"Evolutionary History and Associated Chromosomal Abnormalities of a Segmental
Duplicated Superstructure found on Chromosome 17"
Abstract:
Human chromosome 17 is enriched for segmental duplications, structural variations
& chromosomal abnormality. We have previously identified a segmental duplicated superstructure on the 17q arm. The structure consists of 13 discrete genomic domains significantly enriched for homologous sequence fragments and is found to associate with several retrotransposons.
Our present study is to delineate evolutionary history of duplicated structure and to analyze contribution of duplicated structure to 17q chromosomal abnormality. Specifically, we analyze genome maps of 10 additional mammals
(chimpanzee, orangutan, rhesus monkey, dog, cow, horse, mouse, rat, opossum and platypus). Only genome maps of primate show evidence of complex duplication superstructure. The association of the 2 specific retrotransposons to corresponding duplicated structure across evolutionary time suggests potential roles for retrotransposons serving as initial templates for accelerated chromosomal evolution. To analyze contribution of duplicated structure to structural abnormality on 17q, pairwise sequence comparisons are conducted between all possible duplicated domain pairs. Over 300 sequence fragments pairs are found to be highly homologous (>90%) and over 500bps in size. These sequence pairs serve as potential templates for non-allelic homologous recombination
(NAHR) resulting in chromosomal structural changes. Several well characterized chromosomal abnormalities such as NF1 deletion and BRCA1 gene deletion have been implicated. Lastly, the use of high throughput DNA sequencing technology to efficiently screen for sequence deletions in the region will be examined as well.