Monday, April 17, 2023

Converting BIG Y "Private Variants" into "Named Variants" and possibly getting new terminal ySNPs

If you have taken a BIG Y test to explore and identify your patrilineal descent back into prehistory, you are among the pioneers of the latest wave in genetic genealogy. However, you may be able to learn even more about your line of descent in genealogical times. Chances are that your test results identified some "Private Variants." These are variants which so far have only been identified in one man. As soon as they are identified in others they will become "Named Variants". in the process it is possible that your own terminal ySNP will be named and thus extend your trail to your true "genetic coat of arms."

My cousin is shown to have 2 Private Variants

There are two ways to respond. The passive way is to wait until another person is tested who also is found to share these variants. The more assertive way is to identify another man who is likely to share these variants and ask him to test.


In the case of the cousin whose private variants are shown above, we are currently evaluating whether to test his son or his nephew when the next DNA test sale rolls around.


I recently extended my own terminal ySNP by testing my grandson and then my son as I described in two earlier blog posts:

DNA Testing your descendants with BIG Y

DNA Testing your DESCENDANTS with BIG Y 700--Part 2

In those posts I described that we discovered my grandson was only a 110/111 ySTR match with me. Subsequently, we found that my son was a 111/111 ySTR match with me but he also had one mismatch with his son. So my grandson was the ySTR mutant!  


When it came to our ySNP analyses, my grandson confirmed my 2 "Private Variants" but showed one of his own. In so doing one of the previously private variants became the new terminal ySNP for me. After my son tested, he confirmed my grandson's private variant, and by so doing, uncovered a new terminal ySNP that is shared by my son, grandson but not by me. So none of us currently have private variants but we have two new terminal ySNPs--one shared by all three of us and one only shared by my son and grandson and not by me.


I am advised by Paul Maier, a population geneticist who works for FTDNA that the ySNP shared only by my son and grandson had multiple possibilities as to when it was created:


Regarding your son's mutation of R-FTC50269, what we can say for certain is that it's absent from your somatic cells (e.g., cheek cells from your swab).


The mutation could have occurred:

  1. In your reproductive stem cells (spermalogonia), early during your fetal developing; those cells made the sperm cell that led to your son;
  2. In one of your sperm cells later on (after puberty);
  3. Early in the fetal development of your son, such that both his somatic and reproductive cells inherited the mutation. 

But of course, you and your son only tested cheek cells, making it difficult to know for sure which (1, 2, 3) is the case. If you had multiple sons tested and they all shared the mutation, (1) would be most likely.  


In any case, R-FTC50269 would have been created toward the middle of the 20th century and certainly within the Genealogical Era. What will you find if you explore your "Private Variants?" 

Monday, March 20, 2023

What is a 2nd cousin--once removed?


Degree of cousin-hood:

I'm often asked questions like "what is a 2nd cousin--once removed" and "what is a half=cousin?" The answers all have to do with some simple facts about how you are related to the ancestor(s) you share with your cousin. 

  1. The first question you must answer is, how many "g" s are there in the relationship that defines the shared ancestor(s) you have with this cousin?
  2. Are the two of you the same number of generations removed from this shared ancestor?
  3. Do you share a grandparent couple with this individual or do you share only one grandparent in some previous generation?

With the answers to these questions in mind, you are ready to define your relationship with your cousin. 

Question #1 is how many "g" s are there in the relationship that defines the shared ancestor(s) you have with this cousin? The most common shared ancestors would be a pair of grandparents. Note that there is one "g" in this the definition of relationship with the shared ancestor(s). Whether it is grandfather or grandmother or a pair of grandparents, there is a single "g" in the term that defines their relationship. Cousins who share grandparents with you are your 1st cousins.

By now you should have noticed all the "g's" sprinkled throughout my prose above. That is deliberate both to draw you attention to them but also to emphasize that they are present in "grandparents" and well as great-grandparents which I shall get to shortly.

