Biology subjects

C

Publications and source records attributed to C.

3 recordsLinked to original sources

bioRxiv2024

Steppe Ancestry in western Eurasia and the spread of the Germanic Languages

Today, Germanic languages, including German, English, Frisian, Dutch and the Nordic languages, are widely spoken in northwest Europe. However, key aspects of the assumed arrival and diversification of this linguistic group remain contentious1-3. By adding 712 new ancient human genomes we find an archaeologically elusive population entering Sweden from the Baltic region by around 4000 BP. This population became widespread throughout Scandinavia by 3500 BP, matching the contemporaneous distribution of Palaeo-Germanic, the Bronze Age predecessor of Proto-Germanic4-6. These Baltic immigrants thus offer a new potential vector for the first Germanic speakers to arrive in Scandinavia, some 800 years later than traditionally assumed7-12. Following the disintegration of Proto-Germanic13-16, we find by 1650 BP a southward push from Southern Scandinavia into presumed Celtic-speaking areas, including Germany, Poland and the Netherlands. During the Migration Period (1575-1375 BP), we see this ancestry representing West Germanic Anglo-Saxons in Britain, and Langobards in southern Europe. We find a related large-scale northward migration into Denmark and South Sweden corresponding with historically attested Danes and the expansion of Old Norse. These movements have direct implications for multiple linguistic hypotheses. Our findings show the power of combining genomics with historical linguistics and archaeology in creating a unified, integrated model for the emergence, spread and diversification of a linguistic group.

genetics↗

bioRxiv2018

The Project MinE databrowser: bringing large-scale whole-genome sequencing in ALS to researchers and the public.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive fatal neurodegenerative disease affecting 1 in 350 people. The aim of Project MinE is to elucidate the pathophysiology of ALS through whole-genome sequencing at least 15,000 ALS patients and 7,500 controls at 30X coverage. Here, we present the Project MinE data browser (databrowser.projectmine.com). a unique and intuitive one-stop, open-access server that provides detailed information on genetic variation analyzed in a new and still growing set of 4,366 ALS cases and 1,832 matched controls. Through its visual components and interactive design, the browser specifically aims to be a resource to those without a biostatistics background and allow clinicians and preclinical researchers to integrate Project MinE data into their own research. The browser allows users to query a transcript and immediately access a unique combination of detailed (meta)data, annotations and association statistics that would otherwise require analytic expertise and visits to scattered resources.

genomics↗

bioRxiv2015

Disease variants alter transcription factor levels and methylation of their binding sites

Most disease associated genetic risk factors are non-coding, making it challenging to design experiments to understand their functional consequences1,2. Identification of expression quantitative trait loci (eQTLs) has been a powerful approach to infer downstream effects of disease variants but the large majority remains unexplained.3,4. The analysis of DNA methylation, a key component of the epigenome5, offers highly complementary data on the regulatory potential of genomic regions6,7. However, a large-scale, combined analysis of methylome and transcriptome data to infer downstream effects of disease variants is lacking. Here, we show that disease variants have wide-spread effects on DNA methylation in trans that likely reflect the downstream effects on binding sites of cis-regulated transcription factors. Using data on 3,841 Dutch samples, we detected 272,037 independent cis-meQTLs (FDR < 0.05) and identified 1,907 trait-associated SNPs that affect methylation levels of 10,141 different CpG sites in trans (FDR < 0.05), an eight-fold increase in the number of downstream effects that was known from trans-eQTL studies3,8,9. Trans-meQTL CpG sites are enriched for active regulatory regions, being correlated with gene expression and overlap with Hi-C determined interchromosomal contacts10,11. We detected many trans-meQTL SNPs that affect expression levels of nearby transcription factors (including NFKB1, CTCF and NKX2-3), while the corresponding trans-meQTL CpG sites frequently coincide with its respective binding site. Trans-meQTL mapping therefore provides a strategy for identifying and better understanding downstream functional effects of many disease-associated variants.

Genomics↗