Yun Francisco H J, Wong Betty Y L, Chase Maretta, Shuen Andrew Y, Canaff Lucie, Thongthai Kansuda, Siminovitch Katherine, Hendy Geoffrey N, Cole David E C
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Clin Biochem. 2007 May;40(8):551-61. doi: 10.1016/j.clinbiochem.2006.12.011. Epub 2007 Jan 18.
The calcium-sensing receptor (CASR) is critical for maintenance of blood calcium in a narrow physiologic range. Naturally occurring mutations in the calcium-sensing receptor gene (CASR) cause hypocalcaemia or hypercalcaemia, and molecular diagnosis of these mutations is clinically important. Knowledge of SNP frequency and haplotype structure is essential in understanding molecular test results.
Genotyping and haplotype analysis of 26 CASR SNPs (and a tetranucleotide insertion/deletion polymorphism) in control cohorts of Caucasian, Asian and African-American origin (n=1136, 88 and 104 chromosomes, respectively).
The three SNPs in exon 7 (A986S, R990G, Q1011E) are the only common exonic variants in our cohorts, and synonymous exonic SNPs are uncommon. Linkage disequilibrium analysis of the Caucasian cohort (Haploview) showed that the CASR locus is divided into three haplotype blocks, coincident with 5' regulatory, coding, and 3' regulatory domains.
These analyses provide an important framework for appropriate interpretation of CASR mutation screening now offered by a number of laboratories for the diagnosis of calcium disorders. They will assist in the study of CASR polymorphisms as predictors of complex disease states.
钙敏感受体（CASR）对于将血钙维持在狭窄的生理范围内至关重要。钙敏感受体基因（CASR）的自然发生突变会导致低钙血症或高钙血症，对这些突变进行分子诊断具有重要临床意义。了解单核苷酸多态性（SNP）频率和单倍型结构对于理解分子检测结果至关重要。
对高加索人、亚洲人和非裔美国人对照组（分别为1136、88和104条染色体）中的26个CASR SNP（以及一个四核苷酸插入/缺失多态性）进行基因分型和单倍型分析。
第7外显子中的三个SNP（A986S、R990G、Q1011E）是我们研究对象中仅有的常见外显子变异，同义外显子SNP并不常见。对高加索人队列进行连锁不平衡分析（Haploview）显示，CASR基因座分为三个单倍型块，与5'调控区、编码区和3'调控区一致。
这些分析为目前许多实验室提供的用于诊断钙紊乱的CASR突变筛查的合理解释提供了重要框架。它们将有助于研究CASR多态性作为复杂疾病状态的预测指标。
