Tag Archives: dna

Outbreeding Works in a Single Generation

As I have mentioned before, cousin marriages were fairly common among my family. My parents are first cousins. So are my father’s parents. My mother’s parents are second cousins once removed. So instead of 32 great-great-great grandparents, I have only about 18.

Since my wife and I are not related, I wondered how my inbred genome had transmitted to our daughter.

Using David Pike’s ROH utility, I computed the regions of homozygosity for my parents, me, my wife, and my daughter, all tested by 23andme.

I used the default settings for the utility. The total Mb gives the total size in megabases of the long autosomal regions where both alleles are the same. The longest ROH gives the size of the longest such region. Percent Homozygous is the percentage of the genome where the two alleles are the same.

I included the worst chromosome column because of my chromosome 9, which is beyond crazy. This column gives the percent homozygosity of the worst chromosome.

Person Total Mb Longest ROH (Mb) % Homozygous Worst chromosome (%)
Dad 297.45 57.4 72.498% 76.921%
Mom 112.13 22.99 70.662% 79.802%
Me 402.78 71.38 73.588% 93.542%
Wife 37.33 9.64 70.003% 72.411%
Daughter 42.40 8.82 69.936% 71.759%

As you can see, my Dad has higher levels of homozygosity than my Mom as expected and I have the highest levels. My wife is not inbred at all and our daughter has ROH results about the same as my wife. So one generation of marrying someone unrelated, even if from the same/similar ethnicity, has removed all the long runs of homozygosity bred over generations. Good news!

Related Reading

Philopatry, Inbreeding, and the Evolution of Sex
Keep Your Marriage: What to Do When Your Spouse Says "I don't love you anymore!"
DNA of the Gods: The Anunnaki Creation of Eve and the Alien Battle for Humanity
One New Habit To Fix Your Marriage: 10 Simple Steps To Put The Joy And Intimacy Back In Your Marriage

Zack Ajmal Phased Genome

A few months ago, I made my DNA genotyping results from 23andme public.

Since I got results for both my parents as well, I have now used BEAGLE to phase my genetic data. In simple words, I have been able to separate the contribution of my Dad and my Mom on my DNA.

I am making my phased genome public too. It’s in Plink format.

I haven’t made much use of the phased genome yet. So if you have any ideas about what can be done with a phased genome, please let me know.

I have also pledged to make my full sequenced genome public when genome sequencing becomes cheaper and I get it done.

Related Reading

Genomes 3
Phased Array Antennas : Floquet Analysis, Synthesis, BFNs and Active Array Systems
Finding Family: My Search for Roots and the Secrets in My DNA
Best in Children's Books Volume 12: With Alice in Wonderland, The Man Who Didn't Wash His Dishes, The Three Little Kittens, The Sun Keeps Us Warm, Plink Plink!, America's Lake and River Fish, Val Rides the Oregon Trail, Let's Visit Brazil
Genome: The Autobiography of a Species in 23 Chapters (P.S.)

Family DNA Results

I posted my genetic ancestry results. Now, we’ve got my parents, my sister and my wife tested with 23andme. So I thought a comparison would be interesting.

Here’s the ancestry painting from 23andme which uses three reference populations: Yoruba from Nigeria, Chinese and Japanese, and Utahns of Northwestern European descent.

Dad Mom Sister Me Wife
African 0.56% 0.95% 0.96% 0.34% 0.00%
Asian 8.68% 6.63% 8.00% 6.58% 10.18%
European 90.76% 92.42% 91.04% 93.09% 89.82%

You can basically use my wife as a sort of reference for Punjabi ancestry here (which is 3/4th of our ancestry too). Also, my wife and I are unrelated.

As you can see, while our results are close, my mom and sister have more African and I have the least.

And here are the similarity numbers for us with different reference populations.

Dad Mom Sister Me Wife
Central & South Asians 67.13 67.09 67.05 67.12 67.12
Northern Europeans 66.97 66.92 66.92 66.91 66.94
Southern Europeans 66.97 66.88 66.92 66.90 66.85
Near Easterners 66.85 66.76 66.81 66.79 66.72
Siberians 66.59 66.50 66.48 66.52 66.77
Eastern Asians 66.52 66.41 66.42 66.45 66.70
North Americans 66.48 66.40 66.38 66.44 66.69
South Americans 66.46 66.37 66.40 66.40 66.76
Oceanians 66.39 66.41 66.39 66.35 66.62
Northern Africans 66.17 66.10 66.15 66.13 65.94
Eastern Africans 64.08 64.06 64.11 64.10 63.89
Southern Africans 63.96 64.00 64.06 64.00 63.77
Central Africans 63.93 63.93 64.00 63.97 63.74
Western Africans 63.91 63.91 63.97 63.94 63.70

As compared to my wife, we are closer to Africans and farther from Eastern Asians, Native Americans (who are really a branch of East Asians) and Oceanians.That’s expected because of the 25% Egyptian ancestry we have.

