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Whole-genome resequencing of Hanwoo (Korean cattle) and insight into regions of homozygosity.

Lee KT, Chung WH, Lee SY, Choi JW, Kim J, Lim D, Lee S, Jang GW, Kim B, Choy YH, Liao X, Stothard P, Moore SS, Lee SH, Ahn S, Kim N, Kim TH - BMC Genomics (2013)

Bottom Line: Moreover, 16, 78, and 51 regions of homozygosity (ROHs) were detected in Hanwoo, Black Angus, and Holstein, respectively. 'Regulation of actin filament length' was revealed as a significant gene ontology term and 25 trait-associated genes for meat quality and disease resistance were found in 753 genes that resided in the ROHs of Hanwoo.Additionally, we found 25 trait-associated genes for meat quality and disease resistance among 753 genes that resided in the ROHs of Hanwoo.These findings will provide useful genomic information for identifying genes or casual mutations associated with economically important traits in cattle.

View Article: PubMed Central - HTML - PubMed

Affiliation: Animal Genomics and Bioinformatics Division, National Institute of Animal Science, Rural Development Administration, Suwon 441-706, Republic of Korea.

ABSTRACT

Background: Hanwoo (Korean cattle), which originated from natural crossbreeding between taurine and zebu cattle, migrated to the Korean peninsula through North China. Hanwoo were raised as draft animals until the 1970s without the introduction of foreign germplasm. Since 1979, Hanwoo has been bred as beef cattle. Genetic variation was analyzed by whole-genome deep resequencing of a Hanwoo bull. The Hanwoo genome was compared to that of two other breeds, Black Angus and Holstein, and genes within regions of homozygosity were investigated to elucidate the genetic and genomic characteristics of Hanwoo.

Results: The Hanwoo bull genome was sequenced to 45.6-fold coverage using the ABI SOLiD system. In total, 4.7 million single-nucleotide polymorphisms and 0.4 million small indels were identified by comparison with the Btau4.0 reference assembly. Of the total number of SNPs and indels, 58% and 87%, respectively, were novel. The overall genotype concordance between the SNPs and BovineSNP50 BeadChip data was 96.4%. Of 1.6 million genetic differences in Hanwoo, approximately 25,000 non-synonymous SNPs, splice-site variants, and coding indels (NS/SS/Is) were detected in 8,360 genes. Among 1,045 genes containing reliable specific NS/SS/Is in Hanwoo, 109 genes contained more than one novel damaging NS/SS/I. Of the genes containing NS/SS/Is, 610 genes were assigned as trait-associated genes. Moreover, 16, 78, and 51 regions of homozygosity (ROHs) were detected in Hanwoo, Black Angus, and Holstein, respectively. 'Regulation of actin filament length' was revealed as a significant gene ontology term and 25 trait-associated genes for meat quality and disease resistance were found in 753 genes that resided in the ROHs of Hanwoo. In Hanwoo, 43 genes were located in common ROHs between whole-genome resequencing and SNP chips in BTA2, 10, and 13 coincided with quantitative trait loci for meat fat traits. In addition, the common ROHs in BTA2 and 16 were in agreement between Hanwoo and Black Angus.

Conclusions: We identified 4.7 million SNPs and 0.4 million small indels by whole-genome resequencing of a Hanwoo bull. Approximately 25,000 non-synonymous SNPs, splice-site variants, and coding indels (NS/SS/Is) were detected in 8,360 genes. Additionally, we found 25 trait-associated genes for meat quality and disease resistance among 753 genes that resided in the ROHs of Hanwoo. These findings will provide useful genomic information for identifying genes or casual mutations associated with economically important traits in cattle.

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Genetic variations in Hanwoo, Black Angus, and Holstein.
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Figure 1: Genetic variations in Hanwoo, Black Angus, and Holstein.

