COLD SPRING HARBOR, NY (GenomeWeb News) – Different formation mechanisms may underlie differences in structural variation seen in primate genomes, said Verena Tischler, a graduate student at the European Molecular Biology Laboratory in Heidelberg, Germany during a presentation at the Biology of Genomes meeting here.
In humans, structural variations have been linked to a number of disease states, including autism and schizophrenia. But their extent, formation mechanisms, and impact on other primates have not been as clear.
To address some of those gaps, "we wanted to establish whole-genome sequencing-based maps of structural variation in chimpanzees, orangutans, and rhesus macaques," Tischler said.
With such a map, she and her colleagues examined the mechanisms at work in primates that drive the formation of de novo structural variation. There are a handful of ways such large-scale variations can arise, including through non-allelic homologies, mobile elements, variable number of tandem repeats, and non-homologous rearrangements.
Subsequently, with, RNA-seq data, they studied whether such changes had functional effects.
Tischler and her colleagues sequenced five genomes each of chimpanzees, orangutans, and rhesus macaques, and validated their structural variation calls using a number of techniques, including PCR, qPCR, and FISH. From this, they developed a single-nucleotide resolution map of structural variations and segmental duplications in these primates.
"Once we mapped the structural variations … we just looked and compared the different genomic impacts," she added.
The maps, she said, incorporated thousands of novel changes — including deletions, duplications, and insertions of mobile elements — and revealed differences in the impact of such changes on the genome.
Tischler and her colleagues noted that the mechanisms underlying structural variations differed between the two great apes and the rhesus macaque. For example, in the great apes, non-allelic homologous recombination contributed to about 28 percent of structural variation, but in rhesus monkeys, the combination contributed to a substantially smaller percentage of structural variation. Further, retrotransposons like LINEs also showed variable effects on the primate genomes.
Using their RNA-seq data, Tischler and her colleagues looked at the functional impact of structural variation, particularly gene duplication events. They identified 13 gene duplications that were correlated with gains of expression.
Of those 13 candidate genes, five are linked to brain development while four are associated with the immune system, Tischler noted. This suggested that duplications could be linked to the gain of new functions. She added that they are continuing research on those genes.