Mendelian Randomization

The second law of Mendelian inheritance is about independent assortment of alleles at the time of gamete (sperm & egg cells) formation. Therefore within the population of any given species, genetic variants are likely to be distributed at random, independent of any external factors. This insight forms the basis of Mendelian Randomization (MR) technique, typically applied in studies of epidemiology.

Studies of epidemiology try to establish the causal link (given some known association) between a particular risk factor & a disease. For e.g. smoking to cancer, blood pressure to stroke, etc. The association in many cases is found to be non-causal, or reverse causal, etc. Establishing the true effect becomes challenging due to the presence of confounding factors such as social, behavioral, environmental, physiological, etc. MR helps to tackle the confounding factors in such situations.

In MR, genetic variants (polymorphism) or genotype that have an effect similar to the risk factor/ exposure are identified. An additional constraint being that the genotype must not have any direct influence on the disease. Existence of genotype in the population is random, independent of any external influence. So presence (or absence) of disease within the population possessing the genotype, establishes (or refutes) that the risk factor/ effect is actually the cause for the disease. Several researches based on Mendelian randomization have been done  successfully.

Example 1: There could be a study to establish the causal relationship (given observed association) between raised cholesterol levels & chronic heart disease (CHD). Given the presence of several confounding factors such as age, physiology, smoking/ drinking habits, reverse causation (CHD causing raised cholesterol), etc., MR approach would be beneficial.

The approach would be to identify a genotype/ gene variant that is known to be linked to an increase in total cholesterol levels (but has no direct bearing on CHD). The propensity for CHD is tested for all subjects having the particular genotype, which if/ when found much higher than the general population (not possessing the gene variant) establishes that raised cholesterol levels have a causal relationship with CHD.

Instrumental Variables

MR is an application of the statistical technique of instrumental variables (IV) estimation. IV technique is also used to establish causal relationships in the presence of confounding factors.

When applied to regression models, IV technique is particularly beneficial when the explanatory variable (covariates) are correlated with the error term & give biased results. The choice of IV is such that it only induces changes in the explanatory variables, without having any independent effect on dependent variables. The IV must not be correlated to the error term. Selecting an IV that fulfills these criterias is largely done through an analytical process supported by some observational data, & by leveraging relevant priors about the field of study.

Equating MR to IV 

• Risk Factor/ Effect = Explanatory Variable, 
• Disease = Dependent Variable
• Genotype = Instrument Variable 

Selection of genotype (IV) is based on prior knowledge of genes, from existing sources, literature, etc.

Mendelian Inheritance

Gregor Mendel was a phenomenal scientist of the nineteenth century. Actually a Monk by profession he is considered the founder of modern genetics. In the 1850-60s, in the garden of his monastery he performed systematic hybridization experiments with the Pea plant over successive generations (second - F2, third - F3, etc.). Through these experiments he was able to conclude that traits get inherited by progenies in the form of discrete traits with a perfectly binary (either/ or) characteristic from the ancestors, as opposed to the then existing notion of a blending of traits. 

The following are the laws of Mendelian inheritance:

• Law of Segregation:  During gamete (sperm or egg cell) formation, allele pairs separate out at random & only one of the alleles are carried by each gamete for each gene.
• Law of Independent Assortment: Genes for different traits segregate independently of other pairs of alleles during the formation of gametes.
• Law of Dominance: Some alleles are dominant while others are recessive. When present the dominant ones dominate.

Where,

 Human body is

  made of -> Cells                              
                                                                  (Building block of life, contain
                                                                       biomolecules such as Protein, DNA)

         containing --> Chromosomes            
                                                                 (One DNA Molecule + some proteins
                                                                       in the cell's nucleus, double helix
                                                                       shape, 46 in humans: 23 each
                                                                       inherited from either parent)

                             having     ---> Genes                     
                                                                  (Code to synthesize proteins
                                                                       & biocomponents, 2 Alleles or
                                                                        variant forms of a trait,
                                                                        one inherited per parent)

                                     that get coded to ----> Proteins   
                                                                 (Large biomolecules of amino acid
                                                                       chains, participate in vast variety
                                                                       of cellular processes & biological
                                                                       functions, metabolic reactions,
                                                                       signaling, etc. Exist within & get
                                                                       recycled by the cells)
                                                 
While the findings of Mendel were not popular initially, they were re-discovered almost half a century later. Though Mendel limited the experiments to traits that were governed by a single gene, the results were significant. These helped formed our understanding of genetics & heredity (genes) that continue to this day.

