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Association of chromosome 2q36.1-36.3 and autosomal dominant transmission in ankylosing spondylitis: results of genetic studies across generations of Han Chinese families.

Gu J, Huang J, Li C, Zhao L, Huang F, Liao Z, Li T, Wei Q, Lin Z, Pan Y, Huang J, Wang X, Lin Q, Lu C, Wu Y, Cao S, Wu J, Xu H, Yu B, Shen Y - J. Med. Genet. (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

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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Related in: MedlinePlus

Shared haplotype of family A and B. Marker haplotypes on chromosome 2q36.1–2q36.3 that are linked to ankylosing spondylitis (AS) are indicated by black bars. Marker positions were obtained from Marshfield (http://research.marshfieldclinic.org/genetics/GeneticResearch/compMaps.asp). Microsatellite markers are listed at left from centromere to telomere (top to bottom). The proband was marked with an arrow. Haplotypes were interpreted by minimising recombinants. In each haplotype pair, paternal haplotype is to the left and maternal to the right.
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JMG-46-10-0657-f02: Shared haplotype of family A and B. Marker haplotypes on chromosome 2q36.1–2q36.3 that are linked to ankylosing spondylitis (AS) are indicated by black bars. Marker positions were obtained from Marshfield (http://research.marshfieldclinic.org/genetics/GeneticResearch/compMaps.asp). Microsatellite markers are listed at left from centromere to telomere (top to bottom). The proband was marked with an arrow. Haplotypes were interpreted by minimising recombinants. In each haplotype pair, paternal haplotype is to the left and maternal to the right.

Mentions: The distribution of affected AS patients among the three pedigrees and their family structure are shown in figs 1 and 2. In the 25 AS patients of the 3 families, 15 are male and 10 are female (male: female ratio 3:2). The disease duration (mean (SD)) is 9.82 (5.80) years. The onset age (mean (SD)) is 22.45 (6.21) years, ranging from 9–31 years. In clinical manifestations, all patients have sacroiliac and spinal involvement. Among them, nine patients had peripheral joint involvement and 12 patients had enthesitis in three families, respectively. In family A, three patients had hip involvement. None of the affected individuals had a history of uveitis.


Association of chromosome 2q36.1-36.3 and autosomal dominant transmission in ankylosing spondylitis: results of genetic studies across generations of Han Chinese families.

Gu J, Huang J, Li C, Zhao L, Huang F, Liao Z, Li T, Wei Q, Lin Z, Pan Y, Huang J, Wang X, Lin Q, Lu C, Wu Y, Cao S, Wu J, Xu H, Yu B, Shen Y - J. Med. Genet. (2009)

Shared haplotype of family A and B. Marker haplotypes on chromosome 2q36.1–2q36.3 that are linked to ankylosing spondylitis (AS) are indicated by black bars. Marker positions were obtained from Marshfield (http://research.marshfieldclinic.org/genetics/GeneticResearch/compMaps.asp). Microsatellite markers are listed at left from centromere to telomere (top to bottom). The proband was marked with an arrow. Haplotypes were interpreted by minimising recombinants. In each haplotype pair, paternal haplotype is to the left and maternal to the right.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2748191&req=5

JMG-46-10-0657-f02: Shared haplotype of family A and B. Marker haplotypes on chromosome 2q36.1–2q36.3 that are linked to ankylosing spondylitis (AS) are indicated by black bars. Marker positions were obtained from Marshfield (http://research.marshfieldclinic.org/genetics/GeneticResearch/compMaps.asp). Microsatellite markers are listed at left from centromere to telomere (top to bottom). The proband was marked with an arrow. Haplotypes were interpreted by minimising recombinants. In each haplotype pair, paternal haplotype is to the left and maternal to the right.
Mentions: The distribution of affected AS patients among the three pedigrees and their family structure are shown in figs 1 and 2. In the 25 AS patients of the 3 families, 15 are male and 10 are female (male: female ratio 3:2). The disease duration (mean (SD)) is 9.82 (5.80) years. The onset age (mean (SD)) is 22.45 (6.21) years, ranging from 9–31 years. In clinical manifestations, all patients have sacroiliac and spinal involvement. Among them, nine patients had peripheral joint involvement and 12 patients had enthesitis in three families, respectively. In family A, three patients had hip involvement. None of the affected individuals had a history of uveitis.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

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.

Show MeSH
Related in: MedlinePlus