1
Q
Component of the cell that is responsible for the synthesis of lipids and proteins
A
Endoplasmic reticulum
2
Q
Component of the cell that is responsible for intracellular degradation
A
Lysosome
3
Q
Component of the cell that contains DNA
A
Nucleus
4
Q
Component of the cell responsible for oxidation of toxic molecules
A
Peroxisome
5
Q
Component of the cell responsible for the modification, sorting and packaging of lipids and proteins
A
Golgi apparatus
6
Q
Component of the cell that is the site of adenosine triphosphate (ATP) synthesis by oxidative phosphorylation
A
Mitochondria
7
Q
Restriction point (in the cell cycle) - definition
A
This is the point at which the cell no longer requires growth factors to progress through the cell cycle.
It occurs at the end of G1. From this point, the cell is committed to entering S phase.
8
Q
Cell cycle phases (4)
A
G1 (Gap 1)
S (synthesis
G2 (Gap 2)
M (mitosis)
- G1, S, and G2 are collectively known as ‘Interphase’
Interphase - preparation of the cell for division
Mitosis - actual cell division
9
Q
Gap 1 phase (essence)
A
Preparing the cell for DNA synthesis
10
Q
Synthesis (S) phase (essence)
A
DNA replication
By the end of this phase, each chromosome is replicated into two identical chromatids
11
Q
Gap 2 phase (essence)
A
Preparing the cell for mitosis
12
Q
Mitosis - stages (6)
A
Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis
13
Q
Which stage of mitosis?:
Chromatin condenses and becomes visible as chromosomes
A
Prophase
14
Q
Which stage of mitosis?:
The nuclear membrane dissolves and microtubules become attached to the centromeres
A
Prometaphase
15
Q
Which stage of mitosis?:
Chromosomes become aligned at the middle of the cell (cell equator);
Spindle fibres attach each sister chromatid to an opposite pole
A
Metaphase
Metaphase - M for ‘Middle’ (of the cell, where the chromosomes are aligned)
16
Q
Which stage of mitosis?:
Paired chromosomes separate and begin moving to opposite ends of the cell
A
Anaphase
17
Q
Which stage of mitosis?:
Chromatids arrive at opposite poles of the cell and new nuclear membranes begin to form around them
A
Telophase
18
Q
Which stage of mitosis?:
The cell splits into two daughter cells each with a nucleus
A
Cytokinesis
19
Q
Meiosis (essence)
A
Divided into Meiosis I and II
Meiosis I - ‘reduction division’
- in a prolonged prophase I, homologous maternal and paternal chromatid pairs line up and exchange genetic material in a process called ‘crossing over’
- in anaphase I, chromatid pairs remain attached
- the products of meiosis I are 2 haploid cells
Meiosis II - ‘mitosis for haploid cells’
- essentially the same as mitosis, except without the prior S phase DNA replication
- therefore the product is 4 haploid cells
20
Q
Chromosome structure
- centromere
- telomere
- short arm
- long arm
A
A centromere links a pair a sister chromatids
Arms protrude from the centromere:
- short arm = p
- long arm = q
Telomere - a region of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes
21
Q
Number of chromosomes in human diploids cells
A
46
- 22 pairs of autosomes
- 1 pair of sex chromosomes
22
Q
Chromosome abnormalities - deletions (definition & examples, 4)
A
Genetic material is lost from a single chromosome
- Terminal deletion
- Ring chromosomes
- Interstitial deletions
- Microdeletions
23
Q
A single break occurs and the broken chromosome end is capped by a telomere
A
Terminal deletion
24
Q
Both ends of the chromosome are lost and the broken ends fuse
A
Ring chromosome
25
Two breaks occur in the chromosome and the segment between them is lost
e.g. chromosome 15 in Prader-Willi and Angelman syndromes
Interstitial deletion
26
Small interstitial deletion in a chromosome that is not detectable microscopically
e.g. chromsome 22 in DeGeorge syndrome
Microdeletion
27
Chromosome abnormalities - translocation (definition + examples, 3)
Breaks occur in two different chromosomes and genetic material is exchanged
- Reciprocal translocation
- Robertsonian translocation
- Sex chromosome-autosome translocation
28
A single break occurs in two different chromosomes and the terminal ends are exchanged
Reciprocal translocation
29
The long arm of two different chromosomes fuse, with loss of the genetic material on the short arms
occurs in Downs syndrome on chromosome 21
Robertsonian translocation
--------------------
Acrocentric chromosomes are most susceptible to this
30
Genetic material is exchanged between a sex chromosome and an autosome
Sex chromosome-autosome translocation
31
Chromosome abnormalities - inversion (definition & examples, 2)
Two breaks occur in the same chromosome and the ends are swapped
- Paracentric - both breaks in same arm
- Pericentric - breaks in different arms
32
Aneuploidy (definition, examples)
Gain or loss of a single chromosome e.g.
