--- title: "Genotyping short tandem repeats using ADSP R4" id: "9383" type: "study" slug: "sa000087" published_at: "2026-09-29T19:12:45+00:00" modified_at: "2026-09-29T19:12:45+00:00" url: "https://dss.niagads.org/studies/sa000087/" markdown_url: "https://dss.niagads.org/studies/sa000087.md" excerpt: "Variation in tandem repeats (TRs), particularly large expansions of triplet repeats (e.g., polyCAG), is known to cause a number of late-onset neurological diseases. Due to their repetitive and degenerate nature, variation in TRs is typically not captured by standard genome..." --- ## Description Variation in tandem repeats (TRs), particularly large expansions of triplet repeats (e.g., polyCAG), is known to cause a number of late-onset neurological diseases. Due to their repetitive and degenerate nature, variation in TRs is typically not captured by standard genome analysis pipelines. Furthermore, pathogenic repeat expansions can span hundreds to thousands of bases, making them difficult to detect using short-read sequencing data. However, specialized algorithms have been developed that enable short tandem repeats (STRs; motif sizes of 1–20 bp) to be genotyped from short-read sequencing data, including expanded alleles whose sizes exceed the read length. ExpansionHunter Denovo was first used to screen the ADSP R4 whole-genome sequencing data for expanded STR alleles. These results were then combined with analyses of other diverse genomes to create a custom catalog of approximately 165,000 STRs, representing tandem repeats in the human genome that show high levels of polymorphism and/or a high propensity to undergo rare expansions. These STRs were subsequently genotyped in the ADSP R4 whole-genome sequencing samples using ExpansionHunter. ## PI Andrew Sharp Icahn School of Medicine at Mount Sinai ## Associated Datasets - [NG00196- Genotyping short tandem repeats using the ADSP R4 cohort](https://dss.niagads.org/datasets/ng00196/) A two-step pipeline was used to first identify expanded short tandem repeats (STRs) in ADSP samples using ExpansionHunter Denovo and then genotype the identified STRs, along with additional polymorphic STRs… [Learn more](https://dss.niagads.org/datasets/ng00196/) ## Associated Sample Sets - [snd10147 - ADSP R4 Short Tandem Repeats (STRs)](https://dss.niagads.org/sample-sets/snd10147/) This dataset comprises short tandem repeat (STR) genotypes from 31,681 whole-genome sequencing (WGS) samples from the ADSP R4 data release. The STRs were genotyped using ExpansionHunter with a custom catalog… [Learn more](https://dss.niagads.org/sample-sets/snd10147/) ## Cohorts - [Adult Changes in Thought (ACT)](https://dss.niagads.org/cohorts/adult-changes-in-thought-act/) The Adult Changes in Thought (ACT) study is a longitudinal prospective cohort study that began in 1994. Participants are randomly selected from Seattle area members of Group Health aged 65… [Learn more](https://dss.niagads.org/cohorts/adult-changes-in-thought-act/) - [Alzheimer’s Disease Neuroimaging Initiative (ADNI)](https://dss.niagads.org/cohorts/alzheimers-disease-neuroimaging-initiative-adni/) ADNI is a global research study that actively supports the investigation and development of treatments that slow or stop the progression of AD. In this multisite longitudinal study, researchers at… [Learn more](https://dss.niagads.org/cohorts/alzheimers-disease-neuroimaging-initiative-adni/) - [Amish Protective Variant Study](https://dss.niagads.org/cohorts/amish-protective-variant-study/) The Amish Protective Variant Study, based at Case Western Reserve University and the University of Miami (Cummings et al. 2012; D’Aoust et al. 2015), is being conducted in the Indiana… [Learn more](https://dss.niagads.org/cohorts/amish-protective-variant-study/) - [Case Western Reserve