PMID- 36834511
OWN - NLM
STAT- MEDLINE
DCOM- 20230228
LR  - 20230301
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 4
DP  - 2023 Feb 4
TI  - Contribution of Retrotransposons to the Pathogenesis of Type 1 Diabetes and 
      Challenges in Analysis Methods.
LID - 10.3390/ijms24043104 [doi]
LID - 3104
AB  - Type 1 diabetes (T1D) is one of the most common chronic diseases of the endocrine 
      system, associated with several life-threatening comorbidities. While the 
      etiopathogenesis of T1D remains elusive, a combination of genetic susceptibility 
      and environmental factors, such as microbial infections, are thought to be 
      involved in the development of the disease. The prime model for studying the 
      genetic component of T1D predisposition encompasses polymorphisms within the HLA 
      (human leukocyte antigen) region responsible for the specificity of antigen 
      presentation to lymphocytes. Apart from polymorphisms, genomic reorganization 
      caused by repeat elements and endogenous viral elements (EVEs) might be involved 
      in T1D predisposition. Such elements are human endogenous retroviruses (HERVs) 
      and non-long terminal repeat (non-LTR) retrotransposons, including long and short 
      interspersed nuclear elements (LINEs and SINEs). In line with their parasitic 
      origin and selfish behaviour, retrotransposon-imposed gene regulation is a major 
      source of genetic variation and instability in the human genome, and may 
      represent the missing link between genetic susceptibility and environmental 
      factors long thought to contribute to T1D onset. Autoreactive immune cell 
      subtypes with differentially expressed retrotransposons can be identified with 
      single-cell transcriptomics, and personalized assembled genomes can be 
      constructed, which can then serve as a reference for predicting retrotransposon 
      integration/restriction sites. Here we review what is known to date about 
      retrotransposons, we discuss the involvement of viruses and retrotransposons in 
      T1D predisposition, and finally we consider challenges in retrotransposons 
      analysis methods.
FAU - Stangar, Anja
AU  - Stangar A
AD  - Division of Pediatrics, University Medical Centre Ljubljana, 1000 Ljubljana, 
      Slovenia.
AD  - Department of Pediatrics, Faculty of Medicine, University of Ljubljana, 1000 
      Ljubljana, Slovenia.
FAU - Kovac, Jernej
AU  - Kovac J
AUID- ORCID: 0000-0003-3080-4838
AD  - Division of Pediatrics, University Medical Centre Ljubljana, 1000 Ljubljana, 
      Slovenia.
AD  - Department of Pediatrics, Faculty of Medicine, University of Ljubljana, 1000 
      Ljubljana, Slovenia.
FAU - Sket, Robert
AU  - Sket R
AD  - Division of Pediatrics, University Medical Centre Ljubljana, 1000 Ljubljana, 
      Slovenia.
FAU - Tesovnik, Tine
AU  - Tesovnik T
AD  - Division of Pediatrics, University Medical Centre Ljubljana, 1000 Ljubljana, 
      Slovenia.
FAU - Zajec, Ana
AU  - Zajec A
AD  - Division of Pediatrics, University Medical Centre Ljubljana, 1000 Ljubljana, 
      Slovenia.
AD  - Department of Pediatrics, Faculty of Medicine, University of Ljubljana, 1000 
      Ljubljana, Slovenia.
FAU - Cugalj Kern, Barbara
AU  - Cugalj Kern B
AD  - Division of Pediatrics, University Medical Centre Ljubljana, 1000 Ljubljana, 
      Slovenia.
AD  - Department of Pediatrics, Faculty of Medicine, University of Ljubljana, 1000 
      Ljubljana, Slovenia.
FAU - Jenko Bizjan, Barbara
AU  - Jenko Bizjan B
AD  - Division of Pediatrics, University Medical Centre Ljubljana, 1000 Ljubljana, 
      Slovenia.
AD  - Department of Pediatrics, Faculty of Medicine, University of Ljubljana, 1000 
      Ljubljana, Slovenia.
FAU - Battelino, Tadej
AU  - Battelino T
AUID- ORCID: 0000-0002-0273-4732
AD  - Division of Pediatrics, University Medical Centre Ljubljana, 1000 Ljubljana, 
      Slovenia.
AD  - Department of Pediatrics, Faculty of Medicine, University of Ljubljana, 1000 
      Ljubljana, Slovenia.
FAU - Dovc, Klemen
AU  - Dovc K
AUID- ORCID: 0000-0001-9201-2145
AD  - Division of Pediatrics, University Medical Centre Ljubljana, 1000 Ljubljana, 
      Slovenia.
AD  - Department of Pediatrics, Faculty of Medicine, University of Ljubljana, 1000 
      Ljubljana, Slovenia.
LA  - eng
GR  - P3-0343/Slovenian Research Agency/
PT  - Journal Article
PT  - Review
DEP - 20230204
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Retroelements)
SB  - IM
MH  - Humans
MH  - Retroelements
MH  - *Diabetes Mellitus, Type 1/genetics
MH  - Genetic Predisposition to Disease
MH  - *Endogenous Retroviruses
MH  - Short Interspersed Nucleotide Elements
PMC - PMC9966460
OTO - NOTNLM
OT  - retrotransposons
OT  - retrotransposons analysis methods
OT  - single-cell sequencing
OT  - type 1 diabetes
OT  - type 1 diabetes pathogenesis
OT  - viral infections
COIS- The authors declare no conflict of interest.
EDAT- 2023/02/26 06:00
MHDA- 2023/03/03 06:00
PMCR- 2023/02/04
CRDT- 2023/02/25 02:37
PHST- 2022/11/30 00:00 [received]
PHST- 2023/01/30 00:00 [revised]
PHST- 2023/02/02 00:00 [accepted]
PHST- 2023/02/25 02:37 [entrez]
PHST- 2023/02/26 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2023/02/04 00:00 [pmc-release]
AID - ijms24043104 [pii]
AID - ijms-24-03104 [pii]
AID - 10.3390/ijms24043104 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Feb 4;24(4):3104. doi: 10.3390/ijms24043104.