FREQUENTLY ASKED QUESTIONS
1. FAQs of wellness

What is 'Gene'?

A gene is a 'hereditary unit', which when passed from parents, confers some physical character to the offspring, like eye or hair color, height etc. Biochemically, it is a string of 4 distinct nucleotides (abbreviated as "A, T, G and C"), repeating in many combinations and orders. The order in which the string of 'A,T,G,C' appears, determines the function of the gene and in turn the character it is going to confer in offspring.

What is 'Genome'?

A genome is sum total of all genes (and some more) that is present in an individual. We, human beings, are estimated to have around 20000-25000 genes, which together defines every characteristic of ours, be it eye color or height or predisposition to a disease.

What is 'Genetic Predisposition' to a disease?

Genetic predisposition simply means an increased likelihood of you developing a disease, based on your genetic makeup that you inherited from your parents, caused due to small genetic variations.

What is 'Genetic Variation'?

We now know every gene is a large string of letters (ATGC). If there is a change in one or more of these letters, and if it causes a change in the gene's function, we define it as a genetic variation. Single Nucleotide Polymorphisms, frequently called SNPs (pronounced “snips”), are the most common type of genetic variation among people. Each SNP represents a difference in a single building block (A or T or G or C) of the gene. For example, a SNP may occur by substitution of the nucleotide 'A' by nucleotide 'C' or 'G'.

What happens if there is a 'Genetic Variation'?

When SNPs occur within a gene or in a regulatory region near a gene, they may affect the gene’s function to varying degrees. For example, an individual with a "C", in certain position of Gene X, has a lower risk of getting a disease. However, if this normal "C" is replaced by "T", his/her risk of getting that disease increases by several fold.

So, does it mean all genetic variations cause diseases?

No;

Only a small percentage of such genetic variations can cause genetic disorders, while most others have no impact on your health or development. In fact, a very small percentage of all genetic variations can actually have a positive effect, which might help you to better adapt to changes or protect you from a disease, which are termed "protective variants".

Will one genetic variation cause the disease?

No;

Well, mostly 'NO'. It is critical to understand that most of the diseases are a result of complex interplay of many genetic factors, but not limited to only genetic factors. Many environmental, lifestyle and dietary factors play key roles in developing a particular disease, and such diseases are thus "multifactorial". Hence, the genetic makeup you possess largely contribute to the 'development of' a particular disease, but may not directly cause it.

However, there are some "rare diseases" that are caused as a result of a single variation in a single gene. As said they are rare and amount to less than 1% of the population. We will highlight the presence of such allele duly within this report, if found.

Is it 100% certain, that if I have a certain genetic variation, I 'will' get the disease?

No;

It is also important to understand, some genetic predispositions can have large and significant effect on the likelihood of you developing a particular disease, while some might only aid the process. This is also the reason why some individuals, even with a predisposing genetic factor, might never get the disease, while others will, even with moderate predisposition. A classic example can be, the genetic variations in the BRCA1 or BRCA2 genes, which significantly increases a woman's risk of developing breast cancer and ovarian cancer. On the other hand, variations in other genes, such as BARD1 and BRIP1, increases the risk of her getting breast cancer, but the overall risk appears to be much smaller.

What will we gain by understanding these ''Genetic Variations'?

Since these genetic variations ubiquitously defines everything from your physical characteristics to your predisposition to complex diseases, they are the unique genetic signatures of yourself (Hence the name - Genetic Signature). They can act as indicators of extent of predisposition to disease(s) or risk of developing particular disease(s). Also, the understanding is not limited to just diseases, but extends further to an individual’s response to certain drugs/therapy, susceptibility to environmental factors such as toxins, so on and so forth. More importantly, these genetic variations can also be used to track the inheritance of a disease within families.

What is a PMID?

Every genetic variation and the trait (disease/drug/metabolism) that it is predisposing you to, has been provided with a reference ID. You can find this ID at the bottom of each page and will look like PMID: 123456. If you want to understand the underlying biological mechanisms or if your 'Clinician/Physician' wants to validate the study, this PMID can be used. To get the corresponding article please use the following National Institute of Health (NIH) link "http://www.ncbi.nlm.nih.gov/pubmed" and within the search bar punch in the PMID provided as the reference, which should directly lead you to the reference article you seek.

2. FAQS of Microbiome

What is human microbiome?

Human body hosts a huge number of microbes of many different kinds. These microbes play a role in many fundamental life processes. The collection of microbes that constitute the microbiome is not random; the human microbiome is made up of a set of microbes that complement each other and the human host.

Where does our microbiome come from?

We get most of them from other humans. Like new born babies get it from their mother’s birth canal, by breast milk, and as the babies become mobile they encounter it from the environment.

How big is the microbiome?

Its HUGE! Like as many cells of human body!

Where is, the microbiome located?

Wherever human body is exposed to the outside world, there is a microbial community i.e, entire surface of the skin, and the linings of the nasal passages, lungs, digestive and urogenital tracts are all home to microbial communities and each one of these has its own unique characteristic set of microbes.

What are the functions of microbiomes?

What the microbiome is doing varies from place to place and many of its functions have not yet been elucidated. Like for example, bacteria in the mouth and gut helps in digesting complex carbohydrates and lipids and keeps immune system in check.

Is our microbiome dependent on our genetics?