- Trisomy - three copies of one chromosome, e.g. Trisomy 21 (Down's syndrome)
- Monosomy - one copy of a chromosome e.g. monosomy X (Turner syndrome)
33
DNA/RNA base pairs (summary)
DNA: 'GCAT'
- Guanine pairs to Cytosine
- Adenine pairs to Thymine
RNA: 'GCAU'
- Thymine is replaced by Uracil
Purines: G & A
Pyrimidines: C, T & U
34
DNA base pairs - Purines
Guanine
| Adenine
35
DNA base pairs - Pyrimidines
Cytosine
Thymine
Uracil
36
DNA nucleotide - components (3)
Five-carbon deoxyribose sugar
Phosphate group
Nitrogenous Base
37
RNA - types (3)
```
Messenger RNA (mRNA)
Transfer RNA (tRNA)
Ribosomal RNA (rRNA)
```
38
... carries information from DNA to structures called ribosomes.
These ribosomes are made from proteins and ribosomal RNAs, which come together to form a molecular machine that can read ... and translate the information they carry into proteins.
Messenger RNA (mRNA)
39
... brings amino acids to the ribosome during translation, allowing them to be incorporated into a protein
Transfer RNA (tRNA)
40
... is what ribosomes are made up of and provides a place for mRNA and tRNA to attach during translation
Ribosomal RNA (rRNA)
41
Gene (essence)
The basic unit of heredity
Physically, it is a length of nucleotides within a chromosome - each gene has ~27,000 nucleotide pairs
42
Exon
The part of a gene (~1300 nucleotide pairs) that codes for a protein
43
Intron
The part of a gene that does not code for a protein
(most of a genes' ~27,000 nucleotide pairs are part of the intron)
-------------------------------------
'INtrons are not translated INto protein'
44
Transcription (essence)
the process by which an RNA polymerase sequences an mRNA molecule from a DNA template
remember: 'transcribe' means to make a full written copy
45
Transcription - main steps (3)
Initiation
- binding of RNA polymerase to double-stranded DNA, RNA polymerase binds at a sequence of DNA called the promoter
Elongation
- the development of a short stretch of DNA that is transiently single-stranded
- an mRNA copy of the DNA coding strand is produced, in which thymine is replaced by uracil
Termination
- the recognition of the transcription termination sequence and the release of RNA polymerase
46
Translation (essence)
the process by which a protein is synthesised from its mRNA intermediary in the cytoplasm (in a ribosome)
47
Translation - process
- consecutive groups of 3 nucleotides are called codons - they correspond to the 20 common amino acids, and initiation and stop codons
- tRNA, synthesised in the nucleus, enters the cytoplasm attached to specific amino acids
3 steps:
- a tRNA molecule, to which an amino acid is attached, binds to the mRNA strand via an anticodon
- another tRNA molecule enters the ribosome and binds to the next three mRNA bases - the ribosome then links together the amino acids via a peptide bond
- the tRNAs dissociate and go off to collect more amino acids. The process then repeats to extend the protein chain
48
Start codon for translation
| + amino acid it codes for
AUG
| Methionine
49
Stop codons for translation (3)
UAA
UAG
UGA
'oo-ah, oo-ag, oo-ga'
50
Modification (essence)
post-translational changes to a protein - affecting its structure, stability and function
takes place in the endoplasmic reticulum, golgi apparatus and secretory vesicles
most common type is protein cleavage
51
Tandem repeat - definition and examples (3)
These occur when a nucleotide sequence is replicated into numerous adjacent repeats.
