Genome sequencing of chromosome 1 substitution lines derived from Chinese wild mice revealed a unique resource for genetic studies of complex traits

Fuyi Xu, Tianzhu Chao, Yingming Liang, Kai Li, Shixian Hu, Maochun Wang, Yuxun Zhou, Hongyan Xu, Junhua Xiao

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Mouse resources such as Collaborative Cross, outbred stocks, Hybrid Mouse Diversity Panel, and chromosome substitution strains have been instrumental to many progresses in the studies of complex traits genetics. We have established a population of chromosome 1 (Chr 1) substitution lines (C1SLs) in which donor chromosomes were derived from Chinese wild mice. Genome sequencing of 18 lines of this population showed that Chr 1 had been replaced by the donor chromosome. About 4.5 million unique single nucleotide polymorphisms and indels were discovered on Chr 1, of which 1.3 million were novel. Compared with sequenced classical inbred strains, Chr 1 of each C1SL had fivefold more variants, and more loss of function and potentially regulatory variants. Further haplotype analysis showed that the donor chromosome accumulated more historical recombination events, with the largest haplotype block being only 100 kb, and about 57% of the blocks were < 1 kb. Subspecies origin analysis showed that these chromosomes had a mosaic genome structure that dominantly originated from Mus musculus musculus and M. m. castaneus subspecies, except for the C57BL/6J-Chr1KM line from M. m. domesticus. In addition, phenotyping four of these lines on blood biochemistry suggested that there were substantial phenotypic variations among our lines, especially line C57BL/6J-Chr1HZ and donor strain C57BL/6J. Further gene ontology enrichment revealed that the differentially expressed genes among liver-expressed genes between C57BL/6J and C57BL/6J-Chr1HZ were enriched in lipid metabolism biological processes. All these characteristics enable C1SLs to be a unique resource for identifying and fine mapping quantitative trait loci on mouse Chr 1, and carrying out systems genetics studies of complex traits.

Original languageEnglish (US)
Pages (from-to)3571-3580
Number of pages10
JournalG3: Genes, Genomes, Genetics
Volume6
Issue number11
DOIs
StatePublished - Jan 1 2016

Fingerprint

Chromosomes, Human, Pair 1
Chromosomes
Genome
Haplotypes
Biological Phenomena
Gene Ontology
Quantitative Trait Loci
Lipid Metabolism
Biochemistry
Genetic Recombination
Population
Genes
Single Nucleotide Polymorphism
Liver

Keywords

  • Chinese wild mice
  • Chromosome substitution
  • Genetic polymorphisms
  • Haplotype
  • Whole genome sequencing

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Genome sequencing of chromosome 1 substitution lines derived from Chinese wild mice revealed a unique resource for genetic studies of complex traits. / Xu, Fuyi; Chao, Tianzhu; Liang, Yingming; Li, Kai; Hu, Shixian; Wang, Maochun; Zhou, Yuxun; Xu, Hongyan; Xiao, Junhua.

In: G3: Genes, Genomes, Genetics, Vol. 6, No. 11, 01.01.2016, p. 3571-3580.

Research output: Contribution to journalArticle

Xu, Fuyi ; Chao, Tianzhu ; Liang, Yingming ; Li, Kai ; Hu, Shixian ; Wang, Maochun ; Zhou, Yuxun ; Xu, Hongyan ; Xiao, Junhua. / Genome sequencing of chromosome 1 substitution lines derived from Chinese wild mice revealed a unique resource for genetic studies of complex traits. In: G3: Genes, Genomes, Genetics. 2016 ; Vol. 6, No. 11. pp. 3571-3580.
@article{d26b6acd542c41d8a698f9a03618350f,
title = "Genome sequencing of chromosome 1 substitution lines derived from Chinese wild mice revealed a unique resource for genetic studies of complex traits",
abstract = "Mouse resources such as Collaborative Cross, outbred stocks, Hybrid Mouse Diversity Panel, and chromosome substitution strains have been instrumental to many progresses in the studies of complex traits genetics. We have established a population of chromosome 1 (Chr 1) substitution lines (C1SLs) in which donor chromosomes were derived from Chinese wild mice. Genome sequencing of 18 lines of this population showed that Chr 1 had been replaced by the donor chromosome. About 4.5 million unique single nucleotide polymorphisms and indels were discovered on Chr 1, of which 1.3 million were novel. Compared with sequenced classical inbred strains, Chr 1 of each C1SL had fivefold more variants, and more loss of function and potentially regulatory variants. Further haplotype analysis showed that the donor chromosome accumulated more historical recombination events, with the largest haplotype block being only 100 kb, and about 57{\%} of the blocks were < 1 kb. Subspecies origin analysis showed that these chromosomes had a mosaic genome structure that dominantly originated from Mus musculus musculus and M. m. castaneus subspecies, except for the C57BL/6J-Chr1KM line from M. m. domesticus. In addition, phenotyping four of these lines on blood biochemistry suggested that there were substantial phenotypic variations among our lines, especially line C57BL/6J-Chr1HZ and donor strain C57BL/6J. Further gene ontology enrichment revealed that the differentially expressed genes among liver-expressed genes between C57BL/6J and C57BL/6J-Chr1HZ were enriched in lipid metabolism biological processes. All these characteristics enable C1SLs to be a unique resource for identifying and fine mapping quantitative trait loci on mouse Chr 1, and carrying out systems genetics studies of complex traits.",
keywords = "Chinese wild mice, Chromosome substitution, Genetic polymorphisms, Haplotype, Whole genome sequencing",
author = "Fuyi Xu and Tianzhu Chao and Yingming Liang and Kai Li and Shixian Hu and Maochun Wang and Yuxun Zhou and Hongyan Xu and Junhua Xiao",
year = "2016",
month = "1",
day = "1",
doi = "10.1534/g3.116.033902",
language = "English (US)",
volume = "6",
pages = "3571--3580",
journal = "G3: Genes, Genomes, Genetics",
issn = "2160-1836",
publisher = "Genetics Society of America",
number = "11",

