Oscar Lao

Centro Nacional de Análisis Genómico de Barcelona · Research team of Population Genomics

Background North African human populations present a complex demographic scenario due to the presence of an autochthonous genetic component and population substructure, plus extensive gene flow from the Middle East, Europe, and sub-Saharan Africa. Results We conducted a comprehensive analysis of 364 genomes to construct detailed demographic models...

• The demographic history of AMH includes multiple migration events, population extinctions, genetic adaptations, and hybridization with archaic populations. • Modern non- sub- Saharan African human genomes carry fragments of archaic origin associated with adaptive advantages as well as medical risks, both being mainly related to neurological, derm...

The Evolutionary Roots of Human Brain Diseases takes an innovative approach and assembles recent findings ranging from evolutionary biology and anthropology to clinical neurosciences, all showing the price on health of human brain evolution. Written by experts in their field, the chapters explore the tenet that extensive human brain development dur...

Background The human lineage has undergone a postcranial skeleton gracilization (i.e. lower bone mass and strength relative to body size) compared to other primates and archaic populations such as the Neanderthals. This gracilization has been traditionally explained by differences in the mechanical load that our ancestors exercised. However, there...

Background The human lineage has suffered a skeleton gracilization compared to other primates and archaic populations such as the Neanderthals. This gracilization has been traditionally explained by differences in the mechanical load that our ancestors exercised. However, there is growing evidence that gracilization could be also genetically determ...

In population genetics, the emergence of large-scale genomic data for various species and populations has provided new opportunities to understand the evolutionary forces that drive genetic diversity using statistical inference. However, the era of population genomics presents new challenges in analysing the massive amounts of genomes and variants....

Background: North African human populations present a complex demographic scenario. The presence of an autochthonous genetic component and population substructure, plus extensive gene flow from the Middle East, Europe, and sub-Saharan Africa, have shaped the genetic composition of its people through time. Results: We conducted a comprehensive analy...

Archaic admixture has had a substantial impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. In great apes, archaic admixture has been identified in chimpanzees and bonobos but the possibility of such events has not been explored in other spec...

The genetic variation of the European population at a macro-geographic scale follows genetic gradients which reflect main migration events. However, less is known about factors affecting mating patterns at a micro-geographic scale. In this study we have analyzed 726,718 autosomal single nucleotide variants in 435 individuals from the catalan Pyrene...

Archaic admixture has had a significant impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. Within the great apes archaic admixture has been identified in chimpanzees and bonobos, but the possibility of such events has not been explored in ot...

Mammalian sex is determined by an opposing networks of ovarian and testicular genes that are well characterized. However, its epigenetic regulation is still largely unknown, thus limiting our understanding of a fundamental process for species propagation. Here we explore the 3D chromatin landscape of sex determination in vivo, by profiling FACS-sor...

The genetic variation of the European population at a macro-geographic scale follows genetic gradients which reflect main migration events. However, less is known about factors affecting mating choices at a micro-geographic scale. In this study we have analyzed 726,718 autosomal SNPs in 435 individuals from the Catalan Pyrenees covering around 200...

Heritable genetic variation is a prerequisite for adaptive evolution; however, our knowledge about the heritability of plastic traits, such as behaviors, is scarce, especially in wild populations. In this study, we investigated the heritability of song traits in the collared flycatcher (Ficedula albicollis), a small oscine passerine with complex so...

Attention-deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder characterized by hyperactivity, impulsivity, and/or inattention, which are symptoms also observed in many rare genetic disorders. We searched for genes involved in Mendelian disorders presenting with ADHD symptoms in the Online Mendelian Inheritance in Man (OMI...

The 1000 Genomes Project (1000G) is one of the most popular whole genome sequencing datasets used in different genomics fields and has boosting our knowledge in medical and population genomics, among other fields. Recent studies have reported the presence of ghost mutation signals in the 1000G. Furthermore, studies have shown that these mutations c...

A key question in human evolutionary genetics is whether and how natural selection has shaped the human genome. A new study by Song and colleagues uses GWAS data to examine evidence for the effects of polygenic adaptation in complex traits at different time scales.

The Cycladic, the Minoan, and the Helladic (Mycenaean) cultures define the Bronze Age (BA) of Greece. Urbanism, complex social structures, craft and agricultural specialization, and the earliest forms of writing characterize this iconic period. We sequenced six Early to Middle BA whole genomes, along with 11 mitochondrial genomes, sampled from the...

The area of the Spanish Pyrenees is particularly interesting for studying the demographic dynamics of European rural areas given its orography, the main traditional rural condition of its population and the reported higher patterns of consanguinity of the region. Previous genetic studies suggest a gradient of genetic continuity of the area in the W...

Background Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance. Methods We complemented a new conventional PC GWAS (1D) with genome spatial autocorrelation analysis...

