113 Flashcards
(213 cards)
1
Q
mendels law of segregation
A
- the 2 forms of a gene (alleles) present in each parent segregate independently
-formulated this law by studying the results of monohybrid crosses (a cross between 2 true-breeding individuals differing in only 1 character)
2
Q
gregor mendel overview
A
- The father of genetics
- Worked with peas
- Discovered dominant and recessive traits
- Discovered the concept of gene (‘heritable factor- gene wasn’t discovered yet)
- Discovered the formulation of the basic laws of inheritance
3
Q
what are variations in inherited characteristics due to
A
existence of alternative version of heritable factor called alleles
4
Q
mendels law of independent assortment
A
- Each pair of alleles assorts independently of each pair of alleles during gamete formation
- Relates to the situation where the inheritance of 2 or more different pairs of alleles is being studied
- He made law by looking at the inheritance of 2 characters at the same time
5
Q
dihybrid crosses
A
in F2 2 new phenotypes are called recombinants, ratio of 9:3:3:1, if no independent assortment there would not be 2 new phenotypes
6
Q
what link did sutton make
A
link between behaviour of chromosomes during meiosis and Mendel’s laws
7
Q
what did sutton observe
A
- Chromosomes occur in pairs in somatic cells
- Chromosome pairs segregate equally into gametes- as each allele is on a different member of a chromosome pair and moves to opposite poles in anaphase 1
- Different pairs assort independently- explained by random way that chromosomes line up in metaphase
8
Q
what does chromosome theory of inheritance state
A
-Mendels heritable factors are located at the loci on chromosomes
- its the chromosomes that undergo segregation and independent assortment
9
Q
where does mitosis occur
A
somatic cells
10
Q
where does meiosis occur
A
germ line
11
Q
what does meiosis produce
A
4 haploid gametes
12
Q
what does mitosis produce
A
2 identical diploid cells
13
Q
whats synapsis in meiosis
A
lining of homologous chromosomes
14
Q
mitosis role
A
growth and tissue repair
15
Q
meiosis role
A
to produce gametes and introduce genetic variability
16
Q
whats a chromatid
A
1 of teh 2 identical strands of replicated chromosomes
17
Q
sister chromatids
A
2 identical chromatids held together by common centromere after replication
18
Q
4 processes that leads to genetic variability
A
-mutation
- Independent assortment of chromosomes in meiosis 1 – no. of possible combinations of chromosome types in 2^23
- Crossing over between homologous chromosomes during meiosis 1
- Random fertilization of ova by sperm – random choice of which sperm fuses with egg
19
Q
no. of possible chromosome combinations in the offspring
A
2^46
20
Q
when does crossing over occur
A
during pachytene phase of prophase 1
21
Q
crossing over
A
-The process of genetic recombination that gives rise to new combinations of linked genes
-Begins with synapsis- pairing of homologous chromosomes
-The synaptonemal complex is a protein zipper that holds homologous chromosomes together in the tetrad
-results in recombinant chromosomes with new combinations of linked genes – new combinations of alleles
22
Q
recombination frequency
A
the % of the progeny that inherit a combination of alleles that differs from either parent
RF= no. of recombinants/ total no. of progeny
X100
23
Q
how else is RF estimated
A
studying testcross
e.g. crossing a double heterozygote with a double recessive. For genes on different chromosomes the recombination frequency will be 50% (due to independent assortment)
24
Q
highest Rf value you can possibly get
A
50%
25
gene nomenclature
mutants were given a name that reflects their phenotype usually abbreviated e.g. black(b) and vestigial (vg). normal allele (wild type) is written with a + sign
26
RF to centimorgan
1% recombination = 1cM
27
why don't cM map distances add up
multiple crossovers could occur leading to an underestimate of the distance between 2 loci
28
coupling vs repulsion heterozygotes
– 2 possible arrangements of alleles in a double heterozygotes. Shouldn’t make a difference to the recombinant %. Which offspring a recombinant and parental would be different though. The largest phenotypic classes in the progeny will be the largest classes
29
sex linkage
First observed in drosophila (flies)
Males only need 1 copy of allele whereas females need 2
Males always get their X chromosome from their mother
30
incomplete dominance
