DNA Tandem Repeats as Iterable Objects to Count Cell Divisions: A Computational Model

Cell lineages of nematodes are completely known: the adult male of Caenorhabditis elegans contains 1031 somatic cells, the hermaphrodite 959, not one more, not one less;cell divisions are strictly deterministic (as in the great majority of invertebrates) but so far nothing is known about the mechanism used by cells to count precise numbers of divisions. In vertebrates, each species has its invariable deterministic numbers of somites, vertebrae, fingers, and teeth: counting the number of iterations is a widespread process in living beings;nonetheless, it remains an unanswered question and a great challenge in cell biology. This paper introduces a computational model to investigate the possible role of satellite DNA in counting cell divisions, showing how cells may operate under Boolean logic algebra. Satellite DNA, made up of repeated monomers and subject to high epigenetic methylation rates, is very similar to iterable sequences used in programming: just like in the “iteration protocol” of algorithms, the epigenetic machinery may run over linear tandem repeats (that hold cell-fate data), read and orderly mark one monomer per cell-cycle (cytosine methylation), keep track and transmit marks to descendant cells, sending information to cell-cycle regulators.

Identification and characterization of short tandem repeats in the Tibetan macaque genome based on resequencing data

The Tibetan macaque, which is endemic to China, is currently listed as a Near Endangered primate species by the International Union for Conservation of Nature （IUCN）（2017）. Short tandem repeats （STRs） refer to repetitive elements of genome sequence that range in length from 1-6 bp. They are found in many organisms and are widely applied in population genetic studies. To clarify the distribution characteristics of genome-wide STRs and understand their variation among Tibetan macaques, we conducted a genome-wide survey of STRs with next-generation sequencing of five macaque samples. A total of 1 077 790 perfect STRs were mined from our assembly, with an N50 of 4 966 bp. Mono-nucleotide repeats were the most abundant, followed by tetra- and di-nucleotide repeats. Analysis of GC content and repeats showed consistent results with other macaques. Furthermore, using STR analysis software （IobSTR）, we found that the proportion of base pair deletions in the STRs was greater than that of insertions in the five Tibetan macaque individuals （P〈0.05, t-test）. We also found a greater number of homozygous STRs than heterozygous STRs （P〈0.05, t-test）, with the Emei and Jianyang Tibetan macaques showing more heterozygous loci than Huangshan Tibetan macaques. The proportion of insertions and mean variation of alleles in the Emei and Jianyang individuals were slightly higher than those in the Huangshan individuals, thus revealing differences in STR allele size between the two populations The polymorphic STR loci identified based on the reference genome showed good amplification efficiency and could be used to study population genetics in Tibetan macaques. The neighbor-joining tree classified the five macaques into two different branches according to their geographical origin, indicating high genetic differentiation between the Huangshan and Sichuan populations. We elucidated the distribution characteristics of STRs in the Tibetan macaque genome and provided an effective method for screening polymorphic STRs. Our results also lay a foundation for future genetic variation studies of macaques.

A NORTHWEST DATABASE MODEL OF SHORT TANDEM REPEAT LOCI IN FORENSIC MEDICINE

Objective To establish the northwest database of short tandem repeat(STR) loci in forensic medicine. Methods Bloodstains or whole blood samples were collected from the unrelated prisoners in Xi'an city. Genetic distribution for 13 STR loci and amelogenin locus were determined in prisons based on GeneScan. One primer for each locus was labeled with the fluorescent by 5 FAM, JOE, or NED. The forensic database were generated by using multiple amplification, GeneScan, genotype, and genetic distribution analysis. Results 113 alleles and 302 genotypes were observed, with the corresponding frequency between 0.0050-0.5250 and 0.0100-0.4100. The mean H was 0.7667. The accumulative DP was 0.9999999,. The accumulative EPP was 0.9999999. The scope of PIC was 0.6036- 0.8562 . PM was less than 10 -11 . The observed and expected genotype frequencies were evaluated using χ 2 test and all were in accordance with Hardy Weinberg equilibrium ( P > 0.05 ). Conclusion STR loci is an ideal genetic marker with powerful polymorphism and stable heredity. It can be used for individual identification and paternity in forensic medicine. The forensic DNA database model can be established successfully.