Mentions: The SNPs in genic regions were annotated using 20,955 genes from the NCBI Reference Sequence Database (RefSeq). In total, 1,663,599 SNPs (34.8%) identified in the Hanwoo genome were located in genic regions: 1,591,380 SNPs were located in introns, 21,507 SNPs were located in untranslated regions (UTRs), and 460 SNPs were located in splice sites. In total, 47,823 coding SNPs including 22,752 non-synonymous nucleotide substitutions such as missense and nonsense/read-through SNPs were also found (FigureĀ 1 and Additional file 3). In total, 142,297 indels (36.4%) were in genic regions, of which 2,163 indels were identified as variations that may change amino acid sequences such as frameshift, nonsense, and splice-site SNPs, which may have the potential to cause functional differences. Non-synonymous SNPs, splice-site variants, and coding indels within a coding DNA sequence (NS/SS/I), which may affect gene function, were detected in Hanwoo (24,915 in 8,360 genes), Black Angus (15,107 in 6,563 genes), and Holstein (16,963 in 6,692), respectively (Additional files 3 and 5). The Hanwoo genome contained more NS/SS/Is than those of Black Angus and Holstein. This suggests that Hanwoo is a more genetically distant breed than Black Angus and Holstein based on the reference genome of Hereford, which is consistent with a previous report [17]. Of all reference genes (20,955), 10,906 genes contained NS/SS/I genes and 737 genes revealed more than 10 NS/SS/Is in all breeds (Additional file 5). ATP-binding cassette subfamily C member 4 (ABCC4) and zinc-finger protein 280B (ZNF280B) genes showed more than 100 NS/SS/Is. Four isoforms (copies) of the ABCC4 gene are located on BTA12 in tandem with each other (ENSBTAG00000032603, ENSBTAG00000047764, ENSBTAG00000023309, and ENSBTAG00000047383). Fifty-four variations (NS/SS/Is) in four isoforms are recorded in Ensembl. However, the ZNF280B gene is a single-copy gene (ENSBTAG00000001005) located on BTA17 and 83 NS/SS/Is exist in Ensembl, although ZNF280B has a smaller genome span (8.463 kb) and transcript (1.980 kb) compared to the genome spans (87.521 to 165.199 kb) and transcripts (2.529 to 3.930 kb) of ABCC4 gene copies. These findings show that these two genes surely belong to the gene group of more NS/SS/Is rather than other common genes. A study has reported that the number of copies of the ABCC4 gene increases and the gene is overexpressed in the process of selection for resistant mouse cells against antibiotics such as ciprofloxacin [18]. Therefore, this suggests that genes containing several NS/SS/Is may have evolved into multi-copy genes for environmental adaptation, or that NS/SS/Is may be distorted due to an incorrect reference genome sequence. However, this is necessary for experimental validation based on phenomena such as CNV or segmental duplication. Alternatively, the possibility of the presence of pseudogenes should not be excluded for genes containing several NS/SS/Is. Among 10,906 genes containing NS/SS/Is, the number of genes containing specific NS/SS/Is was 1,983 in Hanwoo, 1,199 in Black Angus, and 900 in Holstein. In Hanwoo, 1,045 genes contained reliable specific NS/SS/Is with more than tenfold depth. Furthermore, of 1,045 genes containing specific NS/SS/Is, 293 genes were revealed in Hanwoo only and 109 genes contained more than one novel damaging NS/SS/I in the functions among them (Additional file 6). Seven NS/SS/Is and six novel damaging NS/SS/Is were found in Hanwoo specifically within the raftlin lipid raft linking protein 1 (RFTN1) gene, which is important in the formation or maintenance of membrane lipid rafts [19] and is overexpressed in smooth muscles (Gene Expression Atlas in EBI).


Whole-genome resequencing of Hanwoo (Korean cattle) and insight into regions of homozygosity.

Lee KT, Chung WH, Lee SY, Choi JW, Kim J, Lim D, Lee S, Jang GW, Kim B, Choy YH, Liao X, Stothard P, Moore SS, Lee SH, Ahn S, Kim N, Kim TH - BMC Genomics (2013)

Genetic variations in Hanwoo, Black Angus, and Holstein.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750754&req=5

Figure 1: Genetic variations in Hanwoo, Black Angus, and Holstein.
Mentions: The SNPs in genic regions were annotated using 20,955 genes from the NCBI Reference Sequence Database (RefSeq). In total, 1,663,599 SNPs (34.8%) identified in the Hanwoo genome were located in genic regions: 1,591,380 SNPs were located in introns, 21,507 SNPs were located in untranslated regions (UTRs), and 460 SNPs were located in splice sites. In total, 47,823 coding SNPs including 22,752 non-synonymous nucleotide substitutions such as missense and nonsense/read-through SNPs were also found (FigureĀ 1 and Additional file 3). In total, 142,297 indels (36.4%) were in genic regions, of which 2,163 indels were identified as variations that may change amino acid sequences such as frameshift, nonsense, and splice-site SNPs, which may have the potential to cause functional differences. Non-synonymous SNPs, splice-site variants, and coding indels within a coding DNA sequence (NS/SS/I), which may affect gene function, were detected in Hanwoo (24,915 in 8,360 genes), Black Angus (15,107 in 6,563 genes), and Holstein (16,963 in 6,692), respectively (Additional files 3 and 5). The Hanwoo genome contained more NS/SS/Is than those of Black Angus and Holstein. This suggests that Hanwoo is a more genetically distant breed than Black Angus and Holstein based on the reference genome of Hereford, which is consistent with a previous report [17]. Of all reference genes (20,955), 10,906 genes contained NS/SS/I genes and 737 genes revealed more than 10 NS/SS/Is in all breeds (Additional file 5). ATP-binding cassette subfamily C member 4 (ABCC4) and zinc-finger protein 280B (ZNF280B) genes showed more than 100 NS/SS/Is. Four isoforms (copies) of the ABCC4 gene are located on BTA12 in tandem with each other (ENSBTAG00000032603, ENSBTAG00000047764, ENSBTAG00000023309, and ENSBTAG00000047383). Fifty-four variations (NS/SS/Is) in four isoforms are recorded in Ensembl. However, the ZNF280B gene is a single-copy gene (ENSBTAG00000001005) located on BTA17 and 83 NS/SS/Is exist in Ensembl, although ZNF280B has a smaller genome span (8.463 kb) and transcript (1.980 kb) compared to the genome spans (87.521 to 165.199 kb) and transcripts (2.529 to 3.930 kb) of ABCC4 gene copies. These findings show that these two genes surely belong to the gene group of more NS/SS/Is rather than other common genes. A study has reported that the number of copies of the ABCC4 gene increases and the gene is overexpressed in the process of selection for resistant mouse cells against antibiotics such as ciprofloxacin [18]. Therefore, this suggests that genes containing several NS/SS/Is may have evolved into multi-copy genes for environmental adaptation, or that NS/SS/Is may be distorted due to an incorrect reference genome sequence. However, this is necessary for experimental validation based on phenomena such as CNV or segmental duplication. Alternatively, the possibility of the presence of pseudogenes should not be excluded for genes containing several NS/SS/Is. Among 10,906 genes containing NS/SS/Is, the number of genes containing specific NS/SS/Is was 1,983 in Hanwoo, 1,199 in Black Angus, and 900 in Holstein. In Hanwoo, 1,045 genes contained reliable specific NS/SS/Is with more than tenfold depth. Furthermore, of 1,045 genes containing specific NS/SS/Is, 293 genes were revealed in Hanwoo only and 109 genes contained more than one novel damaging NS/SS/I in the functions among them (Additional file 6). Seven NS/SS/Is and six novel damaging NS/SS/Is were found in Hanwoo specifically within the raftlin lipid raft linking protein 1 (RFTN1) gene, which is important in the formation or maintenance of membrane lipid rafts [19] and is overexpressed in smooth muscles (Gene Expression Atlas in EBI).