Where dominant allele does not completely mask the effect of the recessive allele at the same locus. E.g. in humans is Familial Hypercholesterolaemia (blending of traits)
31
co-dominance
Where each allele affects the phenotype in separate, distinguishable ways (no blending)
32
pleiotropy
Where a single gene has multiple effects on the phenotype
33
polygenic inheritance
Where a single trait is determined by multiple genes – a characteristic of this is that the trait shows continuous variation in the population e.g. height
34
epistasis
When one gene masks or modifies the expression of another gene. Affects dihybrid cross ratio now being 9:3:3:1
35
deviations from Medelian ratios
sex linkage
incomplete dominance
co-dominance
pleiotropy
polygenic inheritance
epistasis
36
cytogenetics
the study of the structure and function of chromosomes – used for the screening and diagnosis of inherited chromosomal disorders
37
karyotype
preparation of chromosomes arranged in size order – used to detect change in chromosome number and structure
38
whats giemsa staining for
makes chromosomes easier to look at
39
metacentric
centromere in centre
40
sub-metacentric
centromere off-centre
41
acrocentric
centromere very close to end
42
polyploidy
whole extra sets of chromosomes
- Diploid 2n
- Triploid = 3n
- Tetraploid= 4n
Rare in animals, common in plants
43
aneuploidy
some additional or missing chromosomes
-Occurs in 50% of human conceptions
-Most lead to embryonic death or spontaneous abortion
-Only autosomal aneuploidy that isn’t fatal is down syndrome
-More common on the sex chromosomes e.g. XO, XXY, XXXY
44
monosomy
2n-1 (chromosome missing)
45
trisomy
2n+1 (additional chromosome)
46
cause of aneuploidy
non-disjunction
can happen in meiosis 1 or 2
in meiosis 2, 1 of the end cells is normal
47
why does chance of having child with down syndrome increase with age
eggs are held at metaphase so as you get older more of chance of something going wrong
by age 40, 1:100 chance
48
characteristics of down syndrome
short stature
sterile
characteristic facial features
intellectual disability
heart defects
susceptibility to leukaemia and Alzheimers
49
screening for chromosome abnormalities
amniocentesis and karyotyping
blood tests to detect specifc proteins
ultrasound scans- measure size of nuchal pas at nape of neck associated with downs syndrome
50
turners syndrome
only viable human monosomy
1 in 2500 female births
no Y chromosome
sterile as sex organs don't mature
oestrogen replacement therapy leads to the development of secondary sex characteristics
51
Klinefelter's syndrome
most common genetic abnormalities
1:500-1000 male births
multiple X chromosomes
52
Klinefelter's syndrome characteristics
phenotypically male with female characteristics
tall
sterile
may have interlectual disability
treated with hormone therapy (testosterone)
53
cri du-chat syndrome
5p minus syndrome
1 in 50 000 births
- cat like cry
-defects in glottis and larynx
- wide face and saddle nose
-physical and intellectual disability
- range in severity dependent on how much deletion occured
54
prader-willi syndrome
deletion in long arm of chr15 (15q1.12)
1 in 15 000 births
-Poor suckling reflex in infants
-Uncontrollable eating later in life
-Obesity/Diabetes
-Poor sexual development in males
-Only occurs when affected chromosome in inherited from he father
55
why does Prader Willi syndrome come from the father
due to genomic imprinting- process that affects certain genes whereby either maternal or paternal copy of gene is silenced
56
angelman syndrome
when same segment is missing as prader-willi but from the maternally derived chromosome
-Happy demeanour
-Inappropriate outburst of laughter
-intellectual disability
-Severe speech problems
-Stiff limb movements
-Seizures
57
familial downs syndrome
t(14;21)
translocation
accounts for 5% of downs cases
One of the chr21s is attached to one of the chr 14s
58
chronic myelocytic leukaemia
22-9 translocation
spontaneous- not heritable
1: 50-100 000
very high WBC count
95% of people with CML have the Philadelphia chromosome
Translocation creates the BCR-ABL fusion gene- an oncogene that stimulates over-production of white blood cells
CML is most common in middle aged/elderly
Accounts for 15-20% of all cases of leukaemia
59
what did friedrich miescher discover and how
nucleic acid- used pus from used bandages in Crimean war to get WBCs, then purified nuclei and extracted these nuclei.
found precipitate rich in phosphate and nitrogen 'nuclein'
N-rich fraction= protein
acidic p-rich fraction= nucleic acid
60
frederick griffiths transformation experiments
- Used 2 strains of streptococcus pneumoniae – one R that is benign and another S that is virulent
- R is benign as it is lacking a protective capsule, it is recognised and destroyed by hosts immune system
- S strain is virulent ad the polysaccharide capsule prevents detection by hosts immune system
the genetic material was capable of reprogramming R-form cells into S-form disease causing cells.
61
Oswald Avery
built on Griffith experiments by trying to identify the 'transforming principle'
- until this it was thought it was proteins
positive reaction to dische test for deoxyribose of DNA
62
hershey-chase experiment
electron microscope study shows the virus itself doesn't enter cell so they tested to see if it was protein or DNA being inserted into cell
63
bacteriophages
type of virus composed of DN A and protein that infect bacterial cells
64
Chargaff's 'rule'
-interested in the 4 bases
-examined ratios of DNA in various organisms
-discovered ratio of 4 bases is not 1:1:1:1
- ratio is species specific
-base rule composition always obeys a strict rule, A=T and G=C
65
Rosalind franklin
photograph 51- x-ray diffraction photo of DNA taken in 1952 by raymond gosling
helped solve the structure of DNA
66
purines
adenine and guanine
67
pyrimidines
cytosine and thymine
68
conclusion from x-rat diffraction (photo 51)
DNA is double helix
is 2nm
length between each turn is 3.4nm
distance between repeating units is 0.34nm
10 nucleotide pairs per turn
69
Meselson-Stahl experiment
bacteria cultured in medium with 15N
tranferred to medium 14N
DNA sample centrifuged after first replication
70
what does DNA polymerase require
single stranded template DNA
all 4 nucleotide triphosphates (dNTPs)
free 3' hydroxyl (primer)
71
what does DNA polymerase do
synthesises DNA in 5' to 3' direction
inserts complementary nucleotides
uses energy from breaking phosphate bonds
Proofreading ability- can remove incorrectly inserted nucleotides
72
synthesis of leading strand
1- helicase unwinds and separates 2 strands
2-single-stranded binding proteins prevent DNA strands from re-annealing
73
helicase
unwinds the helix
74
single stranded binding proteins
hold helix open
involved in DNA replication
75
primase
synthesis the RNA primers needed for initiation of DNA synthesis
76
DNA polymerase III
in prokaryotes (similar does same job in eukaryotes)
extend the DNA (or RNA) strand from 3' end, copying the template
77
DNA polymerase I
removes the RNA primer and fills in gaps between Okazaki fragments
78
DNA ligase
seals the gaps between Okazaki fragments
79
Archibold Garrod
diseases where the patient is unable to carry out a particular biochemical reacton ( inborn errors of metabolism
studied alkaptonuria
first to connect inherited human disorders with Mendels law of inheritance
80
alkaptonuria observations
Urine of alkaptonuria patient contains large amounts of homogentisic acid (originally called alkapton)
Alkaptonuria is inherited – autosomal recessive
81
alkaptonuria hypothesis
Alkaptonuria patients lack the enzyme (homogentisic acid oxidase) for breaking down homogentisic acid
Lack of enzyme due to defect in a gene
82
beadle and tatums 1 gene 1 enzyme experiments
Were interested in how genetic changes may effect metabolism
Had been using drosophila as model organism but due to their complexity it was difficult to prove a single gene was responsible for a particular chemical reaction
Neurospora (bread mould) a more simple organism lead them to win Nobel prize in physiology or medicine 1958
83
neurospora
bread mould
have a haploid stage in life cycle
so genetic changes are easy to study as recessive traits will apear in offspring
84
auxotroph's
mutant strains that cannot synthesis a particular molecule required for growth
so will only grow if they are supplied with that molecule
85
screening for auxotroph's
- Culture individual spores on complete medium
- Transfer to minimal medium to identify possible auxotroph’s
- Test candidates for growth on MM supplemented with different classes of nutrients (vitamins or amino acids or nucleotides)
- Test candidates for growth on MM supplemented with individual amino acids (or vitamins or nucleotides)
- Identify the amino acid that allows your mutant to grow
86
class 1 of arginine auxotroph's
mutants grow on:
MM +ornithine
MM + citrulline
MM + arginine
87
class 2 of arginine auxotroph
mutation on gene B
mutants grow on
MM + citrulline
MM + arginine
88
class 3 arganine auxotroph
mutation on gene C
mutants grow on
MM + arginine (only)
89
what did beadle and tatum propose
enzyme in a pathways was controlled by 1 gene, role of a gene is to encode an enzyme and that for each enzyme there is a gene, this later devolped into one gene, one polypeptide
90
pulse-chase experiment
- Provided evidence for messenger RNA
- Did by 15, label with radioactive uracil
- Saw the uracil move into the cytoplasm
91
transcription steps
initiation
elongation
termination
92
transcription- initiation -
unlike DNA polymerase RNA polymerase does not require a primer
Catalysed by RNA polymerase
93
transcription- elongation
- RNA polymerase moves along the DNA template, unwinding the double helix and catalysing the addition of ribonucleotides to the 3’ end of the growing RNA molecule
94
UAA, UAG and UGA are what
stop codons to signal end of translation
95
AUG role
start codon and also codes for methionine
96
genetic code is almost universal
the same codons are used for the same basic amino acids from the simplest bacteria to complex organisms, indicating that it must have been established very early during evolution
97
specifying amino acids
- mRNA cannot act as a physical template for amino acids
- adapters required to link mRNA and amino acids
- adapters are transfer RNAs (tRNA)
98
tRNA structure
-approx. 80 nucleotides long
-single stranded but base pairs within the chain
-clover lead structure further fold to make L shaped molecule
-anticodon at 1 end
-amino acid attachment site is the 3’ hydroxyl group at the end of the RNA chain
-each tRNA is specific for a single amino acid determined by its anticodon
-tRNAs are the adapters
-specific attachment carried out by amino-acyl tRNA synthetases (activating enzymes)
99
attachment process for attaching an amino acid to its RNA
1- ATP hydrolysed and amino acid joined to AMP
2- Correct tRNA binds and amino acid transferred from AMP to the tRNA
100
wobble base pairing
Often when different bases code for the same amino acid it is the 3rd base that differs (not always)
101
the ribosome
-Composed of ribosomal RNA and proteins
-2 subunits – large and small
-Binds mRNA and amino acyl-tRNAs
-Catalyses stepwise formation of peptide bonds (amino acids added from N to C terminus)
-Moves in 5’-3’ direction along mRNA
-By recognising the correct start codon, ribosomes ensures correct reading frame is used
102
protein synthesis - initation steps
1-Small ribosomal subunits binds mRNA near its 5 end (recognised AUG start codon)
2-Initiator tRNA binds to AUG start codon
3-Large subunits binds so that the initiator tRNA fits into the p-site on large subunits
4-Require energy from GTP hydrolysis and proteins called initiation factors (help stabilise initiator tRNA and to assemble ribosomes
103
protein synthesis- elongation steps
1-Incoming aminoacyl tRNA base pairs with codon in the a site – requires GTP hydrolysis
2-Peptide bond forms between amino group of new amino acid and the COOH group of the amino acid in the p-site – catalysed by peptidyl transferase
3-Growing polypeptide chain now in the a site
4-Translocation- tRNA moves in the p-site is ejected and the ribosome moves along the mRNA chain- requires GTP hydrolysis
5-Growing chain now in the p site and the a site is free to accept the next incoming aminoacyl tRNA
104
protein synthesis - peptide bond formation
-Bond catalysed by peptidyl transferase
-Peptide bond is between the C and N of different amino acids
105
protein synthesis- termination steps
1- Stop codon in A-site
2- There are no tRNAs for stop codons
3- Release factor enters a site instead of amino acyl tRNA
4- Water added to end of polypeptide chain
5- Completed polypeptide released from tRNA in p site
6- Ribosome dissociated, 2 X GTP hydrolysed
106
polyribosomes in eukaryotes
Nuclear membrane- mRNA transported to cytoplasm before translation occurs
Several different organelles- proteins must be trafficked to correct site
107
polyribosomes in prokaryotes
No nuclear membrane- transcription and translation coupled
No organelles- proteins diffuse through cytoplasm
108
mutations
permanent change in the DNA of a cell, such as a change in gene position/number (chromosomal mutation) or change in nucleotide sequence (point mutation). Mutations are rare and occur randomly also important for genetic variation
109
mutations in somatic tissues
- cells not passed on to offspring
-passed on to all cells descended from the original mutant
-85% of cancers are caused by these mutations
