Human

INTRODUCTION The highest genetic diversity in humans is found in Africa, in line with Africa being the cradle of humanity. While the three articles we discussed previously during this tutorial (1,2,3) mainly focused on determining the most parsimonious “out-of-Africa” scenarios based on genetic diversity data, this article (Skoglund et al. 2017 4) investigates the population structure of Africa prior to the expansion of food producers (i.e. herders and farmers). In order to reconstruct the prehistoric population structure, the authors analyzed the genomes from 16 ancient African individuals who lived up to 8100 years ago (including 15 newly sequenced genomes), as well as SNP genotypes from 584 present-day Africans, and 300 high coverage genomes from 142 worldwide populations. This is the first study to gather and analyze such a high number of ancient genomes, thereby providing an unpreceded insight into the prehistoric human population structure. RESULTS An ancient cline of southern and eastern African hunter-gatherers The authors used principal component analysis (PCA) and automated clustering in order to relate the 16 ancient individuals to present-day sub-Saharan Africans. This reveals that while the two ancient South African individuals share ancestry with present-day South Africans (Khoe-San), 11 of the 12 ancient individuals living …

Introduction In the past two decades, considerable research effort has been made to sequence the human genome and subsequently trying to unveil the demographic history underlying the genetic patterns of diversity we observe today across the globe. Here we discuss a recent research article by Pagani et al. 1 that addresses genomic diversity and historic migration patterns of human populations in Eurasia. The first human genome was sequenced in 2003 by the Human Genome Project2 and larger projects rapidly followed, such as HAPMAP3 and the 1000 Genomes Project4, largely due to the considerable technological improvement of sequencing technologies. Despite being extremely useful tools for a number of studies, these genome databases have some important sampling caveats that limit their use to address some particular topics. Indeed, HAPMAP sampled a reduced number of populations whereas the 1000 Genomes sampled a large number of populations but did not attempt to sample individuals of “pure” ancestry. For instance, the sampling in North America focused considerably on city-based individuals that were found to have a very diverse recent ancestry thus blurring the signal of ancient colonisation history. Importantly, in the studied paper, a considerable effort was made on sampling a broad panel of 447 …

High throughput genotyping and sequencing has led to the discovery of numerous sequence variants associated to human traits and diseases. An important type of variants involved are Loss of Function (LoF) mutations (frameshift indels, stop-gain and essential sites variants), which are predicted to completely disrupt the function of protein-coding genes. In case of Mendelian recessive diseases, for the condition to occur, the LoF variants must be biallelic, i.e. affecting both copies of a gene. The affected gene is then defined as “knockout”. By studying the Icelandic population, authors aim to identify rare LoF mutations (Minor Allele Frequency, MAF < 2%) present in individuals participating in various disease projects. They then investigate at which frequency in the population these LoF mutations are homozygous (i.e. knockout) in the germline genome. The Icelandic population Iceland is well-suited for genetic studies for three main reasons. The island was colonized by human population around the 9th century by 8-20 thousand settlers. Since then the population grew to around 320’000 inhabitants today. The initial founder effect and rare genetic admixture make the Icelandic population a genetic isolate. In addition to an unusual genetic isolation, Iceland’s population benefits of a genealogical database containing family histories reaching centuries …