Tandem repeat查找方法比较

Tandemrepeat在基因组成和进化中起到非常重要的作用,查找和分析Tandemrepeat已经成为当前生物信息学的一个前沿领域和研究焦点。目前在这一研究领域存在多类解决方法,主要有基于LZ分解技术的方法和最近兴起的基于后缀树索引的方法。本文选取了两种时间复杂度达到O(nlogn)数量级的代表性的方法,对这两种方法进行了全面的综述,并对它们的性能进行了系统的比较和分析。

Mapping short tandem repeats for liver gene expression traits helps prioritize potential causal variants for complex traits in pigs

Background:Short tandem repeats(STRs)were recently found to have significant impacts on gene expression and diseases in humans,but their roles on gene expression and complex traits in pigs remain unexplored.This study investigates the effects of STRs on gene expression in liver tissues based on the whole-genome sequences and RNA-Seq data of a discovery cohort of 260 F6 individuals and a validation population of 296 F7 individuals from a heterogeneous population generated from crosses among eight pig breeds.Results:We identified 5203 and 5868 significantly expression STRs(eSTRs,FDR<1%)in the F6 and F7 populations,respectively,most of which could be reciprocally validated(π1=0.92).The eSTRs explained 27.5%of the cisheritability of gene expression traits on average.We further identified 235 and 298 fine-mapped STRs through the Bayesian fine-mapping approach in the F6 and F7 pigs,respectively,which were significantly enriched in intron,ATAC peak,compartment A and H3K4me3 regions.We identified 20 fine-mapped STRs located in 100 kb windows upstream and downstream of published complex trait-associated SNPs,which colocalized with epigenetic markers such as H3K27ac and ATAC peaks.These included eSTR of the CLPB,PGLS,PSMD6 and DHDH genes,which are linked with genome-wide association study(GWAS)SNPs for blood-related traits,leg conformation,growth-related traits,and meat quality traits,respectively.Conclusions:This study provides insights into the effects of STRs on gene expression traits.The identified eSTRs are valuable resources for prioritizing causal STRs for complex traits in pigs.

Associations between IL-1RN variable number of tandem repeat, IL-1β (-511) and IL-1β (+3954) gene polymorphisms and urolithiasis in Uighur children of China

Objective:Interleukin-1(IL-1)is a pro-inflammatory cytokine which may be related to urolithiasis.Genetic polymorphisms of the interleukin-1beta(IL-1β)have been proposed as markers for urolithiasis in some areas.Due to the high incidence of urolithiasis in Uighur children(Xinjiang,China)and existence of ethnic difference,our aim is to explore the potential of IL-1 gene polymorphisms and urolithiasis among these children.Methods:Genomic DNA extracted from peripheral blood of 115 patients and 98 controls were used for genotype polymorphisms analyses.IL-1 receptor antagonist(IL-1RN)gene variable number of tandem repeat(VNTR)gene polymorphisms were analyzed by PCR method.PCR-based restriction analysis was done for the IL-1β(-511)and IL-1β(+3954)gene polymorphisms by endonucleases Ava I and Taq I,respectively.The genotype distribution,allele frequencies,carriage rate,and haplotype frequencies were statistically analyzed.Results:No significant differences were observed in genotypic frequencies between pediatric urolithiasis patients and control group for IL-1RN gene(χ^(2)=1.906,p=0.605),IL-1β(-511)gene(χ^(2)=0.105,p=0.949),or IL-1β(+3954)gene(χ^(2)=3.635,p=0.169).There were yet no significant differences of the allele frequencies of IL-1RN VNTR gene(p=0.779),IL-1β(-511)gene(p=0.941),and IL-1β(+3954)gene(p=0.418)in the case and control groups,as well as the carriage rate and haplotype of them(all p>0.05).Conclusions:The associations between IL-1RN VNTR,IL-1β(-511)and IL-1β(+3954)genes polymorphisms and urolithiasis were not significant in Uighur children.The results need to be confirmed in studies with larger population sample size,as well as in other ethnic groups.

Application of Short Tandem Repeat in Prenatal Diagnosis for Phenmylketonuria during the First Trimester

Objective : To find a simple and rapid way far the prenatal diagnosis of phenyUce-tonuria (PKU) during the first trimester in order to prevent inborn PKU patients as early as possible. Methods :DNA was extracted respectively from the Mood sampleps of 9 families' members and chori-onic tissues of 9 embryoes by cliorionic vittus sampling (CVS). The independent short tandem repeat (STR) alleles of members in 9 families with classic form of PKU were analyzed and prenatal diagnosis were conducted using polymerase chain reaction (PCR) together with denaturing gradient gel elec-trophoresis(DGGE)and silver dyeing. Results-.We identified 1 embryo with PKU, 2 normal individuals and 5 carriers among 9 subjects. Conclusion: Prenatal diagnosis for PKU by STR is available in the first trimester. This procedure was promising and would be widely used in Chinese population.

