Structural variation in the human genome
[1] Single nucleotide polymorphisms (SNPs) are considered to be the largest contributor to genetic variation in humans since they are so abundant and easily detectable.
[2] It is estimated that there are at least 10 million SNPs within the human population but there are also many other types of genetic variants and they occur at dramatically different scales.
With improving sequencing technologies and the reference genome, more and more variations were found of several different sizes that were larger than 1 kb but smaller than microscopic variants.
[1] These recently discovered structural variants are thought to play a very significant role in phenotypic diversity and disease susceptibility.
A study found that forty percent of haemophilia A patients had a factor 8 gene inversion of a certain region that was four hundred kb in size.
A study was done on the olfactory receptor gene clusters where they questioned if there was an association between normal rearrangement of 8p and the repeated inverted sequences.
Therefore, they concluded that the substrate used in order to make rearrangements at the intrachromosomal level are the genes for olfactory receptors.
Copy-number variants are defined as sections of DNA that exist in a variable copy number when comparing it to the reference genome and are larger than 1 kb in size.
It was known that copy number variation in the human genome is important but at this point of time, it had not yet been fully understood.
Human genome variation itself is very diverse as there are many types including inversions, duplication, SNPs, and other forms.
They surveyed the genomes of 270 individuals, from a variety of populations, for copy number variants with technologies such as SNP arrays.
A study was conducted that questioned the role of the organization of copy number variants and wondered what type of duplications they are.
It was known that copy number variation plays a big role in many human diseases but at the time large scale studies of these duplications had not been done.
[8] It was a very interesting result in that the certain architectural features of the genome physically made it possible and probable to develop certain rare and pathogenic structural variants.
[9] This study brought exciting results as structural variation proved an involvement in the evolution of the human population by increasing its amylase copy number over time.
They provided much sequencing data from many populations to analyze as well as a reference human genome for comparison and future studies.
[11] If the individual had only one copy of the PMP22 gene, on the other hand, the result was a clinically different hereditary neuropathy with liability to pressure palsies.
Structural variation studies became increasingly popular due to the discovery of their possible roles and effects in the human genome.
[12] This difference in copy number was shown to play a possibly significant role in HIV susceptibility due to this association.
This led the researchers to conclude that the NPY4R gene played an important role in the pathogenesis of obesity due to its copy number variation.
[14] This was due to the linkage disequilibrium which allowed the researchers to determine the C4 structural variant easily by looking at the SNP haplotype.
Huge projects such as Deciphering Developmental Disorders, UK10K, and International Standards for Cytogenomic Arrays Consortium have already paved the way to create databases for researchers to more easily pursue these studies.
[15] In addition, there has been growth and development in technology to create induced pluripotent stem cells with specific diseases.
This introduces appropriate model systems to recreate disease causing structural variants such as translocations, duplications, and inversions.
[15] The future advancement in technologies and large database efforts will help lead the way to better quality studies and a much better understanding of human genome structural variation.
