Building the sequence map of the human pan-genome

Abstract

Here we integrate the de novo assembly of an Asian and an African genome with the NCBI reference human genome, as a step toward constructing the human pan-genome. We identified approximately 5 Mb of novel sequences not present in the reference genome in each of these assemblies. Most novel sequences are individual or population specific, as revealed by their comparison to all available human DNA sequence and by PCR validation using the human genome diversity cell line panel. We found novel sequences present in patterns consistent with known human migration paths. Cross-species conservation analysis of predicted genes indicated that the novel sequences contain potentially functional coding regions. We estimate that a complete human pan-genome would contain approximately 19-40 Mb of novel sequence not present in the extant reference genome. The extensive amount of novel sequence contributing to the genetic variation of the pan-genome indicates the importance of using complete genome sequencing and de novo assembly.

Structural variation in two human genomes mapped at single-nucleotide resolution by whole genome de novo assembly

“…For indels, most of the variants identified by our approach, of which only 5.6% are expected to be false positives, were not identified by BreakDancer or pIndel (Supplementary Notes and Supplementary Tables 3 and 4 for additional comparisons with other methods, including array comparative genomic hybridization, assemblies obtained using Sanger-sequencing data and a hybrid strategy 23 that incorporates the results of several approaches). These discrepancies between our method and BreakDancer and/or pIndel in the structural variation predictions could be attributed to the varied read lengths (30-75 bp) and library insert sizes 44 used to sequence the YH genome. In summary, our approach provides an accurate method to determine structural variations of different lengths and types.…”

The perspective from EASAC and FEAM on direct-to-consumer genetic testing for health-related purposes

“…However, within the global context, difficulties in interpreting the gene-disease association evidence base are accentuated by differences in the relevance of genetic information for disease susceptibility and drug responsiveness in different populations. 34 There are major implications for a global DTC industry, necessitating global databases on DNA variants and their phenotypes. EASAC-FEAM recommended that these issues be addressed in the WHO global public health initiative 35 to identify genomic research priorities.…”

Why prokaryotes have pangenomes

“…For example, the human pangenome is thought to have between 15-40 Mb of accessory DNA, approximately 0.5-1.3% 14 , while the 14 genomes of the Coccolithophore Emiliania huxleyi, have only 69.5% of identified genes common to all genomes. However, in eukaryotes gene inheritance is somewhat different, with lower HGT levels than in prokaryotes 15 and higher levels of gene duplication 16 .…”