From Spit to SNPs: Decoding My DNA


A few years ago I spit a small amount (about two tablespoons) of my saliva into a specimen collection tube provided in a DNA (deoxyribonucleic acid) testing kit that I ordered through Ancestry.com. My goal was to learn about my ancestors’ through their genealogical beginnings and follow a familial chain of genetic links from generation to generation. Initially, I was disappointed with my scant results and what to me were already obvious findings. That is, that 77 percent of my ancestors originally hailed from Great Britain and Ireland–something I already had discerned from handed down family history and my own 35+ years of genealogical research looking back and identifying family branches across many generations of ancestors. Next came Ancestry.com’s sharing of likely genetic family matches through their own standards for confidence ratings based upon thousands of DNA tests purchased. As the growing number of persons getting tested grew, genetic scientists were busy decoding DNA into SNPs (single nucleotide polymorphisms), which occur normally throughout a person’s DNA. In fact, they occur once in every 300 nucleotides on average, which means there are roughly 10 million SNPs in the human genome.

Recent and rapid scientific, forensic, and technological advances in DNA analysis and the increased understanding and use of these DNA studies has brought forth even more relevant and interesting information about me and my family that goes beyond the former traditional genealogical links to my past.  In fact, studying these SNPs that make up genetic differences has proven to be very important to broadening my understanding of our family’s health issues. These studies also have helped medical geneticists discover how SNPs can help predict individual’s responses to certain drugs, susceptibility to environmental factors such as toxins, and risks of our developing particular diseases. SNPs also can be used to track the inheritance of disease genes within families.  Along this short but fast-paced trek into DNA I have been given new proof of more familial relationships than I had ever been unaware of and have discovered some family members that I hadn’t seen or heard from in years.

Before these new DNA discoveries, when visiting doctors or discussing family health conditions among others, I relied upon personal histories and documentation of conditions, diseases, and  causes of death.  Now, moving forward I can potentially use these new genomic analysis results to look at calculations of risks for genetic health conditions and potentials to increase my quality of life and have a clearer understanding of my inherited conditions and propensities to specific diseases.

So, a few days ago, I simply Googled “advanced analysis of genetic data,” which led me to:  www.impute.me.  Next, I attached my DNA test results from Ancestry.com that I received a couple of years back to their form and emailed them.  Just two days later, free of charge, I received a return email that gave me a web site address so I could download my personal imputed genome analysis file.  They also provided their web site address to modules that would help me explore specific findings of my genome analysis.  Absolutely interesting and amazing data!

On impute’s site appears a GWAS (genome-wide association study) Calculator module, among other modules.  The GWAS module focuses on associations between SNPs and traits like major human diseases. By just entering my assigned unique genome ID, I was able to see if any variant within my SNPs was associated with a trait; in this instance: Acne. The results showed 13 SNPs in my genome (from Navarini AA et al (PMID 24927181), which were reported to be associated with severe Acne.  And, the narrative included a genetic risk score for this trait that “was higher than 36% of the general population. This is a fairly average score.”  The chart below shows 5 of the 13 SNPs examples present in my DNA that present a risk for severe Acne.  I filtered the SNP-score column (fifth column) to display in descending order so you could see my first four SNP scores and reported genes (last column) that resulted in this risk for Acne. Note the fifth row (and, similarly, the remaining 8 rows not shown) indicated a “0” SNP-score.  This is the kind of presentation given throughout this module to describe my risks among about hundred traits provided in the GWAS calculator.

Looking more closely at my GWAS Calculator and appearing before my eyes were confirmations of the presence of specific diseases that exist(ed) among various family members and the higher risk percentages of my having these same diseases. For example, I have a 76 percent higher than the general population risk of being within the Autism spectrum disorder, adhd, bipolar, major depressive disorder, and schizophrenia–some family members have suffered from some of these maladies, but I can’t say that I have personally; a 52% higher than the general population risk of having Cardiovascular Disease; an 82% higher than average risk of food addictions; a 99% higher than average risk of having freckles (if you know me, you know I do or did); then there were the risks of high blood pressure, high cholesterol, asthma and allergies, restless leg syndrome, and hip osteoarthritis (75% higher risk than the general population–all me! And the list continued.

BUT . . . Just how much of who we are, our strengths, capabilities, and limitations is determined by our DNA and genetics?

