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| Status |
Public on Jun 26, 2008 |
| Title |
Expression and genomic changes after exposing drug-selected mutants to short term CQ treatment in Plasmodium falciparum. |
| Platform organisms |
Plasmodium falciparum; Anopheles gambiae |
| Sample organism |
Plasmodium falciparum |
| Experiment type |
Expression profiling by array
Genome variation profiling by array
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| Summary |
Mutations in PfCRT confer chloroquine (CQ) resistance in P. falciparum. Point mutations in the homolog of the mammalian multidrug resistance gene (pfmdr1) can also modulate the levels of CQ response. However, parasites with the same pfcrt and pfmdr1 alleles exhibit a wide range of drug sensitivity, suggesting that additional genes contribute to levels of CQ resistance (CQR).
We used 3 isogenic lines which have different drug resistance profiles corresponding to unique mutations in the pfcrt gene (106/1K76, 106/176I, and 106/76I-352K) to study changes in gene expression with and without CQ and genomic variations, i.e. copy number (CN) changes.
RNA transcription levels from 45 genes were significantly altered in one or both mutants relative to the parent line. Of particular interest are genes encoding proteins involved in transport and/or regulation of cytoplasmic or compartmental pH, e.g. the V-type H+ pumping pyrophosphatase 2, Ca2+/H+ antiporter VCX1 and copy number changes in pfmdr1. A series of deletion (including 15 genes) also occurred at the beginning of chromosome 10.
Keywords: low-dose 3h Chloroquine response, copy number variation
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| Overall design |
Three isogenic parasite lines were treated with and without 3h CQ and synchronized for total RNA extraction and hybridization to Affymetrix GeneChips® to study gene expression profiles. Genomic DNA from mixed culture was also extracted and hybridized to the same Affymetrix GeneChips. Total 18 total RNA samples (3 biological replicates per condition) and 6 genomic DNA samples (2 biological replicates per condition).
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| Contributor(s) |
Jiang H, Patrel JJ, Yi M, Mu J, Ding J, Stephens R, Cooper RA, Ferdig MT, Su X |
| Citation(s) |
18575593 |
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| Submission date |
Dec 26, 2007 |
| Last update date |
Jan 24, 2013 |
| Contact name |
Hongying Jiang |
| E-mail(s) |
hojiang@mail.nih.gov
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| Phone |
3014519033
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| Fax |
3014022201
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| Organization name |
NIAID/NIH
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| Street address |
12735 Twinbrook Parkway
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| City |
Rockville |
| State/province |
MD |
| ZIP/Postal code |
20852 |
| Country |
USA |
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| Platforms (1) |
| GPL1321 |
[Plasmodium_Anopheles] Affymetrix Plasmodium/Anopheles Genome Array |
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| Samples (24)
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| GSM253220 |
RNA 106/1 no CQ-treatment, biological rep1 |
| GSM253221 |
RNA 106/1 no CQ-treatment, biological rep2 |
| GSM253222 |
RNA 106/1 no CQ-treatment, biological rep3 |
| GSM253223 |
RNA 106/1 CQ-treated, biological rep1 |
| GSM253224 |
RNA 106/1 CQ-treated, biological rep2 |
| GSM253225 |
RNA 106/1 CQ-treated, biological rep3 |
| GSM253226 |
RNA 106/1(76I) no CQ-treatment, biological rep1 |
| GSM253227 |
RNA 106/1(76I) no CQ-treatment, biological rep2 |
| GSM253228 |
RNA 106/1(76I) no CQ-treatment, biological rep3 |
| GSM253229 |
RNA 106/1(76I) CQ-treated, biological rep1 |
| GSM253230 |
RNA 106/1(76I) CQ-treated, biological rep2 |
| GSM253231 |
RNA 106/1(76I) CQ-treated, biological rep3 |
| GSM253232 |
RNA 106/1(76I_352K) no CQ-treatment, biological rep1 |
| GSM253233 |
RNA 106/1(76I_352K) no CQ-treatment, biological rep2 |
| GSM253234 |
RNA 106/1(76I_352K) no CQ-treatment, biological rep3 |
| GSM253235 |
RNA 106/1(76I_352K) CQ-treated, biological rep1 |
| GSM253236 |
RNA 106/1(76I_352K) CQ-treated, biological rep2 |
| GSM253237 |
RNA 106/1(76I_352K) CQ-treated, biological rep3 |
| GSM253238 |
gDNA 106/1 no CQ-treatment, biological rep1 |
| GSM253239 |
gDNA 106/1 no CQ-treatment, biological rep2 |
| GSM253240 |
gDNA 106/1(76I) no CQ-treatment, biological rep1 |
| GSM253241 |
gDNA 106/1(76I) no CQ-treatment, biological rep2 |
| GSM253242 |
gDNA 106/1(76I_352K) no CQ-treatment, biological rep1 |
| GSM253243 |
gDNA 106/1(76I_352K) no CQ-treatment, biological rep2 |
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| Relations |
| BioProject |
PRJNA108215 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE10022_RAW.tar |
75.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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