Human Reference point techniques suggestions inside 2021 

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Human Reference point techniques suggestions inside 2021 

Na12878 Human Reference On Oxford Nanopore Minion

The CG SNPs for these individuals should form a super set of those SNPs detected by 1KGP. Surprisingly, a substantial number (19%) of SNPs are still unique to one of the two platforms when comparing the same genomes. This difference is much greater than would be expected and is likely due to differences between data collection and analysis methods in the CG and 1KGP projects. Specifically, the CG genomes were genotyped individually without any reliance on other genomic sequences. Due to the low-coverage of the sequencing in the 1000 Genomes Data , multiple genomes were genotyped together and variation data was imputed between genomes.

The authors explain very well the limitations of the linear reference genome, and describe how a pangenome graph reference would be superior. And it is great that the Conclusions section also raises important non-technical matters related to pangenomes, such as privacy concerns. The purpose of the codeathon was two-fold, to propose technical specifications and standards for a usable human pangenome and to build tools for genome graphs.

We then examined all single-nucleotide variants (SNVs, see the “Methods”) between PGP17 and each of the two reference genomes. To simplify the analysis, we only considered locations where PGP17 was homozygous. In our comparisons to Ash1, we first identified all SNVs and then examined the original Ash1 read data to determine whether, for each of those SNVs, the Ash1 genome contained a different allele that matched PGP17. This was the first major release of the human reference assembly made by the GRC.

There’s no disagreement that, without a more representative reference genome, genetic medicine will never reach some ethnic groups, warns genome scientist Alicia Martin of Mass. Medical genetics is moving away from assessing disease risk from one or two genes and toward calculating a “polygenic risk score” based on hundreds. Several labs have tried to remedy the ethnic bias of the reference genome by producing Chinese, Korean, and Ashkenazi reference genomes. The problem is, people are often mistaken about their ancestry, so geneticists would get nowhere by trying to compare someone’s genome sequence to the wrong reference.

The pipeline would serve as a proof of concept for a graph based approach for inferring allele-specific transcript expression when an individual’s haplotypes are available, similar to the personal genome approach (Rozowsky et al., 2011). The reference genome is not a ‘healthy’ genome, ‘nor the most common, nor the longest, nor an ancestral haplotype’ . Efforts to fix these ‘errors’ include adjusting alleles to the preferred or major allele or the use of targeted and ethnically matched genomes. To create Ash1 v1.3, we added 2,786,257 bases to the beginning of the X chromosome and 2,281,641 bases to the beginning of the Y chromosome, based on careful alignments to GRCh38.

Nonetheless, a reference genome sequence is clearly needed for research. Without a point of reference and common coordinate, or naming system, research and clinical assay results cannot be reported in ways that allow for inter-lab comparisons and independent validation of research results. There are many important questions yet to be addressed as to how to best approach developing a universal reference sequence and establish best practices for using it. Addressing population and individual variability in a universal reference requires that we think about the genome, not as a single sequence, but rather as a union of differences. A basic coordinate system needs to be developed that can accommodate any indel and rearrangements, and analytical tools need to assume higher levels of differences than they do now.

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