University (CWRU) Autopsy](https://dss.niagads.org/cohorts/case-western-reserve-university-cwru-autopsy/) The Case Western Reserve University (CWRU) Autopsy Cohort was an Alzheimer’s Disease Research Center (ADRC) clinic-based sample. Subjects included in the Case Western Reserve Autopsy cohort include individuals who were… [Learn more](https://dss.niagads.org/cohorts/case-western-reserve-university-cwru-autopsy/) - [Case Western Reserve University (CWRU) Rapid Decline](https://dss.niagads.org/cohorts/case-western-reserve-university-cwru-rapid-decline/) The Case Western Reserve University (CWRU) Rapid Decline Cohort (Cohen et al. 2015) represents patients with rapid decline. Subjects included in the Case Western Reserve Rapid Decline dataset include individuals… [Learn more](https://dss.niagads.org/cohorts/case-western-reserve-university-cwru-rapid-decline/) - [Cuban American Alzheimer’s Disease Initiative (CuAADI)](https://dss.niagads.org/cohorts/cuban-american-alzheimers-disease-initiative-cuaadi/) The Cuban American Alzheimer’s Disease Initiative (CuAADI) is a convenience sample ascertained through community outreach to Alzheimer’s and adult day care centers in Southern Florida, lay conferences, and Neurology and Memory Disorders… [Learn more](https://dss.niagads.org/cohorts/cuban-american-alzheimers-disease-initiative-cuaadi/) - [Erasmus Rucphen Family (ERF)](https://dss.niagads.org/cohorts/erasmus-rucphen-family-erf/) A family-based cohort study that is embedded in the Genetic Research in Isolated Populations (GRIP) program in the South West of the Netherlands. The aim of this program was to… [Learn more](https://dss.niagads.org/cohorts/erasmus-rucphen-family-erf/) - [Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA)](https://dss.niagads.org/cohorts/estudio-familiar-de-influencia-genetica-en-alzheimer-efiga/) Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) included 683 at-risk family members from 242 AD-affected families of Caribbean Hispanic descent. These families have 2 or more individuals affected with Alzheimer’s… [Learn more](https://dss.niagads.org/cohorts/estudio-familiar-de-influencia-genetica-en-alzheimer-efiga/) - [Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD)](https://dss.niagads.org/cohorts/harmonized-diagnostic-assessment-of-dementia-for-the-longitudinal-aging-study-of-india-lasi-dad/) LASI-DAD is an in-depth study of late-life cognition and dementia. It draws a sub-sample of 4,000+ LASI respondents aged 60 and older and administers in-depth cognitive tests and informant interviews.… [Learn more](https://dss.niagads.org/cohorts/harmonized-diagnostic-assessment-of-dementia-for-the-longitudinal-aging-study-of-india-lasi-dad/) - [Hillblom Aging Network (HAN)](https://dss.niagads.org/cohorts/hillblom-aging-network/) Participants were enrolled in the Hillblom Aging Network at the University of California, San Francisco (UCSF) Memory and Aging Center. All participants underwent comprehensive neurobehavioral evaluations and met the following… [Learn more](https://dss.niagads.org/cohorts/hillblom-aging-network/) - [Indianapolis-Ibadan (IIAA/IIBD)](https://dss.niagads.org/cohorts/indianapolis-ibadan-iiaa/) The Indianapolis-Ibadan Dementia Project, established in 1991, is a longitudinal prospective population-based comparative epidemiological study of the prevalence and incidence rates and risk factors for Alzheimer’s disease and other age… [Learn more](https://dss.niagads.org/cohorts/indianapolis-ibadan-iiaa/) - [Knight Alzheimer’s Disease Research Center (KGAD)](https://dss.niagads.org/cohorts/knight-alzheimers-disease-research-center-kgad/) The search for novel risk factors for Alzheimer disease relies on access to accurate and deeply phenotyped datasets. The Memory and Aging Project at the Knight-ADRC (Knight ADRC-MAP) collects plasma,… [Learn more](https://dss.niagads.org/cohorts/knight-alzheimers-disease-research-center-kgad/) - [LonGenity](https://dss.niagads.org/cohorts/longenity/) The LonGenity study at Albert Einstein College of Medicine has been recruiting community dwelling Ashkenazi Jewish seniors aged 65 or older in the United States since 2008. Offspring of Parents… [Learn more](https://dss.niagads.org/cohorts/longenity/) - [Longevity Genes Project (LGP)](https://dss.niagads.org/cohorts/longevity-genes-project-lgp/) The Longevity Genes Project (LGP), established in 1998 at Albert Einstein College of Medicine, recruits Ashkenazi Jewish centenarians (age 95 and older) who are in general good health at age… [Learn more](https://dss.niagads.org/cohorts/longevity-genes-project-lgp/) - [Mayo Clinic (MAYO)](https://dss.niagads.org/cohorts/mayo/) All 248 cases and 98 controls consisted of Caucasian subjects from the United States ascertained at the Mayo Clinic. All subjects were diagnosed by a neurologist at the Mayo Clinic… [Learn more](https://dss.niagads.org/cohorts/mayo/) - [Mexican Health and Aging Study (MHAS)](https://dss.niagads.org/cohorts/mexican-health-and-aging-study-mhas/) The Mexican Health and Aging Study (MHAS) is a national longitudinal study of adults 50 years and older in Mexico. The baseline survey, with national and urban/rural representation of adults… [Learn more](https://dss.niagads.org/cohorts/mexican-health-and-aging-study-mhas/) - [Mount Sinai Brain Bank (MSBB)](https://dss.niagads.org/cohorts/mount-sinai-brain-bank-msbb/) Human brains were accessed from the Mount Sinai/JJ Peters VA Medical Center Brain Bank (MSBB–Mount Sinai NIH Neurobiobank) cohort, which holds over 2,040 well-characterized brains. This cohort was assembled after… [Learn more](https://dss.niagads.org/cohorts/mount-sinai-brain-bank-msbb/) - [National Centralized Repository for Alzheimer’s Disease and Related Dementias Family (NCRAD Family)](https://dss.niagads.org/cohorts/national-centralized-repository-for-alzheimers-disease-and-related-dementias-family-ncrad-family/) The National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD) family cohort was started in 1990 and consists of families with two or more members with early or late… [Learn more](https://dss.niagads.org/cohorts/national-centralized-repository-for-alzheimers-disease-and-related-dementias-family-ncrad-family/) - [National Institute of Aging Alzheimer’s Disease Family Based Study (NIA AD-FBS)](https://dss.niagads.org/cohorts/national-institute-on-aging-late-onset-of-alzheimers-disease-family-nia-load/) The FBS collection is a longitudinal, multi-center late onset AD sibling genetics initiative. This NIA-funded study began in 2,002 and maintains DNA and cell lines on families with 2 or… [Learn more](https://dss.niagads.org/cohorts/national-institute-on-aging-late-onset-of-alzheimers-disease-family-nia-load/) - [NIA Alzheimer's Disease Research Centers (ADRC)](https://dss.niagads.org/cohorts/nia-alzheimers-disease-research-centers-adrc/) The NIA ADRC cohort included subjects ascertained and evaluated by the clinical and neuropathology cores of the 32 NIA-funded ADRCs. Data collection is coordinated by the National Alzheimer’s Coordinating Center… [Learn more](https://dss.niagads.org/cohorts/nia-alzheimers-disease-research-centers-adrc/) - [Northern Manhattan Study (NOMAS)](https://dss.niagads.org/cohorts/northern-manhattan-study-nomas/) The Northern Manhattan Study (NOMAS) is a research study of stroke and stroke risk factors among the multi-ethnic community of Northern Manhattan, New York. The study is a collaboration between the… [Learn more](https://dss.niagads.org/cohorts/northern-manhattan-study-nomas/) - [Peru Alzheimer’s Disease Initiative (PeADI)](https://dss.niagads.org/cohorts/peru-alzheimers-disease-initiative-peadi/) The Peru Alzheimer’s Disease Initiative (PeADI) is being conducted at several sites in Peru including Lima (Marca-Ysabel et al. 2021). The Mestizo population living in Lima, the capital city, is comprised of… [Learn more](https://dss.niagads.org/cohorts/peru-alzheimers-disease-initiative-peadi/) - [Progressive Supranuclear Palsy (PSP)](https://dss.niagads.org/cohorts/progressive-supranuclear-palsy-psp/) Patients with a clinical Parkinsonism in life and neuropathological confirmation of Progressive Supranuclear Palsy (PSP) were identified from brain banks, research hospitals and neuropathologists. The top three contributing sites were… [Learn more](https://dss.niagads.org/cohorts/progressive-supranuclear-palsy-psp/) - [Puerto Rican 10/66 Study (PR1066)](https://dss.niagads.org/cohorts/puerto-rican-10-66-study-pr1066/) The Puerto Rican 10/66 Study (PR1066) (https://www.alz.co.uk/1066/), is an Alzheimer’s Disease International study of dementia in Puerto Rico that began in 2007 (Dr. Ivonne Jimenez-Velazquez, PI). Individuals were recruited as part… [Learn more](https://dss.niagads.org/cohorts/puerto-rican-10-66-study-pr1066/) - [Puerto Rican Alzheimer’s Disease Initiative (PRADI)](https://dss.niagads.org/cohorts/puerto-rican-alzheimers-disease-initiative-pradi/) The Puerto Rican Alzheimer’s Disease Initiative (PRADI) is a NIH NIA study of late-onset Alzheimer disease focused on the Caribbean-Hispanic Puerto Rican population. Participants were ascertained for an AD/ADRD Memory Study, including… [Learn more](https://dss.niagads.org/cohorts/puerto-rican-alzheimers-disease-initiative-pradi/) - [Religious Orders Study/Memory and Aging Project (ROSMAP)](https://dss.niagads.org/cohorts/religious-orders-study-memory-and-aging-project-rosmap/) The Religious Orders Study (ROS) is a longitudinal, epidemiologic clinical-pathological study of memory, motor, and functional problems in older Catholic nuns, priests, and brothers aged 65 years and older from… [Learn more](https://dss.niagads.org/cohorts/religious-orders-study-memory-and-aging-project-rosmap/) - [Research in African-American Alzheimer’s Disease Initiative (REAAADI)](https://dss.niagads.org/cohorts/research-in-african-american-alzheimers-disease-initiative-reaaadi/) The Research in African-American Alzheimer’s Disease Initiative (REAAADI) is a NIH NIA study focused on identifying genetic factors for Alzheimer disease within the African-American population in order to detect new targets for… [Learn more](https://dss.niagads.org/cohorts/research-in-african-american-alzheimers-disease-initiative-reaaadi/) - [Stanford Extreme Phenotypes in AD (StEP AD)](https://dss.niagads.org/cohorts/stanford-extreme-phenotypes-in-ad-step-ad/) This cohort contains samples from Brains for Dementia Research (BDR) Genetics project (Dr. Kevin Morgan, PI and Directory of the Alzheimer's Research UK (ARUK) DNA Consortium and BDR). The BDR… [Learn more](https://dss.niagads.org/cohorts/stanford-extreme-phenotypes-in-ad-step-ad/) - [Texas Alzheimer’s Research and Care Consortium (TARCC)](https://dss.niagads.org/cohorts/texas-alzheimers-research-and-care-consortium-tarcc/) Data from the Texas Alzheimer’s Research and Care Consortium (TARCC) includes cases enrolled at several major medical research institutions (as of 2013 this included Baylor College of Medicine, Texas Tech… [Learn more](https://dss.niagads.org/cohorts/texas-alzheimers-research-and-care-consortium-tarcc/) - [University of Miami (MIA)](https://dss.niagads.org/cohorts/university-of-miami-mia/) Each affected individual met NINCDS-ADRDA criteria for probable or definite AD with age at onset greater than 60 years, as determined from specific probe questions within the clinical history provided… [Learn