| 1. |
- Breton, Gwenna, et al.
(författare)
-
Comparison of sequencing data processing pipelines and application to underrepresented African human populations
- 2021
-
Ingår i: BMC Bioinformatics. - : BioMed Central (BMC). - 1471-2105. ; 22:1
-
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.
|
|
| 2. |
- Breton, Gwenna, et al.
(författare)
-
Comparison of sequencing data processing pipelines and application to underrepresented human populations
-
Ingår i: BMC Bioinformatics. - 1471-2105.
-
Tidskriftsartikel (refereegranskat)abstract
- Population genetic studies of humans make increasing use of high-throughput sequencing in order to capture human 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 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.We started by surveying 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, that the GATK “Best Practices” are seldom followed strictly and that processing pipelines are often not reported in full details. We then compared three versions of the 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 pipeline 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.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 a coverage of >30X, and to work with large sample sizes at the variant calling stage, also for underrepresented individuals and populations.
|
|
| 3. |
- Breton, Gwenna, et al.
(författare)
-
Deciphering early human history using Approximate Bayesian Computation and 74 whole genomes from Central and Southern Africa
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Human evolutionary history in Africa before and after the out-of-Africa event remains largely unexplored, due to lack of genome sequence data, limited representation of populations and limitations of presently available inference methods. We generated high-coverage genomes from 49 Central African individuals, from five rainforest hunter-gatherer populations and four neighboring populations, and from 25 Khoe-San individuals, from five populations. We analyzed these genomes jointly with 104 comparative genomes from worldwide populations. We showed that rainforest hunter-gatherers and Khoe-San populations define two distinct major axes of genetic variation both at the worldwide and Sub-Saharan scales. This new data provides unprecedented resolution to unravel complex genetic differentiation among rainforest hunter-gatherer populations in particular. Using both deterministic and Approximate Bayesian Computation inferences, we found strong support for gene flow throughout the entire history of Central and Southern Africa, and an early divergence, some 250-370 kya ago, of Khoe-San ancestors from the lineage ancestral to all Central African populations. This event was followed, still in the presence of gene-flow, some 80-240 kya, by the divergence of lineages ancestral to rainforest hunter-gatherers and their neighbors. Finally, divergence between the different Khoe-San populations likely predated that of eastern and western rainforest hunter-gatherers which occurred 16-44 kya. Altogether, our results indicate that a tree-like history of Central Africa incorporating gene-flow among ancient lineages as well as among recent lineages can explain genomic variation observed among populations today.
|
|
| 4. |
- Breton, Gwenna
(författare)
-
Human demographic history : Insights on the human past based on genomes from Southern through Central Africa
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Evidence from paleontology, archaeology and population genetics support that modern humans originated in Africa. While the out-of-Africa event and subsequent colonization of all continents are well documented, human history in Africa at that time and before is less studied. Some current-day hunter-gatherer populations trace most of their genetic lineages to populations who inhabited Sub-Saharan Africa until the arrival of farming. They are informative about human history before and after the arrival of farming.I studied high-coverage genomes from two such groups, the Khoe-San from Southern Africa and the rainforest hunter-gatherers from Central Africa. I generated a total of 74 genomes, significantly increasing the number of genomes from Sub-Saharan African hunter-gatherers. I compared several versions of a commonly used pipeline for high-coverage genomes and showed that using standard ascertained reference datasets has no significant impact on variant calling in populations from Sub-Saharan Africa. Using the full genome information, I described the genetic diversity in the Khoe-San and in the rainforest hunter-gatherers and showed that gene flow from agropastoralist groups increased the Khoe-San genetic diversity. I also detected a signal of population size decline in the Khoe-San around the time of the out-of-Africa event, and I evaluated the power of the method to detect bottlenecks by applying it to simulated data. I investigated the history of modern humans in Africa by estimating divergence times between populations and applying an Approximate Bayesian Computation analysis. We confirmed that the earliest divergence event was between the Khoe-San ancestral lineage and the rest of modern humans, ~250-350 kya. I also showed that the possibility of high gene flow should be incorporated in models of human evolution.I furthermore examined SNP array data for two BaTwa populations from Zambia and showed that 20-30% of their autosomal diversity is hunter-gatherer-like. The estimated times for the admixture between a presumably local hunter-gatherer population and incoming agropastoralist groups are consistent with archaeological records.In this thesis, I investigated questions related to human history in Sub-Saharan Africa, from the emergence of modern humans ~300 kya to recent events related to the expansion of farming.
|
|
| 5. |
- Breton, Gwenna, et al.
