Whole genome sequencing

The human genome sequence stored in nearly every cell in your body contains all the instructions required to grow and operate a human being, specifically you. Whole genome sequencing reveals the exact sequence of human DNA, the order of 3 billion pairs of nucleotide bases.

There are four different nucleotide bases in DNA — Guanine, Adenine, Thymine and Cytosine — meaning the entire blue-print for human life is spelled out with an alphabet of four letters, G, A, T and C.

Around 20,000 long sequences of nucle-otide base pairs make up genes, which are recognizable instruction sets for mak-ing proteins and other biological func-tions. Only about two per cent of human DNA is made up of genes, the balance is non-coding DNA which remains poorly

understood.Genetic markers indicate locations on genes where mutations have occurred; some markers may be associated with inherited traits or disease. Most of the dif-ferences are harmless copying errors that occur over generations, while others alter the function of a protein in a way that is harmful. Inexpensive direct-to-consumer genome tests look at about 1 million locations on genes where people are known to differ from one another, some of which have well-understood functions. Whole genome sequencing usually identifies 3 to 4 million variations.

Earlier genetic tests typically focus on locations known to be associated with illness, usually screening for one or a handful of mutations. Whole genome

sequencing — based on new high-throughput technology for obtain-ing DNA sequences — simultane-ously screens for tens of thousands of sequence variants known to be associ-ated with disease, along with all the loca-tions that have no known function or association with disease ... yet.

To reveal the entire sequence, a sample containing your DNA is chopped up into small lengths. All the fragments are read by the sequencer at the same time, what is called massively parallel sequencing.

Because most of the code in people’s DNA is so similar, the sequence of let-ters can be put back in the right order by comparing strings of genetic words to those of a standard reference human genome.

Genes and mutations that increase risk of disease

Human

cell

DNA

NucleousNucleous

chromosone

AA TTGG CC

Chromosome 1Protein encoder PSEN2 helps govern chemical signals in the brain. It is one of four genes implicated in Alzheimer’s disease.

Chromosome 3SCLC1 is the genetic location of an inherited code deletion that leads to small cell lung cancer.

Chromosome 4The Huntington gene may contain a repeated sequence of nucleotides — the four-let-ter code that makes up all DNA — resulting in the creation of a dysfunctional protein. Typi-cally, the longer the sequence of repeated code, the earlier the degenerative symptoms appear.

Chromosome 11Three known mutations on the APOA5 gene are strongly asso-ciated with high blood trig-lycerides, which increases the risk of cardiovascular disease. People of Asian and Hispanic ancestry are most likely to carry one of the risk variants.

Chromosome 19APOE contains the code for protein that transports choles-terol and protects against vas-cular disease. Two variants of the gene produce an altered protein structure associated with atherosclerosis.

Chromosome 17 (and 13)Mutations that interfere with the function of BRCA1 gene may be inherited from either parent. Of the hundreds of mutations associated with BRCA1 and BRCA2 (on chromo-some 13), a few are known to increase the risk of ovarian and breast cancer by up to 30 times normal.

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