110
mutations in germ line tissure
- cells are passed on to offspring
- cause of inherited genetic diseases
- raw material from natural selection produces evolutionary change
111
causes of mutation
- spontaneous - DNA replication
- induced (mutagens)
chemical- base analogues, modifying intercalating agents
physical- ionising radiation, Uv
112
spontaneous mutations
occur due to inherited instabilities in DNA
113
base tautomerism
-Nucleotides can change to other conformations e.g. isomers and tautomers (at low rate)
-During DNA replication an incorrect base is inserted to form mismatched pair
114
chemicals that resemble DNA bases - mutations
1.Chemicals that resemble DNA bases but pair incorrectly when incorporated in DNA (base analogues)
5 bromouracil is incorporated into DNA as though it were thymine, once incorporated it rearranges into a form resembling cytosine, upon DNA replication, can result in a point mutation converting AT bp to a GC bp
115
chemicals that remove amio group - mutations
chemicals that remove the amino group from adenine or cytosine e.g. nitrous acid/nitrate
Deamination of C to U
Replication of DNA containing deaminated C results in A being inserted
Daughter strand base pairing changed from CG to TA
Occurs spontaneously at low rates
Uracil not usually found in DNA
Uracil DNA glycosylase has a specific role in removing U from DNA to prevent mutations
116
chemicals that add hydrocarbon groups- mutations
chemicals that add hydrocarbon groups to nucleotide bases
alkylating – many of these chemicals are mutagens, addition of ethyl group at the O6 position alters base pairing, resulting in a point mutation converting GC bp to AT bp
EMS- ethyl methane sulfonate
117
intercalating agents- mutations
Insert between bases and distort DNA helix
Interfere with replication
Tend to cause frameshift mutations
e.g. ethidium bromide
118
mutations- ionising radiation
physical agent
Can directly ionise DNA or ionise water to produce free radicals
Cell cycle arrest and DNA repair (error prone) = apoptosis
Can damage bases and cause double-strand breaks
119
mutations- UV
physical agents
pyrimidine dimers
UV irradiation is absorbed by pyrimidine bases C and T
Covalent bonds can form between adjacent C and T nucleotides- pyrimidine dimers
Blocks DNA synthesis leaving a gap opposite the site of damage
120
xeroderma pigmentosum
hereditary condition
deficient in NER (nucleotide excision repair
characterised by development of skin cancer at early age in parts exposed to sun
121
single gene disorders
caused by point mutations in single genes
individually very rare but collectively affect 1-5% of population
high morbidity and mortality in children
122
autosomes
all chromosomes apart from X and Y
123
cystic fibrosis overveiw
A disorder originating in secretory epithelial tissue
Most common life-shortening genetic disorder affected north European Caucasian population
Carrier frequency 1 in about 25
CF births 1 in about 2500
If untreated they die before their 5th birthday- not life can be extended into adulthood
124
symptoms of CF
accumulation of mucus in the lungs, pancreas, digestive tract, and other organs
multiple effects including chronic bronchitis and recurrent bacterial infections
125
CFTR
Cystic fibrosis transmembrane conductance regulator
126
what does CF gene (CFTR) code for
for chloride channel
regulates the flow of cl- accross the membrane
127
most common mutation causing CF
ΔF508- defect in c- transport causes extracellular mucus to become thicker and stickier
-Deletion of 3 base pairs (bp) results in loss of phe (F) residue at position 508
-Protein does not fold normally and is more quickly degraded
-There are >800 different CFTR mutations that cause CF
128
treatment for CF
life is prolonged by antibiotics and daily massages to clear mucus away from airways
129
medicines for CF
- Drugs to improve function of mutated protein – gating mutations can be treated with gate opening drugs, other mutations treated with combination therapies that bring more of the chloride channels to surface and help those channels to operate more effectively
- Gene therapy- provide patients with a copy of the correct chloride channel
Clinical trials for integrating and non-integrating gene therapies are underway
130
sickle cell anaemia
autosomal recessive
affects 1 in 625 Afro-Caribbean/American births
131
sickle cell anaemia symptoms
anaemia, joint pain, swollen spleen, frequent severe infections
132
sickle cell anaemia treatments/cure
regular blood transfusions
bone marrow transplant
