Novel functional sequences uncovered through a bovine multi-assembly graph

Crysnanto, Danang; Leonard, Alexander S.; Fang, Zih-Hua; Pausch, Hubert

doi:10.1101/2021.01.08.425845

Cited by 6 publications

(4 citation statements)

References 72 publications

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“…By aligning the five cattle assemblies, we illustrate that a substantial portion of the cattle pan-genome is likely missing from the Hereford reference. The amount of non-reference sequence identified by our approach broadly matches that from another study using a different but overlapping set of genomes and graph assembly approach 33 . This has important implications for cattle research as it suggests significant amounts of the bovine genome is inaccessible in most current analyses.…”

Section: Discussionsupporting

confidence: 68%

A cattle graph genome incorporating global breed diversity

et al. 2022

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Despite only 8% of cattle being found in Europe, European breeds dominate current genetic resources. This adversely impacts cattle research in other important global cattle breeds, especially those from Africa for which genomic resources are particularly limited, despite their disproportionate importance to the continent’s economies. To mitigate this issue, we have generated assemblies of African breeds, which have been integrated with genomic data for 294 diverse cattle into a graph genome that incorporates global cattle diversity. We illustrate how this more representative reference assembly contains an extra 116.1 Mb (4.2%) of sequence absent from the current Hereford sequence and consequently inaccessible to current studies. We further demonstrate how using this graph genome increases read mapping rates, reduces allelic biases and improves the agreement of structural variant calling with independent optical mapping data. Consequently, we present an improved, more representative, reference assembly that will improve global cattle research.

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Section: Discussionsupporting

confidence: 68%

A cattle graph genome incorporating global breed diversity

et al. 2022

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“…However, there are currently few high-quality graph genomes available. In livestock, the use of graph genomes has so far been restricted to studies simply incorporating variants from short read sequencing data into the Hereford reference 16,17 or to only very large differences between the assemblies themselves 18 . Although not able to capture wider cattle diversity, these studies illustrated that the variant calls using the graph genome were more consistent between sire-son pairs than those obtained using the linear Hereford reference, with the current standard variant calling algorithms GATK HaplotypeCaller 19 and FreeBayes 20 .…”

Section: Introductionmentioning

confidence: 99%

A cattle graph genome incorporating global breed diversity

Talenti

Powell

Hemmink

et al. 2021

Preprint

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Despite only 8% of cattle being found in Europe, European breeds dominate current genetic resources. This adversely impacts cattle research in other important global cattle breeds. To mitigate this issue, we have generated the first assemblies of African breeds, which have been integrated with genomic data for 294 diverse cattle into the first graph genome that incorporates global cattle diversity. We illustrate how this more representative reference assembly contains an extra 116.1Mb (4.2%) of sequence absent from the current Hereford sequence and consequently inaccessible to current studies. We further demonstrate how using this graph genome increases read mapping rates, reduces allelic biases and improves the agreement of structural variant calling with independent optical mapping data. Consequently, we present an improved, more representative, reference assembly that will improve global cattle research.

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“…Data supporting this study, including the multiassembly graph, nonreference sequences, nonreference genes, transcript abundances, and sequence variants detected from nonreference sequences are available via Zenodo (https://zenodo.org/record/4385983#. YHQwER8zbIU) (74).…”

mentioning

confidence: 99%

Novel functional sequences uncovered through a bovine multiassembly graph

Crysnanto

Leonard

Fang

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Many genomic analyses start by aligning sequencing reads to a linear reference genome. However, linear reference genomes are imperfect, lacking millions of bases of unknown relevance and are unable to reflect the genetic diversity of populations. This makes reference-guided methods susceptible to reference-allele bias. To overcome such limitations, we build a pangenome from six reference-quality assemblies from taurine and indicine cattle as well as yak. The pangenome contains an additional 70,329,827 bases compared to the Bos taurus reference genome. Our multiassembly approach reveals 30 and 10.1 million bases private to yak and indicine cattle, respectively, and between 3.3 and 4.4 million bases unique to each taurine assembly. Utilizing transcriptomes from 56 cattle, we show that these nonreference sequences encode transcripts that hitherto remained undetected from the B. taurus reference genome. We uncover genes, primarily encoding proteins contributing to immune response and pathogen-mediated immunomodulation, differentially expressed between Mycobacterium bovis–infected and noninfected cattle that are also undetectable in the B. taurus reference genome. Using whole-genome sequencing data of cattle from five breeds, we show that reads which were previously misaligned against the Bos taurus reference genome now align accurately to the pangenome sequences. This enables us to discover 83,250 polymorphic sites that segregate within and between breeds of cattle and capture genetic differentiation across breeds. Our work makes a so-far unused source of variation amenable to genetic investigations and provides methods and a framework for establishing and exploiting a more diverse reference genome.

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Novel functional sequences uncovered through a bovine multi-assembly graph

Cited by 6 publications

References 72 publications

A cattle graph genome incorporating global breed diversity

A cattle graph genome incorporating global breed diversity

A cattle graph genome incorporating global breed diversity

Novel functional sequences uncovered through a bovine multiassembly graph

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