A growing body of evidence exists supporting the role that genetic variation plays in athletic performance and injury. This study sought to identify genetic variants associated with performance and lower limb musculoskeletal injury in a high-level athletic cohort. A total of 126 Estonian National Team members (Olympic athletes and participants of International Championships) (104 males, 82.5%) underwent a genome-wide association analysis between 2017 and 2018, to identify single-nucleotide polymorphisms (SNPs) associated with performance and/or injury. The athletic cohort was stratified within each sport based on performance and whether they were a medalist (n = 29) or not (n = 97), whether they sustained an injury (n = 47) or not (n = 79), and the type of injury (patella tendinopathy n = 22, Achilles tendinopathy n = 17, hamstring injury n = 3, anterior cruciate ligament rupture n = 6). Three SNPs demonstrated strong genome-wide association with athletic performance (podium/medalist versus not), including DSG1 (rs10502567, OR 14.3) and DSG4 (rs73410248, OR 17.4), while 76 SNPs demonstrated suggestive significance. Overall, 37 SNPs gave genome-wide suggestive association with any type of injury, including PAPPA2 (rs11580456, OR 13.8) and MAS1 (rs220735, rs170219, OR 3.1) which demonstrated positive signal with multiple SNPs. Several genes demonstrated positive association for the specific injury types, including COL22A1 (rs3924862) and PLXNA2 (rs11799530), as well as PAPPA2 (rs11580456), DOK5 (rs73142922), GNG12 (rs28435277), and DAP (rs267959, rs2930047, rs1080440, rs267939). The current study identified genetic variants associated with high-level athletic performance and musculoskeletal injury. Further work is required to permit integration of this and future knowledge into individualized training practices, as well as injury mitigation and rehabilitation programs.

The Mediodorsal (MD) thalamus that represents a fundamental subcortical relay has been underrepresented in the studies focusing on the molecular changes in the brains of subjects with alcohol use disorder (AUD). In the current study, MD thalamic regions from AUD subjects and controls were analyzed with Affymetrix Clariom S human microarray. Long-term alcohol use induced a significant (FDR ≤ 0.05) upregulation of 2802 transcripts and downregulation of 1893 genes in the MD thalamus of AUD subjects. A significant upregulation of GRIN1 (glutamate receptor NMDA type 1) and FTO (alpha-ketoglutarate dependent dioxygenase) was confirmed in western blot analysis. Immunohistochemical staining revealed similar heterogenous distribution of GRIN1 in the thalamic nuclei of both AUD and control subjects. The most prevalent functional categories of upregulated genes were related to glutamatergic and GABAergic neurotransmission, cellular metabolism, and neurodevelopment. The prevalent gene cluster among down-regulated genes was immune system mediators. Forty-two differentially expressed genes, including FTO, ADH1B, DRD2, CADM2, TCF4, GCKR, DPP6, MAPT and CHRH1, have been shown to have strong associations (FDR p < 10−8) with AUD or/and alcohol use phenotypes in recent GWA studies. Despite a small number of subjects, we were able to detect robust molecular changes in the mediodorsal thalamus caused by alcohol emphasizing the importance of deeper brain structures such as diencephalon, in the development of AUD-related dysregulation of neurocircuitry.

Injuries in sports are the most common causes where athletes are forced to change their training plans temporarily, or more, to interrupt trainings and competitions for a certain time. Several genome-wide association studies have concluded that variations in DNA sequence interacting with non-genetic risk factors may play an important role in the etiology of injuries, including overuse injuries. PURPOSE: To identify potential loci (chromosomal regions) that are associated with the tendinopathy of Achilles and patellar tendons. METHODS: Study group consisted of 121 elite athletes (21 females and 100 males), current and former Estonian national team members, in the age range 27.5±5.1 years, involved in 16 different sports. The case group (n=42) consisted of athletes with patellar and Achilles tendinopathies, and the control group (n=79) was formed by athletes without these injuries. The electronic health record system was used to find clinical diagnoses of the respective injuries of the athletes participating in this study. Peripheral venous blood samples for DNA extraction and genotyping for known SNPs (SNP arrays) from all study subjects were collected. The comparison of allelic frequencies of these SNPs was made between cases and controls. For statistical analysis, we used the software PLINK. To estimate the magnitude of the effectiveness OR was used to estimate the magnitude of the effectiveness, and p-values for the significance of ORs were calculated using the χ2 - test. The p value of 10-8 was set as a threshold for genome-wide statistical significance. To display significant SNPs, the Manhattan plot was used. RESULTS: Association analysis revealed 2 genes that could be important as risk factors for investigated injuries, the PAPPA2 (chr 1: rs1158045, OR 13.8, p= 1.64·10-5) and the GNG12 (chr 1: rs28435277 OR 13.8, p=1.64·10- 5) with the p-value remaining at the level of "suggestive significance" (p=5·10-5). CONCLUSIONS: Our study results identified suggestive significance in allelic differences of PAPPA2 and GNG12 between case and control groups. It is important to continue with further research of genetic risk profile to understand the biological processes associated with injury risk.

