Genome Sequencing of Chromosome 1 Substitution Lines Derived from Chinese Wild Mice Revealed a Unique Resource for Genetic Studies of Complex Traits

et al. 2020

Sci Rep

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MicroRNAs are widely referred to as gene expression regulators for different diseases. The integration between single nucleotide polymorphisms (Snps) and miRnAs has been associated with both human and animal diseases. In order to gain new insights on the effects of SNPs on miRNA and their related sequences, we steadily characterized a whole mouse genome miRNA related SNPs, analyzed their effects on the miRNA structural stability and target alteration. In this study, we collected 73643859 SNPs across the mouse genome, analyzed 1187 pre-miRNAs and 2027 mature miRNAs. Upon mapping the SNPs, 1700 of them were identified in 702 pre-miRNAs and 609 SNPs in mature miRNAs. We also discovered that Snp densities of the pre-miRnA and mature miRnAs are lower than the adjacent flanking regions. Also the flanking regions far away from miRNAs appeared to have higher SNP density. In addition, we also found that transitions were more frequent than transversions in miRNAs. Notably, 841 SNPs could change their corresponding miRNA's secondary structure from stable to unstable. We also performed target gain and loss analysis of 163 miRNAs and our results showed that few miRNAs remained unchanged and many miRNAs from wild mice gained target site. These results outline the first case of SNP variations in the mouse whole genome scale. Those miRNAs with changes in structure or target could be of interest for further studies.

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Genome-Wide Analysis of MicroRNA-related Single Nucleotide Polymorphisms (SNPs) in Mouse Genome

Omariba

et al. 2020

Sci Rep

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“…We randomly chose 65 offspring mice of heterozygous mice to genotype for rs68317494 (T/C), rs71342945 (G/T), rs74107267 (A/G), and rs77085538 (G/A). These four SNPs were derived from genomic island on chromosome 8 of Chr1 daxin mice which was a chromosome 1 substitution strain constructed by our lab . Genome sequence was available on NCBI Sequence Read Archive database (SRX1725678).…”

Section: Methodsmentioning

confidence: 99%

A multiplex SNP genotyping by allele‐specificspecific PCR based on stem‐loop and universal fluorescent primers of Chr1^daxin mice

Chen

et al. 2019

Electrophoresis

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Single nucleotide polymorphisms (SNPs) are one of the most common markers in mammals. Rapid, accurate, and multiplex typing of SNPs is critical for subsequent biological and genetic research. In this study, we have developed a novel method for multiplex genotyping SNPs in mice. The method involves allele‐specific PCR amplification of genomic DNA with two stem‐loop primers accompanied by two different universal fluorescent primers. Blue and green fluorescent signals were conveniently detected on a DNA sequencer. We verified four SNPs of 65 mice based on the novel method, and it is well suited for multiplex genotyping as it requires only one reaction per sample in a single tube with multiplex PCR. The use of universal fluorescent primers greatly reduces the cost of designing different fluorescent probes for each SNP. Therefore, this method can be applied to many biological and genetic studies, such as multiple candidate gene testing, genome‐wide association study, pharmacogenetics, and medical diagnostics.

“…Genetic variants between C1SLs and B6 were identified with whole genome sequencing as previously described (Xu et al, 2016). Variant annotation was performed using Variant Effect Predictor (Mclaren et al, 2016).…”

Section: Identification Of Genetic Variants For the Candidate Genesmentioning

confidence: 99%

“…Previously, we proposed a novel strategy of developing a Chr 1-specific CSS substitution line (C1SL) to dissect the complex traits. With this strategy, Chr 1 of the recipient strain C57BL/6J (B6) was replaced by different wild mice individually (Xiao et al, 2010;Xu et al, 2016). Compared to CSSs, C1SLs are suitable for both association studies and systems genetics analysis.…”

Section: Introductionmentioning

confidence: 99%

Candidate Regulators of Dyslipidemia in Chromosome 1 Substitution Lines Using Liver Co-Expression Profiling Analysis

et al. 2020

Front. Genet.

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Dyslipidemia is a major risk factor for cardiovascular disease. Although many genetic factors have been unveiled, a large fraction of the phenotypic variance still needs further investigation. Chromosome 1 (Chr 1) harbors multiple gene loci that regulate blood lipid levels, and identifying functional genes in these loci has proved challenging. We constructed a mouse population, Chr 1 substitution lines (C1SLs), where only Chr 1 differs from the recipient strain C57BL/6J (B6), while the remaining chromosomes are unchanged. Therefore, any phenotypic variance between C1SLs and B6 can be attributed to the differences in Chr 1. In this study, we assayed plasma lipid and glucose levels in 13 C1SLs and their recipient strain B6. Through weighted gene co-expression network analysis of liver transcriptome and "guilty-by-association" study, eight associated modules of plasma lipid and glucose were identified. Further joint analysis of human genome wide association studies revealed 48 candidate genes. In addition, 38 genes located on Chr 1 were also uncovered, and 13 of which have been functionally validated in mouse models. These results suggest that C1SLs are ideal mouse models to identify functional genes on Chr 1 associated with complex traits, like dyslipidemia, by using gene co-expression network analysis.