DNA MUTATIONS Diseases Types Mutagens Mutations are any change in the genetic make up of an organism and can occur naturally or can be increased by mutagens. Click on an area for more information Diseases Types Mutagens

Error rate is 1 in 1,000,000 replications. TYPES OF MUTATIONS Mutations can be spontaneous or natural as a result of errors in DNA replication or gamete production. Error rate is 1 in 1,000,000 replications. Click on an area for more information POINT BLOCK CHROMOSOMAL ABBERATIONS

Point mutations Involves a change to one of the DNA bases that makes up a gene. Also known as a MISSENSE mutation. Consequence varies depending on type of change. Change DNA Change amino acid sequence Change protein Change organism Click to find out more Three types of point mutation deletion insertion substitution

Base Substitution But… Also Involves one base in the DNA being substituted by another. This mutation only affects one codon in the gene. But… ATA UAU Tyr mRNA DNA ATT UAA STOP T A C T T C A A A C C G C G T DNA C is replaced by T in the DNA. Known as NONSENSE mutation Totally different protein made Effect on organism can be dramatic Also AGA UCU Ser mRNA DNA AGG UCC T A C T T C A A A T C G C G T End result is a different amino acid in protein. Generally minor effect on protein/organism. Serine is still added Known as a SILENT mutation

Dramatic effect on protein made. Known as frame shift mutations. Base Insertion/Deletion Involves one base either being inserted or removed from the DNA sequence. Both these mutations affect all codons after the insertion or deletion. The earlier the mutation occurs in the sequence the greater the effect. T A C T T C A A A C C G C G T DNA Dramatic effect on protein made. Known as frame shift mutations. T A C T T C A A A A C C G C G Trp Arg BASE INSERTION INSERTION T A C T T C A A C C G C G T A

Block mutations Involves large scale changes in DNA segments on chromosome. Only occur during meiosis, formation of gametes (sex cells). Can affect the functioning of many genes Severe effect on functioning and characteristics of organism. Change DNA Change amino acid sequence Change protein Change organism Four types of block mutation inversions translocations deletions Click to find out more duplications

Deletion Section of chromosome is lost, anywhere from three bases to large segments. The DNA breaks due to the effect of mutagens. A D B E C F H G STEP 1 genes A D B E C F H G segment is lost STEP 2 break A D E F H G DNA ligase rejoins chromosome STEP 3

Translocation Section of chromosome breaks and is joined to another chromosome. Problem when gametes formed-some receive extra genes, some deficient. STEP 1 A D B E C F H G 3 4 2 5 1 segment removed STEP 2 3 4 2 5 1 D E F H G break D E F H G DNA ligase joins segment STEP 3 3 4 2 5 1

Duplication Segment of one chromosome is added to the homologous chromosome. Problem when gametes formed-some have double the genes, some have no genes. STEP 1 A D B E C F H G D E F H G A B C STEP 2 segment removed break D E F H G STEP 3 A B C

Inversion Section of chromosome falls out and rotates through 180o. DNA ligase rejoins section but the genes are in reverse order. There is no loss of genetic information. A D B E C F H G STEP 1 A D B E C F H G STEP 2 segment rotates 180o break segment rejoins STEP 3 A D B E C F H G

Chromosomal abberations Loss or gain of entire chromosomes- called aneuploidy. Main cause is non-disjunction of chromosomes during meiosis. Gametes end up with extra chromosome(s) or fewer than 23 chromosomes. 2 x 23 Normal diploid (2N) human cell containing 2 sets of chromosomes. <23, >23 Through meiosis haploid (N) gametes are produced, containing only one set of chromosomes. 23 Mainly occurs with sex chromosomes. Turner syndrome Normal female Metafemale Normal male Jacob syndrome XO XX XXX XY XYY Examples

Mutagens Chemicals or radiation that increase the likelihood of a mutation occurring. Rate of mutation induced by mutagen is proportional to the dose of mutagen. Mutagens cause a decrease in the stability of the DNA molecule. Thus DNA more susceptible to error during replication or meiosis. Viruses & micro-organisms Incorporate into genome Trigger cancers Ionising radiation Nuclear UV rays X rays Types Alcohol & dietary factors High fat, alcohol Trigger cancers Environmental poisons/irritants Benzene, asbestos Tobacco tar, formaldehyde

Diseases Down syndrome Sickle cell disease Cystic fibrosis Click on a disease to find out more about how it is caused by a mutation. Sickle cell disease Down syndrome Cystic fibrosis

Sickle cell disease haemoglobin Haemoglobin is made up of 4 polypeptide chains (2 alpha & 2 beta chains). Gene for beta chain is found on chromosome 11 and consists of 438 bases. A mutation occurs in the gene coding for the beta chain. The mutation is a substitution where adenine replace thymine on the DNA template strand. As a result the amino acid valine replaces glutamic acid. This change the properties of the haemoglobin and results in distorted red blood cells. HBB gene on chromosome 11 normal red blood cell sickle cell This single point mutation has a dramatic effect. Individuals have many health problems, eg weakness, jaundice, anaemia, heart & kidney defects, brain damage, skin lesions and inflamed spleen.

Cystic Fibrosis AAA TAA TAG AAA CCA CAA TAA TAG AAA CCA CAA CFTR gene on chromosome 7 Inherited disorder and occurs when an individual has both copies of the faulty gene. The gene (CFTR) is found on chromosome 7 and normally contains 1480 amino acids. A mutation occurs whereby the 508th triplet (AAA) is deleted resulting in a mutated CFTR protein of 1479 amino acids. The abnormal protein is unable to control chloride ion balance in cells. The build up of chloride ions in cells results in severe effects. Individuals have reduced life expectancy, high salt levels, blocked airways, pancreatic deficiencies and males are infertile. Cystic fibrosis is relatively common and occurs 1 in every 2500 individuals. triplet deleted TAA TAG AAA CCA CAA DNA 506th 507th 508th 509th 510th TAA TAG AAA CCA CAA DNA 506th 507th 508th 509th 510th AAA AUU AUC UUU GGU GGU mRNA AUU AUC GGU GGU ile ile gly val mRNA amino acids ile ile phe gly val amino acids

Down Syndrome 24 23 Non-familial Familial Arise from having 3 copies of chromosome 21 known as trisomy-21. Down Syndrome Individuals have characteristic facial features, are relatively short, slowed intellectual and physical development. Two main types of Down syndrome-97% non-familial, 3% familial. 24 23 One of the parent’s sex cells contains two no. 21 chromosomes, due to non-disjunction during meiosis. Non-familial Familial One of the parents has only 45 chromosomes. A translocation has occurred where one of no.15 and one of no. 21 have joined together. One of the sex cells contain 23 but one of the 23 is the 15/21 chromosome. 15 21 15/21 Parent 1 Parent 2 Down child 3 no.21