• Utopia: Pansophia, sequential outcome analysis

    PANSOPHIA – sequential outcome analysis

    The genomic DNA analysis software Opus 23 includes the Utopia suite of apps for analyzing sequential uBiome data, comparing sequencing-based clinical microbiome data with the client’s own genomic DNA.

    Utopia logo

    PANSOPHIA is an Utopia app that gives you the power to sort your client’s data based upon associations with health and disease as well as several other useful categories including keystone, probiotic, core species and butyrate production.  For those clients who have more than one data sample, PANSOPHIA allows you to visualize treatment progress in a graphical format that can be easily added to your client’s report.

    Navigating PANSOPHIA

    pansophia

    From the Utopia drop down menu, hover over ‘analytics’ until a second list appears, then select PANSOPHIA. You will then be presented with the default table which shows ‘everything’ and is sorted by ‘rank’ or ‘percent’.

    At the bottom of the window is a jump screen that allows you to move from one screen to the next. You can control how many rows to display be selecting an option from the ‘Show’ pull down menu. The default is 15.

    Pansophia initial screen

    Filtering and sorting results

    PANSOPHIA allows you to parse the taxon data based upon desired treatment goals. Taxa are sortable by benefit as well as pathogenic potential.  There are two ways to filter the data.

    Using category tabs:

    You can use the category tabs at the top of app’s main screen to select taxa grouped by their associations with health and disease. Once a category is selected, the information will be displayed in graph form.

    Pansophia screenshot

    The PANSOPHIA graph uses the following symbols:

    • An orange dot  denotes average %, the bar graphic represents the client data- specific %
    • For those with multiple data sets, a blue diamond denotes % change

    Click on any desired taxon to open up its information pop—up window for detailed information including taxonomy, an overview of known disease or health benefit associations, interactions and metabolomics. Click ‘add/ curate’ to include it in your clients report. Additionally, the graph itself can be printed or added to your client’s report.

    Using individual taxon selections:

    From the main screen, you can sort the taxa by ‘name’ or ‘client %’ then select desired taxa individually using the display box selections on the left hand side of the screen.  Once you have made your selections, click the orange ‘display selections’ button at the top of the screen. The individual taxon information will be displayed in graph form. Click ‘add/curate’ to include the graph in your client’s report.

       

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  • Utopia Demonstration Video

    Dr. Peter D’Adamo and Dr. Tara Nayak present an introduction to Utopia, the free microbiome analysis add-on module to Opus 23 for uBiome test results.

     

    To use Utopia, you will need to  have your client’s 23andMe data already uploaded to Opus 23. You can then upload as many raw data files from uBiome tests as you have for that client. Utopia will work with individual uBiome tests, referencing the client’s 23andMe results where appropriate, and also give sequential analysis for multiple uBiome tests.

    The unique combination of Opus 23 and Utopia make this an opportunity for practitioners to get deep insight into their clients on both a genomic and a microbiological level, all sourced from published medical literature. The interaction between the two genomic analyses provides unparalleled informatics tools, and gives the practitioner an edge over any other genomic analysis tool available today.

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  • Utopia: Spectrum, visual community organization

    SPECTRUM: Visual community organization

    Utopia logo

    SPECTRUM provides a visual representation of the taxonomic data at both the genus and phylum levels. The app demonstrates the weight, influence and diversity of your client’s microbiome in two helpful display formats, each of which are clickable for a deeper look and easy report curation.

    Navigating  SPECTRUM

    Spectrum logo

    From the Utopia drop down menu, hover over ‘analytics’ until a second list appears, then select SPECTRUM.  Phyla and genus are displayed in pie chart format, which is accompanied by the spectrum profiler found below.

    The pie charts follow the color-coding conventions found in OPUS23 indicating beneficial, neutral as well as pathogenic organisms. Click on any desired section to open up its information pop—up window for detailed information including taxonomy, an overview of known disease or health benefit associations, descendants and metabolomics. Click ‘add/ curate’ to include it in your client’s report.

    Spectrum pie charts

    The spectrum profiler demonstrates the trends in your client’s biome diversity in a graphical format. Clicking on any of the category headings will open a pop-up window listing the organisms found in your client’s sample. Each genus listed is also clickable, opening a pop-up window for detailed information, including taxonomy, an overview of known disease or health benefit associations, descendants and metabolomics. Click ‘add/ curate’ to include it in your client’s report.

    Screenshot of Spectrum Profiler

    Metabolomics is a powerful addition to the spectrum profiler that provides a comprehensive list of metabolites associated with GI biome species. A list of all metabolites active in your client is included. Click on an individual metabolite for detailed information, including genera that are enhanced, inhibited, and those which generate the metabolite as an end product. Click on the Metabolomics link to open a pop-up with all active and inactive genera.

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  • Utopia: Loam, a fertile soil

    Announcing the launch of Utopia, the suite of apps within Opus 23 that analyzes and reports on sequential data from uBiome tests. uBiome is the world’s first sequencing-based clinical microbiome screening test, giving the user insight into the bacterial population of multiple body areas. Utopia recognizes all bacteria found by uBiome, but is specifically interested in the gut bacteria and its interaction with the client’s own genomic DNA. Utopia is free for existing clients: Once you have uploaded 23andMe raw data for your client, you can add as many uBiome tests as you want for that client without additional charge. Utopia will then give you access to multiple apps to analyze the data and reference it to the client’s genomic data where appropriate.

    Utopia logo

    LOAM: Adaptable taxon data

    LOAM is a highly flexible search and sort tool that allows you to easily navigate through your client’s Ubiome results by taxon. LOAM allows you to filter taxonomic data based upon several useful parameters as well as sort the filtered results. It is similar to the ARGONAUT app in Opus 23.

    loam

    Navigating LOAM

    From the Utopia drop down menu, hover over ‘analytics’ until a second list appears, then select LOAM. You will then be presented with the default table which shows ‘everything’ and is sorted by ‘repute’ or ‘interpretation’.

    At the bottom of the window is a jump screen that allows you to move from one screen to the next. You can control how many rows to display be selecting an option from the ‘Show’ pull down menu. The default is 15.

    Loam Screenshot

    Filtering and sorting results

    LOAM allows you to parse the taxon data based upon desired treatment goals. Taxons are sortable by benefit as well as pathogenic potential.

