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The impact of next-generation sequencing technologies on HLA research.

Hosomichi K, Shiina T, Tajima A, Inoue I - J. Hum. Genet. (2015)

Bottom Line: Recently, the HLA region has received much attention because severe adverse effects of various drugs are associated with particular HLA alleles.Most importantly, NGS may also permit the analysis of HLA-omics.In this review, we summarize the impact of NGS on HLA research, with a focus on the potential for clinical applications.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioinformatics and Genomics, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.

ABSTRACT
In the past decade, the development of next-generation sequencing (NGS) has paved the way for whole-genome analysis in individuals. Research on the human leukocyte antigen (HLA), an extensively studied molecule involved in immunity, has benefitted from NGS technologies. The HLA region, a 3.6-Mb segment of the human genome at 6p21, has been associated with more than 100 different diseases, primarily autoimmune diseases. Recently, the HLA region has received much attention because severe adverse effects of various drugs are associated with particular HLA alleles. Owing to the complex nature of the HLA genes, classical direct sequencing methods cannot comprehensively elucidate the genomic makeup of HLA genes. Thus far, several high-throughput HLA-typing methods using NGS have been developed. In HLA research, NGS facilitates complete HLA sequencing and is expected to improve our understanding of the mechanisms through which HLA genes are modulated, including transcription, regulation of gene expression and epigenetics. Most importantly, NGS may also permit the analysis of HLA-omics. In this review, we summarize the impact of NGS on HLA research, with a focus on the potential for clinical applications.

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Related in: MedlinePlus

HLA typing to provide sequencing data for the HLA gene(s) and regions. The HLA sequencing data of NGS could be analyzed from various points of view. The minimum scope of polymorphisms is the genotype of an SNV, and the maximum scope is the HLA haplotype sequence as a set of alleles from each HLA gene. The phase-determined sequence of the HLA allele can be applied for HLA typing as a reference. The resolution of HLA typing is classified into the following four categories: two-digit for alleles, four-digit for specific HLA proteins, six-digit for specific HLA coding sequence (CDS) and eight-digit as specific HLA genome sequences including untranslated regions and introns.
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fig1: HLA typing to provide sequencing data for the HLA gene(s) and regions. The HLA sequencing data of NGS could be analyzed from various points of view. The minimum scope of polymorphisms is the genotype of an SNV, and the maximum scope is the HLA haplotype sequence as a set of alleles from each HLA gene. The phase-determined sequence of the HLA allele can be applied for HLA typing as a reference. The resolution of HLA typing is classified into the following four categories: two-digit for alleles, four-digit for specific HLA proteins, six-digit for specific HLA coding sequence (CDS) and eight-digit as specific HLA genome sequences including untranslated regions and introns.

Mentions: To date, several high-throughput HLA-typing methods using NGS have been developed.21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42 Importantly, HLA typing using NGS provides both high-throughput and high-resolution capabilities (Figure 1). Additionally, as reported by the ENCODE Project, HLA gene sequencing alone is not sufficient for developing a complete understanding of the genetic makeup of the HLA locus. The expression levels of HLA genes can have crucial roles in the pathogenesis of diseases; thus, detection of regulatory single-nucleotide variants (SNVs) and insertions and deletions (Indels) located outside of exons is necessary. If phase-defined complete sequencing of HLA genes, including functional regulatory regions, is performed, novel alleles associated with disease risks and adverse effects of drugs could be obtained, and the expression levels of genes that affect biological processes could be clarified.


The impact of next-generation sequencing technologies on HLA research.

Hosomichi K, Shiina T, Tajima A, Inoue I - J. Hum. Genet. (2015)

HLA typing to provide sequencing data for the HLA gene(s) and regions. The HLA sequencing data of NGS could be analyzed from various points of view. The minimum scope of polymorphisms is the genotype of an SNV, and the maximum scope is the HLA haplotype sequence as a set of alleles from each HLA gene. The phase-determined sequence of the HLA allele can be applied for HLA typing as a reference. The resolution of HLA typing is classified into the following four categories: two-digit for alleles, four-digit for specific HLA proteins, six-digit for specific HLA coding sequence (CDS) and eight-digit as specific HLA genome sequences including untranslated regions and introns.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4660052&req=5

fig1: HLA typing to provide sequencing data for the HLA gene(s) and regions. The HLA sequencing data of NGS could be analyzed from various points of view. The minimum scope of polymorphisms is the genotype of an SNV, and the maximum scope is the HLA haplotype sequence as a set of alleles from each HLA gene. The phase-determined sequence of the HLA allele can be applied for HLA typing as a reference. The resolution of HLA typing is classified into the following four categories: two-digit for alleles, four-digit for specific HLA proteins, six-digit for specific HLA coding sequence (CDS) and eight-digit as specific HLA genome sequences including untranslated regions and introns.
Mentions: To date, several high-throughput HLA-typing methods using NGS have been developed.21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42 Importantly, HLA typing using NGS provides both high-throughput and high-resolution capabilities (Figure 1). Additionally, as reported by the ENCODE Project, HLA gene sequencing alone is not sufficient for developing a complete understanding of the genetic makeup of the HLA locus. The expression levels of HLA genes can have crucial roles in the pathogenesis of diseases; thus, detection of regulatory single-nucleotide variants (SNVs) and insertions and deletions (Indels) located outside of exons is necessary. If phase-defined complete sequencing of HLA genes, including functional regulatory regions, is performed, novel alleles associated with disease risks and adverse effects of drugs could be obtained, and the expression levels of genes that affect biological processes could be clarified.

Bottom Line: Recently, the HLA region has received much attention because severe adverse effects of various drugs are associated with particular HLA alleles.Most importantly, NGS may also permit the analysis of HLA-omics.In this review, we summarize the impact of NGS on HLA research, with a focus on the potential for clinical applications.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioinformatics and Genomics, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.

ABSTRACT
In the past decade, the development of next-generation sequencing (NGS) has paved the way for whole-genome analysis in individuals. Research on the human leukocyte antigen (HLA), an extensively studied molecule involved in immunity, has benefitted from NGS technologies. The HLA region, a 3.6-Mb segment of the human genome at 6p21, has been associated with more than 100 different diseases, primarily autoimmune diseases. Recently, the HLA region has received much attention because severe adverse effects of various drugs are associated with particular HLA alleles. Owing to the complex nature of the HLA genes, classical direct sequencing methods cannot comprehensively elucidate the genomic makeup of HLA genes. Thus far, several high-throughput HLA-typing methods using NGS have been developed. In HLA research, NGS facilitates complete HLA sequencing and is expected to improve our understanding of the mechanisms through which HLA genes are modulated, including transcription, regulation of gene expression and epigenetics. Most importantly, NGS may also permit the analysis of HLA-omics. In this review, we summarize the impact of NGS on HLA research, with a focus on the potential for clinical applications.

Show MeSH
Related in: MedlinePlus