Biomedical subjects

Antonio Salas

Publications and source records attributed to Antonio Salas.

At least 19 recordsLinked to original sources

PubMed2006

Drug consumption and the risk of microscopic colitis.

BACKGROUND: Microscopic colitis is a rare disease of unknown etiology. It has been described that some drugs could cause or worsen the disease; however, the scientific evidence is limited. AIM: To investigate the possible association of chronic drug consumption with microscopic colitis. METHODS: This was a case-control study in which groups of cases were: Group 1-39 patients with collagenous colitis; Group 2-39 patients with lymphocytic colitis; and Group 3-52 patients with chronic watery diarrhea of functional characteristics. 103 subjects formed the control group. At diagnosis, a drug consumption history of at least 2-wk duration was registered. An age- and sex-adjusted logistic regression analysis was used, and the odds ratio (OR, 95% CI) was calculated. RESULTS: Drug consumption was more frequent in lymphocytic colitis than in the control group (92.3%vs 76.3%, P < 0.05). The mean daily number of drugs by person was also higher in lymphocytic colitis (3.79 +/- 0.44 vs 2.13 +/- 0.22, P= 0.04). The following associations as compared with the control group were observed: Group 1-Consumption of NSAIDs (46.2%vs 23%, OR 2.9, 1.3-6.4), selective serotonin reuptake inhibitors (SSRIs) (18%vs 1%, OR 21, 2.5-177), specifically, sertraline (15.4%vs 0%, P < 0.0005); Group 2-SSRIs (28%vs 1%, OR 37.7, 4.7-304), beta-blockers (13 vs 3%, OR 4.79, 1.04-20), statins (13%vs 3%, OR 4.6, 1.04-20), biphosphonates (8%vs 0%, P= 0.022); Group 3-SSRIs (15%vs 1%, OR 16.2, 2-135), statins (11.5%vs 3%, OR 5.4, 1.2-24). As compared with the chronic diarrhea group, a significant association with the usage of sertraline in LC (P= 0.005) and a trend for NSAIDs in CC (P= 0.057) were found. CONCLUSIONS: Drug consumption increases the risk of microscopic colitis. Some drugs might be trigger factors of colonic inflammation in predisposed hosts, and others might only worsen self-evolving microscopic colitis.

Aged↗

PubMed2006

High penetrance of sequencing errors and interpretative shortcomings in mtDNA sequence analysis of LHON patients.

For identifying mutation(s) that are potentially pathogenic it is essential to determine the entire mitochondrial DNA (mtDNA) sequences from patients suffering from a particular mitochondrial disease, such as Leber hereditary optic neuropathy (LHON). However, such sequencing efforts can, in the worst case, be riddled with errors by imposing phantom mutations or misreporting variant nucleotides, and moreover, by inadvertently regarding some mutations as novel and pathogenic, which are actually known to define minor haplogroups. Under such circumstances it remains unclear whether the disease-associated mutations would have been determined adequately. Here, we re-analyse four problematic LHON studies and propose guidelines by which some of the pitfalls could be avoided.

Artifacts↗

PubMed2006

Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice.

AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice. METHODS: MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-alpha to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24+/-0.1 vs 21.3+/-6.4, P<0.05) and PMN from peripheral blood in wt (0.5+/-0.1 vs 10.4+/-0.7, P<0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-alpha in epithelial intestinal cells (2.5+/-0.5 vs 14.7+/-3.0, P<0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelial injury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modulated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.

Animals↗

PubMed2006

Polyethylene glycol enhances colonic barrier function and ameliorates experimental colitis in rats.

OBJECTIVE: Polyethylene glycol (PEG) has been suggested to protect against pathogen colonization by improving colonic barrier function. We aimed to establish whether PEG 4000 affects colonic barrier function and the development of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. MATERIALS AND METHODS: PEG was included in the drinking water for a period of 48 h before intracolonic administration of TNBS. RESULTS AND DISCUSSION: PEG increased colonic surface hydrophobicity and diminished luminal bacterial load. Moreover, PEG markedly reduced mucosal damage and inflammation induced by TNBS. This protection effect appeared to be independent of its laxative properties since the laxatives mannitol or senna extracts had no effect on TNBS colitis. Using everted colonic sacs, pretreatment with PEG produced a lasting reduction in epithelial permeability to mannitol and dextran-70 K that correlated with decreased surface hydrophobicity. CONCLUSION: Our results suggest that the protective effect of PEG on TNBS colitis is associated with reinforcement of the epithelial barrier.

