DOI: 10.5061/dryad.5tb2rbpgt
title: CGG, CAG, and GAA: genome-wide comparison of the disease linked Trinucleotide short tandem repeat

description: Short tandem repeats (STRs) are tracts of 1–6 bp DNA motifs repeated in a
 head-to-tail fashion, collectively accounting for approximately 3% of the
 human genome. Among these, trinucleotide STRs hold particular relevance
 due to their involvement in human genetic disorders, with CGG, CAG, and
 GAA repeats being causative of Fragile X Syndrome, Huntington’s Disease,
 and Friedreich’s Ataxia, respectively. In this study, we systematically
 examined the genomic distribution, abundance, repeat length, and
 polymorphism of 5,963 CGG, 11,220 CAG, and 16,105 GAA loci across a cohort
 of 191 healthy individuals. Marked differences were observed between the
 three repeat classes. CGG STRs, while the least abundant, were strongly
 enriched within exonic and promoter regions and exhibited the highest
 levels of polymorphism, particularly in genic regions. GAA STRs were by
 far the most abundant and displayed the greatest overall variability, with
 the majority located in intergenic and intronic regions, but showing
 minimal polymorphism in exons and 5′-UTRs. In contrast, CAG STRs were more
 evenly distributed across genic and intergenic regions and were strikingly
 stable, despite being known to drive pathogenic expansions when exceeding
 certain thresholds. These findings demonstrate that trinucleotide STR
 classes are not interchangeable but exhibit unique genomic and
 evolutionary characteristics. Nucleotide composition emerges as a key
 determinant of STR localization, stability, and variability, suggesting
 that the biological roles of these repeats are intrinsically tied to their
 motif sequence. Our study underscores the importance of analyzing STR
 classes individually, as grouping them solely by motif length risks
 overlooking significant functional distinctions.
description: # CGG, CAG, and GAA: genome-wide comparison of the disease linked
 Trinucleotide short tandem repeat Dataset DOI:
 [10.5061/dryad.5tb2rbpgt](10.5061/dryad.5tb2rbpgt) ## Description of the
 data and file structure ## Project Title **CGG, CAG, and GAA: Genome-wide
 comparison of the Disease Linked Trinucleotide Short Tandem Repeats** ##
 Overview Short tandem repeats (STRs) of trinucleotide motifs play distinct
 roles in genome biology and human disease. This project focuses on the
 distribution, variability, and polymorphism of **CAG**, **CGG**, and
 **GAA** repeats—associated with **Huntington’s Disease**, **Fragile X
 Syndrome**, and **Friedreich’s Ataxia**, respectively—across **191 healthy
 genomes**. --- ## Directory Contents The dataset is organized into several
 CSV files, grouped by **repeat motif** and **analysis type**: --- ### **1.
 Summary Files by Motif** For each repeat class (CAG, CGG, GAA), the
 following summary files are included: | File Name | Description | |
 :--------------------------------- |
 :----------------------------------------------------------------------------------------------- | | `*_Platinum_by_chr.csv` | Summary statistics of STRs aggregated by chromosome. | | `*_Platinum_by_sample.csv` | Per-sample statistics (e.g., average repeat length, heterozygosity). | | `*_Platinum_by_heterozygosity.csv` | Summary of heterozygosity levels across samples. | | `*_Platinum_by_locus.csv` | Locus-level data including genomic position, motif length, variability, and annotation category. | **Example:** `GAA_Platinum_by_locus.csv` contains detailed locus-wise STR metrics for all GAA loci found in the Platinum genome cohort. **File Structures:** *_Platinum_by_chr | Column Name | Description | | :---------------- | :---------------------------------------------------------------- | | Chr | Chromosome | | Mbp | Chromosome size | | Total\_Reps | Total repeat loci on the chromosome | | Mean\_Units | Mean repeat length on the chromosome in the screened population | | Med\_Units | Median repeat length on the chromosome in the screened population | | Polymorphic\_Reps | Number of polymorphic repeats detected on the chromosome | | poly\_Ratio | Ratio of polymorphic repeats to stable repeats | | Reps\_per\_Mbp | Total density of repeats on the chromosome (per Mbp) | | Poly\_per\_Mbp | Total density of polymorphicrepeats on the chromosome (per Mbp) | *_Platinum_by_sample | Column Name | Description | | :------------------------- | :----------------------------------------------------------------- | | Sample\_ID | Sample identifier | | Highest\_Repeat | Largest repeat length detected in the sample | | Total\_Repeats | Total number of repeat alleles genotyped within the smaple | | Mean\_Rep\_length | Mean repeat length within the given smaple | | Unstable\_Reps | Number of polymorphic repeats detected within the sample | | Percentage\_Unstable\_Reps | What percentage of repeats that were dected which