GG at rs12913832 in the HERC2 gene results in light eyes (blue/green) eyes; AG and AA results in brown eyes.
My goal is not only look at the rs12913832 SNP itself but to determine the number of DNA segments that carry the SNP rs12913832; the goal is to determine the number of HERC2 variants (=number of different HERC2 segments) in the Kurdish gene pool. 23andme (and other companies) have a chip-based analysis approach, thus, the genetic read-out only contains data about the single SNPs but not in relation to other neighboring SNPs. The only way to determine DNA segments is to have genetic data of multiple close relatives.
Example with very short DNA segment consisting of two SNPs only:
Person A: rs12913832=AG; neighboring SNP rs7183877=AC.
With this amount of information it is impossible to determine the two DNA segments that were inherited from father and mother of person A. Is rs12913832=A and rs7183877=A on the same DNA segment and inherited from the same parent? With this amount of data we cannot know. "Phased DNA", a new tool at gedmatch can somewhat address this question but not in all cases.
Let's say father and mother of person A have rs12913832=AG and rs7183877=AC as well. We still cannot say if rs12913832=A and rs7183877=A are on the same DNA segment.
Let's say we also know the SNP results of as sibling of person A" rs12913832=AA; neighboring SNP rs7183877=AA. Now, we can determine the DNA segments
DNA segment1: rs12913832=A and rs7183877=A
DNA segment2: rs12913832=G and rs7183877=C
Person A and both parents of person A have one copy of segment1 and one of segment2, while the sibling of personA has two copies of segment1.
This example was only based on two SNPs but it is more interesting to cover a larger DNA segment consisting of all tested SNPs of the HERC2 gene (at least all the SNPs tested by 23andme).
Having genetic data of multiple relatives I was able to determine a total 7 DNA segments of the HERC2 gene variants: two HERC2 variants correlate with light eye colors, the five other HERC2 variants of the HERC2 correlate with dark eyes.
The SNP data of the HERC2 variants are presented in the spreadsheet.
Some observations/results:
1.
Kurdish DNA segments for light eye colors are
rs12913832=A
rs1129038=T
rs916977=C
rs1667394=T
2. Kurdish DNA segments for dark eye colors are
rs12913832=G
rs1129038=C
rs916977=C,T*
rs1667394=C,T*
*From other Kurdish SNP data we know that this correlation is always true for Kurdish DNA segments for light eye colors, always true for rs1129038, but not always for rs916977 and rs1667394 (Branch#3 for dark eye colors is also rs916977=C, rs1667394=T).
HERC2 SNP results of all tested Kurds can be described by combining 2 of the 7 HERC2 variants.
Example:
HERC2 SNPs of KD014 are a mix of Branch#1 and Branch#6.
Next, I generated a phylogenetic tree of the 7 HERC2 variants. Branch#7 is the most ancestral branch. The two branches that result in light eye colors (Branch#1 and Branch#2) are closely related and descendent from Branch#3.
The difference of Branch#1 and Branch#2 is the SNP rs11636232; the difference between these two branches and the other five branches is SNP rs12913832. With the help of ALFRED I could determine the frequency of Branch#1 and Branch#2 in several populations (assuming that there is no other HERC2 variant for light eye color):
Sorted by Branch#1:
| Branch#1 | Branch#2 | |
| Brahui | 2% | 2% |
| Balochi | 8% | 2% |
| Balochi | 12% | 6% |
| Kalash | 12% | 16% |
| Sardinian | 16% | 4% |
| Palestinian | 18% | 3% |
| Burusho | 18% | 12% |
| Basque | 19% | 21% |
| Italians | 25% | 19% |
| Adygei | 26% | 6% |
| Orcadian | 28% | 41% |
| Galician | 30% | 17% |
| French | 32% | 30% |
| Russians | 36% | 46% |
| Italians | 42% | 27% |
| Swedes | 42% | 54% |
| Germans | 46% | 33% |
| Danes | 52% | 32% |
| Austrian | 55% | 28% |
| Swiss | 69% | 25% |
Sorted by Branch#2:
| Branch#1 | Branch#2 | |
| Brahui | 2% | 2% |
| Balochi | 8% | 2% |
| Palestinian | 18% | 3% |
| Sardinian | 16% | 4% |
| Balochi | 12% | 6% |
| Adygei | 26% | 6% |
| Burusho | 18% | 12% |
| Kalash | 12% | 16% |
| Galician | 30% | 17% |
| Italians | 25% | 19% |
| Basque | 19% | 21% |
| Swiss | 69% | 25% |
| Italians | 42% | 27% |
| Austrian | 55% | 28% |
| French | 32% | 30% |
| Danes | 52% | 32% |
| Germans | 46% | 33% |
| Orcadian | 28% | 41% |
| Russians | 36% | 46% |
| Swedes | 42% | 54% |
Edit 06/10/2013:
Maju asked for the "percentage of Kurds in each branch". With the limited number of 23andme tested Kurds (N=20) the percentages can be off.
