Extensive genomic, transcriptional diversity identified through massively parallel DNA and RNA sequencing

In a paper published in the online edition of Nature Genetics on July 3, 2011, sequencing specialists at Axeq Technologies, and scientists from Macrogen Inc., Genomic Medicine Institute at Seoul National University, Psoma Therapeutics Inc., Brigham and Women's Hospital and Harvard Medical School reported the discovery of a wide range of novel genetic variants based on the deep sequencing of 18 genomes and 17 transcriptomes of unrelated Korean individuals.

“Extensive genomic and transcriptional diversity identified through massively parallel DNA and RNA sequencing of eighteen Korean individuals”

The analysis of the genomic and transcriptomic data enabled the identifications of 9.56 million genomic variants, 23.2% of which appear to be previously unidentified, and 4,414 novel transcripts.

When comparing the genomic and transcriptomic data, 1,809 sites of transcriptional base modifications were detected, where the transcriptional landscape is different from the corresponding genomic sequences. Approximately 90% of these modifications were located in untranslated regions, suggesting potential functional roles in modifying mRNA stability.

"We identified a considerable number of new variants and found that many rare putative functional variants likely remain to be identified despite major efforts in recent years to catalog human genomic variation. Indeed, our findings suggest that a substantial number of Korean common functional variants may not be tagged well by neighboring 'tagging' SNPs on microarrays. These results suggest that many association studies may have fundamental limitations, especially for populations that were not included in the initial LD assessments on the human genome," said Jeong-Sun Seo, chairman of Axeq Technologies and professor of medicine at the Seoul National University.

With the experience gained from the analysis of the massive genomic and transcriptomic data, Axeq scientists have also concluded the following findings that may benefit researchers in their designs of sequencing strategies -

• Increased lengths of sequencing reads are highly advantageous for short indel detections
• Low-coverage sequencing may miss short indels despite longer read length, especially for heterozygous indels
• Copy number deletions can be detected accurately using whole-genome sequencing, especially if data from multiple genomes can be compared.
• Increased read length of short reads improved efficiency for identification of exact breakpoints in large deletions
• Sequencing with high-coverage and longer DNA reads is necessary for specific structural variations such as smaller deletions (50-500 bp), copy number gains, DNA insertions and inversions.

Axeq Technologies specializes in a wide variety of next-generation sequencing applications, and offer both sequencing and data analysis services. With the "Axeq Turnkey Discovery" services, investigators can access our sequencing specialists and bioinformaticians to formulate specific sequencing strategies. The same Axeq's sequencing team that generated the data for this Nature Genetics article will handle all clients' projects. Axeq's corporate mission is to provide publication-quality data and to exceed client's expectations at all levels.