    The LOAM table displays the following data by column:

    • Taxon name
    • Repute, displaying beneficial !, neutral ! and pathogenic ! 
    • Rank
    • Client-specific % population
    • Average % (if available)
    • Standard deviation (if available)
    • Interpretation (displayed up to +6 times the standard deviation, populations found in a greater abundance are indicated by )
    • Normal variance
    • Order magnitude

    Click on any desired taxon to open up its information pop—up window for detailed information including taxonomy, an overview of known disease or health benefit associations, interactions and metabolomics. Click ‘add/ curate’ to include it in your clients report. The Curated column will then show a green checkmark against all curated taxon after refreshing the page. 

    LOAM columns are sortable. Click on any column title to sort by that column. Click that column again to reverse the sort order.

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  • Cell Danger Response

    Cell Danger Response: Oxidative Shielding or Oxidative Stress?

    Mitochondrial Master Controller of metabolism and gene expression

    My interest in studying the mitochondrion was ignited by a course I completed 3 years ago.[13] As a naturopathic physician and researcher in generative medicine and amateur cosmologist, my explorations in electric universe cosmology have taken me to a deeper appreciation of the electricity of life and its role in methylation and detoxification. Fascinated by the body’s stress and repair response, I wondered about the cytochromes and enzymes of the electron transport chain. Since reviewing the literature on mechanisms of the cell danger response I woke this morning to a new revelation.

    The cell danger response is an ancient innate, immune survival mechanism for sensing the destructivity by exogenous and endogenous stressors from microbial, heavy metal, toxic chemicals, ionising radiation, physical heat and pH shock, and psychological traumas. Redox activity mitochondrial outer membrane (MOMP) activity are at the heart of switching between progenitor  mechanisms, protein synthesis and mitosis and housekeeping cellular functions like autophagy and cell differentiation.[1,9]

    The mitochondrial membrane not only acts a a conveyer of accelerated electrons through the electron transport chain to produce ATP.  This double layered lipid membrane laced with specialised cytochrome proteins with the outer layer, MOMP, serving as a membrane potential platforming cell signalling post translational regulation. Pattern recognition receptors respond to proteins released from cellular or mitochondrial damage and pro-inflammatory cytokines by segmentally reducing the electrical potential.  Specific regions of the  inner membrane responds to corresponding reduction in MOMP and hydrolyzes cardiolipin, a major lipid component involved in mitochondrial fission. Mitochondrial membrane fission is a process that is used to segment and remove damaged fragments of the membrane and dispersing mitochondrial in the cytosol during ATP synthesis.[12]

    MOMP responds to oxygen levels and sulfide oxidation, fluctuating NADH and NADPH redox reactions in order to govern its own folate metabolism and redox as well as influencing cytosolic conditions to initiate nuclear DNA methylation. By altering the NADH/NAD+ and NADPH/NADP ratios mitochondria direct the alternation of cell differentiation activities of DNA methylation and cell cycle arrest to the undifferentiating, demethylating cell cycle activation and the initiation of nucleotide synthesis.[3]

    Changes in proton and electron flux along the membrane generate NADH and NAD+. NADPH and NAD+ concentrations are used for two opposing functions:

    1. the methylation process and cell-differentiating high oxygen states produced in the cytosol during Gº , i.e cell cycle arrest, involving nuclear and mtDNA interactions favoring intra-mitochondrial 10-formyl THF production;
    2. ion-dependent nucleotide formation for its own repair in G1 and S phases.[3]

    Here is a schematic demonstrating the intricacies of mitochondrial interaction with the cytosol involving the glycine-serine shuttle to orchestrate synthesis and repair utilizing oxidative states, with NADH/NAD+ control:

    Mitochondrial control

    The resulting shifts in oxidation-reduction potential triggers the switch in organelle fission which occurs, in the vegetative state, to fusion morphology involved in Gº to S phases in the cell cycle and during oxidative stress. The cytokine-reactive-oxygen-species-response drives innate immunity[1,12].  The intensity of generation of ROS in the intermediate membrane space initiates cytochrome c release followed by upregulating Bcl2 to increase release of caspase-3 and caspase-9 into the cytoplasm. Caspase is the master executioner induces apoptotic autophagy (noted by accumulation of vacuoles, ATP depletion, chromatin condensation, fragmentation and internucleosomal DNA cleavage, fragmentation of the plasma membrane,6) using caspase-3, 8 and 9 for cell death (swelling of organelles including mitochondrion itself and cell membrane rupture) and using caspase-8 and cardiolipin for removing collateral damage by toxins and microbes.[3,12,13]

    Redox reactions are are governed by changes in pH and temperature but the notation is confusing and difficult to track the reduction and oxidation reactions. Reduction is the gain of electrons or a decrease in oxidation state by a molecule, atom, or ion and designated by subtraction of a plus charge. Oxidation is the opposite. It is important to know this because molecular redox agents work strategically within the methionine, folic acid, and urea cycles and the transsulfation, sulfonation and detoxification pathways as well as the cell cycle, and protein synthesis.

    Examples:ROS

    • Redox couples for biopterin heme activation are NADPH/NADP+; 
    • Feedback inhibition of GCLM/GCLC by reduced glutathione;
    • Protein synthesis regulation of GSH/GSSG by SAMe;
    • Cell membrane protection via the sulfide route to oxidize microbial metabolites with H2S+/SH-, and its regulatory function of the electron transport chain with two other gasotransmitters, N2O-/NO- and CO2-/CO-.

    Solubility and cell water structuring influencing protein conformational changes and its activity with SAMe in cystathionine beta synthase.

    The gasosensor, heme protein between the C-regulatory terminal and the N-catalytic terminal is present in the Fe2+/Fe3+ functions to reduce or deactivate CBS enzyme in the presence of CO or NO. Fe2+ displaces the cysteine on the cysteine ligand on the catalytic arm of CBS when it binds with CO (to form Fe-CO) leading to a 40 – 90 % CBS inhibition with no disruption of PLP binding.[2]

    GSH oxidation and reduction is a key mechanism in DNA synthesis.  Glutathione levels relate to maintenance of reduced glutaredoxin or thioredoxin, which are required for the activity of ribonucleotide reductase, the rate-limiting enzyme in DNA synthesis. [6] The ratio of reduced glutathione to oxidized glutathione within cells is often used as a measure of cellular oxidative stress.[6]

    Strategic generation of oxidants and antioxidants govern non-enzymatic redox activation of SAM-SAH, BH2-BH4, GSH-GSSG, NOS-NO.

