AsianScientist (Jul. 28, 2011) – Scientists at BGI in China have developed a novel whole-genome de novo assembly strategy to map structural variations (SVs) in individual genomes.
In the study which was published online in Nature Biotechnology this week, the researchers demonstrated the method’s utility by characterizing SVs in the genomes of two individuals, one Asian and one African, sequenced by second-generation sequencing technologies.
Although various methods have been used to characterize SVs in other genome sequencing studies, they were limited by technical constraints and the complexity of certain types of SV.
“The study was confronted with many difficulties at the start, such as alignment accuracy, rearranged structure (non-linear), breakpoint recovery, and background noises,” said Li Yingrui, co-lead author of the study.
The BGI scientists overcame these challenges by using a strategy that assembled genomes de novo rather than by mapping short sequences onto a reference human genome.
After assembling the genomes, their pipeline could identify small- and intermediate-sized homozygous SVs (ranging from a single base pair to 50,000 base pairs) that were difficult to detect using other approaches. These SVs included insertions, deletions, inversions, and complex rearrangements.
Using their pipeline, the scientists identified 277,243 SVs ranging in size from one base pair to 23,000 base pairs in the assembled regions of both the Asian and African genomes. Many of these SVs were validated through experimental and computational methods, indicating that the method has a high degree of accuracy in detecting SVs.
The researchers then determined the frequency of their identified SVs in the genomes of 106 individuals, available as part of the 1000 Genomes Project pilot study. They found that SVs occurred at a lower frequency than single-nucleotide polymorphisms (SNPs) and were more likely to be associated with strong biological effects.
Their analyses suggest that SVs may be more specific to individuals than SNPs and may be more useful in explaining phenotypic differences between individuals.
“This study makes us understand we need to consider all kinds of genetic variations and potential differences in their impacts on disease and various other phenotypes in medical genomics studies in the future,” said Li.
This study also revealed that de novo assembly of genomes from sequencing studies result in personal genomes that are complete than those obtained from mapping onto a reference human genome, suggesting that many more human genomes should be assembled de novo in future.
The article can be found at: Li Y et al. (2011) Structural variation in two human genomes mapped at single-nucleotide resolution by whole genome de novo assembly.
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Source: BGI.
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