Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/45203
Title: The Malaria-Protective Human Glycophorin Structural Variant DUP4 Shows Somatic Mosaicism and Association with Hemoglobin Levels.
Authors: Algady, W
Louzada, S
Carpenter, D
Brajer, P
Färnert, A
Rooth, I
Ngasala, B
Yang, F
Shaw, M-A
Hollox, EJ
First Published: 1-Nov-2018
Publisher: Elsevier (Cell Press)
Citation: American Journal of Human Genetics, 2018, 103 (5), pp. 769-776
Abstract: 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.
DOI Link: 10.1016/j.ajhg.2018.10.008
eISSN: 1537-6605
Links: https://www.sciencedirect.com/science/article/pii/S0002929718303604?via%3Dihub
http://hdl.handle.net/2381/45203
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2018. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: Sequence data are available from the European Nucleotide Archive for HG02554 (accession number ERP110671) and European Genome-Phenome Archive for the four Tanzanian samples (study accession number EGAS00001003239). Access to the Tanzanian sample sequences is restricted to projects related to malarial research.
Appears in Collections:Published Articles, Dept. of Genetics

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