing gas and SCFAs
What is MCM6?
A gene located next to LCT (gene encodes lactase in humans) which encodes a protein for DNA replication
When some SNPs occur in MCM6, it is associated with lactase persistence
SNP does not have to be located on the gene itself to cause metabolic effect
NPC1L1 is
protein responsible for cholesterol absorption from intestinal lumen
SNPs which encode NPC1L1 change efficacy of protein absorption levels
Different variants of protein may have low protein expression (less protein available) but high efficiency
Responsiveness of genes to nutrient status example
Ex. TF activated in response to presence or absence of nutrients like blood glucose levels
Loss of sensitivity to nutrient cues can result in inappropriate metabolic responses to nutrient availability/deficiency
Bioactive roles of nutrients + examples
Components of cell structures - choline
Substrate of energy production - glucose
Cofactors and coordinators of enzyme activity - vitamin C in hydroxylation of collagen
Signaling molecules - Ca2+ in taste receptors
Regulators of gene expression and function - cholesterol regulates activity of SREBP (endogenous cholesterol/FA production)
Categories of issues with metabolism
Mono-genic diseases - inborn errors of metabolism
SNPs affecting rate limiting enzymes are most susceptible to cause disease
Multi-genic - acquired metabolic syndrome (severity depends on genetic combo individuality)
Involves manifestations of overnutrition
Benefits and disadvantages of the mouse model
Benefits: whole genome sequenced (with corresponding human genes mapped), many inbred varieties, easy to house and reproduce quickly
Disadvantages: genetic differences, metabolic differences and different nutrient requirements
Why engineered mouse breeds are used
Many purebred strains available to increase standardization between labs
Can be ethically genetically modified
Short development cycle
Transgenic vs knockout mice
Transgenic involves addition of new genes
Knockout involves creation of specific mutations
Helps to identify metabolic pathway involvement and regulation
Types of transgenics
Overexpression - many copies of gene integrated or different efficacy of gene introduced
Gain of function - new function gained
Knockout mice
Targeted gene disruption
(Repositories of mutated gene varieties available)
Embryo modified and re-implanted
How are phytosterols metabolized
The R group differs, but Phytosterols can bind NPC1L1 and compete for absorption with cholesterol
Phytosterols are not well absorbed and most are returned to the intestinal lumen for excretion (overall reduction in cholesterol absorption)
But phytosterol metabolites can be used to produce more cholesterol
Uses of cholesterol in the body
Substrate for vitamin D synthesis and steroid hormones
Substrate for the synthesis of bile acids
Control of membrane fluidity
Regulator of gene expression
