Related Experiment Video
Updated: May 16, 2026
06:41
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Structural variants are enriched in deleterious visible phenotypes in Drosophila
Alejandra Samano1, Matthew Musat1, Mihir Junaghare1
1Department of Biology, Texas A&M University, College Station, Texas 77843, USA.
Genome Research
|May 14, 2026
Summary
Structural variants (SVs) are key to genetic variation but often missed by short reads. Long-read sequencing in Drosophila revealed SVs underlying classical phenotypes, showing SVs are enriched in large-effect traits.
Area of Science:
- Genomics
- Evolutionary Biology
- Developmental Biology
Background:
- Structural variants (SVs) contribute significantly to genetic diversity and function.
- Short-read sequencing methods often fail to detect complex SVs.
- The role of SVs in organismal trait variation is not fully understood.
Purpose of the Study:
- To investigate the molecular basis of classical phenotypes in Drosophila melanogaster using long-read sequencing.
- To identify novel structural variants associated with phenotypic variation.
- To construct a pangenome graph for nucleotide-resolution SV mapping.
Main Methods:
- De novo genome assembly using Oxford Nanopore Technologies long reads.
- Pangenome graph construction to map structural variants.
- CRISPR-Cas9 for experimental validation of candidate regulatory elements.
Main Results:
- Identified nucleotide-resolution maps of SVs, including complex rearrangements.
- Uncovered new candidate causal mutations for 15 phenotypes and alleles for 2 mutations.
- Found SVs underlying classical phenotypes like plexus (px1) and Curved (c1).
- Discovered uncharacterized SVs in well-studied genes such as white and yellow.
- Demonstrated enrichment of SVs (>100 bp) in genes causing phenotypic changes.
Conclusions:
- Structural variants are significantly enriched in genes associated with large-effect, deleterious visible phenotypes in Drosophila.
- Long-read sequencing is crucial for comprehensive SV discovery and understanding their role in trait variation.
- This study provides a valuable resource for studying genotype-phenotype relationships in Drosophila.
Related Concept Videos
02:32Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
01:46Types of Selection
Natural selection influences the frequencies of particular alleles and phenotypes within populations in several different ways. Primarily, natural selection can be directional, stabilizing, or disruptive. Directional selection favors one extreme trait and shifts the population towards that phenotype while selecting against individuals displaying alternate traits. Stabilizing selection favors an intermediate trait with a narrow range of variation. Deviation from the optimal phenotype towards an...
01:21Frequency-dependent Selection
When the fitness of a trait is influenced by how common it is (i.e., its frequency) relative to different traits within a population, this is referred to as frequency-dependent selection. Frequency-dependent selection may occur between species or within a single species. This type of selection can either be positive—with more common phenotypes having higher fitness—or negative, with rarer phenotypes conferring increased fitness.
02:46Genetic Screens
Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
02:27Background and Environment Affect Phenotype
Although the genetic makeup of an organism plays a major role in determining the phenotype, there are also several environmental factors, such as temperature, oxygen availability, presence of mutagens, that can alter an organism’s phenotype.
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...