- Microsatellites
- Minisatellites
- Satellites
52
Microsatellite
a tandem repeat of <9 nucleotides, repeated between 5-40 times
- occupy 3% of the human genome
- most common form is a dinucleotide repeat - e.g. CACACACACACACACA
- they are unstable and have a mutation rate >10x the rest of the genome
- this high mutation rate allows genetic distance between individuals to be estimated and is used in linkage analysis
53
Minisatellite
a tandem repeat of >9 nucleotides
much less common than microsatellites
54
Satellite DNA sequence
a tandem repeat of >200 nucleotides, repeated hundreds of times
- occupy 5% of the human genome
- they are a major component of heterochromatin and centromeres
55
Repetitive DNA - 2 kindsq
Tandem repeats
| Dispersed repeats
56
Dispersed repeat (essence)
Repeated nucleotide sequences randomly spread in the genome
57
the complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria.
The human genome
58
A heritable change at a single base
Point mutation
59
... occurs when one base nucleotide is swapped for another during DNA replication
Substitution
60
A purine/purine substitution
Transition
61
A purine/pyramidine substitution
Transversion
62
A point mutation in which the new codon codes for the same amino acid, therefore the end protein is unchanged
Silent (synonymous) mutation
63
A point mutation in which the codon is transformed into a termination code that prematurely truncates the protein
Nonsense mutation
64
A point mutation in which the codon is changed to code for a different amino acid
Missense (nonsynonymous mutation)
65
This kind of mutation occurs when the new amino acid has similar properties to the old one
Conservative mutation
66
This kind of mutation occurs when the new amino acid has different properties, causing a reduction or even loss of protein functioning
Non-conservative mutation
67
... occurs when one or more nucleotide base is added to a DNA strand
Insertion
68
... occurs when one or more nucleotide base is deleted from a DNA strand
Deletion
69
Frame shift mutation (essence)
- the genetic code is read by translating groups of 3 nucleotides into a single amino acid
- any mutation that adds or deletes a sequence of nucleotides not divisible by three alters the reading frame
- every codon read after the mutation is altered. Thus, the earlier in the gene the mutation occurs, the larger the effect on the protein
70
This kind of mutation does not alter the reading frame
In-frame mutation
71
This kind of mutation occurs when a STOP codon is mutated into one encoding an amino acid. The translation machinery continues to extend the amino acid chain until the next STOP codon is reached
Readthrough mutation
72
Trinucleotide repeat (essence)
A form of tandem repeat.
A sequence of three nucleotides is repeated multiple times adjacent to one another.
Abnormal expansion of trinucleotide repeats above the stable threshold for a gene is linked to higher occurrence of genetic disease
The most well-recognised of these are the polyglutamine diseases (repeat CAG)
73
The phenomenon by which the number of trinucleotide repeats increases along with disease severity with each subsequent generation
Anticipation
74
Huntingdon's disease
| inheritance pattern, genetic pathology
Adult-onset autosomal dominant
Trinucleotide repeat of CAG on chromosome 4p
=============================
Normally CAG is repeated less than 27 times
75
Conditional mutations - essence + subtypes (3)
The effect of a mutation depends, in some situations, on the environmental conditions surrounding the organism.
- Unconditionally deleterious mutations
- Conditionally neutral mutations
- Conditionally beneficial mutations
76
This kind of mutation:
- impairs the essential functioning of the organism
- is deleterious in all environments
- is purged by natural selection
Unconditionally deleterious mutation
77
A kind of mutation that is only deleterious in some environments, and neutral in others
Conditionally neutral mutation
78
A kind of mutation that is beneficial in some environments i.e. they increase the organism's fitness, but deleterious in other environments
e.g. the sickle cell anaemia gene is protective against malarial infection
The mutation persists through natural selection in populations exposed to the stressful environment
Conditionally beneficial mutation
79
The DNA sequence defining the set of genes an organism carries, or the pair of alleles at a specific genetic locus
Genotype
80
An individual's observable traits (such as height, eye colour, and blood type) which results from the interaction between the genotype and the environment.
Phenotype
81
The proportion of individuals carrying a particular variant (or allele) of a gene (the genotype) that also express an associated trait (the phenotype).
The probability of a gene or genetic trait being expressed.
Penetrance
| Most genes associated with psychiatric disorders show low penetrance
82
... quantifies variation in a non-binary phenotype across individuals carrying a particular genotype. It is equal to the proportion of individual carriers of a genotype for a trait who show the trait to a specifiable extent
Expressivity
| Most psychiatric disorders, such as autism, show variable expression
83
Hardy-Weinberg Equilibrium (essence)
The phenomenon whereby allele and genotype frequencies in a population will remain constant from generation to generation in the absence of other evolutionary influences.
84
Conditions necessary for maintenance of Hardy-Weinberg equilibrium (5)
- No mutations must occur, so that new alleles do not enter the population.
- No gene flow can occur (no migration of individuals into, or out of, the population).
- No non-random mating - no assortative mating (mating based on phenotype), no consanguinity (mating of blood relatives)
- No genetic drift (random chance) can cause the allele frequencies to change (i.e. population must be sufficiently large to prevent this)
- No natural selection must occur - differences in genotype do not confer disparate survival or reproductive success on an individual
85
This law states that every individual organism contains two alleles for each trait, and that these alleles separate during meiosis such that each gamete contains only one of the alleles. An offspring thus receives a pair of alleles for a trait by inheriting homologous chromosomes from the parent organisms: one allele for each trait from each parent.
The law of segregation (Mendel's first law)
86
This law states that alleles for separate traits are passed independently of one another. That is, the biological selection of an allele for one trait has nothing to do with the selection of an allele for any other trait.
The law of independent assortment (Mendel's second law)
87
Which pattern of inheritance?:
- Heterozygotes display the disease phenotype
- In family trees, the disease is present in every generation (vertical transmission)
- If a parent is homozygous for the disease-causing allele (AA), 100% of their offspring will inherit it
- If a parent is heterozygous for the disease-causing allele (Aa), 50% of their offspring will inherit it
Autosomal dominant
88
Noonan's disease
| inheritance pattern and genetic pathology
Autosomal dominant
Disease gene lies on chromosome 12q
----------------------------
think 'noon' is 12pm i.e. chromosome 12
89
Which pattern of inheritance?:
- Only homozygotes display the disease phenotype
- Heterozygotes are carriers
- In family trees, the disease may not be present in every generation
- Displays horizontal transmission
Autosomal recessive
90
Louis Bar syndrome
aka ataxia telangiectasia
(inheritance pattern and genetic pathology)
Autosomal recessive
Disease gene lies on chromosome 11p
91
X-inactivation
| aka, essence, key facts
aka Lyonisation
this is the random inactivation of one X chromosome in each cell of a female, whose daughter cells then inherit the same pattern
- occurs early in embryogenesis (at 16-32 cells), via DNA methylation
- affects most but not all genes on the inactivated X chromosome - 20% are still expressed
- the inactivated X chromosome is maintained in a silent state called a Barr Body
92
Barr Body
This is the inactivated X chromosome within the cells of a female
93
Which pattern of inheritance?:
- Males and females are both affected, with males typically being more severely affected than females
- An affected father can never pass the disease to his sons; but all daughters will be affected
- A woman with the disorder has a 50% chance of having an affected foetus
X-linked dominant
94
Which pattern of inheritance?:
- Males are more frequently affected than females
- Transmitted through carrier females to their sons (knights move pattern)
- Affected males cannot pass the condition onto their sons
- A woman who is a carrier has a 50% chance of having sons who are affected and a 50% chance of having daughters who are carriers
X-linked recessive
95
Fragile X syndrome
| inheritance pattern and genetic pathology
X-linked dominant
Abnormal CGG trinucleotide repeats on the long arm of the X chromosome
96
Which inheritance pattern?:
- Every son of an affected father will be affected
- Female offspring of affected fathers are never affected
Y-linked
97
In this inheritance pattern, an organism's phenotype depends on small additive effects of a large number of genetic variants
Polygenic inheritance
98
In this inheritance pattern, an organism's phenotype depends on the combined effect of a small number of genetic variants
Oligogenic inheritance
99
Heritability (definition)
The proportion of the variation in a phenotype within a population that is due to variation in genotype
NB: heritability does NOT concern individuals, but rather population-level variations
100
Alzheimer's disease - Heritability (%)
60%
101
ADHD - Heritability (%)
80%
102
Alcohol dependence - Heritability (%)
50-60%
103
Anorexia - Heritability (%)
55%
104
Autistic spectrum disorder - Heritability (%)
90%
105
Bipolar disorder - Heritability (%)
80-95%
===============
SPMM says 75%-80%
106
Major depressive disorder - Heritability (%)
35-50%
107
Schizophrenia - Heritability (%)
80-85%
108
OCD - Heritability (%)
25-50%
109
Panic disorder - Heritability (%)
45%
110
This form of inheritance involves heritable changes to gene expression that are not caused by alterations to the DNA sequence
Epigenetic inheritance
111
Risk of schizophrenia in a monozygotic twin (%)
48%
112
This kind of study is used to determine the genetic location of a disease gene, and utilises the principle of linkage disequilibrium.
