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REYKJAVIK, Iceland, July 24, 2024 /PRNewswire/ -- A new study by scientists at deCODE Genetics, subsidiary of Amgen, shows that sequence variants drive the correlation between DNA methylation and gene expression. The same variants are linked to various diseases as well as other human traits. The research was published today in the scientific journal Nature Genetics under the title: The correlation between CpG methylation and gene expression is driven by sequence variants. Continue Reading deCODE genetics: Variants in the genome affect DNA methylation Kari Stefansson and Olafur Andri Stefansson authors on the paper in Nature Genetics. Nanopore sequencing is a new technology developed by ONT (Oxford Nanopore Technology), that enables us to analyze DNA sequences in real-time. With this technology, DNA molecules are drawn through tiny protein pores, and real-time measurements of electric current indicate which nucleotides in the DNA have passed through the pores. This allows the sequence of nucleotides in the DNA to be read, while also making it possible to detect chemical modifications of the nucleotides from these same measurements. One such modification is called DNA methylation and is thought to be important in determining which genes are used at any given time; commonly referred to as regulation of gene expression by scientist in the field. Nanopore sequencing technology enables direct measurement of DNA methylation, while also yielding longer reads of DNA sequences than pre-existing technologies have been able to achieve. These advances offer new opportunities by enabling the measurement of DNA methylation of all CpG sites in the human genome and, as this technology can read long DNA sequences, it is possible to determine DNA methylation on chromosomes from both parents, separately. In the study, the scientists were able to assign CpG methylation, gene expression and alleles of sequence variants to parental chromosomes, allowing them to investigate correlations between the three sets of measurements on a haplotype level. The study shows that sequence variants affect DNA methylation and, furthermore, some of these variants can be linked to various diseases as well as other human traits. Importantly, the study shows that the correlation between DNA methylation and gene expression can be attributed to sequence variants, indicating that these variants are the driving factor. The majority of sequence variants that have been linked to diseases are found in the noncoding genome, on regions of the genome that do not encode for proteins. For this reason, it has been difficult to understand how noncoding sequence variants lead to diseases. By studying the effects on DNA methylation, the scientists were able to show that many of these variants correspond to sequence variants that had previously been associated with disease, thereby enabling us to better understand how they lead to the progression of diseases. Video - Photo -

A new study from deCODE genetics uses pedigrees and sequence data from 64,806 Icelanders to shed light on the rate and nature of mutations in mitochondrial DNA (mtDNA) and the peculiar dynamics of its maternal transmission REYKJAVIK, Iceland, June 7, 2024 /PRNewswire/ -- In a paper published today in Cell, scientists from deCODE genetics, a subsidiary of Amgen, present the largest study to date of germline mtDNA mutations in humans and their transmission across 116,663 mother-child pairs. The study documents the astonishing extent of hypermutability at some positions in mtDNA, including the well-known deleterious A>G mutation at position 3243 which causes the MELAS syndrome. The mutation occurred 15 times in the 2,548 matrilineal pedigrees, but typically disappeared after several generations, due to its severe impact on the health of carriers. Continue Reading Kari Stefansson senior author on the paper and CEO of deCODE genetics with Agnar Helgason and Erla Rut Arnadottir, scientists at deCODE genetics and authors on the paper Strong aggregate evidence was uncovered for selection against many such short-lived deleterious mtDNA mutations in the pedigrees. The deCODE team also reported evidence for an extensive earlier episode of negative selection affecting mitochondria, called germline selection, where poorly functioning mitochondrial DNA molecules are discarded during the development of oocytes. Finally, they used the large number of transmissisons of mtDNA mutations in the pedigrees to reliably estimate that individuals inherit, on average, only around 3 units of mtDNA from their mothers – fewer than indicated by previous studies. "It is remarkable that the hundreds of thousands of mtDNA carried by oocytes are derived from only about three of the mtDNA molecules originally carried by the mother," noted Agnar Helgason, a corresponding author of the paper. "This drastic bottleneck determines the rapid rate at which new mutations in the mtDNA germline can become lost or fixed over just a handful of generations in a pedigree, and must be in part due to a selection process during the development of oocytes, where mtDNA molecules with deleterious mutations are removed from the germline." "This study takes us a few steps closer to understanding the basis of the extraordinary variation in mutation rates across the nucelotides of the mtDNA genome, even between different alleles at the same position", said Kári Stefánsson, CEO of deCODE and a corresponding author of the paper. "Unfortunately, it is the hypermutability of some pathogenic mutations that has made them so prevalent and thereby easier to discover. However, our findings suggest that many rarer pathogenic mtDNA mutations that are responsible for disease burden in human populations remain to be discovered." Video: Contact: Thora Kristin Asgeirsdottir deCODE genetics 354 894 1909 Email: thoraa@decode.is Photo - Logo - SOURCE deCODE genetics

REYKJAVIK, Iceland, Jan. 29, 2024 /PRNewswire/ -- Scientists at deCODE genetics, a subsidiary of Amgen, and their collaborators from Iceland, Denmark, and the USA published a study today in Nature Structural & Molecular Biology titled "Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effects on recombination". Continue Reading Valgerdur Steinthorsdottir project leader at deCODE genetics and Kári Stefánsson CEO of deCODE genetics. Photo credit: deCODE genetics While it is well established that chromosomal abnormalities are a major cause of miscarriages the biology behind pregnancy losses with or without chromosomal errors is not well understood. Over 114 thousand women from Iceland, Denmark, the UK, USA, and Finland who have experienced pregnancy loss participated in a genome-wide association study, testing 50 million sequence variants. A low-frequency missense variant in the SYCE2 gene was found to increase the risk of pregnancy loss by 22%. In a previous report by deCODE scientists this missense variant was shown to associate with recombination phenotypes in chromosomes that were transmitted from the mother. Recombination between homologous chromosomes is an essential part of meiosis, the generation of the human egg and sperm cell. The product of SYCE2 forms a part of a protein complex that is essential for the alignment of homologous chromosomes for recombination and the missense variant associated with pregnancy loss and recombination is predicted to affect the stability of this protein complex. A closer inspection of the effect of the variant on recombination revealed an effect on the positioning of crossovers that is proportional to the length of the chromosomes, the longer the chromosome the larger the effect. The effect on recombination is measured in live-born individuals. The authors propose that this effect may be more extreme in pregnancies that are lost and may contribute to pregnancy loss. The association with pregnancy loss does not account for embryos lost in early gestation before pregnancy has been detected so the effect of the variant on pregnancy success may be underestimated. The findings reported in this study demonstrate that a variant with a substantial effect on recombinations can be maintained in the population despite increasing the risk of pregnancy loss. Based in Reykjavik, Iceland, deCODE is a global leader in analyzing and understanding the human genome. Using its unique expertise and population resources, deCODE has discovered genetic risk factors for dozens of common diseases. deCODE is a wholly-owned subsidiary of Amgen (NASDAQ: AMGN). Photo: Logo: SOURCE deCODE genetics