P. falciparum Genetic Crosses

 

 

 

Started 2010

The P. falciparum Genetic Crosses project is generating high-quality data on genome sequence variation and sexual recombination for the parents and progeny of parasite crosses.

Objectives & Coordination

Discovering the genetic causes of natural phenotypic variation in P. falciparum requires a combination of epidemiological and laboratory-based approaches. A powerful laboratory approach, which was instrumental in discovering the chloroquine resistance gene PfCRT, involves crossing two parasite strains with different phenotypic characteristics and then studying the resulting progeny.

Unfortunately, it is extremely laborious to perform genetic crosses for P. falciparum, and to date it has been accomplished only four times. The strains that have been crossed are 3D7 with HB3 (Walliker et al, 1987), HB3 with Dd2 (Wellems et al, 1990) and 7G8 with GB4 (Hayton et al, 2008). A fourth cross between clones 803 and GB4 was recently performed to study the genetic basis for artemisinin resistance. The parents and progeny of these genetic crosses represent a hugely valuable resource for the malaria research community to investigate a range of different phenotypes.

Assembling a complete and accurate picture of P. falciparum genome variation from short sequence reads presents many analytical challenges, particularly in regions of the genome that are highly polymorphic or made up of repetitive elements. To provide researchers with data resources to help overcome these challenges, the P. falciparum Genetic Crosses project has:

  • Sequenced the parents and 78 progeny clones from the crosses 3D7xHB3, HB3xDd2 and 7G8xGB4
  • Performed the first integrated analysis of single nucleotide polymorphisms (SNPs), INDELs and complex polymorphisms in P. falciparum, using Mendelian error rates as an indicator of genotypic accuracy
  • Released sequence data and variant calls open access, and provided a dedicated web application to increase the usefulness of these data resources

Data

Data generated by the P. falciparum Genetic Crosses project is made available open access.

Current

18 May 2015

P. falciparum genetic crosses 1.0 data release

Species: P. falciparum

Sample set: Parents and 78 progeny clones from three crosses (3D7xHB3, HB3xDd2 and 7G8xGB4)

Sequence data and variant calls

People

The following investigators are involved in the P. falciparum Crosses project.

Alistair Miles
Head of Epidemiological Informatics
Wellcome Trust Centre for Human Genetics, University of Oxford, UK
Prof Dominic Kwiatkowski
Professor of Genomics and Global Health
Wellcome Trust Centre for Human Genetics, University of Oxford, UK
Head of Malaria Programme
Wellcome Trust Sanger Institute, UK
Director of Centre for Genomics and Global Health
Big Data Institute, University of Oxford
Prof Gilean McVean
Group Head / PI and Unit Director and Acting Director of the Oxford Big Data Institute
Wellcome Trust Centre for Human Genetics, University of Oxford, UK
Professor of Statistical Genetics and University Lecturer in Mathematical Genetics
Department of Statistics, University of Oxford, UK
Dr Jonathan Mwangi
Affiliate Researcher
University of Glasgow, UK
Lecturer
Mount Kenya University, Kenya
Dr Julian C Rayner
Senior Group Leader, Malaria Programme
Wellcome Trust Sanger Institute, UK
Director, Courses, Conferences and Public Engagement Programme
Wellcome Genome Campus, UK
Dr Karen Hayton
NIH National Institute of Allergy and Infectious Diseases (NIAID), USA
Dr Lisa Ranford-Cartwright
Reader
Institute of Infection, Immunity and Inflammation, University of Glasgow, UK
Guest Professor
Wenner-Gren Institute, Dept. of Molecular Biosciences, Stockholm University, Sweden
Assoc Prof Mike Ferdig
University of Notre Dame, France
Dr Thomas E Wellems
Chief, Laboratory of Malaria and Vector Research and Chief, Malaria Genetics Section
NIH National Institute of Allergy and Infectious Diseases (NIAID), USA
US National Academy of Sciences
Dr Xin-zhuan Su
Chief, Malaria Functional Genomics Section, LMVR
NIH National Institute of Allergy and Infectious Diseases (NIAID), USA
Dr Zamin Iqbal
PI/Group Leader
Wellcome Trust Centre for Human Genetics, University of Oxford, UK