{"cache":{"posts_f30bc_5ded6":{"__typename":"RootQueryToPostConnection","nodes":[{"__typename":"Post","id":"cG9zdDoyMjY2Nw==","databaseId":22667,"featuredImage":null,"author":null,"date":"2015-07-21T06:00:06","uri":"/articles/whats-your-type","title_b28e9_bf21a":"What’s Your Type?","slug":"whats-your-type","categories_3cd3e_bf21a":{"__typename":"PostToCategoryConnection","edges":[{"__typename":"PostToCategoryConnectionEdge","node":{"__typename":"Category","id":"dGVybToz","name":"23andMe and You","slug":"23andme-and-you","uri":"/category/23andme-and-you","seo":{"__typename":"TaxonomySEO","title":"23andMe and You Archives - 23andMe Blog","opengraphTitle":"23andMe and You Archives","metaDesc":"23andMe and you show you how to get more out of your 23andMe experience, and tips for using features and tools.","opengraphDescription":"23andMe and you show you how to get more out of your 23andMe experience, and tips for using features and tools.","fullHead":"\n\n\n\n\n\n\n\n\n\n\n\n\n\n"}}},{"__typename":"PostToCategoryConnectionEdge","node":{"__typename":"Category","id":"dGVybTo3","name":"genetics 101","uri":"/category/23andme-and-you/genetics-101","slug":"genetics-101"}}]},"imageOptions":{"__typename":"Post_Imageoptions","featuredImageSquare":{"__typename":"MediaItem","id":"cG9zdDoyMDU3","mediaDetails":{"__typename":"MediaDetails","sizes_cad4b_bf21a":[{"__typename":"MediaSize","name":"thumbnail","sourceUrl":"https://blog-api.23andme.com/wp-content/uploads/2008/11/istock_000000628100xsmall-150x150.jpg"},{"__typename":"MediaSize","name":"medium","sourceUrl":"https://blog-api.23andme.com/wp-content/uploads/2008/11/istock_000000628100xsmall-300x225.jpg"},{"__typename":"MediaSize","name":"square_sm","sourceUrl":"https://blog-api.23andme.com/wp-content/uploads/2008/11/istock_000000628100xsmall-271x271.jpg"},{"__typename":"MediaSize","name":"square_md","sourceUrl":"https://blog-api.23andme.com/wp-content/uploads/2008/11/istock_000000628100xsmall-372x300.jpg"},{"__typename":"MediaSize","name":"wide_sm","sourceUrl":"https://blog-api.23andme.com/wp-content/uploads/2008/11/istock_000000628100xsmall-271x149.jpg"},{"__typename":"MediaSize","name":"wide_md","sourceUrl":"https://blog-api.23andme.com/wp-content/uploads/2008/11/istock_000000628100xsmall-372x204.jpg"}],"height":300,"width":400},"mediaItemUrl":"https://blog-api.23andme.com/wp-content/uploads/2008/11/istock_000000628100xsmall.jpg","sourceUrl_772ce_bf21a":"https://blog-api.23andme.com/wp-content/uploads/2008/11/istock_000000628100xsmall.jpg"},"singleTemplateFeaturedImage":"default"},"content_b28e9_bf21a":"

We are all unique, and knowing our genotypes at specific places in our genomes may give each of us a better understanding as to why. $\"\"$
\nwith an alphabet made up of just four letters – A, T, C and G.

Those four letters represent the nucleotide bases – adenine, thymine, cytosine and guanine – that are the building blocks of life. The sequence of A’s, T’s, C’s and G’s run in long stretches of code that instruct the way the human body is built and functions.

In 2003 after ten years and $3 billion, scientists decoded the first sequence of a human genome. Since then costs have dropped for sequencing a genome to as low as $1,000. While very inexpensive in comparison, it would still be prohibitive for most consumers to have their full genome sequenced.

So how is 23andMe able to provide genetic data to so many people at an affordable price in just a matter of weeks?

The secret lies in a process called “SNP genotyping.”

If you compared two unrelated individuals, you would find that their genetic sequences are about 99.9 percent the same. It is that miniscule variation in their genome that makes all the difference. It’s what makes us each unique.

That small variation is also the key to how 23andMe can efficiently and cost-effectively deliver its service. Scientists have identified the known variation among individuals, specifically locating in the human genome where a single letter differs from one person to the next.

These one-letter variations are called single nucleotide polymorphisms, or SNPs (pronounced “snips”), and they are associated with differences in everything from the color of our eyes, to our risks for certain health conditions, and information about the makeup of our ancestry.

