Tuesday, December 27, 2016

Genomics Revisited the Quest for my BRCA

Rosalind Franklin: the scientist who used
X-ray diffraction images to reveal 
the structure of DNA.
My first foray into exploring my genome was through the Genographic Project. Instead of whetting my curiosity, it lit it on fire. I’ve been reading articles and books, and I dream of one day visiting some of these places. (Read More)

My second peek into my genome was for practical purposes. I needed to know whether or not my boobs are going to try to kill me—a question that has haunted me since adolescence. My mom and her mother were both diagnosed with breast cancer in their early forties. My mom was an only child, as was my grandmother. I have no sisters…so 100% of my maternal, female relatives have had breast cancer. Small sampling group, but still—100%.

Breast cancer before menopause is particularly indicative of a genetic issue. There are two well-known genes related to breast cancer BRCA1 and BRCA2 (BReast CAncer). These two genes contain instructions for building proteins that repair or kill cells with damaged DNA in the tissues of the breasts and ovaries. Mutated genes produce weird proteins that can't carry out their jobs properly. If cancer cells appear, they are more likely to grow unchecked.

According to Cancer.gov, 55-65% of women with mutated BRCA1 genes will develop breast cancer by age 70, and/or 39% will develop ovarian cancer by age 70.  The BRCA2 odds are better at 45 percent for breast cancer and 11-17 percent for ovarian cancer by age 70.  (Source)
BRCA1 Protein
Got any damaged cell DNA
for me to repair?

These are all odds. It's all ifs and percent risks—not a diagnosis.

OK. BRCA genes don't cause cancer. I get it.

My doctors and I have discussed genetic testing in depth since I'm approaching the age my mom and grandma were when they got sick. I was on board with the testing, so my doctor sent in a referral and told me where to call.

I put in a call.  A pleasant voice from the Genetic Testing Department of my local hospital explained that prior to being tested, I would meet with a genetic counselor who would chart my family history, and explain to me how genetic testing works. That part costs $250.

Oh, wow, um, OK, go on.

Then I would be tested by a certified lab costing somewhere between $2,000-$5,000.

WTF—a $3,000 price range? Is there a wheel to spin? Wow, OK.

To get the results, I would be required to meet with my assigned genetic counselor for another $150 to explain the implications of my results.

Pleasant Voice Lady asked if I would like to schedule my first counseling session.

I think I'm going to check with my insurance company first.

So I did, and Annoyed Voice Man said, “Nope.”

See! It's right there. Just tell me what it says!
WTF! For $150, science told me that I have Inuit ancestors from Siberia, and that 1.1% of my genome is Neanderthal in origin, but it's going to cost me upwards of $5,000 to find out if two well-known genes can do their job!? Maybe...

Knowing this information already existed due to my participation in the Genographic Project, I went on a quest to get to it. The FDA boob-blocked me the whole way. The Genographic Project referred me to myFamilyTree.com, who is their partner in the project. I transferred my results and looked into the health information they provide. Here is a list: What are Factoid tests? What will I learn?

No cancer results? What? They can tell me if I have the Warrior Gene but not the state of my BRCA1 or BRCA2? I emailed and asked, they said they replied the FDA prohibits them from giving medical advice. Since when is information synonymous with advice? Doesn't advice imply guidance? I don't want advice; I want data.


Next on my list was 23andMe. They provide genetic health reports too. They can tell me if I carry the gene for Cystic Fibrosis, but again, no BRCA1 or BRCA2. I emailed them to make sure I didn't miss it, and they also replied that the FDA prohibits them from giving medical advice.


I found a few more services, Ancestry.com, and myHeritage.com…FDA says NOPE!

I called bullshit.  In June of 2013, the Supreme Court ruled that naturally occurring genes could not be patented, meaning testing for a specific gene couldn't be patented either. Score one for the old guys in robes! This should have led to a rapid drop in the price of genetic testing, but that's not what happened.  The FDA made sure of that.

This led to a FaceBook vent about the injustice of the FDA protecting the monetary interests of those in the medical profession by withholding information that belongs to ME about MY DNA that is a part of MY BODY. Worse, they are blocking this information under the pretext that the average person is too stupid to understand that a defective gene is not a diagnosis and might do something rash… Like what, get a back alley breast removal? Apparently, only the wealthy deserve to know, whereas us plebeians should just get sick and die and decrease the surplus population. (Apologies to Dickens.)

A reply to my FB post from a caring friend brought me back from Angry Injustice Town. Being involved in a medical field, my friend offered some insights and did some substantial research into the topic. During which, she found Color Genomics. Color is a new online genetic testing service that circumvented the FDA blockade by having an in-house doctor order the test, review the results, and offer counseling services.  All of which is included in the $250 price tag. The FDA still blustered when Color launched their service, but had no way to further derail their mission: “Half of the women who carry mutations of these genes don't have the family history that would allow them to get tested,” says Gil. [Color CEO] “This information can help everybody, not just the select few who can pay for it or have insurance coverage.” (Source Article)

As it happened to be Breast Cancer Awareness month, Color was offering a $25 discount. The genetic test would return results about my BRCA genes and 28 other genes known to be associated with hereditary cancers, e.g., melanoma, colo-rectal, and stomach. Here's a full list, 30-Gene Test for Hereditary Cancer Risk, which includes many lesser known genes related to breast cancer as well.

