Critique of Data Analysis

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This paper addresses a currently relevant topic of detection of associations of copy number polymorphism with traits and will be of interest to readers of Genetics Research.

The simulation study showed that the additional information of CNP could increase the accuracy of predicted genotypic value, compared to using SNP information alone in an association study. The accuracy was heavily dependent on the heritability of CNP phenotypes (correlation of CNP genotype and phenotype) (Table 3). The higher accuracy of the prediction with CNP information might also result in smaller mean squared errors of prediction (Table 4)’.

On the other hand, the authors found that linkage disequilibrium (LD) between SNP and CNP was not much different from that between two SNPs. The authors demonstrated that an increased mutation rate and larger number of segregating alleles hardly affects LD with a nearby SNP.

I have the following major comments.

1) A possible reason for a high accuracy with using CNP information was that the CNP was the causal gene itself in the simulation. If the CNP had negligible effects, and was just linked with a causal gene, the performance might not be much different from SNPs, because as stated above that LD structure was not much different between SNP and CNP. In this situation, the success of using CNP information to predict genotypic values would be conditional on 1) the effects due to the causal CNP should explain significant proportion of genetic variation, 2) those causal CNP should be genotyped, and 3) the genotyping accuracy for CNP should be reasonably high. In general, how easily and accurately are the causal CNPs identified? What is underlying distribution of the effects due to CNPs? Can we expect that the corr...

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... the same effect of the same direction and magnitude. Would this be realistic?

10) Line 158, In case of the copy number is the same (c=b), the equation would give zero. Is this right?

11) Line 171, SNP phenotypes -> CNP phenotypes?

12) Line 242, 2 or 3 alleles > 2 or 3 copies?

13) Table 2. It may be useful to have likelihood ratio for each model.

14) Line 267, fenotype -> phenotype?

15) The introduction is human/livestock orientated, but the remainder of the paper is presented in livestock terminology. Some discussion about the relevance of the results to human populations would be useful.

16) Line 343 “Under the assumption that x copies at a CNP locus lead to the effect of x times the effect of 1 copy,” Is this a realistic assumption? Is CNP genotype of 4 copies likely to have the same functional impact for individuals with alleles 2/2 vs 4/0.

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