A standard data format for a genomic circos plot would be where each row is a data point and each column represents a variable like chromosome, position, p-value, gene expression, etc.
The need to accurately identify the complete structural variation profile of genomes is becoming increasingly evident. In contrast to reference-based methods like sequencing or comparative methods like aCGH, optical mapping is a de novo assembly-based method that enables better realization of true genomic structure.
What role do structural variations play in autism?
Beginning with cytogenetics studies in the 1970s and continuing through the eras of SNP arrays and sequencing, it has been established that many structural variants are implicated in ASD. Large chromosomal abnormalities may be responsible for about 10% of all cases, although some estimates are substantially higher. There are several hotspots for copy number variants, including deletions or duplications on chromosome 16p11.2 and duplication of 22q11.2. I think that 10% is a low estimate because many cryptic structural variations are likely to contribute to ASD. Our ability to “see” structural variation has been relatively limited, so we don’t yet know the true proportion of structural variations that have causal roles.
How has genome mapping impacted your understanding of structural variations in autism?
We are studying the case of a girl who has autism spectrum disorder, global developmental delay, and severe self-injurious behavior. She has a three-way translocation involving chromosomes 3, 10, and 14. We obtained whole genome sequence data at standard (30x) depth of coverage using short-read sequencing technology, and this was useful to begin mapping the breakpoints. But this technology was not sufficient to gain a complete understanding of the nature of the translocations in the mother (who is a carrier harboring balanced translocations) and the affected child.
Using genome mapping we have been able to identify the translocations at high resolution and resolve extremely complex structural variation. Our goal is to further understand which genes are disrupted by the translocations to explore whether any therapeutic intervention is possible based on a new understanding of the genomic basis of the child’s condition.