The hidden heritability of immune-related diseases
A greater understanding of human genetics and disease-related research has fueled the search for a connection between heritability and immune-related diseases. The well-documented association of the human major histocompatibility complex (MHC) and killer immune receptor (KIR) with many immune-related diseases has spurred large investments in a variety of advanced sequencing tools and large cohort studies. Despite these efforts, the fine mapping of causal variants within MHC or KIR remains difficult, limiting our understanding of the mechanisms leading to immune disease1.
The impact of complex immune genes on disease-association studies
The inherent complexity of the immune sub-genomic regions may be why linking associated variants to immune diseases has been challenging. The MHC and KIR gene complex contain large copy number variants (CNVs), a high density of genes, hyper-polymorphic gene alleles, and conserved extended haplotypes (CEH) with enormous linkage disequilibrium (LDs). This level of complexity makes it difficult to de novo assemble or align these haplotypes correctly using next-generation sequencing methods2.
Discover how SMRT Sequencing impacts your immuno-genomic research
Single Molecule, Real-Time (SMRT) Sequencing delivers the long reads, uniform coverage, and high accuracy needed to comprehensively and confidently phase-resolve the complete range of sequence variants observed in complex immune regions.
Featured research: Explore genetic variation in complex immune loci such as KIR genes
Scientists used long-read sequencing to generate unambiguous KIR genotypes in a well-characterized population of Cynomolgus macaques. They identified nine novel allele variants which aided the refinement of Mafa-KIR haplotype organization model (shown above)3.
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For more information about how SMRT Sequencing can advance your immunology research, contact us.
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- Poster: Oh, Steve et al. (2017) T-cell receptor profiling using PacBio sequencing of SMARTer libraries
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- Poster: Cereb, N et al. (2016) Whole gene sequencing of KIR-3DL1 with SMRT Sequencing and the distribution of allelic variants in different ethnic groups
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- Poster: Ekholm, JM et al. (2016) Resolving KIR genotypes and haplotypes simultaneously using Single Molecule, Real-Time Sequencing
- Poster: Baybayan, Primo et al. (2016) Application specific barcoding strategies for SMRT Sequencing
- Poster: Ranade, Swati et al. (2016) Immune regions are no longer incomprehensible with SMRT Sequencing
- Ranade, Swati (2017) Webinar: A Paradigm Shift in HLA Sequencing: From Exons to High-Resolution Allele-Level HLA Typing
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- Laird Smith, Melissa (2016) ASHG PacBio Workshop: SMRT Sequencing as a translational research tool to investigate germline, somatic and infectious diseases
- Pollard, Martin (2016) ASHG Virtual Poster: The MHC Diversity in Africa Project (MDAP) pilot – 125 African high resolution HLA types from 5 populations
- Wenger, Aaron (2016) Video: Using the Integrative Genomics Viewer (IGV) to visualize PacBio long-read SMRT Sequencing data
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- Ranade, Swati (2016) AGBT Virtual Poster: Immune regions are no longer incomprehensible with SMRT Sequencing
- Ryder, Oliver (2016) PAG PacBio Workshop: Conservation genomics of a critically endangered Hawaiian bird: A high quality genome assembly of the ‘alala will assist in population management and reintroduction
- Case study: SMRT sequencing brings clarity to HIV vaccine and transplant research at the Wisconsin national primate research center. (2017)
- PacBio Certified Service Providers (2017)
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- Case Study: Improving precision medicine studies in Asia using ethnicity-specific human reference genomes and PacBio long-read sequencing. (2017)
- Application Brief: Long-read RNA sequencing – Best Practices. (2017)
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- Application Note: Multiplex target enrichment using barcoded multi-kilobase fragments and probe-based capture technologies. (2016)