When the DNA sequence that codes for a protein is altered, the structure and the function of that protein can be affected - to a lesser or to a greater extent. 

This is the third post in the series of genetic mutations associated with obesity. 

In the first part I discussed about the exponentially decreasing costs of genome sequencing (full or partial sequencing), I introduced single nucleotide polymorphisms (SNPs) and I described a few SNPs associated with obesity. You can read it [here](https://steemit.com/research/@cristi/genetic-mutations-linked-to-obesity). 

In the second part I described a couple of SNPs for FTO and MC4R genes and their potential phenotype implications. You can read it [here](https://steemit.com/research/@cristi/genetic-mutations-linked-to-obesity-part-2).
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### Generic Introduction

For the sake of keeping things simple, I'm only going to remind about what SNPs are. According to the [NIH Handbook of Genetics](https://ghr.nlm.nih.gov/handbook/genomicresearch/snp):

_"Each SNP represents a difference in a single DNA building block, called a nucleotide. For example, a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA."_

<center>https://s16.postimg.org/7qx6rjo3p/Genetic_Mutations_linked_to_Obesity_Part_2.jpg</center>

Each of us carry approximately 10 million SNPs, but many of them are not in parts of the genome to negatively impact physiology and phenotype (in general). Some of them are in non-coding regions. As it is pointed out by [Genetics Learning Center of the University of Utah](http://learn.genetics.utah.edu/content/precision/snips/):

_"SNPs and disease causing mutations are not the same."_

Today I'm going to continue with polymorphisms and I'm going to focus on SCG3 and ADIPOQ genes.
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## Genetic Mutations (SNPs) associated with Obesity - Part 3

### SCG3 - gene that codes for Secretogranin III

According to the [National Institutes of Health](https://www.ncbi.nlm.nih.gov/gene/29106):

_"Granins may serve as precursors for biologically active peptides. Some granins have been shown to function as helper proteins in sorting and proteolytic processing of prohormones; however, the function of this protein is unknown."_

SNPedia, or the wikipedia of single nucleotide polymorphisms, currently lists three mutations of SCG3, all being [associated with obesity](http://snpedia.com/index.php/SCG3). 

Two of them have been detailed in a study conducted in 94 obese (BMI >= 30) patients and 658 controls (BMI <= 25). Researchers selected (to look at) 62,663 SNPs. According to [Tanabe and colleagues (2007)](https://www.ncbi.nlm.nih.gov/pubmed/17200173?dopt=Abstract):

_"Twelve SNPs in the SCG3 gene including rs3764220 were in almost complete linkage disequilibrium and significantly associated with an obesity phenotype. Two SNPs (rs16964465, rs16964476) affected the transcriptional activity of SCG3, and subjects with the minor allele seemed to be resistant to obesity."_

In this case, you may be lucky (protected - to a certain extent - from obesity) if you carry the minor allele. 
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### ADIPOQ - gene that codes for adiponectin

- secreted from the adipose tissue, circulates in the plasma, involved in different metabolic and hormonal processes - [[source](https://www.ncbi.nlm.nih.gov/gene/9370)]
- lower adiponectin levels may promote obesity and other disorders of the metabolic syndrome (though it has not been widely confirmed)
- lifestyle modifications and drugs may promote higher circulating levels of adiponectin (which may be a desired outcome)

<center>https://s18.postimg.org/t2sdhd7rt/Genetic_Mutations_linked_to_Obesity_Part_3_2.jpg</center>

Some of the metabolic effects of adiponectin are:

- lower gluconeogenesis and higher uptake of glucose
- promotion of lipid catabolism
- effects on insulin sensitivity and upregulation on uncoupling proteins - [[source](https://dx.doi.org/10.1210%2Fen.2006-0838)]

When the gene that codes for adiponectin (that is ADIPOQ) is mutated, it can promote adiponectin deficiency. 

Hoefle et al. (2007) looked at a mutation in this gene and its possible connection with prevalence of atherosclerosis and other vascular events in 402 male subjects. They found [that](https://www.ncbi.nlm.nih.gov/pubmed/17334513?dopt=Abstract):

_"The -11377 C > G adiponectin gene promoter variant is:_

_(i) associated with decreased serum adiponectin levels and therefore increased risk of obesity,_
_(ii) correlated with the presence of coronary atherosclerosis, and_
_(iii) significantly predictive of vascular events among men undergoing coronary angiography."_

If you carry this mutation, you may want to look more in-depth at other similar mutations that could enhance the risk of developing cardiovascular disorders. 
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## Ending Thoughts 

This type of post is mostly 'readable' by an audience with knowledge of genomics and sequencing related terminology. If you are part of this audience you may experience difficulty in understanding what I am talking about. A 2 minute video that may help you summarily understand what I'm talking about is provided by _23andme_ and it describes [SNPs](https://www.youtube.com/embed/tJjXpiWKMyA). 

As I said in the past, you could use services like _23andme_ to determine your SNPs. One you have your report from them you could investigate the SNPs yourself by browsing through medical libraries (as I did in this post) or you could use services like _Promethease_ that does it for you (to a certain extent). It may be unfeasible to look at 800 thousand to 1 million SNPs manually, which is what you get from the _23andme_ report. 

In future posts I will look at other genetic mutations (SNPs in particular) associated with obesity and other conditions - alcohol addiction seems to be a subject worth paying attention to.
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Credits for Images: [[David Hall CC BY 4.0 via Wikimedia Commons](https://upload.wikimedia.org/wikipedia/commons/archive/2/2e/20141217214625%21Dna-SNP.svg) and [[By Min, Walker and Wang (2012) via RCSB, PDB ID: 4DOU](http://www.rcsb.org/pdb/explore/explore.do?pdbId=4DOU)].

#research #genomics #science
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[Cristi Vlad](http://cristivlad.com), Self-Experimenter and Author