Publications

A total of 72 unrelated Mandenka individuals from Eastern Senegal, Niokholo region, were typed using Next Generation Sequencing (library preparation with the Holotype HLA X2 and MIA FORA NGS HLA Typing kits, sequencing with Illumina MiSeq, and bio-informatic processing with HLA Twin v1.1.1 (Omixon) and MIA FORA NGS software) and yielded reliable genotypes for 8 HLA loci, namely A, B, C, DRB1, DQA1, DQB1, DPA1 and DPB1.

The mammalian HoxD cluster lies between two topologically associating domains (TADs) matching distinct enhancer-rich regulatory landscapes. During limb development, the telomeric TAD controls the early transcription of Hoxd genes in forearm cells, whereas the centromeric TAD subsequently regulates more posterior Hoxd genes in digit cells. Therefore, the TAD boundary prevents the terminal Hoxd13 gene from responding to forearm enhancers, thereby allowing proper limb patterning. To assess the nature and function of this CTCF-rich DNA region in embryos, we compared chromatin interaction profiles between proximal and distal limb bud cells isolated from mutant stocks where various parts of this boundary region were removed. The resulting progressive release in boundary effect triggered inter-TAD contacts, favored by the activity of the newly accessed enhancers. However, the boundary was highly resilient, and only a 400-kb deletion, including the whole-gene cluster, was eventually able to merge the neighboring TADs into a single structure. In this unified TAD, both proximal and distal limb enhancers nevertheless continued to work independently over a targeted transgenic reporter construct. We propose that the whole HoxD cluster is a dynamic TAD border and that the exact boundary position varies depending on both the transcriptional status and the developmental context.

Understanding the processes that drive population genetic divergence in the Amazon is challenging because of the vast scale, the environmental richness and the outstanding biodiversity of the region. We addressed this issue by determining the genetic structure of the widespread Amazonian common sardine fish Triportheus albus (Characidae). We then examined the influence, on this species, of all previously proposed population-structuring factors, including isolation-by-distance, isolation-by-barrier (the Teotônio Falls) and isolation-by-environment using variables that describe floodplain and water characteristics. The population genetics analyses revealed an unusually strong structure with three geographical groups: Negro/Tapajós rivers, Lower Madeira/Central Amazon, and Upper Madeira. Distance-based redundancy analyses showed that the optimal model for explaining the extreme genetic structure contains all proposed structuring factors and accounts for up to 70% of the genetic structure. We further quantified the contribution of each factor via a variance-partitioning analysis. Our results demonstrate that multiple factors, often proposed as individual drivers of population divergence, have acted in conjunction to divide T. albus into three genetic lineages. Because the conjunction of multiple long-standing population-structuring processes may lead to population reproductive isolation, that is, the onset of speciation, we suggest that the multifactorial population-structuring processes highlighted in this study could account for the high speciation rate characterising the Amazon Basin.

The diversity of the haemosporidian genera Plasmodium, Haemoproteus and Leucocytozoon in birds from rain forests in Madagascar is characterized combining techniques of PCR and microscopy and based on the examination of 72 host individuals of 23 species in 15 families. High total prevalence of haemosporidians (68%) is detected, with Leucocytozoon infections being predominant (59.7%) and lower comparable prevalence of Plasmodium (18.0%) and Haemoproteus (23.6%) infections. Using mitochondrial cytochrome b (cytb) marker, 23 genetically distinct lineages are identified: 9 of Plasmodium spp., 6 of Haemoproteus spp. and 8 of Leucocytozoon spp. Fifteen of all lineages have not been reported by previous studies. This study provides the first data on haemosporidian morphological and molecular diversity found in the endemic families Vangidae and Bernieriidae. Two haemoproteid species, Haemoproteus fuscae Mello and Fonseca, 1937 and H. killangoi Bennett and Peirce, 1981, are redescribed based on the present samples and linked to the cytb lineages hCELEC01 and hZOSMAD01, respectively. Phylogenetic analysis is performed to test the relationship of the discovered new lineages with parasites from closely related avian hosts suggesting that multiple colonisation of hosts by haemosporidian parasites has occurred on the island.

