GENEWATCH
 
GENOMIC TESTING AMONG AFRICAN AMERICANS: PROBLEMS, LIMITATIONS, AND SOLUTIONS
By Fatimah L. C. Jackson
 

from GeneWatch 31-1 | Jan-July 2018

The acceptability and feasibility of regular genomic testing has reached the American consumer, and the public is largely receptive. Bolstered by exaggerated and futuristic portrayals of genomic testing in the popular media, actual genomic testing currently falls short in its utility to identify and act on most disease susceptibility genes or accurately elucidate deep ancestry. Although such tests are highly accessible, they remain interpretively problematic for Americans of non-European biological lineages, lacking both the necessary historical context and the appropriate reference databases. As a result, the psychological benefits and physiological gains of genomic testing remain skewed towards clients of European ancestry and expressing European versions of certain diseases.

Problems:

For many non-Europeans, the results look like the case presented below in Figure 1 from a US-born American woman. The analytical results of this individual show huge swaths of her genome (64%) that are either unassigned to any geographical region or for which no data currently exists.

 

[IMAGES HERE]

Figure 1. Geographical assignment of segments of specific chromosomes.

In the case of this individual, more is known about her 20% European heritage than the 15.8% that can be confidently assigned to Sub-Saharan Africa. Of the African component, the majority is from West Africa. Interestingly, the European-identified genomic segments remain short, suggesting historic rather than recent admixture, the African-identified segments are elongated but limited to chromosome 5 and the X chromosomes. So the African-identified segments are recent, but this is incompatible with the 64% of this individual's genome that remain geographically unassigned or has not been seen before. This genomic asynchrony begs the question of actual genomic origins; we clearly know a great deal about a small fraction of humanity (Europeans) and are not yet equipped to process the interaction of multiple continental sources that occur with increasing regularity in normal American genomes.

Limitations:

When the reference databases are predominantly Eurocentric, so are the genomic priorities. This is expected and not problematic in and of itself, yet it does present issues when the client base is ethnically and geographically diverse and decidedly non-European. For example, the opportunity for quantifying one's Neanderthal ancestry, an issue of interest for many European-descended individuals, appears to provide little incentive for genomic testing among many African Americans. Among many African descended individuals, Neanderthal ancestry levels are usually low to virtually non-existent and it appears that no significant introgression of Neanderthal genes occurred among continental Africans in modern human evolutionary history.

Another issue for many Legacy African Americans - that is, African Americans who have been in the country for 11 to 16 generations and whose ancestors have experienced and contributed to the country's development - is that more information is known about the smallest components of their genomes than is revealed about the larger, residual African components. This limits the value of genomic testing of these individuals and, since much of this admixture with Europeans occurred within the context of African American enslavement, the presence of European-based segments in the genomes of African Americans recalls a psychologically painful past. We have found this to be particularly evident among the estimated 30% of Legacy African American men who carry Y-chromosome haplogroups found more commonly in North Atlantic Europe.

For more recent African Americans, the offspring of recent immigrants from continental Africa, current genomic testing is particularly non-illuminating. Results revealing that West African Americans are 99% African with no further stratification are predictable yet devoid of the nuanced regional and ethnic specificity that Americans of European origin have come to expect. If Africa was studied systematically, we expect it to yield as much, if not more, geospatial and ethnic complexity as Europe, particularly since humans have had a protracted residence in Africa and extensive migrations throughout the continent have occurred over hundreds of thousands of years. Among college students who are the first American generation of African immigrants, current genomic testing efforts are discouragingly non-informative. 

In our studies of genomic testing among Legacy African American college students, there is a consistently greater interest in genomic testing to reveal their patterns of African admixture. This is likely because Legacy African Americans are an amalgamation of West and Central African ethnic and regional groups with modest gene flow from specific non-African groups.[1]  Unfortunately, however, the knowledge of intra-African genomic diversity remains lacking. For the majority of these African Americans, the more African their lineage, the less current genomic testing is able to reveal about their disease susceptibilities, ancestry, and phenotypic markers. In previous studies we have shown that personalized genomic testing can have multiple beneficial educational ramifications for African American college students, so in the absence of relevant information, these opportunities (to, for example, enhance interest in STEM) are diminished.[2]