(författare)
-
Lactase Persistence Alleles Reveal Partial East African Ancestry of Southern African Khoe Pastoralists
- 2014
-
Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 24:8, s. 852-858
-
Tidskriftsartikel (refereegranskat)abstract
- The ability to digest milk into adulthood, lactase persistence (LP), as well as specific genetic variants associated with LP, is heterogeneously distributed in global populations [1-4]. These variants were most likely targets of selection when some populations converted from hunter-gatherer to pastoralist or farming lifestyles [5-7]. Specific LP polymorphisms are associated with particular geographic regions and populations [1-4, 8-10]; however, they have not been extensively studied in southern Africa. We investigate the LP-regulatory region in 267 individuals from 13 southern African populations (including descendants of hunter-gatherers, pastoralists, and agropastoralists), providing the first comprehensive study of the LP-regulatory region in a large group of southern Africans. The "East African" LP single-nucleotide polymorphism (SNP) (14010G>C) was found at high frequency (>20%) in a strict pastoralist Khoe population, the Nama of Namibia, suggesting a connection to East Africa, whereas the "European" LP SNP (13910C>T) was found in populations of mixed ancestry. Using genome-wide data from various African populations, we identify admixture (13%) in the Nama, from an Afro-Asiatic group dating to >1,300 years ago, with the remaining fraction of their genomes being from San hunter-gatherers. We also find evidence of selection around the LCT gene among Khoe-speaking groups, and the substantial frequency of the 14010C variant among the Nama is best explained by adaptation to digesting milk. These genome-local and genome-wide results support a model in which an East African group brought pastoralist practices to southern Africa and admixed with local hunter-gatherers to form the ancestors of Khoe people.
|
|
| 6. |
- Breton, Gwenna, et al.
(författare)
-
The “BaTwa” populations from remote areas in Zambia retain ancestry of past forager groups
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Sub-equatorial Africa is inhabited today predominantly by Bantu-speaking farmers of west African descent. However, before the arrival of agriculture and pastoralism ~2,000 years ago, the region was inhabited by hunter-gatherers. The incoming farmer populations replaced, displaced or admixed with local hunter-gatherer groups. In some regions such as southern and central Africa, current-day farming populations have absorbed a large local hunter-gatherer genetic component. In other regions, such as Malawi, and Mozambique current-day populations have absorbed little to none of the local component. In this study, we generated genome-wide SNP data from two populations from Zambia thought to represent former hunter-gatherers, known locally as “BaTwa”, but for which no direct evidence exists of a hunter-gatherer past, either in language or lifestyle. We compared the BaTwa data to three Bantu-speaker agropastoralist populations from Zambia, and to other African and non-African populations. We show that the two BaTwa populations harbor a hunter-gatherer-like genetic component, representing respectively ~20% and ~30% of their genetic ancestry, while the rest is similar to Bantu-speaker agropastoralists. Although the component is closest related to current-day Khoe-San populations from southern Africa, results still suggest a unique local hunter-gatherer component. These results accord with Middle and Late Holocene skeletal evidence from Zambia and Malawi for a regionally separate hunter-gatherer population, which is now only detectable among the BaTwa. A two-way admixture scenario between a Bantu-speaker agropastoralist-like source and a hunter-gatherer-like source is supported for the two populations, occurring ~40 and ~16 generations ago respectively. These estimates are consistent with archaeological records for the arrival of agropastoralists in northern and central Zambia respectively. The study demonstrate the value of studying underrepresented minority groups to better understand the complexity of regional population histories.
|
|
| 7. |
- Hollfelder, Nina, et al.
(författare)
-
The deep population history in Africa
- 2021
-
Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 30:R1, s. R2-R10
-
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.
|
|
| 8. |
- Schlebusch, Carina, 1977-, et al.
(författare)
-
Khoe-San Genomes Reveal Unique Variation and Confirm the Deepest Population Divergence in Homo sapiens
- 2020
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 37:10, s. 2944-2954
-
Tidskriftsartikel (refereegranskat)abstract
- The southern African indigenous Khoe-San populations harbor the most divergent lineages of all living peoples. Exploring their genomes is key to understanding deep human history. We sequenced 25 full genomes from five Khoe-San populations, revealing many novel variants, that 25% of variants are unique to the Khoe-San, and that the Khoe-San group harbors the greatest level of diversity across the globe. In line with previous studies, we found several gene regions with extreme values in genome-wide scans for selection, potentially caused by natural selection in the lineage leading to Homo sapiens and more recent in time. These gene regions included immunity-, sperm-, brain-, diet-, and muscle-related genes. When accounting for recent admixture, all Khoe-San groups display genetic diversity approaching the levels in other African groups and a reduction in effective population size starting around 100,000 years ago. Hence, all human groups show a reduction in effective population size commencing around the time of the Out-of-Africa migrations, which coincides with changes in the paleoclimate records, changes that potentially impacted all humans at the time.
|
|