Attention-deficit/hyperactivity disorder (ADHD) is an impairing neurodevelopmental condition highly prevalent in current populations. Several hypotheses have been proposed to explain this paradox, mainly in the context of the Paleolithic versus Neolithic cultural shift but especially within the framework of the mismatch theory. This theory elaborat...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Previous studies indicated existing, albeit limited, genetic-geographic population substructure in the Dutch population based on genome-wide data and a lack of this for mitochondrial SNP based data. Despite the aforementioned studies, Y-chromosomal SNP data from the Netherlands remain scarce and do not cover the territory of the Netherlands well en...

Correct identification of different human epithelial materials such as from skin, saliva and vaginal origin is relevant in forensic casework as it provides crucial information for crime reconstruction. However, the overlap in human cell type composition between these three epithelial materials provides challenges for their differentiation and ident...

Background: Population demography and gene flow among African groups, as well as the putative archaicintrogression of ancient hominins, have been poorly explored at the genome level. Results: Here, we examine 15 African populations covering all major continental linguistic groups, ecosystems, andlifestyles within Africa through analysis of whole-g...

Since anatomically modern humans dispersed Out of Africa, the evolutionary history of Eurasian populations has been marked by introgressions from presently extinct hominins. Some of these introgressions have been identified using sequenced ancient genomes (Neanderthal and Denisova). Other introgressions have been proposed for still unidentified gro...

Evolutionary medicine applies the principles of evolutionary biology to understand why we get sick rather than how, and it has undergone an exponential growth since the early 1990s [...]

The demographic history of anatomically modern humans (AMH) involves multiple migration events, population extinctions and genetic adaptations. As genome-wide data from complete genome sequencing becomes increasingly abundant and available even from extinct hominins, new insights of the evolutionary history of our species are discovered. It is curr...

The demographic history of anatomically modern humans (AMH) involves multiple migration events, population extinctions and genetic adaptations. As genome-wide data from complete genome sequencing becomes increasingly abundant and available even from extinct hominins, new insights of the evolutionary history of our species are discovered. It is curr...

Our closest living relatives, chimpanzees and bonobos, have a complex demographic history. We analyzed the high-coverage whole genomes of 75 wild-born chimpanzees and bonobos from 10 countries in Africa. We found that chimpanzee population substructure makes genetic information a good predictor of geographic origin at country and regional scales. M...

Of chimpanzees and bonobos Modern non-African human genomes contain genomic remnants that suggest that there was interbreeding between ancient humans and archaic hominoid lineages. Now, de Manuel et al. show similar ancestral interbreeding between the ancestors of today's chimpanzees and bonobos (see the Perspective by Hoelzel). The study also prov...

The population history of Aboriginal Australians remains largely uncharacterized. Here we generate high-coverage genomes for 83 Aboriginal Australians (speakers of Pama-Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25-40 thousand years ago (kya), suggesting pre-H...

Movements of people from one place to another, also referred to as human migrations, played a fundamental role in the history of archaic and modern humans. Here, current evidence and hypotheses on two major prehistoric human migrations are described: the initial colonization of Eurasia by archaic and modern humans, and the Neolithic expansion of mo...

Determining the time a biological trace was left at a scene of crime reflects a crucial aspect of forensic investigations as – if possible – it would permit testing the sample donor’s alibi directly from the trace evidence, helping to link (or not) the DNA-identified sample donor with the crime event. However, reliable and robust methodology is lac...

The identification and investigation of novel clock-controlled genes (CCGs) has been conducted thus far mainly in model organisms such as nocturnal rodents, with limited information in humans. Here, we aimed to characterize daily and circadian expression rhythms of CCGs in human peripheral blood during a sleep/sleep deprivation (S/SD) study and a c...

Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 inde...

In the International Visible Trait Genetics (VisiGen) Consortium, we investigated the genetics of human skin color by combining a series of genome-wide association studies (GWAS) in a total of 17,262 Europeans with functional follow-up of discovered loci. Our GWAS provide the first genome-wide significant evidence for chromosome 20q11.22 harboring...

Detecting and quantifying the population substructure present in a sample of individuals are of main interest in the fields of genetic epidemiology, population genetics, and forensics among others. To date, several algorithms have been proposed for estimating the amount of genetic ancestry within an individual. In the present review, we introduce t...

Genetic admixture plays a fundamental role in a species such as Homo sapiens, which has colonized the world on a relatively small evolutionary time scale, and has gone through complex migratory patterns in modern times. Several statistical methods exploiting different aspects of the genetic variation of admixed populations have been proposed. In th...

