marker-assisted selection in wheat - ictsd

Chapter 12 – Marker-assisted selection in dairy cattle 215N is the sample size. In the case of a granddaughterdesign, the units for the standarddeviation will be either units of the bulls’DYD or genetic evaluations. For example,if d is 0.5 and N is 400, the CI will be 31 percentrecombination, or approximately 35cM. Thus, except for the largest QTL, CIswill generally include several tens of cM.Considering that each cattle cM includes ~8genes and one million bp, detection of theactual polymorphism responsible for theobserved QTL effects (the quantitative traitnucleotide, QTN) appears at first glance tobe a “mission impossible”.Various strategies have been proposedto reduce the CI based on multiplecrosses, but most are not applicable todairy cattle (e.g. Darvasi, 1998). Meuwissenand Goddard (2000) proposed that CI forQTL location could be reduced to individualcM by application of LD mapping.If a QTL polymorphism is due to a relativelyrecent mutation or to a relativelyrecent introduction from another population,then it should be possible to detectpopulation-wide LD between the QTLand closely linked genetic markers. Thecloser the marker to the QTL, the greaterwill be the extent of LD. They developeda method to estimate QTL location and CIbased on LD between a QTL and a seriesof closely linked markers. The CI can befurther reduced by combining linkage andLD mapping (Meuwissen et al., 2002), andby a multitrait analysis (Meuwissen andGoddard, 2004). However, unless the QTLeffect is very large, the CI will still extendover several cM.In order to determine the actual generesponsible for the QTL, most studies haveused the “candidate gene” approach, i.e.to determine a likely candidate among thegenes within the CI, based on known genefunction, or specific gene expression in theorgan of interest. Examples are given inthe following section. However, even if apolymorphism is detected in the candidategene and the polymorphism has a majorLD effect on the QTL, how does one provethat this polymorphism is not merely inLD with the actual QTN?Mackay (2001) proposed two alternativesfor proof positive that a candidatepolymorphism is in fact the QTN, namely,co-segregation of intragenic recombinantgenotypes in a candidate gene with theQTL phenotype, and functional complementationwhere the trait phenotype is“rescued” in a transgenic organism. Neitherof these is applicable to QTL in dairy cattle.In this case, Mackay (2001) postulated thatthe only option to achieve the standard ofrigorous proof for identification of a geneunderlying a QTL in commercial animalpopulations is to collect “multiple piecesof evidence, no single one of which is convincing,but which together consistentlypoint to a candidate gene”. Evidence can beprovided by concordance of polymorphismwith deduced QTL genotype, quantitativedifferences of gene expression in physiologicallyrelevant organs, SNP capableof encoding a non-conservative aminoacid change, protein differences in cowswith contrasting genotypes for the QTN,orthologous QTL in other species (genesthat are derived from a common ancestralgene) and alteration of gene proteinin bovine cell lines by “short interferingRNA” (siRNA) technology. (The siRNAmolecules bind with proteins to form a unitcalled the “RNA-induced silencing complex”that suppresses the expression of thegene to which it corresponds in the viralgenome, silencing the gene from which thesiRNA is derived.)For dairy cattle, to date, the most compellingevidence is “concordance”, i.e. that