High-Throughput Nucleotide Sequencing

Publication Title: 
BMC genomics

BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity. RESULTS: We employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity.

Author(s): 
Gombar, Saurabh
Jung, Hwa Jin
Dong, Feng
Calder, Brent
Atzmon, Gil
Barzilai, Nir
Tian, Xiao-Li
Pothof, Joris
Hoeijmakers, Jan H. J.
Campisi, Judith
Vijg, Jan
Suh, Yousin
Publication Title: 
BMC genomics

BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity. RESULTS: We employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity.

Author(s): 
Gombar, Saurabh
Jung, Hwa Jin
Dong, Feng
Calder, Brent
Atzmon, Gil
Barzilai, Nir
Tian, Xiao-Li
Pothof, Joris
Hoeijmakers, Jan H. J.
Campisi, Judith
Vijg, Jan
Suh, Yousin
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

The decrease of TCR diversity with aging has never been studied by direct methods. In this study, we combined high-throughput Illumina sequencing with unique cDNA molecular identifier technology to achieve deep and precisely normalized profiling of TCR ? repertoires in 39 healthy donors aged 6-90 y. We demonstrate that TCR ? diversity per 10(6) T cells decreases roughly linearly with age, with significant reduction already apparent by age 40. The percentage of naive T cells showed a strong correlation with measured TCR diversity and decreased linearly up to age 70.

Author(s): 
Britanova, Olga V.
Putintseva, Ekaterina V.
Shugay, Mikhail
Merzlyak, Ekaterina M.
Turchaninova, Maria A.
Staroverov, Dmitriy B.
Bolotin, Dmitriy A.
Lukyanov, Sergey
Bogdanova, Ekaterina A.
Mamedov, Ilgar Z.
Lebedev, Yuriy B.
Chudakov, Dmitriy M.
Publication Title: 
Methods (San Diego, Calif.)

DNA methylation plays a vital role in normal cellular function, with aberrant methylation signatures being implicated in a growing number of human pathologies and complex human traits. Methods based on the modification of genomic DNA with sodium bisulfite are considered the 'gold-standard' for DNA methylation profiling on genomic DNA; however they require large amounts of DNA and may be prohibitively expensive when used on the large sample sizes necessary to detect small effects.

Author(s): 
Docherty, Sophia J.
Davis, Oliver S. P.
Haworth, Claire M. A.
Plomin, Robert
Mill, Jonathan
Publication Title: 
Advances in Experimental Medicine and Biology

Nowadays, epigenetics is one of the fastest growing research areas in biomedicine. Studies have demonstrated that changes in the epigenome are not only common in cancer, but are also involved in the pathogenesis of noncancerous diseases like immunological, cardiovascular, developmental and neurological/psychiatric disorders. At the same time, during the last years, a technological revolution has taken place in the field of epigenomics, which is defined as the study of epigenetic changes throughout the whole genome.

Author(s): 
MartÌn-Subero, JosÈ Ignacio
Esteller, Manel
Publication Title: 
The International Journal of Neuropsychopharmacology

This review, the first of an occasional series, tries to make sense of the concepts and uses of deep sequencing of polynucleic acids (DNA and RNA).

Author(s): 
Goldman, D.
Domschke, K.
Publication Title: 
Biological Psychiatry

Virtually all psychiatric traits are genetically complex. This article discusses the genetics of complex traits in psychiatry. The complexity is accounted for by numerous factors, including multiple risk alleles, epistasis, and epigenetic effects such as methylation. Risk alleles can individually be common or rare, and can include, for example, single nucleotide polymorphisms and copy number variants that are transmitted or are new mutations, and other kinds of variation.

Author(s): 
Gelernter, Joel
Publication Title: 
Human Molecular Genetics

To investigate epigenetic contributions to Huntington's disease (HD) pathogenesis, we carried out genome-wide mapping of the transcriptional mark, trimethyl-histone H3-lysine 4 (H3K4me3) in neuronal nuclei extracted from prefrontal cortex of HD cases and controls using chromatin immunoprecipitation followed by deep-sequencing.

Author(s): 
Bai, Guang
Cheung, Iris
Shulha, Hennady P.
Coelho, Joana E.
Li, Ping
Dong, Xianjun
Jakovcevski, Mira
Wang, Yumei
Grigorenko, Anastasia
Jiang, Yan
Hoss, Andrew
Patel, Krupal
Zheng, Ming
Rogaev, Evgeny
Myers, Richard H.
Weng, Zhiping
Akbarian, Schahram
Chen, Jiang-Fan
Publication Title: 
BMC medical genomics

BACKGROUND: Psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP) are projected to lead the global disease burden within the next decade. Several lines of evidence suggest that epigenetic- or genetic-mediated dysfunction is frequently present in these disorders. To date, the inheritance patterns have been complicated by the problem of integrating epigenomic and transcriptomic factors that have yet to be elucidated. Therefore, there is a need to build a comprehensive database for storing epigenomic and transcriptomic data relating to psychiatric disorders.

Author(s): 
Zhao, Zheng
Li, Yongsheng
Chen, Hong
Lu, Jianping
Thompson, Peter M.
Chen, Juan
Wang, Zishan
Xu, Juan
Xu, Chun
Li, Xia
Publication Title: 
Blood

The pathogenesis of mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is unknown. Although genetic alterations have been identified, none are considered consistently causative in MF. To identify potential drivers of MF, we performed whole-genome sequencing of MF tumors and matched normal skin. Targeted ultra-deep sequencing of MF samples and exome sequencing of CTCL cell lines were also performed. Multiple mutations were identified that affected the same pathways, including epigenetic, cell-fate regulation, and cytokine signaling, in MF tumors and CTCL cell lines.

Author(s): 
McGirt, Laura Y.
Jia, Peilin
Baerenwald, Devin A.
Duszynski, Robert J.
Dahlman, Kimberly B.
Zic, John A.
Zwerner, Jeffrey P.
Hucks, Donald
Dave, Utpal
Zhao, Zhongming
Eischen, Christine M.

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