Dajeong Lim has completed his PhD from Seoul National University. She is a Researcher in National Institute of Animal Science (NIAS), Rural Development Administration in Korea. She has published more than 30 papers in academic journals.
Some genes are expressed exclusively or differntially from one of the two parental alleles, resulting in allelic imbalance (AI) in gene expression. Genomic imprinting is a type of AI and determined allele specific expression (ASE) depending on the parent-of-origin. High-throughput transcriptome sequencing strategy can identify ASE through the use of expressed SNPs that have the capacity to detect cis-regulatory variation and imprinted genes by aligning sequence reads to individual alleles. Here, we used RNA-Seq data along with high-resolution to analyze ASE profiles and imprinted genes based on trio data. First, whole-genome resequencing data (average 10X per sample)of one family trio (sire, dam and offspring) was generated by illumina HiSeq 2500 platform. RNA-Seq data (4Gb per tissue) was also produced from twenty three tissues such as backfat, intramuscular fat. Exome SNPs of all individuals were assigned from GATK and SnpEff tools. For each heterozygous SNP, the number of maternal and paternal reads were counted. The deviation between the read numbers was analyzed with the binomial test in R software. To test inactivation of maternal or paternal SNP, we compared parental alleles and offspring’s allele between SNPs from resequencing and RNA-Seq as an additional filtering step. Then, candidate imprinted genes were checked for expression patterns in different tissues to have the tissue-specific imprinting signatures. Finally, we confirmed the expression of SNPs and tissue-specificity within imprintig gene by experimental validation.
Dawei Xu has completed his PhD in 1999 from Karolinska Institutet. He is currently working as an Associate Professor at Department of Medicine, Karolinska Institutet. He has published more than 80 papers in peer-reviewed journals.
Myeloproliferative neoplasms (MPNs) are a group of clonal neoplastic diseases originating from the myeloid lineage of the bone marrow and include essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF). A subset of patients eventually evolve into acute myeloid leukemia. A number of genetic alterations have been identified as MPN drivers, but the exact pathogenesis of MPNs remain incompletely understood. Our recent study showed a widespread dysregulation of telomere binding proteins (TBPs) or shelterins (TRF1, TRF2, TPP1, POT1, TIN2 and RAP1) in MPNs. It is well known that the aberrant expression of shelterins causes telomere dysfunction and genomic instability, however, it is unclear whether such abnormal change has other biological activities that promote the development of MPNs. In the present study, we found that the expression of TPP1, one of key TBPs, was positively correlated with expression of splicing factors SF3A1, ZRSR2 and SRSF2, while POT1 levels were negatively correlated with U2AF1 expression, in myeloid cells derived from patients with MPN. RNA sequencing results demonstrated significant alterations in RNA splicing and editing profiles in MPN patient cells compared to normal myeloid cells from healthy adults. The induction of telomere dysfunction in the MPN-derived cell line similarly leads to dramatic alterations in RNA splicing. Collectively, the dysregulated shelterin expression directly or indirectly induces significant changes in RNA splicing, thereby contributing to the MPN pathogenesis.