Can you spare minutes to tell us what you think of this website? Open survey. In: Facts In the Cell. There are lots of different mutations that can occur in our DNA.
Small-scale mutations Point mutation — a change in one base in the DNA sequence. Related Content:. What is a mutation? What is DNA? Only occurs in sex cells. A chromosomal inversion is when a piece of a chromosome breaks off, flips around, and reattaches. Watch the video above to see what this actually looks like. Inversion is a type of chromosome rearrangement where a segment of a chromosome gets flipped around.
These mutations aren't totally awful because there is still the same amount of genetic material. Chromosomal mutations all happen during meiosis.
Chromosomes in meiosis have the opportunity to line up and cross over. This mixes up the genetic information from the parents in the sperm or egg.
However, during crossing over things can go wrong. All of these chromosomal mutations deletion , inversion, duplication , translocation will go unnoticed in the sperm or egg.
When a mutated egg or sperm becomes fertilized, the mutations that occurred in the parents' cells become noticeable. Biology Chromosome Mutations. However, these strategies are laborious and do not work for global unbiased discovery of new inversion regions on a genome-wide scale. Despite these limitations, a small number of studies have led to the identification of inversion variants using 'genomic' strategies. One approach that led to the identification of three polymorphic inversions was based on investigating regions that are inverted between the human and chimpanzee genomes.
By targeting 23 such regions in human control samples, three inversions were found to be polymorphic in humans. In another study, Bansal et al. By using a statistical method to detect regions where SNPs at a distance from each other on the reference assembly were in higher LD than SNPs in close proximity, a number of putative inversions were identified.
Overlap with several previously validated inversions indicated that the approach was successful. However, the candidate variants identified by this method require experimental validation to distinguish real inversions from false positives.
Although the approaches outlined above have shown some success in the discovery of novel inversion variants, recent data indicate that only a very small fraction of frequent human inversions were found. A major breakthrough in the discovery of inversions and other forms of structural variation came with the introduction of paired-end sequencing and mapping [ 7 ]. By searching for clusters of fragments exhibiting this pattern of alignments to the reference assembly, it is possible to identify putative inversion events.
The first paired-end mapping study was based on end sequencing of fosmid clones using traditional Sanger sequencing [ 7 ].
The study identified 56 inversion breakpoints from a fosmid library representing a single human genome sample NA The same strategy of fosmid end sequencing was later applied to another eight genomes, and a total of inversions were identified and validated [ 6 ]. A large number of inversions were also reported in the first individual genome to be sequenced the genome of Craig Venter, called HuRef [ 25 ].
An assembly comparison analysis gave rise to 90 regions of inverted orientation between the HuRef and NCBI assemblies. Since these initial Sanger sequencing studies, the general strategy of paired-end mapping has been adapted to fragment end-sequencing with second-generation-sequencing platforms [ 26 , 27 ].
Although only a small number of whole-genome sequencing studies have so far employed this strategy to identify inversions, this is likely to be the main approach for identification of inversions in the near future. Overview of inversion discovery by paired-end mapping. The top part of the figure shows the alignment between the reference assembly and an individual carrying an inversion.
The ends of these fragments are then sequenced fragments are depicted in blue and red, with the boxes at the ends showing the parts that are sequenced.
The pairs of end-sequences are then mapped to the reference genome. End-pairs labeled B and C indicate mapping of fragment ends in a region containing an inversion compared to the reference assembly.
Clusters of such read pairs are indicative of an inversion. Only fragments spanning the inversion breakpoint will exhibit this pattern of alignment. Better clone coverage will yield better resolution and more accurate mapping of the breakpoints. Despite the success of paired-end mapping, there are still challenges to overcome.
One important feature of the paired-end mapping approach is that it relies on the reference assembly. It is well established that the reference assembly represents very rare or unique alleles at some loci in the genome.
In rare instances, it is also possible that these unique alleles represent cloning artifacts or are a result of mis-assembly of the reference sequence. For example, this has been suggested for an inversion overlapping an exon of the DOCK3 gene on chromosome 3, for which there is an inversion in the reference assembly as compared to available mRNA sequences for the same gene [ 5 ].
For regions where the reference assembly harbors a unique allele, every study with high enough resolution and sequence coverage will identify a homozygous inversion. Another limitation of paired-end mapping for inversion detection is related to the genome architecture associated with inversions. The segmental duplications associated with inversions cause problems for inversion discovery using paired-end mapping.
As the method depends on alignment to the reference assembly, highly identical sequences in the assembly will cause problems in identifying unique placements for the sequence reads. Many paired-end mapping pipelines simply discard reads that cannot be uniquely mapped. Therefore, the paired-end mapping strategy often fails to identify inversions flanked by long inverted segmental duplications of high identity.
For these regions, targeted assays are required. The map of human inversions is still quite limited, and our understanding of the number of inversions, the size distribution and the frequency distribution is probably biased due to biases in the approaches used for variation identification.
There are currently inversion events reported in the Database of Genomic Variants [ 30 ], a database resource for structural variation in the human genome [ 3 , 31 ]. However, many of these overlap and actually refer to the same locus. If only non-redundant loci are counted, there are a total of inversions in the database. Figure 2 shows an overview of the current inversions reported in the human genome. The inversions are found across the size spectrum up to several megabases. A comparison of the size distribution of inversions and CNVs is shown in Figure 3.
The size distribution shows that most of the inversions discovered to date are in the 10 kb to kb interval. For CNVs, size distribution is shifted more towards smaller size variants. Distribution of inversion variants in the human genome. The blue lines in this ideogram show the human chromosomal distribution of the non-redundant inversion variants reported in the Database of Genomic Variants. Size distribution of inversions and copy number variants.
The size distribution of inversions reported in the Database of Genomic Variants a shows that the majority of inversions reported to date are in the 10 to kb size bin. It is currently unclear whether the difference in size distribution between inversions and CNVs is due to ascertainment bias, or whether there is an actual biological difference in size distribution. Both cytogenetic data and evolutionary comparative genomic data indicate that large inversions are less detrimental than large deletions and duplications.
There are many potential explanations for the difference in size distribution between inversions and CNVs Figure 3. Biologically, large inversions are more likely to be neutral, without obvious phenotypic consequences, compared to large CNVs. Data from cytogenetic studies support this. Here, find out the chromosomal aberrations involving the genes. Skip to content Main Navigation Search. Dictionary Articles Tutorials Biology Forum. Chromosome Mutations Mutations can also influence the phenotype of an organism.
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