Finally, here are our Dodecad Project results.

Dad Mom Sister Me Wife
East_European 4.96% 5.71% 4.59% 4.19% 6.28%
West_European 7.43% 9.59% 8.98% 8.97% 11.10%
Mediterranean 11.10% 9.28% 10.99% 9.24% 5.77%
Neo_African 1.36% 1.12% 1.45% 1.15% 0.26%
West_Asian 23.86% 22.41% 22.88% 23.88% 19.81%
South_Asian 33.94% 37.24% 33.15% 36.57% 45.64%
Northeast_Asian 2.53% 1.64% 1.79% 1.95% 3.22%
Southeast_Asian 3.04% 2.85% 3.95% 2.61% 3.35%
East_African 1.86% 2.18% 3.06% 2.30% 0.00%
Southwest_Asian 7.49% 5.57% 5.75% 6.57% 4.56%
Northwest_African 1.90% 1.49% 2.32% 1.57% 0.00%
Palaeo_African 0.53% 0.92% 1.10% 1.01% 0.00%

Similar results but interesting differences.

Related Reading

DNA: The Secret of Life
Symmetric Generation of Groups: With Applications to many of the Sporadic Finite Simple Groups (Encyclopedia of Mathematics and its Applications)
Finding Family: My Search for Roots and the Secrets in My DNA
Genealogy Bundle: Free Sites - Maps - Cemeteries - Civil War - Case Study
Big Data: A Revolution That Will Transform How We Live, Work, and Think

Genome in the Wild

I tested with 23andme in April 2010 and then upgraded to their version 3 chip with almost a million SNPs last Christmas.

Now I am releasing my personal genome in the public domain.

CC0
To the extent possible under law, Zack Ajmal has waived all copyright and related or neighboring rights to Zack Ajmal 23andme v3 Genome. This work is published from: United States.

You can download my genome data in zipped files:

Razib has a list of people who have made their 23andme genomes public.

When Blaine Bettinger released his genome into the public domain, he issued a challenge:

So, I’m challenging everyone who reads this to download my data and analyze it to find the most interesting or surprising results. For example, you could use my most recent 23andMe V3 data.

I’ve already done a fair amount of analysis myself, including the Promethease reports above (and see here), and a recent blog post about my vastly increased Type 2 Diabetes risk. However, perhaps there’s a recent but relatively study that applies, or perhaps there’s a story you can weave with a handful of SNPs. Or, even better, what can you tell me about my ancestry other than mtDNA and Y-DNA haplogroups? Don’t worry about the strength of the study, reproducibility, etc. – I’m aware of the uncertainties associated with this type of research, and my goal here is to make people aware of possibilities.

Please post your findings in the comments below, and in two weeks I’ll pick the most surprising or interesting findings and make them the focus of a new blog post.

Can you surprise me with my own genome?

I have done a fair amount of analysis on my genome. For example, here’s my Promethease report. My ID is DOD128 in Dodecad, PKEG1 in Eurogenes and HRP0001 in Harappa.

My challenge for you would be to find interesting information about my chromosome 9 which is 93% homozygous.

If you analyze my genome, it would be great if you could let me know about what you found as I am always hungry for more information.

Related Reading

Automate This: How Algorithms Came to Rule Our World
Twelve Sporadic Groups (Springer Monographs in Mathematics)
The House of Crawford: Collected Articles on Our History, Genealogy, Heraldry and Y-DNA
What's in Your Genes?: From the Color of Your Eyes to the Length of Your Life, a Revealing Look at Your Genetic Traits
Forgotten

Genome Similarity

23andme has a feature where you can find out how similar your genes are to your friends and family (who you are sharing with at the site). The result is a bar list with percentages showing similarity.

The number next to each person in the bar list is a measure of similarity. Specifically, it is the percentage of matching genotypes for all of the SNPs on our chip that are located in the genes or regions of interest.

