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Principal Investigator: Graham Scott Erwin
Organization: BAYLOR COLLEGE OF MEDICINE
Fiscal Year: 2024
Award: $249,000
Funding agency: National Human Genome Research Institute
Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), causes more than 30
rare but devastating diseases. Despite their importance to monogenic disease, the frequency and function of
repeat expansions are unknown in complex human diseases. A failure to catalog and understand these repeat
expansions in human disease will make it impossible to capitalize on this information to develop new TR-
targeting therapeutics, which I previously showed can rescue expression of genes dysregulated in disease
(Erwin et al., Science 2017).
My central hypothesis is that repeat expansions are recurrent in complex human diseases and alter cell
function through the regulation of gene expression. While I have extensive training and experience in the study
of TRs with chemical biology, molecular biology, and functional genomics, I am new to bioinformatics and
human genetics. Therefore, my overall objective is to obtain additional training in bioinformatics and human
genetics and to catalog recurrent repeat expansions and determine their relevance to human disease. This
study is the next logical step toward my goal of becoming an independent investigator studying TR sequences
in the genome. To achieve my goal, I will take full advantage of the excellent training environment at Stanford
University.
The expected outcomes include a new set of bioinformatic tools to identify repeat expansions (Aim 1)
and a catalog of recurrent repeat expansions in human disease (Aim 2), which will provide a new angle to
analyze thousands of NIH-funded, publicly-available human genome datasets. Furthermore, characterizing the
function of previously-unrecognized, recurrent repeat expansions will determine whether some of these
expansions are functionally important for human disease (Aim 3). The proposed study will enable me to apply
my background in TR biology to an important problem while receiving additional training in bioinformatics and
human genetics and preparing me for a successful career as an independent investigator. These results will
illuminate our understanding of the human genome and set the stage for a new class of precision-targeted
therapeutics.
Terms: <3-D><3-Dimensional><3D><Accounting><Affect><Bio-Informatics><Bioinformatics><Biology><CRISPR><CRISPR/Cas system><Cancer Genes><Cancer-Promoting Gene><Cancers><Catalogs><Cell Function><Cell Physiology><Cell Process><Cell Survival><Cell Viability><Cellular Function><Cellular Physiology><Cellular Process><Chemicals><Chromatin><Clustered Regularly Interspaced Short Palindromic Repeats><Communities><Complex><Copy Number Polymorphism><DNA><DNA Molecular Biology><DNA Sequence><DNA seq><DNA sequencing><DNAseq><Darkness><Data><Data Set><Deoxyribonucleic Acid><Detection><Development><Disease><Disorder><Dystrophia Myotonica><Environment><Escalante syndrome><FDA approved><Failure><Fragile X><Fragile X Syndrome><Frequencies><Funding><Gene Action Regulation><Gene Expression><Gene Expression Regulation><Gene Regulation><Gene Regulation Process><Genetic Diseases><Genetic Diversity><Genetic Variation><Genome><Goals><Grawitz Tumor><Human Genetics><Human Genome><Hypernephroid Carcinoma><Hypernephroma><Intervening Sequences><Introns><Investigators><Malignant Neoplasms><Malignant Tumor><Maps><Martin-Bell Syndrome><Martin-Bell-Renpenning syndrome><Mendelian disease><Mendelian disorder><Mendelian genetic disorder><Mental disorders><Mental health disorders><Methods><Molecular Biology><Myotonia Atrophica><Myotonia Dystrophica><Myotonic Dystrophy><NHGRI><NIH><National Center for Human Genome Research><National Human Genome Research Institute><National Institutes of Health><Nephroid Carcinoma><Nucleic Acid Regulator Regions><Nucleic Acid Regulatory Sequences><Oncogenes><Outcome><Pathogenicity><Phase><Psychiatric Disease><Psychiatric Disorder><Public Health><Publishing><Recurrence><Recurrent><Regulatory Regions><Renal Adenocarcinoma><Renal Cell Adenocarcinoma><Renal Cell Cancer><Renal Cell Carcinoma><Renpenning syndrome 2><Research><Research Personnel><Researchers><Role><Sampling><Science><Sensitivity and Specificity><Steinert Disease><Structure><Subcellular Process><TCGA><Tandem Repeat Sequences><Tandem Repeats><Testing><The Cancer Genome Atlas><Training><Transforming Genes><UGT2B7><UGT2B7 UDP-glucuronosyltransferase><UGT2B9><United States National Institutes of Health><Universities><Variant><Variation><X-linked mental deficiency-megalotestes syndrome><X-linked mental retardation with fragile X syndrome><X-linked mental retardation-fragile site 1 syndrome><autism-fragile X (AFRAX) syndrome><bio-informatics pipeline><bio-informatics tool><bioinformatics pipeline><bioinformatics tool><career><catalog><copy number variant><copy number variation><developmental><dystrophic myotonia><experience><fra(X) syndrome><fra(X)(28) syndrome><fra(X)(q27) syndrome><fra(X)(q27-28) syndrome><fragile X-mental retardation syndrome><fragile Xq syndrome><fragile site mental retardation 1><functional genomics><genetic condition><genetic disorder><genetic regulatory element><genome scale><genome-wide><genomewide><genomic data><genomic data-set><genomic dataset><genomic tools><human disease><human whole genome><improved><kidney adenocarcinoma><macro-orchidism-marker X (MOMX) syndrome><macro-orchidism-marker X syndrome><malignancy><mar(X) syndrome><marker X syndrome><mental illness><mental retardation-macroorchidism syndrome><monogenic disease><monogenic disorder><neoplasm/cancer><psychiatric illness><psychological disorder><response><single-gene disease><single-gene disorder><social role><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><three dimensional><tool>