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--- geneonyxdec202011:start [2015/05/06 16:39] – magiero
+++ geneonyxdec202011:start [2015/05/06 18:46] (current) – magiero
@@ Line 26: / Line 26: @@
 • The genetic era now opens up the possibility to utilise a deeper understanding of genetics in a customised, i.e. person-specific, way.\\
 • A single-nucleotide polymorphism (SNP) found in the target //(i.e. molecule to be affected)// of an active ingredient //(i.e. the key molecule in the drug)// provides information on the quality of the expected response\\
-• //Use cross-validation of biological target// \\
+• //Use __CROSS-VALIDATION__ of biological target// \\
 • This method uses detection of SNP to estimate protein-protein interaction between an ingredient and its direct or indirect target.\\
 • **As previously discussed**, detecting SNPs to evaluate particular molecule efficacy in a biological pathway is known and is used in pharmacogenetics.\\
@@ Line 34: / Line 34: @@
 === - 1: Identification of ingredients and their biological targets ===
-•
+• The skin's health is based upon 6 health categories or “pillars”. Each ingredient relates to one or more of these categories.\\
+• Each ingredient is included in a product in order to take a specific biological pathway in the skin.\\
+• These pathways are: antioxidant pathways for detoxifying, xenobiotic pathways, anti-ageing pathways and skin lightening pathways.\\
+• The ingredient interacts with its biological target inducing a signalling cascade that is responsive of activation of this pathway, for example as shown in FIG. 2.\\
+• The genes have a proposed or established association with the listed ingredients and efficacy outcomes, but the genetic associations are not limited to the skin.
 === - 2: Identification and selection of a SNP in the ingredient's target ===
+{{ fig4.png?450}}
+• The ingredient's target corresponds to a protein related to a gene.\\
+• Once the gene is identified, the SNP list for this gene is obtained, for example through NCBI website.\\
+• Calculate SNP impact factor (SIF)\\
+• 5 questions are asked (1: SNP has poor effect on ingredient to 5: SNP has considerable effect on ingredient) to determine SIF.\\
+• A "functional" SNP is one with a SIF of 5 is chosen.\\
+^            ^         ^           ^ Target is a    ^        ^ Proven    ^ Disruptive ^ High freq.     ^ Total  ^
+^            ^         ^           ^ major molecule ^ Direct ^ effect of ^ effect for ^ in the pop-    ^ score  ^
+^ Ingredient ^ Target  ^ SNP ID    ^ in the pathway ^ target ^ the SNP   ^ ingredient ^ ulation >0.05  ^ of yes ^
+| Niacin     | HM74    | rs2454726 | yes            | yes    | yes       | yes        | yes            | 5      |
+| Collagen   | MMP-11  | rs1799750 | yes            | yes    | yes       | yes        | yes            | 5      |
+• SNPs are organized into level of interaction with metabolism pathway.\\
+  * 1st level: First protein to interact with ingredient (receptor or enzyme responsible for chemical interaction or ingredient modification).  Severe consequences on ingredient metabolism if target not functioning.
+  * 2nd level: Key molecule involved in metabolism (e.g. enzyme within metabolic pathway of ingredient).  Moderate consequence.
+  * 3rd level: Molecule involved in metabolism with minor consequences.
+• SNPs that are selected are typically well-represented within the whole population (e.g. greater than 5% frequency within the population).\\
+• However, in some circumstances SNPs may be selected that are very specific to one or more groups within the population (i.e. smaller populations)\\
+• SNPs may be selected that have either a beneficial influence on the metabolism of the ingredient (and therefore its efficacy), or conversely that may have a detrimental influence on the metabolism of the ingredient.
 === - 3: Design of specific primers to amplify the specific SNP associated to ingredients ===
+• One of the key aspects of this method is to design specific primers to target the right genotype.\\
+• To amplify DNA, several standard methods can be used such as polymerase chain reaction (PCR), SNAP, or LAPM assay.\\
+• All these techniques are based on the selection of accurate primers.\\
+• Primers were selected according to a number of criteria, including: primer length, the terminal nucleotide in the primer, reasonable GC content and Tm.\\
 === - 4: Matching ingredients to their target and the associated SNP ===
+• Each ingredient has the ability to be “metabolised” by a person. This ability is based upon the genetic makeup of this person. \\
+• **The metabolic pathways of many ingredients are identified and a list is created which details those ingredients that either become inactive due to the presence of a SNP, or a highly beneficial ingredient because the SNP creates a failing or fault that is corrected by this ingredient.**\\
+• __Once the ingredients have been matched to their target and the associated SNP__, this information can be entered into a table or database for future reference.\\
 === - 5: Correlation between ingredients and efficacy associated to SNP ===
+• It can now be determined if an ingredient is efficient or not when affected by a specific SNP(s) in its target (the aforementioned __CROSS-VALIDATION__?).\\
+• The final decision reflects the previously determined efficacy of the ingredient.\\
+• If the target is not functional the ingredient will not be recommended. (i.e. customer's SNP not receptive to ingredient)\\
+• In contrast, if the target is not affected by the SNP the ingredient will be recommended (i.e. just a "normal" SNP)\\
+• If the SNP provides again enhanced efficacy of an ingredient, the dosage of this ingredient might be considered before being recommended\\
+• taken into consideration is the genotype identified by the test. This will affect the correlation given on the efficacy of the test\\
 === - 6: Application: Selection of a group of SNPs associated with the composition of a cosmetic product and its outcome ===
@@ Line 52: / Line 95: @@
 • In this example the cAMP activate the PKA enzyme which releases its catalytic subunits to [[http://en.wikipedia.org/wiki/Phosphorylation | phosphorylate]] (i.e. turn on/off) specific target proteins. (How does PKA know what target to phosphorylate?)\\
 • In this case they activate [[http://en.wikipedia.org/wiki/Hormone-sensitive_lipase | HSL]] which promotes free fatty acid (FFA) secretion by adipocyte cells.\\
-• The presence of FFA in the skin may be very helpful as discussed [[http://www.nature.com/jid/journal/v29/n6/full/jid1957118a.html | here]] back in 1957.\\
+• The presence of FFA in the skin may be very helpful as discussed [[http://www.nature.com/jid/journal/v29/n6/full/jid1957118a.html | here]] back in 1957. (Are we ultimately talking about stimulated collagen production here?)\\
 • This is a complicated process, but as far as the patent is concerned the key step is to look at potential mutations in the DNA coding for the receptor protein.\\
-• In particular genes HM74 (protein GPR109B) and HM74A (GPR109A) code for these proteins with the HM74A apparently coding for a [[http://www.ncbi.nlm.nih.gov/pubmed/15580557 | better receptor]].
+• In particular genes HM74 (protein GPR109B) and HM74A (GPR109A) code for these proteins with the HM74A apparently coding for a [[http://www.ncbi.nlm.nih.gov/pubmed/15580557 | better receptor]].\\
-• If you identify which of these genes is present (or perhaps even some variation on these genes) you can better predict which customer will better metabolize niacin.\\
+• If you identify which of these genes is present (or perhaps even some variation on these genes) you can better predict which customer will better benefit from the metabolic effects of niacin.\\
 ==== - Example 2 ====