The newest studies of DNA suggest that both genetic and environmental factors play a role in who I am, what I look like, my singularities or uniqueness, and my biological, mental, intellectual and physical conditions and capabilities.  Studies suggest that multiple genes are involved, so our inheritance patterns are not straightforward. For example:

  • A person’s fingerprints are unique as you know and are based on the patterns of skin ridges (called dermatoglyphs) on the pads of the fingers. Dermatoglyphs develop before birth and stay the same throughout life. The ridges begin to develop during the third month of fetal development, and they are fully formed by the sixth.The basic size, shape, and spacing of dermatoglyphs seem to be influenced by genetic factors. Studies suggest that multiple genes are involved, so an inheritance pattern is not straightforward.
  •  A child’s eye color often can be predicted by the eye colors of his or her parents and other relatives.   In fact, both my parents and my siblings have blue eyes; my grandparents had blue eyes; and most of my aunts, uncles, and cousins (direct relatives) have blue eyes.   Yet, genetic variations sometimes produce unexpected results.  There are several disorders that can affect the color of our eyes.  One of these examples is ocular albinism characterized by severely reduced pigmentation of the iris.  This causes very light-colored eyes and significant problems with vision.
  • Another condition called oculocutaneous albinism affects the pigmentation of the skin and hair in addition to our eyes. Both ocular albinism and oculocutaneous albinism result from mutations in genes involved in the production and storage of melanin.
  • Hand preference is the tendency to be more skilled and comfortable using one hand instead of the other for tasks such as writing or throwing a ball. It was initially thought that a single gene controlled handedness. However, more recent studies suggest that multiple genes, perhaps up to 40, contribute to this trait. Although the percentage varies by culture, in Western countries 85 to 90 percent of people are right-handed and 10 to 15 percent of people are left-handed and then there are those who have this uncommon trait and are known to be ambidextrous.  They interchange hand preferences depending upon a task.  All the people in my family are right-handed–except for me!  I may have been right-handed at birth, but when I was 18 months old I received second and third degree burns all over my body from a spill of hot bacon grease.  The only part of me that wasn’t bandaged for months on end was my left hand.  I guess like other creatures, I adapted to my situation.  Or, just maybe my left-hand preference is related to differences between my right and left halves (hemispheres) of my brain. Our right hemisphere controls movement on the left sides of our body, while the left hemisphere controls movement on the right sides of our body.  These same studies on hand preference suggest that at least some of these genes help determine the overall right-left asymmetry of the body starting at our earliest stages of development.
    • For example, the PCSK6 gene has been associated with an increased likelihood of being right-handed in people with the psychiatric disorder schizophrenia. Another gene, LRRTM1, has been associated with an increased chance of being left-handed in people with dyslexia (a condition caused by a defect in the brain’s processing of graphic symbols and causes difficulty with reading and spelling).

Is the probability of having twins determined by genetics?

The likelihood of conceiving twins is a complex trait. It is probably affected by multiple
genetic and environmental factors, depending on the type of twins. The two types
of twins are classified as identical and fraternal.  My genealogical research shows twins and even triplets go back generations on both my paternal and maternal sides of my family.  My maternal great-grandmother had three sets of twins among the 13 children she birthed –extremely rare and perhaps unprecedented.  And, yes, I am happy to say that our grandson is a fantastic father of 5-year-old twins – a girl and a boy.

So, did I get my blue eyes and freckles from my mother or my dad? Where did I get my fearless personality and the absence of a talent for singing, as much as I love to sing? Did my intellect come from my mom’s two X chromosomes, or was it predetermined by my genes? It’s still not clear to me how many of my physical characteristics are purely hereditary, and my genetic waters get even murkier when it comes to nature vs. nurture factors like behavior, intelligence, and personality. This argument has never really been won.  So, let’s leave it at this:  we do not yet know how much of what we are is determined by our DNA and how much is contributed by our life experiences. But we do know that DNA and life experiences each plays a part.

 

‘Great Surprise’—Native Americans Have West Eurasian Origins


November is National Native American Heritage Month.  In honor of this occasion, below I share with you National Geographic’s article from November 2013:

“Great Surprise”—Native Americans Have West Eurasian Origins

Photo of a Native American mounted on his horse.

