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Balancing selection is common in the extended MHC region but most alleles with opposite risk profile for autoimmune diseases are neutrally evolving.(Research article)(major histocompatibility complex)(Report)

Background Several susceptibility genetic variants for autoimmune diseases have been identified. A subset of these polymorphisms displays an opposite risk profile in different autoimmune conditions. This observation open interesting questions on the evolutionary forces shaping the frequency of these... Full description

Journal Title: BMC Evolutionary Biology June 17, 2011, Vol.11, p.171
Main Author: Cagliani, Rachele
Other Authors: Riva, Stefania , Pozzoli, Uberto , Fumagalli, Matteo , Comi, Giacomo P. , Bresolin, Nereo , Clerici, Mario , Sironi, Manuela
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Cengage Learning, Inc.
ID: ISSN: 1471-2148
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title: Balancing selection is common in the extended MHC region but most alleles with opposite risk profile for autoimmune diseases are neutrally evolving.(Research article)(major histocompatibility complex)(Report)
format: Article
creator:
  • Cagliani, Rachele
  • Riva, Stefania
  • Pozzoli, Uberto
  • Fumagalli, Matteo
  • Comi, Giacomo P.
  • Bresolin, Nereo
  • Clerici, Mario
  • Sironi, Manuela
subjects:
  • Alleles -- Physiological Aspects
  • Alleles -- Research
  • Major Histocompatibility Complex -- Physiological Aspects
  • Major Histocompatibility Complex -- Genetic Aspects
  • Major Histocompatibility Complex -- Research
  • Autoimmune Diseases -- Risk Factors
  • Autoimmune Diseases -- Genetic Aspects
  • Autoimmune Diseases -- Research
  • Single Nucleotide Polymorphisms -- Research
ispartof: BMC Evolutionary Biology, June 17, 2011, Vol.11, p.171
description: Background Several susceptibility genetic variants for autoimmune diseases have been identified. A subset of these polymorphisms displays an opposite risk profile in different autoimmune conditions. This observation open interesting questions on the evolutionary forces shaping the frequency of these alleles in human populations. We aimed at testing the hypothesis whereby balancing selection has shaped the frequency of opposite risk alleles. Results Since balancing selection signatures are expected to extend over short genomic portions, we focused our analyses on 11 regions carrying putative functional polymorphisms that may represent the disease variants (and the selection targets). No exceptional nucleotide diversity was observed for ZSCAN23, HLA-DMB, VARS2, PTPN22, BAT3, C6orf47, and IL10; summary statistics were consistent with evolutionary neutrality for these gene regions. Conversely, CDSN/PSORS1C1, TRIM10/TRIM40, BTNL2, and TAP2 showed extremely high nucleotide diversity and most tests rejected neutrality, suggesting the action of balancing selection. For TAP2 and BTNL2 these signatures are not secondary to linkage disequilibrium with HLA class II genes. Nonetheless, with the exception of variants in TRIM40 and CDSN, our data suggest that opposite risk SNPs are not selection targets but rather have accumulated as neutral variants. Conclusion Data herein indicate that balancing selection is common within the extended MHC region and involves several non-HLA loci. Yet, the evolutionary history of most SNPs with an opposite effect for autoimmune diseases is consistent with evolutionary neutrality. We suggest that variants with an opposite effect on autoimmune diseases should not be considered a distinct class of disease alleles from the evolutionary perspective and, in a few cases, the opposite effect on distinct diseases may derive from complex haplotype structures in regions with high genetic diversity.
language: English
source: Cengage Learning, Inc.
identifier: ISSN: 1471-2148
fulltext: fulltext
issn:
  • 1471-2148
  • 14712148
url: Link


