Centenarians by Unknown

Author:Unknown
Language: eng
Format: epub
ISBN: 9783030207625
Publisher: Springer International Publishing

6.5 Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS)

The first sequencing technology has been developed by Frederick Sanger in the 1970s, and for this invention, he deserved his second Nobel Prize in chemistry in 1980. The Sanger sequencing took few decades to improve accuracy and speed up the process, since the arrival of next-generation sequencing (NGS), a new technology that allows to perform parallel sequencing with a high speed and low costs. In the last decade, costs for genome sequencing became more and more affordable (around 1000$ for an entire genome), and now, it is one of the most used techniques for unveiling the secrets of DNA. Different from genetic arrays, the target of sequencing analysis is the entire genome and not specific markers. There are two main approaches for the analysis of genetic information: WES and WGS. The WES approach consists in the sequencing of all the coding regions of the genome, which represent around 2% of the entire genome but contain the bigger amount of variability influencing gene function and disease. The WGS is comprehensive of all the genetic information in DNA, i.e., coding and non-coding regions. The latter are becoming more and more important in this kind of research because of the presence of regulatory and recombination sites.

The availability of this huge amount of data does not correspond to an easier and more efficient way to discover genetic variants associated with the phenotype. Especially for complex traits, to reach an adequate statistical power, NGS studies need very large populations of cases and controls because of the big number of genetic variants and because of the rare variants (see above).

Furthermore, data generated by NGS are very complex, and the amount of information for each sample is so large that it is difficult to manage without specialized bioinformatics personnel. Today, computer algorithms, web databases and artificial intelligence are very important tools for the analysis of the output data and for the prediction of the impact of genetic variants.

For the reasons mentioned above, very few association studies based on sequencing technology have been performed. The need of very large populations pushed researchers to use the NGS approach together with other phenotypic data.

However, around the world, centenarian populations took part in different studies such as the Genome of the Netherlands project, with 250 nuclear families [35, 36], or the SardiNIA project, with 1000 individuals [37–39], or the Wellderly study, involving 2000 individuals over 85 years of age [40]. The whole genomes of these populations have been sequenced to identify different genetic variants and to build databank for inter-population analyses.

More in detail, the first whole genome sequencing study on the genetics of human longevity has been performed by Sebastiani et al. [41] and it consists in the sequencing of 2 supercentenarians: a male and a female aged more than 114 years old. Obviously, no statistics have been performed on a such small number of samples, but the study gave interesting information about the genome of the two individuals. The female subject

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