Quantitative Analysis of Single Nucleotide Polymorphisms within Copy Number Variation

Background Single nucleotide polymorphisms (SNPs) have been used extensively in genetics and epidemiology studies. Traditionally, SNPs that did not pass the Hardy-Weinberg equilibrium (HWE) test were excluded from these analyses. Many investigators have addressed possible causes for departure from HWE, including genotyping errors, population admixture and segmental duplication. Recent large-scale surveys have revealed abundant structural variations in the human genome, including copy number variations (CNVs). This suggests that a significant number of SNPs must be within these regions, which may cause deviation from HWE. Results We performed a Bayesian analysis on the potential effect of copy number variation, segmental duplication and genotyping errors on the behavior of SNPs. Our results suggest that copy number variation is a major factor of HWE violation for SNPs with a small minor allele frequency, when the sample size is large and the genotyping error rate is 0~1%. Conclusions Our study provides the posterior probability that a SNP falls in a CNV or a segmental duplication, given the observed allele frequency of the SNP, sample size and the significance level of HWE testing.

On the Size Distribution of Autonomous Systems

This paper explores reasons for the high degree of variability in the sizes of ASes that have recently been observed, and the processes by which this variable distribution develops. AS size distribution is important for a number of reasons. First, when modeling network topologies, an AS size distribution assists in labeling routers with an associated AS. Second, AS size has been found to be positively correlated with the degree of the AS (number of peering links), so understanding the distribution of AS sizes has implications for AS connectivity properties. Our model accounts for AS births, growth, and mergers. We analyze two models: one incorporates only the growth of hosts and ASes, and a second extends that model to include mergers of ASes. We show analytically that, given reasonable assumptions about the nature of mergers, the resulting size distribution exhibits a power law tail with the exponent independent of the details of the merging process. We estimate parameters of the models from measurements obtained from Internet registries and from BGP tables. We then compare the models solutions to empirical AS size distribution taken from Mercator and Skitter datasets, and find that the simple growth-based model yields general agreement with empirical data. Our analysis of the model in which mergers occur in a manner independent of the size of the merging ASes suggests that more detailed analysis of merger processes is needed.