Genome-wide copy number variations in a large cohort of bantu African children

Abstract

Background Copy number variations (CNVs) account for a substantial proportion of inter-individual genomic variation. However, a majority of genomic variation studies have focused on single-nucleotide variations (SNVs), with limited genome-wide analysis of CNVs in large cohorts, especially in populations that are under-represented in genetic studies including people of African descent. Methods We carried out a genome-wide copy number analysis in > 3400 healthy Bantu Africans from Tanzania. Signal intensity data from high density (> 2.5 million probes) genotyping arrays were used for CNV calling with three algorithms including PennCNV, DNAcopy and VanillaICE. Stringent quality metrics and filtering criteria were applied to obtain high confidence CNVs. Results We identified over 400,000 CNVs larger than 1 kilobase (kb), for an average of 120 CNVs (SE = 2.57) per individual. We detected 866 large CNVs (≥ 300 kb), some of which overlapped genomic regions previously associated with multiple congenital anomaly syndromes, including Prader-Willi/Angelman syndrome (Type1) and 22q11.2 deletion syndrome. Furthermore, several of the common CNVs seen in our cohort (≥ 5%) overlap genes previously associated with developmental disorders. Conclusions These findings may help refine the phenotypic outcomes and penetrance of variations affecting genes and genomic regions previously implicated in diseases. Our study provides one of the largest datasets of CNVs from individuals of African ancestry, enabling improved clinical evaluation and disease association of CNVs observed in research and clinical studies in African populations.

Whole-genome sequencing reveals an association between small genomic deletions and an increased risk of developing Parkinson’s disease

“…These CNV regions were split at the identified CNV boundaries, and the number of copies was counted. Thereafter, CNVs overlapping ≥ 50% in centromere, telomere, or segmental duplication regions were removed 27 . Finally, associations between PD and the defined CNV regions ( n = 120,374) for the primary cohort were evaluated using Fisher’s exact test.…”

Identification of RPL5 gene variants and the risk of hepatic vein thrombosis in Saudi patients

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Incorporating CNV analysis improves the yield of exome sequencing for rare monogenic disorders—an important consideration for resource-constrained settings

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