Kim Soo-Jeong, Herzing Laura B K, Veenstra-VanderWeele Jeremy, Lord Catherine, Courchesne Rachel, Leventhal Bennett L, Ledbetter David H, Courchesne Eric, Cook Edwin H
Laboratory of Developmental Neuroscience, Child and Adolescent Psychiatry, Department of Psychiatry MC3077, University of Chicago, Chicago, Illinois 60637, USA.
Am J Med Genet. 2002 Mar 8;114(2):137-43. doi: 10.1002/ajmg.10238.
Autism is a complex genetic disorder. Chromosome 15 is of particular interest in this disorder, because of previous reports of individuals with autism with chromosomal abnormalities in the 15q11-q13 region. Transmission disequilibrium between polymorphisms in this region and autism has been also been reported in some, but not all studies. Recently, a novel maternally expressed gene, ATP10C, was characterized and mapped to the chromosome 15q11-q13 region, 200 kb distal to UBE3A. It encodes a putative aminophospholipid translocase likely to be involved in the asymmetric distribution of proteins in the cell membrane. Preferential maternal expression has been demonstrated in fibroblasts and brain. Because of its physical location and imprinting pattern, ATP10C was considered to be a candidate gene for chromosome 15-associated autism. In an effort to find the genes responsible for autism in this chromosomal region, 1.5 kb of the 5' flanking region, as well as the coding and splicing regions of ATP10C, were screened for sequence variants. Several polymorphic markers including five nonsynonymous SNPs were identified. To investigate transmission disequilibrium between ATP10C and autism, a family-based association study was conducted for 14 markers in 115 autism trios. No significant transmission disequilibrium was found, suggesting ATP10C is unlikely to contribute strongly to susceptibility to autism in these families. However, due to limited power to detect genes of modest effect, the possible functional role of the nonsynonymous SNPs and the functional implications of the SNPs identified from 5' flanking region and intron 2 splicing region may be evaluated in further studies.
自闭症是一种复杂的遗传性疾病。15号染色体在这种疾病中特别受关注，因为此前有报道称患有自闭症的个体在15q11 - q13区域存在染色体异常。在一些（但并非所有）研究中也报道了该区域多态性与自闭症之间的传递不平衡。最近，一个新的母系表达基因ATP10C被鉴定并定位到15号染色体的15q11 - q13区域，位于UBE3A下游200 kb处。它编码一种推定的氨基磷脂转位酶，可能参与细胞膜中蛋白质的不对称分布。在成纤维细胞和大脑中已证实存在母系优先表达。由于其物理位置和印记模式，ATP10C被认为是与15号染色体相关自闭症的候选基因。为了寻找该染色体区域中导致自闭症的基因，对ATP10C的5'侧翼区域1.5 kb以及编码和剪接区域进行了序列变异筛查。鉴定出了几个多态性标记，包括五个非同义单核苷酸多态性（SNP）。为了研究ATP10C与自闭症之间的传递不平衡，对115个自闭症三联体中的14个标记进行了基于家系的关联研究。未发现显著的传递不平衡，这表明ATP10C不太可能对这些家族中自闭症的易感性有强烈影响。然而，由于检测中等效应基因的能力有限，非同义SNP的可能功能作用以及从5'侧翼区域和内含子2剪接区域鉴定出的SNP的功能意义可能需要在进一步研究中进行评估。