Bottom Line: Moreover, 16, 78, and 51 regions of homozygosity (ROHs) were detected in Hanwoo, Black Angus, and Holstein, respectively. 'Regulation of actin filament length' was revealed as a significant gene ontology term and 25 trait-associated genes for meat quality and disease resistance were found in 753 genes that resided in the ROHs of Hanwoo.Additionally, we found 25 trait-associated genes for meat quality and disease resistance among 753 genes that resided in the ROHs of Hanwoo.These findings will provide useful genomic information for identifying genes or casual mutations associated with economically important traits in cattle.

View Article: PubMed Central - HTML - PubMed

Affiliation: Animal Genomics and Bioinformatics Division, National Institute of Animal Science, Rural Development Administration, Suwon 441-706, Republic of Korea.

ABSTRACT

Background: Hanwoo (Korean cattle), which originated from natural crossbreeding between taurine and zebu cattle, migrated to the Korean peninsula through North China. Hanwoo were raised as draft animals until the 1970s without the introduction of foreign germplasm. Since 1979, Hanwoo has been bred as beef cattle. Genetic variation was analyzed by whole-genome deep resequencing of a Hanwoo bull. The Hanwoo genome was compared to that of two other breeds, Black Angus and Holstein, and genes within regions of homozygosity were investigated to elucidate the genetic and genomic characteristics of Hanwoo.

Results: The Hanwoo bull genome was sequenced to 45.6-fold coverage using the ABI SOLiD system. In total, 4.7 million single-nucleotide polymorphisms and 0.4 million small indels were identified by comparison with the Btau4.0 reference assembly. Of the total number of SNPs and indels, 58% and 87%, respectively, were novel. The overall genotype concordance between the SNPs and BovineSNP50 BeadChip data was 96.4%. Of 1.6 million genetic differences in Hanwoo, approximately 25,000 non-synonymous SNPs, splice-site variants, and coding indels (NS/SS/Is) were detected in 8,360 genes. Among 1,045 genes containing reliable specific NS/SS/Is in Hanwoo, 109 genes contained more than one novel damaging NS/SS/I. Of the genes containing NS/SS/Is, 610 genes were assigned as trait-associated genes. Moreover, 16, 78, and 51 regions of homozygosity (ROHs) were detected in Hanwoo, Black Angus, and Holstein, respectively. 'Regulation of actin filament length' was revealed as a significant gene ontology term and 25 trait-associated genes for meat quality and disease resistance were found in 753 genes that resided in the ROHs of Hanwoo. In Hanwoo, 43 genes were located in common ROHs between whole-genome resequencing and SNP chips in BTA2, 10, and 13 coincided with quantitative trait loci for meat fat traits. In addition, the common ROHs in BTA2 and 16 were in agreement between Hanwoo and Black Angus.

Conclusions: We identified 4.7 million SNPs and 0.4 million small indels by whole-genome resequencing of a Hanwoo bull. Approximately 25,000 non-synonymous SNPs, splice-site variants, and coding indels (NS/SS/Is) were detected in 8,360 genes. Additionally, we found 25 trait-associated genes for meat quality and disease resistance among 753 genes that resided in the ROHs of Hanwoo. These findings will provide useful genomic information for identifying genes or casual mutations associated with economically important traits in cattle.

Show MeSH