Whole-exome sequencing analysis in twin sibling males with an anterior cruciate ligament rupture.
Familial predisposition is among the major genetic risk factors for non-contact musculoskeletal tissue injuries. Personal genome sequence shows that different polymorphism profiles may account for the number and the degree of injuries and the recovery time. Genotyping studies allow investigation into genome factors with potential impact on pathogenesis of non-contact ligament injuries. We have studied a family with twin sibling males surgically diagnosed of an anterior cruciate ligament non-contact rupture and non-affected progenitors (father and mother) were subjected to whole exome sequencing (WES) analysis. WES analysis previously carried out on 16 individuals, without ACL injury medical records, were also included in this study for single nucleotide variants (SNVs) and small insertions and deletions detection (indels), variant filtering and to prioritize variants relative to the disease. WES analysis to identify SNVs and indels was performed using open web-based bioinformatics tools. A set of 11 new variants shared by family members can be associated to ACL non-contact injury, including SerpinA11, ARSI, NOCHT4, EPB41, FDFT1, POMC, KIF26A, OLFML2B, ATG7, FAH and WDR6. All of them, except ATG7 and WDR6, have shown a damaging predictive pattern by combinatorial standard predictive scores. In combination to the identified SNVs of EPB41 and SerpinA11 genes, ACTL7A gene showed a predicted deleterious variant reinforcing the idea these variants impact on of fibroblast-like cells deformability and ECM misbalance, Differential gene expression and RNA sequencing analysis will help to understand the combined participation of these protein coding genes in ACL non-contact injuries.
Research & Development Unit, Hospital Universitario Costa del Sol, University of Malaga, Marbella, Malaga, Spain. Electronic address: encape@hcs.es.
Enrique
E
Caso
Department of Orthopaedic Surgery, FREMAP, Gijon, Asturias, Spain.
Antonio
A
Maestro
Research & Development Unit, Hospital Universitario Costa del Sol, University of Malaga, Marbella, Malaga, Spain.
Cristina C
CC
Sabiers
Department of Orthopaedic Surgery and Traumatology, Hospital Universitario Costa del Sol, University of Malaga, Marbella, Malaga, Spain.
Manuel
M
Godino
Research & Development Unit, Hospital Universitario Costa del Sol, University of Malaga, Marbella, Malaga, Spain.
Zaira
Z
Caracuel
Research & Development Unit, Hospital Universitario Costa del Sol, University of Malaga, Marbella, Malaga, Spain.
Joana
J
Pons
Research & Development Unit, Hospital Universitario Costa del Sol, University of Malaga, Marbella, Malaga, Spain.
F Jesus
FJ
Gonzalez
Supercomputing and Bioinnovating Centre (SCBI), University of Malaga, Malaga, Spain.
Rocio
R
Bautista
Supercomputing and Bioinnovating Centre (SCBI), University of Malaga, Malaga, Spain.
M Gonzalo
MG
Claros
Research & Development Unit, Hospital Universitario Costa del Sol, University of Malaga, Marbella, Malaga, Spain.
Jaime
J
Caso-Onzain
Research & Development Unit, Hospital Universitario Costa del Sol, University of Malaga, Marbella, Malaga, Spain.
Elena
E
Viejo-Allende
Academic Department of Trauma & Orthopaedic Surgery, University of Leeds, NIHR Leeds Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK.
Peter V
PV
Giannoudis
NIMgenetics, Madrid, Spain.
Sara
S
Alvarez
NIMgenetics, Madrid, Spain.
Paolo
P
Maietta
Department of Orthopaedic Surgery and Traumatology, Hospital Universitario Costa del Sol, University of Malaga, Marbella, Malaga, Spain.
Enrique
E
Guerado
D000199:Actins / Q000235:genetics; D000328:Adult; D000070598:Anterior Cruciate Ligament Injuries / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D035781:Siblings
C120133:ACTL7A protein, human; D000199:Actins
Anterior cruciate ligament injury; Computational biology; Genome; INDEL mutation; Polymorphism; Single nucleotide; Soft tissue injuries; Whole-exome sequencing; bioinformatics analysis