Biology subjects

Shiferaw, W.

Publications and source records attributed to Shiferaw, W..

3 recordsLinked to original sources

bioRxiv2021

Genetic structure correlates with ethnolinguistic diversity in eastern and southern Africa

African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multigenerational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within the African continent, as well as how within-Africa variation can be informative for broader variant interpretation; many variants appearing rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity within Africa.

genomics↗

bioRxiv2020

Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations

BackgroundGenetic studies of biomedical phenotypes in underrepresented populations identify disproportionate numbers of novel associations. However, current genomics infrastructure--including most genotyping arrays and sequenced reference panels--best serves populations of European descent. A critical step for facilitating genetic studies in underrepresented populations is to ensure that genetic technologies accurately capture variation in all populations. Here, we quantify the accuracy of low-coverage sequencing in diverse African populations. ResultsWe sequenced the whole genomes of 91 individuals to high-coverage ([≥]20X) from the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study, in which participants were recruited from Ethiopia, Kenya, South Africa, and Uganda. We empirically tested two data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole genome sequencing data. We show that low-coverage sequencing at a depth of [≥]4X captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1X) performed comparable to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation, with 4X sequencing detecting 45% of singletons and 95% of common variants identified in high-coverage African whole genomes. ConclusionThese results indicate that low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, including those that capture variation most common in Europeans and Africans. Low-coverage sequencing effectively identifies novel variation (particularly in underrepresented populations), and presents opportunities to enhance variant discovery at a similar cost to traditional approaches.

genomics↗

bioRxiv2019

Survival status and predictors of mortality among Breast cancer patients at Black lion specialized hospital, Adult oncology unit, Addis Ababa, Ethiopia, 2018. A retrospective follow-up study with survival analysis

IntroductionBreast cancer is a foremost cause of death worldwide, ranks fifth among causes of death from all types of cancers; this is the most common cause of cancer death in women among both developing and developed countries. Breast cancer ranks first among most frequent cancers in women of Ethiopia. In spite of the high incidence, mortality rate, and survival status among breast cancer patients was not determined in Ethiopia.\n\nObjectiveThe main aim of the study is to assess the survival status and predictor the mortality among Breast Cancer patients in Adult Oncology Unit at Black Lion Specialized Hospital in 2018.\n\nMethodsAn institution based retrospective follow up study was conducted in Adult Oncology Unit at Black Lion Specialized Hospital. All cases of breast cancer registered from 1st January 2012 to 31th December,2014 were followed for the six-year survival (until 31th December, 2017). Kaplan-Meier survival curve together with log rank test was deployed to test for variations in the survival among predictor variables. Cox regression was used at 5% level of significance to determine the net effect of each independent variable on time to death of breast cancer clients.\n\nResultsThe results indicate that the incidence rate of mortality was 9.8 per 100 person/ years (95% CI: 8.49-11.47).The overall median survival time was 56.5(95% CI (53.46 - 60.83)) months. The overall estimated survival rate was recorded 27% (95% CI, 17.09 to 36.67 %) at 72 months of follow up, whereas at odd years (1, 3, and 5 years) were, 97.2%, 80.8%, and 46.2% respectively. Predictors of mortality were assessed at clinical stage (III&IV),(AHR =1.86), poorly differentiated histology (AHR: 3.1) & positive lymph node status (AHR:3.13),Whereas adjuvant hormone therapy (AHR: 0.67) and chemotherapy (AHR:0.72) were protective.\n\nConclusionThe overall probability of survival in Ethiopia was inferior when compared with other high and middle-income countries. Predictors of mortality were at advanced clinical stage, poorly differentiated histology grade, surgical margin involvement and positive lymph node status. In contrary, adjuvant hormone therapy, modified radical mastectomy and chemotherapy were protective factors. Hence, special emphasis could be given to early screening, stage diagnosis and initiation of treatment.

epidemiology↗