20 - Gene Expression Flashcards
mutation
change in amount or structure of the DNA of an organism
point mutations
change only one nucleotide at a particular locus
eg. substitution, addition, deletion
duplication
one or more bases are repeated, causes frame shift to right
inversion
a group of bases become separated from the DNA sequence and rejoins in the reverse order
translocation
group of bases becomes separated from the DNA sequence on one chromosome and become inserted into the DNA sequence of a different chromosome
mutagens
environmental factors that increase rate of mutation
cons of mutation:
are often harmful
can produce organisms less suited to environment
can lead to problems in cellular activities
benefit of mutation
provide genetic variation required for natural selection and speciation
embryonic stem cells
undifferentiated and totipotent
can divide and produce any type of body cell
totipotent cells
only occur in a limited time in early mammalian embryos
pluripotent cells
found in embryos
can divide in unlimited numbers
can be used in treating human diseases
unipotent cells
found in mature mammals
can only differentiate into a single type of cell
derived from multipotent cells
multipotent cells
found in mature mammals and can differentiate into a limited number of specialised cells
stem cells found in animals (after early development):
inner lining of small intestine skin bone marrow (form blood cells)
expression of genes in differentiated cells
some genes are permanently expressed, some genes are never expressed, some are only expressed when necessary
induced pluripotent cells iPS
genetically altered in labs to acquire characteristics of embryonic stem cells
cells are induced to express genes that were previously switched off
produced from unipotent cells or adult somatic cells using appropriate protein transcription factors
controlling the expression of a gene
- transcriptional factors turn on the gene to allow transcription to begin
- each transcription factor binds to a specific base sequence of DNA
- the region it binds to begins transcription
- mRNA is produced and goes on to be translated into a polypeptide
promoter region
specific region of DNA which the transcriptional factor binds to
oestrogens role in activating genes
binds to the transcriptional factor and causes its DNA binding site to change shape
transcriptional factor is then able to bind to promoter region of DNA, stimulating transcription
epigenetics
heritable changes in gene function, without changes to base sequence of DNA
DNA code is fixed, however epigenome is flexible
epigenome
the chemical tags which determine the shape of the DNA-histone complex (aka chromatin)
these tags can respond to environmental changes
weak association between DNA and histones
chromatin is less condensed
therefore more accessible by transcription factors
strong association between DNA and histones
chromatin more condensed
therefore less accessible by transcription factors
(production of mRNA by transcription cannot be initiated in these areas, so gene switched off)
acetylation
process by which an acetyl group is transferred to a histone (usually donated by acetyl coA)
decreased acetylation increases the positive charge on the histone
increased attraction between histone and phosphate groups of DNA
stronger association between DNA and histone so chromatin more condensed
methylation
addition of a methyl group to the cytosine bases of DNA
inhibits transcription of genes by:
- preventing the binding of transcriptional factors to DNA
- attracting proteins which condense the chromatin by inducing deacetylation
epigenetic therapies
use drugs to inhibit enzymes involved in histone acetylation or DNA methylation
must be targeted specifically at cancer cells
if the drugs affect normal cells they would activate gene transcription, making them cancerous
inhibiting the translation of mRNA
enzyme cuts large double stranded RNA molecules into smaller sections called small interfering RNA (siRNA)
one of the siRNA strands combines with an enzyme
the siRNA molecule guides the enzyme to an mRNA molecule
it pairs with the complementary bases on the mRNA strand and the enzyme cuts the mRNA into small sections
the mRNA can no longer be translated into a polypeptide
tumours and cancer
not all tumours are cancerous
cancerous tumours are malignant
non-cancerous tumours are benign
benign tumours
can grow to a large size
grow very slowly
cell nucleus has relatively normal appearance
cells often well differentiated
tend to have localised effect on body
cells produce adhesion molecules that make them stick together and so they remain within the tissue from which they arise
malignant tumours
can grow to a large size
grow rapidly
cell nucleus is often larger and appears darker due to abundance of DNA
cells become de-differentiated
often have systematic (whole body) effects
do not produce adhesion molecules and so tend to spread to other regions (metastasis producing sceondary tumours)
proto-oncogenes
stimulate a cell to divide when growth factors attach to a protein on its cells surface membrane
oncogenes
they are mutations of proto-oncogenes
an oncogene can be permanently activated:
- receptor protein on the membrane can be permanently activated, so that cell division occurs without the presence of growth factors
- oncogene may code for a growth factor which is then produced in excessive amounts, stimulating excessive cell division
tumour suppressor genes
maintain the rate of cell division, repair mistakes in DNA and cause apoptosis (programmed cell death)
effect of mutated tumour suppressor gene
it is inactivated
as a result stops inhibiting cell division
cells are able to grow out of control
hypermethylation of tumour suppressor genes
- hypermethylation occurs in promoter region of a tumour suppressor gene
- transcription of promote regions of tumour suppressor gene is inhibited
- the tumour suppressor gene becomes inactivated
- its inactivation leads to increased cell division and formation of a tumour
hypomethylation
reduced methylation
can occur in oncogenes, where it leads to their activation and therefore the formation of tumours
oestrogen and breast cancer
increased oestrogen concentrations after menopause are though to cause breast cancer
oestrogen acts on a gene that controls cell division and growth, activating it
continued cell division may produce a tumour
oestrogen causes proto-oncogenes in breast tissue to develop into oncogenes