If your shared ancestors with the cousin in question are a pair of great-grandparents, this cousin is your 2nd cousin. After all, your common ancestor(s) share 2 g's in their designation. Likewise, if your shared ancestors with the cousin in question is a set of great-great-grandparents, how may "g's" is that? The more astute of you have already concluded that this makes the cousin in question is your 3rd cousin. This pattern extends as far back in your family tree as your research may take you. Just count the number of "g's" and make sure to include the one in grandparents! 


Cousin's removed

So far, I've been describing cousins who share the same generation in the family that you do. But as you probably have noticed, many of your closest family members are either a generation older or a generation younger than you. The children of your parents' 1st cousins are your 1st cousins one generation removed. In like manner, the children of your own 1st cousins are also described as 1st cousins one generation removed. These relationships are generally expressed as your "1st cousin--once removed" whether the generation is one generation above you or below you in your family tree.

The same logic continues with additional generations. The grandchildren of your parents' 1st cousins can be characterized as your 1st cousin two generations removed. The mirror image of this relationship would be the grandchildren of your own 1st cousins. They would also be characterized as 1st cousins--twice removed. Again, it does not matter whether or no they are two generations above your or below you in your family tree.

In like manner, the children and grandchildren of your parents' 2nd and 3rd cousins can have the tag of "once removed" or "twice removed" added to their descriptors to help define their relationship to you. Again the mirror image also applies to the children and grandchildren of your own 2nd and 3rd cousins, etc. 

While these distinctions may not be necessary for some genealogical studies, often they become important in deciphering relationships based on the amount of shared atDNA (autosomal DNA) shared with a previously unknown individual.


Half cousins

Half-cousins are an extension of the concepts of half-siblings. It occurs when only one half of an ancestral couple is shared by you and your cousin. It can occur at any level of cousin-hood for any number of reasons. For example, if you had a great-grandfather who had 5 children by his first wife and four more by his second, you would be full 2nd cousins with the children with whom you shared a common biological great-grandmother. The children of the other wife would be your half-2nd cousins and would be expected to share about one half as much atDNA as a full 2nd cousin.             

Counting your "g s"

Remember to count the "g" in grandparents when counting the degree of cousin-hood. 


In the chart above, note that You are located in the box to the right in the row next to the bottom. All those represented in the same row to your left, are your same generation cousins. The one on your immediate left is your 1st cousin; the next one is a 2nd cousin; then 3rd cousin; 4th cousin and 5th cousin on the extreme left. In the bottom row (right to left) are possible 1st cousins -- once removed; 2nd cousins -- once removed etc.

So the answer to the question at the beginning of this blog, "what is a 2nd cousin--once removed", generally would be a person positioned 2 boxes to the left and one down from You in the chart above. If that was your answer, you may be giving a hint to your age. That indicates many of your cousins are younger than you. If you are taking this course for AP credit, you probably figured out that the person 2 boxes to the left of You and one row up would also qualify for this designation. If you caught both, congratulations. You well on your way to becoming a genetic genealogist. Humm. That has two "g s". Maybe 3.

Monday, October 3, 2022

Neanderthals have their 15 minutes of fame!

Do you have Neanderthal DNA?


The early ancestors of most of us who have European ancestors just got their 15 minutes of fame this morning thanks to the Nobel Prize awarded to Svante Pääbo.


Press release: The Nobel Prize in Physiology or Medicine 2022

Nobel Assembly logo

Press release


The Nobel Assembly at Karolinska Institutet has today decided to award the 2022 Nobel Prize in Physiology or Medicine to Svante Pääbo for his discoveries concerning the genomes of extinct hominins and human evolution

Humanity has always been intrigued by its origins. Where do we come from, and how are we related to those who came before us? What makes us, Homo sapiens, different from other hominins?

Through his pioneering research, Svante Pääbo accomplished something seemingly impossible: sequencing the genome of the Neanderthal, an extinct relative of present-day humans. He also made the sensational discovery of a previously unknown hominin, Denisova. Importantly, Pääbo also found that gene transfer had occurred from these now extinct hominins to Homo sapiens following the migration out of Africa around 70,000 years ago. This ancient flow of genes to present-day humans has physiological relevance today, for example affecting how our immune system reacts to infections.

Pääbo’s seminal research gave rise to an entirely new scientific discipline; paleogenomics. By revealing genetic differences that distinguish all living humans from extinct hominins, his discoveries provide the basis for exploring what makes us uniquely human.

