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- Breton, Gwenna, et al.
(författare)
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Comparison of sequencing data processing pipelines and application to underrepresented African human populations
- 2021
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Ingår i: BMC Bioinformatics. - : BioMed Central (BMC). - 1471-2105. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Population genetic studies of humans make increasing use of high-throughput sequencing in order to capture diversity in an unbiased way. There is an abundance of sequencing technologies, bioinformatic tools and the available genomes are increasing in number. Studies have evaluated and compared some of these technologies and tools, such as the Genome Analysis Toolkit (GATK) and its "Best Practices" bioinformatic pipelines. However, studies often focus on a few genomes of Eurasian origin in order to detect technical issues. We instead surveyed the use of the GATK tools and established a pipeline for processing high coverage full genomes from a diverse set of populations, including Sub-Saharan African groups, in order to reveal challenges from human diversity and stratification. Results We surveyed 29 studies using high-throughput sequencing data, and compared their strategies for data pre-processing and variant calling. We found that processing of data is very variable across studies and that the GATK "Best Practices" are seldom followed strictly. We then compared three versions of a GATK pipeline, differing in the inclusion of an indel realignment step and with a modification of the base quality score recalibration step. We applied the pipelines on a diverse set of 28 individuals. We compared the pipelines in terms of count of called variants and overlap of the callsets. We found that the pipelines resulted in similar callsets, in particular after callset filtering. We also ran one of the pipelines on a larger dataset of 179 individuals. We noted that including more individuals at the joint genotyping step resulted in different counts of variants. At the individual level, we observed that the average genome coverage was correlated to the number of variants called. Conclusions We conclude that applying the GATK "Best Practices" pipeline, including their recommended reference datasets, to underrepresented populations does not lead to a decrease in the number of called variants compared to alternative pipelines. We recommend to aim for coverage of > 30X if identifying most variants is important, and to work with large sample sizes at the variant calling stage, also for underrepresented individuals and populations.
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| 2. |
- Breton, Gwenna, et al.
(författare)
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Revisiting the demographic history of Central African populations from a genetic perspective
- 2021
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Ingår i: Human Population Genetics and Genomics. - : Pivot Science Publication Corp.. - 2770-5005. ; , s. 1-29
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Tidskriftsartikel (refereegranskat)abstract
- Africa is the continent of our species’ origin and the deep history of humans is represented by African genetic variation. Through genetic studies, it has become evident that deep African population history is captured by relationships among African hunter-gatherers and that the world’s deepest population divergences occur among these groups. In this review, we look back at a study published by Cavalli-Sforza and colleagues in 1969 entitled “Studies on African Pygmies. I. A pilot investigation of Babinga Pygmies in the Central African Republic (with an analysis of genetic distances)”. The study analyzed 19 classical polymorphisms and found that the deepest divergences in African populations were represented by hunter-gatherer groups such as the southern African San and the central African rainforest hunter-gatherers. We repeated the original analyses from Cavalli-Sforza et al. [1] with about 22 thousand times more genome-wide genetic markers in populations similar to those included in the original study. Our high-resolution analyses gave similar results regarding the relationships of early-diverging African populations compared to the classical polymorphism analyses. This finding, however, does not imply that research has stagnated and that developments in technology and genetic methods over the last fifty years delivered no additional information regarding African history and adaptation. We review how technology and population genetic methods have advanced to give more detailed inferences about population structure, migrations, admixture patterns, timing of admixture, sex-biased admixture, and inferences of selection and adaptive introgression in rainforest hunter-gatherers and other African populations. We also comment on how sequencing of ancient DNA has influenced findings and deliberate on the progress and development of more complex models of African history, including alternatives to tree-models and the inference of possible archaic admixture in African populations. We review the growing complexity of our picture of population history in central Africa and Africa as a whole, emerging from genomic studies and other disciplines investigating human population history and adaptation. While data and knowledge are accumulating, certain populations and areas remain underrepresented in genomic research. Their inclusion, possibly also through ancient DNA studies, together with new methods of analysis and the testing of representative models of deep population history in Africa, will help to build a more complete picture of past population history in Africa.
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| 3. |
- Hollfelder, Nina, et al.
(författare)
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The deep population history in Africa
- 2021
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 30:R1, s. R2-R10
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Forskningsöversikt (refereegranskat)abstract
- Africa is the continent with the greatest genetic diversity among humans and the level of diversity is further enhanced by incorporating non-majority groups, which are often understudied. Many of today's minority populations historically practiced foraging lifestyles, which were the only subsistence strategies prior to the rise of agriculture and pastoralism, but only a few groups practicing these strategies remain today. Genomic investigations of Holocene human remains excavated across the African continent show that the genetic landscape was vastly different compared to today's genetic landscape and that many groups that today are population isolate inhabited larger regions in the past. It is becoming clear that there are periods of isolation among groups and geographic areas, but also genetic contact over large distances throughout human history in Africa. Genomic information from minority populations and from prehistoric remains provide an invaluable source of information on the human past, in particular deep human population history, as Holocene large-scale population movements obscure past patterns of population structure. Here we revisit questions on the nature and time of the radiation of early humans in Africa, the extent of gene-flow among human populations as well as introgression from archaic and extinct lineages on the continent.
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