Quantitative trait locus | EPFL Graph Search

A quantitative trait locus (QTL) is a locus (section of DNA) that correlates with variation of a quantitative trait in the phenotype of a population of organisms. QTLs are mapped by identifying which molecular markers (such as SNPs or AFLPs) correlate with an observed trait. This is often an early step in identifying the actual genes that cause the trait variation. Definition A quantitative trait locus (QTL) is a region of DNA which is associated with a particular phenotypic trait, which varies in degree and which can be attributed to polygenic effects, i.e., the product of two or more genes, and their environment. These QTLs are often found on different chromosomes. The number of QTLs which explain variation in the phenotypic trait indicates the genetic architecture of a trait. It may indicate that plant height is controlled by many genes of small effect, or by a few genes of large effect. Typically, QTLs underlie continuous traits (those traits which vary continuously, e.

A Quantitative Telomeric Chromatin Isolation Protocol (Q-TIP) to Characterize Telomere Composition Changes

Larissa Grolimund

Telomeres protect linear ends of eukaryotic chromosomes by preventing chromosomal end-to-end fusions and telomere attrition. They consist of repetitive DNA sequences, telomeric repeat containing RNAs (TERRAs) and proteins. Telomeres play a crucial role in chromosome stability, cancer biology, and ageing. With each cell division, telomeres shorten, as the replication machinery of the cell is not capable to fully copy the very terminal part of chromosomes. Therefore, after a certain number of cell divisions, telomeres get critically short and elicit signals in order to stop the proliferation. A cell can circumvent the signal for critically short telomeres by activating mechanisms that elongate telomeres. In most of the cases, telomere elongation is achieved by the expression of the telomerase enzyme. In this case, cells gain the ability to divide indefinitely, which can, in combination with other events, eventually lead to cancer. The telomeric protein composition changes during tumorigenesis, aging and in telomere syndromes are poorly defined. Here, we develop a quantitative telomeric chromatin isolation protocol (q-TIP) for human cells in which chromatin is crosslinked, immunopurified and analyzed by mass spectrometry. Q-TIP involves stable isotope labeling by amino acids in cell culture (SILAC) in order to compare and identify quantitative differences in telomere protein composition of cells from various states. With q-TIP, we specifically enrich telomeric DNA and all shelterin components. We identify and validate known and novel telomere associated polypeptides including all THO subunits, SMCHD1 and LRIF1. We apply q-TIP to long and short telomeres and detect increased density of SMCHD1 and LRIF1 and increased association of the shelterin components TRF1, TIN2, TPP1 and POT1 with long telomeres. Our results validate q-TIP to study telomeric states during normal development and in disease.

EPFL2013

Genetic, metabolic, and molecular insights into the diverse outcomes of diet-induced obesity in mouse

Alexis Maximilien Bachmann

Overweight and obesity are increasingly common public health issues worldwide, leading to a wide range of diseases from metabolic syndrome to steatohepatitis and cardiovascular diseases. While the increase in the prevalence of obesity is partly attributable to changes in lifestyle (i.e. increased sedentarity and changes in eating behaviour), the metabolic and clinical impacts of these obesogenic conditions varies between sexes and genetic backgrounds. The conception of personalised treatments of obesity and its complications require a thorough understanding of the diversity of responses to environmental stimuli such as high-fat diet intake. In this thesis, by analysing nine genetically diverse mouse strains, we show that much like humans, mice respond to high-fat diet in a genetic- and sex-dependent manner. Physiological and molecular responses to high-fat diet are associated with the expression of genes involved in immunity and mitochondrial function. Finally, we find that mitochondrial function and mitochondrial supercomplex assembly may explain part of the diversity of physiological responses. By exploring the complex interactions between genetics and metabolic phenotypes via gene expression and molecular traits, we shed light on the importance of genetic background and sex in determining metabolic outcomes. In addition to providing the community with an extensive resource for optimizing future experiments, this work serves as an exemplary design for more generalizable translational studies.

EPFL2021

Natural variation in genome architecture among 205 Drosophila melanogaster Genetic Reference Panel lines

Bart Deplancke, Yi Han, Sandy Lee, Andreas Massouras, Yiming Zhu

The Drosophila melanogaster Genetic Reference Panel (DGRP) is a community resource of 205 sequenced inbred lines, derived to improve our understanding of the effects of naturally occurring genetic variation on molecular and organismal phenotypes. We used an integrated genotyping strategy to identify 4,853,802 single nucleotide polymorphisms (SNPs) and 1,296,080 non-SNP variants. Our molecular population genomic analyses show higher deletion than insertion mutation rates and stronger purifying selection on deletions. Weaker selection on insertions than deletions is consistent with our observed distribution of genome size determined by flow cytometry, which is skewed toward larger genomes. Insertion/deletion and single nucleotide polymorphisms are positively correlated with each other and with local recombination, suggesting that their nonrandom distributions are due to hitchhiking and background selection. Our cytogenetic analysis identified 16 polymorphic inversions in the DGRP. Common inverted and standard karyotypes are genetically divergent and account for most of the variation in relatedness among the DGRP lines. Intriguingly, variation in genome size and many quantitative traits are significantly associated with inversions. Approximately 50% of the DGRP lines are infected with Wolbachia, and four lines have germline insertions of Wolbachia sequences, but effects of Wolbachia infection on quantitative traits are rarely significant. The DGRP complements ongoing efforts to functionally annotate the Drosophila genome. Indeed, 15% of all D. melanogaster genes segregate for potentially damaged proteins in the DGRP, and genome-wide analyses of quantitative traits identify novel candidate genes. The DGRP lines, sequence data, genotypes, quality scores, phenotypes, and analysis and visualization tools are publicly available.

Cold Spring Harbor Laboratory Press2014