TY - JOUR
T1 - The gene responsible for autoimmune polyglandular syndrome type 1 maps to chromosome 21q22.3 in US patients
AU - Chen, Qiao Yi
AU - Lan, Michael S.
AU - She, Jing Xiong
AU - Maclaren, Noel K.
N1 - Funding Information:
We would like to thank Professor Bronya Keats for her advice with the linkage analyses performed herein, Dr Defang Luo for technical advice and Mr Charles Garner for data management assistance. We would also like to thank the physicians and patients for their co-operation in providing DNA samples for our study. QYC is supported by a mentor-based fellowship from the American Diabetes Association.
PY - 1998/4
Y1 - 1998/4
N2 - Autoimmune polyglandular syndrome type 1 [APS-1] comprises multiple organ-specific autoimmunities such as acquired hypoparathyroidism and autoimmune Addison's disease, and a predisposition to certain infections such as chronic mucocutaneous candidiasis. An APS-1 candidate gene was assigned to chromosome 21q22.3 by linkage analyses in patients with APS-1 from Finland. To examine the influence of ethnic and geographic differences on the location of the candidate gene locus, we studied 24 US patients with APS-1 by microsatellite marker typing, using five microsatellite markers, D21S49, PFKL, D21S171, D21S1903 and CD18, selected from chromosome 21q22.3. By allelic association analyses, the frequencies of allele number 5 for D21S171 and allele number 8 for D21S1903 were significantly higher in the 24 patients with APS-1 than in 33 controls (33/48 vs. 31/66, P=0.0207, X2=5.35; 12/48 vs. 7/66, P=0.0418, X2=4.15 respectively). The frequency of homozygosity for allele number 5 of D21S171 was also significantly higher in the patients than in controls, 15/24 vs. 9/33 (P=0.0078, X2=7.07). Maximum lod scores detected for the five markers in nine families (containing 15 of the patients with APS-1) were: 2.384 for D21S49, 3.144 for PFKL, 3.506 for D21S171, 4.329 for D21S1903, and 1.130 for CD18. These results confirm the linkage of the candidate APS-1 gene to 21q22.3 in US APS-1 patients, and suggest that the candidate gene is located near the D21S1903 marker. The demonstration of the location of the APS-1 candidate gene to 21q22.3 in an out-bred heterogeneous patient population should promote the physical mapping of the responsible gene.
AB - Autoimmune polyglandular syndrome type 1 [APS-1] comprises multiple organ-specific autoimmunities such as acquired hypoparathyroidism and autoimmune Addison's disease, and a predisposition to certain infections such as chronic mucocutaneous candidiasis. An APS-1 candidate gene was assigned to chromosome 21q22.3 by linkage analyses in patients with APS-1 from Finland. To examine the influence of ethnic and geographic differences on the location of the candidate gene locus, we studied 24 US patients with APS-1 by microsatellite marker typing, using five microsatellite markers, D21S49, PFKL, D21S171, D21S1903 and CD18, selected from chromosome 21q22.3. By allelic association analyses, the frequencies of allele number 5 for D21S171 and allele number 8 for D21S1903 were significantly higher in the 24 patients with APS-1 than in 33 controls (33/48 vs. 31/66, P=0.0207, X2=5.35; 12/48 vs. 7/66, P=0.0418, X2=4.15 respectively). The frequency of homozygosity for allele number 5 of D21S171 was also significantly higher in the patients than in controls, 15/24 vs. 9/33 (P=0.0078, X2=7.07). Maximum lod scores detected for the five markers in nine families (containing 15 of the patients with APS-1) were: 2.384 for D21S49, 3.144 for PFKL, 3.506 for D21S171, 4.329 for D21S1903, and 1.130 for CD18. These results confirm the linkage of the candidate APS-1 gene to 21q22.3 in US APS-1 patients, and suggest that the candidate gene is located near the D21S1903 marker. The demonstration of the location of the APS-1 candidate gene to 21q22.3 in an out-bred heterogeneous patient population should promote the physical mapping of the responsible gene.
KW - APS-1
KW - Candidate gene
KW - Chromosome 21q22.3
KW - Genetic linkage
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U2 - 10.1006/jaut.1998.0191
DO - 10.1006/jaut.1998.0191
M3 - Article
C2 - 9650097
AN - SCOPUS:0031800658
SN - 0896-8411
VL - 11
SP - 177
EP - 183
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
IS - 2
ER -