    Examples:

    • Oxidized glutathione (GSSG) inhibits SAH hydroxylation reducing homocysteine formation.  High SAH inhibits SAM and DNMT resulting in reduced CpG island methylation3 and by reducing SAH hydroxylation activity more purine and pyrimidine synthesis in G1 phase for DNA-T synthesis can occur; [6,18]
    • Increased GSH, essential for cell cycle progression: GSH levels increase when cells shift from G0 to G1 phase of the cell cycle, modulating the cell cycle; In liver cancer and metastatic melanoma cells, GSH status also correlated with growth [6];
    • Reduced glutathone (GSH) inhibits SAH suppression of methylation by SAM needed for CpG and folate methylation. [18,19]
    • GSH/GSSG controls glutamate cysteine lygase activity and GCLC up regulation. [7]
    • H2S+/SH- regulates cystathionine gamma-lyase and cystathionine beta synthase migration to mitochondrion and CBS and CTH activity during oxidative stress. [4,5]

    The nature of metabolic networks is that they are dynamically interactive within the opened-system dynamics of life.  Enzyme kinetics run the elaborate interplay of methylation, transsulfuration, sulfonation, sumoylation and glucuronidation involved in the metabolic networks, but the oxidation and reduction-producing activity, exchanging protons and electrons, are responsible for these organised processes.

    During housekeeping functions, cells manage noxious stimuli by ramping up free radical oxygen species and hydrogen sulfide in response to microbial antigens. The reciprocal redox relationship  concentrates the oxidizing effect which halts free radical clean up by suppression of CYP and Glutathione formation.3 At the same time ROS inhibit any toxin-inducing DNA damage by shutting down the cell cycle, until detoxification and elimination can resume. If this is an acute and limited response, microbial debris and free radical heavy metals are neutralised and  eliminated via detoxification pathways and transporters in a negative feedback loop. [4]

    Prolonged oxidative states are not well tolerated by cell membranes and succumb to lipid peroxidation resulting in impaired neurological development and neurotransmitters. The chronicity of cellular damage eventually involves more DNA and electron transport chain damage than can be repaired. Eventually mitochondrial turnover is impaired resulting in age-related chronic diseases.[10]

    Minor nucleotide variation in genetic code altering gene expression have made for successful survival debuts when they were adaptive to the varying environmental conditions like starvation and pestilence, most often reducing enzyme efficiency. The popular SNPs come to mind in FTO, MAO, COMT, SHMT2, MTHFR, MTR, MTRR, BHMT, AHCY, NOS1,2,3, (nNOS, iNOS eNOS) GAD1, CBS and its subunits, CAT, CSAD, CDO, GSS, GSR, GST, SUOX, SULT1,2,3 MAT1A, DNMT3, PNMT, that have been established to be associated with modern life disorders. Some not so common ones related with sulfur dysfunction are SLC13A1 the sulfate transporter and SLC3A1, the sulfate/oxalate transporter.

    Enzymes are generally substrate dependent some with very low Km values requiring low concentrations and some with high Km values like CBS to modulate complete degradation of homocysteine. However, enzyme function is regulated by protein and vitamin or mineral binding in different ways.

    Enzyme activation is the product of an allosteric protein binding to its regulatory and a cofactor or coenzyme.

    Examples:

    • Cysteine is utilized for multiple cellular functions including the synthesis of the large reservoir of the antioxidant, glutathione. In fact, cysteine is the limiting reagent in the biosynthesis of glutathione and its synthesis and utilization are tightly regulated.[2]
    • SAMe activating regulatory C-terminal or serine binding to CBS inducing the rate-limiting aminoacrylate of cystathionine for activation by the substrate homocysteine.[2]

    A non-enzymatic metal ions or organic coenzymes, derivatives of vitamins, soluble in water by phosphorylation, activates the catalytic domain, (and pyridoxal 5’ pyrophosphate activating the catalytic terminal of CBS).[2]

    Main methylation schematic

    Examples:

    • Key determinants of GSH synthesis are the availability of the sulfur amino acid precursor, cysteine, a product of CBS, and the activity of the rate-limiting enzyme, glutamate cysteine ligase (GCL), which is composed of a catalytic (GCLC) and a modifier (GCLM) subunit. The second enzyme of GSH synthesis is GSH synthetase (GS). GSH levels down regulate GCLC by feedback inhibition.[5]
    • CBS, under extreme conditions and CTH, under physiological conditions migrate to mitochondria and shift the formation of H2S to SH- to cytokines of acute inflammation, e.g. TNF-a.[15]
    • MOMP sensors will reduce H2S if mtDNA damage is isolated.[1,12]
    • High H2S will induce CAT and MPST 16 to form thiosulfate a potent antioxidant and Ca+ chelator, sparing Ca+ use to preserve MOMP; it is also an electron donor to sustain the electron transport chain.[17]

    COX DAMAGE

    What also modulates H2S formation is high concentrations of H2S itself, will down regulate GCLC, (but not CBS), and also down regulate inducible nitric oxide synthase NOS, and cyclooxyrgenase COX,[14].

    Dysregulation of GSH synthesis by polymorphisms of GCLC and GCLM is increasingly being recognized as contributing to the pathogenesis of many pathological conditions. These include diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells. Manipulation of the GSH synthetic capacity is an important target in the treatment of many of these disorders.[7]

    Redox & Sulfur metabolism schematic

    Small protein molecules, vitamins and minerals have therapeutic implications. Considering the role of oxidation conserving ATP demand for protection and attack and oxidative shielding cell generation to noxious substances, it is wise to know when, where and how much to intervene with vitamins, minerals and antioxidants.

    References:

    1: Scott I, Youle RJ. Mitochondrial fission and fusion. Essays Biochem.2010;47:85-98. doi: 10.1042/bse0470085. Review. PubMed PMID: 20533902; PubMed Central PMCID: PMC4762097.

    2. Banerjee R, Zou CG. Redox regulation and reaction mechanism of human cystathionine-beta-synthase: a PLP-dependent hemesensor protein. Arch Biochem Biophys. 2005 Jan 1;433(1):144-56. Review. PubMed PMID: 15581573.

    3. Naviaux RK. Mitochondrial control of epigenetics. Cancer Biol Ther. 2008 Aug;7(8):1191-3. Epub 2008 Aug 4. PubMed PMID: 18719362.

    4. Li L, Moore PK. Putative biological roles of hydrogen sulfide in health and disease: a breath of not so fresh air? Trends Pharmacol Sci. 2008 Feb;29(2):84-90. doi: 10.1016/j.tips.2007.11.003. Epub 2008 Jan 3. Review. PubMed PMID: 18180046.

