Early linkage studies in our lab and other labs identified significant regions of interest, but these regions are large and contain many genes. Different studies were needed to identify the specific genes that are important for scoliosis.
Several laboratories have completed large studies across the genome, called a genome wide association study. These studies look at millions of common variant markers, called SNPs, across the genome in hundreds or thousands of individuals. These association studies have identified common variants in or near several genes that could contribute to idiopathic scoliosis (CHD7, LBX1, GPR126, and PAX1).
More recently, advances in genetic technology have allowed for sequencing of all of the coding regions of an individual’s genome. The coding regions of the genome are used to produce proteins, which are the main functional molecules in the body. These studies typically identify rare variants that could cause or contribute to a disorder. This type of sequencing is called exome sequencing.
Our laboratory completed exome sequencing in our family population and identified rare variants in a gene, HSPG2, that we believe may contribute to idiopathic scoliosis in these individuals. This finding was replicated in an independent idiopathic scoliosis population.
In addition, our other exome sequencing studies in idiopathic scoliosis have identified potential genes. Our collaborators at Washington University have identified rare variants in the FBN1, FBN2, and collagen genes that could be important for idiopathic scoliosis. Other laboratories have identified variants in the POC5 gene in their families.
There is a substantial amount of research by multiple laboratories to find the genes related to scoliosis. It has become clear that there are likely multiple genes involved in idiopathic scoliosis and that it is a highly complex disorder. Our current research is focused on identifying these genes using our family population.
Definitions of some commonly used words in genetics:
Allele: a word used to describe the alternate version of a gene. People inherit one allele from each parent.
Chromosome: the carrier for genetic information in the cell; made up of DNA and protein. Children get half of their chromosomes from their mother and half from their father.
DNA: the molecule that contains genetic instructions in all living things. DNA is made up of A, C, G, and T. It serves as instructions for assembling protein and RNA.
Gene: Genes are a packet of information used to make a protein. Genes can be very short or very long. We look for changes in genes that may tell us what causes diseases.
Genome: the entire set of instructions found in a cell. The human genome consists of 23 pairs of chromosomes, and contains about 3.1 billion bases of DNA sequence.
Genotype: an individual’s collection of genes. This also commonly refers to a difference in DNA sequence in a specific place in a specific gene.
Heterozygous: having inherited different forms of a particular gene from each of your parents.
Homozygous: having inherited identical forms of a particular gene from each of your parents.
Phenotype: a person’s observable traits, such as height, eye color, or presence of a disease like scoliosis.
Protein: the main functional molecules in the body. Proteins are made from RNA, which is made from DNA.
RNA: a molecule that often transfers information from the DNA into proteins. Other types of RNA perform different functions in the cell.
Sequencing (DNA): the laboratory technique used to determine the exact sequence of bases (A, C, G, T) in DNA. Sequencing many people with a disease like scoliosis can help us find places where they differ from people that do not have the disease (SNPs or variants), and that information may help us understand the disease.
SNP (single nucleotide polymorphism): a single base in the DNA that varies between people. Some SNPs don’t do much, but others can cause an increased risk for a disease.
Variant: DNA sequences that vary between people. These are often small changes of only one base (called a SNP), or they can be much larger in size and involve long stretches of DNA. Common variants are found in many individuals and are sometimes called a polymorphism. Rare variants are found in one or a few individuals and are sometimes called a mutation.
Definitions taken from http://www.genome.gov/glossary/index.cfm