Dr. Tamim Shaikh. Genome-wide Copy Number Variations in a Large Cohort of Bantu African Children

Family-based studies have indicated that genetic factors play a significant role in facial shape and appearance. However, very little is known about the genes that underlie normal facial development and account for inter-individual variability. In an ongoing study to identify the genetic determinants underlying facial shape variation, >3400 Bantu Africans were photographed using 3D morphometric cameras to obtain digitized facial scans and genotyped using high-content genotyping microarrays. The precise facial measurements obtained from 3D facial scans, allowed the extraction of quantitative facial distances and shapes which account for the majority of facial shape variance among study subjects. Genomewide association of single nucleotide polymorphisms (SNPs) with the quantitative facial measurements in these African and European cohorts, are currently ongoing. In addition to SNPs, copy number variations (CNVs) are now recognized as a significant source of genetic variation underlying human variability and disease. Recent studies have led to the association of CNVs to increased risk for several of common diseases, most notably neurodevelopmental diseases like autism and schizophrenia. Furthermore, CNVs have been directly implicated in several genetic disorders such as the 22q11 deletion syndrome and Williams-Beuren syndrome, in which the affected individuals have characteristic facial dysmorphia. We hypothesized that some of the variability in normal facial shape and appearance results from genetic variation mediated by the copy number variation affecting the dosage of genes involved in facial development. To test our hypothesis, we carried out a CNV analysis using the existing data from the SNP microarrays used to genotype the Bantu African cohort. We identified 416,877 CNVs, of which 355,077 are loss, 72,205 are gain CNVs. These CNV calls are provided in this dataset.

家庭为基础的研究表明，遗传因素在面部形态与外观中发挥重要作用。然而，对于调控正常面部发育并导致个体间差异的基因，人们知之甚少。在一项旨在识别面部形态变异背后遗传决定因素的持续研究中，超过3400名班图族非洲人通过3D形态测量相机拍摄，以获取数字化面部扫描数据，并利用高含量基因分型微阵列（genotyping microarrays）进行基因分型。从3D面部扫描中获得的精准面部测量数据，使得研究人员能够提取定量面部距离与形态特征，这些特征解释了研究对象间大部分的面部形态变异。目前，针对这些非洲与欧洲队列中单个核苷酸多态性（single nucleotide polymorphisms, SNPs）与定量面部测量数据的全基因组关联分析（genomewide association）正在进行中。除SNPs外，拷贝数变异（copy number variations, CNVs）目前被认为是人类表型变异与疾病背后遗传变异的重要来源。近期研究发现，CNVs与多种常见疾病风险增加相关，其中最显著的是自闭症和精神分裂症等神经发育疾病。此外，CNVs还直接参与了多种遗传疾病的发生，例如22q11缺失综合征和威廉姆斯-贝伦综合征（Williams-Beuren syndrome），这些疾病患者具有特征性的面部畸形。我们假设，正常面部形态与外观的部分变异源于拷贝数变异介导的遗传变异，这些变异影响了参与面部发育的基因剂量。为验证该假设，我们利用班图族非洲人队列基因分型所用的SNP微阵列数据，进行了CNV分析。我们共识别出416,877个CNVs，其中355,077个为缺失型，72,205个为增益型。本数据集提供了这些CNV检测结果（CNV calls）。