The Necessity of Diploid Genome Sequencing to Unravel the Genetic Component of Complex Phenotypes

Schroeder, Julian

doi:10.3389/fgene.2017.00148

Cited by 7 publications

(4 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have highlighted the importance of including haplotype information and more complete SV identification in genome studies (Chaisson et al 2017, 2017). Analyzing human genomes in their diploid context will be a critical step forward in genome analysis (Aleman 2017). Toolkits that support the representation of sequence and variation, a necessary component of supporting true, diploid assembly, are now becoming available (Garrison et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Resolving the Full Spectrum of Human Genome Variation using Linked-Reads

Marks

Garcia

Barrio

et al. 2017

Preprint

157

View full text Add to dashboard Cite

Large-scale population based analyses coupled with advances in technology have demonstrated that the human genome is more diverse than originally thought. To date, this diversity has largely been uncovered using short read whole genome sequencing. However, standard short-read approaches, used primarily due to accuracy, throughput and costs, fail to give a complete picture of a genome. They struggle to identify large, balanced structural events, cannot access repetitive regions of the genome and fail to resolve the human genome into its two haplotypes. Here we describe an approach that retains long range information while harnessing the advantages of short reads. Starting from only~ ng of DNA, we produce barcoded short read libraries. The use of novel informatic approaches allows for the barcoded short reads to be associated with the long molecules of origin producing a novel datatype known as 'Linked-Reads'. This approach allows for simultaneous detection of small and large variants from a single Linked-Read library. We have previously demonstrated the utility of whole genome Linked-Reads (lrWGS) for performing diploid, de novo assembly of individual genomes (Weisenfeld et al. ). In this manuscript, weshow the advantages of Linked-Reads over standard short read approaches for reference based analysis. We demonstrate the ability of Linked-Reads to reconstruct megabase scale haplotypes and to recover parts of the genome that are typically inaccessible to short reads, including phenotypically important genes such as STRC, SMN and SMN . We demonstrate the ability of both lrWGS and Linked-Read Whole Exome Sequencing (lrWES) to identify complex structural variations, including balanced events, single exon deletions, and single exon duplications. The data presented here show that Linked-Reads provide a scalable approach for comprehensive genome analysis that is not possible using short reads alone.

show abstract

Section: Discussionmentioning

confidence: 99%

Resolving the Full Spectrum of Human Genome Variation using Linked-Reads

Marks

Garcia

Barrio

et al. 2017

Preprint

157

View full text Add to dashboard Cite

show abstract

“…The genetic research of sika deer and related development efforts have not been commensurate with its importance due to the scarcity of genome resources. Currently, we decode the first high-quality haplotype-resolved chromosome-scale genome of diploid sika deer by combining the new sequencing technology and Hi-C scaffolding, which is critical for studying the role of variation in genome function and phenotype [37] . We constructed the expression profile of alleles in the sika deer antler, and proposed the possible molecular basis for rapid antler growth.…”

Section: Discussionmentioning

confidence: 99%

Haplotype-Resolved Genome of Sika Deer Reveals Allele-Specific Gene Expression and Chromosome Evolution

Han

Zhao

et al. 2022

Genomics, Proteomics &Amp; Bioinformatics

View full text Add to dashboard Cite

Despite the scientific and medicinal importance of diploid sika deer (Cervus nippon), its genome resources are limited and haplotype-resolved chromosome-scale assembly is urgently needed. To explore mechanisms underlying the expression patterns of the allele-specific genes in antlers and the chromosome evolution in Cervidae, we report, for the first time, a high-quality haplotype-resolved chromosome-scale genome of sika deer by integrating multiple sequencing strategies, which was anchored to 32 homologous groups with a pair of sex chromosomes (XY). Several expanded genes (RET, PPP2R1A, PPP2R1B, YWHAB, YWHAZ, and RPS6) and positively selected genes (eIF4E, Wnt8A, Wnt9B, BMP4, and TP53) were identified, which could contribute to rapid antler growth without carcinogenesis. A comprehensive and systematic genome-wide analysis of allele expression patterns revealed that most alleles were functionally equivalent in regulating rapid antler growth and inhibiting oncogenesis. Comparative genomic analysis revealed that chromosome fission might occur during the divergence of sika deer and red deer (Cervus elaphus), and the olfactory sensation of sika deer might be more powerful than that of red deer. Obvious inversion regions containing olfactory receptor genes were also identified, which arose since the divergence. In conclusion, the high-quality allele-aware reference genome provides valuable resources for further illustration of the unique biological characteristics of antler, chromosome evolution, and multi-omics research of cervid animals.

show abstract

“…These key elements makes future prospects of this technology include reference-free assembly of complex metagenomic samples and haplotype-resolved genomes from single cells in simple workflows with cost-efficient library preparation. For the purpose of expanding our understanding of population diversity and individual variance, the next frontier for large-scale genomics ought to be de novo and haplotype-resolved genome analyses 30 . The rise of long read sequencing and linked-read platforms show that more and more researchers are realizing the benefits of long-range phasing information.…”

Section: Discussionmentioning

confidence: 99%

High throughput barcoding method for genome-scale phasing

Redin

Frick

Aghelpasand

et al. 2019

Sci Rep

View full text Add to dashboard Cite

The future of human genomics is one that seeks to resolve the entirety of genetic variation through sequencing. The prospect of utilizing genomics for medical purposes require cost-efficient and accurate base calling, long-range haplotyping capability, and reliable calling of structural variants. Short-read sequencing has lead the development towards such a future but has struggled to meet the latter two of these needs. To address this limitation, we developed a technology that preserves the molecular origin of short sequencing reads, with an insignificant increase to sequencing costs. We demonstrate a novel library preparation method for high throughput barcoding of short reads where millions of random barcodes can be used to reconstruct megabase-scale phase blocks.

show abstract

The Necessity of Diploid Genome Sequencing to Unravel the Genetic Component of Complex Phenotypes

Cited by 7 publications

References 19 publications

Resolving the Full Spectrum of Human Genome Variation using Linked-Reads

Resolving the Full Spectrum of Human Genome Variation using Linked-Reads

Haplotype-Resolved Genome of Sika Deer Reveals Allele-Specific Gene Expression and Chromosome Evolution

High throughput barcoding method for genome-scale phasing

Contact Info

Product

Resources

About