Biology subjects

Hodgson, J.

Publications and source records attributed to Hodgson, J..

3 recordsLinked to original sources

bioRxiv2025

tidypopgen: Tidy Population Genetics in R

As genome-wide data has become increasingly available, software libraries for their analysis have proliferated. While new tools for downstream analyses are constantly emerging, existing workflows are hindered by inefficiencies. Switching between coding languages and object types in the early stages of pipelines wastes researchers time, impedes reproducibility, and creates opportunity for error. To confront these obstacles, we introduce tidypopgen, a comprehensive R package for population genetic analysis of biallelic SNP data. Genotype data can be read, filtered, and analysed within a single environment, without the need for prior data cleaning or setup with other software. tidypopgens gen_tibble object structure makes analysis efficient and intuitive, while standardised tidy grammar makes data manipulation clear. Functionality within tidypopgen supports cleaning and merging datasets, basic descriptive statistics, multivariate analysis, clustering algorithms, and F-statistics, as well as integrating with existing tools for population genetic analyses in R. We use the Human Genome Diversity Project SNP dataset (Li et al., 2008) to show that a basic population genetic workflow can be executed in under 25 lines of code in a single environment using one file set, without the need to write superfluous outputs or change directories. By supporting data assembly through to data analysis, tidypopgen significantly streamlines workflows without compromising speed or functionality.

bioinformatics↗

bioRxiv2021

Climate and mountains shaped human ancestral genetic lineages

Extensive sequencing of modern and ancient human genomes has revealed that contemporary populations can be explained as the result of recent mixing of a few distinct ancestral genetic lineages1. But the small number of aDNA samples that predate the Last Glacial Maximum means that the origins of these lineages are not well understood. Here, we circumvent the limited sampling by modelling explicitly the effect of climatic changes and terrain on population demography and migrations through time and space, and show that these factors are sufficient to explain the divergence among ancestral lineages. Our reconstructions show that the sharp separation between African and Eurasian lineages is a consequence of only a few limited periods of connectivity through the arid Arabian peninsula, which acted as the gate out of the Arican continent. The subsequent spread across Eurasia was then mostly shaped by mountain ranges, and to a lesser extent deserts, leading to the split of European and Asians, and the further diversification of these two groups. A high tolerance to cold climates allowed the persistence at high latitudes even during the Last Glacial Maximum, maintaining a pocket in Beringia that led to the later, rapid colonisation of the Americas. The advent of food production was associated with an increase in movement2, but mountains and climate have been shown to still play a major role even in this latter period3,4, affecting the mixing of the ancestral lineages that we have shown to be shaped by those two factors in the first place.

genomics↗

bioRxiv2017

Novel causative genes for heritable pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-{beta} pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlie most heritable forms of PAH. Since the missing heritability likely involves genetic variation confined to small numbers of cases, we performed whole genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses revealed significant overrepresentation of rare variants in novel genes, namely ATP13A3, AQP1 and SOX17, and provided independent validation of a critical role for GDF2 in PAH. We provide evidence for familial segregation of mutations in SOX17 and AQP1 with PAH. Mutations in GDF2, encoding a BMPR2 ligand, led to reduced secretion from transfected cells. In addition, we identified pathogenic mutations in the majority of previously reported PAH genes, and provide evidence for further putative genes. Taken together these findings provide new insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention.

genetics↗