133
what cause sickle cell anaemia
mutation in the gene for b-chains of haemoglobin; leads to incorrect folding of the protein
The defective haemoglobin forms long chains of rigid polymers (after O2 released) which deform the RBC
134
benefits of being sickle cell carrier
resistant to malaria, so where high rates of malaria there's also high rates of sickle cell
135
autosomal dominant pedigree
males and females affected
affected individual have an infected parent
50% chance of the affected parent having an affected child
136
Huntington disease
late-onset degeneration of the brain
occurrence 1 in 24 000
137
Huntington disease symptoms
jerky movements, personality changes, deterioration of walking, speaking, swallowing, death will result from complications such as chocking, infection or heart failure
138
molecular causes of Huntington's disease
defect on chr 4
HD gene contains CAG repeats (glutamine)
11-34 repeats is normal
36-125= HD
139
familial hypercholesterolaemia symptoms
high levels of cholesterol in bloodfrom an early age
cholesterol deposits build up in joints
cardiovascular disease
140
FH treatment
cholesterol-lowering drugs e.g. statins
low cholesterol diet
141
causes of FH
due to low density lipoprotein (LDL) receptor
the LDL binds and carries cholesterol in the blood stream
142
FH frequency and homo/het
incomplete dominance
homozygous- have 6 fold increase in blood cholesterol
heterozygous- have 2 fold increase in blood cholesterol-heart attacks by age 35
hh= 1 in a million
Hh- 1 in 500 birth
143
what is dominant phenotype cause by in FH
haploinsufficiency
144
pedigree for sex linked recessive traits
- Female are carriers and mostly males are affected
- Carrier female will transmit 50% of sons affected and 50% female are carriers
- Affected male cannot transmit to sons by will transmit to 100% of daughters
145
haemophilia
sex linked recessive disease
blood clotting disorder
146
haemophilia symptoms
uncontrollable bleeding, tendency to extensive brusing, bleeding joints
147
haemophilia A
mutation in the gene for factor VIII on X chromosome, 1 in 5000 males
148
haemophilia B
- Christmas disease
mutation in gene factor IX on X chromosome
1 in 30 000 males
149
duchenne muscular dystrophy
muscle wasting disease
1 in 3500 males
sex-linked recessive
currently incurable- new gene therapies under research
150
how is duchenne muscular dystrophy caused
affected gene codes for a muscle protein called dystrophin, the dystrophin gene is largest known human gene making it prone to rearrangements
dystrophin is part of a protein complex that connects cytoskeleton of a muscle fibre to the surrounding extracellular matrix through the cell membrane
muscles in DMD die, death occurs by age 20 from respiratory or cardiac failure
151
bioinformatics definition
using computer technology to collect, store, analyse and disseminate biological data and information
(simply- computer-aided biology)
152
why do we need bioinformatics
We need bioinformatics as the growth databases of genetic information and sequencing cost of per human genome is reducing- becoming possible to analyse genome to diagnose disease
153
example uses of bioinformatics
- Genome sequence and annotation
- Protein structure and molecular binding
- DNA identification
- Omics studies
154
common problems for bioinformatic begginners
- Large number of tools available – when to use and what
- Most tools and databases are not very user friendly
- The outputs can look intimidating
- Many different file formats
155
DNA barcoding
allows species identification through short section of DNA
- Cost effective
- genes regions that are similar within the same species and distinct across different species
- Commonly used genes
Animals: MT-CO1, 16S rRNA
Fungi: ITS (internal transcribed spacer)
Bacteria: 16S rRNA or 18S rRNA
The different bases forms a unique ‘barcode’ for each species in the selected gene region
156
FASTA
a smple format for nucleotide/amino acid sequence and little else
157
sequencer
device that can automate the process of determining the DNA bases
158
read (bioinformatics)
nucleotide sequence generated by a sequencer
159
search (database)
Typically you would say you “search” a database or perform a “search”, to describe the process of looking for specific information in a database
160
query (database)
The formal and structured request for data in databases. Often used interchangeably with search. In BLAST, it refers to your input sequence
161
subject (BLAST database)
The sequences that your query sequence is compared to.
