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.

 

John Rolfe Letter to Governor Thomas Dale, 1614


marriage-of-john-rolfe-and-pocahontas

Wedding of John Rolfe and Princess Pocahontas,  April 5, 1614

Continuing to further document and understand the lives of our earliest ancestors – emigrants from England to Jamestown, Virginia, I have included below, the 1614 letter  (transcribed and updated to today’s word usage and spellings by me–I made no changes to word choices or punctuation and kept present day English spellings).  My  11th great-grandfather, John Rolfe, (English Explorer), penned this letter to Sir Thomas Dale, then Governor of the Jamestown Colony.  In this deeply moving and revealing letter, John Rolfe asks permission to marry Princess Pocahontas, daughter of Indian Chief Powhatan, who presided over the Powhatan Empire until his death in 1618. If you would like to see the online letter with 400 year-old English words and spellings, please visit  “Virtual Jamestown’s” site .

Honourable Sir, and most worthy Governor:

When your leisure shall best serve you to peruse these lines, I trust in God, the beginning will not strike you into a greater admiration, than the end will give you good content. It is a matter of no small moment, concerning my own particular, which here I impart unto you, and which toucheth me so dearly, as the tenderness of my salvation. Howbeit I freely subject myself to your grave and mature judgment, deliberation, approbation, and determination; assuring myself of your zealous admonitions, and godly comforts, either persuading me to desist, or encouraging me to persist therein, with a religious and godly care, for which (from the very instant, that this began to root itself within the secret bosom of my breast) my daily and earnest prayers have been, still are, and ever shall be produced forth with as sincere a godly zeal as I possibly may to be directed, aided and governed in all my thoughts, words, and deeds, to the glory of God, and for my eternal consolation. To persevere wherein I never had more need, nor (til now) could ever imagine to have been moved with the like occasion.

But (my case standing as it doth) what better worldly refuge can I here seek, then to shelter myself under the safety of your favourable protection? And did not my ease proceed from an unspotted conscience, I should not dare to offer to your view and approved judgement, these passions of my troubled soul, so full of fear and trembling in hypocrisy and dissimulation. But knowing my own innocence and godly fervor, in the whole prosecution hereof, I doubt not of your benign acceptance, and clement construction. As for malicious depravers, and turbulent spirits, to whom nothing is tasteful but what pleaseth their unsavory palate, I pass not for them being well assured in my persuasion (by the often trial and proving of myself, in my holiest meditations and prayers) that I am called hereunto by the spirit of God; and it shall be sufficient for me to be protected by yourself in all virtuous and pious endeavours. And for my more happy proceeding herein, my daily oblations shall ever be addressed to bring to pass so good effects, that yourself, and all the world may truly say: This is the work of God, and it is marvelous in our eyes.

But to avoid tedious preambles, and to come nearer the matter: first suffer me with your patience, to sweep and make clean the way wherein I walk, from all suspicions and doubts, which may be covered therein, and faithfully to reveal unto you, what should move me hereunto.

Let therefore this my well advised protestation, which here I make between God and my own conscience, be a sufficient witness, at the dreadful day of judgment (when the secret of all men’s hearts shall be opened) to condemn me herein, if my chief intent and purpose be not, to strive with all my power of body and mind, in the undertaking of so mighty a matter, no way led (so far forth as man’s weakness may permit) with the unbridled desire of carnal affection: but for the good of this plantation, for the honour of our country, for the glory of God, for my own salvation, and for the converting to the true knowledge of God and Jesus Christ, an unbelieving creature, namely Pocahontas. To whom my hearty and best thoughts are, and have a long time been so entangled, and enthralled in so intricate a labyrinth, that I was even wearied to unwind myself thereout. But almighty God, who never faileth his, that truly invocate his holy name hath opened the gate, and led me by the hand that I might plainly see and discern the safe paths wherein to trade.

