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Explaining ethnicity

How we understand your DNA

Over time, due to historic bottleneck events, genetic drift, and selection, genetic mutations get enriched to varying degrees in different populations. The type of mutation used for ethnicity estimation is called SNP, or Single Nucleotide Polymorphism. An SNP is a mutation of a single base in DNA that occurs in a significant proportion of a large population. The bases of DNA are Adenine, Thymine, Cytosine and Guanine, which are abbreviated to A, T, C and G. An example of an SNP would be a stretch of reference DNA that coded ATTGCCAT, and your DNA having the code ATTCCCAT. This would show that you posses an SNP that has changed a G to a C, and could be a mutation that is commonly found in your ethnic group. By creating a database of genetic data from various ethnic groups, statistical models can be employed to estimate what ethnic groups you descend from, and in what proportions.

In 2003 the human genome project was completed, and we gained the first ever fully sequenced human genome. By using this as a reference genome and comparing all other genomes to it, it became possible to carry out sequencing at a far higher rate. The creation of this reference led to new methods of genome sequencing that can be completed in a day. The methods that will be used by our lab are Next Generation Sequencing (NGS) and Microarray genotyping. NGS allows us to sequence your entire genome. This is done in 4 steps.

First, your DNA is isolated and purified. Then, your sample is converted into what is referred to as an NGS library. This itself is a multi-step process where your DNA is amplified (copied multiple times to increase its quantity) and then fragmented, creating short stands that are required for the sequencing method. Adapters are then added to the ends of the fragments so that they can bind to the sequencing platform. The concentration of the DNA fragments is then measured to ensure optimal sequencing. After these steps are undertaken, sequencing begins where your DNA is bound to a plate through the use of the previously mentioned adapters and replicated with DNA bases that posses fluorescent tags. These tags are read as they are added, and as each of the four bases has a uniquely coloured tag, the sequence based off of this florescence is recorded by the machine and the raw data is converted into the nucleotide sequence of DNA.

This data is then analysed by aligning the fragments to a known reference genome, which will show us your whole genome and highlight the unique SNPs your DNA holds. This in turn will allow us to estimate your ethnic breakdown, by employing statistical methods to unearth your most likely ancestral background. The second method mentioned is Microarray genotyping. This differs from NGS in that rather than sequencing your entire genome and comparing it to reference genomes, we instead look for the specific SNPs within your genome that we know vary between certain historic populations and use this to inform your ancestry estimate. The essential difference in methodology is that rather than having your DNA bind directly to a sequencing platform, and be replicated with fluorescent bases that are then recorded, which is what occurs in NGS, your DNA is instead replicated in a way that causes fluorescence when bound to a sister strand of DNA to create the double helix. This DNA is then added to wells with reference SNPs bound to the surface, and should the complimentary SNP be present in your DNA, the two strands will bind (referred to as hybridize) and fluoresce. This fluorescent can then be read and reveal to us which SNPs can be found in your genome. This method creates a greater amount of privacy as your whole genome is not sequenced and thus not on record, meaning your ethnic makeup can be determined with a minimal loss of privacy. To summarise, your DNA contains unique genetic markers called SNPs, and by looking at your genome and identifying these SNPs we can estimate your ethnic groupings.

References

  1. The Genetic Structure and History of Africans and African Americans - PMC
  2. Genetic differences among ethnic groups | BMC Genomics | Springer Nature
  3. What is Next-Generation Sequencing Technology? | Thermo Fisher Scientific - UK
  4. End-to-End Genotyping by Sequencing (GBS) Service - Low-Cost SNP Discovery - CD Genomics