Related Experiment Video
Updated: Jul 17, 2026
06:41
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Hypomorphic lethal mutations and their implications for the interpretation of lethal complementation studies in
1Department of Genetics, University of Alberta, Edmonton, Alberta, Canada T6G 2E9.
Genetics
|December 1, 1983
Summary
A third of lethal mutations in Drosophila melanogaster X chromosome are viable as homozygotes. These haplo-specific lethal mutations are hypomorphic alleles of essential genes, potentially causing errors in genetic tests.
Area of Science:
- Genetics and Genomics
- Developmental Biology
- Drosophila melanogaster Research
Background:
- Essential genes are critical for organism survival.
- Mutations in essential genes often result in lethality.
- Haploidy and homozygosity can reveal different phenotypic effects of mutations.
Purpose of the Study:
- To investigate mutations appearing lethal in haploid states but viable in homozygous states in Drosophila melanogaster.
- To characterize the nature and genetic behavior of these unique mutations.
- To understand the implications for genetic complementation tests.
Main Methods:
- Analysis of mutations in a specific region of the X chromosome in Drosophila melanogaster.
- Viability assessment of mutations in segmental haploids versus homozygous individuals.
- Complementation group analysis of viable homozygous mutations.
Main Results:
- One-third of mutations lethal in haploids were viable in homozygous mutants.
- These viable mutations formed four distinct complementation groups.
- The findings suggest these are hypomorphic alleles of essential genes with activity levels between 1x and 2x.
Conclusions:
- Identified a class of 'haplo-specific lethal mutations' in Drosophila melanogaster.
- These mutations represent functionally hypomorphic alleles of essential genes.
- Accidental inclusion of these mutations in autosomal lethal complementation tests can lead to spurious interallelic complementation results.
Related Concept Videos
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...
00:49Complementation Tests
A complementation test is a simple cross to identify whether the two mutations are located on the same gene or different genes. It was first performed by Edward Lewis in the 1940s while working on fruit flies. He developed the test to identify the location and arrangement of different mutations on chromosomes.
Organisms heterozygous for different mutations are crossed pairwise in all combinations. If present on different genes, the mutations can complement each other by providing the missing...
Organisms heterozygous for different mutations are crossed pairwise in all combinations. If present on different genes, the mutations can complement each other by providing the missing...
02:50Dosage Compensation
In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
02:45The Ratio of X Chromosome to Autosomes
In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
01:43Incomplete Dominance
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.