Gabriel Rosanio

Genetic studies of autism spectrum disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variants (SVs) has been restricted by the coarse resolution of current approaches. By applying a custom pipeline for SV discovery, genotyping, and de novo assembly to genome sequencing of 235 subjects (71 affected individuals, 26 healthy siblings, and their parents), we compiled an atlas of 29,719 SV loci (5,213/genome), comprising… Show more

Genetic studies of autism spectrum disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variants (SVs) has been restricted by the coarse resolution of current approaches. By applying a custom pipeline for SV discovery, genotyping, and de novo assembly to genome sequencing of 235 subjects (71 affected individuals, 26 healthy siblings, and their parents), we compiled an atlas of 29,719 SV loci (5,213/genome), comprising 11 different classes. We found a high diversity of de novo mutations, the majority of which were undetectable by previous methods. In addition, we observed complex mutation clusters where combinations of de novo SVs, nucleotide substitutions, and indels occurred as a single event. We estimate a high rate of structural mutation in humans (20%) and propose that genetic risk for ASD is attributable to an elevated frequency of gene-disrupting de novo SVs, but not an elevated rate of genome rearrangement. Show less

A novel protocol was devised to select for DNA molecules that efficiently form circles from a library of DNAs containing randomized base pairs. Several rounds of this selection resulted in a sub-library that formed circles significantly more efficiently than the initial library. Sequence analysis of this sub-library uncovered a strong and highly detailed motif family correlated with this increased circlization efficiency. This sub-library's sequence characteristics closely match those present… Show more

A novel protocol was devised to select for DNA molecules that efficiently form circles from a library of DNAs containing randomized base pairs. Several rounds of this selection resulted in a sub-library that formed circles significantly more efficiently than the initial library. Sequence analysis of this sub-library uncovered a strong and highly detailed motif family correlated with this increased circlization efficiency. This sub-library's sequence characteristics closely match those present in accurately mapped yeast nucleosomes, confirming the importance of DNA bending in nucleosome formation. Further, disagreements between the data sets suggesting sequence specific contacts that form between histones and DNA. Show less