The whole package was less than what was required for my first counseling session!

I ordered the test and submitted my doctors' contact information so they would receive a copy of the results. The box arrived, I followed the directions and popped it back in the mailbox. A few days later, an email arrived stating that the test was received and would be analyzed. Then a week or so later the results were in. Before I even had a chance to log in to see them, my OB/GYN doctor called me to let me know he had received the results. Happy news—my BRCA genes were fine! I logged in and took a look, all 30 genes are happy and productive.

OK. Wow. That was easy and awesome.  This test saved me three doctor appointments and somewhere between two and five thousands dollars.

So Amy, what were you going to do if the test reported a mutation?

Excellent question! My plan was to share that information with my doctors and do what they told me to do, then go home and fix dinner for the family.

I needed to know.

I'm not totally off the cancerous hook. My family history component of cancer is still there. At first, I wondered how something related to family history wouldn't be revealed in my DNA. Then after some reflection, I reasoned that 3.3 billion base pairs is...well…a lot. And we are only starting to understand our genome—there are infinite ways the genes could play against each other. Also, there is a nurture component; if I mimic behaviors that led to my mom's cancer, I elevate my risk factors. So based on my mom and grandma's cancer alone, I will need to continue getting mammograms et. al. even though I am not yet 40 years old. Fine with me. Momentary discomfort is better than being dead.

Also, since all females get two X chromosomes, one from each parent, I have a 50-50 chance of passing a bad one onto my girls, even though it didn't express for me. Luckily they get an X chromosome from their dad too, giving them a 25% risk of inheriting a faulty gene from me. (If I even have one, the only way for me to know would be to test my mom.) When they are grown, it'll be worthwhile for them to get tested too.

To the CEOs of Color:
Thanks Gil.
Thanks Laraki.
You guys rock.

Further Reading:

Press about Color:

Genetics - BreastCancer.org
Excellent breakdown of the genes associated with breast cancer and how they function.

BRCA1 and BRCA2: Cancer Risk and Genetic Testing - Cancer.Gov

Monday, December 5, 2016


This might come as a shock to you, brace yourself—I'm a little bit of a geek. Not a nerd exactly, as they tend to be more academically inclined than I am, whereas I just get super-passionate about something for a while. The more irrelevant it is to my daily life, the more I seem to enjoy immersion in the topic. Lately, that topic has been DNA.

If you and I are FaceBook friends, you probably already know a little bit about this already.

I’ve had my DNA tested twice.  For the first test, I signed up for The Genographic Project to slake my curiosity about my family heritage.  For the second, I used Color Genomics service to find genetic mutations that are linked to cancers and other diseases. (Read More)  Just to end the suspense: “No mutations were identified.”  Woo hoo! Light me up a cigarette, pass me some red meat, and let me slather on some aluminum-based deodorant. Hoo yeah, that felt good.


Anthropology and Human Migrations
In addition to my personal family heritage, I also have a lingering interest in Anthropology that evolved into an interest in understanding the waves of people migrating out of Africa into Asia and Europe, and finally into Australia (about 50,000 years ago) and the New World at the end of the Pleistocene (about 12,000 years ago).

*Breathe Amy *

To make a very long story short, early migrations washed proto-humans in, stranding them in human tide pools for hundreds of thousands of years.  This left the early humans (likely Homo heidelbergensis) to become Neanderthals and Denisovans, and other yet-to-be-discovered species.  Then waves of modern humans emerged from Africa, starting about 60,000 years ago, and flooded them out.

Sitting in Anthropology 101 back in ‘99, our professor told us of two theories behind the extinction of Neanderthals: 
  1. War: Modern humans, equipped with their superior numbers and intellect, actively fought and killed the Neanderthals and/or passively out-competed them for resources. 
  2. Love: Modern humans interbred with the Neanderthals and overwhelmed their phenotype through greater numbers. 
Although War was the generally accepted theory, he favored the Love theory.

About ten years later, DNA evidence would prove him right, at least partially. Neanderthal numbers had already been declining at the end of the Pleistocene, but modern humans and Neanderthals co-existed for around 20,000-30,000 years before the last of the Neanderthals disappeared around 40,000 years ago. Today, traces of Neanderthal DNA live on in almost all people of European descent. My results show that 1.1 percent of my DNA is Neanderthal in origin. They weren't wiped out, they were absorbed. Ah, la'more.

"Dad, what are we?"
My Family Heritage
As a kid, I'd often ask my dad, “What are we?” The story goes that our family began from a soldier in Lafayette's army, (I'm unclear as to whether the soldier was  French or American) and a Native American woman. In the 200ish years since that time, his heritage came to also include Scotch-Irish, (whatever that means) and English on his father's side, and German from his mother. She was born from immigrant parents.

On the other side of my family bramble, my mom had no idea about her heritage. She had never met her father, so other than “some French” heritage from her mother, she had no clue from whence she came.

