Related Experiment Video
Updated: Jun 28, 2025
00:06
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
13.6K
Loss-of-function variants affecting the STAGA complex component SUPT7L cause a developmental disorder with
Johannes Kopp1,2,3, Leonard A Koch1, Hristiana Lyubenova1,2
1Institute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, 13353, Berlin, Germany.
Human Genetics
|April 9, 2024
Summary
Genetic variants in SUPT7L cause generalized lipodystrophy and progeroid features by impacting DNA repair. Restoring SUPT7L function normalizes DNA damage, suggesting it as a novel disease gene.
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Generalized lipodystrophy and progeroid appearance are features of hereditary disorders.
- The SUPT7L gene encodes a component of the STAGA transcriptional coactivator complex.
Purpose of the Study:
- To identify the genetic cause of intrauterine growth retardation, generalized lipodystrophy, and progeroid features in a patient.
- To investigate the functional consequences of identified genetic variants on SUPT7L function and cellular processes.
Main Methods:
- Genetic analysis to identify variants in SUPT7L.
- Transcriptome sequencing to assess gene expression and splicing.
- Cellular assays to evaluate DNA damage rates and repair.
- Overexpression studies to determine the effect of wildtype SUPT7L.
Main Results:
- A compound heterozygous state of missense and frameshift variants in SUPT7L was identified.
- The missense variant led to aberrant splicing and complete absence of SUPT7L in fibroblasts.
- Increased DNA damage was observed in patient-derived cells and normalized upon SUPT7L reintroduction.
- Altered expression of DNA repair pathway genes was detected.
Conclusions:
- SUPT7L is implicated as a novel disease gene associated with generalized lipodystrophy and progeroid phenotypes.
- The findings highlight a link between SUPT7L dysfunction, genome instability, and progeroid features.
- SUPT7L plays a crucial role in maintaining genomic integrity.
Keywords:
SUPT7LAberrant splicingLipodystrophyProgeroid disorderSTAGA complexWiedemann-Rautenstrauch syndromeMore Related Videos
09:37Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
9.7K
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
33.7K
Related Concept Videos
01:33Pleiotropy
40.4K
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,...
40.4K
03:14Notch Signaling Pathway
4.3K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.3K
02:18Alternative RNA Splicing
21.1K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.1K
01:22Lysosomal Hydrolases
3.8K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.8K
01:43Incomplete Dominance
22.5K
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.
22.5K
01:20Inborn Errors of Metabolism
157
Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
157