162
what can DNA barcoding be used for
building phylogenetic trees
often recorded in Newick format
163
Newick format
designed for computer and hard to read for humans
164
phylogenetics
the study of the evolutionary history and relationships
165
clade
a group of organisms that includes a single ancestor and all of its descendent.
166
branch
: Shows the path of transmission of genetic information from one generation to the next; the longer the lines, the more genetic change (or divergence) has occurred. The branch length are usually the number of genetic changes per site (i.e. if 1 base difference for a 100-base sequence, the length will be 0.01) .
167
sequence alignment
A way of arrange amino acids or nucleotides sequences to identify regions of similarity (put the sequences next to each other in a way that they line up well)
168
primary key (database)
A unique ID for identifying an entry in a table in a database. Minor technical difference to Accession number.
169
fields
a set of attributes
170
retrieve (database)
identifying and extracting data from a database
171
accession number (database)
Unique IDs used in databases, a bit like how your bank account number is unique
172
genecards
a human gene databae with extensive info on each gene - it collects information from different databases and provides links to the sources
173
advantages of bacteria for genetics
- Easily cultured
- Short generation time: 20 -30 mins
- Haploid- only 1 copy of gene- can see phenotype much easier as if diploid you would need 2 copies if It was recessive
174
bacteriophages
infect bacteria- structurally and functionally diverse
175
lytic (or virulent) bacteriophage life cycle
multiply and then lyse bacterial cell which releaes bacteriophage particles
176
temperate bacteriophage life cycle
(or lysogenic bacteriophage) can integrate into bacterial chromosome and then remain dormant, replicating with the bacterial DNA
177
recombination definitions
the coming of DNA from 2 individualls into a single genome
178
Gene transfer and recombination occurs through 3 processes
transformation- uptake of naked DNA
transduction- transfer of bacterial genes from 1 bacteria to another bacteri
179
2 types of transduction
generalised- occurs with virulent phage t4
specialised- occurs with temperate phage- lambda
180
conjugation
The ability to form sex pili and to transfer DNA by conjugation is determined by a plasmid called F (for fertility) factor
F factor replicates in synchrony with bacterial chromosome, in a way that one end of the DNA molecule passes through the cytoplasmic bridge into the recipient cell (called an exconjugant) where it circularises
The donor keep a copy of the F factor
181
regulation of gene expression in bacteria
- Often controlled at the level of initiation of transcription
- Transcription begins when RNA polymerase binds to a promoter
182
control of tryptophan biosynthesis
regulated synthesis of repressible enzymes
183
negative regulation
binding of repressor/tryptophan to operator blocks transcription
184
control of lactose metabolism
regulated synthesis of inducible enzymes
185
negative expression in bacteria
binding of a protein to an operator prevents transcription
Trp operon, expression is off when tryptophan binds to repressor which then binds to the operator
Lac operon, expression is off in the absence of lactose when the repressor binds to the operator
186
positive regulation in bacteria
binding of molecule to the operator turns on gene expression
cAMP receptor protein
187
cAMP receptor protein (cRP)
lactose is present
glucose is scarce (cAMP high)
abundent lac mRNA synthesis
188
prokaryotes
- Unicellular
- No membrane-bound organelles
- Between 500 and 4000 genes
- Small genomes
- Circular DNA
189
eukaryotes
