Single nucleotide polymorphism discovery in TBX1 in individuals with and without 22q11.2 deletion syndrome.
Single nucleotide polymorphism discovery in TBX1 in individuals with and without 22q11.2 deletion syndrome.
复制标题
有或没有22Q11.2缺失综合征的个体中TBX1中的单核苷酸多态性发现。
DOI：
10.1002/bdra.20604
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发表时间：
2010-01
期刊：
影响因子：
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通讯作者：
Crawford DC
中科院分区：
文献类型：
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作者：
Heike CL;Starr JR;Rieder MJ;Cunningham ML;Edwards KL;Stanaway IB;Crawford DC
22q11.2缺失综合征（22q11.2DS）患儿具有广泛的临床特征。TBX1已被提出作为候选基因的一些功能，在这种情况下。非缺失型TBX1的多态性可能影响22q11.2DS个体中唯一TBX1基因的功能，这可能是理解具有共享缺失的个体之间表型变异的关键。通过对候选基因重新测序的综合性单核苷酸多态性（SNP）发现可以鉴定影响给定表型的遗传变异。本研究的目的是通过鉴定TBX1基因中所有常见的SNP来进一步表征该基因的序列变异性。我们对29名22q11.2缺失的儿童和95名未缺失的健康个体进行了TBX1重测序。我们估计了等位基因频率，进行了tagSNP选择并推断了单倍型。我们还比较了22q11.2DS和对照样本之间的SNP频率。我们确定了355个双等位基因标记的190条染色体中的控制面板重新测序。鉴定的绝大多数标记是SNP（n=331），其余为indel（n=24）。我们没有在TBX1上游的顺式调节元件（FOX结合位点）中鉴定出SNP或插入缺失。在患有22q11.2DS的儿童中，我们检测到187个双等位基因标记，其中6个是插入缺失。在对照组中发现的7个编码SNPs中有4个在22q11.2DS儿童中发现。这种全面的SNP发现数据可用于选择SNP进行基因分型，用于未来的关联研究，评估TBX1的作用和22q11.2DS个体的表型变异性。
Children with 22q11.2 deletion syndrome (22q11.2DS) have a wide range of clinical features. TBX1 has been proposed as a candidate gene for some of the features in this condition. Polymorphisms in the non-deleted TBX1, which may affect the function of the sole TBX1 gene in individuals with the 22q11.2DS, may be a key to understanding the phenotypic variability among individuals with a shared deletion. Comprehensive single nucleotide polymorphism (SNP) discovery by resequencing candidate genes can identify genetic variants that influence a given phenotype. The purpose of this study was to further characterize the sequence variability in TBX1 by identifying all common SNPs in this gene. We resequenced TBX1 in 29 children with a documented 22q11.2 deletion and 95 non-deleted, healthy individuals. We estimated allele frequencies, performed tagSNP selection, and inferred haplotypes. We also compared SNP frequencies between 22q11.2DS and control samples. We identified 355 biallelic markers among the 190 chromosomes resequenced in the control panel. The vast majority of the markers identified were SNPs (n=331), and the remainder indels (n=24). We did not identify SNPs or indels in the cis- regulatory element (FOX–binding site) upstream of TBX1. In children with 22q11.2DS we detected 187 biallelic markers, six of which were indels. Four of the seven coding SNPs identified in the controls were identified in children with 22q11.2DS. This comprehensive SNP discovery data can be used to select SNPs to genotype for future association studies assessing the role of TBX1 and phenotypic variability in individuals with 22q11.2DS.