The goal is to identify a piece of DNA of known location that is inherited by all family members affected by the disorder being studied, and is not inherited by any of the unaffected family members. Once this piece of DNA is found, one knows that the disease gene must lie somewhere close by.
Linkage analysis
113
LOD Score
Logarithm of the odds - a statistic used in Linkage Analysis
a statistical estimate of whether two genes, or a gene and a disease gene, are likely to be located near each other on a chromosome and are therefore likely to be inherited
By convention:
>3 is considered evidence for linkage
114
Linkage disequilibrium
the tendency of alleles to be inherited together due to their proximity on the same chromosome
115
This kind of study is used to determine the pattern of inheritance for a trait.
Segregation analysis
116
Early-onset Familial Alzheimer's Disease (EOFAD) - associated genes (3)
amyloid precursor protein (APP)
- accounts for 10-15% of EOFAD
```
presenilin one (PSEN-1)
- accounts for 30-70% of EOFAD
```
```
presenilin two (PSEN-2)
- accounts for 5% of EOFAD
```
117
APP gene (location and association)
Chromosome 21
Accounts for 10-15% of Early-onset Familial Alzheimer's Disease (EOFAD)
118
PSEN-1 gene (location and association)
Chromosome 14
Accounts for 30-70% of Early-onset Familial Alzheimer's Disease (EOFAD)
119
PSEN-2 gene (location and association)
Chromosome 1
Accounts for 5% of Early-onset Familial Alzheimer's Disease (EOFAD)
120
Late onset Alzheimer's disease - associated gene (1 + function)
apolipoprotein E (APOE)
APOE is thought to be involved in the breakdown of amyloid plaques and different forms of it seem to vary in how effective they can do this.
121
APOE gene - location, alleles (3) + their association with risk of alzheimer's
Chromosome 19
APOE2 - protective
APOE3 - neutral
APOE4 - increases risk of late onset Alzheimer's
- Heterozygous - 3x increased risk
- Homozygous - 10-30x increased risk
- each E4 allele lowers the age of onset by 10 years.
122
a set of DNA variations, or polymorphisms, that tend to be inherited together
Haplotype
123
an individual's collection of chromosomes
karyotype
124
Pleiotropy (essence)
when one gene influences two or more seemingly unrelated phenotypic traits
125
3 aneuploidies compatible with life (+chromosomes involved)
Trisomy 21 (Down's syndrome) - 1 in 800 births
Trisomy 18 (Edwards syndrome) - 1 in 6000 births
Trisomy 13 (Patau syndrome) - 1 in 10,000 births
126
Prader-Will Syndrome (genetic pathology)
deletion of genetic material from the chromosome 15 (15q11-13) inherited of paternal origin
is a classic example of imprinting
127
Prader-Will Syndrome (features)
Hyperphagia (excessive eating) and obesity
Short stature
Delayed puberty, hypogonadism, infertility
Learning difficulties
Compulsive behaviour (e.g. skin picking)
128
APOE4 - risk of late onset Alzheimer's
- heterozygous
- homozygous
- Heterozygous - 3x increased risk
- Homozygous - 10-30x increased risk
- each E4 allele lowers the age of onset by 10 years.
129
Downs Syndrome (genetic pathology)
Trisomy 21
-------------------------------
Short stature, simian crease, almond shaped eyes due to epicanthic folds, upslanting palpebral fissures, low set ears, brushfield spots, and poor muscle tone. Most have mild (IQ 50-70) to moderate (IQ 35-50) mental retardation
130
Name the condition:
```
Short stature
simian crease, almond shaped eyes due to epicanthic folds
upslanting palpebral fissures
low set ears
brushfield spots
poor muscle tone.