Let’s look at an example of a SNP.

Say a certain percentage of people have a specific stretch of DNA code that reads ATGCCCGT, but everyone else has the sequence ATGCACGT along that same stretch.

The nucleotide bases come in pairs, so in this case the difference is between whether a person is CC or AC at this position. $\"Image$

Since these two letters are known to vary among individuals, we would call this position in the sequence a SNP. The difference between two people at a single position – whether you are CC or AC in this case – is also referred to as the genotype for that SNP. Some of those differences may have no effect, some could be beneficial and some could be deleterious.

The benefit or harm of one version or the other can even change depending on one’s environmental surroundings. 23andMe provides individuals with information on hundreds of thousands of these SNPs.

To do that, 23andMe first has to extract DNA from saliva submitted by a customer. Once the DNA is extracted, it is amplified many times so that there is enough DNA to analyze. The amplified DNA is then cut into smaller pieces and washed over a microarray chip.

This genotyping chip contains thousands and thousands of tiny probes that are designed to detect specific bits of DNA. Each probe on the chip contains a bit of DNA that matches a genetic variant of interest. Remember the nucleotide bases always come in pairs, an A always pairs with T, while a G pairs with C. On the microarray chip, when a piece of DNA finds its complementary probe, it will stick to it.

These probes are triggered to glow in a way that indicates which version of each SNP is present in the sample. That fluorescent signal is read by a computer, and the data is then uploaded to the customer’s 23andMe account. $\"image$

Our customers have the ability to view this raw data in a feature called Browse Raw Data.

Our latest genotyping chip, v4, is unlike any of our previous genotyping platforms. Previous genotyping platforms included standard probes included by Illumina, the manufacturer of the chip, as well as additional probes selected by 23andMe.

The v4 chip, consists of a completely custom panel of probes that were hand picked by our researchers. Although our current genotyping chip contains about half a million SNPs (whereas the entire human genome has around 10 million SNPs), we can learn a lot about the human genome simply by looking at these locations where individual genotypes are known to differ. Full genome sequencing provides information on all 3 billion markers in the entire human genome, however it is difficult to predict when full sequencing will be available at an affordable price point for the general public.

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This interview is part of an occasional series of profiles introducing you to the people behind 23andMe’s compelling research. In his $\"Arnab$ previous scientific life, Arnab Chowdry received a SmileTrain grant for his work with Dr. Simeon Boyadjiev at the Johns Hopkins Children’s Hospital to determine the disease-causing loci for rare genetic diseases such as oculodentodigital dysplasia, which causes abnormalities to many parts of the body particularly the eyes, teeth or fingers.

At 23andMe, Arnab is responsible for designing and establishing the analytical validity of our genotyping chip.\n

\n“We don’t just want to learn about genetics. We want to make genetics useful.”\n

\nHow did you become excited about genetics?

\nI’ve been interested in genetics since high school. At that time, the human genome sequence was yet to be completed and I wondered why it was such a complicated problem. Being young, I had some very naive ideas about how we could improve the science.\n

\nDuring college, I was involved in research at Johns Hopkins which looked at rare variants. That introduced me to the common frustrations in the field of genetics at that time. There was a lot of noise around the publication of the first human genome, but practically it didn’t help my research. The genome was a draft and the region I was investigating was still largely unknown. To really advance medicine, we needed a faster way to assay mutations than what was available at the time.\n

\nAfter grad school, I came across 23andMe and thought, “if there’s any company that can realize these ideas, this is the one.” I had been in academics for years and had grown used to the hymn of “this new finding could be medically useful, in ten years.” Researchers get grants based around the potential to improve our lives but publications rarely connect their findings to a medical use case.

23andMe is different; we are working to make genetics useful today.\n

Arnab Chowdry, Sr. Manager of Research Engineering

\nOriginally from: Rochester, NY

\nBS/A: Johns Hopkins University

\nPhD: Biophysics from the University of California, Berkeley

\nFun Fact: I like building things and breaking things.

\nTell us about a recent breakthrough in genetics research that you think will have a big impact.

\nNext-generation sequencing is the breakthrough I’ve been waiting for. Currently, the genetic testing industry is very segmented. We have individual tests for the conditions we understand, but they’re slow, expensive, and their accuracy is poorly determined.

FDA-approved next-generation sequencing won’t replace all genetic tests, but it will commoditize a chunk of the industry, pushing consumers and physicians to evolve.

