Biology subjects

de Groot, N. G.

Publications and source records attributed to de Groot, N. G..

3 recordsLinked to original sources

bioRxiv2024

Unravelling the architecture of Major Histocompatibility Complex class II haplotypes in rhesus macaques

The regions in the genome that encode components of the immune system are often featured by polymorphism, copy number variation and segmental duplications. There is a need to thoroughly characterize these complex regions to gain insight into the impact of genomic diversity on health and disease. Here we resolve the organization of complete major histocompatibility complex (MHC) class II regions in rhesus macaques by using a long-read sequencing strategy (Oxford Nanopore Technologies) in concert with adaptive sampling. In particular, the expansion and contraction of the primate DRB-region appears to be a dynamic process that involves the rearrangement of different cassettes of paralogous genes. These chromosomal recombination events are propagated by a conserved pseudogene, DRB6, which features the integration of two retroviral elements. In contrast, the DRA locus appears to be protected from rearrangements, which may be due to the presence of an adjacently located truncated gene segment, DRB9. With our sequencing strategy, the annotation, evolutionary conservation, and potential function of pseudogenes can be reassessed, an aspect that was neglected by most genome studies in primates. Furthermore, our approach facilitates the characterization and refinement of an animal model essential to study human biology and disease.

genetics↗

bioRxiv2023

Behavioural, physiological, and genetic drivers of coping

Animals regularly experience stressful situations, ranging from predation to social stress, yet successfully deal with them on most occasions. This adaptive mechanism, coping, reduces the adverse effects of stressors through behavioural and physiological efforts, failing to which may result in reduced fitness. However, considerable variation in coping is observed. Unlike in humans, coping is often considered a personality trait in non-human animals due to construct similarity, resulting in conceptual ambiguity. Besides, limited multidisciplinary research has rendered comprehending the drivers of coping in animals challenging. We assessed repetitive behavioural coping or coping styles (n=30), emotional arousal (n=12), and consistent inter-individual differences, i.e., personalities (n=32) of long-tailed macaques (Macaca fascicularis) using observations, ecologically relevant experiments, and infrared thermography. We finally investigated the association of coping with a Valine/Methionine polymorphism encoded by the Catechol-O-methyltransferase (COMT) gene (n=26), which is widely known for its involvement in human stress regulation. Our findings suggest that personality and the presence of the human equivalent COMT Val158Met polymorphism in long-tailed macaques are associated with emotion-focused and problem-focused coping styles. These coping styles were consistent with emotional arousal as measured with infrared thermography. We discuss these proximate drivers of coping for a better understanding of its evolution in primates.

animal behavior and cognition↗

bioRxiv2021

Rapid characterization of complex genomic regions using Cas9 enrichment and Nanopore sequencing

Long-read sequencing approaches have considerably improved the quality and contiguity of genome assemblies. Such platforms bear the potential to resolve even extremely complex regions, such as multigenic families and repetitive stretches of DNA. Deep sequencing coverage, however, is required to overcome low nucleotide accuracy, especially in regions with high homopolymer density, copy number variation, and sequence similarity, such as the MHC and KIR gene clusters of the immune system. Therefore, we have adapted a targeted enrichment protocol in combination with long-read sequencing to efficiently annotate complex genomic regions. Using Cas9 endonuclease activity, segments of the complex KIR gene cluster were enriched and sequenced on an Oxford Nanopore Technologies platform. This provided sufficient coverage to accurately resolve and phase highly complex KIR haplotypes. Our strategy facilitates rapid characterization of large and complex multigenic regions, including its epigenetic footprint, in multiple species, even in the absence of a reference genome.

molecular biology↗