Project: Population genetics, anthropology and evolution

Population genetics, anthropology and evolution (PGAE)

Project leaders: Alicia Sanchez-Mazas and Natasja De Groot

Detailed project description:

The project aims at building an up-to-data mapping of the HLA molecular polymorphism in human populations and at developing a well-grounded methodological framework to analyse these data in an anthropological/evolutionary perspective. The component is both traditional and new: traditional, because it is in line with the “Anthropology components” of previous workshops, the aim of which was to characterize the HLA genetic diversity of human populations at a large geographic scale; new, because we wish to address more evolutionary issues through the data analyses. Indeed, with the progress of NGS technologies, an increasing amount of HLA sequence data is produced, that offers new opportunities to unravel how the MHC genomic region evolved at the molecular level in relation to both demographic events and selective pressures. This is why we open this Component not only to HLA laboratories wishing to include their population and/or donor data to our data analysis pipeline, but also to researchers working in population genetics and molecular evolution to share their expertise in order to analyse collectively the submitted data with sound evolutionary questions and co-author the resulting publications.

Besides using molecular evolutionary approaches, we wish to include data from our closest living relatives, the non-human primates (NHP), as they also exhibit a fascinating MHC polymorphism that merits to be analysed in parallel and will contribute to better understand how evolution shaped the immune genes in humans.

More concretely,

  • We encourage laboratories to submit high-resolution HLA population data, from a minimum 2nd-field level molecular typing to full-gene DNA sequencing. Our objective is to extend the HLA diversity maps built during previous workshops to additional populations/regions worldwide and to refine these maps by including as much as possible full-gene (i.e. exons, introns and UTRs) nucleotide information. Useful datasets may include both anthropologically-defined populations and donor registry samples.
  • We encourage researchers that investigate NHP-MHC or have NHP-MHC available at the molecular level, to submit these data. Our objective is to include as much NHP data to the analyses, which will add in the understanding of the evolution of the primate MHC genes.
  • We invite researchers working in population genetics and molecular evolution to share their expertise for the analysis of these data. Our objective is to define various kinds of biostatistical/computational approaches, including data comparisons to other related species, to investigate the evolutionary process that shaped the HLA polymorphism.

Milestones in years:

2019:

  • Setting up a webpage for submitting the data (hla-net.eu platform)
  • Encouraging laboratories/researchers to participate (EFI meeting, e-mails,..)
  • Starting collection of data
  • Component meeting at EFI Conference 2019 (Lisbon)

2020:

  • Continuing collection of data
  • Starting data analyses
  • Component meeting at EFI Conference 2020

2021:

  • Finalizing the analyses
  • Summarizing the results
  • Preparing preliminary publication drafts
  • Preparing the presentations at 18th IHIW in Amsterdam

Patient/sample description (if applicable, details, inclusion/exclusion criteria):

  1. For HLA data:

Human population samples from any country of the world, composed of:

  • unrelated individuals representative of a well-defined population, or
  • unrelated individuals from a blood or bone marrow donor registry

(Note that we may also consider unrelated patients of a particular disease, to discuss).

Population definitions: each population sample will have to be defined according to hla-net.eu recommendations (a questionnaire will be available online).

Sample sizes: we encourage a minimum of 100 individuals for well-defined populations. No maximum (very large samples are encouraged).

  1. For non-human primates (NHP) MHC data:

NHP population samples, in particular of Great-ape species, composed of

– unrelated individuals from which (sub)species definition is required.

Data required (number, type of data, inclusion/exclusion criteria):

  1. HLA data:

HLA high-resolution multi-locus genotypes or DNA sequences for HLA-A, -B, -C, -DRB1, DQB1, DQA1, DPB1 and DPA1.

Full-length DNA sequences are encouraged. Fewer loci may be considered.

  1. Non-human primate (NHP) MHC data:

Full-length gDNA or cDNA MHC typing for MHC-A, -B, -C, -DRB, DQB1, DQA1, DPB1 and DPA1. Any data from one of these loci is more than welcome from NHP.

Samples required (if applicable, number, type of samples, inclusion/exclusion criteria):

If no molecular typing is available, gDNA (or cDNA) would be required for the HLA or NHP-MHC typing to be performed.

Reagents/additional assays required:

Provided gDNA (or cDNA) samples of HLA or NHP-MHC require MHC typing.

Data infrastructure required:

Data submission tool (under preparation) at http://hla-net.eu


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