Trends in Genetics
Feature ReviewSeries: Celebrating the Human Genome Project and its outcomesAdvances in integrative African genomics
Section snippets
African integrative genomics is important for precision medicine globally
Genetic variants that contribute to human disease risk often vary in frequency amongst global ethnic groups. Differences in the evolutionary history of populations can lead to population-level differences in the prevalence of common and rare genetic diseases (recently reviewed in [1]). From this perspective, precision or personalized medicine is fundamentally intertwined with evolutionary history. Fossil and genetic evidence indicate that Africa is the origin of modern humans, approximately 300
African genomics in 2021
Most human genomic studies have focused on European populations. It is estimated that only 2% of genomic data are from individuals with African ancestries [11] and most of these were generated by genotyping array technologies [12]. African whole-genome sequencing (WGS) data is still very scarce.
The first high-coverage African WGS data (~40× coverage) was from a male individual from the Yoruba ethnic group in Nigeria generated in 2008 [13]. Two years later, complete genomes of one Khoesan
African genomics beyond 2021
Including more WGS data for African populations will not be enough to catalogue African genomic diversity accurately. The main issue is that the majority (70%) of the sequence in the human reference genome (HRG) was obtained from a single individual, ignoring global diversity and, thus, can introduce biases when used as a reference genome. The HRG bias makes it difficult to map short reads generated by next-generation sequencing (NGS) unambiguously to the HRG. For instance, reads with
Recent progress in African integrative genomics
Genomic sequences alone are insufficient to understand the functional implications of variation, since they do not directly link genotypes to phenotypes. Although GWAS have uncovered many variants associated with human traits, GWAS usually provides insufficient information about the underlying biological mechanisms influencing variable traits. Integrative genomics approaches aim to fill in this information by combining genomic data with intermediate phenotypes that link genetic variation to
Concluding remarks
The lack of representation of ethnically diverse African ancestries in genomic studies leads to healthcare inequities in Africans, as integrative genomics analysis based on non-African populations do not necessarily transfer well (e.g., replication rates <95%) to African populations (Box 2). Current African integrative genomics research is limited in several respects. One is that many studies are based on international reference panels that only include a small number of populations with
Declaration of interests
No interests are declared.
Acknowledgments
CZ, MEBH and SAT are supported by NIH 1R35GM134957, R01AR076241, and ADA 1-19-VSN-02.
Glossary
- caQTLs
- chromatin accessibility quantitative trait loci (caQTLs) are genomic loci that are associated with chromatin accessibility.
- Genetic architecture
- the characteristics of genetic variation that influences heritable phenotypic variability. The genetic architecture of a trait depends on the number of genetic variants affecting a trait, their frequencies in the population, the magnitude of their effects, and their interactions with each other and the environment.
- Genomics
- the study of whole genomes
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These authors contributed equally to this work