Very rare CNVs overlapping 26 putative candidate genes for tetralogy of Fallot.

Candidate gene, official HGNC symbol; Locus, cytogenetic location of candidate gene; Case, subjects from discovery sample (n = 433) with TOF; CNV start, hg18 (NCBI Build 36.1, March 2006); CNV size, in base pairs; CN, type of copy number aberration; Exonic, CNV overlaps exon of candidate gene (•); Confirmed, by qPCR (•) or not done (ND); CV involvement, known cardiovascular system involvement (•; not necessarily in human); Structural CV phenotype, known structural cardiovascular system phenotype associated with mutation (•; not necessarily in human); References derived from systematic searches of human (e.g., Online Mendelian Inheritance in Man; www.omim.org/) and model organism (e.g., Mouse Genome Informatics; http://www.informatics.jax.org/) databases are presented in Table 5 in Supporting Information S1.aNovel and previously proposed candidate genes for TOF identified because of overlap with two or more CNVs in unrelated subjects (at least one Caucasian) with TOF, where the CNVs were not observed in 2,773 controls (see text). We have also shown selected candidate genes overlapped by very rare singleton CNVs in our cohort, including all those that overlapped rare CNVs reported by Greenway et al. [12].bFigure 2 in Supporting Information S1.cGreenway et al. [12].dFigure 3 in Supporting Information S1.eFigure 1.

候选基因：官方人类基因命名委员会（HGNC）符号；基因座：候选基因的细胞遗传学定位；病例组：来自发现队列的法洛四联症（TOF）受试者（n=433）；拷贝数变异起始位点：hg18版本（NCBI Build 36.1，2006年3月）；拷贝数变异长度：单位为碱基对；拷贝数变异类型：拷贝数异常的类型；外显子重叠：拷贝数变异与候选基因的外显子存在重叠（•）；验证情况：通过定量聚合酶链反应（qPCR）验证（•）或未完成（ND）；心血管受累情况：已知存在心血管系统受累（•；不一定限于人类）；结构性心血管表型：与突变相关的已知结构性心血管表型（•；不一定限于人类）；参考文献源自对人类数据库（如在线人类孟德尔遗传数据库（Online Mendelian Inheritance in Man；www.omim.org/））以及模式生物数据库（如小鼠基因组信息数据库（Mouse Genome Informatics；http://www.informatics.jax.org/））的系统性检索，相关内容详见补充材料S1中的表5。
a. 本研究鉴定出的法洛四联症（TOF）候选基因（含新发现及既往提出的候选基因），其筛选依据为与至少2个非相关性法洛四联症患者（至少1名高加索裔）的拷贝数变异（CNV）存在重叠，且该类拷贝数变异在2773名对照个体中未被检出（详见正文）。本研究同时纳入了本队列中由极罕见单例拷贝数变异覆盖的候选基因，包括所有与Greenway等人[12]报道的罕见拷贝数变异存在重叠的基因。
b. 详见补充材料S1中的图2。
c. Greenway等人[12]。
d. 详见补充材料S1中的图3。
e. 详见图1。