Where do we come from?

The question of our origin and what makes us unique has engaged humanity since ancient times. Paleontology and archeology are important for studies of human evolution. Research provided evidence that the anatomically modern human, Homo sapiens, first appeared in Africa approximately 300,000 years ago, while our closest known relatives, Neanderthals, developed outside Africa and populated Europe and Western Asia from around 400,000 years until 30,000 years ago, at which point they went extinct. About 70,000 years ago, groups of Homo sapiens migrated from Africa to the Middle East and, from there they spread to the rest of the world. Homo sapiens and Neanderthals thus coexisted in large parts of Eurasia for tens of thousands of years. But what do we know about our relationship with the extinct Neanderthals? Clues might be derived from genomic information. By the end of the 1990’s, almost the entire human genome had been sequenced. This was a considerable accomplishment, which allowed subsequent studies of the genetic relationship between different human populations. However, studies of the relationship between present-day humans and the extinct Neanderthals would require the sequencing of genomic DNA recovered from archaic specimens.

A seemingly impossible task

Early in his career, Svante Pääbo became fascinated by the possibility of utilizing modern genetic methods to study the DNA of Neanderthals. However, he soon realized the extreme technical challenges, because with time DNA becomes chemically modified and degrades into short fragments. After thousands of years, only trace amounts of DNA are left, and what remains is massively contaminated with DNA from bacteria and contemporary humans (Figure 1). As a postdoctoral student with Allan Wilson, a pioneer in the field of evolutionary biology, Pääbo started to develop methods to study DNA from Neanderthals, an endeavor that lasted several decades.

Ancient DNA

Figure 1. DNA is localized in two different compartments in the cell. Nuclear DNA harbors most of the genetic information, while the much smaller mitochondrial genome is present in thousands of copies. After death, DNA is degraded over time and ultimately only small amounts remain. It also becomes contaminated with DNA from e.g. bacteria and contemporary humans.

In 1990, Pääbo was recruited to University of Munich, where, as a newly appointed Professor, he continued his work on archaic DNA. He decided to analyze DNA from Neanderthal mitochondria – organelles in cells that contain their own DNA. The mitochondrial genome is small and contains only a fraction of the genetic information in the cell, but it is present in thousands of copies, increasing the chance of success. With his refined methods, Pääbo managed to sequence a region of mitochondrial DNA from a 40,000-year-old piece of bone. Thus, for the first time, we had access to a sequence from an extinct relative. Comparisons with contemporary humans and chimpanzees demonstrated that Neanderthals were genetically distinct.

Sequencing the Neanderthal genome

As analyses of the small mitochondrial genome gave only limited information, Pääbo now took on the enormous challenge of sequencing the Neanderthal nuclear genome. At this time, he was offered the chance to establish a Max Planck Institute in Leipzig, Germany. At the new Institute, Pääbo and his team steadily improved the methods to isolate and analyze DNA from archaic bone remains. The research team exploited new technical developments, which made sequencing of DNA highly efficient. Pääbo also engaged several critical collaborators with expertise on population genetics and advanced sequence analyses. His efforts were successful. Pääbo accomplished the seemingly impossible and could publish the first Neanderthal genome sequence in 2010. Comparative analyses demonstrated that the most recent common ancestor of Neanderthals and Homo sapiens lived around 800,000 years ago.


Figure 2. A. Pääbo extracted DNA from bone specimens from extinct hominins. He first obtained a bone fragment from Neandertal in Germany, the site that gave name to the Neanderthals. Later, he used a finger bone from the Denisova Cave in southern Siberia, the site that gave name to Denisovans. B. Phylogenetic tree showing the evolution and relationship between Homo sapiens and the extinct hominins. The phylogenetic tree also illustrates the gene flows discovered by Pääbo.

Pääbo and his co-workers could now investigate the relationship between Neanderthals and modern-day humans from different parts of the world. Comparative analyses showed that DNA sequences from Neanderthals were more similar to sequences from contemporary humans originating from Europe or Asia than to contemporary humans originating from Africa. This means that Neanderthals and Homo sapiens interbred during their millennia of coexistence. In modern day humans with European or Asian descent, approximately 1-4% of the genome originates from the Neanderthals (Figure 2).

