short tandom repeat

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‎short tandem repeats ==‏ وود ‎Producer : Professor: ‎ ‎ ‎ ‎ ‎ 

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What is a short tandem repeats? also known as microsatellites (simple sequence repeats) a repetitive unit of 1-6 bp eries with lengths of up to 100 nucleotides polymorphic ccounting for about 3% of the entire genome + found most in the noncoding regions found in prokaryotes and eukaryotes created by Strand-slippage replication the stepwise mutation model + Stably inherited on a human time scale (for most) 

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In genome the highest density in chromosome one STR occurs per 2,000 bp in the human genome The most common STRs in humans are A-rich units: A, AC, AAAN, AAN, and AG STRs are classified into mono-, di-, tri-, tetra-, penta-, and hexanucleotide repeats The most common STRs in the human genome are dinucleotide repeats While GC-rich trinucleotide expansions predominate in exonic regions, intronic repeats are composed of 3-6 nucleotide tandems and vary considerably in GC content 

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Number of STRs my 

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classified ۰ STRs are classified into perfect repeats (simple repeats) * containing only one repetitive unit, and imperfect repeats (compound repeats * consisting of different composition repeats 

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Function contingency genes” reside in STR sequences cause frameshift mutations Some STRs may take part in regulating the transcription ome STRs can regulate the transcription of the epidermal growth factor gene the tyrosine hydroxylase gene, and the PIG3 gene. some STRs may influence the regulation of gene expression STRs may also affect recombination generation of nucleosome positioning signals maintenance of chromatin spatial organization 

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High Mutation Rates of STRs * several orders of magnitude higher than Unique DNA sequences. = * ranging from 10-° to 10-? nt per generation. * specific for organisms in vivo. in yeast (10-5 nt per cell division ) in human(10-5 nt and 10-—10-5 nt per cell division) 

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elucidating the mutation rates of STRs * the familial approach * biological model approach, * population approach * germline cell approach 

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Mechanisms of STR Mutation * (1) unequal crossing over in meiosis = * (2) retrotransposition mechanism * (3) strand-slippage replication 

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1.unequal crossing over in meiosis * generating large blocks of satellite DNA * exchange of repeat units between homologous chromosomes 

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2.retrotransposition mechanism ۰ A-rich STRs are generated by a 3’ extension of retrotranscripts * the association between the most common human STRs with A-rich content and transposable elements 

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3.strand-slippage replication as the main explanation of the STR mutation process occurs during DNA replication a functional mismatch repair system reduces the STR mutation rate between 100 and 1,000 folds Several factors can affect the rate of slippage events -the length of the repeat unit -the number -location, and -sequence of repeats 

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Models of STR Mutation * Infinite alleles model (IAM) * Stepwise mutation model (SMM) 

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Factors Influencing STR Mutation Repeat number Repeat unit Repeat structure Base composition of repeat unit Flanking sequence Recombination Sex Age Interruptions in STR 

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STR Mutation and Diseases ۰ STR expansion diseases are caused by a variety of AT- and GC-rich tandem repeat sequences = * at least twenty-two disorders caused by expansions of STRs ‏ع‎ ‎* Diseases caused by -STR expansions in the promoter, - 5’ untranslated region (5'UTR) - introns, - coding region - 3’ untranslated region (3’UTR) 

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STR Mutation and Diseases Promoter. Baratela-Scott Syndrome (BSS) linked to XYLT1 gene 5’UTR. Glutaminase Deficiency (GAD)-GLS ,Fragile XA Syndrome (FRAXA or FXS)- FMRI Intron. Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (ALS/FTD)- Myotonic Dystrophy Type 2 (DM2)-CNBP Coding region (polyglutamine). Dentatorubral-Pallidoluysian Atrophy (DRPLA)-ATN1 Coding region (polyalanine). Blepharophimosis Syndrome (BPES)-FOXL2 Coding region (polyaspartic acid). Pseudoachondroplasia and Multiple Epiphyseal Dysplasia (PSACH/MED) 3’UTR. Myotonic Dystrophy Type 1 (DM1) 