    5. Dugbartey GJ, Bouma HR, Lobb I, Sener A. Hydrogen sulfide: A novel nephroprotectant against cisplatin-induced renal toxicity. Nitric Oxide. 2016 Jul 1;57:15-20. doi: 10.1016/j.niox.2016.04.005. Epub 2016 Apr 16. Review. PubMed PMID: 27095538.

    6. Lu SC. Glutathione synthesis. Biochim Biophys Acta. 2013 May;1830(5):3143-53. doi: 10.1016/j.bbagen.2012.09.008. Epub 2012 Sep 17. Review. PubMed PMID: 22995213; PubMed Central PMCID: PMC3549305.

    7. Lu SC. Regulation of glutathione synthesis. Mol Aspects Med. 2009 Feb-Apr;30(1-2):42-59. doi: 10.1016/j.mam.2008.05.005. Epub 2008 Jun 14. Review. PubMed PMID: 18601945; PubMed Central PMCID: PMC2704241.

    8. Naviaux RK. Oxidative shielding or oxidative stress? J Pharmacol Exp Ther. 2012 Sep;342(3):608-18. doi: 10.1124/jpet.112.192120. Epub 2012 Jun 13. Review. PubMed PMID: 22700427.

    9. Naviaux RK. Metabolic features of the cell danger response. Mitochondrion. 2014 May;16:7-17. doi: 10.1016/j.mito.2013.08.006. Epub 2013 Aug 24. Review. PubMed PMID: 23981537.

    10. de Grey AD. A proposed refinement of the mitochondrial free radical theory of aging. Bioessays. 1997 Feb;19(2):161-6. Review. PubMed PMID: 9046246.

    11. Shimizu T, Huang D, Yan F, Stranava M, Bartosova M, Fojtíková V, Martínková M. Gaseous O2, NO, and CO in signal transduction: structure and function relationships of heme-based gas sensors and heme-redox sensors. Chem Rev. 2015 Jul 8;115(13):6491-533. doi: 10.1021/acs.chemrev.5b00018. Epub 2015 May 29. Review. PubMed PMID: 26021768.

    12. Tait SW, Green DR. Mitochondria and cell signalling. J Cell Sci. 2012 Feb 15;125(Pt 4):807-15. doi: 10.1242/jcs.099234. Review. PubMed PMID: 22448037; PubMed Central PMCID: PMC3311926.

    13. Anderson P. “Genomics” Webinar. Key Compounding Series. 2013

    14. Ahangarpour A, Abdollahzade Fard A, Gharibnaseri MK, Jalali T, Rashidi I. Hydrogen sulfide ameliorates the kidney dysfunction and damage in cisplatin-induced nephrotoxicity in rat. Vet Res Forum. 2014 Spring;5(2):121-7. PubMed PMID: 25568705; PubMed Central PMCID: PMC4279637.

    15. Hüttemann M, Helling S, Sanderson TH, Sinkler C, Samavati L, Mahapatra G, Varughese A, Lu G, Liu J, Ramzan R, Vogt S, Grossman LI, Doan JW, Marcus K, Lee I. Regulation of mitochondrial respiration and apoptosis through cell signaling: cytochrome c oxidase and cytochrome c in ischemia/reperfusion injury and inflammation. Biochim Biophys Acta. 2012 Apr;1817(4):598-609. doi:10.1016/j.bbabio.2011.07.001. Epub 2011 Jul 13. Review. PubMed PMID: 21771582; PubMed Central PMCID: PMC3229836.

    16. Furne J, Springfield J, Koenig T, DeMaster E, Levitt MD. Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues: a specialized function of the colonic mucosa. Biochem Pharmacol. 2001 Jul 15;62(2):255-9. PubMed PMID: 11389886.

    17. Subhash N, Sriram R, Kurian GA. Sodium thiosulfate protects brain in rat model of adenine induced vascular calcification. Neurochem Int. 2015 Nov;90:193-203. doi: 10.1016/j.neuint.2015.09.004. Epub 2015 Sep 9. PubMed PMID: 26363090.

    18. Reed MC, Thomas RL, Pavisic J, James SJ, Ulrich CM, Nijhout HF. A mathematical model of glutathione metabolism. Theor Biol Med Model. 2008 Apr 28;5:8. doi: 10.1186/1742-4682-5-8. PubMed PMID: 18442411; PubMed Central PMCID: PMC2391141.

    19. Tisman G, Garcia A. Control of prostate cancer associated with withdrawal of a supplement containing folic acid, L methyltetrahydrofolate and vitamin B12: a case report. J Med Case Rep. 2011 Aug 25;5:413. doi: 10.1186/1752-1947-5-413. PubMed PMID: 21867542; PubMed Central PMCID: PMC3199279.

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  • Protection against risk of Parkinson’s disease

    Parkinson’s disease was described in 1817 by Dr James Parkinson, who published an essay reporting six cases of ‘paralysis agitans’ (the disorder that was later renamed after Parkinson). He described the characteristic resting tremor, abnormal posture and gait, paralysis and diminished muscle strength, and the way that the disease progresses over time. [1]

    Since the advent of genetic testing several genes have been found to be associated with Parkinson’s disease (PD), resulting in various classifications. Autosomal dominant Parkinson disease type 8 (PARK8) is caused by heterozygous mutation in LRRK2, the gene encoding the dardarin protein. [2] The G2019S variant is one of the most common genetic causes of PD. Although the clinical motor signs of PD in carriers of the G2019S mutation are largely typical, an earlier age at onset of motor symptoms has been reported in some studies. [3]

    The word dardarin was taken from a Basque word for tremor, as the gene was first identified in families from England and the north of Spain. Mutations in LRRK2 are the most common known cause of familial and sporadic PD, accounting for approximately 5% of individuals with a family history of the disease and 3% of sporadic cases. They account for up to 10% of autosomal dominant familial and 3.6% of sporadic PD. More than 40 different variants, almost all missense, have been found. Seven seem to be proven pathogenic mutations, and are clustered in functionally important regions which are highly conserved through evolution. [4]

    23andMe carried out a privately-funded genome-wide association study (GWAS) to search for novel genetic variants associated with PD. The results, which were published in PLOS in 2011, replicated existing associations and discovered two novel variants. [5] In addition, 23andMe researched genes conferring protection on those with high-risk genes. [6] They found that of the approximately 1 in 10,000 people who have the G2019S  variant, those who also had a mutation in SGK1 were found to have a lower risk of PD than those with just the G2019S variant, conferring protection against the increased risk of PD. [7]

    Other causes of, or factors contributing to PD include pesticide exposure, [8] head trauma, medication, prolonged oxidative stress from infection or high homocysteine. Genetic factors include increased function of MAOB enzymes, high histamine from HNMT mutations, elevated L-dopa from DDC mutations or B6 deficiency. The Opus 23 software contains algorithms for Parkinson’s disease associated with some of these genetic causes, risk or contributory factors found in the 23andMe raw data. A new algorithm added to the Opus 23 Lumen app looks for both the LRRK2 G2019S and the SGK1 variants to assess for both risk of PD and protection from the risk genotype, and lists natural agents associated with gene function.

