Assembly and annotation of an Ashkenazi human reference genome

Alaina Shumate^{1

2}, Aleksey V Zimin^{1

2}, Rachel M Sherman^{1

3}, Daniela Puiu^{1

3}, Justin M Wagner⁴, Nathan D Olson⁴, Mihaela Pertea^{1

2}, Marc L Salit⁵, Justin M Zook⁴, Steven L Salzberg^{6

7

8

9}

Affiliations

¹ Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA.
² Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
³ Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA.
⁴ National Institute of Standards and Technology, Gaithersburg, MD, USA.
⁵ Joint Initiative for Metrology in Biology, Stanford University, Stanford, CA, USA.
⁶ Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA. salzberg@jhu.edu.
⁷ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA. salzberg@jhu.edu.
⁸ Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA. salzberg@jhu.edu.
⁹ Department of Biostatistics, Johns Hopkins University, Baltimore, MD, USA. salzberg@jhu.edu.

PMID: 32487205
PMCID: PMC7265644
DOI: 10.1186/s13059-020-02047-7

Comparative Study

Assembly and annotation of an Ashkenazi human reference genome

Alaina Shumate et al. Genome Biol. 2020.

. 2020 Jun 2;21(1):129.

doi: 10.1186/s13059-020-02047-7.

Authors

Affiliations

¹ Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA.
² Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
³ Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA.
⁴ National Institute of Standards and Technology, Gaithersburg, MD, USA.
⁵ Joint Initiative for Metrology in Biology, Stanford University, Stanford, CA, USA.
⁶ Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA. salzberg@jhu.edu.
⁷ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA. salzberg@jhu.edu.
⁸ Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA. salzberg@jhu.edu.
⁹ Department of Biostatistics, Johns Hopkins University, Baltimore, MD, USA. salzberg@jhu.edu.

PMID: 32487205
PMCID: PMC7265644
DOI: 10.1186/s13059-020-02047-7

Abstract

Background: Thousands of experiments and studies use the human reference genome as a resource each year. This single reference genome, GRCh38, is a mosaic created from a small number of individuals, representing a very small sample of the human population. There is a need for reference genomes from multiple human populations to avoid potential biases.

Results: Here, we describe the assembly and annotation of the genome of an Ashkenazi individual and the creation of a new, population-specific human reference genome. This genome is more contiguous and more complete than GRCh38, the latest version of the human reference genome, and is annotated with highly similar gene content. The Ashkenazi reference genome, Ash1, contains 2,973,118,650 nucleotides as compared to 2,937,639,212 in GRCh38. Annotation identified 20,157 protein-coding genes, of which 19,563 are > 99% identical to their counterparts on GRCh38. Most of the remaining genes have small differences. Forty of the protein-coding genes in GRCh38 are missing from Ash1; however, all of these genes are members of multi-gene families for which Ash1 contains other copies. Eleven genes appear on different chromosomes from their homologs in GRCh38. Alignment of DNA sequences from an unrelated Ashkenazi individual to Ash1 identified ~ 1 million fewer homozygous SNPs than alignment of those same sequences to the more-distant GRCh38 genome, illustrating one of the benefits of population-specific reference genomes.

Conclusions: The Ash1 genome is presented as a reference for any genetic studies involving Ashkenazi Jewish individuals.

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Conflict of interest statement

None.

Figures

**Fig. 1**
Snapshot showing alignments of long PacBio reads to the Ash1 genome, centered on the left end of the location in chromosome 20 (position 65,079,275) where a translocation occurred between chromosome 15 (GRCh38) and 20 (Ash1). The top portion of the figure shows the coordinates on chr20. Below that is a histogram of read coverage, and the individual reads fill the bottom part of the figure. The indels in the reads, shown as colored bars on each read, are due to the relatively high error rate of the long reads

See this image and copyright information in PMC

References

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Assembly and annotation of an Ashkenazi human reference genome

Affiliations

Assembly and annotation of an Ashkenazi human reference genome

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources