NICHD-California Birth Defects Study

我们扩大了与加州卫生部和斯坦福大学的合作。 完成了第一项实验室工作，即测定典型异位病例中的拷贝数变异。分析是完整的，数据以摘要形式呈现。使用含有250万个单核苷酸多态性（SNP）的微阵列对1998-2009年间从加州活产婴儿中鉴定出的69例典型异位症进行基因分型。使用PennCNV软件鉴定CNV。我们鉴定了56个CNV，包括NODAL（NIPBL，TBX 6），BMP（PPP 4C）和WNT（FZD 3）信号通路中的基因，以前与经典的异位无关。我们还发现了一个涉及FGF 12的CNV，这是一个以前在经典的异位病例中发现的基因。在多个病例中检测到涉及RBFOX 1和MIRNA 302 F的CNV。 我们的研究结果说明了心脏发育和左/右轴确定的身体模式途径的重要性。FGF 12、RBFOX 1和MIRNA 302 F在人类异位症中可能很重要，因为它们在多个病例中被注意到。需要进一步研究参与NODAL、BMP和WNT身体模式途径的基因，以及FGF 12、RBFOX 1和MIRNA 302 F的剂量效应。 已经编写了一份文件并提交出版。 来自加州的其他样本已经被鉴定、选择和提取DNA来研究其他先天性心脏缺陷。 已对样本进行拷贝数变体基因分型。 目前正在清理和编辑数据以供分析。 在2017财政年度，该研究将扩大，包括其他罕见的非心脏缺陷。 由于加州的出生人数非常多，我们预计能够识别非常罕见的缺陷病例进行调查。 由于我们在纽约州的工作，我们也应该能够确定来自纽约的受试者，以验证我们在加州的调查结果。

We have expanded our collaboration with The California Department of Health and Stanford Universiy. The first laboratory work, assaying copy number variants in classic heterotaxy cases was completed. The analysis is complete and data have been presented in abstract form. A microarray containing 2.5 million single-nucleotide polymorphisms (SNPs) was used to genotype 69 cases of classic heterotaxy identified from California live births from 1998-2009. CNVs were identified using PennCNV software. We identified 56 CNVs encompassing genes in the NODAL (NIPBL, TBX6), BMP (PPP4C), and WNT (FZD3) signaling pathways, previously unlinked to classic heterotaxy. We also identified a CNV involving FGF12, a gene previously noted in a classic heterotaxy case. CNVs involving RBFOX1 and MIRNA302F were detected in multiple cases. Our findings illustrate the importance of body patterning pathways for cardiac development and left/right axis determination. FGF12, RBFOX1 and MIRNA302F could be important in human heterotaxy because they were noted in multiple cases. Further investigation into genes involved in the NODAL, BMP, and WNT body patterning pathways and into the dosage effects of FGF12, RBFOX1, and MIRNA302F is warranted. A paper has been prepared and submitted for publication. Additional samples from California have been identified, selected and the DNA extracted to look at other congenital heart defects. The samples have been genotyping for copy number variants. The data are currently being cleaned and edited for analysis. This study will be expanded, funding being available, in fiscal year 2017 to include other, rare, non-cardiac defects. Because of the very large number of births in California, we anticipate being able to identify cases of very rare defects for investigation. Because of our work in New York State, we also should be able to identify subjects from NY to verify findings from our investigations in California.