Luisa F Pallares

Friedrich Miescher Laboratory of the Max Planck Society | FML

The missing heritability problem, defined as the failure of genetic variants to explain variance in phenotypes, has been an unsolved issue in genetics for the past two decades. A potential solution to this problem stems from the idea that single nucleotide polymorphisms and copy-number variants, the most commonly studied forms of genomic diversity,...

Understanding the evolutionary potential of mutations in gene regulatory networks is essential to furthering the study of evolution and development. However, in multicellular systems, genetic manipulation of regulatory networks in a targeted and high-throughput way remains challenging. In this study, we designed TF-High-Evolutionary (HighEvo), a tr...

Finding communities in gene co-expression networks is a common first step toward extracting biological insight from these complex datasets. Most community detection algorithms expect genes to be organized into assortative modules, that is, groups of genes that are more associated with each other than with genes in other groups. While it is reasonab...

Evolutionary adaptation to new environments likely results from a combination of selective sweeps and polygenic shifts, depending on the genetic architecture of traits under selection. While selective sweeps have been widely studied, polygenic responses are considered more prevalent but challenging to quantify. The infinitesimal model makes explici...

The composition of mammalian gut microbiomes is highly conserved within species, yet the mechanisms by which microbiome composition is transmitted and maintained within lineages of wild animals remain unclear. Mutually compatible hypotheses exist, including that microbiome fidelity results from inherited dietary habits, shared environmental exposur...

Gene expression variance has been linked to organismal function and fitness but remains a commonly neglected aspect of molecular research. As a result, we lack a comprehensive understanding of the patterns of transcriptional variance across genes, and how this variance is linked to context-specific gene regulation and gene function. Here, we use 57...

Finding communities in gene co-expression networks is a common first step toward extracting biological insight from such complex datasets. Most community detection algorithms expect genes to be organized into assortative modules, that is, groups of genes that are more associated with each other than with genes in other groups. While it is reasonabl...

Decades of genome-wide mapping have shown that most genetic polymorphisms associated with complex traits are found in non-coding regions of the genome. Characterizing the effect of such genetic variation presents a formidable challenge, and eQTL mapping has been a key approach to understand the non-coding genome. However, comprehensive eQTL maps ar...

Validating associations between genotypic and phenotypic variation remains a challenge, despite advancements in association studies. Common approaches for signal validation rely on gene-level perturbations, such as loss-of-function mutations or RNAi, which test the effect of genetic modifications usually not observed in nature. CRISPR-based methods...

Evolutionary theory suggests that lifespan-reducing alleles should be purged from the gene pool, and yet decades of genome-wide association and model organism studies have shown that they persist. One potential explanation is that alleles that regulate lifespan do so only in certain environmental contexts. We exposed outbred Drosophila to control a...

Gene expression variance has been linked to organismal function and fitness but remains a commonly ne-glected aspect of molecular research. As a result, we lack a comprehensive understanding of the patterns of transcriptional variance across genes, and how this variance is linked to context-specific gene regulation and gene function. Here, we use 5...

Individual animals vary in their behaviors. This is true even when they share the same genotype and were reared in the same environment. Clusters of covarying behaviors constitute behavioral syndromes, and an individual’s position along such axes of covariation is a representation of their personality. Despite these conceptual frameworks, the struc...

Several evolutionary forces are thought to maintain genetic variation for fitness-related traits, such as lifespan, but experimental support is limited. Using a powerful experimental design, we identified lifespan-associated variants by exposing outbred Drosophila melanogaster to standard and high-sugar diets and tracking genome-wide allele frequen...

The field of Genetics started flourishing after the rediscovery of the Mendelian laws of inheritance at the beginning of the 20th century. These laws are based on a discrete classification of phenotypes and their causative genes. Such a Mendelian way of thinking forms the foundation of modern molecular biology, with its experimental paradigm that a...

