Our blog always tries to be informative and approachable, and we write it with the aim of making it simple and understandable for any reader. On this occasion, we have allowed ourselves to be a little more technical in order to explain certain fundamentals of genetic ancestry. But you don’t need to understand every word or every statement in detail. We are sure that, by the end of reading this post, you will have the main concepts that will have allowed you to better understand what is behind the creation of a 24Genetics personalized ancestry study.
What is genetic inheritance?
In order to understand the scope of ancestry testing and to understand the science behind it, it is necessary to explain how genetic material is organized and how genetic inheritance works.
How is genetic material organized?
Genetic material is the chemical base in which all the information necessary for the production and regulation of proteins is stored, and it determines the fate of our cells and the information that defines us as individuals. The genetic material of virtually all known organisms, except for certain viruses, is organized in the form of DNA (deoxyribonucleic acid).
The total DNA content of an organism is called a genome. The human genome can be divided into nuclear genome and mitochondrial genome.
On the one hand, the nuclear genome consists of 23 pairs of chromosomes that together contain information on approximately 20,000 genes, consisting of more than 3 billion nucleotides. It is worth noting that of these more than 3 billion nucleotides that make up the human genome, the variability between individuals resides in only 0.1% of the positions. These 23 pairs of chromosomes are organized into 22 pairs of autosomal chromosomes (or autosomes) and 1 pair of sex chromosomes, XX for biological males and XY for biological females.
The mitochondrial genome, on the other hand, consists of a single circular chain, the inheritance of which is exclusively maternal.
We can understand the genome as a collection of encyclopedias containing all the information a person needs to grow and develop. This encyclopedia has 23 volumes, each representing each of the pairs of chromosomes, in which we can read the genes, which we could represent as the words of this encyclopedia. In turn, these words are made up of letters, which, in the case of genes, correspond to the four types of nucleotides that make up DNA: adenine, thymine, cytosine and guanine. For each of the positions there will be two possible letters (two possible nucleotides), which will be the alleles.
Figure 1. Representation of human genetic material.
Genetic inheritance can be defined as characteristics that are inherited from parents to offspring. The transmissible traits are those that are fixed in the genes, which constitute the genotype, while the manifestation of these traits is what constitutes the phenotype. It is important to bear in mind that in many cases the phenotype is not only determined by the genotype but is also influenced by environmental factors (1). To make a simple analogy for ease of understanding, we could say that in a painting, the genotype is made up of the canvas, the type of pigment, the colors, the brush, the stroke, etc. and the phenotype is the image we see.
The term genetic variability refers to differences in the DNA sequence between individuals or populations, which, as mentioned above, is reduced to 0.1% of the human genome. The main sources of variability are mutations and genetic recombination.
What are mutations?
Mutations are permanent and heritable changes in the DNA sequence. De novo mutations are generated when an error occurs in DNA replication that is not corrected by repair enzymes. In other words, they are mainly errors that have no known or justified cause and lead to a genetic modification. Depending on the consequences for the organism, mutations are classified into the following types:
- Deleterious: detrimental to the organism, thus decreasing reproductive effectiveness, i.e. the probability of leaving offspring.
- Beneficial: confer an adaptive advantage that increases reproductive effectiveness.
- Neutral (2).
Most mutations that occur in the genome and are passed on to offspring are beneficial or neutral, because they do not negatively affect the viability of organisms.
What is genetic recombination?
Genetic recombination is the process by which homologous chromosomes or chromosome segments break and join together, involving the rearrangement of DNA sequences. This process takes place during meiosis, which is the process of cell division that occurs in sexual reproduction for the formation of gametes or sex cells, both male (sperm) and female (ova).
Figure 2. Genetic recombination
Of the 23 pairs of chromosomes that each person possesses, each pair has one chromosome inherited from the father and one from the mother. Therefore, in the formation of gametes (sperm and ovum) of an individual, recombination occurs between the two chromosomes of the 23 pairs (homologous chromosomes), after which the 23 recombined individual chromosomes will form part of each of the gametes. The next generation will inherit one chromosome from each parent, thus having a unique combination of their own genetic material. This is illustrated in the figure below:
There are chromosomal positions, technically called loci, some of which present possible variants of nucleotide sequences in a gene (alleles). These variants include single nucleotide polymorphisms (SNPs), which are single nucleotide variations present in at least 1% of the population, and the allele frequencies of these variations have been described in different populations. Allele frequency is defined as the proportion of a specific allele out of all possible alleles at a given position in a given population (3).
