Speaker
Description
Background: Orofacial clefts (OFCs) are the most common congenital craniofacial defect. Its aetiology involves genetic and environmental risk factors and their interactions. Significantly, the incidence of OFCs varies by human ancestry. The transatlantic slave trade and high migration rate have increased interactions and admixture of genomes across populations. However, few studies have explored ancestry-specific and enriched OFC aetiologic loci in the context of haplotypes. This pioneering study aimed to estimate the genetic ancestry and population structure of affected families to inform ancestry-specific risk factors.
Methods: DNA was extracted from saliva and cheek swab samples collected from 103 case-parent trios and subjected to whole genome sequencing (WGS) to obtain 309 genome sequences. Variant calling and annotation were performed using the GATK workflow. WGS data were harmonised and combined with an integrated reference panel comprising 1000 Genomes Project and Human Genome Diversity Project. GCTA software was used to perform principal component analysis (PCA) to assess the population structure, while patterns of ancestry and admixture were characterised using ADMIXTURE software to estimate the proportions of ancestry of the Ghanaian cohort. Haplotypes were reconstructed using SHAPEIT5 and haplotype blocks estimated with PLINK 1.9.
Results: Population structure in the Ghanaian cohort reflected geography, with northern and southern ethnic groups clustering separately. PCA showed Ghanaians were more genetically similar to African Americans in the US and African Caribbeans than Nigerians. Admixture analysis also revealed three main African-specific ancestries in the Ghanaian cohort, with one ancestry dominating across all the ethnic groups. Haplotype reconstruction and local ancestry analyses are underway to identify Ghanaian- and ethnic-specific haplotypes and ancestry enriched in aetiologic loci for OFCs.
Conclusion: This study demonstrates, for the first time in the Ghanaian population, that population structure is aligned with ethnicity. We look forward to identifying ancestry-enriched aetiologic loci for OFCs among Ghanaians.