Lecture 1 - Inheritance Flashcards
1
Q
Deoxyribonucleic Acid
A
- double helix
- four chemical ‘bases’
- Adenine, Thymine (2x H bonds)
- Cytosine, Guanine (3x H bonds)
- bases are attached to 2x phosphate backbones
- DNA is tightly packed (space saving)
- 3.2b bases in the human genome
2
Q
DNA packaging
A
- DNA+RNA+Protein = Chromatin
- main chromatin protein: Histones
- DNA wound around histones 2x = Nucleosome
- Nucleosomes organised into SOLENOIDS
- SOLENOIDS loop into chromatin
3
Q
Histones
A
- made up of 8 proteins: H2A, H2B, H3 and H4
- H1 is a LINKER HISTONE: binds to DNA entry and exit sites of the nucleosome
- DNA is wound around each histone twice
4
Q
Chromatin
A
- Euchromatin: open, prevalent in parts of the genome that are regularly used
- Heterochromatin: condensed, not active in expression
5
Q
Chromosomes
A
- two identical chromatids
- p arm = short, q arm = long
- centromere in the centre
- 22 autosomes and 2 sex chromosomes = 24
6
Q
Human cells
A
- Haploid: 23 chromosomes (inc 1 sex chromosome)
- Diploid: 46 chromosomes (inc 2 sex chromosomes)
7
Q
Genes
A
- basic physical unit of heredity
- vary in length: 100s - >2.5m bases
- approx 20,000-23,000 genes in human genome
- why fewer genes than expected? alternative splicing, alternative post translational modification
8
Q
Genes to proteins
A
- RNA and protein synthesis
- transcription - translation
- degenerate code (more than one codon/aa)
- non overlapping
- 64 codons in total
- stop codons implicated in disease (premature stop)
9
Q
When you have a premature stop codon
A
No protein is generated
Nonsense mediated decay, NMD surveillance pathway, cell eliminates incorrect mRNA
10
Q
Transcription: DNA-> RNA
A
- RNA polymerase is the main transcription enzyme
- RNA pol binds to a PROMOTER SEQUENCE near the beginning of a gene (directly or through helper proteins)
- RNA pol uses one of the DNA strands (the TEMPLATE strand) to make a complementary RNA molecule (PRIMARY RNA)
- Transcription ends in TERMINATION which depends on stop codon in the DNA sequence
11
Q
Difference between DNA and RNA
A
- RNA single stranded
- Uracil instead of Thymine
12
Q
RNA processing
A
Primary RNA is modified before it leaves the nucleus
- splicing
- capping
- polyadenylation
13
Q
RNA capping
A
- 5’ end is capped with 7-methylguanosine
- capping precedes other modifications that protect the mRNA from RNAses
14
Q
Poly A tails
A
- protect the 3’ end from phosphatases and nucleases
- approx 200 nucleotides
- necessary for nuclear export
15
Q
Splicing
A
- removes introns
- snRPS spliceosomal proteins (U1, U2, U4, U5, U6) bind to the preMRNA
- mRNA is removed in a lariat
- the 2 exons are ligated to make mature mRNA
16
Q
Translation
A
- occurs in the cytoplasm on a ribosome
- Initiation: ribosome connects the mRNA with the first tRNA, translation begins
- Elongation: amino acids on the tRNAs are linked
- Termination: finished polypeptide is released and folds
17
Q
Junk DNA
A
- genes only 2% DNA
- rest of genome is mostly repetitive sequences
- can be short repeated segments or long repeats of 1000s of bases repeated 100s of times
- some junk DNA plays a role in gene regulation
18
Q
Introns/Intragenic regions
A
- non coding regions within genes
- can regulate expression
19
Q
Intergenic regions
A
- genome segments between genes
- can regulate expression
20
Q
Mitochondrial DNA (genome)
A
- 16.6kb codes mtDNA
- codes 37 genes
- 2x rRNA
- 22 transfer RNA
- 13 protein subunits for enzymes (eg cytb and cyt oxidase - used in oxidative phosphorylation)
- mtDNA different from nuclear DNA
- encodes genes necessary for mitochondrial function
Mitochondria inherited exclusively from the oocyte leading to a maternal pattern of inheritance that characterises mitochondrial disorders
21
Q
Mitosis
A
- rapid cell division leading to an adult human 10(14) somatic cells