Reduced cost, improved accuracy and the establishment of new technologies is moving the needle both for clinical testing and research. (23andMe currently does genotyping, which tells customers your genotype at a certain subset of locations in your DNA. Full-genome sequencing tells you your genotype at every position.)\n

\nWhat interesting thing have you learned about yourself from being tested?

\nEven though I work for 23andMe as a scientist and engineer and I analyze genetic data for a living, up until 2012, my work had always been abstract. I never expected life-altering information to come out of my personal genetics. Then I found out that I carry a mutation in the MYBPC3 gene that is associated with familial hypertrophic cardiomyopathy (HCM). South Asians that carry this mutation are at greatly increased risk for HCM.

Since then, I’ve talked to my family, visited doctors and specialists and changed my exercise routine.

I’ve also worked with other researchers to uncover the biological ramifications of the genetic mutation and presented the findings at a national meeting of geneticists. You can read more about my experience here.\n

\nWhat’s one thing the average person should know about genetics?

\nPeople believe genetics to be more deterministic than it is. In fact, there is no “genes vs. environment” debate. Researchers understand that most complex diseases and traits are determined by a combination of genetic and environmental factors, neither of which should be ignored. If we — and our physicians — can take that view, it will help us to better understand ourselves and improve our lives.

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23andMe will soon be genotyping customers with a newly designed custom microarray chip. $\"an$

The new version – along with completion of additional lab space – will ultimately improve both the efficiency and speed by which we will be able to process samples and then return genetic data to our customers.

Custom Chip

Unlike previous changes to our chip, this new version, dubbed v4, consists of a fully custom panel of probes for detecting single nucleotide polymorphisms (SNPs) selected by our researchers. The selection was made to maximize the number of actionable health and ancestry features available to customers as well as offer flexibility for future research.

Unlike previous changes to our chips, this one will not significantly alter what is reported to customers, so there would be little reason to retest on the latest platform.

The new chip includes both common variants that provide genome-wide coverage and rare variants. Rare variants are found in certain medically relevant genes and exons. Researchers also ensured that the chip covers SNPs with known disease associations. In addition the chip has variants that are known to be involved with drug metabolism and side effects.

The New V-4 Chip

In addition, v4 includes SNPs that our researchers use to assign genetic ancestry. They use autosomal DNA markers as well as variants in both mitochondrial DNA and in the Y chromosome. The custom chip will also allow our researchers to better impute many variants present on larger chips. Imputation is a powerful statistical method allowing researchers to fill in missing data.

Researchers use publicly available full-sequence data and 23andMe’s own data to impute the genotype at specific locations.

The new chip was designed to be compatible with all our current features. However there may be some small differences in some reports. 23andMe will inform our customers of those differences in community posts.

If you haven’t seen it already, the video below fills you in on how a sample is processed at the lab.

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$\"labtechs\"$

Curiosity. The desire to be informed and healthier. The need to know ourselves and our histories better.

Whatever your reason is for joining 23andMe, we make it pretty simple. Order a kit, create an account, spit in a tube, and mail it back.

In just a few weeks, you log on to the website and learn what your DNA says about your health, ancestry, and traits. But how do we get all of that information from just a little bit of spit?

A lot goes on at the lab to turn the contents of that tube into the genetic data you see on the screen. Technicians inspect your tube to check for obvious problems like leaks. Then they extract the DNA out of cells in the saliva and make sure there’s enough DNA to analyze. (If there isn’t, you’re given another kit to spit again.)

Once the DNA is out, it’s broken up and “amplified” — a little bit of DNA becomes a lot of DNA. That DNA is then spread onto a custom chip that allows us to read out your genetic data at hundreds of thousands of places in the genome, places that contain information about our health and ancestry.

For a behind the scenes look at what happens at the lab, check out our video:

