HLA-DR16: distribution map, subtypes, SNPs and associated medical conditions


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Here is a map showing the allele frequency of HLA-DR16. The maximum frequencies are observed in the United Emirates (18%), Bulgaria (17.5%), Macedonia (15.5%), Greece (13.5%), Albania (12.5%), Serbia (11%), Croatia (10.5%) and Sardinia (10.5%).

It is completely absent from the Saami, Breton, Basque and Pasiegos populations, three population isolates with high Mesolithic European ancestry. DR16 is also nearly absent (less than 1%) from Finland, Scandinavia, Ireland, Wales and (supposedly) Highland Scotland, but also from Morocco. All these ethnic groups and regions have in common a high percentage of mtDNA haplogroup U5, associated with Mesolithic Europeans.


Overall, the distribution is fairly similar to that of Y-haplogroup E-V13. It is likely that the HLA-DR16 gene was found among E-V13 people in Southeast Europe during the Mesolithic period and was spread around Europe by Neolithic farmers after they mixed with E-V13 people. Neolithic farmers would thus have brought DR16 to places like Sardinia, but not to the Atlantic and Baltic fringes of Europe. Unsurprisingly, E-V13 is also completely absent from the Saami, Breton, Basque and Pasiegos populations.


Medical associations

HLA-DR16 is associated with Chaga's cardiomyopathy, rheumatic heart disease, coronary artery ectasia, and chronic discoid lupus erythematosus.

DRB1*1601 is associated with tuberculosis risk.

DRB1*1602: Juvenile rheumatoid arthritis, rheumatic heart disease, Takayasu arteritis, systemic sclerosis (SSc) & anti-DNA topoisomerase I (anti-topo I) antibody, melioidosis (Burkholderia pseudomallei) infection.


You can verify if you carry HLA-DR16 by checking your raw data from 23andMe, Geno 2.0 or FamilyFinder, although I am not sure which allele is positive or negative. There are two subclades (16:01 and 16:02) but 99% of Europeans belong to 16:01.

- DRB1*16:01 : rs3129891 (A = DR16+) or rs6923504 (G = DR16+).

You normally need to be positive for both alleles.

Link to prehistoric populations

I have checked these SNP's in over 20 Mesolithic to Bronze Age genomes from Haak et al. 2015 and other papers.

Rs3129891 was positive in:

- Mesolithic Samara (homozygous AA)
- Mesolithic Karelia
- one Neolithic LBK sample (homozygous AA)
- one Neolithic sample from Spain
- one Yamna sample (I0231)

Rs6923504 was positive in:

- LBK Stuttgart
- Neolithic Halberstadt (I0099) (homozygous GG)
- one Yamna sample (I0231)
- one Corded Ware sample (I0104)

Apparently only the Yamna sample carried both mutations and was DR16.
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