Understanding the peopling of the Americas remains an important and challenging question. Here, we present 14C dates, and morphological, isotopic and genomic sequence data from two human skulls from the state of Minas Gerais, Brazil, part of one of the indigenous groups known as ‘Botocudos’. We find that their genomic ancestry is Polynesian, with n...

Context: It is well established that ethnicity is associated with the phenotype of polycystic ovary syndrome (PCOS). Self-reported ethnicity was shown to be an inaccurate proxy for ethnic origin in other disease traits, and it remains unclear how in PCOS patients self-reported ethnicity compares with a biological proxy such as genetic ancestry. O...

Attempts to detect genetic population substructure in humans are troubled by the fact that the vast majority of the total amount of observed genetic variation is present within populations rather than between populations. Here we introduce a new algorithm for transforming a genetic distance matrix that reduces the within-population variation consid...

Unclassified sudden infant death (USID) is the sudden and unexpected death of an infant that remains unexplained after thorough case investigation including performance of a complete autopsy and review of the circumstances of death and the clinical history. When the infant is below 1 year of age and with onset of the fatal episode apparently occurr...

This study investigated the impact of sleep deprivation on the human circadian system. Plasma melatonin and cortisol levels and leukocyte expression levels of 12 genes were examined over 48 h (sleep vs. no-sleep nights) in 12 young males (mean ± SD: 23 ± 5 yrs). During one night of total sleep deprivation, BMAL1 expression was suppressed, the heat...

Background The presence of a southeast to northwest gradient across Europe in human genetic diversity is a well-established observation and has recently been confirmed by genome-wide single nucleotide polymorphism (SNP) data. This pattern is traditionally explained by major prehistoric human migration events in Palaeolithic and Neolithic times. Her...

Objectives: The population history of European Romani is characterized by extensive bottleneck and admixture events, but the impact of this unique demographic history on the genetic risk for disease remains unresolved. Methods: Genome-wide SNP data on Romani, non-Romani Europeans and Indians were analyzed. The excess of homozygous variants in Ro...

The Romani, the largest European minority group with approximately 11 million people [1], constitute a mosaic of languages, religions, and lifestyles while sharing a distinct social heritage. Linguistic [2] and genetic [3-8] studies have located the Romani origins in the Indian subcontinent. However, a genome-wide perspective on Romani origins and...

Natural variation in human skin pigmentation is primarily due to genetic causes rooted in recent evolutionary history. Genetic variants associated with human skin pigmentation confer risk of skin cancer and may provide useful information in forensic investigations. Almost all previous gene-mapping studies of human skin pigmentation were based on ca...

Correlation matrix between pair-wise Euclidean distances and size in discovery cohorts. (XLSX)

Effect of sex and age on facial shape in discovery cohorts. Distances are presented in millimeters. P values were adjusted for centroid size. (XLSX)

Raw genotype and respective phenotype data for all SNPs that revealed genome-wide significant and suggestive evidence. (XLSX)

SNPs (n = 102) associated (P<5e-7) with facial shape phenotypes in discovery phase GWAS. Trait, the phenotype for which the minimal P value was obtained. MinP, the minimal P value. (XLSX)

Thin plate spline deformation illustrating facial shape differences in males compared to females in discovery cohorts (N = 5388). The pixel information obtained from the mean shape of males was mapped to that of females. The deformed images illustrate the difference between the mean shpae of males (the curved plates) compared to that of females (im...

Correlation between PC and Euclidean distances in discovery cohorts. The color shade is independent between columns. (XLSX)

Heritability of facial shape phenotypes derived from 3D MRI in QTIMS. Twin correlations and proportions of variance due to additive genetic (A), common environmental (C), and unique environmental (E) influences, shown with 95% confidence intervals (age and sex adjusted). (XLSX)

Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replicatio...

The sleep/wake cycle is accompanied by changes in circulating numbers of immune cells. The goal of this study was to provide an in-depth characterization of diurnal rhythms in different blood cell populations and to investigate the effect of acute sleep deprivation on the immune system, as an indicator of the body's acute stress response. Observati...

African Pygmies are hunter-gatherer populations from the equatorial rainforest that present the lowest height averages among humans. The biological basis and the putative adaptive role of the short stature of Pygmy populations has been one of the most intriguing topics for human biologists in the last century, which still remains elusive. Worldwide...

Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replicatio...

Description of the approximate bayesian computation/Markov chain Monte Carlo (ABC-MCMC) implemented in this study. Linkage disequilibrium (LD) plots of the considered regions.

P values for each test.

Histograms of the posterior distributions (in black) of the selective parameters (σ (4 × Ne × s), h and tsel) of (A) SLC45A2, (B) OCA2, (C) DCT, (D) TYRP1 , (E) KITLG and (F) a neutral simulated sequence. These should be compared with the histograms of the prior distributions (in red) for the same parameters, using as population under selective pre...

Details of all primers used in this study.