Relevance of MUC1 mucin variable number of tandem repeats polymorphism in H pylori adhesion to gastric epithelial cells

AIM:To evaluate the influence of MUC1 mucin variable number of tandem repeats (VNTR) variability on H pylori adhesion to gastric cells. METHODS: Enzyme linked immunosorbent assay (ELISA)-based adhesion assays were performed to measure the adhesion of different H pylori strains (HP26695 and HPTx30a) to gastric carcinoma cell lines (GP202 and MKN45) and GP202 clones expressing recombinant MUC1 with different VNTR lengths. RESULTS: Evaluation of adhesion results shows that H pylori pathogenic strain HP26695 has a significantly higher (P < 0.05) adhesion to all the cell lines and clones tested, when compared to the non-pathogenic strain HPTx30a. Bacteria showed a significantly higher (P < 0.05) adhesion to the GP202 cell line, when compared to the MKN45 cell line. Furthermore, both strains showed a significantly higher (P < 0.05) adhesion to GP202 clones with larger MUC1 VNTR domains. CONCLUSION: This work shows that MUC1 mucin variability conditions H pylori binding to gastric cells. The extent of bacterial adhesion depends on the size of theMUC1 VNTR domain. The adhesion is further dependent on bacterial pathogenicity and the gastric cell line. MUC1 mucin variability may contribute to determine H pylori colonization of the gastric mucosa.

Broader pattern of tandem repeats in the mitochondrial control region of Perciformes

Perciformes,the largest order of vertebrates with 20 suborders,is the most diverse fish order that dominates vertebrate ocean life.The complete mitochondrial control region(CR) of Trichiurus japonicus(Trichiuridae,Scombroidei) and Pampus sp.(Stromateidae,Stromateoidei) were amplified and sequenced.Together with data from GenBank,the tandem repeats in the mitochondrial CR from 48 species,which covered nine suborders of Perciformes,are reported in this study.The tandem repeats tend to be long in the suborder Percoidei and Stromateoidei.The identical repeats in 21 species of Cichlidae suggest a common origin and have existed before species divergence.Larimichthys crocea shows tandem repeats instead of the typical structure of the central conserved sequence blocks,which was first reported in Perciformes and vertebrates.This might have resulted from interruption of the polymerase activity during the H-strand synthesis.The four broader patterns presented here for the tandem repeats,including those in both the 5' and 3' ends,only in the either 5' or 3' end,and in the central conserved domain of the control region,will be useful for understanding the evolution of species.

ALLELE DISTRIBUTION OF FIVE X-CHROMOSOME SHORT TANDEM REPEAT LOCI IN EWENKE POPULATION OF NORTH CHINA

Objective To study the allele genetic polymorphism of five short tandem repeat(STR) loci on X-chromosome in Ewenke population of north China and to provide basic data for forensic identification. Methods Genomic DNA was extracted from EDTA-whole blood of Ewenke population by Chelex-100. The DNA samples were amplified by PCR and were analyzed by polyacrylamide gel electrophoresis and silver staining. The sequence length variations of DXS6799,DXS8378,DXS101,HPRTB,and DXS6789 loci on X-chromosome in 98 unrelated Ewenke individuals were investigated. Results All five loci analyzed showed high polymorphism and genetic stability. The data of the five X-chromosome STR loci in Ewenke ethnic group of China was in accordance with Hardy-Weinberg equilibrium by Chi-square test. Conclusion Allele polymorphism of five X-chromosome STR loci can be used as a genetic marker for forensic identification and population genetic research.

Utilizing Short Tandem Repeats (STRs) as a Resolving Matrix in Parental Dispute DNA Analysis

Interest in DNA analysis using short tandem repeats (STR) as finger printing tools in forensic medicine has gained tremendous application, as expression of these nuclear factors have enhanced forensic examination. Here we used this Biochemical characterization after conventional extraction process, polymerase chain reaction (PCR), gel electrophoresiss and a sequencer to distinguish and resolve parental dispute. The differential migration of labeled DNA fragments which attains excitation energy with a laser elicits fluorescent light of different wavelength depending on the dye used. A data collection software (Genemapper) collects raw data (spectrograph) and converts it to an electropherogram that is interpreted. By comparing the DNA profiles, inclusion and exclusion criteria were elucidated to resolve disputes. The inherent discriminating power of STRs used in analysis enhances resolution of cell mixtures, genetic aberration, substantiation of tissue origin and provides genetic distinction which is a robust and reliable approach in resolving parental disputes.

Exploring diversity of different classificatory human tandem repeats

Tandem repeats (TRs) are associated with dis-ease genes, play an important role in evolution and are important in genomic organization and function. Much research has been done on de-scriptions of properties of tandem repeats, such as copy-number, period, etc, and correlation be-tween mutations within tandem repeats and dis-ease. This project aims to detect some differ-ences which may exist within the features of dif-ferent tandem repeats associated with disease in human whole-genome. The features of tandem repeats associated with diabetes genes were compared to the counterparts of non-diabetes disease genes.

