Biology subjects

Adebamowo, C.

Publications and source records attributed to Adebamowo, C..

3 recordsLinked to original sources

bioRxiv2026

Community member, community liaison and researcher perspectives on the creation of HapMap and 1000 Genomes Project iPSCs

The National Human Genome Research Institute (NHGRI) Repository for Human Genetic Research (NHGRI Repository) distributes renewable lymphoblastoid cell lines (LCL) and cell line DNAs donated by members of 26 communities who have taken part in the International HapMap and 1000 Genomes Projects. The relatively recent introduction of induced pluripotent stem cell (iPSC) reprogramming technologies offers a new opportunity to create iPSCs from HapMap and 1000 Genomes Project biospecimens. However, since relevant iPSC technology did not exist when the HapMap and 1000 Genomes Projects began, it was not explicitly included in the consent process. To explore donor community and researcher perspectives on potential HapMap and 1000 Genomes Project iPSC creation, we conducted an online, semi-structured survey. The majority of community (86%) and research (86%) respondents agreed that creating iPSCs from HapMap and 1000 Genomes Project biospecimens could benefit the research community; however non-trivial concerns (36% community respondents and 16% researcher respondents) and doubts (21% community respondents and 11% researcher respondents) about HapMap and 1000 Genomes Project iPSC creation were also shared. Given these results, we will continue to explore opportunities to engage with HapMap and 1000 Genomes Project communities that include educational materials and detailed discussions regarding the potential for creating iPSCs from their community biospecimens. In parallel, we will continue to grow the existing NHGRI Repository iPSC collection with new donor submissions through the Human Pangenome Reference Consortium (HPRC) that explicitly consented to the creation of iPSCs.

genomics↗

bioRxiv2020

The extent and impact of variation in ADME genes in sub-Saharan African populations

Investigating variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are key to characterising pharmacogenomic (PGx) relationships. ADME gene variation is relatively well characterised in European and Asian populations, but African populations are under-studied - which has implications for safe and effective drug use in Africa. The genetic diversity of ADME genes across sub-Saharan African populations is large. The Southern African population cluster is most distinct from that of far West Africa. PGx strategies based on European variants will be of limited use in African populations. Although established variants are important, PGx must take into account the full range of African variation. This work urges further characterisation of variants in African populations including in vitro and in silico studies, and to consider the unique African ADME landscape when developing precision medicine guidelines and tools for African populations. Author summaryThe ADME genes are a group of genes that play a key role in absorption, distribution, metabolism and excretion of drugs. Variations in these genes can have a significant impact on drug safety and efficacy. Africa has a high level of genetic variation and is under-studied in drug development, which makes study of variations in these genes in African populations very important. Using a new data set of 458 high-coverage genomes from across Africa, we characterise the extent and impact of variation in the ADME genes, looking at both single nucleotide and copy number variations. We identified 343,368 variants, including 40,692 novel variants, and 930 coding variants which are predicted to have high impact on function. Our discovery curves indicate that there will be considerable value in sequencing more African genomes. Moreover, relatively few of these novel variants are captured on common genotyping arrays. We show that there is considerable diversity within Africa in some important genes, and this will have significant consequences for the emerging field of precision medicine in Africa.

genetics↗

bioRxiv2019

A Novel Type 2 Diabetes Locus in sub-Saharan Africans, ZRANB3, is Implicated in Beta Cell Proliferation

Genome analysis of diverse human populations has contributed to the identification of novel genomic loci for diseases of major clinical and public health impact. Here, we report the largest genome-wide analysis of type 2 diabetes (T2D) in sub-Saharan Africans, an understudied ancestral group. We analyzed ~18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana and Kenya. TCF7L2 rs7903156 was the most significant locus (p=7.288 x 10-13). We identified a novel genome wide significant locus: ZRANB3 (Zinc Finger RANBP2-Type Containing 3, lead SNP chr2:136064024, T allele frequency=0.034, p=2.831x10-9). Knockdown of the zebrafish ortholog resulted in reduction in pancreatic beta cell number in the developing organism, suggesting a potential mechanism for its effect on glucose hemostasis. We also showed transferability in our study of 32 established T2D loci. Our findings provide evidence of a novel candidate T2D locus and advance understanding of the genetics of T2D in non-European ancestry populations.

genetics↗