@article{fdi:010052849, title = {{P}olymorphisms in {A}nopheles gambiae immune genes associated with natural resistance to {P}lasmodium falciparum}, author = {{H}arris, {C}aroline and {L}ambrechts, {L}. and {R}ousset, {F}. and {A}bate, {L}uc and {N}sango, {S}andrine and {F}ontenille, {D}idier and {M}orlais, {I}sabelle and {C}ohuet, {A}nna}, editor = {}, language = {{ENG}}, abstract = {{M}any genes involved in the immune response of {A}nopheles gambiae, the main malaria vector in {A}frica, have been identified, but whether naturally occurring polymorphisms in these genes underlie variation in resistance to the human malaria parasite, {P}lasmodium falciparum, is currently unknown. {H}ere we carried out a candidate gene association study to identify single nucleotide polymorphisms ({SNP}s) associated with natural resistance to {P}. falciparum. {A}. gambiae {M} form mosquitoes from {C}ameroon were experimentally challenged with three local wild {P}. falciparum isolates. {S}tatistical associations were assessed between 157 {SNP}s selected from a set of 67 {A}. gambiae immune-related genes and the level of infection. {I}solate-specific associations were accounted for by including the effect of the isolate in the analysis. {F}ive {SNP}s were significantly associated to the infection phenotype, located within or upstream of {A}g{MDL}1, {CEC}1, {S}p {PPO} activate, {S}p {SNAKE}like, and {TOLL}6. {L}ow overall and local linkage disequilibrium indicated high specificity in the loci found. {A}ssociation between infection phenotype and two {SNP}s was isolate-specific, providing the first evidence of vector genotype by parasite isolate interactions at the molecular level. {F}our {SNP}s were associated to either oocyst presence or load, indicating that the genetic basis of infection prevalence and intensity may differ. {T}he validity of the approach was verified by confirming the functional role of {S}p {SNAKE}like in gene silencing assays. {T}hese results strongly support the role of genetic variation within or near these five {A}. gambiae immune genes, in concert with other genes, in natural resistance to {P}. falciparum. {T}hey emphasize the need to distinguish between infection prevalence and intensity and to account for the genetic specificity of vector-parasite interactions in dissecting the genetic basis of {A}nopheles resistance to human malaria.}, keywords = {}, booktitle = {}, journal = {{P}los {P}athogens}, volume = {6}, numero = {9}, pages = {e1001112}, ISSN = {1553-7366}, year = {2010}, DOI = {10.1371/journal.ppat.1001112}, URL = {https://www.documentation.ird.fr/hor/fdi:010052849}, }