Linkage analysis of genetic loci for kyphoscoliosis on chromosomes 5q13, 13q13.3, and 13q32
Linkage analysis of genetic loci for kyphoscoliosis on chromosomes 5q13, 13q13.3, and 13q32
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DOI：
10.1002/ajmg.a.31211
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发表时间：
2006-05-15
影响因子：
2
通讯作者：
Wilson, AF
中科院分区：
文献类型：
--
作者：
Miller, NH;Marosy, B;Wilson, AF
脊柱后凸是一种脊柱生长的三维畸形，其特征是冠状面的弯曲（脊柱侧凸）以及矢状面超出正常范围的胸椎后凸。我们在七个家庭的成员（53 人）中发现了脊柱后侧凸，最初是作为家族特发性脊柱侧凸大型合作研究的一部分而确定的。全基因组微卫星筛选的模型独立连锁分析确定了染色体 2q22、5p13、13q 和 17q11 上暗示连锁的区域。对另外 25 个侧翼微卫星市场的单点和多点分析证实了与这些区域的联系，其中染色体 5p13、13q13 和 13q32 上的区域最为显着（P < 0.005）。对 5 号染色体候选区域中的单核苷酸多态性 (SNP) 标记的分析将该区域缩小到大约 3.5 Mb (p < 0.05)，“显着性 P 值丢失 (P < 0.01) 发生在大约 1.3 Mb 的区域。该区域的候选基因座包括 Iroquois 同源盒蛋白家族的 IRX1、IRX2 和 IRX4。在 13 号染色体上，单点和多点分析结果显示，五个候选基因中的多个 SNP 的 P 值 < 0.05：成骨细胞特异性因子 2 或骨膜素、叉头框 O1A、A-激酶锚定蛋白 11、TBC1 结构域家族成员 4 和磷脂酰肌醇蛋白聚糖 5，从而支持该区域在脊柱后凸发病机制中的潜在相关性 (c) 2006 Wiley-Liss, Inc.。
Kyphoscoliosis, a three-dimensional deformity of spinal growth, is characterized by a curvature in the coronal plane (scoliosis) in conjunction with thoracic kyphosis in excess of the normal range in the sagittal plane. We identified kyphoscoliosis within members of seven families (53 individuals) originally ascertained as part of a large collaborative study of familial idiopathic scoliosis. Model-independent linkage analysis of a genome-wide microsatellite screen identified areas suggestive of linkage on chromosomes 2q22, 5p13, 13q, and 17q11. Single-point and multipoint analyses of an additional 25 flanking microsatellite markets corroborated linkage to these regions, with areas on chromosomes 5p13, 13q13, and 13q32 being the most: significant (P < 0.005). Analyses of single nucleotide polymorphism (SNP) markers in the candidate region oil chromosome 5 narrowed the region to approximately 3.5 Mb (p < 0.05), with the "lost significant P values (P < 0.01) occurring ill approximately a 1.3-Mb region. Candidate loci in this region include IRX1, IRX2, and IRX4 of the Iroquois Homeobox protein family. On chromosome 13, single-point and multipoint analyses resulted in multiple SNPs having P values < 0.05 within five candidate genes: Osteoblast-specific factor 2 or periostin, forkhead box O1A, A-kinase anchor protein 11, TBC1 domain family member 4, and glypican 5, thus supporting the potential relevance of this region in the pathogenesis of kyphoscoliosis. (c) 2006 Wiley-Liss, Inc.