Genetic Polymorphism and Relationship Analyses of Standard Poodle and Bichon Frise Groups Based on 19 Short Tandem Repeat Loci

Context:As the increasing number of pet canines,the identification of canine has attracted much attentions in the forensic field,however,the genetic diversities of pet canines still remained unknown.Aims:To explore genetic polymorphisms of 19 short tandem repeat(STR)loci and genetic relationships between the two studied canine groups and reference group.Subjects and Methods:In the present study,genetic polymorphisms of 19 STR loci and a sex-linked zinc finger locus were analyzed in a total of 594 canines in Standard Poodle and Bichon Frise groups from China.Results:A total of 166,159 alleles were observed in the Standard Poodle,Bichon Frise groups with the corresponding allelic frequencies ranging from 0.0030-0.6108 to 0.0012-0.6148,respectively.The combined discrimination power and probability of exclusion of 19 STR loci in Standard Poodle and Bichon Frise groups were 0.9999999999999497,0.999962884;and 0.99999999999999995,0.999965955,respectively.Furthermore,the genetic distances between the two canine groups and Labrador retriever group were calculated,and the results indicated that Standard Poodle and Bichon Frise groups showed a closer genetic relationship,while the two canine groups had distant genetic relationships with Labrador retriever group.The result of population genetic structure revealed that genetic component distributions in the three canine groups were different.The predicted accuracies of the constructed random forest prediction model for three validation sets(25%individuals randomly selected from three populations with 808 individuals)were higher than 0.9,especially for the individuals in validation set from the Bichon Frise group is 1.Conclusions:The 19 STR loci could be used for individual identification,canine breed identification and paternity testing in the two canine groups.

Identification of Half‑Sisters from Different Mothers by Autosomal and X Chromosomal Short Tandem Repeats:A Case Study

Complex kinship identification such as half‑sibling identification is a difficult task in forensic biology Here we represented an approach in dealing with half‑sisters from different mothers,with the combination of autosomal and X chromosomal short‑tandem repeats(STRs)data.X chromosomal STRs can offer additional information,especially in some cases where autosomal STRs alone may not provide enough information for an accurate opinion.In this case,half‑sister or unrelated relationship between two women(S_(1)and S_(2))with different mothers were distinguished.23 autosomal and 31 X chromosomal STRs of S_(1),S_(2),S_(1)’s mother(M1),S_(2)’s mother(M2)and S_(1)’s grandmother(G1)were profiled with three different commercial kits.As to X‑chromosome STRs,likelihood ratios(LRs)were calculated by FamLinkX with consideration of linkage,linkage disequilibrium,and mutations.When only the profiles of the two individuals(S_(1)and S_(2))were available,LRs between S_(1)and S_(2)were 1.1110×10^(2)based on 23 autosomal STRs and 3.2257 om107 based on 31 X chromosomal STRs.When the maternal genotypes were taken into consideration,LRs increased to 2.5297×10^(3)and 3.0563×10^(18).Therefore,both the DNA profiles of each mothers and X chromosomal STRs are important in dealing with the identification of half‑sisters from different mothers.

A Brief Review of Short Tandem Repeat Mutation

Short tandem repeats （STRs） are short tandemly repeated DNA sequences that involve a repetitive unit of 1-6 bp. Because of their polymorphisms and high mutation rates, STRs are widely used in biological research. Strand-slippage replication is the predominant mutation mechanism of STRs, and the stepwise mutation model is regarded as the main mutation model. STR mutation rates can be influenced by many factors. Moreover, some trinucleotide repeats are associated with human neurodegenerative diseases. In order to deepen our knowledge of these diseases and broaden STR application, it is essential to understand the STR mutation process in detail. In this review, we focus on the current known information about STR mutation.

Carrier Detection and Presymptomatic Identification of Wilson Disease in Chinese by Non-Isotopic Linkage Analysis with Four Short Tandem Repeat Polymorphisms

Summary: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. To establish an efficient, accurate and fast diagnostic method for carrier detection and presymptomatic identification of WD in Chinese population, we studied haplotypes of short tandem repeat (STR) polymorphisms flanking the WD gene in 40 Chinese WD families. The results suggested that this genetic diagnosis system based on the four STR polymorphisms is of high value for the detection of potential carriers and WD homozygotes in families with at least one previously affected child. It is an efficient, accurate and fast diagnostic method that can be well suited for routine use in clinical laboratories.