SNPs

Various scientific endeavors had already started even before the completion of the first human genome reference sequence to identify unique genetic differences between individuals. 99.9% of one individual DNA sequences will be identical to that of another person. Of the 0.1% difference, over 80% will be single nucleotide polymorphisms (SNPs). A SNP is a single base substitution of one nucleotide with another, and both versions are observed in the general population at a frequency greater than 1%. Human DNA is comprised of only four chemical entities, e.g. A, G, C, T, whose specific chemical order is the alphabet of the genome. An example of a SNP is individual "A" has a sequence GAACCT while individual "B" has sequence GAGCCT, the polymorphism is a A/G. The most recognized public effort was spearheaded by The SNP Consortium (TSC) whose mission was to determine and map about 300,000 evenly spaced single nucleotide polymorphisms within the human genome.

99.9% of one individual DNA sequences will be identical to that of another person. Of the 0.1% difference, over 80% will be single nucleotide polymorphisms (SNPs).

Current estimates are that SNPs occur as frequently as every 100-300 bases. This implies in an entire human genome there are approximately 10 to 30 million potential SNPs. More than 4 million SNPs have been identified and the information has been made publicly available through the efforts of TSC and others. Many of these SNPs have unknown associations. Compilation of public SNPs by NCBI has produced a subset of SNPs defined as a non-redundant set of markers that are used for annotation of reference genome sequence and are thus referred to as reference SNPs (rsSNPs). Over 2.6 million SNPs have currently been assigned as "rsSNPs".

Recent work has suggested that about 10 million SNPs that are common in human population are not inherited independently; rather, sets of adjacent SNPs are present on alleles in a block pattern, so called haplotype. Many haplotype blocks in human have been transmitted through many generations without recombination. This means although a block may contain many SNPs, it takes a few SNPs to identify or tag each haplotype in the block.

Click Here for a SNP map of human Chromosome 5   (Courtesy of NCI Cancer Genome Anatomy Project site)

^ Back to Top

SNPs and Diagnostics

Eventually, SNP profiles that are characteristic of a variety of diseases will be established. Then, it will only be a matter of time before physicians can screen individuals for susceptibility to a disease just by analyzing their DNA samples for specific SNP patterns.

Many common diseases in humans are not caused by one genetic variation within a single gene, but are determined by complex interactions among multiple genes, environmental and lifestyle factors. Genetic factors confer susceptibility or resistance to a disease and influence the severity or progression of disease. Since we do not yet know all of the factors involved in these intricate pathways, researchers have found it difficult to develop screening tests for most diseases and disorders, such as diabetes, many cardiovascular diseases, Alzheimer's disease, arthritis, to name just a few. By studying SNP profiles or haplotypes associated with a disease trait, researchers may begin to reveal relevant genes associated with a disease. Association study can detect and indicate which pattern is most likely associated with the disease-causing genes. Eventually, SNP profiles that are characteristic of a variety of diseases will be established. Then, it will only be a matter of time before physicians can screen individuals for susceptibility to a disease just by analyzing their DNA samples for specific SNP patterns.

^ Back to Top

SNPs and Drug Discovery - Pharmacogenomics

The race among pharmaceutical companies today is to apply new system genomics approach to identify novel targets and validate these targets in the most efficient fashion. SNP research will provide fundamental understanding of many polygenic diseases, thus providing new therapeutic targets. Another significant goal is to identify those SNPs which are associated with significant biological effects in response to chemical drugs. A large percentage of people given a drug respond in the intended medically beneficial way, however some smaller percentage might either have no response or have a life threatening response and death. This adverse drug response (ADR) is believed to cause thousands of deaths annually. The SNP effort will serve as the bedrock of pharmacogenomics, the emerging field of personalized medicine: the right drug, in the right dose, to the right person, at the right time.

The SNP effort will serve as the bedrock of pharmacogenomics, the emerging field of personalized medicine: the right drug, in the right dose, to the right person, at the right time.

SNP study is also extremely important in organisms other than humans. Within agriculture, genetic modification of the agriculturally important crops (corn, wheat, rice, soybeans, etc.) could lead to improve crop yields at lower cost by reducing the amounts of fertilizer, insecticides, herbicides required. Within microorganisms and viruses, SNPs are known to cause increased drug resistance. Some of the recent E. coli outbreaks are due to new evolving strains of the bacterium. HIV the causative agent of AIDS has historically been so difficult to treat with drugs due to very high mutation frequency primarily in the form of SNPs.

^ Back to Top

Useful Links

1. The SNP Consortium LTD.

The SNP Consortium, Ltd. ("TSC") has been formed to advance the field of medicine and the development of genetic based diagnostics and therapeutics, through the creation of a high density single nucleotide polymorphism (SNP) map of the human genome. This map will be freely available to all parties [members and non-members] at the same time.

2. NCBI LocusLink

LocusLink provides a single query interface to curate sequence and descriptive information about genetic loci. It represents information on official nomenclature, aliases, sequence accessions, phenotypes, EC numbers, MIM numbers, UniGene clusters, homology, map locations, and related web sites.

3. dbSNP

A central repository for both single base nucleotide substitutions and short deletion and insertion polymorphisms supported by the National Center for Biotechnology Information and the National Human Genome Research Institute.

4. Human Genome Variation database

HGVbase is an attempt to summarize all known sequence variations in the human genome, to facilitate research into how genotypes affect common diseases, drug responses, and other complex phenotypes.

5. GeneDis

A small, focused web site designed as an "everything you always wanted to know" about 12 human diseases.

6. PharmGKB

The pharmacogenetics and pharmacogenomics Knowledge Base. PharmGKB is an integrated resource about how variation in human genes leads to variation in our response to drugs. Genomic data, molecular and cellular phenotype data, and clinical phenotype data are accepted from the scientific community at large.

7. GeneCards

GeneCards is a database of human genes, their products and their involvement in disease. It offers concise information about the functions of all human genes that have an approved symbol as well as selected others.

 

^ Back to Top

SNP Animation

Click to view animation

 

^ Back to Top