Human Variation Versus Ethnic Groups and Pharmacogenomics

7/28/2019 Human Variation Versus Ethnic Groups and Pharmacogenomics

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Human Variation Versus Ethnic Groups and Pharmacogenomics Help

By Claudia Englbrecht (Guest Author)

Genomics research has taught us how amazingly similar humans are,

genetically speaking. On average, two humans differ in their genome once

every thousand base pairs. The differences can be the change or loss of a

base (A, C, G, T), or the insertion of an additional base. Furthermore, we

observe differences in copy number, i.e., your neighbor might have more

copies of one particular gene than you. Differences that only affect one

nucleotide are called "single nucleotide Polymorphisms" (SNPs, pronounced

"snips"). Polymorphism means "many forms," from the Greek poly for many

and morph for form. In genetics, Polymorphism refers to the natural genetic

variation within a populationthe differences that natural selection acts

upon.

The International HapMap Project

The HapMap (short for haplotype map) was an international project that

identified and catalogued genetic similarities and differences among human

beings. It was a great effort and provided a detailed map of single nucleotide

differences in human populations. This knowledge can be useful in several

ways.

The Study of Human Genetic Variation

An understanding of human diversity sheds light on our ancestry and the

migration routes human populations took when they populated the world.

Most scientific evidence indicates that modern humans originated in Africa.

Migration patterns and individual histories of populations can be deciphered

from our DNA. For example, the higher the variation in a population, the older

it usually is. Accordingly, African populations show the highest genetic

variability. If a population has a very low variabilityi.e. if many people have

identical SNPsit is probably younger or was reduced in size by some

external factor.

Of course, populations in the world are not discrete, but have migrated and

mixed for thousands and thousands of years. Therefore, genetic variants are

usually not exclusive to a single population. However, some SNPs occur more

or less frequently in certain populations. The distribution of A-B-O blood types

around the world is an example of varying frequency patterns around the


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world. For example, the B allele is the rarest and is extremely rare in the

indigenous populations of the Americas. The O blood type has the highest

frequency overall, with the lowest in Eastern Europe and Central Asia.

In other words, the pool of genetic variation is distributed worldwide, with

slight differences in the frequencies of some variants. There is no single,

fixed, exclusive genetic character that every member of a given ethnic group

possesses and that is not found outside that group. However, if we look at a

very large number of variable sites (some areas of our genome are much

more variable than others), we can usually predict ancestrywhether

someone's ancestors came from Central Africa or Siberia. This is due to our

knowledge of the frequency distributions of several hundred genetic variants.

The distribution pattern reflects the historic migration history of modern

humans. The specific genomic areas that scientists look at usually do not

code for any phenotypic traits, unlike the A-B-O blood-type alleles, andtherefore cannot tell us anything about the physical appearance of an

individual.

Biomedical Research

Understanding human genetic variation also has important implications for

the detection, prevention, treatment, and cures of diseases. The discipline of

pharmacogenomics studies genomes in order to understand susceptibility to

diseases and response to drugs and treatments. Drugs are metabolized in our

bodies via complex pathways that involve many enzymes. Therefore,

variations in the genetic code of these enzymes could influence how theywork, how we metabolize drugs, and what the side effects might be.

As discussed above, some genetic variants have different frequencies in

populations worldwide. Accordingly, we would also expect that some drugs

would have different effects in different ethnic groups. Indeed, there are a

several drugs that have been shown to work differently depending on the

ethnicity of the patient; many of them affect the cardiovascular system. Often

the reason for the difference in efficiency or side effects is not really

understood. For example, the drug BiDil has been approved for African-Americans because it only shows benefits in the treatment of hypertension in

this ethnic group. The reason for the difference is likely a genetic variant that

is particularly frequent in African-Americans and not as frequent in other

ethnic groups. However, there might be whites or Asians who could also

benefit from the drug, or, conversely, African-Americans who do not. The fact

that one variant is more frequent in a group does not automatically mean


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that everyone in that group carries it, or that it is exclusive to that group.

Therefore, the ultimate goal of pharmacogenomics is individualized or

personalized medicine, and not medicine based on ethnic or population

categories.

If guidelines for drug prescription were guided by self-defined ancestry and

ethnicity, medical care would most likely not be very good. As the thousand-

dollar genome approaches reality, it seems more likely that individual

genomes will be screened on a regular basis and drugs prescribed

accordingly. In some rare cases, genetic tests are already performed before a

drug is administered.

There are several obstacles on the road to personalized medicine. First, we

have to be able to understand the genetic variant that is associated with a

drug response. This is not easy. Second, a thousand dollars is still a lot of

money, and the genetic test might be appropriate only if the potential

treatment were very expensive. Third, knowing your entire genetic code is

problematic. Could you handle all that information, including your

predispositions to disease? Do you want your employer to have access to it?

Do existing laws adequately protect your privacy? These questions must be

addressed publicly. We're not talking about science fiction, but about

developments in the near future. It's time to reflect deeply on these personal

and cultural choices.

Related Resources

Johnson, J.A. "Ethnic Differences in Cardiovascular Drug Response: Potential

Contribution of Pharmacogenetics." Circulation 118.13 (2008): 1383-1393.

Urban, T.J. "Race, Ethnicity, Ancestry, and Pharmacogenetics." Mount Sinai

Journal of Medicine 77 (2010): 133-139.

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Human Variation Versus Ethnic Groups and Pharmacogenomics