Animals↗

PubMed2006

What is a 'novel' mtDNA mutation--and does 'novelty' really matter?

The hunt for pathogenic mitochondrial DNA (mtDNA) mutations is often fueled by the seeming novelty of mutations that are either nonsynonymous or affect the protein synthesis machinery in patients. In order to determine the novelty of a detected mutation, the working geneticist nearly always consults MITOMAP--often exclusively. By reanalyzing some case studies of refractory anemia with ring sideroblasts, prostate cancer, and hearing impairment, we demonstrate that the practice of solely relying on MITOMAP can be most misleading. A notorious example is the T1243C mutation, which was assessed to be novel and deemed to be associated with some (rare) disease simply because researchers did not realize that T1243C defines a deep branch in the Eurasian mtDNA phylogeny. The majority of 'novel' mutations suspected of being pathogenic are in actual fact known (and presumably neutral) polymorphisms (although unknown to MITOMAP), and this becomes glaringly evident when proper database searches and straightforward Internet queries are carried out.

Anemia, Refractory, with Excess of Blasts↗

PubMed2006

ERCC4 associated with breast cancer risk: a two-stage case-control study using high-throughput genotyping.

The failure of linkage studies to identify further high-penetrance susceptibility genes for breast cancer points to a polygenic model, with more common variants having modest effects on risk, as the most likely candidate. We have carried out a two-stage case-control study in two European populations to identify low-penetrance genes for breast cancer using high-throughput genotyping. Single-nucleotide polymorphisms (SNPs) were selected across preselected cancer-related genes, choosing tagSNPs and functional variants where possible. In stage 1, genotype frequencies for 640 SNPs in 111 genes were compared between 864 breast cancer cases and 845 controls from the Spanish population. In stage 2, candidate SNPs identified in stage 1 (nominal P < 0.01) were tested in a Finnish series of 884 cases and 1,104 controls. Of the 10 candidate SNPs in seven genes identified in stage 1, one (rs744154) on intron 1 of ERCC4, a gene belonging to the nucleotide excision repair pathway, was associated with recessive protection from breast cancer after adjustment for multiple testing in stage 2 (odds ratio, 0.57; Bonferroni-adjusted P = 0.04). After considering potential functional SNPs in the region of high linkage disequilibrium that extends across the entire gene and upstream into the promoter region, we concluded that rs744154 itself could be causal. Although intronic, it is located on the first intron, in a region that is highly conserved across species, and could therefore be functionally important. This study suggests that common intronic variation in ERCC4 is associated with protection from breast cancer.

Adult↗

PubMed2006

Testing for genetic structure in different urban Argentinian populations.

Fifteen autosomal short tandem repeat (STR) markers (D3S1358, HUMTH01, D21S11, D18S51, PENTA E, D5S818, D13S317, D7S820, D16S539, CSF1PO, PENTA D, HUMvWA, D8S1179, HUMTPOX, FGA) were analyzed in 1734 individuals living in urban areas of cities from six different Argentinian provinces (Buenos Aires, Neuquén, Tucumán, La Pampa, San Luis, Santa Cruz) in order to determine if a common urban database could be used in Argentina for forensic purposes. Frequencies estimates, Hardy-Weinberg equilibrium (HWE), and other parameters of forensic interest were computed. Comparisons between the six populations, and with published data from one Native American population from Argentina and other urban populations from Argentina and Europe were also performed. Our results reveal evidences for population structure, both when testing for genetic differentiation and when comparing frequencies distributions between different pairs of populations. Therefore, caution should be taken when using a common pooled database with general forensic purposes in Argentina.

