Sunday, October 20, 2019

Human Reference Genome Will Upgrade

Source: (google images)
On September 24, 2019,  Genomeweb reported that the National Institutes of Health (NIH) awarded $29.5 million to two research centers in the USA and one in Europe for creation of a new human genome reference sequence to "better represent human diversity."

Approximately $12.5 million over five years will be distributed to Washington University, St. Louis, MO; the University of California, Santa Cruz; and the European Bioinformatics Institute, Cambridge, UK, to form the WashU-UCSC-EBI Human Genome Reference Center. In coordination with the National Center for Biotechnology Information (NCIB), the new center will provide a multi-genome reference sequence or "pan-genome." [You can read the full details here].

However for my layperson readers, I want to take this opportunity to explain in simple terms what a human reference genome is and why it's important. 

What is a reference genome for humans?
A human reference genome is a library or database of nucleic acid sequences representing a species (here human) set of genes. A human reference genome is created or assembled using the DNA of different donor individuals and therefore do not represent the set of genes of any single person. In other words the human reference genome is stitched together from genes of several individuals. 

Where there are differences in genes [at the same reference location] in the donors—and that are not in human reference genes or regions where their would be high allelic diversity (determines a population's long-term potential for adaptability and persistence; see Templeton et al)—those additional genes are then annotated alongside the human reference genome. 

What is the human reference genome used for? 
The human reference genome ultimately is for sample comparison with single-individual human genomes; to show genomic differences and similarities, as well as to solve biological questions. Some human reference genome applications include:
  •  use by geneticists and biologists to identify gene mutations and misalignments that cause abnormalities and diseases in humans, which can lead to better treatment, medicines and cures, and to create a better genome; 
  • in palaeogenomic studies of human populations (ie mapping against the human reference genome is used to identify endogenous human sequences in ancient samples);
  •  use by personal whole genomic sequence testing companies (ie Full Genomes CorpYSeq and Dante Labs) to provide customers with the most accurate DNA results for deep genetic ancestry, uniparental inheritance testing and personal health profiling. This is achieved by the company generating our results, usually a BAM and FASTQ file, and  comparing it to the latest human reference genome (known as a "build").
Why do we need an updated human reference genome?
Sequencing a human reference genome is a very complicated process. Needless to say earlier versions of the human reference genome contained many gaps and problems areas that were complicated to read properly (ie incorrect reads, missing model centromere sequences, lack of alternate loci). The last human reference genome released in December 2013 sought to improve some of these issues.

More pointedly the prior versions and current human reference genome cater to European populations. At current more than 300 million letters of DNA are missing from the human genome according to The Atlantic, a discovery which came to light after a analysis of 910 people of African descent. This is a travesty because Africa, the cradle of humanity, harbors the most genetic diversity in the world. 

What is the timeline history of the human reference genome and who maintains it?
The first reference human genome was assembled by the National Center for Biotechnology Information (NCBI) in July 2003, and it was updated in 2004 and 2006.

In 2009 the Genome Reference Consortium created "an international collective of academic and research institutes with expertise in genome mapping, sequencing, and informatics, formed to improve the representation of reference genomes," which includes:
Recent human genome assemblies:
Recent human genome assemblies chart, Wikipedia.
Today we are using GRCh38 (Genome Reference Consortium human 38), although some companies and researchers still utilize GRCh37.

I've had two whole genome sequence tests—one each from Full Genomes Corp and Dante Labs—and both of my results were compared using the the latest human reference genome build GRCh38. Personally I'm hoping a more updated human reference genome(s) will help solve the riddles of human genomic diversity, bring improvements in health, and of course provide more answers contained in my own genome, including my understudied Y-chromosome.

Thus, a new human reference genome, perhaps several, is long overdue. This is why the National Institutes of Health's $29.5 million grant will be important to making it a reality. I look forward to all of the new discoveries that will benefit me, you and humanity. 


Thursday, May 17, 2018

Fine Scaling Genetic Admixture: 23andMe vs AncestryDNA

Some genetic genealogists and genealogists pan genetic ancestry or ethnicity admixture estimates. They see them as not useful and wouldn't mind if ethnicity predicting was discontinued. On the other hand, I see genetic ancestry estimates as part of the genealogy cycle of life.