Aside from our music, American culture basically consists of a penchant for being overweight consumers fast food, lattes, and Ikea shelving. This always bothered me. I want to know what pockets of the world have vestiges of my roots. Where did I come from? Who are my people? What are our stories? How am I connected?

I ordered my DNA testing kit for my birthday last year. With dancing feet, I opened it, and read and re-read the directions. I registered my kit online, then swabbed my cheek, packaged it back up, and dropped it in the mailbox. Like Raphie from A Christmas Story, I checked my electronic mailbox daily for updates. Unlike Raphie, my decoded genome did not tell me to drink my Ovaltine. The results were fascinating and surprising. My dad’s family story was vindicated (see the 2% Native American) and the mystery of my mother’s revealed.

Here is a snapshot:
What surprised me the most was how blobby and undefined the regions are. There are no crisp lines delineating heritage of particular countries. Apparently, you can't put borders on love.  Check out the "Southern Europe" region:  that's a big part of the map.  Humm, looks somewhat similar to many of the Roman Empire maps...

Also, check out the Siberian Region. These people were roaming this gigantic polar region sharing DNA long enough to create distinct markers unique to this population. That then somehow came to comprise 5% of my DNA—have Eurasian Inuit DNA? Sweet!

I just found out that it is likely that my Siberian and Native American markers originated from the same woman who married the soldier of my family's lore. DNA was extracted from a baby who was determined to be of the Clovis people.  They are thought to be among the first to cross the landbridge to North America during the ice age.  The child's DNA shows Siberian markers and DNA common to 80% of Native American tribes.  (The article.)

My ancestors were there, walking across a land bridge that would be swallowed by the rising seas into a land where no other humans lived. There they lived for almost 13,000 years until a woman fell in love with a European soldier, married, and raised a family.

I can also see a map my maternal ancestors took out of Africa as revealed through mitochondrial DNA, which is only passed through mothers. So freaking cool. The deep paternal roots are only available on the Y chromosome so my brother would need to do the test to find our migratory paths of our paternal line.

What was also interesting is that I could compare my results with a genetic breakdown of average people who are from those areas. Over half of my DNA markers originated in Great Britain and Ireland. But, it shows that average British natives only have a slightly higher percentage of genetic markers that originated in Britain. Contained in their DNA, is physical evidence of the historical mixing during the era of the Roman Empire and the later the settlements (and invasions) by Saxons, Vikings, and Normans (and others) during the Early Middle Ages appropriately coined the Migration Period.

Learning about history is so much more engaging knowing that my ancestors were living (surviving) and raising their families during these times.

It also shows me just how ridiculous racism is. Aside from some remote tribes in deep forgotten parts of the world, there are no pure races. The angriest KKK members, or other rampaging terrorist cells, likely share lineage with groups they persecute. If Hitler's DNA is similar to the average German native today, at least 5% of his DNA was of Jewish origin.  In fact, we're all a little more closely related than we should be—several times during our prehistory we experienced what scientists call a "population bottleneck" meaning we narrowly avoided extinction and barely maintained a minimum viable population.

We are all one big inbred family.

The other thing that struck me is the incredible luck involved with any of us being here. Each one of the seven billion of us descended from an unbroken line from the first life form on earth. Every one of our ancestors survived every cataclysmal event, disease, random accident, act of violence, predation, floods, fires, giant dinosaur feet… We are the result of an unbroken line extending back 3.8 billion years and all of that is still with us, written in 3.3 billion base pairs that comprise the human genome.

There are no lines.
Our very existence is a miracle.
We are all interconnected through time and space and love.

Sources and Further Reading:

DNA traces Native Americans’ ancestry to Siberia - PBS Newshour

The Human Genome Project - Genome.Gov

National Geographic Genographic Project

Genghis Khan Effect - Nature.Com

Close Calls: Three Times When Humanity Barely Escaped Extinction - Gizmoto

Human Journey - Featuring Mitochondrial Even and Y Chromosome Adam - National Geographic

Why are we the only human species still alive?  - BBC Earth

Sequencing Neanderthal DNA - Smithsonian


What's in Your Genes?: From the Color of Your Eyes to the Length of Your Life, a Revealing Look at Your Genetic Traits, by Katie McKissick
An exceptionally informative, yet-FUN-to-read book.  She explains what DNA is and how it functions in clear language with pencil illustrations at just the right moments in the text.  She explains base pairs, RNA, mDNA, protein construction and how your genetics are responsible for everything from your eye color to your hairy asscrack.

Saxons, Vikings, and Celts: The Genetic Roots of Britain and Ireland, by Bryan Sykes
A bit of a slog at times as Bryan talks DNA collection procedures, but he makes some interesting points and gives a good overall picture of the genetic composition of Britain and Ireland.

The Sea Wolves: A History of the Vikings  by Lars Brownsworth
Although it could benefit from better organization, the book is fun to read as well as informative.

The Normans: From Raiders to Kings by Lars Brownsworth
A highly readable history of the Normans movements to Britain, which includes their relationship to the Vikings and some of the major players from the Sea Wolves book.