```
Most have mild (IQ 50-70) to moderate (IQ 35-50) mental retardation
Downs syndrome (trisomy 21)
131
Angelman syndrome
| aka, genetic pathology
Happy puppet syndrome
15q11 maternal origin
---------------------------------
Flapping hand movements (uplifted, flexed arms when walking), ataxia, pronounced verbal delay (compared to comprehension), serveve to profound learning disability, seizures and sleep problems
132
Name the condition:
Flapping hand movements (uplifted, flexed arms when walking)
ataxia
pronounced verbal delay (compared to comprehension)
servere to profound learning disability
seizures
sleep problems
Angelman syndrome
aka Happy puppet syndrome
15q11 maternal origin
133
Prader-Willi Syndrome (genetic pathology)
15q11 paternal origin
------------------------------------
Hyperphagia, excessive weight gain, short stature, frequent skin picking, mild learning disability, small gonads, and hypotonia
134
Name the condition:
```
Hyperphagia
excessive weight gain
short stature
frequent skin picking
mild learning disability
small gonads
hypotonia
```
Prader-Willi Syndrome
15q11 paternal origin
135
Cri du chat (genetic pathology)
5p deletion
----------------------------------
Characteristic cry like a meowing kitten, hypotonia, hypertelorism, a down-turned mouth, and microcephaly
136
Name the condition:
```
Characteristic cry like a meowing kitten
hypotonia
hypertelorism
down-turned mouth
microcephaly
```
Cri du chat
5p deletion
137
Di George syndrome
| aka, genetic pathology
aka Velocardiofacial syndrome
22q deletion
------------------------------------------
Cleft palate, cardiac problems, and learning disabilities. A higher rate of psychiatric disorders is also seen
Hypoparathyroidism leading to hypocalcemia (60%)
138
Name the condition:
Cleft palate, cardiac problems, and learning disabilities. A higher rate of psychiatric disorders is also seen
Hypoparathyroidism leading to hypocalcemia (60%)
Di George syndrome
aka Velocardiofacial syndrome
22q deletion
139
Edwards's syndrome (genetic pathology)
Trisomy 18
--------------------------
Kidney malformations, upturned nose, webbing of second and third toes, and clubbed feet (rocker bottom)
140
Name the condition:
Kidney malformations
upturned nose
webbing of second and third toes
clubbed feet (rocker bottom)
Edwards's syndrome
Trisomy 18
141
Lesch-Nyhan syndrome (genetics pathology)
Xq26-27
----------------------------------------
(mutations in the HPRT gene)
Self mutilation, dystonia and writhing movements
hyperuricemia
142
Name the condition:
Self mutilation, dystonia and writhing movements
hyperuricemia
Lesch-Nyhan syndrome
| Xq26-27
mutations in the HPRT gene
143
Smith-Magenis syndrome (genetic pathology)
17p11 (microdeletion)
--------------------------------
Pronounced self injurious behaviour, self hugging, and a hoarse voice
144
Name the condition:
Pronounced self injurious behaviour
self hugging
hoarse voice
Smith-Magenis syndrome
17p11 (microdeletion)
145
Fragile X Syndrome (genetic pathology)
Abnormal CGG trinucleotide repeats on the long arm of the X chromosome
--------------------------------------------
Elongated face, large ears, large testicles, hand flapping, shyness, and little eye contact
146
Name the condition:
```
Elongated face
large ears
large testicles
hand flapping
shyness and little eye contact
```
Fragile X Syndrome
Abnormal CGG trinucleotide repeats on the long arm of the X chromosome
(X-linked dominant inheritance)
147
Wolf Hirschhorn syndrome (genetic pathology)
4p deletion
---------------------------
Profound mental retardation, microcephaly, seizures, down turned fishlike mouth, Greek warrior helmet face, and cleft lip
148
Name the condition:
```
Profound mental retardation
microcephaly
seizures
down turned fishlike mouth
Greek warrior helmet face
cleft lip
```
Wolf Hirschhorn syndrome
4p deletion
149
Patau syndrome (genetic pathology)
Trisomy 13
--------------------------------
Mental retardation, polydactyl, microcephaly, overlapping of fingers over thumb
150
Name the condition:
Mental retardation
polydactyl
microcephaly
overlapping of fingers over thumb
Patau syndrome
Trisomy 13
151
Rett syndrome (genetic pathology, inheritance)
Xq28
(genetic mutation of the MECP2 gene)
X-linked dominant
---------------------------------------------
Normal for the first 12 months. Regression and loss of skills from around 18 months onwards. Hand-wringing movements are the most common feature. Associated learning disability is profound. Affects girls almost exclusively
152
Name the condition:
Normal for the first 12 months.
Regression and loss of skills from around 18 months onwards.
