Artemisinin resistance in rodent malaria - mutation in the AP2 adaptor μ-chain suggests involvement of endocytosis and membrane protein trafficking

Table 1 Confirmed and high confidence mutations in the ART-resistant Plasmodium chabaudi clone AS-ART (relative to progenitor clone, AS-sens)

Chromosome	Type	Analysis	Nucleotide start	Nucleotide end	reference base	variant base	SSAHA quality	Confirmation of mutation by dideoxy sequencing	P. chabaudi gene ID	Amino acid change	Nearest gene ID ( *P. chabaudi*)	P. falciparum orthologue
SNPs
2	SNP	SSAHA/MAQ	216,954		C	A	99	confirmed*	PCHAS_020720	V2728F		PF3D7_0104300
3	SNP	SSAHA/MAQ	70,553		G	T	99	confirmed*	PCHAS_030200	T707N		None
3	SNP	SSAHA/MAQ	474,123		C	A	99	confirmed*	PCHAS_031370	T719N		PF3D7_0214800
7	SNP	SSAHA/MAQ	994,546		G	A	99	confirmed*	PCHAS_072830	S106N		PF3D7_0417200
10	SNP	SSAHA/MAQ	634,932		T	C	99	confirmed*	PCHAS_101550	Y162H		PF3D7_1430000
11	SNP	SSAHA/MAQ	996,332		G	T	99	confirmed*	PCHAS_112780	A173E		PF3D7_0629500
14	SNP	SSAHA/MAQ	936,945		T	G	92	confirmed*			5'-PCHAS_142600	PF3D7_0813400
14	SNP	SSAHA/MAQ	1,270,184		T	C	99	confirmed*	PCHAS_143590	I568T		PF3D7_1218300
					approximate size		comparative coverage
Indels
4	indel	SSAHA/MAQ	793,940	793,988	49		0.16	tbc**			PCHAS_042080-5	None
5	deletion	SSAHA/MAQ	683,724	684,989	1,266		0.21	tbc**	PCHAS_051920			None
7	deletion	SSAHA/MAQ	876,907	876,921	15		0.18	34bp deletion*			PCHAS_072420-3'	PF3D7_0815700
bin	indel	SSAHA/MAQ	261,129	284,496	23,368		0.02	tbc**	PCHAS_000700-760		None

All point mutations and 34 bp deletion (*) were confirmed by di-deoxy sequencing. A small deletion on chromosome 4 and large deletions on chromosome 5 and ‘bin’ (**), have strong supporting evidence (extended area of low and zero coverage, SNP-proxies for deletions). Base quality scores (which only apply to SNPs) are derived from the SSAHA2 algorithm (with 99 being the best score). For indels, the approximate size of the affected area (as measured by SSAHA2) and a comparative coverage are given. Amino acid substitutions (non-synonymous mutations) are in bold characters. One point mutation in AP2-μ chain specific to AS-ART (relative to preceding clone, AS-30CQ) is in bold and underline characteres. Tbc: to be confirmed.

ISSN: 1475-2875