If person 1 has AA and person 2 has AA at a particular position, they are 100% similar. If person 1 has AA and person 2 has AG, they are 50% similar at that position. If person 1 has AA and person 2 has GG, they are 0% similar at that position. We then average the percent similarity over all positions included in that comparison.

You can also calculate these similarity measures (IBS, Identical by State, distances) using plink if you have the genetic data for someone.

Discussing the expected similarity percentages, I figured that siblings and parents generally have similarity measures around the mid-80s. Usually for South Asians, it seems like their similarity percentage with other unrelated South Asians is close to 74%, especially for similar ethnic or geographic groups. Please note that this specific number 74% is valid for the specific set of SNPs included in the 23andme v2 chip. For v3 chip, people are getting higher numbers.

However, I looked far and wide and shared data with 81 people. My highest similarity percentage came out to be 73.22% with Amber, followed closely by a Bihari guy at 73.2% and a couple of other Punjabis. While most of my top matches are South Asian, with a large number of Punjabis, there is no particular pattern with several South Indians and Biharis matching highly too. My top non-South Asian matches are Iranians.

I expected my similarity percentages to be lower like they turned out to be due to my quarter non-South Asian ancestry. So that wasn’t a surprise.

I asked my parents and uncles and aunts about my great-grandmother’s ancestry. I knew she was from Egypt, but I found out that her ancestors had arrived in Egypt with Muhammad Ali Pasha. Since Muhammad Ali Pasha was an Albanian who worked for the Ottoman Sultanate, my relatives deduced that we have some Turk and/or Balkan ancestry.

So I asked a number of Turks, Southern Europeans and North Africans to share. I expected my similarity with them to be less than my similarity with South Asians, since 3/4 ancestry is more than 1/4. But I found something strange.

Let’s take any random person I am comparing my genes to who is not South Asian. If I compare how similar that person is to me against how similar he is to any South Asian, it turns out he’s more similar to the South Asian. This turns out to be true for similarity measures between me and all non-South Asians vs similarity measures between that non-South Asian and all South Asians. In brief, all East Africans, North Africans, Southern Europeans, Northern Europeans, Turks and Iranians (that are in my friends list) are more similar to all the South Asians among my friends list than they are to me.

I found this weird. If I had someone in my friends list who belonged to my great grandmother’s ethnicity or a closely related one, then I should be more similar to that friend than any random South Asian, instead of being the least similar like I was in all cases.

Clearly there was a need for better ancestry analysis in my case.

Related Reading

Advanced Genealogy Research Techniques
What's in Your Genes?: From the Color of Your Eyes to the Length of Your Life, a Revealing Look at Your Genetic Traits
The Twelve Layers of DNA: An Esoteric Study of the Mastery Within (Kryon)
DNA & Genealogy
Genome: The Autobiography of a Species in 23 Chapters (P.S.)

Inbreeding

I have found out I am actually from West Virginia. Ok, I am just joking.

I knew that my family had a history of marriages among relatives. After all I have only 10 great-great-grandparents instead of the usual 16. With my genome in hand, I set about to quantify the inbreeding.

First, I used David Pike’s Homozygosity tool. It analyzes your genome to find significant runs where the same haplotype is inherited from both parents. Large portions of the human genome are like that. The length of these homozygous regions, however, varies depending on the relation of your parents. If your parents are closely related (first cousins in my case), then you will have longer runs. If your parents are distantly related, then over the generations those genes have had a chance to recombine and so you will have shorter runs that are homozygous.

Overall, the percentage of my autosomal (i.e. on chromosomes 1-22) SNPs that are homozygous is 71.767 and I have 41 runs of homozygosity (ROH) of length at least 200. Here are some of my longest runs:

  • Chr 1 has a ROH of length 6009 (30.95 Mb)
  • Chr 8 has a ROH of length 5819 (33.00 Mb)
  • Chr 9 has a ROH of length 5877 (57.81 Mb)
  • Chr 9 has a ROH of length 5941 (24.38 Mb)

Let’s look at my homozygosity percentage by chromosome.

Chr 1: 71.734 %
Chr 2: 69.952 %
Chr 3: 65.741 %
Chr 4: 71.563 %
Chr 5: 69.270 %
Chr 6: 76.025 %
Chr 7: 69.445 %
Chr 8: 72.690 %
Chr 9: 93.323 %
Chr 10: 69.765 %
Chr 11: 71.866 %
Chr 12: 68.443 %
Chr 13: 74.184 %
Chr 14: 68.571 %
Chr 15: 73.087 %
Chr 16: 66.541 %
Chr 17: 77.555 %
Chr 18: 67.763 %
Chr 19: 66.267 %
Chr 20: 66.228 %
Chr 21: 79.902 %
Chr 22: 69.896 %

A majority of chromosomes seem to have reasonable percentages while chromosomes 4, 6, 8, 11, 13, 15, 17 and 21 are high. However, chromosome 9 is really weird: It is 93.323% homozygous.

