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The assembly and characterisation of two structurally distinct cattle MHC class I haplotypes point to the mechanisms driving diversity.

Schwartz JC, Hammond JA - Immunogenetics (2015)

Bottom Line: This variable region appears to have undergone block gene duplication and likely deletion at regular breakpoints, suggestive of a site-specific mechanism.Phylogenetic analysis using complete gene sequences provided evidence of allelic diversification via gene conversion, with breakpoints between each of the extracellular domains that were associated with high guanine-cytosine (GC) content.Advancing our knowledge of cattle MHC class I evolution will help inform investigations of cattle genetic diversity and disease resistance.

View Article: PubMed Central - PubMed

Affiliation: Livestock Viral Diseases Programme, The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, GU24 0NF, UK.

ABSTRACT
In cattle, there are six classical MHC class I genes that are variably present between different haplotypes. Almost all known haplotypes contain between one and three genes, with an allele of Gene 2 present on the vast majority. However, very little is known about the sequence and therefore structure and evolutionary history of this genomic region. To address this, we have refined the MHC class I region in the Hereford cattle genome assembly and sequenced a complete A14 haplotype from a homozygous Holstein. Comparison of the two haplotypes revealed extensive variation within the MHC class Ia region, but not within the flanking regions, with each gene contained within a conserved 63- to 68-kb sequence block. This variable region appears to have undergone block gene duplication and likely deletion at regular breakpoints, suggestive of a site-specific mechanism. Phylogenetic analysis using complete gene sequences provided evidence of allelic diversification via gene conversion, with breakpoints between each of the extracellular domains that were associated with high guanine-cytosine (GC) content. Advancing our knowledge of cattle MHC class I evolution will help inform investigations of cattle genetic diversity and disease resistance.

No MeSH data available.


Related in: MedlinePlus

Comparison of previously published cattle genome assemblies (Birch et al. 2008; Ellis and Hammond 2014) with the assembly in this study. Gaps within each assembly are indicated by broken lines. Closed boxes represent putatively functional genes, open boxes (and RPL35aψ) represent pseudogenes. BACs used for the current analyses are shown at left
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Fig1: Comparison of previously published cattle genome assemblies (Birch et al. 2008; Ellis and Hammond 2014) with the assembly in this study. Gaps within each assembly are indicated by broken lines. Closed boxes represent putatively functional genes, open boxes (and RPL35aψ) represent pseudogenes. BACs used for the current analyses are shown at left

Mentions: A comparison between the current genome builds (Btau 4.1 and UMD 3.1) and the assembled BAC clones reveals that the current assemblies, although broadly correct, likely contain some significant errors (Fig. 1). Although the order of the MHC class I genes and pseudogenes is mostly correct, the number and size of several pseudogene loci and intergenic intervals are substantially different, particularly between NC1 and Gene 5. Of note is pseudogene 3 which is a putatively functional gene in our assembly, although the large intron 1 and 2 sequences (2853 and 1971 bp, respectively) are likely to impact negatively on expression. We also found no evidence of TRIM26 pseudogenes between Gene 2 and Gene 5, and a less gene dense region telomeric of Gene 2 that only contains functional TRIM genes. It is likely that the sequence data from more than one haplotype has been incorrectly incorporated into the genome assemblies creating assembly and annotation problems.Fig. 1


The assembly and characterisation of two structurally distinct cattle MHC class I haplotypes point to the mechanisms driving diversity.

Schwartz JC, Hammond JA - Immunogenetics (2015)

Comparison of previously published cattle genome assemblies (Birch et al. 2008; Ellis and Hammond 2014) with the assembly in this study. Gaps within each assembly are indicated by broken lines. Closed boxes represent putatively functional genes, open boxes (and RPL35aψ) represent pseudogenes. BACs used for the current analyses are shown at left
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4539362&req=5

Fig1: Comparison of previously published cattle genome assemblies (Birch et al. 2008; Ellis and Hammond 2014) with the assembly in this study. Gaps within each assembly are indicated by broken lines. Closed boxes represent putatively functional genes, open boxes (and RPL35aψ) represent pseudogenes. BACs used for the current analyses are shown at left
Mentions: A comparison between the current genome builds (Btau 4.1 and UMD 3.1) and the assembled BAC clones reveals that the current assemblies, although broadly correct, likely contain some significant errors (Fig. 1). Although the order of the MHC class I genes and pseudogenes is mostly correct, the number and size of several pseudogene loci and intergenic intervals are substantially different, particularly between NC1 and Gene 5. Of note is pseudogene 3 which is a putatively functional gene in our assembly, although the large intron 1 and 2 sequences (2853 and 1971 bp, respectively) are likely to impact negatively on expression. We also found no evidence of TRIM26 pseudogenes between Gene 2 and Gene 5, and a less gene dense region telomeric of Gene 2 that only contains functional TRIM genes. It is likely that the sequence data from more than one haplotype has been incorrectly incorporated into the genome assemblies creating assembly and annotation problems.Fig. 1

Bottom Line: This variable region appears to have undergone block gene duplication and likely deletion at regular breakpoints, suggestive of a site-specific mechanism.Phylogenetic analysis using complete gene sequences provided evidence of allelic diversification via gene conversion, with breakpoints between each of the extracellular domains that were associated with high guanine-cytosine (GC) content.Advancing our knowledge of cattle MHC class I evolution will help inform investigations of cattle genetic diversity and disease resistance.

View Article: PubMed Central - PubMed

Affiliation: Livestock Viral Diseases Programme, The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, GU24 0NF, UK.

ABSTRACT
In cattle, there are six classical MHC class I genes that are variably present between different haplotypes. Almost all known haplotypes contain between one and three genes, with an allele of Gene 2 present on the vast majority. However, very little is known about the sequence and therefore structure and evolutionary history of this genomic region. To address this, we have refined the MHC class I region in the Hereford cattle genome assembly and sequenced a complete A14 haplotype from a homozygous Holstein. Comparison of the two haplotypes revealed extensive variation within the MHC class Ia region, but not within the flanking regions, with each gene contained within a conserved 63- to 68-kb sequence block. This variable region appears to have undergone block gene duplication and likely deletion at regular breakpoints, suggestive of a site-specific mechanism. Phylogenetic analysis using complete gene sequences provided evidence of allelic diversification via gene conversion, with breakpoints between each of the extracellular domains that were associated with high guanine-cytosine (GC) content. Advancing our knowledge of cattle MHC class I evolution will help inform investigations of cattle genetic diversity and disease resistance.

No MeSH data available.


Related in: MedlinePlus