Genotyping vs Sequencing DNA

[Jovialis]

https://customercare.23andme.com/hc...difference-between-genotyping-and-sequencing-


https://www.helix.com/blog/dna-technologies-genotyping-vs-sequencing/


https://www.illumina.com/clinical/illumina_clinical_laboratory/genomics-101/reading-genome.html


https://www.genome.gov/10001177/dna-sequencing-fact-sheet/


https://en.wikipedia.org/wiki/Genotyping


https://en.wikipedia.org/wiki/Sequencing

For anyone that's adept in the science behind analyzing DNA, I'd like to hear your opinion about genotyping vs sequencing.

As I understand it, sequencing is supposed to read the entire genome, while genotyping only looks for clues for predetermined outcomes. The advantage of genotyping seems to be that it's cost effective. I understand that some of this might be marketing, or am I just being cynical in that regard? However, I'm led to believe that sequencing is the better method, if other DNA testing companies are planning to move in that direction when it gets cheaper. Can sequencing really give you a 100x more accurate analysis of your DNA?

 

[LeBrok]

I think, methode which is able to tell us which allele we have for least amount of money will always win. However, in 10 or 100 years when both methods are dirt cheap, Sequencing of whole genome will be the only way.

 

[Jovialis]

I think, methode which is able to tell us which allele we have for least amount of money will always win. However, in 10 or 100 years when both methods are dirt cheap, Sequencing of whole genome will be the only way.

The Helix test will sequence people for $80.

 

[Jovialis]

What is the difference between genotyping and sequencing?

Though you may hear both terms in reference to DNA, genotyping and sequencing refer to slightly different techniques.


Genotyping is the process of determining which genetic variants an individual possesses. Genotyping can be performed through a variety of different methods, depending on the variants of interest and the resources available. For looking at many different variants at once, especially common variants, genotyping chips are an efficient and accurate method. They do, however, require prior identification of the variants of interest.


Sequencing is a method used to determine the exact sequence of a certain length of DNA. You can sequence a short piece, the whole genome, or parts of the genome (such as the “exome," which are the regions of the genome that contain the the instructions for RNAs (ribonucleic acid) and proteins). Depending on the region, a given stretch of sequence may include some DNA that varies between individuals, in addition to regions that are constant. Thus, sequencing can be used to genotype someone for known variants, as well as identify variants that may be unique to that person.
23andMe uses genotyping, not sequencing, to analyze your DNA. Sequencing technology has not yet progressed to the point where it is feasible to sequence an entire person’s genome quickly and cheaply enough to keep costs down for consumers. It took the Human Genome Project, a consortium of multiple research labs, over 10 years to sequence the whole genomes of just a few individuals.
For people with specific needs (undiagnosed medical issues, for example, or intense curiosity and a generous budget), sequencing will become a more and more attractive option. For now, though, genotyping technologies, such as those used by 23andMe, provide an efficient and cost-effective way of evaluating genetic variation in individuals and across populations.

https://customercare.23andme.com/hc...difference-between-genotyping-and-sequencing-

What does this sentence mean?

"They do, however, require prior identification of the variants of interest."

 

[Salento]

What does this sentence mean?

"They do, however, require prior identification of the variants of interest."

Probably means that a General Database of Autosomal/Health related Genes is required, so they can Search and Compares, and Find the relevant Genes of the customer Genome.
So they have a List of All Genes/Segment Important to them, and all they is Look for them in the DNA of the Customer.
No chance of New Genes' Discovery, because they already know what they're looking for, from the Data containing "Identified Genes' Variants of Interest".

 

[Jovialis]

Probably means that a General Database of Autosomal/Health related Genes is required, so they can Search and Compares, and Find the relevant Genes of the customer Genome.
So they have a List of All Genes/Segment Important to them, and all they is Look for them in the DNA of the Customer.
No chance of New Genes' Discovery, because they already know what they're looking for, from the Data containing "Identified Genes' Variants of Interest".

I see, so they look for clues for their predetermined categories, in regards to autosomal DNA and health.