- Unicellular or multicellular
- All organelles are membrane-bound
- Between 6000 and 30 0000
- Large genomes
- Linear DNA organised into chromatin
190
why are eukaryotic genomes so large
- lots of genes
lots of non-coding DNA
191
non coding DNA consists of
1. Gene regulatory sequences (e.g. promoters)
2. Introns (non-coding sequences within genes)
3. Sequences of no known function (including repetitive DNA sequences)
192
exon
represented in final mRNA
193
intron
intervening sequence in the transcribed region that is not represented in the final mRNA
194
repetitive sequences
interspersed repetitive DNA
tandemly repetitive (satellite) DNA
195
interspersed DNA
- Repeated units scattered throughout genome
- Single unit 100-10 000bp
- Copies not necessarily identical but closely related
- Makes up 25-40% of most mammalian genomes
- E.g. alu elements make up 5% of the mammalian genome
196
tandemly repetitive (satellite) DNA
- Can be broadly classified according to the length of a single repetitive region:
Regular satellite DNA- 100 000-10 million bp per site
Minisatellite DNA- 100-100 000 bp per site
Microsatellite DNA- 10-100 bp per site
- Much satellite DNA is located at telomers and centromeres – suggesting structural role
- Some genetic disorders are caused by long repeats of a sequence within a gene e.g. hunting tons disease
197
heterochromatin
highly condensed during interphase, not actively transcribed
198
euchromatin
less condensed during the interphase, able to be transcribed
199
chromatin structure
- Chromosomes are composed of chromatin (protein + DNA)
- Chromatin is an intricate form of packaging for DNA (10 000- fold compaction)
- DNA in a cell must be packed in an organized manner to be accessible for transcription and replication
- This involves association with specific proteins (Histones) and the formation of chromatin
- Eukaryotic chromatin is much more complex than prokaryotic chromatin
200
histones
proteins with positively charged amino acids that binds to the negatively charged DNA
201
what form is most chromosomes in during interphase
euchromatin
202
what happens to chromatin during meiosis and mitosis
chromatin folds further- condenses- highly condensed chromatin also occurs during interphase in some regions of the chromosomes – heterochromatin
203
DNA methylation
(associated with gene silencing)
Attachment of methyl groups (-CH3) to DNA bases
Triggers formation of a compact chromatin structure
Associated with inactive DNA
Accounts for genomic imprinting in mammals
204
histone acetylation
(associated with gene activation)
Attachment of acetyl group (-COCH3) to histones
Acetylated histones grip DNA less tightly
Acetylation/deacetylation is involved in switching genes of and on
205
closed chromatin
DNA methylated
histones now acetylated
206
open chromatin
DNA unmethylated
histones acetylated
207
RNA polymerase 1 in eukaryotes
ribosomal RNA
208
RNA polymerase 2 in eukaryotes
mRNA
209
RNA polymerase 3 in eukaryotes
small RNAs e.g. tRNA
210
how does transcription begin
when RNA polymerase binds to promotor
211
what do DNA sequences adjacent to gene (promotor) do
- Determine where the transcription of the gene is initiated
- Determine the rate of transcription
212
the TATA box
- A key part of the promoter
- Provides the site of initial binding of the transcription initiation machinery
- Located 10-35 bp upstream of the transcription start site
213
preinitiation complex before transcription processes
1. Binding of TFIID: includes the TATA-binding protein (TBP) + TATA-associated proteins (TAFs)
2. Sequential addition of other ‘general transcription factors’- first TFIIA and TFIIB
3. Then binding of TFIIF + RNA polymerase OO
4. Followed by the TFIIE + TFIIH- to form the preinitiation complex
