TY - JOUR
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 - Sørensen, Lasse Maretty
AU - Petersen, Bent
AU - Sibbesen, Jonas Andreas
AU - Liu, Siyang
AU - Skov, Laurits
AU - Belling, Kirstine G
AU - Have, Christian Theil
AU - Izarzugaza, Jose M. G.
AU - Grosjean, Marie
AU - Bork-Jensen, Jette
AU - Grove, Jakob
AU - Als, Thomas D.
AU - Huang, Shujia
AU - Chang, Yuqi
AU - Xu, Ruiqi
AU - Ye, Weijian
AU - Rao, Junhua
AU - Guo, Xiaosen
AU - Sun, Jihua
AU - Cao, Hongzhi
AU - Ye, Chen
AU - Beusekom, Johan V.
AU - Espeseth, Thomas
AU - Flindt, Esben
AU - Halager, Anders E.
AU - Hellard, Stephanie Le
AU - Hultman, Christina M.
AU - Lescai, Francesco
AU - Li, Shengting
AU - Lund, Ole
AU - Løngren, Peter
AU - Matey-Hernandez, Maria Luisa
AU - Mors, Ole
AU - Pedersen, Christian N. S.
AU - Sicheritz-Pontén, Thomas
AU - Sullivan, Patrick
AU - Syed, Ali
AU - Westergaard, David
AU - Yadav, Rachita
AU - Li, Ning
AU - Xu, Xun
AU - Hansen, Torben
AU - Bolund, Lars
AU - Krogh, Anders
AU - Sørensen, Thorkild I. A.
AU - Pedersen, Oluf Borbye
AU - Gupta, Ramneek
AU - Rasmussen, Simon
AU - Børglum, Anders D.
AU - Wang, Jun
AU - Eiberg, Hans Rudolf Lytchoff
AU - Kristiansen, Karsten
AU - Brunak, Søren
AU - Schierup, Mikkel Heide
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.
U2 - 10.1101/gr.218891.116
DO - 10.1101/gr.218891.116
M3 - Journal article
C2 - 28774965
AN - SCOPUS:85028744509
VL - 27
SP - 1597
EP - 1607
JO - Genome Research
JF - Genome Research
SN - 1088-9051
IS - 9
ER -