Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.

DNA polymorphism of dogs (Canis familiaris L.). III. VNTR- and STR-loci. Their use in dog breeding and in criminalistics.

The application of mini- and microsatellite polymorphisms of dog DNA, also referred to as VNTR- and STR-loci, respectively, in dog breeding and criminalistics is considered. Their use in dog breeding is shown to clarify pedigrees, establish paternity and purebred, as well as to differentiate breeds mainly in the form of microsatellite DNA polymorphism. In criminalistics, dogs can be both participants in crime scenes in the form of attacks on humans or pets, and some witnesses through whose DNA extracted from their fur or feces, by DNA identification of a particular dog, it may be help to get out to the perpetrator or at least to the crime scene, which is also a good help in its disclosure. At the same time, population studies of dogs, during which the prevalence of certain alleles of marker traits in the form of STR loci in different territories is established, contribute to making the right decisions. The databases on STR-polymorphism of dog DNA or their prototypes are briefly described. Attention is paid to the sources of forensic canine DNA, as well as methods of its extraction and preliminary evaluation of isolated preparations. The use of VNTR polymorphism was rather short-lived, and was quickly replaced by STR polymorphism. There are some trends in the introduction of new polymorphic traits in this area in the form of single-nucleotide polymorphism or SNPs, potentially providing more accurate information, including for DNA identification of individuals. The issues of universal DNA certification of dogs are discussed, which can contribute to improving the culture of keeping dogs and will allow the elimination of stray dogs in the future, which will be humanistic character and potentially reduce the number of aggressor dogs.

The Short Tandem Repeat of the DMT1 Gene as a Molecular Marker of Elite Long-Distance Runners

The DMT1 gene encodes divalent metal transporter 1, a membrane iron transport protein. Divalent metal transporter 1 influences cellular iron availability, which might further affect aerobic exercise capacity. Short tandem repeat (STR) polymorphisms have been used as genetic markers in the literature, yet the STR polymorphisms of the DMT1 gene have not been well studied. In this current study, we explored the polymorphisms of the DMT1 gene in a group of elite long-distance runners and controls, by using the PCR-RFLP (Restriction Fragment Length Polymorphism) and Gene scan technology. We found that the genotype frequency of the homozygous 258 bp STR polymorphism of the DMT1 gene (258 bp/258 bp) was significantly higher in the athlete group than in the controls (χ2=14.01, p=0.006) so does the allele frequency of the 258 bp STR polymorphism (χ2=12.867, p=0.008). These data suggested that the STR polymorphism of the DMT1 gene might be correlated with aerobic exercise capacity and the 258 bp homozygous (25 bp/258 bp) could be used as a molecular marker for the talent identification of elite long-distance runners.

Evidence of transcription at polyT short tandem repeats

BackgroundUsing the Cap Analysis of Gene Expression technology, the FANTOM5 consortium provided one of the most comprehensive maps of Transcription Start Sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers.ResultsHere, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at short tandem repeats (STRs) corresponding to homopolymers of thymidines (T). Additional analyse confirm that these CAGEs are truly associated with transcriptionally active chromatin marks. Furthermore, we train a sequence-based deep learning model able to predict CAGE signal at T STRs with high accuracy (~81%) Extracting features learned by this model reveals that transcription at T STRs is mostly directed by STR length but also instructions lying in the downstream sequence. Excitingly, our model also predicts that genetic variants linked to human diseases affect this STR-associated transcription.ConclusionsTogether, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism. We also provide a new metric that can be considered in future studies of STR-related complex traits.

CATT polymorphism in MIF gene promoter is closely related to human pulmonary tuberculosis in a southwestern China population

Macrophage migration inhibitory factor (MIF) is deemed as an immunoregulatory and proinflammatory cytokine related to the progression of tuberculosis. A CATT short tandem repeat (STR) polymorphism at position −794 in the MIF gene promoter region is associated with the susceptibility to tuberculosis (TB). To investigate whether macrophage MIF gene mif CATT variants are associated with susceptibility to retreatment cases of TB and drug-resistant TB prevalence, genotyping of MIF −794 CATT polymorphism and quantifying of serum MIF were performed to associate MIF−794 CATT polymorphism with new patients and retreatment cases. Significant increases in MIF −794 CATT genotypes 7/8 and allele CATT 8 were observed in TB patients. Significant differences in the genotypic frequencies of MIF −794 CATT (5/X + 6/X vs 7/7 + 7/8) were demonstrated upon comparing the total cases and the new cases of TB with the controls. Significant differences in the allelic frequencies of MIF −794 CATT (5 + 6 vs 7 + 8) were observed in the total cases and new cases of TB. No differences in the genotypic frequencies of the MIF −794 CATT (5/X + 6/X vs 7/7 + 7/8) were observed between the retreatment cases and the controls or between the new cases and retreatment cases. In conclusion, the MIF −794 CATT genotypes 7/8 and allele CATT 8 were highly associated with TB; no differences in the genotypic frequencies of the MIF −794 CATT (5/X + 6/X vs 7/7 + 7/8) were observed between the new cases and retreatment cases.