Related Experiment Video
Updated: Jun 26, 2026
06:41
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes
Mika Asai-Coakwell1, Curtis R French, Ming Ye
1Department of Ophthalmology, University of Alberta, Edmonton, Canada.
Human Molecular Genetics
|January 9, 2009
Summary
Mutations in growth differentiation factor 6 (GDF6) cause ocular and vertebral anomalies in humans. Studies in zebrafish and mice confirm GDF6
Area of Science:
- Developmental Biology
- Human Genetics
- Molecular Biology
Background:
- Bone morphogenetic proteins (BMPs) are crucial for skeletal and ocular development.
- Identifying individual BMP roles in human disease is challenging due to functional redundancy and widespread expression.
- Growth differentiation factor 6 (GDF6) is a member of the BMP family.
Purpose of the Study:
- To investigate the role of Growth Differentiation Factor 6 (GDF6) in human ocular and vertebral development.
- To characterize the effects of GDF6 mutations.
- To establish GDF6's contribution to human disease.
Main Methods:
- Identification of heterozygous mutations in GDF6 in patients with ocular and vertebral anomalies.
- Functional characterization using SOX9-reporter assays and western analysis.
- Phenotypic analysis in morphant zebrafish and Gdf6(+/-) mice.
Main Results:
- Seven heterozygous GDF6 mutations were identified in patients with ocular and vertebral anomalies.
- Reduced Gdf6 function in zebrafish and mice led to comparable ocular and skeletal phenotypes, including defective tail formation.
- Animal models displayed variable expressivity and incomplete penetrance, differing from human patient presentations.
Conclusions:
- GDF6 is a critical determinant of ocular and vertebral development.
- Mutations in GDF6 contribute to a spectrum of human developmental anomalies.
- These findings highlight the complex genetic inheritance patterns and pleiotropic effects associated with BMP family members in human disease.
Related Concept Videos
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
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.
01:11Genetic Lingo
Overview
01:19X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
01:19X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
01:35Pedigree Analysis
Overview