 

[Salento]

DNA Test From Customer Perspective. Some Sequencing/Genotyping info.
https://www.youtube.com/watch?v=U3EEmVfbKNs&feature=youtu.be

 

[Jovialis]

DNA Test From Customer Perspective. Some Sequencing/Genotyping info.
https://www.youtube.com/watch?v=U3EEmVfbKNs&feature=youtu.be

Interesting, so genotyping reads .02% of the genome, targeting points of interest. While sequencing reads 100% of the genome.

Edit: here's the specific part of the video that explains it.

https://youtu.be/U3EEmVfbKNs?t=2m43s

(80 GBs of Raw data vs 5mbs, no wonder they aren't releasing it yet. There's no way it would be compatible with the other apps you can upload your results to with other platforms).

 

[LeBrok]

Interesting, so genotyping reads .02% of the genome, targeting points of interest. While sequencing reads 100% of the genome.

Isn't it engenius to be able to read so little but know so much, and for a very low prices?! But as I said, eventually with low cost, sequencing is the future.

 

[Jovialis]

Isn't it engenius to be able to read so little but know so much, and for a very low prices?! But as I said, eventually with low cost, sequencing is the future.

Autosomal results tend to be fairly the same from what I've been told. So I guess that's all you need to determine ancestry. But one thing that bugs me is how are they able to read such small percents, like 0.1% of an ancestry. Is there high confidence in that regard to traces?

 

[LeBrok]

Autosomal results tend to be fairly the same from what I've been told. So I guess that's all you need to determine ancestry. But one thing that bugs me is how are they able to read such small percents, like 0.1% of an ancestry. Is there high confidence in that regard to traces?

I might be wrong, but I understood that by measuring 0.2% of DNA, they are able to determine alleles of the functional genes. Though probably roughly. So let's say that they can determine most forms of your functional genes by measuring only 0.2% of all DNA base pairs. IIRC the coding genes are only 2% of all DNA information, rest is the "junk" DNA. So it looks like they measure 10% of every gene to determine alleles. By nailing exact alleles they can extrapolate this info on ancestry.

 

[Salento]

I might be wrong, but I understood that by measuring 0.2% of DNA, they are able to determine alleles of the functional genes. Though probably roughly. So let's say that they can determine most forms of your functional genes by measuring only 0.2% of all DNA base pairs. IIRC the coding genes are only 2% of all DNA information, rest is the "junk" DNA. So it looks like they measure 10% of every gene to determine alleles. By nailing exact alleles they can extrapolate this info on ancestry.

Speculating.
The Dodecanese in the southeastern Aegean Sea, which together with the surrounding islets were ruled by the Kingdom of Italy from 1912 to 1943.
In some of this Islands the Sailors of the Italian Navy Outnumbered the Locals.
That's 30 years of Italian Occupation in the Dodecanese. (Recent Genetic Exchange)
Now DNA results can get confusing. Greeks pass for Italians, and Italians pass for Greeks.
Standard Autosomal DNA Data is not sufficient. Other patterns are needed to figure out who's who, So the more Data is available the better.

 

[Jovialis]

Here's an interesting blog that talks a little bit about the science behind sequencing.

https://blog.insito.me/your-dna-from-spit-in-a-tube-to-traits-in-an-app-60407388d507

At Insitome, we work to design storytelling experiences about your DNA; what we call the “Story of You”. To begin this genetic story, you send a saliva kit to the Helix lab. Although your responsibility as the end user stops there, your DNA continues on a futuristic journey from the tube to your account, where it transforms from molecule to digital information. This post will discuss the methods and science that make this possible, and kickoff a series about genomics that hopefully intrigues new users and scientists alike.
The exome

After a Biology 101 course or some Wikipedia wormholes starting with genetics, you will learn that not all of your genome has a known function. In fact, current genetics research has determined that only a small piece — around 1.5 percent — of the genome is translated. The proteins that your cells translate from these portions of your DNA compose your physical traits. In genomics, these portions are collectively called the “exome”, short for “exons in the genome”.

