Biology subjects

Reimer, C.

Publications and source records attributed to Reimer, C..

4 recordsLinked to original sources

bioRxiv2023

Sequence-based GWAS in 180 000 German Holstein cattle reveals new candidate genes for milk production traits

BackgroundThe use of genome-wide association studies (GWAS) has led to the identification of numerous quantitative trait loci and candidate genes in dairy cattle. To obtain sufficient power of GWAS and to identify quantitative trait nucleotides, whole-genome sequence data is required. Sequence data facilitates the identification of potential causal variants; however, sequencing of whole genomes is still expensive for a large number of animals. Imputation is a quick and efficient way of obtaining sequence data from large datasets. Milk production traits are complex and influenced by many genetic and environmental factors. Although extensive research has been performed for these traits, with many associations unveiled thus far, due to their crucial economic importance, complex genetic architecture, and the fact that causative variants in cattle are still scarce, there is a need for a better understanding of their genetic background. In this study, we aimed to identify new candidate loci associated with milk production traits in German Holstein cattle, the most important dairy breed in Germany and worldwide. For that purpose, 252,285 cattle were imputed to the sequence level and large-scale GWAS was carried out to identify new association signals. ResultsWe confirmed many known and identified 30 previously unreported candidate genes for milk, fat, and protein yield. While all of the genes were functionally associated with the traits, some showed pleiotropic effects as well. Specifically, association with mammary gland development, fatty acid synthesis, metabolism of lipids, or milk production QTLs in other farm animals has been reported. Variants associated with these genes explained a large percentage of genetic variance, compared to random ones. ConclusionsOur findings proved the power of large samples and sequence-based GWAS in detecting new association signals. In order to fully exploit the power of GWAS, one should aim at very large samples combined with whole-genome sequence data. Although milk production traits in cattle are comprehensively researched, the genetic background of these traits is still not fully understood, with the potential for many new associations to be revealed, as shown in our study. With constantly growing sample sizes, we expect more insights into the genetic architecture of production traits in the future.

genomics↗

bioRxiv2020

Multiple loci linked to inversions are associated with eye size variation in species of the Drosophila virilis phylad

The size and shape of organs is tightly controlled to achieve optimal function. Natural morphological variations often represent functional adaptations to an ever-changing environment. For instance, variation in head morphology is pervasive in insects and the underlying molecular basis is starting to be revealed in the Drosophila genus for species of the melanogaster group. However, it remains unclear whether similar diversifications are governed by similar or different molecular mechanisms over longer timescales. To address this issue, we used species of the virilis phylad because they have been diverging from D. melanogaster for at least 40 million years. Our comprehensive morphological survey revealed remarkable differences in eye size and head shape among these species with D. novamexicana having the smallest eyes and southern D. americana populations having the largest eyes. We show that the genetic architecture underlying eye size variation is complex with multiple associated genetic variants located on most chromosomes. Our genome wide association study (GWAS) strongly suggests that some of the putative causative variants are associated with the presence of inversions. Indeed, northern populations of D. americana share derived inversions with D. novamexicana and they show smaller eyes compared to southern ones. Intriguingly, we observed a significant enrichment of genes involved in eye development on the 4th chromosome after intersecting chromosomal regions associated with phenotypic differences with those showing high differentiation among D. americana populations. We propose that variants associated with chromosomal inversions contribute to both intra- and inter-specific variation in eye size among species of the virilis phylad.

evolutionary biology↗

bioRxiv2020

Genetic diversity in global chicken breeds as a function of genetic distance to the wild populations

Migration of populations from their founder population is expected to cause a reduction in genetic diversity and facilitates population differentiation between the populations and their founder population as predicted by the theory of genetic isolation by distance. Consistent with that, a model of expansion from a single founder predicts that patterns of genetic diversity in populations can be well explained by their geographic expansion from the founders, which is correlated to the genetic differentiation. To investigate this in the chicken, we have estimated the relationship between the genetic diversity in 172 domesticated chicken populations and their genetic distances to wild populations. We have found a strong inverse relationship whereby 87.5% of the variation in the overall genetic diversity of domesticated chicken can be explained by the genetic distance to the wild populations. We also investigated if different types of SNPs and genes present similar patterns of genetic diversity as the overall genome. Among different SNP classes, the non-synonymous ones were the most deviating from the overall genome. However, the genetic distances to wild populations still explained more variation in domesticated chicken diversity in all SNP classes ranging from 81.7 to 88.7%. The genetic diversity seemed to change at a faster rate within the chicken in genes that are associated with transmembrane transport, protein transport and protein metabolic processes, and lipid metabolic processes. In general, such genes are flexible to be manipulated according to the population needs. On the other hand, genes which the genetic diversity hardly changes despite the genetic distance to the wild populations are associated with major functions e.g. brain development. Therefore, changes in the genes may be detrimental to the chickens. These results contribute to the knowledge of different evolutionary patterns of different functional genomic regions in the chicken. Author summaryThe chicken was first domesticated about 6000 B.C. in Asia from the jungle fowl. Following domestication, chickens were taken to different parts of the world mainly by humans. Evolutionary forces such as selection and genetic drift have shaped diversification within the chicken species. In addition, new breeds or strains have been developed from crossbreeding programs facilitated by man. These events, together with other breeding practices, have led to genomic alterations causing genetic differentiation between the domesticated chickens and their ancestral/wild population as well as manipulation of the genetic diversity within the domesticated chickens. We investigated the relationship between 172 domesticated chicken populations from different selection, breeding and management backgrounds and their genetic distance to the wild type chickens. We found that the genetic diversity within the populations decreases with the increasing genetic distances to the wild types. Human manipulation of chicken genetic diversity has more effect on the genetic differentiation than simple geographic separations (through migrations) do. We further found that some genes associated with vital functions show evolutionary constraints or persistent selection across the populations and do not comply with this relationship i.e. the genetic diversity within the populations is constant despite the change in the genetic distance to the wild types.

genetics↗

bioRxiv2017

Mapping The Malaria Parasite Drug-Able Genome Using In Vitro Evolution And Chemogenomics

Chemogenetic characterization through in vitro evolution combined with whole genome analysis is a powerful tool to discover novel antimalarial drug targets and identify drug resistance genes. Our comprehensive genome analysis of 262 Plasmodium falciparum parasites treated with 37 diverse compounds reveals how the parasite evolves to evade the action of small molecule growth inhibitors. This detailed data set revealed 159 gene amplifications and 148 nonsynonymous changes in 83 genes which developed during resistance acquisition. Using a new algorithm, we show that gene amplifications contribute to 1/3 of drug resistance acquisition events. In addition to confirming known multidrug resistance mechanisms, we discovered novel multidrug resistance genes. Furthermore, we identified promising new drug target-inhibitor pairs to advance the malaria elimination campaign, including: thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This deep exploration of the P. falciparum resistome and drug-able genome will guide future drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms of the deadliest malaria parasite.\n\nOne Sentence SummaryWhole genome sequencing reveals how Plasmodium falciparum evolves resistance to diverse compounds and identifies new antimalarial drug targets.

genomics↗