Related Experiment Video
Updated: Jul 17, 2026
07:15
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Evolutionary comparison provides evidence for pathogenicity of RMRP mutations
Luisa Bonafé1, Emmanouil T Dermitzakis, Sheila Unger
1Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Luisa.Bonafe@chuv.ch
Plos Genetics
|October 26, 2005
Summary
Cartilage-hair hypoplasia (CHH) is a rare genetic disorder caused by RMRP gene mutations. Identifying novel mutations aids in diagnosis and understanding the disease
Area of Science:
- Genetics
- Molecular Biology
- Human Disease
Background:
- Cartilage-hair hypoplasia (CHH) is a pleiotropic disorder.
- It results from recessive mutations in the RMRP gene.
- CHH presents with diverse symptoms including short stature, sparse hair, immune deficiency, and cancer predisposition.
Purpose of the Study:
- To report novel mutations in the RMRP gene in patients with CHH.
- To describe the phenotypic spectrum associated with these mutations.
- To develop a method for predicting mutation pathogenicity.
Main Methods:
- Genomic sequencing to identify mutations in 36 CHH patients.
- Comparative genomic analysis of RMRP gene sequences across mammals.
- Alignment of genomic sequences to identify conserved and non-conserved regions.
Main Results:
- Identified 20 novel RMRP mutations in 36 patients.
- Established a correlation between mutation location in conserved nucleotides and pathogenicity.
- Observed high mutational heterogeneity and diversity in the RMRP gene.
- Found that CHH may be underdiagnosed due to variable presentation.
Conclusions:
- RMRP molecular testing is valuable for diagnosing CHH.
- Comparative genomics aids in predicting mutation pathogenicity for RMRP variants.
- CHH is likely more common than previously thought and warrants consideration in patients with metaphyseal dysplasia, anemia, or immune dysregulation.
Related Concept Videos
01:36Mismatch Repair
Overview
00:36Viral Mutations
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...
02:54Evolutionary Relationships through Genome Comparisons
Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...
01:20Mismatch Repair
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
01:18Mutations in Microorganisms
Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
01:24Evolution of New Traits in Microbes
Microorganisms evolve rapidly due to their large population sizes and short generation times, often exhibiting measurable changes within days under laboratory conditions. Natural selection acts on standing genetic variation, enabling the retention and amplification of beneficial traits that confer fitness advantages in changing environments.Adaptive Pigment Regulation in RhodobacterIn Rhodobacter, a genus of purple non-sulfur bacteria, light-harvesting pigments such as bacteriochlorophyll and...