Trends in Genetics
Volume 38, Issue 2, February 2022, Pages 152-168
Journal home page for Trends in Genetics

Feature Review
Series: Celebrating the Human Genome Project and its outcomes
Advances in integrative African genomics

https://doi.org/10.1016/j.tig.2021.09.013Get rights and content

Highlights

  • Africans harbor great genetic, phenotypic, cultural and linguistic diversity. Disparity remains in genetic studies representing African ancestries.

  • Whole-genome sequencing (WGS) for African populations lags behind European and Asian ancestries. More WGS efforts to capture genetic variation in Africa are warranted.

  • The human reference genome (HRG) lacks diversity, which can bias downstream analysis. Population-specific reference genomes for African populations would enable the detection of more complex variation and variation that would be difficult to map to the current HRG.

  • Combining genomic data with intermediate phenotypes is required to understand the biological mechanisms underlying phenotype and disease in the post-genomic era.

  • African integrative genomics is in its infancy. The scientific rewards and translational health benefits of dramatically expanded integrative omics studies in African populations is high.

There has been a rapid increase in human genome sequencing in the past two decades, resulting in the identification of millions of previously unknown genetic variants. However, African populations are under-represented in sequencing efforts. Additional sequencing from diverse African populations and the construction of African-specific reference genomes is needed to better characterize the full spectrum of variation in humans. However, sequencing alone is insufficient to address the molecular and cellular mechanisms underlying variable phenotypes and disease risks. Determining functional consequences of genetic variation using multi-omics approaches is a fundamental post-genomic challenge. We discuss approaches to close the knowledge gaps about African genomic diversity and review advances in African integrative genomic studies and their implications for precision medicine.

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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