Effects of Mutations PDF

01/10/23 Effects of mutations: Learning objectives: understand why some mutations lead to dominant inheritance patterns, whilst others are recessive. Learning objectives: de ne t wo majors disorders that arise from DNA mutations affecting a single gene that affects protein function: sickle cell anae...

01/10/23 Effects of mutations: Learning objectives: understand why some mutations lead to dominant inheritance patterns, whilst others are recessive. Learning objectives: de ne t wo majors disorders that arise from DNA mutations affecting a single gene that affects protein function: sickle cell anaemia and cystic brosis. Learning objectives: understand the difference bet ween somatic and inherited mutations, and the consequences of such mutations: such as Huntington’s disease and cancer. How mutations can be acquired or inherited: Father or mother has mutation in all cells- transmits to child. Child is heterozygous in every cell. X Father or mother has mosaic mutation that affects the germ line and somatic cells. Child is heterozygous in every cell. Y d N I Father or mother has germline mosaic mutation. Child is heterozygous in every cell. Germlime is referring to affecting sperm. All three have different parental combo but all children get the disease. De novo mutations: Father or mother has mutation in single egg or sperm and transmits to child. Child is heterozygous in every cell. Or mutation occurs in zygote during rst few cell divisions. Child is heterozygous is every cell. Somatic mutations: Child has mosaic somatic mutation that occurs early in post-zygotic development and is present in a percentage of cells. Or child has a mosaic mutation that occurs later in development and affects fewer cells. For example, skin cells. Mutations will not be passed on from child, following classic Mendelian inheritance rules, unless it affects the gem cells. Somatic mutations are a strong driver of cancers. Dominant mutations: Mutations that activates an aberrant function or alters a structure or in proteins that are very sensitive to abundance are likely to have a dominant effect. Recessive mutations: Mutations that lead to loss of function are likely to be recessive. Example: Dominant Huntingtons disease: In normal Huntington protein, there is less than 27 repeats of CAG, which codes for glutamine. In the mutated Huntington protein, there is more than 35 and up to hundreds. This is called polyglutamine expansion. This leads to breakdown of neurones and effects the Brain. Example: Recessive cystic brosis: Cystic brosis receptor ( CFTR ). Mutant doesn’t work as an ion channel. However, I’m heterozygous individuals with one functioning ion channel, there are still enough areas where the ion channels work. Example: recessive sickle cell anaemia: Mutation in CTC to CAC means that Val is produced instead of Glu. This effects the beta chain. It isn’t that bad as there are still 3 non affected and it works satisfactorily. Beta 88888 Beta alpha The disease results in sticky weird shaped red blood cells and they end up blocking blood ow.