PMID- 38031415
OWN - NLM
STAT- MEDLINE
DCOM- 20240123
LR  - 20240310
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 248
IP  - 23
DP  - 2023 Dec
TI  - Regulation of expression quantitative trait loci by SVA retrotransposons within 
      the major histocompatibility complex.
PG  - 2304-2318
LID - 10.1177/15353702231209411 [doi]
AB  - Genomic and transcriptomic studies of expression quantitative trait loci (eQTL) 
      revealed that SINE-VNTR-Alu (SVA) retrotransposon insertion polymorphisms (RIPs) 
      within human genomes markedly affect the co-expression of many coding and 
      noncoding genes by coordinated regulatory processes. This study examined the 
      polymorphic SVA modulation of gene co-expression within the major 
      histocompatibility complex (MHC) genomic region where more than 160 coding genes 
      are involved in innate and adaptive immunity. We characterized the modulation of 
      SVA RIPs utilizing the genomic and transcriptomic sequencing data obtained from 
      whole blood of 1266 individuals in the Parkinson's Progression Markers Initiative 
      (PPMI) cohort that included an analysis of human leukocyte antigen (HLA)-A 
      regulation in a subpopulation of the cohort. The regulatory properties of eight 
      SVAs located within the class I and class II MHC regions were associated with 
      differential co-expression of 71 different genes within and 75 genes outside the 
      MHC region. Some of the same genes were affected by two or more different SVA. 
      Five SVA are annotated in the human genomic reference sequence GRCh38.p14/hg38, 
      whereas the other three were novel insertions within individuals. We also 
      examined and found distinct structural effects (long and short variants and the 
      CT internal variants) for one of the SVA (R_SVA_24) insertions on the 
      differential expression of the HLA-A gene within a subpopulation (550 
      individuals) of the PPMI cohort. This is the first time that many HLA and non-HLA 
      genes (multilocus expression units) and splicing mechanisms have been shown to be 
      regulated by eight structurally polymorphic SVA within the MHC genomic region by 
      applying precise statistical analysis of RNA data derived from the blood samples 
      of a human cohort population. This study shows that SVA within the MHC region are 
      important regulators or rheostats of gene co-expression that might have potential 
      roles in diversity, health, and disease.
FAU - Kulski, Jerzy K
AU  - Kulski JK
AD  - Department of Molecular Life Sciences, School of Medicine, Tokai University, 
      Isehara, Kanagawa 259-1193, Japan.
AD  - Health and Medical Science. Division of Immunology and Microbiology, School of 
      Biomedical Sciences, The University of Western Australia, Nedlands, WA 6009, 
      Australia.
FAU - Pfaff, Abigail L
AU  - Pfaff AL
AD  - Perron Institute for Neurological and Translational Science, Perth, WA 6009, 
      Australia.
AD  - Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, 
      Perth, WA 6150, Australia.
FAU - Marney, Luke D
AU  - Marney LD
AD  - Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and 
      Integrative Biology, University of Liverpool, Liverpool, L69 3BX, UK.
FAU - Frohlich, Alexander
AU  - Frohlich A
AUID- ORCID: 0000-0001-9083-7485
AD  - Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and 
      Integrative Biology, University of Liverpool, Liverpool, L69 3BX, UK.
FAU - Bubb, Vivien J
AU  - Bubb VJ
AUID- ORCID: 0000-0003-2763-7004
AD  - Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and 
      Integrative Biology, University of Liverpool, Liverpool, L69 3BX, UK.
FAU - Quinn, John P
AU  - Quinn JP
AD  - Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and 
      Integrative Biology, University of Liverpool, Liverpool, L69 3BX, UK.
FAU - Koks, Sulev
AU  - Koks S
AUID- ORCID: 0000-0001-6087-6643
AD  - Perron Institute for Neurological and Translational Science, Perth, WA 6009, 
      Australia.
AD  - Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, 
      Perth, WA 6150, Australia.
LA  - eng
PT  - Journal Article
DEP - 20231130
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Retroelements)
SB  - IM
MH  - Humans
MH  - *Retroelements/genetics
MH  - *Quantitative Trait Loci/genetics
MH  - Polymorphism, Genetic
MH  - Major Histocompatibility Complex/genetics
PMC - PMC10903234
OTO - NOTNLM
OT  - HLA
OT  - MHC
OT  - SVA
OT  - eQTL
OT  - enhancers
OT  - multilocus expression units
COIS- Declaration of conflicting interestsThe author(s) declared no potential conflicts 
      of interest with respect to the research, authorship, and/or publication of this 
      article.
EDAT- 2023/11/30 06:43
MHDA- 2024/01/23 06:43
PMCR- 2023/11/30
CRDT- 2023/11/30 03:38
PHST- 2024/01/23 06:43 [medline]
PHST- 2023/11/30 06:43 [pubmed]
PHST- 2023/11/30 03:38 [entrez]
PHST- 2023/11/30 00:00 [pmc-release]
AID - 10.1177_15353702231209411 [pii]
AID - 10.1177/15353702231209411 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2023 Dec;248(23):2304-2318. doi: 
      10.1177/15353702231209411. Epub 2023 Nov 30.