High Frequency of the TCRBV20S1 Null Allele in the Sardinian Population

Bonfigli, Silvana; Fozza, Claudio; Contini, Salvatore; Buzzetti, Raffaella; Cucca, Francesco; Longinotti, M

doi:10.1016/j.humimm.2007.01.011

Cited by 4 publications

(2 citation statements)

References 23 publications

(33 reference statements)

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“…Thirty one healthy Greek children (mean age ± SD: 6.58 years ± 3.65, 26 males-5 females) undergoing minor surgery at the First and Second Department of Surgery at “Aghia Sophia” Children’s Hospital were included as controls. Taking into account that several germ line polymorphisms of the TCR Vβ genes have been described in different ethnicities [22,23], this study was restricted to children of Greek origin in order to include an ethnically homogeneous population. A standardized interview was held with parents of all children.…”

Section: Methodsmentioning

confidence: 99%

Flow cytometric analysis of the CD4+ TCR Vβ repertoire in the peripheral blood of children with type 1 diabetes mellitus, systemic lupus erythematosus and age-matched healthy controls

et al. 2013

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BackgroundData regarding the quantitative expression of TCR Vβ subpopulations in children with autoimmune diseases provided interesting and sometimes conflicting results. The aim of the present study was to assess by comparative flow cytometric analysis the peripheral blood CD4+ TCR Vβ repertoire of children with an organ-specific autoimmune disorder, such as type 1 diabetes mellitus (T1DM), in comparison to children with a systemic autoimmune disease, such as Systemic Lupus Erythematosus (SLE) in comparison to healthy age-matched controls of the same ethnic origin. The CD4+ TCR Vβ repertoire was analysed by flow cytometry in three groups of participants: a) fifteen newly diagnosed children with T1DM (mean age: 9.2 ± 4.78 years old), b) nine newly diagnosed children with SLE, positive for ANA and anti-dsDNA, prior to treatment (mean age: 12.8 ±1.76 years old) and c) 31 healthy age-matched controls (mean age: 6.58 ± 3.65 years old), all of Hellenic origin.ResultsCD4 + TCR Vβ abnormalities (± 3SD of controls) were observed mainly in SLE patients. Statistical analysis revealed that the CD4 + Vβ4 chain was significantly increased in patients with T1DM (p < 0.001), whereas CD4 + Vβ16 one was significantly increased in SLE patients (p < 0.001) compared to controls.ConclusionsCD4 + Vβ4 and CD4 + Vβ16 chains could be possibly involved in the cascade of events precipitating the pathogenesis of T1DM and SLE in children, respectively.

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Section: Methodsmentioning

confidence: 99%

Flow cytometric analysis of the CD4+ TCR Vβ repertoire in the peripheral blood of children with type 1 diabetes mellitus, systemic lupus erythematosus and age-matched healthy controls

et al. 2013

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“…This is a striking finding when compared with the extreme degree of homozygosis found in our study population in spite of the relatively high allelic variability. We estimated an apparently high null allele frequency per locus [ranging from 43.2%, Brookfield method, to 48.5% (Oosterhouth method, similar for example to that described for T-cell receptor gene segments in human Sardinian population, one of the most elevated so far reported in the literature, Bonfigli et al, 2007). One possibility is that undetermined selective pressure could have played a role in determining the high frequency of this inactivating polymorphism in deer, although alternatively, due to the relatively short period of time since population foundation, these findings are more consistent with a sound founder effect due to original introduction of deer carrying MHC DRB-2 locus null alleles], contrasting with allele frequency data from external control animals.…”

Section: Discussionmentioning

confidence: 99%

Reduced major histocompatibility complex class II polymorphism in a hunter‐managed isolated Iberian red deer population

Fernández-de-Mera¹,

Vicente²,

Lastra³

et al. 2009

Journal of Zoology

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The major histocompatibility complex (MHC) contains the most variable functional genes described in vertebrates. Individuals from natural populations deal constantly with a diverse range of pathogens and the polymorphism at MHC loci is what determines the diversity of foreign antigens that the host immune system can recognize. Polymorphism at individual loci may result in variable MHC class II (MHC-II) haplotypes. We characterized for the first time, the allelic diversity at the second DRB locus of the MHC-II in the Iberian red deer Cervus elaphus hispanicus. The studied population was sampled from a fenced estate that has been managed for hunting purposes and may provide information of the effect of game management on the genetic diversity of this species. Deer presented high levels of variation at MHC-II DRB-2 with 18 different alleles detected in 94 individuals. However, a significant heterozygous deficiency was found for MHC-II DRB-2 locus (92.5% of individuals only amplified one allele), whereas genotype frequencies at three neutral microsatellite loci were according to Hardy-Weinberg equilibrium, with heterozygosity over 50%. The analysis of control Iberian red deer from different geographic locations identified two expressed DRB-2 loci with a high degree of heterozygosis. The annual diversity index of MHC-II DRB-2 alleles significantly decreased along the 16-year study period, which was confirmed with losses in microsatellite markers. Although we cannot exclude positive nonassortative mating and/or substructured breeding (Wahlund effect) within our reference population, such unexpected apparent homozygosity at MHC DRB-2 loci is suggestive of null alleles occurring at our population. The observed pattern could be the result of a founder effect in this recently established population. Nonetheless, the loss of MHC-II DRB-2 allele diversity could reflect the effects of inbreeding in this fenced population managed for hunting. These findings support the importance of immunogenetic studies to assess management decisions, especially in isolated ungulate populations.

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TCRBV20S1 polymorphism does not influence the susceptibility to type 1 diabetes and multiple sclerosis in the Sardinian population

et al. 2011

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Among the different T-cell receptor (TCR) BV20S1 polymorphisms, nucleotide substitution at position 524 results in the introduction of a stop codon, whose potential functional relevance is still unknown. We have recently showed in Sardinian subjects the most elevated allele frequency ever reported worldwide for this "null allele" (0.44). As this variant generates a gap in the TCR repertoire, this preliminary finding prompted us to further analyze the role of this polymorphism in the susceptibility to type 1 diabetes (T1D) and multiple sclerosis (MS), which are extremely common in this population. With this aim, we evaluated the influence of the TCRBV20S1 polymorphism by assessing it with the transmission disequilibirum test (TDT) in 652 T1D and 616 MS families, without detecting any significant difference. We conclude that the high frequency of this null allele in Sardinia is not directly related to the high incidence of these autoimmune diseases observed in this founder population.

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High Frequency of the TCRBV20S1 Null Allele in the Sardinian Population

Cited by 4 publications

References 23 publications

Flow cytometric analysis of the CD4+ TCR Vβ repertoire in the peripheral blood of children with type 1 diabetes mellitus, systemic lupus erythematosus and age-matched healthy controls

Flow cytometric analysis of the CD4+ TCR Vβ repertoire in the peripheral blood of children with type 1 diabetes mellitus, systemic lupus erythematosus and age-matched healthy controls

Reduced major histocompatibility complex class II polymorphism in a hunter‐managed isolated Iberian red deer population

TCRBV20S1 polymorphism does not influence the susceptibility to type 1 diabetes and multiple sclerosis in the Sardinian population

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