Decoding Genetic Connections: Relatedness in Multiple Sclerosis Research with WES
Multiple sclerosis (MS) is a complex disease characterized by the degeneration of the central nervous system. Whole exome sequencing (WES) is increasingly used to uncover genetic variations that contribute to MS, providing insights into its molecular mechanisms and potential therapeutic targets. This blog post delves into the role of WES in understanding the genetic relatedness and identifying potential genetic markers in MS.
Insights from Recent Studies
Identifying Genetic Variants in Families:
A study utilized WES to analyze families with multiple MS patients, identifying rare genetic variants that may contribute to MS susceptibility (Horjus et al., 2022). This approach pinpointed several genes, such as MBP and MECP2, previously linked to MS, highlighting the hereditary patterns and potential familial relatedness in the disease's pathology.
Linkage Analysis and WES:
In another study, linkage analysis combined with WES identified a novel candidate gene in a Dutch family affected by MS, suggesting the power of WES in revealing intra-familial genetic links (Mescheriakova et al., 2018).
Exploring Multiple Genetic Loci:
Research has shown that MS can involve mutations at multiple genetic loci, illustrating complex genetic interactions and the importance of analyzing genetic relatedness to understand disease phenotypes (Posey et al., 2017). This study emphasized the need for comprehensive genetic profiling to capture the full spectrum of genetic contributions to MS.
Novel Susceptibility Genes:
A comprehensive WES study in MS families identified 12 candidate genes, suggesting that variations in these genes could be linked to the onset and progression of MS (Vilariño-Güell et al., 2019). These findings propose that genetic relatedness within families can illuminate critical pathways involved in MS.
Conclusion
Whole exome sequencing has proven to be a valuable tool in uncovering the genetic underpinnings of multiple sclerosis, particularly in understanding how relatedness between affected individuals can guide the discovery of genetic variants that contribute to the disease. By exploring familial genetic patterns and identifying rare and common variants, researchers can better understand the complexities of MS and develop targeted treatments. The studies discussed here underscore the necessity for detailed genetic analysis in familial cases of MS to uncover the intricate relationships and mechanisms driving this debilitating disease.
Reference:
Horjus, J., Mourik-Banda, T., Heerings, M., Hakobjan, M., Witte, W., Heersema, D., Jansen, A., Strijbis, E., Jong, B., Slettenaar, A., Zeinstra, E., Hoogervorst, E., Franke, B., Kruijer, W., Jongen, P., Visser, L., & Poelmans, G. (2022). Whole Exome Sequencing in Multi-Incident Families Identifies Novel Candidate Genes for Multiple Sclerosis. International Journal of Molecular Sciences, 23.
Mescheriakova, J., Verkerk, A., Amin, N., Uitterlinden, A., Duijn, C., & Hintzen, R. (2018). Linkage analysis and whole exome sequencing identify a novel candidate gene in a Dutch multiple sclerosis family. Multiple Sclerosis (Houndmills, Basingstoke, England), 25, 909 - 917.
Posey, J., Harel, T., Liu, P., Rosenfeld, J., James, R., Akdemir, Z., Walkiewicz, M., Bi, W., Xiao, R., Ding, Y., Xia, F., Beaudet, A., Muzny, D., Gibbs, R., Boerwinkle, E., Eng, C., Sutton, R., Shaw, C., Plon, S., Yang, Y., & Lupski, J. (2017). Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation. The New England Journal of Medicine, 376, 21–31.
Vilariño-Güell, C., Zimprich, A., Martinelli-Boneschi, F., Herculano, B., Wang, Z., Matesanz, F., ... & Sadovnick, A. D. (2019). Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease. PLoS genetics, 15(6), e1008180.
