Article Text
Abstract
Background: Ankylosing spondylitis (AS) is a chronic, potentially crippling, spondyloarthropathy with strong genetic components affecting approximately 0.3% of the population. Its exact genetic mechanism and mode of transmission, however, remains obscure.
Methods and results: The authors conducted a genome wide scan on 75 individuals across multiple generations of three Han Chinese families affected with AS. Segregation analysis and pedigree investigation suggested an autosomal dominant inheritance. Pairwise logarithm of odds (LOD) scores were calculated using LINKAGE package for the obtained genotypes. High resolution mapping was then performed based on markers with significant LOD scores. To minimise the number of crossovers in each family, haplotype were constructed and assigned. Two of the pedigrees shared one candidate region for AS on 2q36.1–2q36.3 spanning 6-cM (maximum heterogeneity LOD score of 12.41 at marker D2S2228), while the other showed strong linkage to the HLA-B region.
Conclusions: This is the first report which proposes one of the new genetic models of autosomal dominant transmission in AS. The breakthrough in the identification of linkage to chromosome 2q36.1–2q36.3 and the HLA-B region highlights the future potential of more comprehensive genetic studies of determinants of disease risk.
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Footnotes
JG, JH, CL and LZ contributed equally to this article
Funding This study was funded by grants (30325019, 30571735, 30471611 and 30872328) from the National Natural Sciences Foundation of China, and grants (2002Z3-E4021 and 2005A30801005) from Foundation of Guangzhou and Guangdong province of China.
Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.