Study links sequence variants to DNA methylation and diseases

A brand new examine by scientists at deCODE Genetics reveals that sequence variants drive the correlation between DNA methylation and gene expression. The identical variants are linked to numerous ailments and different human traits.

The analysis is printed within the journal Nature Genetics underneath the title “The correlation between CpG methylation and gene expression is pushed by sequence variants.”

Nanopore sequencing is a brand new expertise developed by ONT (Oxford Nanopore Know-how), that permits us to investigate DNA sequences in real-time. With this expertise, DNA molecules are drawn by means of tiny protein pores, and real-time measurements of electrical present point out which nucleotides within the DNA have handed by means of the pores. This permits the sequence of nucleotides within the DNA to be learn, whereas additionally making it attainable to detect chemical modifications of the nucleotides from these similar measurements.

One such modification is known as DNA methylation, considered necessary in figuring out which genes are used at any given time, and generally known as regulation of gene expression by scientists within the discipline. Nanopore sequencing expertise allows direct measurement of DNA methylation, whereas additionally yielding longer reads of DNA sequences than pre-existing applied sciences have been in a position to obtain.

These advances supply new alternatives by enabling the measurement of DNA methylation of all CpG websites within the human genome and, as this expertise can learn lengthy DNA sequences, it’s attainable to find out DNA methylation on chromosomes from each mother and father, individually.

Within the examine, the scientists had been in a position to assign CpG methylation, gene expression and alleles of sequence variants to parental chromosomes, permitting them to analyze correlations among the many three units of measurements on a haplotype stage.

The examine reveals that sequence variants have an effect on DNA methylation, and moreover, a few of these variants could be linked to numerous ailments in addition to different human traits. Importantly, the examine reveals that the correlation between DNA methylation and gene expression could be attributed to sequence variants, indicating that these variants are the driving issue.

Nearly all of sequence variants which were linked to ailments are discovered within the noncoding genome, on areas of the genome that don’t encode for proteins. Because of this, it has been obscure how noncoding sequence variants result in ailments.

By finding out the results on DNA methylation, the scientists had been in a position to present that many of those variants correspond to sequence variants that had beforehand been related to illness, thereby enabling us to raised perceive how they result in the development of ailments.

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deCODE genetics