June 19, 2009

HAPMIX for detection of chromosomal segments of distinct ancestry

The authors claim:
The three Middle Eastern populations (Bedouin, Palestinian, and Druze) all show a substantial African-related mixture (3%–9% African-related ancestry). The inferred dates of 60–90 generations correspond to about 2,000–4,000 years ago – contemporaneous with our estimate of the oldest admixture time for the North African Mozabite population – taking into account the fact that HAPMIX systematically underestimate mixture dates by up to 25% for mixtures this old (see simulations above). These results are historically interesting, allowing us to conclude that there is likely to be African ancestry in Middle Eastern populations today that dates to population mixture that occurred in Biblical times.
This is, however, contradicted, by the finding of virtually no "Yoruba" ancestry in the same Middle Eastern populations the best study to date.

It is not really difficult to see what went wrong. By using CEU and YRI populations as parentals, the authors were unable to discover the true ancestral components. Middle Eastern populations are composed primarily of Middle Eastern Caucasoids, not Northwestern Europeans; moreover, their African influences are mainly Northeastern, not West African.

As we know (see previous link), Caucasoids from Europe, Central/South Asia and the Near East are not uniform, but form separate clusters. Indeed, even Europeans themselves are not uniform.

Nor are Africans themselves uniform, according to the latest study of Tishkoff et al, and Middle Eastern populations (see Table S8) have no significant admixture from West Africa, but a noticeable "Cushitic" admixture.

This paper could serve as a warning to the limitations of statistical inference. A good tool (and HAPMIX is indeed such), can lead to erroneous results (biblical-era admixture with Sub-Saharan Africans), if it is used with the wrong input data.

PLoS Genetics doi:10.1371/journal.pgen.1000519

Sensitive Detection of Chromosomal Segments of Distinct Ancestry in Admixed Populations

Alkes L. Price et al.


Identifying the ancestry of chromosomal segments of distinct ancestry has a wide range of applications from disease mapping to learning about history. Most methods require the use of unlinked markers; but, using all markers from genome-wide scanning arrays, it should in principle be possible to infer the ancestry of even very small segments with exquisite accuracy. We describe a method, HAPMIX, which employs an explicit population genetic model to perform such local ancestry inference based on fine-scale variation data. We show that HAPMIX outperforms other methods, and we explore its utility for inferring ancestry, learning about ancestral populations, and inferring dates of admixture. We validate the method empirically by applying it to populations that have experienced recent and ancient admixture: 935 African Americans from the United States and 29 Mozabites from North Africa. HAPMIX will be of particular utility for mapping disease genes in recently admixed populations, as its accurate estimates of local ancestry permit admixture and case-control association signals to be combined, enabling more powerful tests of association than with either signal alone.



Diogenes said...

It's interesting that this admixture event was dated by HAPMIX to roughly the same era as Nile agriculturalists developed into Egyptian Pharaonic civilization, which likely happened as they evolved their food producing techs allowing formation of enough surpluses for relatively much larger upper classes...

ejm said...

Neat post!
Late comment on an old thread- but I am interested in applying HAPMIX to non-human data, but some human aspects seem to be hard coded into the SNP filtering. Anyone else using HAPMIX for other taxa? Or even other human data sets? Send me an email! ejmctavish [at] utexas.edu