• Constance Hilliard

When “Genetic Diversity” Clashes with Our Medical Notions of “Inclusion”

In recent years, I've come to realize that the term "genetic diversity" is often confused with "ethno-cultural diversity" by the public at large and sometimes even among scientists. Genetic diversity relates to the number of genetic variations or Single Nucleotide Polymorphisms (SNPs-pronounced SNIPS) that will be found in the genomes of genetic populations. The other use of diversity refers to adding marginalized minorities to mainstream institutions and activities. The two are not interchangeable. This is especially so because the evolution of our human species in Africa and the migration of a branch or branches of that population out-of-Africa led to a lopsided gene variant count among different populations. Africans have the greatest amount of genetic diversity because they carry the full range of homo sapien ancestral gene variants. Other populations carry a portion of that whole. At the time of the completion of the Human Genome Project, researchers estimated that in addition to the 23,000+ genes that all humans carried, there existed as well approximately 2 million variants of those genes carried by "genetic niche populations" and individuals. However, by 2017, that number had risen to 324 million.

The implications for precision medicine or immunotherapy involving populations of African descent can be dire, because only 3% of the African genome has been sequenced compared to 81% of the European genome. So, populations in Africa may have twice as many gene variants as non-Africans, but so little of these SNPs have been studied. The problem created by this reality is only now coming into focus. That is, different genetic populations may display the same disease symptoms, but the variants triggering these diseases may not be the same from one genetic population to the next. An excellent example is the case of lactose intolerance or lactase non-persistence. Geneticists Sarah Tishkoff and Michael Campbell at the University of Pennsylvania have found that lactase persistence (lactose tolerance) involved different sets of genetic variants or SNPs in diverse genetic populations. For instance, the SNP associated with the adult ability to hydrolyze milk in Europeans was C/T-13910. But in Africans, this function was regulated by G/C-14010 in Tanzanians, T/G-1395 in Kenyans and C/G-13907 in Sudanese, which reflected the greater degree of genetic variation on that continent. Would this also be the case with other traits or disorders, or in short, were disease-causative variants genetic population specific?

If the answer was "yes", then disease variants that were being identified by GWAS and other big data studies might not pertain to non-European populations, whose genomic profile and genetic variants were not being extensively studied. So, how could this deficit be corrected? One effort has been to bring greater "diversity" to the reference genome that is used to match diseases to variants, but has been found to be predominantly European. However, if Africans contain the major portion of human gene variants, then attaching occasional African segments to a predominantly European genome may be insufficient to identify disease-triggering gene variants in the non-Europeans.

If we look at the Chinese, they are not waiting for western medicine to patch up America’s ethnocentric reference genome. In 2016, the Chinese Academy of Medicine launched a major project to create ancestry-specific reference genomes in order to match disease-causative SNPs within their own genetic groupings, such as the Northern Han, Southern Han and Koreans.

And lest we forget -- ancestry is not race. The 37 million African-Americans of slave descent in the United States are a genetic niche population, whose admixed genomic profile is distinct from that of Nigerian-Americans or any other African population that might be called “Black”. The technological advances created by the fast-growing DNA ancestry industry has provided the first step in identifying genetic niche populations, at a level of precision that will allow us to finally discard racial classification schemes in medicine. But in order to do so, we will first need to discard America’s one-size-fits-all health and medical model, which universalizes the biological traits of Europeans. This confusion may be inadvertent. But it leads to a conflating of "genetic diversity" with "ethno-cultural diversity," which can only worsen the health disparities crisis for underrepresented minorities, particularly in the field of genomic medicine.

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