Genome-wide association studies (GWAS) allow to dissect complex traits and map genetic variants, which often explain relatively little of the heritability. One potential reason is the preponderance of undetected low-frequency variants. To increase their allele frequency and assess their phenotypic impact in a population, we generated a diallel pane...

RNA-seq has become the standard tool for collecting genome-wide expression data in diverse fields, from quantitative genetics and medical genomics to ecology and developmental biology. However, RNA-seq library preparation is still prohibitive for many laboratories. Recently, the field of single-cell transcriptomics has reduced costs and increased t...

Individual animals vary in their behaviors. This is true even when they share the same genotype and were reared in the same environment. Clusters of covarying behaviors constitute behavioral syndromes, and an individual's position along such axes of covariation is a representation of their personality. Despite these conceptual frameworks, the struc...

Individual animals vary in their behaviors. This is true even when they share the same genotype and were reared in the same environment. Clusters of covarying behaviors constitute behavioral syndromes, and an individual's position along such axes of covariation is a representation of their personality. Despite these conceptual frameworks, the struc...

RNA-seq has become the standard tool for collecting genome-wide expression data in diverse fields, from quantitative genetics and medical genomics to ecology and developmental biology. However, RNA-seq library preparation is still prohibitive for many laboratories. Recently, the field of single-cell transcriptomics has reduced costs and increased t...

The genetic architecture of skull shape has been extensively studied in mice and the results suggest a highly polygenic and additive basis. In contrast few studies have explored the genetic basis of the skull variability. Canalization and developmental stability are the two components of phenotypic robustness. They have been proposed to be emergent...

Two subspecies of the house mouse, Mus musculus domesticus and Mus musculus musculus, meet in a narrow contact zone across Europe. Mice in the hybrid zone are highly admixed, representing the full range of mixed ancestry from the two subspecies. Given the distinct morphologies of these subspecies, these natural hybrids can be used for genome-wide a...

Numerous loci of large effect have been shown to underlie phenotypic variation between species. However, loci with subtle effects are presumably more frequently involved in microevolutionary processes, but have rarely been discovered. We explore the genetic basis of shape variation in the first upper molar of hybrid mice between Mus musculus muscul...

Shape data used in the association mapping. The dimensionality of the molar shape data was reduced using a PCA. The centroid size and PC scores for the first 18 PCs for each mouse are shown. These PC scores were used as phenotypes in the association mapping implemented in GEMMAX.

(A) Shape comparison between Mitf mutants and wild-type B6 mice. A Hotelling T2 test was performed to evaluate the difference in mean shape between mutant and wildtype groups; p-value, test statistic, and sample size (N) are shown. The Procrustes distances between mutant and wild type mean shapes are also indicated. *The comparison between heterozy...

Craniofacial shape differences between taxa have often been linked to environmental adaptation, e.g., new food sources, or have been studied in the context of domestication. Evidence for the genetic basis of such phenotypic differences to date suggests that between-species as well as between-population variation has an oligogenic basis, i.e., few l...

Craniofacial shape differences between taxa have often being linked to environmental adaptation, e.g. to new food sources, or have been studied in the context of domestication. Evidence for the genetic basis of such phenotypic differences to date suggests that within- as well as between-species variation has an oligogenic basis, i.e. few loci of la...

The vertebrate cranium is a prime example of the high evolvability of complex traits. While evidence of genes and developmental pathways underlying craniofacial shape determination is accumulating, we are still far from understanding how such variation at the genetic level is translated into craniofacial shape variation. Here we used 3D geometric m...

The identification of the genes involved in morphological variation in nature is still a major challenge. Here we explore a new approach: we combine 178 samples from a natural hybrid zone between two subspecies of the house mouse (Mus musculus domesticus and Mus musculus musculus), and high coverage of the genome (~145K SNPs) to identify loci under...

Mandible shape in the mouse is a complex trait that is influenced by many genetic factors. However, little is known about the action of single genes on adult mandible shape so far, since most developmentally relevant genes are already required during embryogenesis, i.e., knockouts lead to embryonic death or severe deformations, before the mandible...