\n","seo":{"__typename":"PostTypeSEO","title":"Behind the Scenes at the Lab - 23andMe Blog","opengraphTitle":"Behind the Scenes at the Lab","metaDesc":"","opengraphDescription":"See what happens to your saliva sample at our partner laboratory. A new video shows the finely tuned process that turns the DNA in your saliva into the genetic information you see when you log in to your account at 23andMe.","fullHead":"\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\t\n\t\n\t\n\n"},"title_b28e9_bf21a":"Behind the Scenes at the Lab","date":"2013-06-06T09:00:28","imageOptions":{"__typename":"Post_Imageoptions","singleTemplateFeaturedImage":"default","featuredImageSquare":null},"featuredImage":null,"tags_67cce_bf21a":{"__typename":"PostToTagConnection","edges":[{"__typename":"PostToTagConnectionEdge","node":{"__typename":"Tag","id":"dGVybTo0NzY=","name":"genotyping","uri":"/tag/genotyping","seo":{"__typename":"TaxonomySEO","title":"genotyping Archives - 23andMe Blog","opengraphTitle":"genotyping Archives","metaDesc":"","opengraphDescription":"","fullHead":"\n\n\n\n\n\n\n\n\t\n\t\n\t\n\n\n\n"}}},{"__typename":"PostToTagConnectionEdge","node":{"__typename":"Tag","id":"dGVybToyMDA4","name":"lab","uri":"/tag/lab","seo":{"__typename":"TaxonomySEO","title":"lab Archives - 23andMe Blog","opengraphTitle":"lab Archives","metaDesc":"","opengraphDescription":"","fullHead":"\n\n\n\n\n\n\n\n\t\n\t\n\t\n\n\n\n"}}},{"__typename":"PostToTagConnectionEdge","node":{"__typename":"Tag","id":"dGVybToyMDA5","name":"saliva sample","uri":"/tag/saliva-sample","seo":{"__typename":"TaxonomySEO","title":"saliva sample Archives - 23andMe Blog","opengraphTitle":"saliva sample Archives","metaDesc":"","opengraphDescription":"","fullHead":"\n\n\n\n\n\n\n\n\t\n\t\n\t\n\n\n\n"}}}]},"databaseId":18411,"author":null,"slug":"behind-the-scenes-at-the-lab"},{"__typename":"Post","id":"cG9zdDoyMTU=","databaseId":215,"featuredImage":null,"author":null,"date":"2008-05-03T20:08:53","uri":"/articles/23andme-genotyping-technology-aces-independent-tests","title_b28e9_bf21a":"23andMe Genotyping Technology Aces Independent Tests","slug":"23andme-genotyping-technology-aces-independent-tests","imageOptions":{"__typename":"Post_Imageoptions","featuredImageSquare":null,"singleTemplateFeaturedImage":null},"categories_3cd3e_bf21a":{"__typename":"PostToCategoryConnection","edges":[{"__typename":"PostToCategoryConnectionEdge","node":{"__typename":"Category","id":"dGVybTo5","name":"News","slug":"news","uri":"/category/news","seo":{"__typename":"TaxonomySEO","title":"News Archives - 23andMe Blog","opengraphTitle":"News Archives","metaDesc":"23andMe News are blog post where our research or innovative products have pushed new boundaries that are worth sharing and make news.","opengraphDescription":"23andMe News are blog post where our research or innovative products have pushed new boundaries that are worth sharing and make news.","fullHead":"\n\n\n\n\n\n\n\n\n\n\n\n\n"}}}]},"content_b28e9_bf21a":"

$\"illuminachip.png\"$ Sometimes our customers ask us about the accuracy of their 23andMe data. How certain are we that they really do have the genotypes we report?

The answer is, very certain. We typically claim that the genotyping technology we use reports the correct call for more than 99.9 percent of the approximately 580,000 single-letter DNA variations we report. Those variations, known as single-nucleotide polymorphisms, or SNPs, are the raw data upon which the 23andMe Personal Genome Service is built.

Testing Accuracy

But apparently one of our customers decided to do more than ask. He designed a simple experiment to test the reproducibility of the SNP chips that 23andMe and other companies use to give people access to their genetic data.

Antonio C.B. Oliveira signed himself up for 23andMe and a similar service, then wrote a computer program to compare the genotype calls at the 560,299 SNPs where both companies reported data. He found a grand total of 23 discrepancies, or about 0.004% of the common reported SNPs.

“This error rate seems to me to be quite acceptable,” Oliveira concluded on Longa Vista, a blog he established to share his results.

Another Comparison

Oliveira is actually the second customer to conduct such an experiment. When Ann Turner compared two datasets for the same person (not herself) back in January, she discovered 35 discrepancies.

And when Craig Venter and his colleagues published his full genome last October, they also found the discrepancies between their own sequencing results and two different SNP genotyping platforms to be negligible.

We aren’t surprised — these results confirm experiments that 23andMe performed before launching our Personal Genomics Service last year. But now 23andMe can say with confidence that independent testing has shown that the Illumina genotyping technology we use is extremely robust.

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23andMe Genotyping Technology Aces Independent Tests

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