- two identical diploid cells are formed from a single diploid cell
- Prophase: chromosomes condense, spindle is formed, nuclear envelope disintegrates
- Metaphase: chromosomes connect to spindle, align on the metaphase plate
- Anaphase: centromeres split, chromosomes separate and move to opposite poles
- Telophase: chromosomes cluster at poles and nuclear and organelle envelopes reform
- Cytokinesis: contractile actin ring divides the cell
22
Q
Meiosis
A
- gametes produce genetically different organism on fertilisation
- 2 steps: produced 4 genetically different haploid cells
- contain a single set of 23 chromosomes
- spermatogenesis or oogenesis
- Meiosis I: reduction division, 46 to 23
- Meiosis II: equational division, 23 to 23 (duplication)
23
Q
Variation during meiosis
A
- crossing over: of maternal and paternal chromosomes
- independent assortment: maternal and paternal chromosomes split across the spindle
- errors in DNA replication
24
Q
Consequences of variation
A
- changes in protein structure and function
- natural variatio (eye colour, height etc)
- inherited/genetic disease (huntingtons, downs, CF)
25
Classification of variation
- size: large and small scale
- DNA structure: substitution, insertion, deletion
- protein structure: synonymous, non synonymous (has it changed the a.a. it codes for)
- change in coding/non coding regions
- protein function: loss/gain, dominant/negative
26
DNA repair
- germline changes: heritable
- somatic changes: non heritable
- mutation drives evolution
27
Crossing over
- homologous chromosomes exchange genetic material at the end of chiasma (prophase I)
- Resulting chromosomes contain parts of the other pair
28
Independent assortment
- during anaphase I the chromosomes do NOT duplicate
- only one pair moves to each daughter cell
- paternal and maternal chromosomes are randomly sorted
- chromosomes vary from gamete to gamete
29
Meiotic mutations
- Turner's syndrome XO
- Down's syndrome Trisomy 21
- Edward syndrome Trisomy 18
- Patau syndrome Trisomy 13
result from non disjunction at meiosis I or II
30
Cell fate
- zygote grows mitotically to the 8 cell stage (embryonic stem cells)
- they then undergo differentiation
- all cells have 3 possible destinies:
1. Remain alive (functioning but not dividing)
2. Grow and divide
3. Die (necrosis/apoptosis)
- these events are controlled by the cell cycle
31
The cell cycle
- interphase: G1, S, G2
- G1: synthesis of RNA and proteins
- S: DNA replication
- G2: some DNA repair, cell contains 2 x 23 pairs of
chromosomes
- G0: when the cell stops dividing for a long time
- G0 length of time varies - liver = 1year, epithelium = 10 hours, muscle and neurones never divide
32
Checkpoints
- in G1, S and G2
- tumour suppressors act to inhibit cell proliferation
- oncogenes stiimulate cell growth
- cyclins and Cdks (transition controlled by phosphorylation, cyclin levels vary in the cycle)
33
S phase
- DNA replication
- DNA helicase unwinds
- proteins bind the unwound DNA
- the leading strand is synthesised 5 to 3 by DNA pol
- the lagging strand has an RNA primer added by RNA primase
- RNA primer is then extended by DNA pol into an Okaskai fragment
- Okasaki fragments joined by DNA ligase
34
Uncontrolled cell division
- cell cycle regulators can become mutated
- tumour suppressors can become inactive or oncogenes overactive
- retinoblastoma is caused by a mutation in tumour suppressor RB1
- Li Fraumeni multi organ cancer syndrome caused by mutations in tumour suppressor p53
- lung cancers often have mutation in kras (oncogene)
35
Cell death
- apoptosis (webbing between fingers)
| - necrosis (trauma, infection)
36
Roles of apoptosis
- shaping tissues and organs
- immune system: ineffective or self reactive T cells removed
- cancer: too little apoptosis
- too much apoptosis: neurodegenerative disease