    References:

    1. Parkinson J. An essay on the shaking palsy. London: Sherwood, Neely and Jones; 1817.
    2. Kachergus J, Mata IF, Hulihan M, et. al. Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder  across European populations. Am J Hum Genet. 2005 Apr;76(4):672-80. Epub 2005 Feb 22. PMCID: PMC1199304.
    3. Thaler A, Mirelman A, Gurevich T,  et. al. Lower cognitive performance in healthy G2019S LRRK2 mutation carriers. Neurology. 2012 Sep 4;79(10):1027-32. PMCID: PMC3430708.
    4. Davie CA (2008). “A review of Parkinson’s disease”. Br. Med. Bull. 86 (1): 109–27. PMID 18398010
    5. Do CB, Tung JY, Dorfman E, et. al. Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson’s disease. PLoS Genet. 2011 Jun;7(6):e1002141. PMCID: PMC3121750
    6. 23andMe Blog: 23andMe Discovers Genetic Variant That May Protect Those at High Risk for Parkinson’s Disease. Accessed Aug 28, 2016.
    7. Polymorphisms associated with Parkinson’s disease. Patent US8187811 B2.
    8. Van Maele-Fabry G, Hoet P, Vilain F, Lison D. Occupational exposure to pesticides and Parkinson’s disease: a systematic review and meta-analysis of cohort studies. Environ Int. October 2012, 46: 30–43. PMID: 22698719.

     

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  • Kava-kava for panic attacks

    A 2008 paper by Thoeringer et. al., published in the Journal of Neural Transmission [1] described a study of 238 adult Caucasian patients recruited from an Anxiety Disorders Outpatient Clinic in Europe presenting various anxiety disorders, including panic disorder, agoraphobia, social phobia and generalized anxiety disorder. As there are many genetic studies linking the GABA system to anxiety disorders and related personality traits, the patients were genotyped for various polymorphisms in the SLC6A1 (GABA transporter 1), along with 267 controls without anxiety disorder.

    Five polymorphisms in SLC6A1 or in the promoter region were found to be nominally associated with anxiety disorders. Although none were statistically significant alone, the authors found a significant combined effect of all investigated polymorphisms, which strongly suggested a major role of SLC6A1 in the genetic susceptibility of pathological anxiety. Looking at patients with panic disorder, those with the most severe panic disorder were significantly more likely than controls to have two related polymorphisms in the SLC6A1.

    GABA (gamma-aminobutyric acid) is a neurotransmitter that decreases activity in the neurons of the brain and inhibits the excitability of nerve cells. Drugs that block the GABA transporter molecule inhibit the removal of GABA from the nerve synapses, thereby prolonging the action of GABA. Tiagabine, a selective GABA transporter 1 blocker, is used as an antiepileptic, but has off-label use for anxiety disorder. This is thought to be due to the augmentation of GABA function as a neurotransmitter in the brain. This drug has side-effects, however, and other methods of reducing panic disorder have been investigated.

    Kava-kava (Piper methysticum) is a traditional plant-based medicine found in the Western Pacific region which has been shown to reduce anxiety. Kava-kava is legal in most countries, and is generally safe when the root from a ‘noble’ cultivar is used. A study of kava-kava for anxiety reduction using the Hamilton Anxiety Rating Scale (HAMA) as the primary outcome found that patients with generalized anxiety disorder who had polymorphisms in SLC6A1 and in the 5′ flanking region potentially responded to kava-kava supplementation with a more significant reduction in HAMA rating than in patients without the polymorphisms. [2] Treatment consisted of tablets standardized to contain 60 mg of  kavalactones per tablet for a total daily dose of 120 mg of kavalactones for the first 3-week controlled phase, being titrated to 240 mg of kavalactones in nonresponse at the 3-week mark for the second 3-week controlled phase, or placebo.

    An algorithm in the Lumen app in Opus 23 determines how many relevant SNPs a client has in SLC6A1 that are reported in their 23andMe raw data, and which may make treatment with kava-kava more effective in reducing anxiety disorder and panic symptoms.

    References:

    1. Thoeringer, C.K., Ripke, S., Unschuld, P.G. et al. The GABA transporter 1 (SLC6A1): a novel candidate gene for anxiety disorders. J Neural Transm (2009) 116: 649. doi:10.1007/s00702-008-0075-y. PMCID: PMC2694916
    2. Sarris J, Stough C, Bousman CA, et.al. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 2013 Oct;33(5):643-8. doi: 10.1097/JCP.0b013e318291be67. PMID: 23635869
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  • Genetic factors in depression, neuroticism and well-being

    Raining DNA

    Depressive and neurotic behaviours have many potential triggers and contributory factors, but few associated genetic variants have been found, most likely due to the large numbers of subjects needed: Genome-Wide Association Studies (GWAS) require large sample sizes to have sufficient statistical power, which is often achieved by aggregating results in multiple cohorts in a meta-analysis. A paper to be published in Nature Genetics in June 2016 [1] reports on the results of combining several large conducted on three phenotypes:

    • subjective well-being (n = 298,420)
    • depressive symptoms (n = 161,460)
    • neuroticism (n = 170,911).

    Using a meta-analysis on publicly available results from a study performed by the Psychiatric Genomics Consortium together with new results from analyses of the initial release of UK Biobank (UKB) data and the Resource for Genetic Epidemiology Research on Aging cohort, two variants were found to be associated with depressive symptoms. In the UKB cohort  the researchers measured depressive symptoms by combining responses to two questions asked of 23andMe customers with European ancestry. The questionnaire asked about the frequency in the past 2 weeks with which the respondent experienced feelings of low levels of enthusiasm or disinterest, and feelings of depression or hopelessness. The other cohorts included case-control data on major depressive disorder.

