Genetics Flashcards
Strands of dna are replicated how?
5–>3 direction and pair up int anti parallel directoin
4 bases:
thymine-adenine
guinine-cytosine
sugar phosphate back bone
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DNA strand associates with proteins (including Histones) and is wound into a structure called a chromosome
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DNA can be damaged during replication, repair mechanisms exist, when these are defected, disease occurs
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cell cycle:
G1–>S–>G2–>M–>G1
what occurs at the s phase
DNA synthesis
function of DNA helicase
unzips DNA
function of DNA polymerase
copies 5-3 strand and 3-5 strand in okazaki fragments
funtion of DNA ligase
joins okazaki fragments
mitosis
One diploid parent cell becomes 2 identical diploid daughter cells
meiosis
One diploid parent cell becomes 4 haploid daughter cells
Crossing over occurs
Gamete formation
RNA
single stranded
ribose sugar
uracil replaces thymine
Transcription/Translation
DNA transcribed to pre mRNA
Pre mRNA spliced (removal of introns [non-coding sections of DNA] to mRNA
mRNA translated to protein
3 bases encode 1 amino acid or a stop codon
Protein is modified and moved around the cell
variation between cells
changes in promoter sequence
changes in exon sequence
cell cycle more detail
GO cell cycle: most cells are resting, carrying out their normal function
G1 cell cycle: 1st growth phase as chromosomes become ready to be replicated
S phase: DNA replication
G2 cell cycle: 2nd growth phase involving proteins
M phase: mitosis, mechanical separation of cell into two daughter cells. Identical, diploid cells
23 pairs of chromosomes
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SNPs (Single Nucleotide Polymorphisms)
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where do mutations occur in the cell cycle
between G2 and M or between G1 and S
how does variation occur in meioisis
- Crossing over
- Independent segregation of homologous chromosomes
what is polymorphism
a change in the genome that does not cause disease in its own right but can predispose to a common disease
what is a mutation
gene change that causes a genetic disorder
Neuploidy
an abnormal number of chromosomes
what are histones
proteins wrappped around DNA
PCR
- Can select one small piece of human genome from a patient and amplify it
- Pieces can be sequenced to find mutations
Microarray CGH
- 1st line chromosome test
- Detects any missing or duplicated piece of chromosome
- Find polymorphisms
FISH
fluorescent probe is attached to a gene, can recognise changes to sequence
what is expression
is the process by which info from a gene is used in the synthesis of a functional gene product
what is penetrance
the extent to which a particular gene is expressed in the phentype
Mendelian diseases are rare and likely to have a huge effect on individual. Common mutations are likely to have little effect on individual and may require other things for disease to actually be triggered. Mendelian Disorders (umbrella term for below) = a disease that is caused by a change in a single gene
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Autosomal dominant
- disease seen in all generations
- 50% risk of affected child if parent affected
- males and females are equally affected
Autosomal recessive
- 2 faulty copies required to cause disease
- oftern only one generation affected
- 1 in 4 risk of contraction disease if parents are carriers
- increased likelihood in incestious families
X linked- recessive
- y chromosome is irrelevent
- eg Haemophilia
- If mother carrier, 50% chance daughter carrier, 50% chance male affected
- no male to male transmission
- X-linked inheritance almost always affects males because mutation on X chromosome and males do not have allele on Y chromosome to counteract.
X-inactivation
cell only requires one working copy of the x chromosome. in females, each cell has a random X chromosome inactivated
Mitochondrial
- Mitochondrial DNA contains important genes for mitochondrial metabolic pathways and ribosomal RNAs
- Inherited almost exclusively maternally
Mitochondrial disease occurs when diseased mitochondria passed from mother to child
Epigenetic variation functional modifications to the genome that do not involve a change in nucleotide sequence
symptoms: oMyopathy oDiabetes oDeafness oOptic atrophy oStroke like episodes oEncephalitis
how do mutations cause disease?
- only have one working copy is not enough eg Haploinsufficiency
- abnormal protein interferences with normal protein eg dominant negative
- mutation activated gene eg gain of funtion mutation
- loss of hereozygosity
Mendelian disorders
- High penetrance
- Small environmental contribution
Multifactorial disease
- Genetic change just another risk factor
- Penetrance for any one mutation is low
- Individual genetic factors can be treated the same way as other environmental risk factors. Mutation in genes combine with environmental factors to cause disease.
Characteristics gained by cells on progression to cancer
- Proliferation
- Evasion of immune response
- Acquire a vascular supply
- Avoid apoptosis
- Metastasis
mutations in cells can cause damage to control genes that allow cells to divide in uncontrolled fashion
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tumour suppressors
stop cells dividing if switched on
oncogenes
start cells dividing when switched on
mosaicism
the presence of 2+ populations of cells with different genotypes in one individual. Somatic happens within body cells and not passed onto children. Gonadal affects sex cells and is passed onto children. (in all cancers there are normally at least 3 different groups of cells with different genotypes.)
gonadal mosaicism
Causes recurrence risk for autosomal dominant conditions even if parent unaffected
somatic mosaicism
All cells suffer mutations as they divide
Repair mechanisms exist
BRCA 1/2
responsible for a small proportion of familial breast/ovarian cancer. Patients have 80% lifetime risk of developing cancer. The gene is associated with DNA repair.
CF
common mutations are F508Del and G551D. Population carrier frequency of a CF mutation is either 1/24 or 1/25
turners syndrome
monosomy of the sex chromosomes (missing chromosome from one pair)
downs syndrome
trisomy of chromosome 21 (extra chromosome)
Methylation inhibits DNA transcription
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imprinting
Variation in gene expression depending on which parent you inherit the gene from
e.g. in Angelman’s syndrome, mother’s UBE3A works fine but father’s is methylated
Heteroplasmy
different daughter cells contain different proportions of mutant mitochondria
47 XY +21 - Down syndrome, trisomy 21 47 XY +14 - Miscarriage, trisomy 14 47 XY +18 - Edward Syndrome, trisomy 18 45 X - Turner syndrome 47 XXY - Klinefelter syndrome
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