Argentina↗

PubMed2006

Microsatellite autosomal genotyping data in four indigenous populations from El Salvador.

Fifteen microsatellite loci (D3S1358, TH01, D21S11, D18S51, PENTA E, D5S818, D13S317, D7S820, D16S539, CSF1PO, PENTA D, vWA, D8S1179, TPOX, and FGA) have been genotyped in four indigenous populations from El Salvador (Central America), namely, Conchagua, Izalco, Panchimalco, and San Alejo. Here we have obtained values for several indices of forensic interest for these population samples. Population differentiation test showed no significant statistical differences between these four populations, and an AMOVA test indicates that most of the genetic variation (approximately 100%) occurs within individuals. Population pairwise genetic comparisons with other population samples seem to indicate the existence of a major Native American component in the populations from El Salvador.

DNA Fingerprinting↗

PubMed2006

Updating the East Asian mtDNA phylogeny: a prerequisite for the identification of pathogenic mutations.

Knowledge about the world phylogeny of human mitochondrial DNA (mtDNA) is essential not only for evaluating the pathogenic role of specific mtDNA mutations but also for performing reliable association studies between mtDNA haplogroups and complex disorders. In the past few years, the main features of the East Asian portion of the mtDNA phylogeny have been determined on the basis of complete sequencing efforts, but representatives of several basal lineages were still lacking. Moreover, some recently published complete mtDNA sequences did apparently not fit into the known phylogenetic tree and conflicted with the established nomenclature. To refine the East Asian mtDNA tree and resolve data conflicts, we first completely sequenced 20 carefully selected mtDNAs--likely representatives of novel sub-haplogroups--and then, in order to distinguish diagnostic mutations of novel haplogroups from private variants, we applied a 'motif-search' procedure to a large sample collection. The novel information was incorporated into an updated East Asian mtDNA tree encompassing more than 1000 (near-) complete mtDNA sequences. A reassessment of the mtDNA data from a series of disease studies testified to the usefulness of such a refined mtDNA tree in evaluating the pathogenicity of mtDNA mutations. In particular, the claimed pathogenic role of mutations G3316A, T3394C, A4833G and G15497A appears to be most questionable as those initial claims were derived from anecdotal findings rather than e.g. appropriate association studies. Following a guideline based on the phylogenetic knowledge as proposed here could help avoiding similar problems in the future.

Asian People↗

PubMed2006

A reappraisal of complete mtDNA variation in East Asian families with hearing impairment.

In a number of recent studies, we summarized the obvious errors and shortcomings that can be spotted in many (if not most) mitochondrial DNA (mtDNA) data sets published in medical genetics. We have reanalyzed here the complete mtDNA genome data published in various recent reports of East Asian families with hearing impairment, using a phylogenetic approach, in order to demonstrate the persistence of lab-specific mistakes in mtDNA genome sequencing in cases where those caveats were (deliberately) neglected. A phylogenetic reappraisal of complete mtDNAs with mutation A1555G (or G11778A) indeed supports the suggested lack of association between haplogroup background and phenotypic presentation of these mutations in East Asians. In contrast, the claimed pathogenicity of mutation T1095C in Chinese families with hearing impairment seems unsupported, basically because this mutation is rather basal in the mtDNA phylogeny, being specific to haplogroup M11 in East Asia. The roles of other haplogroup specific or associated variants, such as A827G, T961C, T1005C, in East Asian subjects with aminoglycoside-induced and non-syndromic hearing loss are also unclear in view of the known mtDNA phylogeny.

DNA, Mitochondrial↗

PubMed2006

Matrix metalloproteinase-9 modulates intestinal injury in rats with transmural colitis.

