The 3D nuclear conformation of the major histocompatibility complex changes upon cell activation both in porcine and human macrophages.

Background: The crucial role of the major histocompatibility complex (MHC) for the immune response to infectious diseases is well-known, but no information is available on the 3D nuclear organization of this gene-dense region in immune cells, whereas nuclear architecture is known to play an essential role on genome function regulation. We analyzed the spatial arrangement of the three MHC regions (class I, III and II) in macrophages using 3D-FISH. Since this complex presents major differences in humans and pigs with, notably, the presence of the centromere between class III and class II regions in pigs, the analysis was implemented in both species to determine the impact of this organization on the 3D conformation of the MHC.

Multi-species annotation of transcriptome and chromatin structure in domesticated animals.

Background: Comparative genomics studies are central in identifying the coding and non-coding elements associated with complex traits, and the functional annotation of genomes is a critical step to decipher the genotype-to-phenotype relationships in livestock animals. As part of the Functional Annotation of Animal Genomes (FAANG) action, the FR-AgENCODE project aimed to create reference functional maps of domesticated animals by profiling the landscape of transcription (RNA-seq), chromatin accessibility (ATAC-seq) and conformation (Hi-C) in species representing ruminants (cattle, goat), monogastrics (pig) and birds (chicken), using three target samples related to metabolism (liver) and immunity (CD4+ and CD8+ T cells).

Results: RNA-seq assays considerably extended the available catalog of annotated transcripts and identified differentially expressed genes with unknown function, including new syntenic lncRNAs.

Accounting for linkage disequilibrium in genome scans for selection without individual genotypes: The local score approach.

Detecting genomic footprints of selection is an important step in the understanding of evolution. Accounting for linkage disequilibrium in genome scans increases detection power, but haplotype-based methods require individual genotypes and are not applicable on pool-sequenced samples. We propose to take advantage of the local score approach to account for linkage disequilibrium in genome scans for selection, cumulating (possibly small) signals from single markers over a genomic segment, to clearly pinpoint a selection signal.

Expressed alleles of imprinted IGF2, DLK1 and MEG3 colocalize in 3D-preserved nuclei of porcine fetal cells.

Background: To explore the relationship between spatial genome organization and gene expression in the interphase nucleus, we used a genomic imprinting model, which offers parental-specific gene expression. Using 3D FISH in porcine fetal liver cells, we compared the nuclear organization of the two parental alleles (expressed or not) of insulin-like growth factor 2 (IGF2), a paternally imprinted gene located on chromosome 2. We investigated whether its nuclear positioning favors specific locus associations.

Meiotic recombination analyses of individual chromosomes in male domestic pigs (Sus scrofa domestica).

For the first time in the domestic pig, meiotic recombination along the 18 porcine autosomes was directly studied by immunolocalization of MLH1 protein. In total, 7,848 synaptonemal complexes from 436 spermatocytes were analyzed, and 13,969 recombination sites were mapped. Individual chromosomes for 113 of the 436 cells (representing 2,034 synaptonemal complexes) were identified by immunostaining and fluorescence in situ hybridization (FISH).

The sheep genome illuminates biology of the rumen and lipid metabolism.

Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution.

3D organization of telomeres in porcine neutrophils and analysis of LPS-activation effect.

Background: While the essential role of 3D nuclear architecture on nuclear functions has been demonstrated for various cell types, information available for neutrophils, essential components of the immune system, remains limited. In this study, we analysed the spatial arrangements of telomeres which play a central role in cell fate. Our studies were carried out in swine, which is an excellent model organism for both biomedical research and agronomic applications.

Pool-hmm: a Python program for estimating the allele frequency spectrum and detecting selective sweeps from next generation sequencing of pooled samples.

Due to its cost effectiveness, next generation sequencing of pools of individuals (Pool-Seq) is becoming a popular strategy for genome-wide estimation of allele frequencies in population samples. As the allele frequency spectrum provides information about past episodes of selection, Pool-seq is also a promising design for genomic scans for selection. However, no software tool has yet been developed for selection scans based on Pool-Seq data.

Transcriptomic and nuclear architecture of immune cells after LPS activation.

Changes in the nuclear positioning of specific genes, depending on their expression status, have been observed in a large diversity of physiological processes. However, gene position is poorly documented for immune cells which have been subjected to activation following bacterial infection. Using a pig model, we focused our study on monocyte-derived macrophages and neutrophils, as they are the first lines of defence against pathogens.

Detecting local high-scoring segments: a first-stage approach for genome-wide association studies.

Genetic epidemiology aims at identifying biological mechanisms responsible for human diseases. Genome-wide association studies, made possible by recent improvements in genotyping technologies, are now promisingly investigated. In these studies, common first-stage strategies focus on marginal effects but lead to multiple-testing and are unable to capture the possibly complex interplay between genetic factors.

seq++: analyzing biological sequences with a range of Markov-related models.

The seq++ package offers a reference set of programs and an extensible library to biologists and developers working on sequence statistics. Its generality arises from the ability to handle sequences described with any alphabet (nucleotides, amino acids, codons and others). seq++ enables sequence modelling with various types of Markov models, including variable length Markov models and the newly developed parsimonious Markov models, all of them potentially phased.

SIC: A tool to detect short inverted segments in a biological sequence.

The web software SIC provides a tool to search for short inverted segments (length 3-5000 bp) in a DNA sequence. The sequence is assumed to follow a Markov model. A statistic which is sensitive to inversion is presented.