Academic journal article Genetics

Mapping Quantitative Trait Loci in Noninbred Mosquito Crosses

Academic journal article Genetics

Mapping Quantitative Trait Loci in Noninbred Mosquito Crosses

Article excerpt

ABSTRACT

The identification of genes that affect quantitative traits has been of great interest to geneticists for many decades, and many statistical methods have been developed to map quantitative trait loci (QTL). Most QTL mapping studies in experimental organisms use purely inbred lines, where the two homologous chromosomes in each individual are identical. As a result, many existing QTL mapping methods developed for experimental organisms are applicable only to genetic crosses between inbred lines. However, it may be difficult to obtain inbred lines for certain organisms, e.g., mosquitoes. Although statistical methods for QTL mapping in outbred populations, e.g., humans, can be applied for such crosses, these methods may not fully take advantage of the uniqueness of these crosses. For example, we can generally assume that the two grandparental lines are homozygous at the QTL of interest, but such information is not be utilized through methods developed for outbred populations. In addition, mating types and phases can be relatively easy to establish through the analysis of adjacent markers due to the large number of offspring that can be collected, substantially simplifying the computational need. In this article, motivated by a mosquito intercross experiment involving two selected lines that are not genetically homozygous across the genome, we develop statistical methods for QTL mapping for genetic crosses involving noninbred lines. In our procedure, we first infer parental mating types and use likelihood-based methods to infer phases in each parent on the basis of genotypes of offspring and one parent. A hidden Markov model is then employed to estimate the number of high-risk alleles at marker positions and putative QTL positions between markers in each offspring, and QTL mapping is finally conducted through the inferred QTL configuration across all offspring in all crosses. The performance of the proposed methods is assessed through simulation studies, and the usefulness of this method is demonstrated through its application to a mosquito data set.

MOST statistical methods for QTL mapping developed for experimental organisms are applicable only to crosses starting from two inbred lines differing in the trait of interest, with each inbred line genetically homozygous between the two sets of chromosomes. Crossing between the two lines yields Fj progeny, who receive a copy of each chromosome from the two homozygous inbred lines; thus they are heterozygous at all loci where the two inbred lines differ. Therefore, genotypes of the F2 progeny are highly informative for the inheritance pattern at putative QTL sites. For example, if the two parental lines are denoted by a high- (H) trait line and a low- (L) trait line, respectively, having genotype HH, HL, or LL at one putative QTL for an F2 individual offers full information on the number of high-trait alleles at the QTL, i.e., 2, 1, or O, respectively.

However, crosses may be carried out between individuals who are not completely homozygous across the genome. Although we can generally assume that the two lines being crossed are still homozygous at the QTL, other loci along the genome may be heterozygous. For example, a mosquito intercross experiment was conducted to detect QTL in Anopheles gambiae that control melanotic encapsulation response against Plasmodium cynomolgi Ceylon (ZHENG et al. 2003). The encapsulation response is defined as the proportion of the encapsulated oocysts among all oocysts in a single mosquito. The crosses were carried out between a laboratory-selected A. gambiae refractory strain L3-5 and a susceptible strain 4Ar/r. The A. gambiae female is recognized as the most successful vector of human malarias. Refractoriness to P. cynomolgi Ceylon in the original refractory strain L3-5 seems to be largely but not completely recessive, which is also called incomplete recessive (CoLLiNS et al. 1986; VERNICK and COLLINS 1989). The encapsulation responses of 167 F2 females, among which 123 became infected, from six intercrosses among offspring of L3-5 females and 4Ar/r males were tested and genotype data were collected on these F2 females and their F1 maternal parents at 52 microsatellite markers spanning the current genetic map of A. …

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