David Pike writes that:

So far the largest ROHs in 23andMe V2 data that I am aware of consist of:

  • 9191 consecutive tested SNPs, corresponding to a DNA segment of length 49.99 Mb.
  • 6129 consecutive tested SNPs, corresponding to a DNA segment of length 39.05 Mb.
  • 5594 consecutive tested SNPs, corresponding to a DNA segment of length 28.95 Mb.
  • 4644 consecutive tested SNPs, corresponding to a DNA segment of length 27.71 Mb.

The highest percentage for overall autosomal homozygosity that I have so far seen from 23andMe V2 data is 71.763%.

As you can see, I am an extreme case.

A number of members at DNA Forums reported their homozygous percentage. Of all those listed, mine is the 2nd highest.

According to the paper Genomic Runs of Homozygosity Record Population History and Consanguinity:

South/Central Asians and West Asians have more than three times as many ROH in all categories over 4 Mb long than sub-Saharan Africans and other Eurasians. 19% of individuals from these populations have ROH over 16 Mb in length, consistent with the high prevalence of consanguineous marriage (marriage between individuals who are second cousins or closer) in these populations.

My total ROH length (segments > 0.5Mb) is about 282Mb which is about 1.2 standard deviations above the Central/South Asian sample mean in that paper. But I am more than 1.7 standard deviations above the mean for longer segments (>5Mb).

Let’s take a look at a graph from the paper’s supplemental material which plots total ROH length versus number of homozygous segments:

My inbreeding coefficient based on the length of long (>5Mb) runs of homozygosity in my genome (fROH5) is about 0.11 while the average in the Central and South Asian sample for the HGDP dataset is 0.015 (not directly comparable due to different number of SNPs used to calculate).

Finally, I used Plink to calculate my inbreeding coefficient F using all the South Asians from my reference datasets. That coefficient comes out to be 0.1184.

Related Reading

DNA: The Secret of Life
How to Improve Your Marriage Without Talking About It
The Meaning of Marriage: Facing the Complexities of Commitment with the Wisdom of God
What's in Your Genes?: From the Color of Your Eyes to the Length of Your Life, a Revealing Look at Your Genetic Traits
DNA of the Gods: The Anunnaki Creation of Eve and the Alien Battle for Humanity

Harappa Project New Site

As several people had asked, I have set up a separate website for the Harappa Ancestry Project at http://www.harappadna.org/.

I am keeping a link to the new site on the top menu bar here titled Harappa DNA.

I might also crosspost some items from the project here.

I have also set up a Facebook page for the Harappa Ancestry Project. Please like it on Facebook so I can get a nice short name for the Facebook page URL.

I have received several samples and will be reporting some analysis results soon. However, I do need lots of participants, so please spread the word.

Cross-posted at Harappa Ancestry Project.

Related Reading

Script of Harappa & Mohenjodaro & Its Connection With Other Scripts
Facebook All-in-One For Dummies
The Twelve Layers of DNA: An Esoteric Study of the Mastery Within (Kryon)
The Family Tree German Genealogy Guide: How to Trace Your Germanic Ancestry in Europe

Harappa Ancestry Project

I have become interested (some would say obsessed) with genetics recently. I wrote about getting my DNA test done and there’s a lot more about my own results that I plan to bore you with.

One fun application of genetic testing is inferring ancestry: Which ancestral group are you descended from? Can we estimate the admixture of the different population groups you are descended from?

Most DNA testing companies provide information about ancestry and genetic genealogy has taken off. With several genome databases (HapMap, HGDP, etc) and software (like plink, admixture, Structure) publicly available, the days of the genome bloggers are here. And I am trying to be the latest one.

In starting this project, I have been inspired by the Dodecad Ancestry Project by Dienekes Pontikos and Eurogenes Ancestry Project by David Wesolowski. The catalyst for this project was my friend Razib who I bug whenever I need to talk genetics.