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cone at coding SS ‏سح‎ ‎aR ‏تست و‎ aot ‏ما تاو الخدت‎ 7 sca | _ apna 9043) —l- Vorteal Berle cacnata ةعمممب‎ | —— 1519 HSea x ana ‏ام 18960 39759 | م تممه‎ 9 ‏ات‎ = ams ‏سوسحت | به همه‎ wera ‏معامة‎ eon ver ‏ممصم‎ ae — | Furs Fama) ] Sura ruse bux ‏رد‎ ‎20 ‏تس‎ ‎209 ‏موه‎ ‎ops ‎ano ScA106) | __inton.8 esra cous ‏له رد‎ ۱ ۵ ‏امعم مممومم‎ ‏ل زم فيه دودمم عمجم‎ vRNA 1 7 +0 3 10000 repeat nat) 

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TRE TRF Reference ‏هم‎ indel STR se 22939 ۶و وواو و و وود وووو و Untable star repeat Suand 5 umber ad State repeat umber if ۱6 5 a 1122 a a 0 0 عي ‎within‏ ‎‘ene‏ Gene ‏د‎ 3 سس ۷ مرو Disease مس كه جر شب 

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Counting short tandem repeats polymerase chain reaction (PCR) Southern blotting next-generation sequencing (NGS) Software CRISPR 

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Software * (1) STR specific methods that use the repeat structure in some way to make repeat size calls * (2) methods to detect expansions * (3) general MPS variant calling methods 

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1.STR specific methods use the repeat structure in some way to make repeat size calls lobSTR RepeatSeq STRViper ( HipSTR STRait Razor GenoTan 

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2.methods to detect expansions * ExpansionHunter ٠١ exSTRa ¢ STRetch 

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3.general MPS variant calling methods ٠ 5 Genome Analysis Toolkit’s (GATK) Unified Genotyper and HaplotypeCaller Dindel 

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Application of STRs . Forensics . Bone marrow transplant follow up . DNA profiling . Authenticating Cell Lines . Tracking and Confirming Tissue Provenance and Detecting Contamination . Detecting Maternal Cell Contamination and Fetal Aneuploidy . Cancer Research . Determining Twin Zygosity UPwWwne No 

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1.Forensics The federal bureau of investigation (FBI) has chosen 13 specific STR loci to serve as the standard for CODIS. Mass disasters Paternity testing Military DNA “dog tag” Convicted felon DNA databases 

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2.Bone marrow transplant follow up * Important for estabilishing graft rejection and disease relapse 23 * The ratio of allele peak heights between donor and = rrecipient good indication of success. 

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3.DNA profiling 

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4.Authenticating Cell Lines ° Authenticate cultured cells * STR analysis to confirm the identity of cell lines 

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5.Tracking and Confirming Tissue Provenance and Detecting Contamination * Areference sample to determine the sample’s identity ¢ STR analysis can be used to detect sample contamination 

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6.Detecting Maternal Cell Contamination and Fetal Aneuploidy * STR analysis can help ensure that a prenatal fetal sample is not contaminated with maternal cells prior to assaying = the prenatal fetal sample * STR analysis can be used to detect fetal DNA in maternal blood samples during research and development of less invasive prenatal genetic tests STR analysis to detect fetal chromosomal abnormalities ¢ determine fetal gender using the sexually dimorphic |___ Amelogenin locus 

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7.Cancer Research * Cancer researchers can determine genetic changes by examining STR loci. 

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8.Determining Twin Zygosity * used to determine whether twins are monozygotic = (identical) or dizygotic (fraternal) * Confirming zygosity also has been informative in studies that examine the rate of monozygotic twin or triplet births as a result of natural conception or assisted reproductive techniques