To you therefore (most noble Sir) the patron and Father of us in this country do I utter the effects of this settled and long continued affection (which hath made a mighty war in my meditations) and here I do truly relate, to what issue this dangerous combat is come unto, wherein I have not only examined, but thoroughly tried and pared my thoughts even to the quick, before I could end and fit wholesome and apt applications to cure so dangerous an ulcer. I never failed to offer my daily and faithful prayers to God, for his sacred and holy assistance. I forgot not to set before mine eyes the frailty of mankind, his prones to evil, his indulgence of wicked thoughts, with many other imperfections wherein man is daily ensnared, and oftentimes overthrown, and them compared to my present estate. Nor was I ignorant of the heavy displeasure which almighty God conceived against the sons of Levi and Israel for marrying strange wives, nor of the inconveniences which may thereby arise, with other the like good motions which made me look about warily and with good circumspection, into the grounds and principal agitations, which thus should provoke me to be in love with one whose education hath been rude, her manners barbarous, her generation accursed, and so discrepant in all nature from myself, that oftentimes with fear and trembling, I have ended my private controversy with this: surely these are wicked instigations, hatched by him who seeketh and delighteth in man’s destruction; and so with fervent prayers to be ever preserved from such diabolical assaults (as I took those to be) I have taken some rest.

Thus, when I had thought I had obtained my peace and quietness, behold another, but more gracious temptation hath made breaches into my holiest and strongest meditations; with which I have been put to a new trial, in a straighter manner then the former: for besides the many passions and sufferings which I have daily, hourly, yea and in my sleep endured, even awaking me to astonishment, taxing me with remissness, and carelessness, refusing and neglecting to perform the duty of a good Christian, pulling me by the ear, and crying: why dost not thou endeavour to make her a Christian? And these have happened to my greater wonder, when she hath been furthest separated from me, which in common reason (were it not an undoubted work of God) might breed forgetfulness of a far more worthy creature. Besides, I say the holy spirit of God often demanded of me, why I was created?

If not for transitory pleasures and worldly vanities, but to labour in the Lord’s vineyard, there to sow and plant, to nourish and increase the fruits thereof, daily adding with the good husband in the Gospel, somewhat to the talent, that in the end the fruits may be reaped, to the comfort of the laborer in this life, and his salvation in the world to come? And if this be, as undoubtedly this is, the service Jesus Christ requireth of his best servant: who unto him that hath these instruments of piety put into his hands and wilfully despiseth to work with them. Likewise, adding hereunto her great appearance of love to me, her desire to be taught and instructed in the knowledge of God, her capableness of understanding, her aptness and willingness to receive any good impression, and also the spiritual, besides her own incitements stirring me up hereunto.

What should I do? Shall I be of so untoward a disposition, as to refuse to lead the blind into the right way? Shall I be so unnatural, as not to give bread to the hungry or uncharitable, as not to cover the naked? Shall I despise to actuate these pious duties of a Christian? Shall the base fear of displeasing the world, overpower and withhold me from revealing unto man these spiritual works of the Lord, which in my meditations and prayers, I have daily made known unto him? God forbid. I assuredly trust He hath thus dealt with me for my eternal felicity, and for his glory; and I hope so to be guided by his heavenly grace, that in the end by my faithful pains, and christian-like labour, I shall attain to that blessed promise pronounced by that holy Prophet Daniel unto the righteous that bring many unto the knowledge of God. Namely, that they shall shine like the stars forever and ever. A sweeter comfort cannot be to a true Christian, nor a greater encouragement for him to labour all the days of his life, in the performance thereof, nor a greater gain of consolation, to be desired at the hour of death, and in the day of judgment.

Again by my reading, and conference with honest and religious persons, have I received no small encouragement, besides serena meaconscientia, the clearness of my conscience, clean from the filth of impurity, quo est instar muri chennai, which is unto me, as a brasen wall. If I should set down at large, the prohibitions and godly motions, which have striven within me, I should but make a tedious and unnecessary volume. But I doubt not these shall be sufficient both to certify you of my true intents, in discharging of my duty to God, and to yourself, to whose gracious providence I humbly submit myself, for his glory, your honour, our Country’s good, the benefit of this Plantation, and for the converting of one unregenerate, to regeneration; which I beseech God to grant, for his dear Son Christ Jesus his sake.

Now if the vulgar sort, who square all men’s actions by the base rule of their own filthiness, shall tax or taunt me in this my godly labour: let them know, it is not any hungry appetite, to gorge myself with incontinency; sure (if I would, and were so sensually inclined) I might satisfy such desire, though not without a seared conscience, yet with Christians more pleasing to the eye, and less fearful in the offense unlawfully committed. Nor am I in so desperate a state, that I regard not what becometh of me; nor am I out of hope but one day to see my Country, nor so void of friends, nor mean in birth, but there to obtain a match to my great content: nor have I ignorantly passed over my hopes there, or regardlessly seek to loose the love of my friends, by taking this course: I know them all, and have not rashly overstepped any.

