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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.


Sequence identity comparison of the assembled Hereford genome “Domino” and A14 cattle MHC class I regions using DOTTER (Sonnhammer and Durbin 1995) and a sliding window size of 200 bp. Putatively functional genes are shown with closed arrows, while pseudogenes are shown with open arrows. Arrows point in the direction of transcription. The positions of the BAC clones used for each assembly are indicated by each haplotype. Gaps in the CH240-463M1 assembly are indicted by broken lines and are not to scale. There are three additional contigs from this clone which are not shown due to their small (~1 kb) size
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Fig2: Sequence identity comparison of the assembled Hereford genome “Domino” and A14 cattle MHC class I regions using DOTTER (Sonnhammer and Durbin 1995) and a sliding window size of 200 bp. Putatively functional genes are shown with closed arrows, while pseudogenes are shown with open arrows. Arrows point in the direction of transcription. The positions of the BAC clones used for each assembly are indicated by each haplotype. Gaps in the CH240-463M1 assembly are indicted by broken lines and are not to scale. There are three additional contigs from this clone which are not shown due to their small (~1 kb) size

Mentions: Detailed annotation of our A14 assembly confirmed the four previously mapped MHC class Ia genes upstream from NC1 and four MHC class I-like pseudogenes (Fig. 2). All four MHC class Ia genes are separated by between 63 and 68 kb. Initially, the most upstream of these was named Gene “Z” and later designated 6*04001 based on phylogenetic evidence using cDNA sequence (Di Palma et al. 2002; Hammond et al. 2012). Although direct functional evidence for 6*04001 has not been published, mRNA expression has been confirmed by several studies. The A14 haplotype had previously been designated a three-gene haplotype, this data strongly suggests that the A14 haplotype possesses four functional MHC class Ia genes.Fig. 2


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)

Sequence identity comparison of the assembled Hereford genome “Domino” and A14 cattle MHC class I regions using DOTTER (Sonnhammer and Durbin 1995) and a sliding window size of 200 bp. Putatively functional genes are shown with closed arrows, while pseudogenes are shown with open arrows. Arrows point in the direction of transcription. The positions of the BAC clones used for each assembly are indicated by each haplotype. Gaps in the CH240-463M1 assembly are indicted by broken lines and are not to scale. There are three additional contigs from this clone which are not shown due to their small (~1 kb) size
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4539362&req=5

Fig2: Sequence identity comparison of the assembled Hereford genome “Domino” and A14 cattle MHC class I regions using DOTTER (Sonnhammer and Durbin 1995) and a sliding window size of 200 bp. Putatively functional genes are shown with closed arrows, while pseudogenes are shown with open arrows. Arrows point in the direction of transcription. The positions of the BAC clones used for each assembly are indicated by each haplotype. Gaps in the CH240-463M1 assembly are indicted by broken lines and are not to scale. There are three additional contigs from this clone which are not shown due to their small (~1 kb) size
Mentions: Detailed annotation of our A14 assembly confirmed the four previously mapped MHC class Ia genes upstream from NC1 and four MHC class I-like pseudogenes (Fig. 2). All four MHC class Ia genes are separated by between 63 and 68 kb. Initially, the most upstream of these was named Gene “Z” and later designated 6*04001 based on phylogenetic evidence using cDNA sequence (Di Palma et al. 2002; Hammond et al. 2012). Although direct functional evidence for 6*04001 has not been published, mRNA expression has been confirmed by several studies. The A14 haplotype had previously been designated a three-gene haplotype, this data strongly suggests that the A14 haplotype possesses four functional MHC class Ia genes.Fig. 2

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.