Yes, Microbes sense and interact with specific markers that are secreted by cells or found on their surfaces and use these cues to “decide” where to grow. Thus, there is a role for human genetics in the eventual structure of the microbiome. The exact mechanisms that govern these selection processes are also under active study, but they certainly include a great deal of chemical communication, as well as physical cues like temperature and moisture levels.

What is the significance of gut microbiome?

The gut is the best-studied site in the human microbiome and it contains the largest, densest, and most diverse microbial community in the human body. The gut microbiome acts as a highly efficient bioreactor, helping to extract energy and nutrients from the food we eat. Compounds that humans cannot digest on their own can be broken down by microbes. Evolutionarily, these microbial capabilities allowed humans to benefit from a wider variety of foodstuffs. The gut microbiome has complex effects on human metabolism and changes in its composition have been linked to several diseases including inflammatory bowel disease, Clostridium difficile infections, autoimmune disorders, and even diabetes and obesity. There are intriguing indications that the gut microbiome may affect sleep patterns, mood, and other behaviors.

Is everyone’s microbiome the same?

No, they are not the same, it differs from person to person. Though the microbiome carries out many similar functions, but the jobs are not necessarily done by the same microbial species in each person. Also, the species carrying out the various functions in any given individual may change over time, differs based on the sex of the individual, ecological niche etc.

Does this mean I am unique with respect to the microbiome?

Yes, The microbiomes of various body sites are similar in everyone. Though there is a quite a bit of variation from one person to the next, but one’s own microbiome is stable over time and also varies by the presence of functional capabilities.

Does this mean I am unique with respect to the microbiome?

Yes, The microbiomes of various body sites are similar in everyone. Though there is a quite a bit of variation from one person to the next, but one’s own microbiome is stable over time and also varies by the presence of functional capabilities.

What is the relationship between the microbiome, human health and disease?

There are many studies that show a correlation between certain mixtures of microbes and certain disease states, but evidence that any microbial community causes a disease is still limited. What is clear, however, is that the microbiome is probably an important factor in many diseases, a factor that has been neglected in the past. Koch developed a set of postulates laying out the conditions that had to be fulfilled for a disease to be attributed to a microbe.

Koch’s postulate #1: The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms.

Koch’s postulate #2: The microorganism must be isolated from a diseased organism and grown in pure culture.

Koch’s postulate #3: The cultured microorganism should cause disease when introduced into a healthy organism.

Koch’s postulate #4: The microorganism must be re-isolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

Is gut microbiome only known to be associated with diseases?

The gut microbiome is not the only one with a role in disease and health; the microbiomes of the mouth, skin, vagina, lungs, and stomach are also altered in various disease states. The microbes in these body sites are not simply passive bystanders but are playing active roles in the dynamic balance between health and disease.

How to take care of my microbial partners?

Right now, what we can state is that we just don’t yet know what characterizes a healthy microbiome, or how our behavior affects it. But still we can avoid taking broad spectrum antibiotics very often, washing hands with antibiotics; instead switch over to a to a healthy diet and consume more prebiotics and probiotics regularly.

What does the normal gut microbiota constitute? Where do you stand with respect to the gut microbiota?

Normal gut microbiome is a scientifically established baseline of abundance of a certain set of gut microbes, consistently seen within normal healthy individuals. This baseline may vary depending on the geography (Indian, Asian, American etc.), gender, culture and demographics, genetics (of your own and that of the race), diet, and many environmental factors. Hence, the gut microbiome of every individual follows certain larger patterns. These types and their abundances are not static, and it changes with age, geography, culture, and most importantly diet, and any shift in the above categories, can lead to a shift in the type and abundance of microbiota. Largely a healthy human gut contains the following phylum of bacteria.
   -> Bacteroidetes [~80%]
   -> Firmicutes [~20%]
   -> Proteobacteria [~4%]
   -> Actinobacteria [~2%]
Another depiction of gut microbiome diversity, representing the above listed bacterial units, is shown below.


Reference: http://www.ncbi.nlm.nih.gov/pubmed/27059297

What is a PMID?

Every genetic variation and the trait (disease/drug/metabolism) that it is predisposing you to, has been provided with a reference ID. You can find this ID at the bottom of each page and will look like PMID: 123456. If you want to understand the underlying biological mechanisms or if your 'Clinician/Physician' wants to validate the study, this PMID can be used. To get the corresponding article please use the following National Institute of Health (NIH) link "http://www.ncbi.nlm.nih.gov/pubmed" and within the search bar punch in the PMID provided as the reference, which should directly lead you to the reference article you seek.

What is OTUs?

“OTUs” is the abbreviation for “Operational Taxonomic Units”, which are units of microbial diversity, assigned and used to refer a cluster(s) of microorganisms in a sample/environment. More specifically, microorganisms with more than 97% similarity in their sequences are clustered as one OTU and assigned a number. So, when your sample is analyzed, based on the sequence information of the microbiota, we will identify many of these clusters with OTUs. Further, we will be able compare these with the normal gut microbiota of a healthy individual (see above), to make logical interpretations about your health.

What is Range?

The comparison between the microbiome of a healthy individual with that of yours, does not limit to just the presence or absence of OTUs. Instead, we will estimate the “Range in Number” of the OTUs present in your sample, and compare it with the reported range in normal healthy individual. These reported range can be represented in mg or Colony forming units (CFUs) or other units, and will be utilized as evidence to understand your health in a better way.