Dataset Information

Expansion of stochastic expression repertoire by tandem duplication in mouse Protocadherin-? cluster.

ABSTRACT: Tandem duplications are concentrated within the Pcdh cluster throughout vertebrate evolution and as copy number variations (CNVs) in human populations, but the effects of tandem duplication in the Pcdh cluster remain elusive. To investigate the effects of tandem duplication in the Pcdh cluster, here we generated and analyzed a new line of the Pcdh cluster mutant mice. In the mutant allele, a 218-kb region containing the Pcdh-?2 to Pcdh-?c2 variable exons with their promoters was duplicated and the individual duplicated Pcdh isoforms can be disctinguished. The individual duplicated Pcdh-? isoforms showed diverse expression level with stochastic expression manner, even though those have an identical promoter sequence. Interestingly, the 5'-located duplicated Pcdh-?c2, which is constitutively expressed in the wild-type brain, shifted to stochastic expression accompanied by increased DNA methylation. These results demonstrate that tandem duplication in the Pcdh cluster expands the stochastic expression repertoire irrespective of sequence divergence.

SUBMITTER: Kaneko R

PROVIDER: S-EPMC4151104 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Expansion of stochastic expression repertoire by tandem duplication in mouse Protocadherin-α cluster.

Kaneko Ryosuke R Abe Manabu M Hirabayashi Takahiro T Uchimura Arikuni A Sakimura Kenji K Yanagawa Yuchio Y Yagi Takeshi T

Scientific reports 20140902

Tandem duplications are concentrated within the Pcdh cluster throughout vertebrate evolution and as copy number variations (CNVs) in human populations, but the effects of tandem duplication in the Pcdh cluster remain elusive. To investigate the effects of tandem duplication in the Pcdh cluster, here we generated and analyzed a new line of the Pcdh cluster mutant mice. In the mutant allele, a 218-kb region containing the Pcdh-α2 to Pcdh-αc2 variable exons with their promoters was duplicated and t ...[more]

PMID: 25179445

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Project description:BackgroundTandem repeat sequences are common in the genomes of many organisms and are known to cause important phenomena such as gene silencing and rapid morphological changes. Due to the presence of multiple copies of the same pattern in tandem repeats and their high variability, they contain a wealth of information about the mutations that have led to their formation. The ability to extract this information can enhance our understanding of evolutionary mechanisms.ResultsWe present a stochastic model for the formation of tandem repeats via tandem duplication and substitution mutations. Based on the analysis of this model, we develop a method for estimating the relative mutation rates of duplications and substitutions, as well as the total number of mutations, in the history of a tandem repeat sequence. We validate our estimation method via Monte Carlo simulation and show that it outperforms the state-of-the-art algorithm for discovering the duplication history. We also apply our method to tandem repeat sequences in the human genome, where it demonstrates the different behaviors of micro- and mini-satellites and can be used to compare mutation rates across chromosomes. It is observed that chromosomes that exhibit the highest mutation activity in tandem repeat regions are the same as those thought to have the highest overall mutation rates. However, unlike previous works that rely on comparing human and chimpanzee genomes to measure mutation rates, the proposed method allows us to find chromosomes with the highest mutation activity based on a single genome, in essence by comparing (approximate) copies of the pattern in tandem repeats.ConclusionThe prevalence of tandem repeats in most organisms and the efficiency of the proposed method enable studying various aspects of the formation of tandem repeats and the surrounding sequences in a wide range of settings.AvailabilityThe implementation of the estimation method is available at http://ips.lab.virginia.edu/smtr .

Dataset Information

Expansion of stochastic expression repertoire by tandem duplication in mouse Protocadherin-? cluster.

Publications

Expansion of stochastic expression repertoire by tandem duplication in mouse Protocadherin-α cluster.

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