Native Americans may have a more complicated heritage than previously believed.

PHOTOGRAPH BY ROLAND W. REED, NATIONAL GEOGRAPHIC

Brian Handwerk

National Geographic

PUBLISHED NOVEMBER 20, 2013

Nearly one-third of Native American genes come from west Eurasian people linked to the Middle East and Europe, rather than entirely from East Asians as previously thought, according to a newly sequenced genome.

Based on the arm bone of a 24,000-year-old Siberian youth, the research could uncover new origins for America’s indigenous peoples, as well as stir up fresh debate on Native American identities, experts say.

The study authors believe the new study could also help resolve some long-standing puzzles on the peopling of the New World, which include genetic oddities and archaeological inconsistencies. (Explore an atlas of the human journey.)

“These results were a great surprise to us,” said study co-author and ancient-DNA specialist Eske Willerslev, of the University of Copenhagen, Denmark.

“I hadn’t expected anything like this. A genome related to present-day western Eurasian populations and modern Native Americans as well was really puzzling in the beginning. How could this happen?”

So what’s new?

The arm bone of a three-year-old boy from the Mal’ta site near the shores of Lake Baikal in south-central Siberia (map) yielded what may be the oldest genome of modern humans ever sequenced.

DNA from the remains revealed genes found today in western Eurasians in the Middle East and Europe, as well as other aspects unique to Native Americans, but no evidence of any relation to modern East Asians. (Related: “Is This Russian Landscape the Birthplace of Native Americans?”)

A second individual genome sequenced from material found at the site and dated to 17,000 years ago revealed a similar genetic structure.

It also provided evidence that humans occupied this region of Siberia throughout the entire brutally cold period of the Last Glacial Maximum, which ended about 13,000 years ago.

Why is it important?

Prevailing theories suggest that Native Americans are descended from a group of East Asians who crossed the Bering Sea via a land bridge perhaps 16,500 years ago, though some sites may evidence an earlier arrival. (See “Siberian, Native American Languages Linked—A First [2008].”)

“This study changes this idea because it shows that a significant minority of Native American ancestry actually derives not from East Asia but from a people related to present-day western Eurasians,” Willerslev said.

“It’s approximately one-third of the genome, and that is a lot,” he added. “So in that regard I think it’s changing quite a bit of the history.”

While the land bridge still formed the gateway to America, the study now portrays Native Americans as a group derived from the meeting of two different populations, one ancestral to East Asians and the other related to western Eurasians, explained Willerslev, whose research was published in the November 20 edition of the journal Nature.

“The meeting of those two groups is what formed Native Americans as we know them.” (Learn more about National Geographic’s Genographic Project.)

What does this mean?

Willerslev believes the discovery provides simpler and more likely explanations to long-standing controversies related to the peopling of the Americas.

“Although we know that North Americans are related to East Asians, it’s striking that no contemporary East Asian populations really resemble Native Americans,” he said.

“It’s not like you can say that they are really closely related to Japanese, Chinese, or Koreans, so there seems to be something missing. But this result makes a lot of sense regarding why they don’t fit so well genetically with contemporary East Asians—because one-third of their genome is derived from another population.”

The findings could also allow reinterpretation of archaeological and anthropological evidence, like the famed Kennewick Man, whose remains don’t look much like modern-day Native American or East Asian populations, according to some interpretations.

“Maybe, if he looks like something else, it’s because a third of his ancestry isn’t coming from East Asia but from something like the western Eurasians.” (Read about history’s great migration mysteries.)

What’s next?

Many questions remain unanswered, including where and when the mixing of west Eurasian and East Asian populations occurred.

“It could have been somewhere in Siberia or potentially in the New World,” Willerslev said.

“I think it’s much more likely that it occurred in the Old World. But the only way to address that question would be to sequence more ancient skeletons of Native Americans and also Siberians.”

Intriguing questions also exist about the nature of the advanced Upper Paleolithic Mal’ta society that now appears to figure in Native American genomes.

The Siberian child “was found buried with all kinds of cultural items, including Venus figurines, which have been found from Lake Baikal west all the way to Europe.

“So now we know that the individual represented with this culture is a western Eurasian, even though he was found very far east. It’s an interesting question how closely related this individual might have been to the individuals carving these figurines at the same time in Europe and elsewhere.”