Research Article: Genomes, Populations and Diseases: Ethnic Genomics and Personalized Medicine

Date Published: , 2010

Publisher: A.I. Gordeyev

Author(s): V.A. Stepanov.



This review discusses the progress of ethnic genetics, the genetics of common diseases, and the concepts of personalized medicine. We show the relationship between the structure of genetic diversity in human populations and the varying frequencies of Mendelian and multifactor diseases. We also examine the population basis of pharmacogenetics and evaluate the effectiveness of pharmacotherapy, along with a review of new achievements and prospects in personalized genomics.

Partial Text

The concept of personalized medicine, which puts the individual patient, with all of his specific peculiarities, into the center of attention, is not new. The 19th-century Russian physicians M.Y. Mudrov and N.I. Pirogov were well aware of this principle. “A doctor treats the patient, not the disease… Each patient needs special treatment depending on his physical constitution, even if the disease is the same,” wrote Mudrov. The great medical practitioners of the past also acknowledged the prophylactic value of personalized medicine – “Healthy people should be kept in hand… they should be advised on keeping to a healthy lifestyle” [1] and “a disease is easier to prevent than to treat” [2]. A new appreciation and the real potential for personalized medicine have re-appeared in the age of molecular genetics. By the end of the 1990s, a new concept of genomic medicine had started to take form [3, 4], and this concept involved “the routine use of genotyping methods, usually in the form of DNA-testing, for improving the quality of healthcare” [3]. The modern understanding of personalized medicine is based on the principles of preventive medicine, which were postulated by Nobel-prize laureate Jean Dausset [5]. The outlines of this concept are eloquently described by the 4P medicine principle or system medicine, which was suggested by Leroy Hood [6–8]. This principle states that “reactive” medicine (which reacts to a disease and fights its symptoms) must turn into predictive, preventative, personalized, and participatory medicine; namely, medicine that will be aimed at predicting the disease before it manifests itself through symptoms, take into account any individual (mainly genetic) traits of the patient, as well as involve the active help of the patient in identifying his or her genetic traits and in determining preventive measures.

The geographical region, ethnic group, and population largely determine the genetic traits of an individual. Setting aside the issues of the substance, the terminological and meaningful differences in the geographic, ethnic and population levels of gene-pool organization, we shall review these terms in the context of personalized medicine in which they are essentially synonymous – they reflect the individual traits of a human that are dependent on his genetic origins.

How different are human populations genetically? Human population genetics give a precise answer to this question – interpopulation differences in a global sense (comparing the populations of different continents) are responsible for 10–15% of the genetic variability in humans (Table 1). In other words, the Wright Fixation Index ( Fst ) is 0.10-0.15 when estimating the global level of genetic differentiation in human populations. This interval includes values obtained for most systems of genetic markers in classical and molecular population genetics of humans — blood type, protein polymorphism, RFLP, Alu-repeats, hypervariable segments of mtDNA [28, 32]. Exceptions are the highly mutable microsatellites (STR), whose level of genetic differentiation is much lower (4–5%), and the  Y -chromosome, whose variants differ (20-30%) between populations much more than other marker systems. These two types of markers are so distinctly different because of specific evolutional, population, and social mechanisms we will not discuss in this work (see [28]).

One of the main advantages of personalized medicine is the individualization of drug therapy. Response to a drug, choice of the optimal drug class, dosage, and usage schedules can, at least partially, be determined using genetic factors. Information on individual genetic markers can help a clinician select the appropriate drug strategy. Based on these principles, pharmacogeneticists attempt to identify the genes and gene variants that influence the efficiency of drug therapy and lower the risk of side effects. It has been shown that the most widely used drugs are only effective in 25-60% of patients, and there have been 2 million cases of side effects per year in the U.S. alone, including more than a 100,000 deaths [78].

Re-sequencing of complete individual genomes yields new data on the genetic variability of humans and can help create individual health prognoses in the future. The first personal genome to be sequenced was the genome of Craig Venter, one of the key figures in the study of the human genome. Venter’s genome sequence was completed in October 2007 [84]. Data on the second sequenced genome (of Nobel Laureate James Watson) were published half a year later [85]. Currently (from the middle of 2010), there are data on 20 re-sequenced genomes (Table 4), which include those of Craig Venter, James Watson, archbishop Desmond Tutu, the twice-sequenced genome of a Yoruba individual, a Chinese genome, two Koreans, several Europeans, an ancient Eskimo, a Russian, and an Indian [84–99].

Humans display a relatively low level of genetic variability (both at the level of population differentiation and at the level of individual genomes), which is set on a background of high phenotypic variability and strict geographical structure of the genetic variation, which is manifested in the clustering of geographically adjacent populations. The spatial nature of the genetic variability distribution of modern humans can be observed at different levels of population structure and in various groups of markers, including the genes associated with MFD development. Genetic differences between human populations are responsible for only 10-15% of the genetic variability in humans. However, these differences prove significant in the field of personalized medicine in terms of diagnosing monogenic diseases, estimating the susceptibility to common diseases, and making health prognoses, and the efficiency of drug therapy.