Low linkage disequilibrium in wild Anopheles gambiae s.l. populations

The level of LD between SNP pairs in cloned sequences of each gene was determined for 7 species (or incipient species) of the An. gambiae complex. In all tested genes and species, LD between SNPs was low: even at short distances (< 200 bp), most SNP pairs gave an r2 < 0.3. Mean r2 ranged from 0.073 to 0.766. In most genes and species LD decayed very rapidly with increasing inter-marker distance.These results are of great interest for the development of large scale polymorphism studies, as LD generally falls below any useful limit. It indicates that very fine scale SNP detection will be required to give an overall view of genome-wide polymorphism. Perhaps a more feasible approach to genome wide association studies is to use targeted approaches using candidate gene selection to detect association to phenotypes of interest.When alleles at different loci appear together in individuals more often than would be expected by chance they are said to be in Linkage Disequilibrium (LD) [1]. LD is an indicator of the rate of recombination events between markers during meiosis. In addition to nucleotide distance, the effective recombination rate can be affected by numerous forces in natural populations such as selection that maintains certain allele associations (epistasis), genetic drift, population structure and demographic changes. Non random association between variants has recently become the focus of intense study in the hope that it might facilitate the mapping of complex trait loci through genome wide association studies (GWAS). Indeed, recent progress in the technological ability to genotype genetic variation [2] opens promising possibilities for identification of variants linked to phenotypes of interest. However, the ability to detect association critically depends on the extent of LD between causative alleles and surrounding markers. When LD extends over large genomic regions, there is a higher chance of finding association with the drawback that the potentially long