But shall it please God thus to dispose of me (which I earnestly desire to fulfill my ends before set down) I will heartedly accept of it as a godly tax appointed me, and I will never cease, (God assisting me) until I have accomplished, and brought to perfection so holy a work, in which I will daily pray God to bless me, to mine, and her eternal happiness. And thus desiring no longer to live, to enjoy the blessings of God, then this my resolution doth tend to such Godly ends, as are by me before declared: not doubting of your favourable acceptance, I take my leave, beseeching Almighty God to rain down upon you, such plenitude of his heavenly graces, as your heart can wish and desire, and so I rest,

At your command most willing to be disposed of,

John Rolfe


Source:

Jameson, J, Franldin. Narratives of Early Virginia. New York: Charles Scribner’s Sons, 1907. (237-244)

Thanksgiving Invites–Anyone Dead or Alive


Who’s On Your Guest List?

How many times in life have you been asked; “If you could invite anyone dead or alive to dinner, who would be your quests?”  And sometimes this question has a follow-up or two: “Why?” And, “What would you say to them?”

My Honored Guest List:

I would first invite Jesus Christ who has always been there for me and my family in good times and bad. He would lead us in a prayer of thanksgiving for our food and this special time together. He also would keep the conversations focused on what’s truly important in this life and impart a special message to us just before our time together ended.

For entertainment, I would invite the truly unique talent and voice of  Elvis Presley with his Jordanaire backup band. Elvis was more than a pop or rock n roll artist. His early love of music came from his spiritual and gospel beginnings.  In fact, I’d ask Elvis to sing “How Great Thou Art.”  “How Great Thou Art” appeared on the title track of Presley’s 1967 gospel album which won him his first Grammy. And then his live performance of it earned him yet another Grammy in 1974.

Mamma, Roy, and Uncle Johnny Mixing It Up with Family

And sitting around the table with today’s extended family would be my maternal grandparents, Roy and Loretta, and their son, my uncle, Johnny.  These are the people who loved and cared for me in my formative years.  These are the family members that taught me the importance of family and what it means to be a part of a nurturing environment.  I was so very blessed to have them in my life.  As I wrote in several of my posts over the past two years they all had qualities that made them larger than life in my eyes and my heart.

I recognize that my invite to them this Thanksgiving is solely selfish yet, they still could bestow their wisdom and guidance on those family members who followed after their passings and I would love for everyone to get to know these ancestors.

My grandfather, Roy, exemplified what it was to be “man of the house,” family provider, and strong in his silence rather than speak anything derogatory about others.  And, Roy could enlighten my brothers and other male family members about his days’ times and how extended families flocked together during hard times to more than just “weather through.”  Instead, families received their greatest gifts of quality times and fighting the good fights in trying times of survival mode.  Our son, Bobby, who says that Thanksgiving is his favorite holiday because of time spent with family would truly enjoy conversing with Roy.

I truly believe ’til this day that Mamma Loretta is my spiritual guide.  And, I talk with her nearly daily. I believe granddaughter Kylie and other female family members would thrive around Mamma and be in awe of some of the stories she could share from her past. Meanwhile, our daughter Jennifer and mamma could compare notes about women’s schedules of yesteryear vs. today’s women’s roles and responsibilities. Please believe me when I say my mamma was well ahead of her times and was a self-made female who shared her zest for life and confidence in going for it with me.

Uncle Johnny lived his life to the fullest in his short 37 years on this earth. He was always upbeat and full of energy.  Johnny had an overall great aura, if you will.  Everybody loved him and loved being around him because he added fun into our lives.  I just know our son and Johnny would get along famously because Jeff is so much like how I remember him.

A Line from Shapespeare…

Good night, good night! Parting is such sweet sorrow That I shall say good night till it be morrow?

Unlike today’s thanksgivings when we so look forward to having the long day of preparation, hosting, clean up, and travel home come to a close, the end of this day would be the absolute hardest despite and because of all the good times with lost loved ones and reflections of memories now past.  Here’s where we rely on our faith to get us through it.–knowing that we will all be together again some day.