Background: Total joint arthroplasty (TJA) is one of the most frequent surgical procedures performed in modern hospitals, and aseptic loosening is the most common indication for revision surgeries. We conducted a systemic exploration of potential genetic determinants for early aseptic loosening. Methods: Data from 423 patients undergoing TJA were collected and analyzed. Three analytical groups were formed based on joint arthroplasty status. Group 1 were TJA patients without symptoms of aseptic loosening of at least 1 year, group 2 were patients with primary TJA, and group 3 were patients receiving revision surgery because of aseptic loosening. Genome-wide genotyping comparing genotype frequencies between patients with and without aseptic loosening (group 3 vs groups 1 and 2) was conducted. A case-control association analysis and linear modeling were applied to identify the impact of the identified genes on implant survival with time to the revision as an outcome measure. Results: We identified 52 single-nucleotide polymorphisms (SNPs) with a genome-wide suggestive P value less than 10-5 to be associated with the implant loosening. The most remarkable odds ratios (OR) were found with the variations in the IFIT2/IFIT3 (OR, 21.6), CERK (OR, 12.6), and PAPPA (OR, 14.0) genes. Variations in the genotypes of 4 SNPs-rs115871127, rs16823835, rs13275667, and rs2514486-predicted variability in the time to aseptic loosening. The time to aseptic loosening varied from 8 to 16 years depending on the genotype, indicating a substantial effect of genetic variance. Conclusion: Development of the aseptic loosening is associated with several genetic variations and we identified at least 4 SNPs with a significant effect on the time for loosening. These data could help to develop a personalized approach for TJA and loosening management. (C) 2019 Elsevier Inc. All rights reserved.

Background Emotional health disturbances are common after aneurysmal subarachnoid hemorrhage (aSAH) and their causes are largely unexplored. Corticotropin-releasing hormone receptor 1 (CRHR1) is a key factor in stress reactivity and development of mental health disturbances after adverse life-events. Methods We explore the effect of CRHR1 genotype on mental health after aSAH in a retrospective cohort study. One hundred twenty-five patients have been assessed using EST-Q mental health questionnaire. Genotyping of CRHR1 single nucleotide polymorphisms (SNP-s) was performed (Rs7209436, Rs110402, Rs242924). Results Fatigue was present in almost half of aSAH patients, depression and anxiety in one-third. There was a high prevalence of insomnia and panic complaints. Rs110402 minor allele decreased the risk of depression (OR = 0.25, p = 0.027 for homozygotes). Depression was present in 14% vs 41% in minor and major allele homozygotes, respectively. Rs110402, Rs242924 and Rs7209436 minor alleles and TAT-haplotype, formed by them, were protective against fatigue. After Bonferroni correction only the association of Rs110402 with fatigue remained statistically significant (OR = 0.21, p = 0.006 for minor allele homozygotes). Results remained statistically significant when adjusted for gender, admission state, age and time from aSAH. In multiple regression analysis occurrence of fatigue was dependent on anxiety, modified Rankin score and Rs110402 genotype (R 2 = 0.34, p < 0.001). Conclusions CRHR1 minor genotype was associated with a lower risk of fatigue and depression after aSAH. Genetic predisposition to mental health disturbances associated with negative life-events could be a risk factor for fatigue and depression after aSAH and selected patients might benefit from advanced counselling in the recovery phase.