}

TY - JOUR

T1 - Genome sequencing of chromosome 1 substitution lines derived from Chinese wild mice revealed a unique resource for genetic studies of complex traits

AU - Xu, Fuyi

AU - Chao, Tianzhu

AU - Liang, Yingming

AU - Li, Kai

AU - Hu, Shixian

AU - Wang, Maochun

AU - Zhou, Yuxun

AU - Xu, Hongyan

AU - Xiao, Junhua

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Mouse resources such as Collaborative Cross, outbred stocks, Hybrid Mouse Diversity Panel, and chromosome substitution strains have been instrumental to many progresses in the studies of complex traits genetics. We have established a population of chromosome 1 (Chr 1) substitution lines (C1SLs) in which donor chromosomes were derived from Chinese wild mice. Genome sequencing of 18 lines of this population showed that Chr 1 had been replaced by the donor chromosome. About 4.5 million unique single nucleotide polymorphisms and indels were discovered on Chr 1, of which 1.3 million were novel. Compared with sequenced classical inbred strains, Chr 1 of each C1SL had fivefold more variants, and more loss of function and potentially regulatory variants. Further haplotype analysis showed that the donor chromosome accumulated more historical recombination events, with the largest haplotype block being only 100 kb, and about 57% of the blocks were < 1 kb. Subspecies origin analysis showed that these chromosomes had a mosaic genome structure that dominantly originated from Mus musculus musculus and M. m. castaneus subspecies, except for the C57BL/6J-Chr1KM line from M. m. domesticus. In addition, phenotyping four of these lines on blood biochemistry suggested that there were substantial phenotypic variations among our lines, especially line C57BL/6J-Chr1HZ and donor strain C57BL/6J. Further gene ontology enrichment revealed that the differentially expressed genes among liver-expressed genes between C57BL/6J and C57BL/6J-Chr1HZ were enriched in lipid metabolism biological processes. All these characteristics enable C1SLs to be a unique resource for identifying and fine mapping quantitative trait loci on mouse Chr 1, and carrying out systems genetics studies of complex traits.

AB - Mouse resources such as Collaborative Cross, outbred stocks, Hybrid Mouse Diversity Panel, and chromosome substitution strains have been instrumental to many progresses in the studies of complex traits genetics. We have established a population of chromosome 1 (Chr 1) substitution lines (C1SLs) in which donor chromosomes were derived from Chinese wild mice. Genome sequencing of 18 lines of this population showed that Chr 1 had been replaced by the donor chromosome. About 4.5 million unique single nucleotide polymorphisms and indels were discovered on Chr 1, of which 1.3 million were novel. Compared with sequenced classical inbred strains, Chr 1 of each C1SL had fivefold more variants, and more loss of function and potentially regulatory variants. Further haplotype analysis showed that the donor chromosome accumulated more historical recombination events, with the largest haplotype block being only 100 kb, and about 57% of the blocks were < 1 kb. Subspecies origin analysis showed that these chromosomes had a mosaic genome structure that dominantly originated from Mus musculus musculus and M. m. castaneus subspecies, except for the C57BL/6J-Chr1KM line from M. m. domesticus. In addition, phenotyping four of these lines on blood biochemistry suggested that there were substantial phenotypic variations among our lines, especially line C57BL/6J-Chr1HZ and donor strain C57BL/6J. Further gene ontology enrichment revealed that the differentially expressed genes among liver-expressed genes between C57BL/6J and C57BL/6J-Chr1HZ were enriched in lipid metabolism biological processes. All these characteristics enable C1SLs to be a unique resource for identifying and fine mapping quantitative trait loci on mouse Chr 1, and carrying out systems genetics studies of complex traits.

KW - Chinese wild mice

KW - Chromosome substitution

KW - Genetic polymorphisms

KW - Haplotype

KW - Whole genome sequencing

UR - http://www.scopus.com/inward/record.url?scp=84996558112&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84996558112&partnerID=8YFLogxK

U2 - 10.1534/g3.116.033902

DO - 10.1534/g3.116.033902

M3 - Article

AN - SCOPUS:84996558112

VL - 6

SP - 3571

EP - 3580

JO - G3: Genes, Genomes, Genetics

JF - G3: Genes, Genomes, Genetics

SN - 2160-1836

IS - 11

ER -