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Related Concept Videos

Complement System01:27

Complement System

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The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
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Complementation Tests00:49

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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...
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The Concept of Multiple Allelism
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Multiple Regression01:25

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Multiple regression assesses a linear relationship between one response or dependent variable and two or more independent variables. It has many practical applications.
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Combinatorial Gene Control02:33

Combinatorial Gene Control

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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
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Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

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Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
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Updated: Jan 22, 2026

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
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Early complement genes are associated with visual system degeneration in multiple sclerosis.

Kathryn C Fitzgerald1, Kicheol Kim2, Matthew D Smith1

  • 1Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Brain : a Journal of Neurology
|July 11, 2019
PubMed
Summary

Genetic variants in the early complement pathway are linked to multiple sclerosis severity. These findings may help predict disease progression using sensitive visual pathway measures.

Keywords:
early complement pathway genesgenome-wide association studiesmultiple sclerosisoptical coherence tomography

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Area of Science:

  • Neuroimmunology
  • Genetics
  • Ophthalmology

Background:

  • Multiple sclerosis (MS) is a heterogeneous neurological disease with unpredictable severity.
  • Current genetic associations primarily focus on MS risk, not disease progression.
  • Clinical rating scales have limitations in detecting early degenerative changes.

Purpose of the Study:

  • To identify genetic predictors of multiple sclerosis severity using sensitive visual pathway phenotypes.
  • To investigate associations between genetic variants and retinal nerve fiber layer atrophy and low-contrast letter acuity loss in MS patients.

Main Methods:

  • Genome-wide association studies (GWAS) were performed on longitudinal visual pathway phenotypes in MS cohorts.
  • Analyses included mixed-effects models for structural measures (ganglion cell/inner plexiform layer atrophy) and Cox proportional hazards models for functional measures (low-contrast letter acuity loss).
  • Both discovery and replication cohorts were utilized, employing single-variant and network-based analyses.

Main Results:

  • Novel subnetworks linked to early complement activation were associated with MS disease severity.
  • The complement component 3 (C3) gene showed a strong association with ganglion cell/inner plexiform layer atrophy.
  • Variants in C1QA (rs158772) and CR1 (rs61822967) were significantly associated with increased risk of sustained low-contrast letter acuity loss.

Conclusions:

  • Early complement pathway gene variants are consistently associated with structural and functional measures of MS severity.
  • These findings support the role of complement factors in MS neurodegeneration and suggest potential biomarkers for disease course.
  • Sensitive visual phenotypes may aid in discovering genetic predictors for MS progression.