Quality of life (QoL) disturbances are common after aneurysmal subarachnoid hemorrhage (aSAH) both in physical and mental health domains and their causes are not clearly understood. Corticotropin-releasing hormone receptor 1 (CRHR1) is involved in stress reactivity and development of mental health disturbances after negative life-events. We performed a retrospective cohort study of long-term QoL outcomes among 125 surgically treated aSAH patients (2001–2013). QoL was assessed with Short Form Health Survey (SF-36) and compared to an age and gender matched general population. Genotyping of CRHR1 single nucleotide polymorphisms was performed (Rs7209436, Rs110402, Rs242924) and their effect on QoL scores was explored. aSAH patients experienced a reduced quality of life in all domains. CRHR1 minor genotype was associated with higher SF-36 mental health (OR = 1.31–1.6, p < 0.05), role-emotional (OR = 1.57, p = 0.04) and vitality scores (OR = 1.31–1.38, p < 0.05). Association of all studied SNP’s with vitality and Rs242924 with mental health scores remained statistically significant after Bonferroni correction. Mental quality of life scores were associated with physical state of patients, antidepressant history and CRHR1 genotype. Predisposition to mental health disturbances after stressful life-events might be associated with reduced mental QoL after aSAH and selected patients could be provided advanced counselling in the recovery phase.

Nicotine dependence is an addiction to tobacco products and a global public health concern that in part would be influenced by our genetics. Smokers are reported to have reduced MAOA activity, but the results from genetic associations with this gene have been inconclusive. Two functionally relevant variable number tandem repeat (VNTR) domains, termed uVNTR and dVNTR, in the MAOA gene are well characterized transcriptional regulatory elements. In the present study, we analyzed uVNTR and dVNTR polymorphisms in the MAOA gene in the Vietnamese male population of smokers and non-smokers in order to assess the association of MAOA with the nicotine dependence measured by the Fagerström Test for Nicotine Dependence (FTND). Individual analysis of VNTRs separately identified uVNTR to be associated with the F6 question of the FTND indicating the stronger addiction to nicotine. No associations were found between the dVNTR and smoking behavior. The combination of dVNTR and uVNTR, that predicts low expression of MAOA (10–3 haplotypes), was significantly associated with the higher nicotine dependence (FTND score), longer smoking duration, and more persistent smoking behavior (fewer quit attempts). In conclusion, our study confirms that low MAOA expression is genetically predictive to the higher nicotine dependence. Impact statement The present study combined the analysis of two transcriptional regulators, uVNTR and dVNTR, in the MAOA gene that is an enzyme responsible for the monoamine degradation and identified genetic interaction between these VNTRs in association with the nicotine dependence. The main impact is that when analyzing different populations in the genetic studies, the functionally meaningful variants should be combined rather than addressing individual elements separately (a mini polygenic risk score for a particular gene/locus). This combination is very rarely analyzed and therefore the study sets an example. Another impact is that we analyzed the genetic variability in the Asian population and therefore our data present a piece of information from underrepresented populations.

Psoriasis is a chronic inflammatory skin disease with numerous involved factors. miR‐146a and miR‐146b (miR‐146a/b) are anti‐inflammatory miRNAs that are increased in psoriatic skin. SERPINB2 has been shown to be upregulated in the inflammation and infections. Here we aimed to study the relationship between miR‐146a/b and SERPINB2 and to delineate the role of SERPINB2 in association of plaque psoriasis. We report increased SERPINB2 expression in the skin of psoriasis patients, which was in a positive relationship with psoriasis severity and in a negative relationship with miR‐146a/b in psoriatic lesions. In cultured keratinocytes, both cellular and secreted SERPINB2 levels were strongly induced in response to IFN‐γ and TNF‐α. Interestingly, SERPINB2 mRNA was downregulated by IL‐17A and the combination of TNF‐α and IL‐17A at time points when miR‐146a was increased. The predicted binding site for miR‐146a/b in 3’ untranslated region of SERPINB2 revealed no activity in luciferase assay, while siRNA silencing of miR‐146a/b direct targets IRAK1 and CARD10 resulted in reduced expression of SERPINB2, suggesting that miR‐146a/b indirectly control SERPINB2 expression in the skin. The siRNA silencing of SERPINB2 increased the expression of IL‐8, CXCL5 and CCL5 and migration of neutrophils revealing its anti‐inflammatory role in keratinocytes. Our data together suggest that SERPINB2 and miR‐146a/b are part of disease‐related network of molecules that are coordinately regulated and act in controlling the inflammatory responses in psoriatic skin.

