Recently, I traveled on the train to the far corner of northeastern Montana to attend a family funeral. Although the event was sad, I had the privilege of a personalized tour by my elderly father of the homestead where my grandparents settled and farmed in the 1920s. The experience piqued my interest in my ancestors, several of whom came from Norway to the United States in the late 1800s, and how their experiences and the genetic background affect me and my children. In fact, much of that part of the country was settled by Scandinavians, and many of my immediate family share the fair skin and light eyes of that northern European region.
Stanford geneticist Carlos Bustamante, PhD, studies this type of gene flow across geographic regions, and its result on the genetic diversity of current populations, on a much larger scale. In research published online today in the Proceedings of the National Academy of Sciences (subscription required), he and former postdoctoral scholar Brenna Henn, PhD, describe a similar phenomenon in southern Europe, which tends to — for reasons not well understood — be more genetically diverse than northern Europe.
They’ve discovered that many southern Europeans, particularly in Spain, Portugal and other parts of Iberia, share genetic traits of northwestern Africans found in a geographic region called Maghreb. (This was somewhat surprising because previous research comparing Southern Europeans with a benchmark sub-Saharan African population had found little genetic flow between the two groups.) The findings suggest that at least some of the genetic diversity seen in southern European populations is due to gene flow from North Africa that occurred during the past few centuries.
Bustamante and Henn described their results to me in an email exchange. According to Henn:
For me, it was most surprising that we were really able to pinpoint the source of the gene flow to the Maghreb (or northwestern Africa). Populations in the Western Sahara, Morocco and the Tunisian Berbers clearly showed a strong signal of genetic ancestry with Iberian populations. It is this connection to the Maghreb and Berbers which is both consistent with historical records and highlights the heterogeneity of populations across North Africa as well.
But the researchers, who studied small genetic differences called single nucleotide polymorphisms, or SNPs, in more than 2000 individuals from 43 populations to conduct the study, also found differences among the southern Europeans themselves. According to Bustamante:
To me, the differences among Southern European populations were really interesting. Populations in southwestern Europe, such as Spain and Portugal, showed clear evidence of North African gene flow, but there was little in south-central regions such as Italy, or in the southeastern populations of Greece or Turkey. We attribute this to relatively recent gene flow in historical times (most likely during the period of Moorish inhabitation in Iberia) that differentially impacted European regions.
On the other hand, Middle Eastern ancestry is seen across southern European populations, presumably due to the expansion of Neolithic farmers. There is likely a secondary wave of Middle Eastern ancestry also during historical times which underlies a south-southeast to southwest gradient.
In other words, the expansion from the Middle East due to the rise of farming preceded by thousands of years another genetic wave that occurred during a period of conquest and occupation of the Iberian Peninsula by North Africans.
This is all fascinating stuff to me. My ancestors, too, were motivated by both politics and agriculture when they moved from Europe to the United States, and then to eastern Montana. But the research has more than just cultural or historic relevance. Understanding how populations across the world are related to one another allows researchers to more accurately determine the prevalence, and the clinical importance, of genetic variants related to disease risk. In particular, Bustamante and his colleagues found that North Africans have a higher genetic risk for multiple sclerosis than most populations — something that would not have been discovered if that population had not been studied and compared to neighboring regions.
The finding is a strong argument that the genetic study of many ethnic groups is critical to truly tap the power of genetic risk estimates and their potential to meaningfully affect clinical care. Said Bustamante:
Multi- and trans-ethnic medical genetic studies are critical to accurately estimate the genomic risk of disease. There is a somewhat surprising substructure of genetics, where common variants are well-shared across populations, but rare variants tend to be population specific, and increase the importance of multi-ethnic cohorts.
Eliminating health disparities in minority populations is clearly a passion of Bustamante’s. Last weekend, he co-chaired the 2013 Health Disparities and Genomic Conference in San Francisco. The conference’s subtitle? ‘Why we can’t wait.’ I’d like to think that my pragmatic, hard-working grandparents and great-grandparents would have approved.
Previously: Cracking the code of 1000 (make that 1092!) genomes, Stanford researcher aims to develop database built on the DNA of Latin American descendants and Non-European representation woefully lacking in genomics studies, say Stanford geneticists
Photo by Kevin Hale.