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  The Magnesium Project - Genomics

The role of proteins in living organisms has been addressed elsewhere.  One of the issues is how proteins are synthesized in the cells and what governs the sequence of amino acids that are stitched together.  The answer to that lies in large part with the genetic code or set of instructions given.  The code and how it is read and applied is the province of genomics.  As we shall see, the system for the regulation of and functioning of cations depends upon discovering the codes for various proteins and how the codes are read and under what circumstances mis-reading and self-correction can occur.  The topic of how other non-genetic factors might impact  the faithful reproduction of proteins comes under the heading of epi-genetics and is considered elsewhere.

In the early days of genetics, studies were done by observing the results of breeding plants or animals of particular phenotypes such as leaf or eye color.  One determined whether inherited characteristics were dominant or recessive according to whether each parent or only one parent had a particular trait.  With today's tools, and our understanding of the nature of genetic material (DNA - deoxyribonucleic acid), studies are more likely done on a molecular scale rather than a whole organism scale.  This has ushered in the field of genomics - the study of genetics at the molecular level.  We now know that DNA that resides in the cell nucleus carries all of the information needed to direct the synthesis of all of the chemicals needed by the organism.  In the early days of genomics studies it was believed that for each protein made there was one gene on the DNA strand that was responsible for that protein.  We now know that there may be multiple proteins produced from a gene and that there may be multiple genes involved in the synthesis of a particular protein.

Genetic conditions may be pre-disposing for most of the diseases under consideration.  Typically diseases are the result of multiple genetic defects which is the case for most cancers.  Breast cancer for example is associated with at least 7 defects (copy number variations (CNV) or single nucleotide polymorphism (SNP)).  Prostate cancer is associated with more than a dozen.   A few diseases are of a single locus.

Genomics starts with the DNA structure as elucidated by Watson and Crick is an alpha helix formed of a long string of nucleotides stitched together through four different base pairs and all attached to a phosphorylated sugar backbone.  The four bases serve as the basis for a triplet code that identifies which amino acid should attach to which during protein synthesis.  Other codes are for stopping or starting the reading of the code or carrying out other control functions.  The tertiary structure is depicted in the figure in which each colored "ball" represents molecular components including the purines (adenine and guanine), pyrimidines (cytosine, uracil, thymine), phosphate and sugar (ribose) along with atoms of carbon, oxygen, hydrogen, nitrogen and phosphorous.

Photo made available for free at:
www.all-about-forensic-science.com

Replication / Mitosis
Throughout life, one grows and replaces lost cells through a process of cell division known as mitosis.  In mitosis, the DNA strands that are in the cell nucleus open up so that new strands can be synthesized through a copying process that provides a new set of DNA for each new cell.  This process of creating new DNA is called replication.

Translation to RNA
For normal functioning of the cell, new compounds are being continually produced, these may be proteins to add muscle mass, develop connective tissue,  produce hormones or any one of tens of thousands of other functions.  These processes are directed by the DNA through an intermediaries known as RNAs (ribonucleic acids).  The RNA has a similar structure as DNA and contains a copy of a segment of the master DNA.  These on-going copying process is known as translation in which DNA produces RNA which is then released from the cell nucleus to cell matrix or cytosol.

Transcription to Protein Synthesis
Transcription is the term for the process whereby a section of the messenger RNA (mRNA) is copied to a transfer RNA (tRNA) that then attaches to structures  (endoplasmic reticulum) in the cell where the actual synthesis of proteins occur adding one amino acid at a time to form a chain according to the triplet code of the tRNA.  The RNA also contains regulatory codes for starting and stopping the reading of the strand for example.  Additional layers of complexity of regulation of this process by various enzymes, hormones and co-factors continue to be added with further research. New forms and functions of RNA continue to be discovered in current times.

Genetics of Key Proteins in Cation Activity
The regulation of cations in the mammals is comprised of many pathways each having many proteins or enzymes or compounds whose synthesis is directed by enzymes.  Any one of those hundreds of steps could be compromised by a genetic anomaly.

Genetics of Diseases linking to Cation Regulation Dysfunction
The genetics of diseases of cation regulation dysfunction is beyond the scope of this website at present.

Genomic Research and Gene Expression
We have identified a significant opportunity in furthering our understanding of the role of cations in metabolism and homeostasis. Homeostasis is that collection of interdependent reactions and systems that make the difference between being healthy, pain free and feeling good or being run-down, ailing or suffering from acute illnesses, pain and vulnerable to infections. The level of magnesium ions is critical to hundreds of enzymatic reactions in the body and is known to be involved in many diseases, yet its regulation and regulating entities are not well known.

These little understood mechanisms for magnesium ion regulation include their role in disease processes - diseases such as heart arrhythmia, maternal pre-eclampsia and eclampsia, high blood pressure, cell replication dysfunction, deficient energy production, muscle and nerve hyper- or hypo-activity, diabetes and more. We need your support to help us develop an international collaboration between government, academic and industrial scientists.

GWAS - Genome Wide Association Studies.  This is one type of study in which differences in expression of various genes is observed in a group of individuals.  Studies may be conducted of multiple groups having different "phenotypes"; such as those with a high incidence of cancers versus those with a low incidence of the same disease.  NGS (Next Generation Sequencing) tools continue to be developed bringing down the cost of sequencing.  As a result it is more practical to identify transcription activity even at the cellular level.  This has ushered in a new activity known as Transcriptomics.  This discipline provides a huge boost to our protein/mRNA expression research enabling the discovery of novel proteins and regulatory systems.

Epi-genetics
Epi-genetics is the discipline of studying external/environmental factors in the expression and modification of genes. In particular it is the study of how environmental factors become incorporated into the "intelligence" of the genome. This growing field will also help in our understanding of how Mg is regulated under different environmental conditions (such as when fish migrate from fresh water to salt water or vice versa.

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