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.

Harappa Ancestry Project Update

I have got 25 participants to the Harappa Ancestry Project now. But we still need more especially from the Hindi belt.

I have been detailing the datasets I am using:

I have also started admixture analysis of the reference populations and first batch of project participants.

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.

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.