A sensational discovery: Denisova

In 2008, a 40,000-year-old fragment from a finger bone was discovered in the Denisova cave in the southern part of Siberia. The bone contained exceptionally well-preserved DNA, which Pääbo’s team sequenced. The results caused a sensation: the DNA sequence was unique when compared to all known sequences from Neanderthals and present-day humans. Pääbo had discovered a previously unknown hominin, which was given the name Denisova. Comparisons with sequences from contemporary humans from different parts of the world showed that gene flow had also occurred between Denisova and Homo sapiens. This relationship was first seen in populations in Melanesia and other parts of South East Asia, where individuals carry up to 6% Denisova DNA.

Pääbo’s discoveries have generated new understanding of our evolutionary history. At the time when Homo sapiens migrated out of Africa, at least two extinct hominin populations inhabited Eurasia. Neanderthals lived in western Eurasia, whereas Denisovans populated the eastern parts of the continent. During the expansion of Homo sapiens outside Africa and their migration east, they not only encountered and interbred with Neanderthals, but also with Denisovans (Figure 3).

Paleogenomics and its relevance

Through his groundbreaking research, Svante Pääbo established an entirely new scientific discipline, paleogenomics. Following the initial discoveries, his group has completed analyses of several additional genome sequences from extinct hominins. Pääbo’s discoveries have established a unique resource, which is utilized extensively by the scientific community to better understand human evolution and migration. New powerful methods for sequence analysis indicate that archaic hominins may also have mixed with Homo sapiens in Africa. However, no genomes from extinct hominins in Africa have yet been sequenced due to accelerated degradation of archaic DNA in tropical climates.

Thanks to Svante Pääbo’s discoveries, we now understand that archaic gene sequences from our extinct relatives influence the physiology of present-day humans. One such example is the Denisovan version of the gene EPAS1, which confers an advantage for survival at high altitude and is common among present-day Tibetans. Other examples are Neanderthal genes that affect our immune response to different types of infections.

Pääbo's discoveries

Figure 3. Pääbo’s discoveries have provided important information on how the world was populated at the time when Homo sapiens migrated out of Africa and spread to the rest of the world. Neanderthals lived in the west and Denisovans in the east on the Eurasian continent. Interbreeding occurred when Homo sapiens spread across the continent, leaving traces that remain in our DNA.

What makes us uniquely human?

Homo sapiens is characterized by its unique capacity to create complex cultures, advanced innovations and figurative art, as well as by the ability to cross open water and spread to all parts of our planet (Figure 4). Neanderthals also lived in groups and had big brains (Figure 4). They also utilized tools, but these developed very little during hundreds of thousands of years. The genetic differences between Homo sapiens and our closest extinct relatives were unknown until they were identified through Pääbo’s seminal work. Intense ongoing research focuses on analyzing the functional implications of these differences with the ultimate goal of explaining what makes us uniquely human.

Denisova, Neanderthal and H. sapiens

Figure 4. Pääbo’s seminal work provides a basis for explaining what makes us uniquely human.

Key publications

Krings M, Stone A, Schmitz RW, Krainitzki H, Stoneking M, Pääbo S. Neandertal DNA sequences and the origin of modern humans. Cell. 1997:90:19-30.

Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, Patterson N, Li H, Zhai W, Fritz MH, Hansen NF, Durand EY, Malaspinas AS, Jensen JD, Marques-Bonet T, Alkan C, Prüfer K, Meyer M, Burbano HA, Good JM, Schultz R, Aximu-Petri A, Butthof A, Höber B, Höffner B, Siegemund M, Weihmann A, Nusbaum C, Lander ES, Russ C, Novod N, Affourtit J, Egholm M, Verna C, Rudan P, Brajkovic D, Kucan Ž, Gušic I, Doronichev VB, Golovanova LV, Lalueza-Fox C, de la Rasilla M, Fortea J, Rosas A, Schmitz RW, Johnson PLF, Eichler EE, Falush D, Birney E, Mullikin JC, Slatkin M, Nielsen R, Kelso J, Lachmann M, Reich D, Pääbo S. A draft sequence of the Neandertal genome. Science. 2010:328:710-722.

