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Yakubu, A.

Publications and source records attributed to Yakubu, A..

4 recordsLinked to original sources

Whole-genome sequencing across 449 samples spanning 47 ethnolinguistic groups provides insights into genetic diversity in Nigeria

African populations have been drastically underrepresented in genomics research and failure to capture the genetic diversity across the numerous ethnolinguistic groups (ELGs) found in the continent has hindered the equity of precision medicine initiatives globally. Here, we describe the whole-genome sequencing of 449 Nigerian individuals across 47 unique self-reported ELGs. Population structure analysis reveals genetic differentiation amongst our ELGs, consistent with previous findings. From the 36 million SNPs and INDELs discovered in our dataset, we provide a high-level catalog of both novel and medically-relevant variation present across the ELGs. These results emphasize the value of this resource for genomics research, with added granularity by representing multiple ELGs from Nigeria. Our results also underscore the potential of using these cohorts with larger sample sizes to improve our understanding of human ancestry and health in Africa.

genomics↗

A survey of proteomic variation across two ethnic groups in Nigeria and its relationship to obesity risk

Proteomic variation between individuals has immense potential for identifying novel drug targets and disease mechanisms. However, with high-throughput proteomic technologies still in their infancy, they have largely been applied in large majority European ancestry cohorts (e.g. the UK Biobank). An open question is the degree to which proteomic signatures seen in European and other groups mirror those seen in diverse populations, such as cohorts from Africa. Coupled with genetic information, we can also gain a better understanding of the role of genetic variants in the regulation of the proteome and subsequent disease mechanisms. To address the gap in our understanding of proteomic variation in individuals of African ancestry, we collected proteomic data from 176 individuals across two ethnic groups (Igbo and Yoruba) in Nigeria. These individuals were also stratified into high BMI (BMI > 30 kg/m2) and normal BMI (20 kg/m2 < BMI < 30 kg/m2) categories. We characterized differences in plasma protein abundance using the Olink Explore 1536 panel between high and normal BMI individuals, finding strong associations consistent with previously known signals in individuals of European descent. We additionally found 73 sentinel cis-pQTL in this dataset, with 21 lead cis-pQTL not observed in catalogs of variation from European-ancestry individuals. In summary, our study highlights the value of leveraging proteomic data in cohorts of diverse ancestry for investigating trait-specific mechanisms and discovering novel genetic regulators of the plasma proteome.

genomics↗

Multivariate Characterization of Morpho-biometric Traits of Indigenous Helmeted Guinea Fowl (Numida meleagris) in Nigeria

This study was embarked upon to characterise phenotypically helmeted guinea fowls in three agro-ecologies in Nigeria using multivariate approach. Eighteen biometric characters, four morphological indices and eleven qualitative (phaneroptic) traits were investigated in a total of 569 adult birds (158 males and 411 females). Descriptive statistics, non-parametric Kruskal-Wallis H test followed by the Mann-Whitney U test for post hoc, Multiple Correspondence Analysis (MCA), General Linear Model, Canonical Discriminant Analysis, Categorical Principal Component Analysis and Decision Trees were employed to discern the effects of agro-ecological zone and sex on the morphostructural parameters. Agro-ecology had significant effect (P<0.05; P <0.01) on all the colour traits. In general, the most frequently observed colour phenotype of guinea fowl had pearl plumage colour (54.0%), pale red skin colour (94.2%), black shank colour (68.7%), brown eye colour (49.7%), white earlobe colour (54.8%) and brown helmet colour (72.6%). The frequencies of helmet shape and wattle size were significantly influenced (P <0.01) by agro-ecology and sex. Overall, birds from the Southern Guinea Savanna zone had significantly higher values (P <0.05) for most biometric traits compared to their Sudano-Sahelian and Tropical Rainforest counterparts. They were also more compact (120.83{+/-}1.61 vs. 113.96{+/-}0.97 vs. 111.33{+/-}1.19) and had lesser condition index (8.542{+/-}0.17 vs. 9.92{+/-}0.10 vs. 9.61{+/-}0.13) than their counterparts in the two other zones. The interaction between agro-ecology and sex had significant effect (P <0.05) on some quantitative variables. The MCA and discriminant analysis revealed considerable intermingling of the phaneroptic, biometric traits and body indices especially between the Sudano-Sahelian and Tropical Rainforest birds. Inspite of the high level of genetic admixture, the guinea fowl populations could best be distinguished using wing length, body length and eye colour. However, further complementary work on genomics will guide future selection and breeding programmes geared towards improving the productivity, survival and environmental adaptation of indigenous helmeted guinea fowls in the tropics.

genetics↗

Identifying Therapeutic Strategies in IgA Nephropathy through Comprehensive Transcriptomic Characterization

IgA nephropathy (IgAN) is an autoimmune disease and the most common primary glomerulonephritis. The four-hit hypothesis describes mechanism of the disease, from synthesis of galactose deficient IgA (GD-IgA), to recognition of GD-IgA by anti-glycan antibodies and deposition of the formed immune complex in the mesangium. Complement and coagulation cascade activation ensues, resulting in mesangial activation and cytokine release, podocyte injury, mesangial sclerosis and tubulointerstitial damage. Currently, there is no disease cure, and 30-40% of patients progress to end stage renal disease. Using complementary bioinformatic approaches, we demonstrate different levels of deviation of the transcriptome of the glomerulus in IgAN from normal, with the aim of identifying therapeutic targets. Approaches used herein include, deconvolution of the transcriptome to estimate immune constitution, co-regulation-based functional analysis of differentially expressed genes, modular co-expression analysis, network analysis of metabolic pathways and differential gene correlation analysis. We describe the immune composition in IgAN and the relatively low fold changes of the abundance of different immune cells and strength of immune signatures compared with control. Additionally, we identify enrichment of the intestinal network for IgA synthesis, repression of expression and dysregulation of networks of amino acid metabolism and PPAR signaling pathways in IgAN glomeruli. We also find loss of correlation between expression of matrix synthesizing and matrix degrading genes in IgAN. We conclude by discussing how therapies based on some nodes in these altered pathways described have been shown to be efficacious in IgAN and/or other inflammatory diseases and the potential of others in effective treatment.

bioinformatics↗