Assembly and analysis of 100 full MHC haplotypes from the Danish population

Jacob M. Jensen; Palle Villesen; Rune M.  Friborg; Thomas Mailund; Søren Besenbacher; Mikkel H. Schierup; Jose Maria Gonzalez-Izarzugaza

doi:10.1101/gr.218891.116

Assembly and analysis of 100 full MHC haplotypes from the Danish population

Jacob M. Jensen, Palle Villesen, Rune M. Friborg, Thomas Mailund, Søren Besenbacher, Mikkel H. Schierup, Jose Maria Gonzalez-Izarzugaza

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Abstract

Genes in the major histocompatibility complex (MHC, also known as HLA) play a critical role in the immune response and variation within the extended 4 Mb region shows association with major risks of many diseases. Yet, deciphering the underlying causes of these associations is difficult because the MHC is the most polymorphic region of the genome with a complex linkage disequilibrium structure. Here we reconstruct full MHC haplotypes from de novo assembled trios without relying on a reference genome and perform evolutionary analyses. We report 100 full MHC haplotypes and call a large set of structural variants in the regions for future use in imputation with GWAS data. We also present the first complete analysis of the recombination landscape in the entire region and show how balancing selection at classical genes have linked effects on the frequency of variants throughout the region.

Original language	English
Journal	Genome Research
ISSN	1088-9051
DOIs	https://doi.org/10.1101/gr.218891.116
Publication status	Accepted/In press - 2017
Externally published	Yes

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title = "Assembly and analysis of 100 full MHC haplotypes from the Danish population",

abstract = "Genes in the major histocompatibility complex (MHC, also known as HLA) play a critical role in the immune response and variation within the extended 4 Mb region shows association with major risks of many diseases. Yet, deciphering the underlying causes of these associations is difficult because the MHC is the most polymorphic region of the genome with a complex linkage disequilibrium structure. Here we reconstruct full MHC haplotypes from de novo assembled trios without relying on a reference genome and perform evolutionary analyses. We report 100 full MHC haplotypes and call a large set of structural variants in the regions for future use in imputation with GWAS data. We also present the first complete analysis of the recombination landscape in the entire region and show how balancing selection at classical genes have linked effects on the frequency of variants throughout the region.",

author = "Jensen, {Jacob M.} and Palle Villesen and Friborg, {Rune M.} and Thomas Mailund and S{\o}ren Besenbacher and Schierup, {Mikkel H.} and Gonzalez-Izarzugaza, {Jose Maria}",

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language = "English",

journal = "Genome Research",

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T1 - Assembly and analysis of 100 full MHC haplotypes from the Danish population

AU - Jensen, Jacob M.

AU - Villesen, Palle

AU - Friborg, Rune M.

AU - Mailund, Thomas

AU - Besenbacher, Søren

AU - Schierup, Mikkel H.

AU - Gonzalez-Izarzugaza, Jose Maria

PY - 2017

Y1 - 2017

N2 - Genes in the major histocompatibility complex (MHC, also known as HLA) play a critical role in the immune response and variation within the extended 4 Mb region shows association with major risks of many diseases. Yet, deciphering the underlying causes of these associations is difficult because the MHC is the most polymorphic region of the genome with a complex linkage disequilibrium structure. Here we reconstruct full MHC haplotypes from de novo assembled trios without relying on a reference genome and perform evolutionary analyses. We report 100 full MHC haplotypes and call a large set of structural variants in the regions for future use in imputation with GWAS data. We also present the first complete analysis of the recombination landscape in the entire region and show how balancing selection at classical genes have linked effects on the frequency of variants throughout the region.

AB - Genes in the major histocompatibility complex (MHC, also known as HLA) play a critical role in the immune response and variation within the extended 4 Mb region shows association with major risks of many diseases. Yet, deciphering the underlying causes of these associations is difficult because the MHC is the most polymorphic region of the genome with a complex linkage disequilibrium structure. Here we reconstruct full MHC haplotypes from de novo assembled trios without relying on a reference genome and perform evolutionary analyses. We report 100 full MHC haplotypes and call a large set of structural variants in the regions for future use in imputation with GWAS data. We also present the first complete analysis of the recombination landscape in the entire region and show how balancing selection at classical genes have linked effects on the frequency of variants throughout the region.

U2 - 10.1101/gr.218891.116

DO - 10.1101/gr.218891.116

M3 - Journal article

C2 - 28774965

SN - 1088-9051

JO - Genome Research

JF - Genome Research

ER -

Assembly and analysis of 100 full MHC haplotypes from the Danish population

Abstract

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