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Complementation Tests

Complementation 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...

Pleiotropy

Pleiotropy

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,...

Lethal Alleles

Lethal 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...

Genetic Lingo

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Epistasis Analysis

Epistasis Analysis

Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...

Mutations

Mutations

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Related Experiment Video

Updated: Jan 1, 2026

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

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One novel GRN null mutation, two different aphasia phenotypes.

Cinzia Coppola¹, Mariano Oliva¹, Dario Saracino¹

¹Second Division of Neurology, University of Campania "Luigi Vanvitelli", Naples, Italy.

Neurobiology of Aging

|December 16, 2019

Summary

A novel progranulin gene (GRN) mutation, GRN 708+4A>T, causes frontotemporal lobar degeneration. This genetic finding highlights the diverse clinical presentations and genetic underpinnings of this neurodegenerative disease.

Keywords:

Frontotemporal lobar degeneration GRN Mutation Primary progressive aphasia Progranulin protein Progressive nonfluent aphasia

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Last Updated: Jan 1, 2026

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Published on: June 15, 2011

Area of Science:

Genetics
Neuroscience
Molecular Biology

Background:

Progranulin gene (GRN) mutations are a primary cause of frontotemporal lobar degeneration (FTLD).
FTLD presents with significant clinical heterogeneity, impacting cognition, behavior, and motor function.

Observation:

A novel GRN splicing mutation (708+4A>T) was identified in two siblings from a family with neurological disorders.
Patients exhibited predominant language impairment, with one diagnosed with progressive nonfluent aphasia and the other with mixed aphasia.

Findings:

Genetic and molecular analyses, including in silico predictions, confirmed the pathogenicity of the GRN 708+4A>T mutation.
The mutation leads to progranulin (PGRN) haploinsufficiency, a known mechanism in progranulinopathies.
Neuroimaging revealed anatomical changes consistent with the distinct clinical phenotypes observed in the patients.

Implications:

This discovery expands the spectrum of known GRN mutations associated with FTLD.
It underscores the importance of genetic testing in diagnosing heterogeneous neurodegenerative conditions.
Understanding this mutation's impact on PGRN levels and clinical presentation aids in comprehending FTLD pathogenesis and developing targeted therapies.