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titleBalancing selection is common in the extended MHC region but most alleles with opposite risk profile for autoimmune diseases are neutrally evolving.(Research article)(major histocompatibility complex)(Report)
creatorCagliani, Rachele ; Riva, Stefania ; Pozzoli, Uberto ; Fumagalli, Matteo ; Comi, Giacomo P. ; Bresolin, Nereo ; Clerici, Mario ; Sironi, Manuela
ispartofBMC Evolutionary Biology, June 17, 2011, Vol.11, p.171
identifierISSN: 1471-2148
subjectAlleles -- Physiological Aspects ; Alleles -- Research ; Major Histocompatibility Complex -- Physiological Aspects ; Major Histocompatibility Complex -- Genetic Aspects ; Major Histocompatibility Complex -- Research ; Autoimmune Diseases -- Risk Factors ; Autoimmune Diseases -- Genetic Aspects ; Autoimmune Diseases -- Research ; Single Nucleotide Polymorphisms -- Research
descriptionBackground Several susceptibility genetic variants for autoimmune diseases have been identified. A subset of these polymorphisms displays an opposite risk profile in different autoimmune conditions. This observation open interesting questions on the evolutionary forces shaping the frequency of these alleles in human populations. We aimed at testing the hypothesis whereby balancing selection has shaped the frequency of opposite risk alleles. Results Since balancing selection signatures are expected to extend over short genomic portions, we focused our analyses on 11 regions carrying putative functional polymorphisms that may represent the disease variants (and the selection targets). No exceptional nucleotide diversity was observed for ZSCAN23, HLA-DMB, VARS2, PTPN22, BAT3, C6orf47, and IL10; summary statistics were consistent with evolutionary neutrality for these gene regions. Conversely, CDSN/PSORS1C1, TRIM10/TRIM40, BTNL2, and TAP2 showed extremely high nucleotide diversity and most tests rejected neutrality, suggesting the action of balancing selection. For TAP2 and BTNL2 these signatures are not secondary to linkage disequilibrium with HLA class II genes. Nonetheless, with the exception of variants in TRIM40 and CDSN, our data suggest that opposite risk SNPs are not selection targets but rather have accumulated as neutral variants. Conclusion Data herein indicate that balancing selection is common within the extended MHC region and involves several non-HLA loci. Yet, the evolutionary history of most SNPs with an opposite effect for autoimmune diseases is consistent with evolutionary neutrality. We suggest that variants with an opposite effect on autoimmune diseases should not be considered a distinct class of disease alleles from the evolutionary perspective and, in a few cases, the opposite effect on distinct diseases may derive from complex haplotype structures in regions with high genetic diversity.
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titleBalancing selection is common in the extended MHC region but most alleles with opposite risk profile for autoimmune diseases are neutrally evolving.(Research article)(major histocompatibility complex)(Report)
descriptionBackground Several susceptibility genetic variants for autoimmune diseases have been identified. A subset of these polymorphisms displays an opposite risk profile in different autoimmune conditions. This observation open interesting questions on the evolutionary forces shaping the frequency of these alleles in human populations. We aimed at testing the hypothesis whereby balancing selection has shaped the frequency of opposite risk alleles. Results Since balancing selection signatures are expected to extend over short genomic portions, we focused our analyses on 11 regions carrying putative functional polymorphisms that may represent the disease variants (and the selection targets). No exceptional nucleotide diversity was observed for ZSCAN23, HLA-DMB, VARS2, PTPN22, BAT3, C6orf47, and IL10; summary statistics were consistent with evolutionary neutrality for these gene regions. Conversely, CDSN/PSORS1C1, TRIM10/TRIM40, BTNL2, and TAP2 showed extremely high nucleotide diversity and most tests rejected neutrality, suggesting the action of balancing selection. For TAP2 and BTNL2 these signatures are not secondary to linkage disequilibrium with HLA class II genes. Nonetheless, with the exception of variants in TRIM40 and CDSN, our data suggest that opposite risk SNPs are not selection targets but rather have accumulated as neutral variants. Conclusion Data herein indicate that balancing selection is common within the extended MHC region and involves several non-HLA loci. Yet, the evolutionary history of most SNPs with an opposite effect for autoimmune diseases is consistent with evolutionary neutrality. We suggest that variants with an opposite effect on autoimmune diseases should not be considered a distinct class of disease alleles from the evolutionary perspective and, in a few cases, the opposite effect on distinct diseases may derive from complex haplotype structures in regions with high genetic diversity.
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abstractBackground Several susceptibility genetic variants for autoimmune diseases have been identified. A subset of these polymorphisms displays an opposite risk profile in different autoimmune conditions. This observation open interesting questions on the evolutionary forces shaping the frequency of these alleles in human populations. We aimed at testing the hypothesis whereby balancing selection has shaped the frequency of opposite risk alleles. Results Since balancing selection signatures are expected to extend over short genomic portions, we focused our analyses on 11 regions carrying putative functional polymorphisms that may represent the disease variants (and the selection targets). No exceptional nucleotide diversity was observed for ZSCAN23, HLA-DMB, VARS2, PTPN22, BAT3, C6orf47, and IL10; summary statistics were consistent with evolutionary neutrality for these gene regions. Conversely, CDSN/PSORS1C1, TRIM10/TRIM40, BTNL2, and TAP2 showed extremely high nucleotide diversity and most tests rejected neutrality, suggesting the action of balancing selection. For TAP2 and BTNL2 these signatures are not secondary to linkage disequilibrium with HLA class II genes. Nonetheless, with the exception of variants in TRIM40 and CDSN, our data suggest that opposite risk SNPs are not selection targets but rather have accumulated as neutral variants. Conclusion Data herein indicate that balancing selection is common within the extended MHC region and involves several non-HLA loci. Yet, the evolutionary history of most SNPs with an opposite effect for autoimmune diseases is consistent with evolutionary neutrality. We suggest that variants with an opposite effect on autoimmune diseases should not be considered a distinct class of disease alleles from the evolutionary perspective and, in a few cases, the opposite effect on distinct diseases may derive from complex haplotype structures in regions with high genetic diversity.
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