When you order from Insitome, your whole exome is sequenced, and then the traits we deliver are the interpretations of segments of your digitized exome. Receiving exome sequencing is the cutting edge of consumer genomics technology: 30 million DNA bases directly relevant to translation, allowing the usefulness of your DNA to grow alongside new scientific breakthroughs without needing to be re-sequenced. Comparatively, 23AndMe’s chip technique provides around 600 to 700 thousand markers, and adding new markers for new science would require a redesign of the chip and re-sequencing of your sample. More to come in a future blog post on the differences between DNA sequencing techniques and the implications they have for consumer genomics! In summary: your sample is going to receive exome sequencing.

Sequencing in the lab

Like preparing raw ingredients to cook on the stove, the DNA in your saliva needs some preparation before a run in the sequencing machine. After careful handling by a series of robots and lab technicians, preparing your DNA means first extracting it from your cells, fragmenting it, and then amplifying those fragments.

Extraction and purification is an intuitive starting point. By either acoustic or enzyme-based methods, cells are destroyed and the DNA is released.

With the newly exposed DNA comes the opportunity to break it into fragments feasible for the sequencing machine to read. Specifically designed preparation kits for this purpose reduce your DNA into a library of fragments, usually between 150 bases to 250 bases long. While this seems like a lot of fragments, it’s not even close to the amount we need to begin to cover 30 million bases! By amplifying each of the fragments the lab is able to reduce the number of blind spots across the intended genomic regions as well as the quality of machine reading.
With the extraction, fragmentation, and amplification steps completed, your DNA is finally ready for the journey to information. There are many sequencing technologies with different pros and cons in use today. Most exomes are performed on Illumina’s “next generation sequencing” machines. These machines use an incredible approach, in which the fragments that were previously created from your DNA are used as templates for replication. The key difference with the fragments’ machine replicants is that each base is tagged with fluorescent compounds that emit light, and where light signals are around there is data to be found!

From the aligned fragments to your results

When geneticists around the world can all agree that coordinate 11,185,292 on chromosome 1 is a C, some really amazing things begin to happen. The coordinate system gives us a foundation to compare results between populations of individuals, within a family, or two people who want to have a child. It gives us the ability to even compare archaic Neanderthal genomes to those of modern humans. By using this coordinate system to examine and reproduce the results of breakthrough work in your own exome, we are able to weave you into the tales of human history, and deliver on the Insitome mission to tell the Story of You.

 

[Jovialis]

https://www.nature.com/news/the-future-of-dna-sequencing-1.22787

Here's an interesting article on the future of DNA sequencing.

 

[LeBrok]

https://www.nature.com/news/the-future-of-dna-sequencing-1.22787Here's an interesting article on the future of DNA sequencing.

It is a prime example how technology makes everything inexpensive and more democratic. Long live technology!

 

[Jovialis]

It is a prime example how technology makes everything inexpensive and more democratic. Long live technology!

Here's an interesting screen cap from the video Angela shared the other day. It's from when David Reich was talking about new technology being used in genetics. By 2025, computers will be close to as powerful as the human brain.

 

[LeBrok]

Here's an interesting screen cap from the video Angela shared the other day. It's from when David Reich was talking about new technology being used in genetics. By 2025, computers will be close to as powerful as the human brain.

Yes we'll get there, though I think computers will not understand like people right away. They will need very complicated and powerful software to operate on, and this will be a huge mountain to climb even for army of people to write such thing. Probably this complicated electronic brain will need to experience the world like a baby and slowly learn to understand the world by itself, in many aspects of existence. This, most likely, will move the date closer to 2030.
Well, this is of course in general sense of comparison to human brain ability. There are areas where computers are already much better than humans, like calculations, multi spectrum vision, precision, or attention to details and patience in doing tasks. On other hand, there are areas where computer might "never" catch up like feelings of compassion or how to bond and make friends. As long as my robot moves around the house and outside with ease, fixes stuff, cooks, cleans, and understands spoken language, learns new tasks, repeats news from TV, I would say generally we are there, because this is what half of human population can do too. Well, minus the easy stuff like sleeping, drinking, eating, smoking and having sex.