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Genetic Lingo

Genetic Lingo

Pleiotropy

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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,...

Genetic Variation

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Genetic variation is the diversity in DNA sequences found among individuals of the same species. This diversity is crucial for a species' survival because it helps organisms adapt to environmental changes. Genetic variation begins with fertilization, where an egg and sperm cell merge. Each of these cells carries 23 chromosomes, up to 46 in the fertilized egg. Chromosomes are long DNA strands that contain genes, the basic units of heredity.
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Incomplete Dominance

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Lethal Alleles

Agouti: A Lethal Allele
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Related Experiment Video

Updated: Sep 10, 2025

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

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Published on: August 15, 2019

Heterozygous variants in PLCG1 affect hearing, vision, cardiac, and immune function.

Mengqi Ma^1,2, Yiming Zheng^1,2, Mingxi Deng^1,2

¹Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.

|August 27, 2025

Summary

Seven individuals with new Phospholipase C Gamma 1 (PLCG1) variants show hearing, vision, cardiac, and immune issues. Drosophila models reveal these PLCG1 variants cause distinct gain-of-function effects, impacting cellular signaling and organismal health.

Keywords:

D. melanogaster Drosophila Phospholipase C genetics genomics human medicine phenotypic heterogeneity

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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

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Published on: April 4, 2018

Area of Science:

Molecular Biology
Genetics
Cellular Signaling

Background:

Phospholipase C isozymes (PLCs) generate key signaling molecules (IP3 and DAG) from PIP2, regulating cellular processes like calcium release.
PLCG1, encoding PLCγ1, is widely expressed, and its hyperactive somatic mutations are linked to cancers, but germline variants are rare.

Purpose of the Study:

To characterize seven novel heterozygous missense variants in PLCG1 identified in individuals with syndromic features.
To investigate the functional impact of these PLCG1 variants using a Drosophila melanogaster model system.

Main Methods:

Clinical evaluation of seven individuals with identified PLCG1 variants.
Generation of analogous missense variants in the Drosophila ortholog, small wing (sl).
Assessment of Drosophila phenotypes including wing development, photoreceptor formation, lifespan, and locomotor activity; rescue experiments with wild-type sl; ectopic expression studies.

Main Results:

Individuals presented with hearing impairment, ocular pathology, cardiac septal defects, and immunological issues.
Drosophila models exhibited reduced wing size, ectopic wing veins, supernumerary photoreceptors, reduced lifespan, and age-dependent locomotor defects.
Specific PLCG1 variants (p.Asp1019Gly, p.Asp1165Gly) demonstrated gain-of-function activity in Drosophila, while others (p.His380Arg, p.Leu597Phe) showed milder or variable effects.

Conclusions:

Heterozygous missense variants in PLCG1 can cause a spectrum of developmental and physiological abnormalities.
The studied PLCG1 variants exhibit differential gain-of-function effects, contributing to the observed clinical phenotypes.
The Drosophila model effectively recapitulates and helps elucidate the functional consequences of human PLCG1 variants.