Genetic mapping of susceptibility loci in the genes involved in rheumatoid arthritis.

Eighty-nine multicase rheumatoid arthritis families, each containing at least one affected sib pair, have been studied for evidence of genetic linkage to a panel of 315 microsatellite DNA markers. The families were located through the UK national data repository of the Arthritis and Rheumatism Council. Microsatellites were genotyped by semiautomated technology using Applied Biosystems sequencers (ABI 373). Using the SIBPAIR statistical package, linkage to HLA was confirmed (p < 0.0003). Several possible linkages outside HLA were noted, including at least one (p < 0.004) that merits further investigation

Rheumatoid arthritis susceptibility and interleukin 10: a study of two ethnically diverse populations.

INTRODUCTION: IL-10 is an immunoregulatory cytokine which may modulate disease expression in rheumatoid arthritis (RA). The IL-10 gene is highly polymorphic with a number of single nucleotide polymorphisms in the promoter region and two microsatellite loci, IL10.R and IL10.G, 4 kb and 1.1 kb 5' of the transcription initiation site. It has been reported that allele 2 of the IL10.R microsatellite (IL10.R2) is associated with increased IL-10 secretion and IL10.R3 with reduced secretion. Subsequently, over-representation of IL10.R2 and under-representation of IL10.R3 in three independent RA groups has been reported. The aim of the current study is to determine whether there is an association between the IL10.R2 allele and RA in two ethnically distinct populations. METHODS: IL10.R genotypes were determined by semi-automated DNA sequencing technology in 186 UK Caucasians and 138 South Africans of Zulu or Sotho origin, fulfilling the 1987 American College of Rheumatology (ACR) criteria for RA. The Caucasian patients had relatively severe disease and comprised 75 patients with RA vasculitis, 22 with Felty's syndrome and 89 who had undergone a joint replacement (hip or knee) within 15 years of the onset of disease. Allele frequencies were compared with 296 Caucasians and/or 73 South Africans. RESULTS: The frequency of the IL10.R2 allele was significantly greater in the South Africans (RA and controls) than in the Caucasians (0.78 vs 0.66, P=1 x 10(-6)), while the frequency of IL10.R3 was less common (0.16 vs 0.3, P=1 x 10(-8)). No differences were observed in either IL10.R2 or IL10.R3 frequencies between patients and controls in either population. CONCLUSIONS: We were unable to confirm any association between IL10.R alleles and RA in this study. However, significant differences were demonstrated in the frequency of IL10.R2 and IL10.R3 between the two ethnic groups. The relatively high frequency of IL10.R2 in the South African population (0.78) would have reduced the power to detect an association with RA

Post-fire Management Affects Species Composition but not Douglas-fir Regeneration in the Klamath Mountains

Ensuring adequate conifer regeneration after high severity wildfires is a common objective for ecologists and forest managers. In the Klamath region of Oregon and California, a global hotspot of botanical biodiversity, concerns over regeneration have led to post-fire management on many sites, which involves salvage logging followed by site preparation, conifer planting, and manual shrub release. To quantify the impacts of post-fire management, we sampled 62 field sites that burned at high severity nearly 20 years ago in the Klamath-Siskiyou Mountain bioregion, stratifying by management and aspect. We measured cover of shrubs and trees and density and frequency of trees and used Nonmetric Multidimensional Scaling to compare community composition, plant community assemblage based on regenerative traits, and density of tree species between aspect and management. On average, shrub cover exceeded the cover of conifers, hardwoods or grasses, regardless of management history or aspect. The average number of species was lower and resprouting species were less abundant on south aspect sites; seed banking species were most abundant on north aspects. Post-fire management was associated with greater cover of seed banking and nitrogen-fixing species but it did not affect diversity. Management had no impact on Douglas-fir regeneration, the main species of concern in the region. Regeneration of ponderosa pine was higher on sites with post-fire management, but only on south slopes. The frequency of Douglas-fir was associated with aspect, while the frequency of ponderosa pine was associated with management. Overall, our study demonstrates the important role that aspect plays in determining the effectiveness of management after high severity wildfires. Indeed, the effect of aspect on site conditions often overwhelmed the ability of management to influence community composition (including different regenerative strategies), species diversity, and regeneration. Managed sites differed from unmanaged sites in several diverse ways with varied implications for longer-term forest development. Managed sites had taller dominant conifers, which suggests that post-fire management could hasten the period needed to achieve fire resistance. Managed sites were similar in plant community composition but had more homogeneous structure--e.g., managed sites had fewer snags, which are an important habitat feature for several bird species in the region. Finally, management was not associated with conifer regeneration success on north slopes, suggesting that interventions may not be needed uniformly across post-fire landscape. New policies of ecosystem-based management in the Klamath region should consider the important interactions between aspect and post-fire management, and tailor management practices based on specific objectives and landscape context

The role of germline polymorphisms in the T-cell receptor in susceptibility to ankylosing spondylitis.

The role of germline polymorphisms of the T-cell receptor A/D and B loci in susceptibility to ankylosing spondylitis was investigated by linkage studies using microsatellite markers in 215 affected sibling pairs. The presence of a significant susceptibility gene (lambda > or = 1.6) at the TCRA/D locus was excluded (LOD score < -2.0). At the TCRB locus, there was weak evidence of the presence of a susceptibility gene (P = 0.01, LOD score 1.1). Further family studies will be required to determine whether this is a true or false-positive finding. It is unlikely that either the TCRA/D or TCRB loci contain genes responsible for more than a moderate proportion of the non-MHC genetic susceptibility to ankylosing spondylitis