Osteogenesis imperfecta (OI) covers a spectrum of bone fragility disorders. OI is classified into five types; however, the genetic causes of OI might hide in pathogenic variants of 20 different genes. Often clinical OI types mimic each other. This sometimes makes it impossible to identify the OI type clinically, which can be a risk for patients. Up to 90% of OI types I–IV are caused by pathogenic variants in the COL1A1/2 genes. OI type V is caused by the c.-14C > T pathogenic variant in the 5′UTR of the IFITM5 gene and is characterized by hyperplastic callus formation and the ossification of interosseous membranes. In the current study, we performed IFITM5 5′UTR region mutational analysis using Sanger sequencing on 90 patients who were negative for COL1A1/2 pathogenic variants. We also investigated the phenotypes of five patients with genetically confirmed OI type V. The proportion of OI type V patients in our cohort of all OI patients was 1.48%. In one family, there was a history of OI in at least three generations. Phenotype severity differed from mild to extremely severe among patients, but all patients harbored the same typical pathogenic variant. One patient had no visible symptoms of OI type V and was suspected to have had OI type IV previously. We also identified a case of extremely severe hyperplastic callus in a 15-year-old male, who has hearing loss and brittleness of teeth. OI type V is underlined with some unique clinical features; however, not all patients develop them. The phenotype spectrum might be even broader than previously suspected, including typical OI features: teeth brittleness, bluish sclera, hearing loss, long bones deformities, and joint laxity. We suggest that all patients negative for COL1A1/2 pathogenic variants be tested for the presence of an IFITM5 pathogenic variant, even if they are not expressing typical OI type V symptoms. Further studies on the pathological nature and hyperplastic callus formation mechanisms of OI type V are necessary.

Plaque psoriasis is a non-contagious skin disease in which characteristic red and flaky lesions result from a dysregulation involving both innate and adaptive immune mechanisms. Several cytokines have been implicated in these processes and lately interleukin (IL)-36 family members have become more recognised among them. Thus far, genetic studies have only investigated IL36RN gene of this family in relation to pustular psoriasis. Since IL36G has previously demonstrated markedly increased levels in plaque psoriasis patients and is linked to IL-23/IL-17 axis critical in psoriasis pathology, it was chosen to be the focus of current report.

BACKGROUND:Osteogenesis imperfecta (OI) is a rare genetic bone fragility disorder. In the current study, differences between the genotypes and phenotypes of de novo and inherited collagen-related OI were investigated.METHODS:A comparative analysis was performed of the genotypes and phenotypes of 146 unrelated inherited and de novo collagen I OI cases from Estonia, Ukraine, and Vietnam. Mutational analysis of the subjects and all available parents were performed with Sanger sequencing.RESULTS:Results showed that 56.16% of the OI cases were caused by de novo pathogenic variants. The proportion of OI types OI1, OI4, and OI3 among subjects with inherited OI was 45.31%, 46.88%, and 7.81%, respectively. Among subjects with de novo OI, the proportions of OI types (OI1, OI4, and OI3) were almost equal. Both inherited and de novo OI pathogenic variants occurred more often in the COL1A1 gene than in the COL1A2. The majority of de novo cases were missense pathogenic variants, whereas inherited OI was mostly caused by loss of function pathogenic variants.CONCLUSION:In summary, there were significant differences between the phenotypes and genotypes of subjects with de novo and inherited OI. These findings may promote the further understanding of OI etiology, and assist with diagnostics procedures, as well as with family planning.

Osteogenesis imperfecta (OI) is a hereditary bone disorder caused by defects of type I collagen. Although up to 90% of patients harbor pathogenic variants in the COL1A1/2 gene, which codes for collagen α1/2 chains, the spectrum of OI genotypes may differ between populations, and there is academic controversy around OI genotype-phenotype correlations. In the current study, 94 Ukrainian OI families were interviewed. Clinical and genealogical information was collected from patients in spoken form, and their phenotypes were described. To identify the spectrum of collagen I pathogenic variants, COL1A1/2 mutational analysis with Sanger sequencing was performed on the youngest affected individual of every family. Of the 143 patients investigated, 67 (46.85%) had type I OI, 24 (16.78%) had type III, 49 (34.27%) had type IV, and III (2.10%) had type V. The mean number of fractures suffered per patient per year was 1.32 ± 2.88 (type I 0.50 ± 0.43; type III 3.51 ± 6.18; type IV 1.44 ± 1.77; and type 5 0.77 ± 0.23). 87.23% of patients had skeletal deformations of different severity. Blue sclera, dentinogenesis imperfecta, and hearing loss were present in 87%, 55%, and 22% of patients, respectively. COL1A1/2 pathogenic variants were harbored by 60 patients (63.83%). 27 pathogenic variants are described herein for the first time. The majority of the pathogenic variants were located in the COL1A1 gene (76.19%). Half (49.21%) of the pathogenic variants were represented by structural variants. OI phenotype severity was highly correlated with type of collagen I defect. The current article presents an analysis of the clinical manifestations and COL1A1/2 mutational spectrum of 94 Ukrainian OI families with 27 novel COL1A1/2 pathogenic variants. It is hoped that this data and its analysis will contribute toward the increased understanding of the phenotype development and genetics of the disorder.

