Biology subjects

Gueye, S. M.

Publications and source records attributed to Gueye, S. M..

3 recordsLinked to original sources

bioRxiv2025

Mitochondrial pull-out controls mitochondrial structure in response to mitochondrial activity

Mitochondrial networks undergo continuous remodeling through fusion and fission, processes that are essential for maintaining energy production and cellular homeostasis. Rapid elongation of the tip of mitochondrial tubules, a process termed dynamic tubulation, also participates in mitochondrial network formation. However, these mechanisms alone cannot fully account for the formation of highly interconnected mitochondrial networks that are required for rapid distribution of mitochondria material. Here, we identify a distinct type of dynamic tubulation, mitochondrial pull-outs characterized by the lateral extrusion from pre-existing mitochondrial tubules, as metabolically regulated determinants of mitochondrial network formation. Pull-outs are distinct from the tip elongation form of dynamic tubulation as they are modulated by the mitochondrial dynamins MFN1 and DRP1 and are stimulated by conditions favoring oxidative phosphorylation. Pull-outs also depend on mitochondrial actin polymerization and are required to increase mitochondrial connectivity and respiratory activity. Together, these findings establish mitochondrial pull-out as a metabolically sensitive mechanism that promotes mitochondrial network connectivity and links organelle architecture to cellular energy demands.

cell biology↗

bioRxiv2024

Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men

Androgenetic alopecia is a highly heritable trait. However, much of our understanding about the genetics of male pattern baldness comes from individuals of European descent. Here, we examined a novel dataset comprising 2,136 men from Ghana, Nigeria, Senegal, and South Africa that were genotyped using a custom array. We first tested how genetic predictions of baldness generalize from Europe to Africa, finding that polygenic scores from European GWAS yielded AUC statistics that ranged from 0.513 to 0.546, indicating that genetic predictions of baldness in African populations performed notably worse than in European populations. Subsequently, we conducted the first African GWAS of androgenetic alopecia, focusing on self-reported baldness patterns at age 45. After correcting for present age, population structure, and study site, we identified 266 moderately significant associations, 51 of which were independent (p-value < 10-5, r2 < 0.2). Most baldness associations were autosomal, and the X chromosomes does not appear to have a large impact on baldness in African men. Finally, we examined the evolutionary causes of continental differences in genetic architecture. Although Neanderthal alleles have previously been associated with skin and hair phenotypes, we did not find evidence that European-ascertained baldness hits were enriched for signatures of ancient introgression. Most loci that are associated with androgenetic alopecia are evolving neutrally. However, multiple baldness-associated SNPs near the EDA2R and AR genes have large allele frequency differences between continents. Collectively, our findings illustrate how evolutionary history contributes to the limited portability of genetic predictions across ancestries.

genomics↗

bioRxiv2019

A custom genotyping array reveals population-level heterogeneity for the genetic risks of prostate cancer and other cancers in Africa

Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. We find that samples from Ghana and Nigeria cluster together, while samples from Senegal and South Africa yield distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores were also generated for each genome in the MADCaP pilot dataset, and we found that predicted risks of CaP are lower in Senegal and higher in Nigeria.\n\nSignificanceWe have developed an Africa-specific genotyping array which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers.

genomics↗