Proteolysis and degradation of extracellular matrix by metalloproteinases (MMPs) may contribute to intestinal injury in inflammatory bowel disease. In the present study, we investigated the pathogenic role of gelatinases (MMP-9 and MMP-2) on transmural colonic injury in a rat model of chronic colitis, which was induced by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS). The activity and expression of MMP-2 and MMP-9 were measured in colonic tissue and peripheral neutrophils by fluorescence, zymography, Western blot, or immunohistochemistry at different time-points. Furthermore, myeloperoxidase content in colonic homogenates was analyzed to evaluate inflammation. Finally, morphological changes were assessed following early or delayed administration of CGS-27023-A, a synthetic inhibitor of MMPs. We found that the induction of colitis led to a significant up-regulation in tissue gelatinase concentration, whereas no changes in collagenase activity were observed. In addition, up-regulation of pro-MMP-9, but not of pro-MMP-2, was found on Days 7 and 10 following the induction of colitis. Furthermore, transmural MMP-9 was detected by immunofluorescent staining in the inflamed tissue. Consistent with tissue samples, neutrophils from colitic rats showed a significantly increased activity of pro-MMP-9. Finally, early but not delayed treatment with CGS-27023-A attenuated colonic mucosal injury in rats with TNBS-induced colitis. In conclusion, up-regulation of MMP-9 in peripheral and colonic neutrophils modulates transmural colonic injury in rats with TNBS-induced colitis.

Animals↗

PubMed2006

A multiplex assay with 52 single nucleotide polymorphisms for human identification.

A total of 52 SNPs reported to be polymorphic in European, Asian and African populations were selected. Of these, 42 were from the distal regions of each autosome (except chromosome 19). Nearly all selected SNPs were located at least 100 kb distant from known genes and commonly used STRs. We established a highly sensitive and reproducible SNP-typing method with amplification of all 52 DNA fragments in one PCR reaction followed by detection of the SNPs with two single base extension reactions analysed using CE. The amplicons ranged from 59 to 115 bp in length. Complete SNP profiles were obtained from 500 pg DNA. The 52 loci were efficiently amplified from degraded samples where previously only partial STR profiles had been obtained. A total of 700 individuals from Denmark, Greenland, Somalia, Turkey, China, Germany, Taiwan, Thailand and Japan were typed, and the allele frequencies estimated. All 52 SNPs were polymorphic in the three major population groups. The mean match probability was at least 5.0 x 10(-19) in the populations studied. Typical paternity indices ranged from 336 000 in Asians to 549 000 in Europeans. Details of the 52 SNP loci and population data generated in this work are freely available at http://www.snpforid.org.

DNA Fingerprinting↗

PubMed2006

Dissection of mitochondrial superhaplogroup H using coding region SNPs.

Haplogroup H (hg H) includes about 40-50% of the West Eurasian mitochondrial DNA (mtDNA) samples investigated so far. In order to enhance discrimination within this haplogroup we selected 45 coding region SNPs that allow to ascribe samples to the main phylogenetic branches of super hg HV (that embraces hg H) and, in particular, to H sublineages with a much finer resolution than previous studies. SNP selection was carried out using the most up-to-date available literature on population and forensic genetics and extended by means of phylogenetic analysis of complete or coding region genomes (<430) and control region sequences. A meticulous inspection of the H phylogeny led us to the observation of various but uncharacterized subclades of hg H. The selected SNPs were amplified in two PCR-multiplex reactions and subsequently targeted in three single-base extension multiplex reactions. A total of 2214 West Eurasian samples were screened for hg H specific loci 2706 and 7028, of which 859 fell in hg H and were further subjected to subhaplogroup typing. We observed 35 different subhaplogroups in total, 33 of which were found at frequencies below 5%. This assay can be used as a prescreening tool in forensic casework for rapid discrimination between divergent lineages (very effective for high-volume crime cases) or as discriminatory assay, when identical hg H haplotypes were obtained by control region sequencing.

Adolescent↗

PubMed2006

Mutation spectra of ABCC8 gene in Spanish patients with Hyperinsulinism of Infancy (HI).