Recent advances in sequencing technologies have allowed for the retrieval of ancient DNA data (aDNA) from skeletal remains, providing direct genetic snapshots from diverse periods of human prehistory. Comparing samples taken in the same region but at different times, hereafter called "serial samples", may indicate whether there is continuity in the peopling history of that area or whether an immigration of a genetically different population has occurred between the two sampling times. However, the exploration of genetic relationships between serial samples generally ignores their geographical locations and the spatiotemporal dynamics of populations. Here, we present a new coalescent-based, spatially explicit modelling approach to investigate population continuity using aDNA, which includes two fundamental elements neglected in previous methods: population structure and migration. The approach also considers the extensive temporal and geographical variance that is commonly found in aDNA population samples.

PurposeCopy-number variants (CNVs) are generally interpreted by linking the effects of gene dosage with phenotypes. The clinical interpretation of noncoding CNVs remains challenging. We investigated the percentage of disease-associated CNVs in patients with congenital limb malformations that affect noncoding cis-regulatory sequences versus genes sensitive to gene dosage effects.MethodsWe applied high-resolution copy-number analysis to 340 unrelated individuals with isolated limb malformation. To investigate novel candidate CNVs, we re-engineered human CNVs in mice using clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing.ResultsOf the individuals studied, 10% harbored CNVs segregating with the phenotype in the affected families. We identified 31 CNVs previously associated with congenital limb malformations and four novel candidate CNVs. Most of the disease-associated CNVs (57%) affected the noncoding cis-regulatory genome, while only 43% included a known disease gene and were likely to result from gene dosage effects. In transgenic mice harboring four novel candidate CNVs, we observed altered gene expression in all cases, indicating that the CNVs had a regulatory effect either by changing the enhancer dosage or altering the topological associating domain architecture of the genome.ConclusionOur findings suggest that CNVs affecting noncoding regulatory elements are a major cause of congenital limb malformations.Genetics in Medicine advance online publication, 12 October 2017; doi:10.1038/gim.2017.154.

Aquatic oligochaetes represent valuable indicators of the quality of sediments of watercourses and lakes, but their difficult identification based on morphological criteria compromises their more common use for eco-diagnostic analyses. This issue could be overcome by using DNA barcodes for species identification. A 10% threshold of cytochrome c oxidase (COI) divergence was proposed for differentiating between oligochaete species based on molecular and morphological data. A Swiss database of COI sequences of aquatic oligochaetes was initiated in 2012. The aim of this study is to complement the Swiss oligochaete database of COI sequences and to confirm the relevance of this threshold for species delimitation.

Tropical mountains are areas of high species richness and endemism. Two historical phenomena may have contributed to this: (i) fragmentation and isolation of habitats may have promoted the genetic differentiation of populations and increased the possibility of allopatric divergence and speciation and (ii) the mountain areas may have allowed long-term population persistence during global climate fluctuations. These two phenomena have been studied using either species occurrence data or estimating species divergence times. However, only few studies have used intraspecific genetic data to analyse the mechanisms by which endemism may emerge at the microevolutionary scale. Here, we use landscape analysis of genomic SNP data sampled from two high-elevation plant species from an archipelago of tropical sky islands (the Trans-Mexican Volcanic Belt) to test for population genetic differentiation, synchronous demographic changes and habitat persistence. We show that genetic differentiation can be explained by the degree of glacial habitat connectivity among mountains and that mountains have facilitated the persistence of populations throughout glacial/interglacial cycles. Our results support the ongoing role of tropical mountains as cradles for biodiversity by uncovering cryptic differentiation and limits to gene flow.

From a biogeographic perspective Africa is subdivided into distinct horizontal belts. Human populations living along the Sahel/Savannah belt south of the Sahara Desert have often been overshadowed by extensive studies focusing on other African populations such as hunter-gatherers or Bantu in particular. However, the Sahel together with the savannah bordering it in the south, is a challenging region where people had and still have to cope with harsh climatic conditions and show resilient behaviours. Besides exponentially growing urban populations, several local groups leading various lifestyles and speaking languages belonging to three main linguistic families still live in rural localities across that region today. Thanks to several years of consistent population sampling throughout this area, the genetic history of the African Sahelian populations has been largely reconstructed and a deeper knowledge has been acquired regarding their adaptation to peculiar environments and/or subsistence modes. Distinct exposures to pathogens - in particular malaria - likely contributed to their genetic differentiation for HLA genes. In addition, although food-producing strategies spread within the Sahel/Savannah belt relatively recently, during the last five millennia according to recent archaeological and archaeobotanical studies, remarkable amounts of genetic differences are also observed between sedentary farmers and more mobile pastoralists at multiple neutral and selected loci, reflecting both demographic effects and genetic adaptations to distinct cultural traits, such as dietary habits.