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Gao W.,Sun Yat Sen University | Peng Y.,Sun Yat Sen University | Liang G.,Sun Yat Sen University | Liang A.,Sun Yat Sen University | And 6 more authors.
PLoS ONE | Year: 2013

Background: Adolescent idiopathic scoliosis (AIS) is one of the most common spinal deformities found in adolescent populations. Recently, a genome-wide association study (GWAS) in a Japanese population indicated that three single nucleotide polymorphisms (SNPs), rs11190870, rs625039 and rs11598564, all located near the LBX1 gene, may be associated with AIS susceptibility [1]. This study suggests a novel AIS predisposition candidate gene and supports the hypothesis that somatosensory functional disorders could contribute to the pathogenesis of AIS. These findings warrant replication in other populations. Methodology/Principal Findings: First, we conducted a case-control study consisting of 953 Chinese Han individuals from southern China (513 patients and 440 healthy controls), and the three SNPs were all found to be associated with AIS predisposition. The ORs were observed as 1.49 (95% CI 1.23-1.80, P = 5.09E-5), 1.70 (95% CI 1.42-2.04, P = 1.17E-8) and 1.52 (95% CI 1.27-1.83, P = 5.54E-6) for rs625039, rs11190870 and rs11598564, respectively. Second, a case-only study including a subgroup of AIS patients (N = 234) was performed to determine the effects of these variants on the severity of the condition. However, we did not find any association between these variants and the severity of curvature. Conclusion: This study shows that the genetic variants near the LBX1 gene are associated with AIS susceptibility in Chinese Han population. It successfully replicates the results of the GWAS, which was performed in a Japanese population. © 2013 Gao et al.

Tansey K.E.,Shepherd Center | Tansey K.E.,Emory University | Tansey K.E.,Atlanta Veterans Administration Medical Center | Seifert J.L.,University of Texas at Arlington | And 4 more authors.
Annals of Biomedical Engineering | Year: 2011

Peripheral nerve damage is routinely repaired by autogenic nerve grafting, often leading to less than optimal functional recovery at the expense of healthy donor nerves. Alternative repair strategies use tubular scaffolds to guide the regeneration of damaged nerves, but despite the progress made on improved structural materials for the nerve tubes, functional recovery remains incomplete. We developed a biosynthetic nerve implant (BNI) consisting of a hydrogel-based transparent multichannel scaffold with luminar collagen matrix as a 3-D substrate for nerve repair. Using a rat sciatic nerve injury model we showed axonal regeneration through the BNI to be histologically comparable to the autologous nerve repair. At 10 weeks post-injury, nerve defects repaired with collagen-filled, single lumen tubes formed single nerve cables, while animals that received the multi-luminal BNIs showed multiple nerve cables and the formation of a perineurial-like layer within the available microchannels. Total numbers of myelinated and unmyelinated axons in the BNI were increased 3-fold and 30%, respectively, compared to collagen tubes. The recovery of reflexive movement confirmed the functional regeneration of both motor and sensory neurons. This study supports the use of multi-luminal BNIs as a viable alternative to autografts in the repair of nerve gap injuries. © 2011 Biomedical Engineering Society.

Londono D.,Rutgers University | Kou I.,RIKEN | Johnson T.A.,RIKEN | Sharma S.,Seay Center for Musculoskeletal Research | And 28 more authors.
Journal of Medical Genetics | Year: 2014

Background: Adolescent idiopathic scoliosis (AIS) is a common rotational deformity of the spine that presents in children worldwide, yet its etiology is poorly understood. Recent genome-wide association studies (GWAS) have identified a few candidate risk loci. One locus near the chromosome 10q24.31 LBX1 gene (OMIM #604255) was originally identified by a GWAS of Japanese subjects and replicated in additional Asian populations. To extend this result, and to create larger AIS cohorts for the purpose of large-scale meta-analyses in multiple ethnicities, we formed a collaborative group called the International Consortium for Scoliosis Genetics (ICSG). Methods: Here, we report the first ICSG study, a metaanalysis of the LBX1 locus in six Asian and three non- Asian cohorts. Results: We find significant evidence for association of this locus with AIS susceptibility in all nine cohorts. Results for seven cohorts containing both genders yielded P=1.22-10-43 for rs11190870, and P=2.94-10-48 for females in all nine cohorts. Comparing the regional haplotype structures for three populations, we refined the boundaries of association to a ̃25 kb block encompassing the LBX1 gene. The LBX1 protein, a homeobox transcription factor that is orthologous to the Drosophila ladybird late gene, is involved in proper migration of muscle precursor cells, specification of cardiac neural crest cells, and neuronal determination in developing neural tubes. Conclusions: Our results firmly establish the LBX1 region as the first major susceptibility locus for AIS in Asian and non-Hispanic white groups, and provide a platform for larger studies in additional ancestral groups.

Londono D.,Rutgers University | Chen K.-M.,Rutgers University | Musolf A.,Rutgers University | Wang R.,State University of New York at Stony Brook | And 12 more authors.
Statistical Applications in Genetics and Molecular Biology | Year: 2013

Knowledge of genes influencing longitudinal patterns may offer information about predicting disease progression. We developed a systematic procedure for testing association between SNP genotypes and longitudinal phenotypes. We evaluated false positive rates and statistical power to localize genes for disease progression. We used genome-wide SNP data from the Framingham Heart Study. With longitudinal data from two real studies unrelated to Framingham, we estimated three trajectory curves from each study. We performed simulations by randomly selecting 500 individuals. In each simulation replicate, we assigned each individual to one of the three trajectory groups based on the underlying hypothesis (null or alternative), and generated corresponding longitudinal data. Individual Bayesian posterior probabilities (BPPs) for belonging to a specific trajectory curve were estimated. These BPPs were treated as a quantitative trait and tested (using the Wald test) for genome-wide association. Empirical false positive rates and power were calculated. Our method maintained the expected false positive rate for all simulation models. Also, our method achieved high empirical power for most simulations. Our work presents a method for disease progression gene mapping. This method is potentially clinically significant as it may allow doctors to predict disease progression based on genotype and determine treatment accordingly.

Griffin H.,McKesson | Toombs J.P.,Iowa State University | Bronson D.G.,Seay Center for Musculoskeletal Research | Ross J.D.,Seay Center for Musculoskeletal Research | Browne R.H.,Seay Center for Musculoskeletal Research
Veterinary and Comparative Orthopaedics and Traumatology | Year: 2011

An in vitro mechanical study was performed to compare the stiffness, maximum load, and cyclic load-to-failure of a new external fixation half-pin design utilizing a tapered thread-run-out (TRO) feature with currently available positive profile thread (PP) halfpins. Five different sizes of each of the two pin types were evaluated. Under static loading, TRO pins were significantly stiffer and had a higher maximum load compared to the similar sized PP pins (p <0.0001 for all comparisons). In cyclic fatigue testing, TRO pins lasted 2.3- to 4.9-fold more cycles than PP pins of similar size (p <0.0001 for all comparisons). The increased pin stiffness and improved cyclic lifespan provided by TRO pins may be especially valuable in the stabilization of biologically and mechanically challenging fracture cases where healing is prolonged. © Schattauer 2011.

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