Diversity of extended HLA-DRB1 haplotypes in the Finnish population.

The Major Histocompatibility Complex (MHC, 6p21) codes for traditional HLA and other host response related genes. The polymorphic HLA-DRB1 gene in MHC Class II has been associated with several complex diseases. In this study we focus on MHC haplotype structures in the Finnish population. We explore...

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Autores principales:	Annika Wennerström, Efthymia Vlachopoulou, L Elisa Lahtela, Riitta Paakkanen, Katja T Eronen, Mikko Seppänen, Marja-Liisa Lokki
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3cc81cb7be214ddb82042e64986280fd
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spelling	oai:doaj.org-article:3cc81cb7be214ddb82042e64986280fd2021-11-18T08:45:19ZDiversity of extended HLA-DRB1 haplotypes in the Finnish population.1932-620310.1371/journal.pone.0079690https://doaj.org/article/3cc81cb7be214ddb82042e64986280fd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278156/?tool=EBIhttps://doaj.org/toc/1932-6203The Major Histocompatibility Complex (MHC, 6p21) codes for traditional HLA and other host response related genes. The polymorphic HLA-DRB1 gene in MHC Class II has been associated with several complex diseases. In this study we focus on MHC haplotype structures in the Finnish population. We explore the variability of extended HLA-DRB1 haplotypes in relation to the other traditional HLA genes and a selected group of MHC class III genes. A total of 150 healthy Finnish individuals were included in the study. Subjects were genotyped for HLA alleles (HLA-A, -B, -DRB1, -DQB1, and -DPB1). The polymorphism of TNF, LTA, C4, BTNL2 and HLA-DRA genes was studied with 74 SNPs (single nucleotide polymorphism). The C4A and C4B gene copy numbers and a 2-bp silencing insertion at exon 29 in C4A gene were analysed with quantitative genomic realtime-PCR. The allele frequencies for each locus were calculated and haplotypes were constructed using both the traditional HLA alleles and SNP blocks. The most frequent Finnish A∼B∼DR -haplotype, uncommon in elsewhere in Europe, was A03∼B35∼DRB101∶01. The second most common haplotype was a common European ancestral haplotype AH 8.1 (A01∼B08∼DRB103∶01). Extended haplotypes containing HLA-B, TNF block, C4 and HLA-DPB1 strongly increased the number of HLA-DRB1 haplotypes showing variability in the extended HLA-DRB1 haplotype structures. On the contrary, BTNL2 block and HLA-DQB1 were more conserved showing linkage with the HLA-DRB1 alleles. We show that the use of HLA-DRB1 haplotypes rather than single HLA-DRB1 alleles is advantageous when studying the polymorphisms and LD patters of the MHC region. For disease association studies the HLA-DRB1 haplotypes with various MHC markers allows us to cluster haplotypes with functionally important gene variants such as C4 deficiency and cytokines TNF and LTA, and provides hypotheses for further assessment. Our study corroborates the importance of studying population-specific MHC haplotypes.Annika WennerströmEfthymia VlachopoulouL Elisa LahtelaRiitta PaakkanenKatja T EronenMikko SeppänenMarja-Liisa LokkiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79690 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Annika Wennerström Efthymia Vlachopoulou L Elisa Lahtela Riitta Paakkanen Katja T Eronen Mikko Seppänen Marja-Liisa Lokki Diversity of extended HLA-DRB1 haplotypes in the Finnish population.
description	The Major Histocompatibility Complex (MHC, 6p21) codes for traditional HLA and other host response related genes. The polymorphic HLA-DRB1 gene in MHC Class II has been associated with several complex diseases. In this study we focus on MHC haplotype structures in the Finnish population. We explore the variability of extended HLA-DRB1 haplotypes in relation to the other traditional HLA genes and a selected group of MHC class III genes. A total of 150 healthy Finnish individuals were included in the study. Subjects were genotyped for HLA alleles (HLA-A, -B, -DRB1, -DQB1, and -DPB1). The polymorphism of TNF, LTA, C4, BTNL2 and HLA-DRA genes was studied with 74 SNPs (single nucleotide polymorphism). The C4A and C4B gene copy numbers and a 2-bp silencing insertion at exon 29 in C4A gene were analysed with quantitative genomic realtime-PCR. The allele frequencies for each locus were calculated and haplotypes were constructed using both the traditional HLA alleles and SNP blocks. The most frequent Finnish A∼B∼DR -haplotype, uncommon in elsewhere in Europe, was A03∼B35∼DRB101∶01. The second most common haplotype was a common European ancestral haplotype AH 8.1 (A01∼B08∼DRB103∶01). Extended haplotypes containing HLA-B, TNF block, C4 and HLA-DPB1 strongly increased the number of HLA-DRB1 haplotypes showing variability in the extended HLA-DRB1 haplotype structures. On the contrary, BTNL2 block and HLA-DQB1 were more conserved showing linkage with the HLA-DRB1 alleles. We show that the use of HLA-DRB1 haplotypes rather than single HLA-DRB1 alleles is advantageous when studying the polymorphisms and LD patters of the MHC region. For disease association studies the HLA-DRB1 haplotypes with various MHC markers allows us to cluster haplotypes with functionally important gene variants such as C4 deficiency and cytokines TNF and LTA, and provides hypotheses for further assessment. Our study corroborates the importance of studying population-specific MHC haplotypes.
format	article
author	Annika Wennerström Efthymia Vlachopoulou L Elisa Lahtela Riitta Paakkanen Katja T Eronen Mikko Seppänen Marja-Liisa Lokki
author_facet	Annika Wennerström Efthymia Vlachopoulou L Elisa Lahtela Riitta Paakkanen Katja T Eronen Mikko Seppänen Marja-Liisa Lokki
author_sort	Annika Wennerström
title	Diversity of extended HLA-DRB1 haplotypes in the Finnish population.
title_short	Diversity of extended HLA-DRB1 haplotypes in the Finnish population.
title_full	Diversity of extended HLA-DRB1 haplotypes in the Finnish population.
title_fullStr	Diversity of extended HLA-DRB1 haplotypes in the Finnish population.
title_full_unstemmed	Diversity of extended HLA-DRB1 haplotypes in the Finnish population.
title_sort	diversity of extended hla-drb1 haplotypes in the finnish population.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/3cc81cb7be214ddb82042e64986280fd
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Diversity of extended HLA-DRB1 haplotypes in the Finnish population.

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