Very limited genomic studies of indigenous Africans have been done and even fewer are publically available and integrated in general reference databases for comparative research purposes. Although the 1000 Genomes Project reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping, Africa was not adequately represented given its status as the homeland of our species, continent of longest residence, and therefore the indigenous peoples with the greatest expected collective accumulations of acquired mutations.[3] Although the 1000 Genomes Project characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms [SNPs], 3.6 million short insertions/deletions [indels], and 60,000 structural variants), all phased onto high-quality haplotypes, coverage of the non-European populations from whom many American lineages can be traced remains insufficient - particularly given the long presence of African-descended individuals in this hemisphere, the extensive opportunities for gene flow with non-Africans, and the continentally diverse origins of these early Africans to America. This was noted over twenty years ago, yet the deficiency in our databases persists.[4]

Solutions:

How can we remediate this situation and bring parity to genomic testing? A first step is to increase the number of diverse non-European individuals in the reference databases, creating truly comprehensive and representative databases for meaningful world-wide comparisons. A particular need is to capture the high variability of indigenous African and tropical Asian and Amerindian groups since much of this genomic diversity is not yet characterized. This has to be done in an intentional fashion, not haphazardly or opportunistically. We need clear hypothesis-driven sampling strategies for studying genomic diversity in non-European peoples and these need to be coupled with relevant historical and geospatial data.

We need to identify the salient population substructure of American donors so that their genomics can be ecologically and historically contextualized. Using ethnogenetic layering, we have hypothesized that microethnic groups such as the Gullah/Geechee of the South Carolina Lowcountry may retain unique genomic markers as a consequence of their relative geographic and cultural isolation compared to other more inland African American microethnic groups.[5] Lumbee Native Americans of North and South Carolina may have different genomic profiles than Dene (Navajo) Native Americans of Arizona and New Mexico, not only because of the geographical distances between these groups, but also because of their differing population histories, migration stories, admixture patterns, dietary exposures, and other relevant variables. African Americans admixed historically with east coast Native Americans may have their Native American ancestry discounted since the reference standard is based on southwestern U.S. Native American peoples.

At Howard University, we have launched the 1000 African Diaspora Genome Project in conjunction with research collaborators at Helix and National Geographic. Our aim is to provide historically-informed, geospatially diverse sampling to the study of African-descended peoples in the Americas. To this we hope to embrace a 10,000 African Genomes Project to more effectively capture the magnitude of genomic variability in the homeland of humanity. The third phase of this series is the 1000 Red Sea African Diaspora Genome Project which seeks to trace the migration pathways of African-descended groups eastward across the Red Sea and Indian Ocean. Once completed, these databases will provide the scientific community with greater referencing depth with expected positive ramifications for a public increasingly interested in and dependent upon the results of genomic interpretations. 

 

Fatimah L. C. Jackson, Ph.D., is a Professor of Biology and Director of the W. Montague Cobb Research Laboratory at Howard University. (fatimah.jackson@howard.edu)

 

 

ENDNOTES

1. Jackson FLC and Borgelin LFJ 2010 How Genetics Can Provide Detail to the Transatlantic African Diaspora  IN The African Diaspora, Edited by Tejumola Olaniyan and  James H. Sweet, Indiana University Press, pp. 25-75.

2. Johnson J and Jackson F 2015 Use of multiple intelligence modalities to convey genetic and genomic concepts in African American college biology students.Natural Sciences 7(6):299-308.  doi: 10.4236/ns.2015.76033

3. The 1000 Genomes Project Consortium. 2015 A global reference for human genetic variation. Nature 526: 68-74 (01 October 2015) doi:10.1038/nature15393

4. Jackson, F.L.C. 1997a Assessing the Human Genome Project: An African American and Bioanthropological Critique. IN Plain Talk about the Human Genome Project, E. Smith and W. Sapp, eds., Tuskegee University: Tuskegee, AL, pp. 95-103.

Jackson, F.L.C. 1997b Concerns and priorities in genetic studies: Insights from recent African American biohistory. Seton Hall Law Review, 27(3): 951-970.

Jackson, F.L.C. 1998 Scientific limitations and ethical ramifications of a non-representative Human Genome Project: African American responses. Science and Engineering Ethics 4:155-170.

5. Jackson, FLC 2008 Ethnogenetic Layering (EL): An alternative to the traditional race model in human variation and health disparity studies. Annals of Human Biology Mar-Apr 35(2):121-144.

 

 

 

 
 
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