It is the difference in allele frequencies between populations that allow ancestry calculations to be made.
What is ancestry?
Ancestry is a very broad and difficult term to define, as it is subject to various interpretations. In a broad sense, it can be genetically, geographically, historically or culturally based.
From the point of view of genetics, ancestry could be defined as the study of all the genetic information inherited from our ancestors, with certain mutations and genetic variations, which allow us to define our origins.
Populations show genetic variability as a result of the demographic events in which they have been involved throughout human history, such as migrations and mixing with other populations, diseases with high mortality rates, geographical isolation, etc. (4). Thus, our ancestry is the result of a complex mixing of populations over time, from the origin of the human species in Africa, some 300,000 years ago, to the present day (5). Given these patterns of genetic variability, it is possible to carry out an analysis of the genetic differences and similarities that exist between an individual and various populations around the world to infer ancestry (6).
How are ancestry calculations performed?
There are three types of ancestry tests: autosomal, mitochondrial and Y-chromosomal. We will focus on autosomal ancestry tests.
Autosomal ancestry tests perform an analysis of the autosomal chromosomes, i.e. the pairs of chromosomes 1 to 22, not including the 23rd pair, which are sex chromosomes (XX or XY). These 22 pairs of chromosomes are inherited from both parents, thus providing joint information on the maternal and paternal lineages (7).
As mentioned above, ancestry analyses are based on finding similarities between the sample of a particular individual and a set of diverse samples, which make up the reference panel or database, and whose ancestry is known in advance. To infer ancestry, the SNPs between the two are compared, so that the greater the coincidence between the sample to be analysed and the reference sample, the greater the probability of having a common ancestry. These results reflect, in a way, which populations the genetic information we have inherited today is related to and, therefore, what our genetic origins are.
Ancestry at 24Genetics
At 24Genetics we offer you information about your genetic ancestry at a geographical level. That is, we associate your genetic origins with the geographical regions in which your ancestors lived or with which they have had close contact (6). Our ancestry test is one of the most comprehensive on the market, with a reference database that includes DNA from people representing more than 1,500 regions, because their ancestors have lived in a region for generations. Our information is classified in 175 countries, by states, regions or even provinces, going back 700 to 900 years, and can even detect genetic signals from more than 2,000 years ago.
1. Fenotipo | NHGRI [Internet]. [cited 2022 Jun 20]. Available from: https://www.genome.gov/es/genetics-glossary/Fenotipo
2. What is genetic variation | Human genetic variation [Internet]. [cited 2022 Jun 20]. Available from: https://www.ebi.ac.uk/training/online/courses/human-genetic-variation-introduction/what-is-genetic-variation/
3. Strachan T, Read AP. Human Molecular Genetics. Human Molecular Genetics. New York: Garland Science; 2018. 784 p.
4. Mathieson I, Scally A. What is ancestry? Flint J, editor. PLOS Genetics [Internet]. 2020 Mar 9 [cited 2020 Mar 23];16(3):e1008624. Available from: https://dx.plos.org/10.1371/journal.pgen.1008624
5. Jobling M, Hollox E, Hurles M, Kivisild T, Tyler-smith C. Human Evolutionary Genetics. New York (USA): Garland Science; 2013. 650 p.
6. Royal CD, Novembre J, Fullerton SM, Goldstein DB, Long JC, Bamshad MJ, et al. Inferring Genetic Ancestry: Opportunities, Challenges, and Implications. American Journal of Human Genetics [Internet]. 2010 May 5 [cited 2022 Jun 17];86(5):661. Available from: /pmc/articles/PMC2869013/
7. Templeton AR. Human Population Genetics and Genomics. Academic Press; 2019.