Single Amino Acid Repeat Proteins (SARPs) are a class of peptides that contain extended stretches of the same amino acid. At the DNA level they are represented by a repetition of the same triplet of bases. Their influence can be on gene regulation, transcription and protein function depending on the number of repeats. Mutations that add or subtract repeat units are both frequent and reversible.
Several human diseases have been identified that are caused by variations in the size of repeated DNA sequences. Animal and plant genetic studies showed that variations in repeat sequences can lead to complex phenotypes and that variations within a normal (i.e. non-pathological) range of repeat number commonly yields small, quantitative functional effects.
Even though triplet repeats present an intriguing disease mechanism for other complex human diseases, methods for a fast, inexpensive and systematic search have never been utilized. We have devised an assay that can be used for a high throughput, genome wide detection of SARPs in those diseases. We have optimized our method for low cost and validated our results through direct sequencing.
We also showed that inferring SARP alleles from SNP data derived from genome wide association studies (GWAS) is often not possible and therefore a SNP based GWAS approach will be underpowered or may even fail if the disease studied is caused by a triplet repeat allele. In addition, we found that current methods of next generation sequencing may miss the detection of triplet repeat variations, probably due to technical limitations of the technology.
|Commitee:||Ball, William, Johnson, Jeffrey|
|School:||University of Cincinnati|
|School Location:||United States -- Ohio|
|Source:||DAI-B 72/07, Dissertation Abstracts International|
|Subjects:||Genetics, Biochemistry, Biomedical engineering|
|Keywords:||Amino acid repeat proteins, HapMap tagSNPs, Polymorphisms, Repeat variations, Repeated DNA sequences, Triplet repeats|
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