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

TY - JOUR

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

AU - Jensen, Jacob Malte

AU - Villesen, Palle

AU - Friborg, Rune M

AU - Mailund, Thomas

AU - Besenbacher, Søren

AU - Schierup, Mikkel H

AU - Danish Pan-Genome Consortium (Jakob Grove, member of -)

AU - Børglum, Anders

AU - Grove, Jakob

N1 - Published by Cold Spring Harbor Laboratory Press.

PY - 2017/9

Y1 - 2017/9

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.

KW - Journal Article

U2 - 10.1101/gr.218891.116

DO - 10.1101/gr.218891.116

M3 - Journal article

C2 - 28774965

SN - 1088-9051

VL - 27

SP - 1597

EP - 1607

JO - Genome Research

JF - Genome Research

IS - 9

ER -