more](https://dss.niagads.org/cohorts/university-of-miami-mia/) - [University of Miami Brain Bank (MBB)](https://dss.niagads.org/cohorts/university-of-miami-brain-bank-mbb/) The University of Miami Brain Bank Cohort was ascertained through self-referred cases and controls to the University of Miami Brain Endowment Bank, a National Institutes of Health (NIH) NeuroBioBank, one… [Learn more](https://dss.niagads.org/cohorts/university-of-miami-brain-bank-mbb/) - [University of Pittsburgh (PITT)](https://dss.niagads.org/cohorts/university-of-pittsburgh-pitt/) Study participants were enrolled at the University of Pittsburgh Alzheimer's Disease Research Center (ADRC), all of whom met the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and… [Learn more](https://dss.niagads.org/cohorts/university-of-pittsburgh-pitt/) - [University of Washington Families (RAS)](https://dss.niagads.org/cohorts/university-of-washington-families-ras/) 131 families with LOAD (751 individuals) were ascertained and evaluated through the University of Washington Alzheimer Disease Research Center. Clinical and neuropathological assessments of cases and controls, including blood sampling,… [Learn more](https://dss.niagads.org/cohorts/university-of-washington-families-ras/) - [Vanderbilt University (VAN)](https://dss.niagads.org/cohorts/vanderbilt-university-van/) The UM/VU dataset contains 1,186 cases and 1,135 CNEs (new and previously published) ascertained at the University of Miami and Vanderbilt University, including 409 autopsy-confirmed cases and 136 controls. An… [Learn more](https://dss.niagads.org/cohorts/vanderbilt-university-van/) - [Washington Heights and Inwood Community Aging project (WHICAP)](https://dss.niagads.org/cohorts/washington-heights-and-inwood-community-aging-project-whicap/) Unrelated Nondemented (initially), 65 years of age or older including non‐Hispanic whites (32%), African Americans (28%), and Caribbean Hispanics from the Dominican Republic (44%). Assessments include: medical evaluation, cognitive testing,… [Learn more](https://dss.niagads.org/cohorts/washington-heights-and-inwood-community-aging-project-whicap/) - [Wisconsin Registry for Alzheimer’s Prevention (WRAP)](https://dss.niagads.org/cohorts/wisconsin-registry-for-alzheimers-prevention-wrap/) The Wisconsin Registry for Alzheimer’s Prevention (WRAP) is an ongoing longitudinal observational cohort study of individuals age 40-65 at baseline who do not have dementia. Since 2001, WRAP has enrolled… [Learn more](https://dss.niagads.org/cohorts/wisconsin-registry-for-alzheimers-prevention-wrap/) ## Grants This work was supported by NIA grant 1RF1AG075051-01A1 to AJS. ## Acknowledgement ### Acknowledgment statement for any data distributed by NIAGADS: Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging. ### For investigators using Genotyping short tandem repeats using ADSP R4 data: This work was supported by NIA grant 1RF1AG075051-01A1 to AJS. The Alzheimer’s Disease Sequencing Project (ADSP) is comprised of two Alzheimer’s Disease (AD) genetics consortia and three National Human Genome Research Institute (NHGRI) funded Large Scale Sequencing and Analysis Centers (LSAC). The full acknowledgment for the ADSP dataset can be found here: [ADSP Acknowledgement](https://dss.niagads.org/datasets/ng00067/#acknowledgement) . ## Publications - Dolzhenko E. **ExpansionHunter: a sequence-graph-based tool to analyze variation in short tandem repeat regions.***Bioinformatics (Oxford, England). 2019 Nov 1.*[PubMed link](https://pubmed.ncbi.nlm.nih.gov/31134279/) - Dolzhenko E. **ExpansionHunter Denovo: a computational method for locating known and novel repeat expansions in short-read sequencing data.***Genome biology. 2020 Apr 28.*[PubMed link](https://pubmed.ncbi.nlm.nih.gov/32345345/)