Mutation, genetic disease, and modern genetics
Mistakes in DNA create variation and sometimes disease. New technologies now let us read and edit genes directly.
Mutations
A mutation is a change in DNA sequence. Point mutations change single bases; insertions and deletions add or remove bases, and if the number is not a multiple of three they shift the reading frame and scramble the protein. Mutations arise from copying errors, radiation, and certain chemicals.
Effects of mutations
Many mutations are neutral, changing nothing important. Some are harmful, disrupting a protein. A few are beneficial in a particular environment and are the raw material of evolution. Mutations in body cells affect only that individual; those in sex cells can be inherited.
Single-gene disorders
Cystic fibrosis is recessive, caused by mutations in a gene for a chloride channel, leading to thick mucus. Sickle cell disease comes from a single base change that alters haemoglobin. Huntington's disease is dominant, so one copy causes it, typically appearing in middle age.
Chromosomal disorders
Errors in meiosis can give gametes an extra or missing chromosome (nondisjunction). Down syndrome usually results from three copies of chromosome 21. Turner syndrome results from a single X chromosome. Most other changes in whole chromosome number are not survivable.
Genetic testing
DNA tests can identify carriers, diagnose conditions before birth, and predict risks of some diseases. Newborn screening catches treatable conditions early. Testing raises ethical questions about privacy, insurance, and how people use information about their risks.
Biotechnology
Recombinant DNA technology inserts genes into other organisms: bacteria now make human insulin. The polymerase chain reaction (PCR) copies a DNA segment billions of times, enabling forensic and medical testing. Genetically modified crops can resist pests or tolerate drought.
Gene editing
CRISPR-Cas9 is a tool, adapted from a bacterial defence system, that cuts DNA at a chosen sequence so genes can be disabled or corrected. In 2023 the first CRISPR-based therapy was approved for sickle cell disease. Editing embryos, whose changes would be inherited, remains highly controversial.
Worked example
A sickle-cell carrier (Ss) and a non-carrier (SS) have children. Each child has a 1/2 chance of being SS and 1/2 of being Ss; none will have sickle cell disease (ss). Carriers are partly protected against malaria, which explains why the allele is common in regions where malaria is widespread.
Key takeaways
Mutations change DNA; frameshifts are often severe. Most mutations are neutral, some harmful, a few beneficial. Single-gene disorders can be recessive or dominant; nondisjunction causes chromosomal disorders such as Down syndrome. PCR, recombinant DNA, and CRISPR let scientists read and edit genes, raising ethical questions.
Flashcard
Change in DNA sequence
Check your understanding
Why is a deletion of one DNA base often more harmful than a single base substitution?