    According to Eysenck and Eysenck, [2] neurotic people become easily nervous or upset due to a lowered activation threshold in the sympathetic nervous system, and experience emotional instability in the form of fight-or-flight symptoms resulting from apparently minor stressors. Using twin studies, Eysenck concluded that, “the factor of neuroticism is not a statistical artefact, but constitutes a biological unit which is inherited as a whole….neurotic predisposition is to a large extent hereditarily determined.” [3]

    To analyse this potential genetic association with neuroticism (n = 170,911), the research combined statistics from a published study by the Genetics of Personality Consortium (GPC) with results from a new analysis of UKB data. Eleven variants were found to be associated with neuroticism. The GPC data harmonised different neuroticism batteries, and in the UKB cohort the measure was the respondent’s score on a 12-item version of the Eysenck Personality Inventory Neuroticism.

    This was also the first study to find SNPS that have a significant association with subjective well-being, of which the researchers identified three relevant variants. Questionnaires measured both positive affect (a state of pleasant arousal enthusiasm) and life satisfaction, even though these are different concepts of well-being.

    The SNPs in this study were found mainly in loci regulating expression in tissues of the central nervous system, adrenals or pancreas, including CSE1L , DCC , HNRNPA1P1, KSR2, MTCH2 NMUR2  PAFAH1B1 and RAPGEF6. Previous studies had found a relevant variant in MAGI1, accounting for approximately 15% of the variability in neuroticism, [4] as well as SNPs in TMPRSS9 and GRIN2B. [5]

    23andMe typically reports on up to six of the SNPs in this study related to neuroticism and two related to depression. Two algorithms in the Opus 23 Pro [6] Lumen app can determine the relevant genotypes for these phenotypes from SNPs available in 23andMe raw data.

    References:

    1. Okbay A, Baselmans BM, De Neve JE, et. al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat Genet. 2016 Jun;48(6):624-33. doi:10.1038/ng.3552. PMID: 27089181.
    2. Eysenck, H. J. & Eysenck, S. B. G. (1969). Personality Structure and Measurement. London: Routledge.
    3. The Journal of Mental Health, July 1951, Vol. XCVII, “The Inheritance of Neuroticism: An Experimental Study”, H. J. Eysenck and D. B. Prell, p. 402.
    4. Genetics of Personality Consortium, de Moor MH, van den Berg SM, et. al. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder. JAMA Psychiatry. 2015 Jul;72(7):642-50. doi:10.1001/jamapsychiatry.2015.0554. [PMID: 25993607].
    5. Aragam N, Wang KS, Anderson JL, Liu X. TMPRSS9 and GRIN2B are associated with neuroticism: a genome-wide association study in a European sample. J Mol Neurosci. 2013 Jun;50(2):250-6. doi: 10.1007/s12031-012-9931-1. [PMID: 23229837].
    6. Opus 23 Pro software by Dr Peter D’Adamo.
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  • Lewis negative and secretor status

    Fucus vesiculosis
    Fucus vesiculosis, by Emőke Dénes CC BY-SA 2.5 via Wikimedia Commons

    Many people are aware of the concept that their blood group influences their interaction with the environment: intestinal secretions of blood group antigens affect a person’s interaction with foods through being a marker of self recognised by the immune system. Similar to the way that a transfusion of blood from the wrong blood group causes a powerful IgM immune reaction, food lectins can also lead to a reaction (albeit less immunologically strong) by stimulating release of IL4 and IL13 from basophils, potentially leading to type I allergy. [1] Depending on diet, this could result from lectins incompatible with specific blood group glycoproteins, which would create an immune response individual to the person’s blood group: lectins from some foods are used to preferentially agglutinate specific glycoprotein antigens when testing saliva. [2]

    Secretor status is under genetic control: 15-20% of people of Western European descent are unable to secrete their blood group antigens due to a homozygous mutation on the fucosyltransferase 2 (FUT2) gene at the rs601338 SNP. The FUT2 (secretor) gene is expressed predominantly in secretory tissues, giving rise to glycoprotein products in mucin secretions. [3] This mutation is rare in Chinese and Japanese populations, and instead the more common homozygous FUT2 rs1047781 missense mutation is responsible for dramatically decreased expression of ABH antigens (partial ABH secretors). [4]

    Non-secretor status is associated with immunity to norovirus, [5] higher vitamin B12 levels, [PMID: 18776911] and secretor status also affects phagocytic activity of the leukocytes in a manner that places non-secretors at an advantage from increased activity, [6] in addition to the influence of the ABO blood group on phagocytosis. [7] Many disease risks are also associated with non-secretor status: antigen barrier function favours secretors, the free ABH antigen on the mucosal barriers of ABH secretors acts as an effective anti-adhesive mechanism against ABH specific bacterial fimbriae lectins. [8] Non-secretors may have an increased risk for Crohn’s disease, [9] type 1 diabetes, [10] and vaginal candidiasis. [11]

    One way to determine whether a person is a secretor of their blood group is to test their saliva for their ABO blood group antigens. This method is not commonly available, as a supply of red blood cells is needed for testing the saliva. Another way to find secretor status is to test for Lewis blood group. The Lewis a (Le a) antigen is normally secreted into the blood and then adsorbed onto red blood cells, [12] where it can be agglutinated with anti-Lewis a reagent. Fucose is a common sugar, found in seaweeds such as fucus vesiculosus (bladderwrack), and also forms the terminal sugar of the H antigen in people with blood group O. Fucosyltransferase enzymes can attach the fucose molecule onto another sugar or glycoprotein through fucosylation, such as that of the blood group A or B antigen or Lewis antigens. If there is a working copy of the FUT2 SNP the Lewis a antigen will be catalysed into Lewis b by the FUT2 enzyme. Consequently those with a functional FUT2 enzyme don’t have any Lewis a antigen on their erythrocytes, but they will have the Lewis b antigen, and therefore a finding of Lewis b on erythrocytes indicates an ABH secretor. The problem arises with the small number of people who don’t have the Lewis blood group antigens on their blood cells. This is similar to the rare ‘Bombay’ blood group, which results in a loss of production of ABH antigens on erythrocytes (from loss of FUT1 function): the fucosyltransferase 1 (FUT1) gene is expressed predominantly in erythroid tissues, giving rise to FUT1 (H enzyme) giving rise to products found on erythrocytes. About 5% of the European population (and more in some other populations) lack a functional fucosyltransferase 3 (FUT3) enzyme. These FUT3 negative people are unable to make any Lewis antigens. They may be either ABH secretors or non-secretors, but the Lewis test cannot be used to determine secretor status due to the lack of any Lewis antigen for agglutination.

