Reading the human genome

1. The human genome is the complete set of genetic material in a human cell.
2. The Human Genome Project worked out the order of the bases in human DNA and was declared complete in $2003$.
3. Scientists from several countries, including a large team in the UK, shared the work and made the results freely available to researchers everywhere.
4. The project found that the human genome contains around $20000$ genes that code for proteins.
5. Since then, reading a genome has become much faster and cheaper, so a person's whole genome can now be sequenced in a few days.
6. Comparing the genomes of many people shows which alleles are more common in people who have a particular disease.
7. This allows scientists to link particular alleles to an increased risk of disease, and to find out how different alleles affect the way the body responds to drugs.
8. In England, the 100,000 Genomes Project sequenced the genomes of NHS patients with rare diseases and cancers to find the genetic causes of their conditions.

Predicting the likelihood of disease

1. Genetic testing analyses a person's DNA to see whether they carry alleles linked to a disease.
2. For a disorder caused by a single faulty allele, such as cystic fibrosis or Huntington's disease, a test can show whether a person has the disorder or carries the allele.
3. For most common diseases, such as heart disease, type 2 diabetes and many cancers, a test can show only an increased risk, because these diseases also depend on many other genes and on lifestyle.
4. For example, women who carry a faulty BRCA1 or BRCA2 allele have a much higher chance of developing breast cancer or ovarian cancer during their lives.
5. Knowing about an increased risk allows a person to act early.
   1. They can have more frequent screening, such as regular scans, so that a disease is found and treated at an early stage.
   2. They can make lifestyle changes, such as stopping smoking or losing weight, that lower their overall risk.
   3. Some women with a faulty BRCA1 allele choose surgery to remove their breasts or ovaries before cancer can develop.
6. Couples who carry a faulty allele can find out the chance that their children will inherit a genetic disorder.

Drugs targeted to the genome

1. People respond differently to the same drug, partly because they carry different alleles.
2. Some alleles code for liver enzymes that break down drugs faster or more slowly than usual.
   1. A person who breaks a drug down quickly may need a higher dose for it to work.
   2. A person who breaks a drug down slowly may suffer harmful side effects from a normal dose.
3. Testing a patient's genome before treatment lets a doctor choose the drug and dose most likely to work for them with the fewest side effects.
4. This approach is called personalised medicine.
5. Cancer cells carry their own mutations, so reading the genome of a tumour shows which drug is most likely to attack it.
   1. Some breast cancers have cells with extra copies of a gene called HER2, and a drug that targets the protein made by this gene works only on these cancers.
6. Knowing which genes are involved in a disease also helps scientists design new drugs that act on the proteins those genes produce.

Problems and concerns

1. A genetic test for a common disease gives a probability rather than a certainty, so a person told they have a high risk may never develop the disease, while a person told they have a low risk still might.
2. Learning about a high risk of a disease that cannot be prevented or cured, such as Huntington's disease, can cause great anxiety.
3. Genetic information about one person also reveals information about their relatives, who may not want to know it.
4. There are concerns that insurance companies or employers could treat people unfairly if they had access to their genetic information.
5. Genome data must be stored securely, because it is personal and cannot be changed if it is leaked.
6. Genetic testing and targeted drugs are expensive, so they may not be available to everyone who could benefit.
7. The effects of many alleles are not yet understood, so some test results are difficult to interpret.