Related Experiment Video

Updated: Dec 20, 2025

A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene
08:22

A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene

Published on: September 16, 2019

8.2K

Quantifying the Genetic Basis of Marfan Syndrome Clinical Variability

Thomas Grange1, Mélodie Aubart1,2, Maud Langeois3,4

  • 1INSERM U1148, 75018 Paris, France.

Genes
|May 24, 2020
PubMed

Insights

Inherited genetic factors significantly influence Marfan syndrome (MFS) variability, particularly within specific organ systems. This study quantifies the heritability of MFS clinical features, revealing shared modifiers across related traits.

Area of Science:

  • Genetics
  • Medical Genetics
  • Quantitative Genetics

Background:

  • Marfan syndrome (MFS) is an inherited connective tissue disorder characterized by significant clinical variability.
  • The role of inherited genetic modifiers in this variability remains largely unquantified.

Purpose of the Study:

  • To quantify the contribution of inherited modifiers to the clinical variability observed in Marfan syndrome.
  • To analyze the distribution and heritability of 23 distinct clinical features in MFS patients with FBN1 mutations.

Main Methods:

  • Analysis of phenotypic correlations among 1306 well-phenotyped MFS patients carrying FBN1 mutations.
  • Application of a quantitative genetics model to estimate heritability of clinical features.
  • Investigation of major locus contribution and the 'Carter effect' for cardiovascular phenotypes.

Main Results:

  • Strong correlations observed between clinical features within the same organ system (ophthalmologic, skeletal, cardiovascular), suggesting shared genetic determinants.
  • Most MFS clinical features demonstrated significant familial aggregation and high heritability.
  • The major locus significantly influenced only ectopia lentis; evidence for a polygenic model in cardiovascular variability was found, including the 'Carter effect'.

Conclusions:

  • A substantial portion of Marfan syndrome phenotypic variability is attributable to inherited genetic modifiers.
  • These modifiers appear to be shared among features within the same organ system but not across different systems.
  • Further research is needed to identify specific genetic modifiers influencing MFS severity.
Keywords:
fibrillinheritabilitymarfanmodifiers

More Related Videos

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information09:37

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

Published on: August 15, 2019

10.2K
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

11.2K

Related Concept Videos

Polygenic Traits01:18

Polygenic Traits

When more than one gene is responsible for a given phenotype, the trait is considered polygenic. Human height is a polygenic trait. Studies have uncovered hundreds of loci that influence height, and there are believed to be many more. Due to the high number of genes involved, as well as environmental and nutritional factors, height varies significantly within a given population. The distribution of height forms a bell-shaped curve, with relatively few individuals in the population at the...
68.6K
Human Genetics01:28

Human Genetics

Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
1.3K
X-linked Traits01:19

X-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”.
58.1K
Incomplete Dominance01:43

Incomplete 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.
29.4K
Genetic Variation01:25

Genetic Variation

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.
Genes exist in different versions called alleles,...
1.1K
Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
15.1K