I understand that matching to genetic relatives is a natural progression from traditional genealogy methodology and practices, but genetic ancestry estimates are a natural extension of DNA relative matching and both can be used synergistically to achieve optimal results.

I'm sure by now you've seen or heard about 23andMe's new Recent Ancestor Locations feature added to its Ancestry Composition tool or last year's AncestryDNA Genetic Communities included with its Ethnicity Estimates—each touts unprecedented granularity with genetic ancestry estimates and addition of over 100 regions or reference populations.

Thus 23andMe ($99 US; $199 w/Health) and AncestryDNA ($99 US) have figured out a way to make their ethnicity admixture tools more relevant by "marrying" genetic ancestry to our genetic relatives! Both DNA testing market leaders have been able to achieve this matrimony by "fine-scaling" their respective ethnicity admixture offerings, which I will review for this blog. 

  • PINK ELEPHANT IN THE ROOM: On May 11, 2018, 23andMe hit AncestryDNA with a patent infringement and false advertising lawsuit [see here]. Based upon the bones of the case my analysis may seem to implicate a party. However it's unintentional as I've been working on this blog prior to the lawsuit. I hope the legal issue is amicably resolved between the parties.

Tuesday, May 8, 2018

Mama's Got A Brand New Clade

My 1st Cousin 2x removed Clara Harvey 
This blog is in honor of my cousin Clara Harvey, who turned 95 on April 26, 2018, just one day after National DNA Day. She is truly one of the last Mohicans — one of two surviving first cousins from my maternal grandfather's generation. 

With Mother's Day fast approaching, this is the perfect time to share phenomenal news about matriarch Clara's MATERNAL (mitochondrial-DNA or mtDNA) HAPLOGROUP, and we took it to the "Bank" (more on this later).

I'm also making an urgent appeal to add Cousin Clara's maternal haplogroup to the mtDNA phylogenetic tree so we can present it to her at an upcoming family event. 
I also have a new hypothesis about the source of our Native American ancestry. 

In my recent blog Guide to Building Your Family's Haplotree I revealed that cousin Clara's Maternal Haplogroup was B2, which is exclusively found in Native Americans. Since cousin Clara's mother and my grandfather's mother were full sisters this proved that the direct matrilineal line of my maternal grandfather — and by extension myself — biologically descend from a foremother of Native American descent.

I pray this blog inspires more relatives from my maternal grandfather's branch (Gillette, Hall, Jackson, Shipley, Van Horn, Van Ness, Winkey, Wyckoff) to participate in DNA testing; see my Family History & Genetic Genealogy Book Project. Our cousin Cousin Clara (and her brothers) tested without hesitation and in return unlocked a rich legacy that keeps exceeding all expectations. 

Special thanks to cousin Richard Oakley and genetic experts Claudio BraviJames Lick, and Ian Logan for their invaluable assistance. Read on:

Monday, April 16, 2018

MyHeritage Adoption Program Goes Global

I must say MyHeritage is thee new rockstar DNA company and it continues to impress:

In March 2018, MyHeritage launched DNA Quest,"a new pro bono initiative to help adoptees and their birth families reunite through genetic testing." DNA Quest, first available in the United States, received such an outstanding response that the program is now being expanded globally! 

According to MyHeritage
The initiative, initially launched in the USA only, received an amazing response. More than 10,000 applications were submitted so far to receive free DNA kits, from the quota of 15,000 free DNA kits pledged by MyHeritage, worth more than one million dollars.

Being that the deadline for submissions is the end of April 2018 and there are still about 3 more weeks to go, and in light of the many requests we received from the community to expand DNA Quest worldwide, we decided to increase the scope of the project, from USA-only to global.
This means that people are now eligible to participate in DNA Quest regardless of their place of residence  and regardless of where the adoption took place. 
Remember the deadline to participate in MyHeritage DNA Quest is April 30, 2018. So if you're interested in this important initiative please visit NOW to enroll. 

You can read more at MyHeritage blog but here's some quick information about the project:

Who can participate
Participation in DNA Quest is open to adoptees seeking to find their biological family members, or anyone looking for a family member placed for adoption. Preference will be given to those unable to afford genetic testing, and to those who apply first.

How to apply

Adoptees and family members searching for their biological relatives can apply for a free MyHeritage DNA kit at through April 30, 2018. Participants will be selected, and their free DNA kits will be shipped to them by the end of May 2018. Results are expected as early as July 2018.

I wish you all abundant success and great luck with your search!


Saturday, March 17, 2018

Finding Your Wakanda Africa with DNA Testing

The instantly iconic Marvel Comics film Black Panther (2018) sparked an epic socio-cultural movement by the masses to take pride in their African roots, to don haute tribal couture, and even hold voter registration drives at movie theaters. Featuring a mostly Black cast and a young African-American director, Ryan Coogler, the nascent epic triggered one of those Malcolm Gladwell tipping points—an uplifting of our collective self-image; a renewed conversation sparked between African-Americans and continental Africans about their connection, and a vibrant curiosity in people lusting to find their specific African roots.

It harkened me back to my adolescence when I was known as "The Great Black One" and became the first student at my famous high school ("Lean On Me") to found an African-American club. My conscience allowed me to exude the same African pride I'm seeing today. Of course my T'Challa then was Kunte Kinte, the Mandinka warrior from the village of Juffra in present-day Gambia.

I knew it would be nearly impossible to find a paper trail like that of Alex Haley's "factional" Roots because the proof was invisible, scarce and scant...we didn't even have the internet. Yet I've always carried within me an innate desire to know more about the beauty, culture, identity, and power that was raped from us. Can I now find my pot of Kwandan vibranium, or was it forever plundered like Akan gold?

It wasn't until 2012 as genetic genealogist "King Genome" that I discovered I can use DNA testing to find the specific tribal origins of my enslaved African ancestors. In this blog I'm going to discuss (1) how to identify your genetic African relatives; (2) you'll "meet" four of my African cousins, and (3) I'll tell you about a fascinating African named Ari Van Guinea, who became the richest Black man in New Jersey 50 years before the US Revolutionary War.

Me as "The Great Black One" at Eastside High School, Paterson, NJ, circa 1990 
Wakanda, Africa, is not a real place. Academic Jelani Cobb wrote in his New Yorker magazine review: "Africa—or, rather, “Africa”—is a creation of a white world and the literary, academic, cinematic, and political mechanisms that it used to give mythology the credibility of truth. No such nation as Wakanda exists on the map of the continent, but that is entirely beside the point."

For the majority of African descendants in the Americas our "Africa" might as well be in Wakanda because our actual ethnic origins felt like a sort of mythical—and stereotypical—place often shaped by what we saw on TV, absorbed in schools, read in books or ingrained in our psyche by a society still shackled by the psychological chains of chattel slavery. A desert. A disease. A famine. A jungle. A place with primitive people who lived somewhere in the Motherland.

I certainly didn't learn about real-life kingdoms like Manden Kurufaba (Mali Empire), or the fierce Dahomey Amazons of Benin, or the fact that Ethiopia has never been colonized by Europeans. Or that Africa has lush and luxe beauty. Black Panther director Coogler as co-writer was brilliant to draw on these factual gems to create a desirable place to claim like Wakanda.

I was raised around African immigrant communities in the New York City area, and exposed to great Africana intellectuals (Drs. John Henrik Clarke, Wendell Holbrook, Said Samatar, Yosef Ben-Johchannan, Amiri Baraka, Clement A. Price) during my college years at Rutgers University. But in my home ghetto there was no common fellowshipping between Africans and African-Americans about our blood connection to the Trans-Atlantic slave trade. The concept seemed to be as foreign to them as their (and our) ancestral homeland was to us.

The point is it took a heroic landmark film about a Black Marvel Comics superhero and an imaginary African utopia to get the masses interested in using DNA testing as a tool to learn about their true Africa. 
Let's start our Sankofa...

Thursday, February 22, 2018

We Are the 23andMe World

On February 8, 2018, DTC personal genome service 23andMe announced a new Global Genetics Project23andMe's goal with the new Global Genetics Project is over the next two years to test over 5000 people whose recent ancestry is from Africa, the Americas, Asia and Oceania covering over 61 qualifying countries.* It's FREE and totally worth sharing with all of your friends.

According to 23andMe, "This work will help 23andMe expand its reference data sets, improve the ability of our scientists to study groups who are currently underrepresented in genetic research and reveal new insights into patterns of human migration and genetic diversity." Read 23andMe's blog release here.

23andMe's Global Genetics Project takes off after the success of its 2016 African Genetics Project, which recruited people whose grandparents were born in certain West African countries connected to the Trans-Atlantic Slave Trade. To this extent, 23andMe has been at the forefront of improving genetic diversity in genetics with such past initiatives as the Roots Into The Future Project and African American Sequencing Project.

Of course 23andMe's Global Genetics Project has rules (see Qualifications below), and one them is you must reside in the United States. Now some of you may wonder why 23andMe did not open the project to people who actually live in the qualifying countries,* but I suspect it is due to federal regulations, grant restrictions and avoidance of foreign government bureaucracy because health testing is involved.

In order to join the Global Genetics Project you must:
  • be at least 18 years of age
  • reside in the U.S. and have U.S. shipping address
  • be willing to have your entire genome sequenced for health research
  • have all four grandparents born in one of 61 qualifying countries* (listed below) 

KING GENOME'S TIP: If you've tested previously at 23andMe and you meet the qualifications then you can still join the Global Genetics Project for FREE (but you won't receive any health results). This is a great opportunity to retest on 23andMe's powerful new v5 chip (see my blog here).

*Qualifying Countries:

Burkina Faso
Central African Republic
Congo (Republic of Congo)
Cote d'Ivoire
Equatorial Guinea
Papua New Guinea
Sierra Leone
South Sudan
United Arab Emirates

ENROLL NOW IN THE Global Genetics Project.


Monday, January 1, 2018

23andMe Chip Versions Comparison (ancestry only)

Illumina Global Screening Array Chip
Back on August 8, 2017, DTC personal genome service 23andMe quietly announced that it was upgrading its genotyping chip for a fifth time to the Illumina Infinium Global Screening Array-24 v1.0 Bead Chip (GSA) — aka 23andMe version 5 or v5 — and promised new customers more improved ethnicity reports, especially those with non-European ancestry, and those with African ancestry would be the first to receive more specific African ancestry updates. I'm excited already.

23andMe's latest chip upgrade comes on heels of the US Food & Drug Administration relaxing its restrictions on health testing for DTC personal genome companies. However it's unclear if customers on 23andMe's prior chips versions will be upgraded — and it may cost you. 

23andMe also has been notoriously slow with past major upgrades — the transition to 23andMe's revamped site took more than 2 years — so I jumped at the chance to test a third time (actually 4th) to be on the new promising v5 chip. 

Since I've 23andMe results from the two prior chip versions (v3 and v4), I can compare all three to determine if v5 lives up to the hype. You can read about all the bells and whistles of the GSA chip at genetic genealogist Debbie Cruwys Kennett's excellent blog here. My comparative analysis will focus mostly on ancestry features for 23andMe's last three chip versions (v3, v4, v5).  

At close of this deep dive I will reveal my new 23andMe v5 Ancestry Composition results and tell you whether it's worth testing NOW to be on the v5 chip. And if you're a current customer on an older chip version, I'll tell you if you should take a chance waiting on a future fee-based upgrade.

King Genome's Wisdom: 
  • There are about 15 million known SNPs (aka Ancestry Informative Markers) for genetic ancestry but only 1-to-5 million are utilized by advanced genetic studies, and much less (~700,000) by vendors like DTC DNA testing companies (ie 23andMe). 
  • According to ISOGG Wiki Chip Versions, here are the different microarray chip versions utilized by 23andMe for genotyping since the debut of its DTC personal genome service:
    • v1: November 2007 
    • v2: September 2008, ~555K SNPs (Illumina)
    • v3: November 2010, >900K SNPs (Illumina OmniExpress)
    • v4: November 2013, ~570K SNPs (Illumina OmniExpress)
    • v5: August 2017, ~640K SNPs (Illumina Global Screening Array)