Hyperinsulinism of Infancy (HI) is a clinical disorder characterized by deregulation of insulin secretion that leads to profound hypoglycemia. Mutations in genes encoding the ATP-regulated potassium channels of the pancreatic beta-cell, namely ABCC8 (SUR1) and KCNJ11 (Kir6.2), are the major genetic known cause of the disease. To elucidate the genetic etiology of HI in the uncharacterized Spanish population, we conducted extensive sequencing analysis of the ABCC8 (83.5Kb) and KCNJ11 (1.7Kb) genes in 34 Spanish HI patients. Mutations in ABCC8 were detected for both alleles in 13 patients, while ten patients carried only one mutation in one of the ABCC8 alleles. We have detected 22 novel and seven previously described mutations in ABCC8, approximately 60% of them lead to a premature termination signal, which would result in truncated SUR1 proteins. No mutations were found in the KCNJ11 gene. In addition, we report for the first time a 3914bp macrodeletion associated with the HI disorder. The potential pathogenicity of several additional variants is discussed. The spatial pattern of three pathological mutations suggests possible geographical founder effects. This work reveals for first time the involvement of KATP channels in the pathogenesis of an important proportion (approximately 68%) of Spanish HI patients. The spectrum of mutations in Spanish HI patients provides an important tool for diagnosis and prognosis of HI patients in the Spanish population, as well as for genetic counseling of HI families.

ATP-Binding Cassette Transporters↗

PubMed2006

Intestinal spirochetosis and chronic watery diarrhea: clinical and histological response to treatment and long-term follow up.

BACKGROUND: The clinical significance of intestinal spirochetosis is uncertain, therefore the aim of the present paper was to assess the prevalence of histological intestinal spirochetosis in patients with and without chronic watery diarrhea and to evaluate its clinical relevance. METHODS: A prospective diagnostic work-up of intestinal spirochetosis was made on biopsy samples taken from patients with chronic watery diarrhea submitted between 1994 and 2004 (1174 colonoscopies with multiple biopsies). Three other positive cases identified from routine endoscopic biopsies also were reviewed. In addition, samples from 100 asymptomatic control patients and a random sample of another 104 colonic specimens were reviewed for intestinal spirochetosis. The diagnosis was established by light and electron microscopy. Polymerase chain reaction (PCR) amplification of the 16S ribosomal RNA and reduced nicotinamide adenine dinucleotide (NADH) oxidase genes of the intestinal spirochetes Brachyspira aalborgi and Brachyspira pilosicoli was performed on tissue biopsies of the 11 positive patients. After diagnosis, treatment with penicillin benzatine (PB) or metronidazole was offered to all symptomatic patients and they were followed for a mean of 45.4 months (range: 37-113 months). RESULTS: Eight patients with chronic watery diarrhea were positive for intestinal spirochetosis. Intestinal spirochetosis was not diagnosed in the controls. Histological resolution of the infection paralleled clinical recovery in six patients (following metronidazole treatment in three). Most patients showed mild, non-specific colonic inflammation. Invasion by the spirochetes was not demonstrated by electron microscopy. Brachyspira aalborgi and B. pilosicoli each were identified by PCR in two cases. CONCLUSIONS: Histological intestinal spirochetosis appears to be relatively uncommon in Catalonia (Spain) compared to previous reports from other countries, but was identified in patients (0.7%) with chronic watery diarrhea. Sustained clinical recovery after spontaneous or drug-induced spirochetal disappearance in these individuals suggests that intestinal spirochetosis may play a pathogenic role in chronic watery diarrhea. Treatment with metronidazole is advisable in patients with persistent symptoms.

Adult↗

PubMed2005

Evaluating HapMap SNP data transferability in a large-scale genotyping project involving 175 cancer-associated genes.