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Human endogenous retrovirus (HERV) sequences make up at least 8% of the human genome. Transcripts originating from these loci as well as proteins encoded by them have been detected in various tissues. HERVs are believed to be implicated in autoimmune diseases, however the extent to which, has remained unclear. Differential expression studies have so far been limited to certain HERV subfamilies with conserved sequences. No studies have been published describing the genome-wide expression pattern of HERVs and repetitive elements in the context of psoriasis. In the present study, we analysed total RNA sequencing data from skin samples of 12 psoriasis patients and 12 healthy controls, which enabled us to describe the entire transcriptional landscape of repetitive elements. We report high levels of repetitive element expression in the skin of psoriasis patients as well as healthy controls. The majority of differentially expressed elements were downregulated in lesional and non-lesional skin, suggesting active HERV suppression in the pro-inflammatory environment of psoriatic skin. However, we also report upregulation of a small subset of HERVs previously described in the context of autoimmune diseases, such as members of the HERV-K and W families, with the potential to affect the immunopathogenesis of psoriasis.

Nicotine dependence is an addiction to tobacco products and a global public health concern. Association between the SLC6A4 polymorphisms and nicotine dependence is controversial. Two variable number tandem repeat (VNTR) domains, termed HTTLPR and STin2, in the SLC6A4 gene are well characterized transcriptional regulatory elements. Their polymorphism in the copy number of the repeat correlates with the particular personality and psychiatric traits. We analyzed nicotine dependence in 1,804 participants from Central Vietnam. The Fagerström Test (FTND) was used to evaluate the nicotine dependence and PCR was used to determine the SLC6A4 HTTLPR and STin2 VNTRs. The HTTLPR VNTR was associated with difficulties to refrain from smoking in a prohibiting environment. The STIn2 10/10 genotype was associated with (1) years of smoking, (2) difficulties to quit the first cigarette, and (3) higher number of cigarettes smoked per day (CPD). Stratification analysis was used to find the genetic interaction between these two VNTRs in nicotine dependence as they may synergistically regulate the SLC6A4 expression. Smokers with the S/S HTTLPR genotypes showed a much stronger association between STin2 10/10 variant and CPD. This finding is consistent with the molecular evidence for the functional interaction between HTTLPR and STin2 in cell line models, where STin2 has described as a stronger expressional regulator. Similarly, we found that STin2 is a much stronger modifier of smoking with 10/10 genotype related to higher nicotine dependence. The present study supports genetic interaction between HTTLPR and STin2 VNTRs in the regulation of nicotine dependence with the dominance of the STin2 effects. This finding could be explained by their differential effect on the SLC6A4 expression.

Vitiligo is a chronic multifactorial depigmentation disorder characterized by the destruction and functional loss of melanocytes. Although a direct cytotoxic T cell attack is thought to be responsible for melanocyte damage, the events leading to the loss of self-tolerance toward melanocytic antigens are not understood. This research aimed to identify novel cellular and molecular factors that participate in vitiligo pathogenesis through the application of gene expression and immunofluorescence analysis of skin biopsy samples along with immunophenotyping of circulating cells. Our study provides insights into the mechanisms involved in melanocyte destruction. The upregulation of stress-ligand MICA/MICB, recognized by activating receptors on innate and innate-like T cells, imply involvement of lymphoid stress surveillance responses in vitiligo lesions. A simultaneous increase in the expression of transcription factor EOMES that is characteristic for innate-like virtual memory T cells, suggest a similar scenario. Local lymphoid stress surveillance has been previously associated with the amplification of systemic humoral responses that were mirrored in our study by increased T follicular helper cells and switched memory B cell proportions in patients with active vitiligo. In addition, microtubule-associated protein light chain 3 staining was compatible with the activation of autophagy in keratinocytes and in the remaining melanocytes of vitiligo lesional skin.

