TY - JOUR

T1 - A haplotype-resolved genome assembly of the Nile rat facilitates exploration of the genetic basis of diabetes

AU - Toh, Huishi

AU - Yang, Chentao

AU - Formenti, Giulio

AU - Raja, Kalpana

AU - Yan, Lily

AU - Tracey, Alan

AU - Chow, William

AU - Howe, Kerstin

AU - Bergeron, Lucie A.

AU - Zhang, Guojie

AU - Haase, Bettina

AU - Mountcastle, Jacquelyn

AU - Fedrigo, Olivier

AU - Fogg, John

AU - Kirilenko, Bogdan

AU - Munegowda, Chetan

AU - Hiller, Michael

AU - Jain, Aashish

AU - Kihara, Daisuke

AU - Rhie, Arang

AU - Phillippy, Adam M.

AU - Swanson, Scott A.

AU - Jiang, Peng

AU - Clegg, Dennis O.

AU - Jarvis, Erich D.

AU - Thomson, James A.

AU - Stewart, Ron

AU - Chaisson, Mark J. P.

AU - Bukhman, Yury V.

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - Background: The Nile rat (Avicanthis niloticus) is an important animal model because of its robust diurnal rhythm, a cone-rich retina, and a propensity to develop diet-induced diabetes without chemical or genetic modifications. A closer similarity to humans in these aspects, compared to the widely used Mus musculus and Rattus norvegicus models, holds the promise of better translation of research findings to the clinic. Results: We report a 2.5 Gb, chromosome-level reference genome assembly with fully resolved parental haplotypes, generated with the Vertebrate Genomes Project (VGP). The assembly is highly contiguous, with contig N50 of 11.1 Mb, scaffold N50 of 83 Mb, and 95.2% of the sequence assigned to chromosomes. We used a novel workflow to identify 3613 segmental duplications and quantify duplicated genes. Comparative analyses revealed unique genomic features of the Nile rat, including some that affect genes associated with type 2 diabetes and metabolic dysfunctions. We discuss 14 genes that are heterozygous in the Nile rat or highly diverged from the house mouse. Conclusions: Our findings reflect the exceptional level of genomic resolution present in this assembly, which will greatly expand the potential of the Nile rat as a model organism.

AB - Background: The Nile rat (Avicanthis niloticus) is an important animal model because of its robust diurnal rhythm, a cone-rich retina, and a propensity to develop diet-induced diabetes without chemical or genetic modifications. A closer similarity to humans in these aspects, compared to the widely used Mus musculus and Rattus norvegicus models, holds the promise of better translation of research findings to the clinic. Results: We report a 2.5 Gb, chromosome-level reference genome assembly with fully resolved parental haplotypes, generated with the Vertebrate Genomes Project (VGP). The assembly is highly contiguous, with contig N50 of 11.1 Mb, scaffold N50 of 83 Mb, and 95.2% of the sequence assigned to chromosomes. We used a novel workflow to identify 3613 segmental duplications and quantify duplicated genes. Comparative analyses revealed unique genomic features of the Nile rat, including some that affect genes associated with type 2 diabetes and metabolic dysfunctions. We discuss 14 genes that are heterozygous in the Nile rat or highly diverged from the house mouse. Conclusions: Our findings reflect the exceptional level of genomic resolution present in this assembly, which will greatly expand the potential of the Nile rat as a model organism.

KW - Arvicanthis niloticus

KW - Diabetes

KW - Diurnal

KW - Genome

KW - Germline mutation rate

KW - Heterozygosity

KW - Long-read genome assembly

KW - Orthology

KW - Positive selection

KW - Retrogenes

KW - Segmental duplications

U2 - 10.1186/s12915-022-01427-8

DO - 10.1186/s12915-022-01427-8

M3 - Journal article

C2 - 36344967

AN - SCOPUS:85141516597

VL - 20

JO - B M C Biology

JF - B M C Biology

SN - 1741-7007

M1 - 245

ER -