Percentage of Kurds in each HERC2 branch
| Branch#1 | 22.5% |
| Branch#2 | 5.0% |
| Branch#3 | 20.0% |
| Branch#4 | 10.0% |
| Branch#5 | 17.5% |
| Branch#6 | 20.0% |
| Branch#7 | 5.0% |
From the few East-Europeans 23andme results of HERC2 I have seen so far I can say that East-Europeans have Branch#1, #2, #5 and #6, but not Branch#3, Branch#4 and Branch#7 (Note: Branch#3 and Branch#4 are the ancestral haplotypes of the two light eye color branches #1 and#2).
Besides Kurds, I found Branch#3 in one person from the Philippines (Branch#3 and #5), one Maltese (Branch#3 and #5), one Turk (Branch#3 and #1), and one multi-ethnic Canadian (Branch#3 and #2).
Besides Kurds, I found Branch#4 in one multi-ethnic US American (Branch#4 and #6), one Assyrian (Branch#4 and #1), and one British (Branch#4 and #2). I found one Ethiopian 23andme result that cannot be described with the 7 branches, so there might be more branches for brown eye color in Africa.
In the spreadsheet I now added all potential combinations of the 7 variants in a separate sheet.
Edit: July 02, 2013:
I got some questions why some populations have let's say 20% Branch/haplotype #1 and #2 but not 20% of the population has light eye colors. The reasons is because haplotype 1 and 2 are recessive.
Thus, in order to get light eye colors not one but 2 copies/alleles are needed, one inherited from the father, one from the mother.
How to calculate frequency of light eyes in a population based on my presented tables (based on the Hardy-Weinberg principle):
Frequency of light eyes in a population = (%ht1 +%ht2)2
Example1: Germans have 46% ht1 and 33% ht2.
(46%+33%)2
= (0.46 + 0.33)2
= 0.792
= 0.62
= 62%
62% of the Germans have light eye color based on the HERC2 genotype.
Related:
The color of the eyes: 7 HERC2 variants in the Kurdish gene pool
The color of the eyes: 7 HERC2 variants in the Eurasian gene pool
The color of the eyes: at least 17 HERC2 variants in Human gene pool
This study is most interesting, thanks a lot. The only thing that I'm missing (other than maybe a map) is the percentage of Kurds in each branch (after all it is a genetic blog with Kurdish focus, right?)
ReplyDeleteBut, regardless, it is most informative re. eye color genetics and its geographical variance. I'm not aware of any such HERC2 haplotype geographical study, so I must vehemently congratulate and again thank you for your effort.
Assuming, as would be natural, a West Asian origin for both haplotypes, which we could label maybe 'Kalash' (K) and 'Burusho-Palestinian' (BP) based on the highest haplotype frequencies you report in the region, it seems apparent to me that:
1. West Asia is almost homogeneously dominated by the BP type with the K type being secondary to it everywhere (excepted the Kalash). This is consistent, I think, with the phylogenetic history you describe.
2. In Europe, the BP (ancestral) type shows a similar patter in Central Europe (Swiss, Danes, Austrians, Germans, Italians) and also among the Adygei (who, for population genetic purposes, should be rather considered among West Asians) and Galicians.
4. However in Russia and Northernmost Europe (Sweden, Orkney), it is the K type (derived) which is the dominant one.
5. French and Basque have the two variants quite balanced.
Fascinating. I'm so much mentioning this in my blog right now! Thanks again.
Mentioned at my blog: http://forwhattheywereweare.blogspot.com/2013/06/herc2-haplotypes-phylogeny-and.html
ReplyDeleteIf you have any issue with that, just tell me, please.
Interesting little analysis here. Here are my family members results for these SNPs.
ReplyDeleters12913832
Father: AA
Mother: GG
Uncle (father's brother): AG
Me: AG
Brother: AG
rs1129038
Father: CC
Mother: TT
Uncle (father's brother): CT
Me: CT
Brother: CT
Now my father has pure brown eyes which seems to match his results quite well. My mother has blue eyes which also seems to match her results quite well. My uncle, brother and I all have the same results for these SNPs but my uncle and I both have hazel eyes whereas my brother has pure brown eyes. That is my uncle's and my own eyes have a light brown ring around the pupil in the center and then they are green on the outside. My brother on the other hand has no green in his eyes. They are pure brown.
Thanks for the great effort!! I've checked all my SNPs and I'm in the Branch #5..
ReplyDeleteMfA(KD036)
Made a map out of your data, Palisto (including Kurds).
ReplyDelete