Related Experiment Video
Updated: Jan 28, 2026
12:04
Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
Published on: March 10, 2023
4.8K
The functional importance of disease-associated mutation
1Department of Genetics and Stanford Medical Informatics Division, Stanford University, Stanford, California, 94305, USA. mooney@smi.stanford.edu
BMC Bioinformatics
|September 11, 2002
Summary
Scientists discovered that disease-associated mutations in genes occur in conserved regions, aiding in the identification of likely disease-causing mutations using phylogenetic analysis.
Area of Science:
- Genetics
- Bioinformatics
- Genomic Medicine
Background:
- Historically, point mutations were considered the primary genetic drivers of diseases like cystic fibrosis, phenylketonuria, and cancer.
- These mutations were presumed to alter protein function detrimentally, particularly in functionally critical gene regions.
Purpose of the Study:
- To investigate the conservation patterns of disease-associated mutations.
- To develop a method for identifying likely disease-causing mutations based on evolutionary conservation.
Main Methods:
- Analyzed conservation patterns for 6,185 non-synonymous and heritable disease-associated mutations across 231 genes.
- Defined a 'conservation ratio' to quantify mutation conservation relative to overall gene sequence conservation.
Main Results:
- Found that 84.0% of the 231 genes analyzed exhibited conservation ratios below one.
- Among genes with eleven or more mutations, 88.0% also showed conservation ratios less than one.
Conclusions:
- Phylogenetic information is a valuable tool for studying disease-associated mutations.
- A database of alignments and analyses is available to identify likely disease-causing mutations.
Related Concept Videos
01:30Point and Frameshift Mutations
1.1K
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
1.1K
01:18Mutations in Microorganisms
715
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,...
715
01:39Mutations
94.4K
Overview
94.4K
01:35Mutations
44.4K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.4K
00:36Viral Mutations
39.8K
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...
39.8K
01:09Mutation, Gene Flow, and Genetic Drift
63.8K
In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
63.8K