    People with no Lewis antigens are classed as Lewis negative, however this phenotype might not always be only caused by FUT3 mutation. Erythrocyte membranes have been found to lose their Lewis antigens during pregnancy and during diseases such as cancer: individuals have been identified who change from Lewis positive to Lewis negative on erythrocytes, although they persistently express Lewis enzyme activity in saliva. The reason for this change has been attributed to an increased level of circulating lipoproteins during the burden of disease or pregnancy, which alter the balance between production of Lewis glycolipids, transport in lipoproteins, and incorporation into erythrocyte membranes. Fucosyltransferase activity in saliva is variable, being lower in FUT3 heterozygotes than it is in homozygous wild-type individuals, and those with mutation in the FUT2 gene (non-secretors) do not fucosylate the Lewis a structure to H and the Lewis b, in competition with a sialyltransferase. [13]

    There are also epigenetic influences on FUT3 expression. Certain cancer markers are not found in patients with FUT3 mutation: it is not thought useful to measure the CA19-9 titer of Lewis negative cancer patients. A study found that Lewis-negative individuals consisting of a homozygous negative FUT3 genotype had completely negative CA19-9 values, irrespective of the FUT2 secretor genotype. [14] Very few Lewis-positive patients exhibit positive DU-PAN-2 values. [15]

    Although Lewis negative status may be protective against Rotavirus, [16] it is also linked with markers of inflammation: WBC, hs-CRP and ESR were significantly elevated, and rheological parameters (RBC aggregation, plasma viscosity) were found to be abnormal in Lewis negative subjects. [17] Lewis negative men were found to have a higher systolic blood pressure (6 mm Hg), higher values for BMI (8%) and total body fat mass than Lewis positive individuals. [18] Lewis negative status is a genetic risk factor for ischemic heart disease (IHD), particularly in men, and is associated with high triglycerides. Lewis negative status also confers protection from IHD with moderate alcohol intake: Studies found that the risk of IHD was negatively correlated with alcohol consumption. [19] The authors suggest that alcohol consumption may modify insulin resistance in Le(a-b-) men. [20] Asthma is related to both non-secretor and Lewis negative phenotypes, and low lung function values have been observed in Lewis negative non-secretors. Alcohol intake is also protective against asthma in Lewis negative individuals, [21] but Lewis negative individuals are more likely to suffer from alcoholism. [22] Lewis negative phenotype confers a three times greater risk of diabetes, [23] and an increased risk for Sjögren’s syndrome. [24] The intestinal microbiota of individuals with Lewis negative blood groups were reported to contain a less rich and diverse range of bacteria than those with Lewis a phenotype. [25] Urinary tract infections in women are more common amongst non-secretors, and most common in Lewis negative individuals. [26] Polymorphisms in FUT3 and its intestinal expression might be associated with pathogenesis of ulcerative colitis. [27]

    Despite the differences in disease risk between ABH secretors and non-secretors, clinical experience suggests that Lewis negative individuals appear to have unique interactions with certain disease states. [8] Opus 23 Pro [28] provides algorithms in the Lumen app to find secretor status from the FUT2 rs601338 SNP, and to estimate Lewis status from 23andMe raw data based on the SNPs available for FUT3 (all except one of the most common FUT3 SNPs resulting in Lewis negative status are typically reported by 23andMe). This can give the practitioner another level of insight into the likely glycosylation levels, immune status, inflammatory and health risks of the patient, as well as the likelihood of relevance of testing for tumour markers.