We performed whole transcriptome analysis of osteosarcoma bone samples. Initially, we sequenced total RNA from 36 fresh-frozen samples (18 tumoral bone samples and 18 non-tumoral paired samples) matching in pairs for each osteosarcoma patient. We also performed independent gene expression analysis of formalin-fixed paraffin-embedded samples to verify the RNAseq results. Formalin-fixed paraffin-embedded samples allowed us to analyze the effect of chemotherapy. Data were analyzed with DESeq2, edgeR and Reactome packages of R. We found 5365 genes expressed differentially between the normal bone and osteosarcoma tissues with an FDR below 0.05, of which 3399 genes were upregulated and 1966 were downregulated. Among those genes, BTNL9, MMP14, ABCA10, ACACB, COL11A1, and PKM2 were expressed differentially with the highest significance between tumor and normal bone. Functional annotation with the reactome identified significant changes in the pathways related to the extracellular matrix degradation and collagen biosynthesis. It was suggested that chemotherapy may induce the modification of ECM with important collagen biosynthesis. Taken together, our results indicate that changes in the degradation of extracellular matrix seem to be an important mechanism of osteosarcoma and efficient chemotherapy induces the genes related to bone formation. Impact statement Osteosarcoma is a rare disease but it is of interest to many scientists all over the world because the current standard treatment still has poor results. We sequenced total RNA from 36 fresh-frozen paired samples (18 tumoral bone samples and 18 non-tumoral paired samples) from osteosarcoma patients. We found that differences in the gene expressions between the normal and affected bones reflected the changes in the regulation of the degradation of collagen and extracellular matrix. We believe that these findings contribute to the understanding of OS and suggest ideas for further studies.

Genetic predisposition has a substantial role in the development of athletic physical performance and is characterized by a large number of gene polymorphisms and the interaction of these variations. PURPOSE: (1) to examine the prevalence of genotypes of 6 genes related to physical performance (ACE I/D, ACTN3 R577X, PPARGC1A Gly482Ser,AGT Met235Thr, AMPD1 Gln12Ter, NOS3786C/T) in Estonian elite athletes; (2) to compare the distribution of gene variations between representatives of 2 sports groups (predominantly endurance-oriented and mostly for speed and/or power-oriented sports groups). METHODS: the study group consisted of 130 elite athletes (23 females and 107 males); current and former Estonian national team members; in age range 28.3±5.6 years; involved in 19 different sports disciplines. There were 77 representatives of endurance-oriented sports (17 females and 60 males) and 53 representatives of speed and power-oriented sports (6 females and 47 males). 26 athletes of the study group were medallists or finalists in the Olympic Games, World or European championships. Peripheral venous blood samples were collected for DNA extraction and genotyping (6 candidate genes) from all study subjects. For statistical analysis, a descriptive analysis and χ2 test were used to determine significant differences between the frequencies of gene variations. P-values of ≤ 0.05 were set as statistically significant. RESULTS: the higher prevalence of the RR genotype of the ACTN3 gene among athletes of endurance-oriented sports compared to athletes of speed and power-oriented sports was statistically significant (p=0.025). We did not find any significance in the distribution of other gene variations between the two sports groups. We observed the trend of a higher prevalence of the NOS3 TT genotype (p=0.076) and a lower prevalence of the AMPD1 TT genotype (p=0.09) in the endurance-oriented sports group compared to the speed and power-oriented sports group, but it was not statistically significant. CONCLUSIONS: our study results reveal a significantly higher prevalence of the ACTN3 RR genotype in athletes of the endurance-oriented sports group, which is in accordance with our previous study among young skiers and this may be an advantage for the explosive speed and power capacity in endurance sports.

Osteogenesis imperfecta (OI) is a rare bone disorder. In 90% of cases, OI is caused by mutations in the COL1A1/2 genes, which code procollagen α1 and α2 chains. The main aim of the current research was to identify the mutational spectrum of COL1A1/2 genes in Estonian patients. The small population size of Estonia provides a unique chance to explore the collagen I mutational profile of 100% of OI families in the country.

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)