Not all lactose tolerance SNPs are known, several SNPs resulting in lactose tolerance still need to be discovered.
Today, I want to present 6 haplotypes (ht1-6) I could discover in the Kurdish gene pool.
ht3 represents the "European" haplotype which correlates with lactose tolerance. Individuals with "CT" or "TT" at rs4988235 (also called C/T-13910) are genetically lactose tolerant; at 23andme it is "AG" or "AA" (because MCM6 gene is in minus orientation but 23andme does not address it).
Interestingly, 13910T (rs4988235: "A" at 23andme) and 22018A (rs182549: "T" at 23andme) are strongly linked with one another, at least for ht3, the "European" haplotype. However, this is not always the case. There is some literature about 22018A, see here, here, here, and here.
ht3 itself is derived from ht2, which only carries the 22018A mutation. ht2 is fairly rare and does not provide lactase persistence which explains why 22018A is strongly, but not completely related to lactase persistence.
The origin of the "European" lactose persistence 13910T (rs4988235: "A" at 23andme) can be found in populations where the frequency of 22018A (ht2 + ht3) is higher than 13910T (ht3).
In Kurds (N=20) the frequency of 22018A is 8% (ht2 + ht3), the frequency of 13910T is 5% (ht3). Both, ht2 and ht3 are derived from ht1, which has a frequency of 20% among Kurds.
Raz et al., 2013 found that Iraqi Jews (N=96) have a frequency 8.3% for 22018A (ht2 + ht3) and 3.6% for 13910T (ht3), which fits quite well with the Kurdish results.
Find below the frequency of the six MCM6 haplotypes in the Kurdish gene pool:
| ht1 | ht2 | ht3 | ht4 | ht5 | ht6 |
| 20% | 3% | 5% | 15% | 10% | 48% |
Find below the six haplotypes (ht1 - ht6) identified in the Kurdish gene pool (ht7 was identified in the Denisova genome. The coverage of the Neanderthal genome was too low to identify the haplotype.)
| SNP | ht1 | ht2 | ht3 | ht4 | ht5 | ht6 | ht7 |
| rs4988283 | C | C | C | C | C | C | C |
| rs4988262 | C | C | C | C | C | C | T |
| rs2082730 | T | T | T | T | T | T | T |
| rs4988243 | T | T | T | T | C | T | T |
| rs4954492 | A | A | A | A | A | A | A |
| rs41525747 | G | G | G | G | G | G | G |
| rs4988236 | G | G | G | G | G | G | G |
| rs4988235 | G | G | A | G | G | G | G |
| rs41380347 | A | A | A | A | A | A | A |
| rs4988234 | C | C | C | C | C | C | C |
| rs4988233 | G | G | G | G | G | G | G |
| rs2304369 | G | G | G | G | G | G | G |
| rs4988232 | G | G | G | G | G | G | G |
| rs4988226 | G | G | G | A | A | A | A |
| rs309180 | A | A | A | G | G | G | G |
| rs309181 | G | G | G | C | C | C | C |
| rs3213871 | C | C | C | T | T | C | C |
| rs4988203 | C | C | C | C | C | C | T |
| rs182549 | C | T | T | C | C | C | C |
| rs4988199 | A | A | A | A | A | A | A |
| rs4988189 | T | T | T | T | T | T | T |
| rs4988186 | G | G | G | G | G | G | G |
| rs309176 | C | C | C | T | T | T | T |
| rs3087343 | T | T | T | T | T | G | T |
| rs4988177 | T | T | T | T | T | T | T |
| rs3087353 | C | C | C | C | C | C | T |
| rs2289049 | G | G | G | G | G | G | A |
| rs2070068 | G | G | G | G | G | G | A |
| rs1435577 | C | C | C | C | C | G | C |
| rs3769001 | A | A | A | A | A | G | A |
| rs1057031 | G | G | G | G | G | A | A |
Find below the phylogenetic tree of MCM6 haplotypes.
Coehlo et al., 2005 predicted that 22018A mutation occured prior to the 13910T mutation.
Bersaglieri et al., 2004 provided the frequency of both 22018A and 13910T in various populations showing that the frequency of 22018A (ht2 + ht3) is higher than 13910T (ht3) in Pakistan (excluding Kalash).
ht2 (22018A only) is the ancestor of ht3 (22018A + 13910T). ht2 can be found among Kurds, Iraqi Jews and Pakistanis.
I suspect that lactase persistence is also present among a subgroup of ht6.
Very interesting high quality research again. Thank you, Palisto.
ReplyDeleteDo you think that the high frequencies of ht3 in Pakistan could support a "european" genetic impact via Indo-Aryans, possibly aided by local selection afterwards, maybe in relation to the high role of dairy products in Indian tradition (holy cow and all that)?
Thanks.
DeleteThe high frequencies of ht3 in Pakistan (and some regions/castes of India) could be explained with a genetic impact via Indo-Aryans but it is tricky, lifestyle plays a major role. We should keep in mind that some Dravidian speakers show higher frequencies of ht3 as well. An interesting case are the Toda people (45% ht3): They traditionally trade dairy products with their Nilgiri neighbour people. Toda religion centres on the buffalo; consequently, rituals are performed for all dairy activities as well as for the ordination of dairymen-priests. Their Y-chromosome is mostly L and J (Basuet al., 2003).
The lack of ht2 in Europe suggests that ht3 itself did not originate in Europe.
"The lack of ht2 in Europe suggests that ht3 itself did not originate in Europe".
ReplyDeleteThat's a good argument. I can't but agree.
So, the origin could be in India.
ReplyDeletePalisto, I think you will like to take a look at this:)-
ReplyDeletehttp://eurogenes.blogspot.in/2015/05/the-time-and-place-of-european-gene.html
Palisto, I think you will like to take a look at this:)-
ReplyDeletehttp://eurogenes.blogspot.in/2015/05/the-time-and-place-of-european-gene.html