    1. Haas H, Falcone FH, Schramm G, et.al. Dietary lectins can induce in vitro release of IL-4 and IL-13 from human basophils. Eur J Immunol. 1999 Mar;29(3):918-27. PMID: 10092096.
    2. Albertolle ME, Hassis ME, Ng CJ, et. al. Mass spectrometry-based analyses showing the effects of secretor and blood group status on salivary N-glycosylation. Clin Proteomics. 2015 Dec 30;12:29. doi: 10.1186/s12014-015-9100-y. PMID: 26719750; PMCID: PMC4696288.
    3. Prakobphol A, Leffler H, Fisher SJ. The high-molecular-weight human mucin is the primary salivary carrier of ABH, Le(a), and Le(b) blood group antigens. Crit Rev Oral Biol Med. 1993;4(3-4):325-33. PMID: 7690601.
    4. Hu D, Zhang D, Zheng S, et. al. Association of Ulcerative Colitis with FUT2 and FUT3 Polymorphisms in Patients from Southeast China. PLoS One. 2016 Jan 14;11(1):e0146557. doi: 10.1371/journal.pone.0146557. PMID: 26766790; PMCID: PMC4713070.
    5. Lindesmith L, Moe C, Marionneau S, et. al. Human susceptibility and resistance to Norwalk virus infection. Nat Med. 2003 May;9(5):548-53. PMID: 12692541.
    6. Tandon OP, Bhatia S, Tripathi RL, Sharma KN. Phagocytic response of leucocytes in secretors and non-secretors of ABH (O) blood group substances. Indian J Physiol Pharmacol. 1979 Oct-Dec;23(4):321-4. PMID: 528036.
    7. Tandon OP. Leucocyte phagocytic response in relation to abo blood groups. Indian J Physiol Pharmacol. 1977 Jul-Sep;21(3):191-4. PMID: 612601.
    8. D’Adamo PJ, Kelly GS. Metabolic and immunologic consequences of ABH secretor and Lewis subtype status. Altern Med Rev. 2001 Aug;6(4):390-405. Review. PMID: 11578255.
    9. McGovern DP, Jones MR, Taylor KD, et. al. International IBD Genetics Consortium. Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn’s disease. Hum Mol Genet. 2010 Sep 1;19(17):3468-76. doi: 10.1093/hmg/ddq248. PMID: 20570966; PMCID: PMC2916706.
    10. Smyth DJ, Cooper JD, Howson JM, et. al. FUT2 nonsecretor status links type 1 diabetes susceptibility and resistance to infection. Diabetes. 2011 Nov;60(11):3081-4. doi: 10.2337/db11-0638. PMID: 22025780; PMCID: PMC3198057.
    11. Hurd EA, Domino SE. Increased susceptibility of secretor factor gene Fut2-null mice to experimental vaginal candidiasis. Infect Immun. 2004 Jul;72(7):4279-81. PMID: 15213174; PMCID: PMC427463.
    12. Henry S, Oriol R, Samuelsson B. Lewis histo-blood group system and associated secretory phenotypes. Vox Sang. 1995;69(3):166-82. Review. PMID: 8578728.
    13. Orntoft TF, Vestergaard EM, Holmes E, et. al. Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels. J Biol Chem. 1996 Dec 13;271(50):32260-8. PMID: 8943285.
    14. Narimatsu H, Iwasaki H, Nakayama F, et. al. Lewis and secretor gene dosages affect CA19-9 and DU-PAN-2 serum levels in normal individuals and colorectal cancer patients. Cancer Res. 1998 Feb 1;58(3):512-8. PMID: 9458099.
    15. Vestergaard EM, Hein HO, Meyer H, et.al. Reference values and biological variation for tumor marker CA 19-9 in serum for different Lewis and secretor genotypes and evaluation of secretor and Lewis genotyping in a Caucasian population. Clin Chem. 1999 Jan;45(1):54-61. PMID: 9895338.
    16. Nordgren J, Sharma S, Bucardo F, et. al. Both Lewis and secretor status mediate susceptibility to rotavirus infections in a rotavirus genotype-dependent manner. Clin Infect Dis. 2014 Dec 1;59(11):1567-73. doi: 10.1093/cid/ciu633. PMID: 25097083; PMCID: PMC4650770.
    17. Alexy T, Pais E, Wenby RB, et al. Abnormal blood rheology and chronic low grade inflammation: possible risk factors for accelerated atherosclerosis and coronary artery disease in Lewis negative subjects. Atherosclerosis. 2015;239(1):248-251. doi:10.1016/j.atherosclerosis.2015.01.015.PMID: 25626016; PMCID: PMC4331217
    18. Clausen JO, Hein HO, Suadicani P, et. al. Lewis phenotypes and the insulin resistance syndrome in young healthy white men and women. Am J Hypertens. 1995 Nov;8(11):1060-6. PMID: 8554728.
    19. Hein HO, Sørensen H, Suadicani P, Gyntelberg F. Alcohol intake, Lewis phenotypes and risk of ischemic heart disease. The Copenhagen Male Study. Ugeskr Laeger. 1994 Feb 28;156(9):1297-302. PMID: 8009753.
    20. Hein HO, Sørensen H, Suadicani P, Gyntelberg F. Alcohol consumption, Lewis phenotypes, and risk of ischaemic heart disease. Lancet. 1993 Feb 13;341(8842):392-6. PMID: 8094167.
    21. Kauffmann F, Frette C, Pham QT, Nafissi S, Bertrand JP, Oriol R. Associations of blood group-related antigens to FEV1, wheezing, and asthma. Am J Respir Crit Care Med. 1996 Jan;153(1):76-82. PMID: 8542166.
    22. Cruz-Coke R. Genetics and alcoholism. Neurobehav Toxicol Teratol. 1983 Mar-Apr;5(2):179-80. PMID: 6346123.
    23. Melis C, Mercier P, Vague P, Vialettes B. Lewis antigen and diabetes. Rev Fr Transfus Immunohematol. 1978 Sep;21(4):965-71. PMID: 734307.
    24. Manthorpe R, Staub Nielsen L, Hagen Petersen S, Prause JU. Lewis blood type frequency in patients with primary Sjögren’s syndrome. A prospective study including analyses for A1A2BO, Secretor, MNSs, P, Duffy, Kell, Lutheran and rhesus blood groups. Scand J Rheumatol. 1985;14(2):159-62. PMID: 4001887
    25. Wacklin P, Tuimala J, Nikkilä J. Faecal microbiota composition in adults is associated with the FUT2 gene determining the secretor status. PLoS One. 2014 Apr 14;9(4):e94863. doi: 10.1371/journal.pone.0094863. PMID: 24733310; PMCID: PMC3986271.
    26. Sheinfeld J, Schaeffer AJ, Cordon-Cardo C, Rogatko A, Fair WR. Association of  the Lewis blood-group phenotype with recurrent urinary tract infections in women. N Engl J Med. 1989 Mar 23;320(12):773-7. PMID: 2922027.
    27. Hu D, Zhang D, Zheng S, et. al. Association of Ulcerative Colitis with FUT2 and FUT3 Polymorphisms in Patients from Southeast China. PLoS One. 2016 Jan 14;11(1):e0146557. doi: 10.1371/journal.pone.0146557. PMID: 26766790; PMCID: PMC4713070.
    28. Opus 23 Pro genetic analysis and reporting software by Dr P. D’Adamo www.opus23.com.
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  • Opus Training and Certification

    seminar5

    Thank you for this brilliant creation. I am honored to be a part of this game-changing program. –Robert Lang, MD

    Opus 23 Pro is designed to be as intuitive to use as it is powerful. However, mastery requires understanding and fully utilizing all the nuances of the many available apps in the program. For those who specialize in genomic testing and focus a large part of their practice on nutrigenomics, we are developing a weekend seminar intensive on Opus 23 mastery. Participants will work directly with Dr. Peter D’Adamo and his team of teaching assistants in a hands-on environment, using Opus 23 Pro to develop fully formatted and curated genomic reports. Attendees successfully completing the seminar will be certified as official Opus 23 consultants.

    photo: Bob Messineo
    photo: Bob Messineo


    The tentative dates for the next seminar are 8/20 – 8/21 at the Center of Excellence in Generative Medicine at the University of Bridgeport, in Bridgeport Connecticut.


    seminargroup

    Because the seminar is designed to be experiential, seating is extremely limited. Please check back here for further details. Seating is on a first come, first served basis. You can soft-reserve seating (no obligation) by completing the form below. This seminar will not be recorded or available as a webinar. The total cost of the seminar is $850 USD and includes lunch on Saturday. All participants completing the seminar will have three (3) complimentary client licenses assigned to their account for their own future use ($210 USD value).

    Note: This seminar is open to all licensed professionals.

    International Professionals: we plan to do a similar seminar in London (UK) area sometime later in the year.


    I’m interested in attending the next Opus 23 Training Seminar.



    Please supply your professional qualifications (required)

    ND MD/DO DC LAc RN RPH RD PhD CCN PA


    This has been a wonderful month for attending training and conferences and for reconnecting with so many friends and colleagues. The Opus Pro new software that Dr. D’Adamo designed is phenomenal! The software is cutting edge and user friendly. Those of us that attended the CT training now have access to software that analyzes SNPs (genetic variations) and helps identify important patterns for current and predisposed health conditions. Wow!!!

    Ivory Raye, ND

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