What is Harappa Ancestry Project?
It is a project to analyze (autosomal) genetic data of participants of South Asian origin for the purpose of providing detailed ancestry information. So the focus of the project is on South Asians: Indians, Pakistanis, Bangladeshis and Sri Lankans.

The project will collect 23andme raw genetic data from participants to better understand the ancestry relationships of different South Asian ethnicities.

I have named it after Harappa, an archaeological site of the Indus Valley Civilization in Punjab, Pakistan.

Participation
People of South Asian origin, or from neighboring countries, are eligible to participate. The list of countries of origin I am accepting are as follows:

  • Afghanistan
  • Bangladesh
  • Bhutan
  • Burma
  • India
  • Iran
  • Maldives
  • Nepal
  • Pakistan
  • Sri Lanka
  • Tibet

Right now, I am only accepting raw data samples from people who have tested with 23andme.

Please do not send samples from close relatives. I define close relatives as 2nd cousins or closer. If you have data from yourself and your parents, it might be better to send the samples from your parents (assuming they are not related to each other) and not send your own sample.

If you are unsure if you are eligible to participate, please send me an email (harappa@zackvision.com) to inquire about it before sending off your raw data.

What to send?
Please send your All DNA raw data text file (zipped is better) downloaded from 23andme to harappa@zackvision.com along with ancestral background information about you and all four of your grandparents. Background information would include where they were born, mother tongue, caste/community to which they belonged, etc. Please provide as much ancestry information as possible and try to be specific. Do especially include information about any ancestry from outside South Asia.

Data Privacy
The raw genetic data and ancestry information that you send me will not be shared with anyone.

Your data will be used only for ancestry analysis. No analysis of physical or health/medical traits will be performed.

The individual ancestry analysis published on this blog will be done using an ID of the form HRPnnnn known to only you and me.

What do you get?
All results of ancestry analysis (individual and group) will be posted on this blog under the Harappa Ancestry Project category. This will include admixture analysis as well as clustering into population groups etc.

I suggest you read about Dienekes’ analysis on South Asians for an idea about what to expect.

You can access all blog posts related to this project from the Harappa Ancestry Project link on the navigation menu on every page of my website. You can also subscribe to the project feed.

Related Reading

Bioinformatics and Functional Genomics
The Art of Not Being Governed: An Anarchist History of Upland Southeast Asia (Yale Agrarian Studies Series)
Asian Godfathers: Money and Power in Hong Kong and Southeast Asia
Women, War, and the Making of Bangladesh: Remembering 1971
Signature in the Cell: DNA and the Evidence for Intelligent Design

Personal Genomics: DNA Test

Last year in April, 23andme were having a sale for DNA Day, selling their 550,000 SNP test with ancestry and health information for $99 instead of its regular price of $499 at that time. So I decided to take the plunge and sent my spit from the East coast to the West to be analyzed.

Then 23andme had another sale ($99 again but with the catch of a minimum of a year of $5/month subscription in addition), I got my wife and my sister to do it on 23andme’s new version 3 genotyping chip with more than a million SNPs.

I got my results in May 2010 and have been having fun with them since. So let’s take a look.

There are reports for your genetic risk of a bunch of diseases. Those are interesting and useful in some cases, but there is still a lot of work to be done in the area of genetic associations of diseases and for now except for a few important discoveries, family history is probably a better predictor of your disease risk than genetic testing. Oh yeah and there are a couple of scary-looking numbers in my reports.

The health reports also show carrier status and drug response.

In terms of other traits, it’s mostly information I already knew like:

  • I can taste bitter tastes
  • I have wet earwax
  • My eye color is brown
  • I have curlier than average hair

One thing that was a surprise was that I am likely to be lactose intolerant. It’s possible I am somewhat tolerant due to environmental reasons.

Since I wanted more analysis than the 23andme reports gave, I downloaded Promethease which is a freeware software which uses all the information at SNPedia to create a report about your SNPs and what features, traits and health factors are influenced by them. The report it generates is long and interesting, though not formatted very well.

PS. Yes, this is the sort of topic I alluded to in my return announcement.

While there is more navel-gazing coming (mostly about ancestry and genetics), there’s going to be posts of more general interest. Let me just go ahead and say that the friend Razib mentioned is me.

Related Reading

DNA & Genealogy
SNP: The History of the Scottish National Party (Second Edition) (Political Studies)
Trace Your Roots with DNA: Using Genetic Tests to Explore Your Family Tree
Finding Family: My Search for Roots and the Secrets in My DNA
Human Genetics and Genomics, Includes Wiley E-Text