Krause J, Fu Q, Good JM, Viola B, Shunkov MV, Derevianko AP, Pääbo S. The complete mitochondrial DNA genome of an unknown hominin from southern Siberia. Nature. 2010:464:894-897.

Reich D, Green RE, Kircher M, Krause J, Patterson N, Durand EY, Viola B, Briggs AW, Stenzel U, Johnson PL, Maricic T, Good JM, Marques-Bonet T, Alkan C, Fu Q, Mallick S, Li H, Meyer M, Eichler EE, Stoneking M, Richards M, Talamo S, Shunkov MV, Derevianko AP, Hublin JJ, Kelso J, Slatkin M, Pääbo S. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature. 2010:468:1053-1060.

Meyer M, Kircher M, Gansauge MT, Li H, Racimo F, Mallick S, Schraiber JG, Jay F, Prüfer K, de Filippo C, Sudmant PH, Alkan C, Fu Q, Do R, Rohland N, Tandon A, Siebauer M, Green RE, Bryc K, Briggs AW, Stenzel U, Dabney J, Shendure J, Kitzman J, Hammer MF, Shunkov MV, Derevianko AP, Patterson N, Andrés AM, Eichler EE, Slatkin M, Reich D, Kelso J, Pääbo S. A high-coverage genome sequence from an archaic Denisovan individual. Science. 2012:338:222-226.

Prüfer K, Racimo F, Patterson N, Jay F, Sankararaman S, Sawyer S, Heinze A, Renaud G, Sudmant PH, de Filippo C, Li H, Mallick S, Dannemann M, Fu Q, Kircher M, Kuhlwilm M, Lachmann M, Meyer M, Ongyerth M, Siebauer M, Theunert C, Tandon A, Moorjani P, Pickrell J, Mullikin JC, Vohr SH, Green RE, Hellmann I, Johnson PL, Blanche H, Cann H, Kitzman JO, Shendure J, Eichler EE, Lein ES, Bakken TE, Golovanova LV, Doronichev VB, Shunkov MV, Derevianko AP, Viola B, Slatkin M, Reich D, Kelso J, Pääbo S. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature. 2014:505: 43-49.

>Svante Pääbo was born 1955 in Stockholm, Sweden. He defended his PhD thesis in 1986 at Uppsala University and was a postdoctoral fellow at University of Zürich, Switzerland and later at University of California, Berkeley, USA. He became Professor at the University of Munich, Germany in 1990. In 1999 he founded the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany where he is still active. He also holds a position as adjunct Professor at Okinawa Institute of Science and Technology, Japan.

Illustrations: © The Nobel Committee for Physiology or Medicine. Illustrator: Mattias Karlén

The Nobel Assembly, consisting of 50 professors at Karolinska Institutet, awards the Nobel Prize in Physiology or Medicine. Its Nobel Committee evaluates the nominations. Since 1901 the Nobel Prize has been awarded to scientists who have made the most important discoveries for the benefit of humankind.

Nobel Prize® is the registered trademark of the Nobel Foundation

Press release: The Nobel Prize in Physiology or Medicine 2022. Nobel Prize Outreach AB 2022. Mon. 3 Oct 2022. 


Do you have Neanderthal DNA?

23andMe is currently the only major DNA testing company which reports to us information about our Neanderthal DNA inheritance:

"Hey David! You have more Neanderthal DNA than 45% of other customers."

"You inherited a small amount of DNA from your Neanderthal ancestors. Out of the 7,462 variants we tested, we found 236 variants in your DNA that trace back to the Neanderthals."

"All together, your Neanderthal ancestry accounts for less than ~2 percent of your DNA."

"You have one variant associated with being less likely to have a fear of heights.
You have one variant associated with being a better sprinter than distance runner.
You have one variant associated with being more likely to sweat during a workout.
You have one variant associated with being less likely to have a chin dimple." 

Read more Neanderthal DNA in Svante's best selling 2014 book: