PMID- 30359423
OWN - NLM
STAT- MEDLINE
DCOM- 20190404
LR  - 20231004
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 10
DP  - 2018
TI  - Defining the molecular signatures of Achilles tendinopathy and anterior cruciate 
      ligament ruptures: A whole-exome sequencing approach.
PG  - e0205860
LID - 10.1371/journal.pone.0205860 [doi]
LID - e0205860
AB  - Musculoskeletal soft tissue injuries are complex phenotypes with genetics being 
      one of many proposed risk factors. Case-control association studies using the 
      candidate gene approach have predominately been used to identify risk loci for 
      these injuries. However, the ability to identify all risk conferring variants 
      using this approach alone is unlikely. Therefore, this study aimed to further 
      define the genetic profile of these injuries using an integrated omics approach 
      involving whole exome sequencing and a customised analyses pipeline. The exomes 
      of ten exemplar asymptomatic controls and ten exemplar cases with Achilles 
      tendinopathy were individually sequenced using a platform that included the 
      coverage of the untranslated regions and miRBase miRNA genes. Approximately 200 
      000 variants were identified in the sequenced samples. Previous research was used 
      to guide a targeted analysis of the genes encoding the tenascin-C (TNC) 
      glycoprotein and the alpha1 chain of type XXVII collagen (COL27A1) located on 
      chromosome 9. Selection of variants within these genes were; however, not 
      predetermined but based on a tiered filtering strategy. Four variants in TNC 
      (rs1061494, rs1138545, rs2104772 and rs1061495) and three variants in the 
      upstream COL27A1 gene (rs2567706, rs2241671 and rs2567705) were genotyped in 
      larger Achilles tendinopathy and anterior cruciate ligament (ACL) rupture sample 
      groups. The CC genotype of TNC rs1061494 (C/T) was associated with the risk of 
      Achilles tendinopathy (p = 0.018, OR: 2.5 95% CI: 1.2-5.1). Furthermore, the AA 
      genotype of the TNC rs2104772 (A/T) variant was significantly associated with ACL 
      ruptures in the female subgroup (p = 0.035, OR: 2.3 95% CI: 1.1-5.5). An inferred 
      haplotype in the TNC gene was also associated with the risk of Achilles 
      tendinopathy. These results provide a proof of concept for the use of a 
      customised pipeline for the exploration of a larger genomic dataset. This 
      approach, using previous research to guide a targeted analysis of the data has 
      generated new genetic signatures in the biology of musculoskeletal soft tissue 
      injuries.
FAU - Gibbon, Andrea
AU  - Gibbon A
AD  - Division of Exercise Science and Sports Medicine, Department of Human Biology, 
      Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
FAU - Saunders, Colleen J
AU  - Saunders CJ
AD  - South African National Bioinformatics Institute/SA MRC Unit for Bioinformatics 
      Capacity Development, University of the Western Cape, Bellville, Cape Town, South 
      Africa.
AD  - Division of Emergency Medicine, Department of Surgery, Faculty of Health 
      Sciences, University of Cape Town, Cape Town, South Africa.
FAU - Collins, Malcolm
AU  - Collins M
AUID- ORCID: 0000-0002-2564-0480
AD  - Division of Exercise Science and Sports Medicine, Department of Human Biology, 
      Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
FAU - Gamieldien, Junaid
AU  - Gamieldien J
AD  - South African National Bioinformatics Institute/SA MRC Unit for Bioinformatics 
      Capacity Development, University of the Western Cape, Bellville, Cape Town, South 
      Africa.
FAU - September, Alison V
AU  - September AV
AUID- ORCID: 0000-0003-0950-286X
AD  - Division of Exercise Science and Sports Medicine, Department of Human Biology, 
      Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181025
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (COL27A1 protein, human)
RN  - 0 (Fibrillar Collagens)
RN  - 0 (Tenascin)
SB  - IM
MH  - Achilles Tendon/*pathology
MH  - Adult
MH  - Alleles
MH  - Anterior Cruciate Ligament/pathology
MH  - Anterior Cruciate Ligament Injuries/*genetics/pathology
MH  - Case-Control Studies
MH  - *Exome
MH  - Female
MH  - Fibrillar Collagens/blood/*genetics
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - Risk
MH  - Rupture/pathology
MH  - South Africa
MH  - Tenascin/blood/*genetics
MH  - Tendinopathy/*genetics/pathology
MH  - Exome Sequencing
PMC - PMC6201890
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/10/26 06:00
MHDA- 2019/04/05 06:00
PMCR- 2018/10/25
CRDT- 2018/10/26 06:00
PHST- 2018/07/12 00:00 [received]
PHST- 2018/10/02 00:00 [accepted]
PHST- 2018/10/26 06:00 [entrez]
PHST- 2018/10/26 06:00 [pubmed]
PHST- 2019/04/05 06:00 [medline]
PHST- 2018/10/25 00:00 [pmc-release]
AID - PONE-D-18-20679 [pii]
AID - 10.1371/journal.pone.0205860 [doi]
PST - epublish
SO  - PLoS One. 2018 Oct 25;13(10):e0205860. doi: 10.1371/journal.pone.0205860. 
      eCollection 2018.