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(8.1) Genetic Mutations & Stem Cells - Coggle Diagram
(8.1) Genetic Mutations & Stem Cells
Mutations
Changes to the base sequence of DNA
can be caused by errors during DNA Replication
Types of Genetic Mutation
Substitution: 1 or more bases swapped for another
Deletion: 1 or more bases removed
Addition: 1 or more bases added
Duplication: 1 or more bases repeated
Inversion: A sequence of bases is reversed
Translocation: Sequence of bases moved from 1 location in genome to another
Mutations can impact tertiary structure of proteins that the amino acids code for e.g. may leave an enzyme with an active site unable to bind to substrate
Can cause genetic disorders - inherited disorders caused by abnormal genes or chromosomes e.g. cystic fibrosis
some can increase likelihood of developing certain cancers e.g. mutation of BRCA1 can increase breast cancer risk
Can cause hereditary mutations - gamete containing mutation is fertilised and mutation is present in fetus
Degenerate genetic code means that some amino acids are coded for by more than 1 DNA triplet
Not all types of mutation = change in amino acid sequence e.g. some substitutions will code for the same amino acid
Additions, duplications & deletions almost ALWAYS result in change to amino acid sequence of a polypeptide
change no. of bases in DNA code
leads to
frameshift
in bases that follow
Mutagenic Agents
increase rate of mutation
UV radiation, ionising radiation, some chemicals and viruses
Base analogs
can substitute for a base in DNA replication, changes base sequence for new DNA e.g. 5-bromouracil
Altering bases
can delete/alter bases e.g. alkylating agents add alkyl group to guanine (pairs with thymine instead)
Some radiation can change DNA structure, causing problems during DNA replication
Cancer
Acquired Mutations
= mutations in individual cells after fertilisation
can cause uncontrolled cell division in genes that control rate of mitosis
results in a tumour
Cancers
= tumours that invade/destroy surrounding tissue
Genes controlling cell division
Tumour Supressor Genes
can be inactivated by mutation in the DNA sequence
when functioning normally, slow cell division by producing proteins that stop cells dividing or by causing apoptosis
if mutated, do not produce proteins so rate of mitosis is unchecked
Proto-oncogene
effect of porto-oncogene can be increased if mutated, forms an oncogene
when functioning normally, stimulate cell division by producing proteins that cause cells to divide
when mutated, turns into oncogene & becomes overactive, cells divide uncontrollably -> tumour
Tumours
Malignant
Grow rapidly & invade/destroy surrounding tissues
can break off tumours and spread around body via blood or lymphatic system
Benign
Not cancerous
grow slower than malignant tumours & often covered in fibrous tissue that stops cells invading other tissues.
often harmless but can cause blockages/put pressure on organs
can become malignant
Tumour cells
irregular shape
nucleus = larger & darker or have more than one
don't produce all proteins needed to function correctly
have different surface antigens
don't respond to growth regulating processes
divide by mitosis more frequently than normal cells
Abnormal Methylation of cancer related genes can cause tumour growth
Methylation of DNA is important to regulating gene expression - controls transcription & translation
When tumour supressor genes are
hypermethylated
(too much CH3) genes are not transcribed, proteins to slow cell division aren't made & tumours can form
When photo-oncogenes are
hypomethylated
they act as oncogenes, increasing production of proteins that encourage cell division & stimulates cells to divide uncontrollably
Increased Oestrogen can contribute to some breast cancers
increased exposure may be result of starting menstruation earlier or menopause later or via oestrogen-containing drugs
Oestrogen can stimulate certain breast cells to divide & replicate, natural higher chances of developing cancer
Stimulated division means if cells do become cancerous, they will replicate more quickly
Research suggests that Oestrogen is able to introduce mutations directly to DNA of certain breast cells, increasing chances of them becoming cancerous
Interpreting data on Cancer
Cancer risk factors
Genetic:
some cancers linked to specific inherited alleles, if that allele is inherited risk for cancer increases
Environmental:
exposure to radiation, lifestyle choices & high fat diets are all linked to developing some cancers
knowing the mutation is helpful in the prevention & treatment of cancer
Cancer prevention
if a specific cancer-causing mutation is known, it can be screened for in a person's DNA e.g. the BRCA1 tumour suppressor gene can be screened for
knowing of increased risks mean preventative steps can be taken to reduce it, e.g. women with the BRCA1 mutation may have masectomies to reduce risk of cancer developing or they may be screened more often than the rest of the population for signs of breast cancer
Treatment & cure
knowing how specific mutations cause cancer means drugs can be developed to target them e.g. Herceptin is used to treat breast cancer caused by mutation of the HER2 photo-oncogene
if a mutation is know to cause an aggressive cancer, high doses of radiotherapy or removing large areas of the tumour/tissue surgically is needed
Gene therapy - faulty alleles in a person's cells are replaced by working versions of this same alleles)
can be used to treat cancer caused by some mutations
Stem Cells
unspecialised cells that can develop into other types of cell
found in the embryo & bone marrow
Totipotent Stem Cells
Stem cells that can mature into any type of body cell in an organism
only present in mammals in the first few cell divisions of an embryo
after this point, embryonic stem cells become pluripotent (can still specialise into any cell but not cells that make up the placenta)
Multipotent Stem Cells
able to differentiate into a few different types of cell e.g. red & white blood cells
Unipotent Stem Cells
can only differntiate into 1 type of cell e.g. theres a unipotent cell that only specialises into epidermal skin cells
How stem cells specialise
Stem cells all contain same genes - only some are transcribed/translated during development. Under right conditions, some are expressed & some turned off. mRNA only transcribed from specific genes & then translated into proteins. These proteins modify cells (determine structure/processes). Modification leads to specialisation (difficult to reverse)
Cardiomyocytes
heart muscle cells
its thought they can't divide/replicate themselves
we thought we couldn't regenerate our heart cells, major problem if damaged by heart attacks etc
it's now thought that old damaged cardiomyocytes can be replaced by new ones derived from a small supply of unipotent stem cells in the heart
some believe it's a slow process and not all will even be replaced during a lifetime
some think it's a fast process and all cardiomyocytes are replaced multiple times in a lifetime
Stem cell therapies
Severe Combined Immunodeficiency (SCID)
is a genetic disorder causing defective white blood cells
bone marrow contains stem cells that can specialise into any cell
bone marrow transplants can be used to regenerate healthy white blood cells
this has also been used to treat leukaemia & lymphomas
also being researched to treat: spinal cord injuries, heart disease, bladder conditions, respiratory diseases, organ translplants
Benefits of Stem Cells in medicine
save lives - used in organ transplants when people don't have much time left
improve quality of life - could be used to replaced damaged cells in the eyes of blind people
Sources of Stem Cells
Adult Stem Cells
can be obtained from body tissues of an adult e.g. bone marrow, little risk in operation but very painful and gives multipoint cells
Embryonic Stem Cells
obtained from embryos at early stages of development, created via IVF and harvested when embryo is 4-5 days old, give pluripotent cells
Induced Pluripotent Stem Cells (iPS Cells)
created in a lab, specialised adult body cells are reprogrammed to become pluripotent, made to express series of transcription factors similar to pluripotent cells. Transcription factors introduced to adult cells via specially modified virus
Ethical Issues
obtaining stem cells from embryos via IVF could grow into living fetuses but are destroyed
people less objected from obtaining stem cells from egg cells that haven't been fertilised but artificially divide - can't produce a fetus
some think scientists should only use adult stem cells however they're not pluripotent
where iPS Cells prove useful
can be made into patient's own cells