Memory Gene

Have a conjecture that soon someone's going to be discovering a memory gene in the human genome. This doesn't seem to be have been done or published in any scientific literature so far. The concept of Genetic Memory from an online game is close, but then that's fiction.

The idea of the memory gene is that this gene on the human genome will act as a memory card. Whatever data the individual writes to the memory gene in their lifetime can be later retrieved by their progenies in their lifetimes. The space available in the memory gene would be small compared to what is available in the brain. If the disk space of the human brain is a Petabyte (= 10^12 Kilobytes), space of the memory gene would be about 10 Kilobytes. So very little can be written to the memory gene.

Unlike the brain to which every bit of information (visual, aural, textual, etc.) can be written to at will, writing to the memory gene would require some serious intent & need. Writing to the memory gene would be more akin to etching on a brass plate - strenuous but permanent. The intent would be largely triggered by the individual's experience(s), particularly ones that triggers strong emotions perhaps beneficial to survival. Once written to the memory gene this information would carry forward to the offsprings.

The human genome is known to have about 2% coding DNA & the rest non-coding DNA. The coding portions carry the instructions (genetic instructions) to synthesize proteins, while the purpose of the non-coding portions is not clearly known so far. The memory gene is likely to have a memory addressing mechanism, followed by the actual memory data stored in the large non coding portion.

At the early age of 2 or 3 years, when a good portion of brain development has happened in the individual, the memory recovery will begin. The mRNA, ribosome & the rest of the translation machinery will get to work in translating the genetic code from the memory gene to synthesize the appropriate proteins & biomolecules of the brain cell. In the process the memory data would be restored block by block in the brain. This would perhaps happen over a period of low activity such as night's sleep. The individual would later awaken to new transferred knowledge about unknowns, that would appear to be intuitive. Since the memory recovery would take place at an early age, conflicts in experiences between the individual and the ancestor wouldn't happen.
  
These are some basic features of the very complex memory gene. As mentioned earlier, this is purely a conjecture and shouldn't be taken otherwise. Look forward to exploring genuine scientific researches in this space as they get formalized & shared.

Update 1 (27-Aug-19):
For some real research take a look at the following:

 =>> Arch Gene:
 Neuronal gene Arc required for synaptic plasticity and cognition. Resemble  retroviral/retrotransposon in their transfer between cells followed by activity dependent translation. These studies throw light on a completely new way through which neurons could send genetic information to one another. More details from the 2018 publication available here:

•    https://www.nih.gov/news-events/news-releases/memory-gene-goes-viral
•    https://www.cell.com/cell/comments/S0092-8674(17)31504-0
•    https://www.ncbi.nlm.nih.gov/pubmed/29328915/

  =>> Memories pass between generations (2013):
 When grand-parent generation mice are taught to fear an odor, their next two generations (children & grand-children) retain the fear:

•    https://www.bbc.com/news/health-25156510
•    https://www.nature.com/articles/nn.3594
•    https://www.nature.com/articles/nn.3603

 =>> Epigenetics & Cellular Memory (1970s onwards):

•    https://en.wikipedia.org/w/index.php?title=Genetic_memory_(biology)&oldid=882561903
•    https://en.wikipedia.org/w/index.php?title=Genomic_imprinting&oldid=908987981

  =>> Psychology - Genetic Memory (1940s onwards):Largely focused on the phenomenon of knowing things that weren't explicitly learned by an individual:

•    https://blogs.scientificamerican.com/guest-blog/genetic-memory-how-we-know-things-we-never-learned/
•    https://en.wikipedia.org/w/index.php?title=Genetic_memory_(psychology)&oldid=904552075
•    http://www.bahaistudies.net/asma/The-Concept-of-the-Collective-Unconscious.pdf
•    https://en.wikipedia.org/wiki/Collective_unconscious