were polymorphic | *_Platinum_by_heterozygosity.csv | Column Name | Description | | :---------------- | :------------------------------------------------------------------------------ | | Med\_Units | Repeats grouped by population median length | | Stable\_Reps | The number of repeats that were stable across the population | | Unstable\_Reps | The number of repeats that were polymorphic across the population | | Total\_Reps | Total number repeats of that median population repeat length | | Flagged\_Unstable | Total proportion of polymorphic repeats of that median population repeat length | *_Platinum_by_locus.csv | Column Name | Description | | :------------------ | :-------------------------------------------------- | | Call\_ID | Repeat locus identifier  | | Chr | Chromosome | | Start | Genomic co-ordiante start position | | Ref\_Units | Repeat length in hg38 reference genome | | Mean\_Units | Mean repeat length in screened population | | Med\_Units | Median repeat length in screened population | | Min\_Units | Smallest repeat length in screened population | | Max\_Units | Largest repeat length in screened population | | Hits | Number of times repeat was successfully genotyped | | Instability\_Rating | Rate of repeat instability (0 - 1) | | SD | Standard devation of repeat length | | EE50 | Number repeat expansion events detected (Above 50) | | EE100 | Number repeat expansion events detected (Above 100) | | Status | Repeat status (STABLE or POLYMORPHIC) | | Gene | Gene most positionally associated with repeat | | Region | Genetic region in which the repeat occours | --- ### 2. Read Coverage Files | File Name | Description | | :---------------------------- | :----------------------------------------------------------------------------------------------------- | | `ReadCoverage_*_Platinum.csv` | Read depth information for each STR locus, used to assess reliability of genotyping across the cohort. | **Structure:** `ReadCoverage_*_Platinum.csv` | Column Name | Description | | :-------------- | :------------------------------------------------ | | Sample\_ID | Sample identifier | | Call\_ID | Repeat locus identifier  | | MaxSpanningRead | Number and size of spanning reads detected | | MaxFlankingRead | Number and size of flanking reads detected | | MaxInrepeatRead | Number and size of in repeat reads reads detected | --- ### **3. Raw and Filtered Repeat Data** | File Name | Description | | :-------------------------------- | :----------------------------------------------------------- | | `Repeats_*_Platinum.csv` | Raw STR calls from the Platinum genomes. | | `Repeats_*_Platinum_filtered.csv` | High-confidence subset of STR calls after quality filtering. | **Structure:** `Repeats_*_Platinum.csv` & `Repeats_*_Platinum_filtered.csv` | Column Name | Description | | :------------- | :------------------------------------- | | Call\_ID | Repeat locus identifier  | | Sample\_ID | Sample identifier | | Chr | Chromosome | | Start | Genomic co-ordiante start position | | End | Genomic co-ordiante end position | | GT | Overall genotype, vcf notation | | Ref\_Units | Repeat length in hg38 reference genome | | Allele1\_Units | Repeat length of the 1st allele | | Allele2\_Units | Repeat length of the 2nd allele | --- ### **4. MSSNG Unaffected Dataset** These files provide repeat data from unaffected individuals in the MSSNG cohort, serving as an independent control dataset: | File Name | Description | | :---------------------------------------- | :----------------------------------------------------------------------- | | `*_Repeats_MSSNG_Unaffected_by_locus.csv` | Locus-level repeat data for unaffected individuals in the MSSNG project. | **Structure:** `*_Repeats_MSSNG_Unaffected_by_locus.csv` has the same file structure as `*_Platinum_by_locus.csv` outlined in Section 1. --- ## File Naming Convention * `CAG`, `CGG`, `GAA`: Motif class * `Platinum`: Refers to the 191 high-quality genomes used for the core analysis * `MSSNG_Unaffected`: Refers to unaffected individuals from the MSSNG autism genomics cohort * `by_chr`, `by_sample`, `by_locus`, etc.: Summary scope * `filtered`: Indicates data has passed stringent quality control filters --- ## Notes * All files are in **CSV or TSV format** and can be opened in R, Python, or spreadsheet software. * Locus-based files include genomic coordinates (chr, start, end), motif size, repeat counts, and annotation categories (e.g., exonic, intronic). * Summary statistics were generated using custom pipelines for STR genotyping and annotation. ## Access information Data was derived from the following sources: * The MSSNG Project ([https://research.mss.ng/](https://research.mss.ng/)) * Platinum Genomes ([https://emea.illumina.com/platinumgenomes.html](https://emea.illumina.com/platinumgenomes.html)) ## Human subjects data I confirm that we have received explicit consent and all data has been de-identified .