One of the many potential uses of the HapMap project is its application to the investigation of complex disease aetiology among a wide range of populations. This study aims to assess the transferability of HapMap SNP data to the Spanish population in the context of cancer research. We have carried out a genotyping study in Spanish subjects involving 175 candidate cancer genes using an indirect gene-based approach and compared results with those for HapMap CEU subjects. Allele frequencies were very consistent between the two samples, with a high positive correlation (R) of 0.91 (P<<1x10(-6)). Linkage disequilibrium patterns and block structures across each gene were also very similar, with disequilibrium coefficient (r (2)) highly correlated (R=0.95, P<<1x10(-6)). We found that of the 21 genes that contained at least one block larger than 60 kb, nine (ATM, ATR, BRCA1, ERCC6, FANCC, RAD17, RAD50, RAD54B and XRCC4) belonged to the GO category "DNA repair". Haplotype frequencies per gene were also highly correlated (mean R=0.93), as was haplotype diversity (R=0.91, P<<1x10(-6)). "Yin yang" haplotypes were observed for 43% of the genes analysed and 18% of those were identical to the ancestral haplotype (identified in Chimpazee). Finally, the portability of tagSNPs identified in the HapMap CEU data using pairwise r (2) thresholds of 0.8 and 0.5 was assessed by applying these to the Spanish and current HapMap data for 66 genes. In general, the HapMap tagSNPs performed very well. Our results show generally high concordance with HapMap data in allele frequencies and haplotype distributions and confirm the applicability of HapMap SNP data to the study of complex diseases among the Spanish population.

Biomarkers, Tumor↗

PubMed2005

Results of the 2003-2004 GEP-ISFG collaborative study on mitochondrial DNA: focus on the mtDNA profile of a mixed semen-saliva stain.

We report here a review of the seventh mitochondrial DNA (mtDNA) exercise undertaken by the Spanish and Portuguese working group (GEP) of the International Society for Forensic Genetics (ISFG) corresponding to the period 2003-2004. Five reference bloodstains from five donors (M1-M5), a mixed stain of saliva and semen (M6), and a hair sample (M7) were submitted to each participating laboratory for nuclear DNA (nDNA; autosomal STR and Y-STR) and mtDNA analysis. Laboratories were asked to investigate the contributors of samples M6 and M7 among the reference donors (M1-M5). A total of 34 laboratories reported total or partial mtDNA sequence data from both, the reference bloodstains (M1-M5) and the hair sample (M7) concluding a match between mtDNA profiles of M5 and M7. Autosomal STR and Y-STR profiling was the preferred strategy to investigate the contributors of the semen/saliva mixture (M6). Nuclear DNA profiles were consistent with a mixture of saliva from the donor (female) of M4 and semen from donor M5, being the semen (XY) profile the dominant component of the mixture. Strikingly, and in contradiction to the nuclear DNA analysis, mtDNA sequencing results yield a more simple result: only the saliva contribution (M4) was detected, either after preferential lysis or after complete DNA digestion. Some labs provided with several explanations for this finding and carried out additional experiments to explain this apparent contradictory result. The results pointed to the existence of different relative amounts of nuclear and mtDNAs in saliva and semen. We conclude that this circumstance could strongly influence the interpretation of the mtDNA evidence in unbalanced mixtures and in consequence lead to false exclusions. During the GEP-ISFG annual conference a validation study was planned to progress in the interpretation of mtDNA from different mixtures.

Clinical Laboratory Techniques↗

PubMed2005

A critical reassessment of the role of mitochondria in tumorigenesis.

BACKGROUND: Mitochondrial DNA (mtDNA) is being analyzed by an increasing number of laboratories in order to investigate its potential role as an active marker of tumorigenesis in various types of cancer. Here we question the conclusions drawn in most of these investigations, especially those published in high-rank cancer research journals, under the evidence that a significant number of these medical mtDNA studies are based on obviously flawed sequencing results. METHODS AND FINDINGS: In our analyses, we take a phylogenetic approach and employ thorough database searches, which together have proven successful for detecting erroneous sequences in the fields of human population genetics and forensics. Apart from conceptual problems concerning the interpretation of mtDNA variation in tumorigenesis, in most cases, blocks of seemingly somatic mutations clearly point to contamination or sample mix-up and, therefore, have nothing to do with tumorigenesis. CONCLUSION: The role of mitochondria in tumorigenesis remains unclarified. Our findings of laboratory errors in many contributions would represent only the tip of the iceberg since most published studies do not provide the raw sequence data for inspection, thus hindering a posteriori evaluation of the results. There is no precedent for such a concatenation of errors and misconceptions affecting a whole subfield of medical research.

Artifacts↗