It’s All About That “Baste”

To lighten this somewhat solemn and somber ending to this post, I thought I’d share this clever parody of Meghan Trainor’s It’s All About That Bass:

And, now I’m asking you–“Who would be on your guest list?”

Have a Safe and Happy Thanksgiving Everyone!

 

THANKFUL THURSDAY: The Best Things In Life Are Free – Part 1


The best things in life are free, especially the gifts of our ancestors whose trail blazing contributions started first in the colony of Virginia (Jamestown, 1607) and then in Plymouth (1620) over 400 years ago. These settlers from England, Wales, Scotland, Holland, and Ireland bonded together to form our religious, social, business and industry, government, education and transportation infrastructures that continue today. But wait a minute. We should pause here to remember that their legacies and gifts are free to us but came at great costs to them. They gave up everything to journey across the seas; they suffered hunger, disease, and death aboard ships; they lost many family members—especially heavy losses of women, in their initial settlements due to cold, hunger, and disease. They were befriended by Indians and then battled them for land to build homes and towns and to cultivate crops; waters to cross, bridges to build and waters to fish in; and hunting grounds for sources of meat. With industry came slavery and then brothers fought brothers in the American Civil War.

Rev James Blair

Rev James Blair

Yet, everywhere we look we can see the benefits of their often inhumane struggles which gave us the freedom of religion and speech, their cultivation of tobacco and other crops that attracted purchasers from around the world, the creation and building of colleges and universities like William and Mary in Williamsburg by commissary Rev. James Blair (related to me through my paternal 2nd great grandfather and my 1st great aunt). He became president of William and Mary in 1693 and served in that position until his death in 1743; and, the University of Virginia (UVA) in Charlottesville, founded by our third president, Thomas Jefferson, after he completed his eight year term of office from 1801 to 1809. He founded UVA to give young people in Virginia a school where they could learn to be our country’s leaders of tomorrow. Upon quick reflection, I ask myself “how can so many Americans remain unaware, apathetic, dissatisfied, or even hostile about how far we’ve come and what we have achieved?”

Despite 2+ inches of snow on the ground from the night before (Wednesday, January 23, 2013), gusts of harsh winds, and mid-teen temperatures—very little in comparison to our ancestors’ times and travel conditions, so we happily packed up the truck, our three small dogs (Jake, Baby, and Odie), snacks, and warm snugglies, to take to the roads of Virginia again. We begin our journey by entering our itinerary into our iPad-based GPS system. We expect the GPS to guide us south from Calvert County, Maryland to our destination planned for late afternoon in Petersubrg, Virginia. Interestingly enough, Ms. GPS wants to steer us 20+ miles north and have us use Interstate 95 which is a much traveled road with little to no local scenery or history about our ancestors from hundreds of years before. It was at this moment that we decided we would show Ms. GPS who’s who in day tripping at our first leg of our trip. Thus, we ignored her voice as she continued to tell us; “please turn around at the first possible opportunity.” We are traveling south on U.S. Route 301 going through Waldorf, White Plains, and LaPlata. And, guess what? Our choice was “spot on”. We drove over the two-lane continuous truss Governor Harry W. Nice Bridge that spans the Potomac River between Newburg (in Charles County, Maryland at Cobb Island) into the town of Dahlgren in King George County, Virginia. We realized almost instantly that this was probably the route (in reverse) used by our ancestors when they migrated from Virginia and into southern Maryland. We spotted our first colonial history roadside markers in Dahlgren, Virginia.

Dahlgrens Raid Sign

Dahlgrens Raid History Marker

And now in King George County, my genealogy confirms that my paternal 6th great grandfather, Colonel Robert Bolling IV (1759-1839) married Sally Washington here on September 1, 1796.

Colonel Robert Bolling IV

Colonel Robert Bolling IV

This Robert Bolling in 1823 also built the Bollingbrook Mansion, now known as the Centre Hill Mansion Museum in Petersburg, VA. This will be our end destination when we tour it in Petersburg City at 6 o’clock. But there’s time for us to see much more of Virginia before we arrive at the mansion. I hope you will continue our journey with us in my next blog to follow.