Identification of genomic regions on chromosome 22 associated with schizophrenia using exploratory eye movements

我们在48名精神分裂症先证者中筛查了β-肾上腺素能受体激酶2（ADRBK 2）基因和肽基异构酶（亲环素）样2（PPIL 2）基因的突变，并在113名精神分裂症先证者的家庭三人组中评估了检测到的多态性和JSNP数据库中报道的与精神分裂症的关联。ADRBK 2基因有4个单核苷酸变异，PPIL 2基因有8个单核苷酸变异。其中ADRBK 2基因Cys 208 Ser变异是唯一的非同义突变。等位基因，基因型和单倍型分析提供了在这些多态性和精神分裂症的等位基因之间的关联没有证据。结果表明，ADRBK 2和PPIL 2基因不太可能对精神分裂症的易感性有很大的贡献。我们分析了68个家庭，274名成员。每个家庭至少有一名精神分裂症患者。对1505例无关日本受试者进行了缺失筛选。短.检测串联重复序列多态性（STRP）和单核苷酸多态性（SNP），并进行基因分型，以评估连锁不平衡（LD）区块。LD区组由GOLD程序计算，LD/与精神分裂症的相关性由Trade-mission不平衡检验（TDT）评估。除22q11.2、22q12.1和22q12.3外，还筛选了22q12.3中APOL 1、APOL 2、APOL 3和APOL 4四种基因的突变。我们在22q11.2区域发现了新的STRP，并检测到与精神分裂症相关的LD阻滞。我们还发现APOL 1和APOL 4基因的基因组相邻区域与精神分裂症相关。我们清楚地证明了PRODH基因的缺失不会大大增加精神分裂症的风险。该研究获得了日本大学和筑波大学伦理委员会的批准。

We screened the beta-adrenergic receptor kinase 2 (ADRBK2) gene and peptidyl isomerase (cyclophiin)-like 2 (PPIL2) gene for mutations in 48 schizophrenia probands, and evaluated the detected polymorphisms and those reported in the JSNP database for associations with schizophrenia in 113 family trios of schizophrenia probands. Four single nucleotide variants in ADRBK2 gene and eight single nucleotide variants in PPIL2 gene were identified. Among them, the Cys208Ser variant in ADRBK2 gene was the only non-synonymous mutation. Allelic, genotypic and haplotypic analyses provided no evidence for association between alleles at these polymorphisms and schizophrenia. The results indicate that the ADRBK2 and PPIL2 genes are unlikely to contribute strongly to schizophrenia susceptibility in this set of families.We analyzed a total of 68 families with 274 members. At least one schizophrenic patient was included in each family. Deletion screening was performed for 1505 unrelated Japanese subjects. Short. tandem repeat polymorphisms (STRPs) and single nucleotide polymorphisms (SNPs) were detected and genotyped for assessing linkage disequilibrium (LD) blocks. LD blocks were computed by a GOLD program and LD/association with schizophrenia was assessed by trarismission disequilibrium test (TDT). In addition to 22q11.2, 22q12.1, and 22q12.3, mutations were screened for four genes of APOL1, APOL2, APOL3, and APOL4 in 22q12.3. We identified novel STRPs in 22q11.2 region and detected LD blocks associated with schizophrenia. We also found that genomic neighboring regions of the APOL1 and APOL4 genes were associated with schizophrenia. We clearly demonstrated that deletion of the PRODH gene do not raise a risk of schizophrenia greatly. The study was approved by the Ethics Committees of Nihon University and University of Tsukuba.