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.