%0 Journal Article
%T The Malaria-Protective Human Glycophorin Structural Variant DUP4 Shows Somatic Mosaicism and Association with Hemoglobin Levels
%A Anna F£¿rnert
%A Billy Ngasala
%A Danielle Carpenter
%A Fengtang Yang
%A Ingegerd Rooth
%A Marie-Anne Shaw
%A Paulina Brajer
%A Sandra Louzada
%A Walid Algady
%J Archive of "American Journal of Human Genetics".
%D 2018
%R 10.1016/j.ajhg.2018.10.008
%X Glycophorin A and glycophorin B are red blood cell surface proteins and are both receptors for the parasite Plasmodium falciparum, which is the principal cause of malaria in sub-Saharan Africa. DUP4 is a complex structural genomic variant that carries extra copies of a glycophorin A-glycophorin B fusion gene and has a dramatic effect on malaria risk by reducing the risk of severe malaria by up to 40%. Using fiber-FISH and Illumina sequencing, we validate the structural arrangement of the glycophorin locus in the DUP4 variant and reveal somatic variation in copy number of the glycophorin B-glycophorin A fusion gene. By developing a simple, specific, PCR-based assay for DUP4, we show that the DUP4 variant reaches a frequency of 13% in the population of a malaria-endemic village in south-eastern Tanzania. We genotype a substantial proportion of that village and demonstrate an association of DUP4 genotype with hemoglobin levels, a phenotype related to malaria, using a family-based association test. Taken together, we show that DUP4 is a complex structural variant that may be susceptible to somatic variation and show that DUP4 is associated with a malarial-related phenotype in a longitudinally followed population
%K structural variant
%K copy number variation
%K glycophorin
%K sub-Saharan Africa
%K malaria
%K genome rearrangement
%K mosaicism
%K CNV
%K fusion gene
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218809/