Linkage and association with type 1 diabetes on chromosome 1q42.
Linkage and association with type 1 diabetes on chromosome 1q42.
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DOI：
10.2337/diabetes.51.11.3318
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发表时间：
2002-11
期刊：
影响因子：
7.7
通讯作者：
K. Ewens;L. Johnson;B. Wapelhorst;K. O'Brien;S. Gutin;V. A. Morrison;C. Street;S. Gregory;R. Spielman;P. Concannon
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文献类型：
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作者：
K. Ewens;L. Johnson;B. Wapelhorst;K. O'Brien;S. Gutin;V. A. Morrison;C. Street;S. Gregory;R. Spielman;P. Concannon
1型糖尿病是一种复杂的疾病，具有多个基因位点和环境因素，导致疾病的发生。在目前的研究中，染色体1q42上的人类1型糖尿病候选区域在616个多基因1型糖尿病家系中以高标记密度被定位。为了便于识别和评估候选基因，构建了最大优势对数(LOD)分数(2.46，P=0.0004)周围7 cM区域的物理图谱。在标记周围的500kb区域确定了基因，产生了最高的LOD得分，并通过重新测序评估了多态。在这些基因中发现的单核苷酸多态(SNPs)以及其他匿名标记通过基于家庭和病例对照的方法被检测与1型糖尿病的等位基因关联。在1型糖尿病家系中，D1S225、D1S2383和D1S251三个相邻标记上的共同等位基因形成的单倍型优先传递给患病后代(标称P=0.006)。这些发现扩展了支持在染色体1q42上存在1型糖尿病易感基因的证据，并确定了一个符合定位克隆努力的候选区域。
Type 1 diabetes is a complex disorder with multiple genetic loci and environmental factors contributing to disease etiology. In the current study, a human type 1 diabetes candidate region on chromosome 1q42 was mapped at high marker density in a panel of 616 multiplex type 1 diabetic families. To facilitate the identification and evaluation of candidate genes, a physical map of the 7-cM region surrounding the maximum logarithm of odds (LOD) score (2.46, P = 0.0004) was constructed. Genes were identified in the 500-kb region surrounding the marker yielding the peak LOD score and evaluated for polymorphism by resequencing. Single-nucleotide polymorphisms (SNPs) identified in these genes as well as other anonymous markers were tested for allelic association with type 1 diabetes by both family-based and case-control methods. A haplotype formed by common alleles at three adjacent markers (D1S225, D1S2383, and D1S251) was preferentially transmitted to affected offspring in type 1 diabetic families (nominal P = 0.006). These findings extend the evidence supporting the existence of a type 1 diabetes susceptibility locus on chromosome 1q42 and identify a candidate region amenable to positional cloning efforts.