Hand-wringing movements are the most common feature.
Associated learning disability is profound.
Affects girls almost exclusively
Rett syndrome
| Xq28
genetic mutation of the MECP2 gene
153
Tuberous sclerosis (genetic pathology)
Genetically heterogenous - mutation of either of two genes:
- TSC1 (9q)
- TSC2 (16p)
---------------------------------
Hamartomatous tumours affect various organs including the brain. 80% suffer with epilepsy. Autism, ADHD, and sleep problems are common
154
Name the condition:
```
Hamartomatous tumours affect various organs including the brain.
80% suffer with epilepsy.
Autism
ADHD
sleep problems
```
Tuberous sclerosis
------------------------------------------
Genetically heterogenous - mutation of either of two genes:
- TSC1 (9q)
- TSC2 (16p)
155
Williams syndrome (genetic pathology)
7q11 deletion
---------------------------
Elfin like features, social disinhibition, and abnormal friendliness towards strangers. Very sensitive hearing is also seen. Advanced verbal skills, speech is articulate but superficial (referred to as cocktail party speech)
156
Name the condition:
```
Elfin like features
social disinhibition
abnormal friendliness towards strangers
Very sensitive hearing
Advanced verbal skills - speech is articulate but superficial (referred to as cocktail party speech)
```
Williams syndrome
7q11 deletion
157
Rubinstein-Taybi syndrome (genetic pathology)
Unclear, 16p deletions have been reported
--------------------------------
Tend to be short with small heads. Associated with a friendly disposition and moderate learning disability
158
Name the condition:
Tend to be short with small heads.
Associated with a friendly disposition and moderate learning disability
Rubinstein-Taybi syndrome
Unclear, 16p deletions have been reported
159
Klinefelter syndrome (genetic pathology)
Extra X chromosome in phenotypic males (47 XXY)
---------------------------------------------
Tend to be tall with small testicles. Typically introverted with poor social and school performance
160
Name the condition:
Tend to be tall with small testicles.
Typically introverted with poor social and school performance
Klinefelter syndrome
Extra X chromosome in phenotypic males (47 XXY)
161
Jacob's syndrome (aka, genetic pathology)
aka 'Super-males', XYY Syndrome
Extra Y chromosome (47 XYY)
-------------------------------
It is usually asymptomatic. Affected individuals tend to be taller than average. Testosterone levels are normal and fertility and sexual development are usually unaffected.
There is an increased risk of learning difficulties. Aggression is not seen in higher levels than the normal population.
162
Name the condition:
usually asymptomatic
Affected individuals tend to be taller than average.
Testosterone levels are normal and fertility and sexual development are usually unaffected.
There is an increased risk of learning difficulties. Aggression is not seen in higher levels than the normal population.
Jacob's syndrome
aka 'Super-males', XYY Syndrome
163
Coffin-Lowry syndrome (genetic pathology)
Xp22 (mutations)
--------------------------------
Short stature, slanting eyes with short broad nose. Severe learning difficulty
164
Name the condition:
Short stature, slanting eyes with short broad nose. Severe learning difficulty
Coffin-Lowry syndrome
Xp22 (mutations)
165
Turner syndrome (genetic pathology)
45 X0
----------------------------------------
Short stature
Webbed neck
Broad chest (widely spaced nipples)
Gonadal dysfunction (amenorrhoea and infertility)
Congenital heart disease (cardiac malformation in approx 1/3 of cases)
Hypothyroidism
166
Name the condition:
Short stature
Webbed neck
Broad chest (widely spaced nipples)
Gonadal dysfunction (amenorrhoea and infertility)
Congenital heart disease (cardiac malformation in approx 1/3 of cases)
Hypothyroidism
Turner syndrome
45 X0
167
Niemann Pick disease (types A and B)
| genetic pathology
11p15
---------------------------------------------
(Mutations in the SMPD1 gene)
Abdominal swelling, cherry red spot, feeding difficulties
168
Name the condition:
Abdominal swelling, cherry red spot, feeding difficulties
Niemann Pick disease (types A and B)
| 11p15
Mutations in the SMPD1 gene
169
The total number of possible different codons that can occur in a human DNA is ---
64
170
First-degree relatives share --- of their genes.
Second-degree relatives share ---
Third-degree relatives share ---
50%
25%
12.5%
171
The gene that encodes the serotonin transporter
+ location (chromosome)
SLC6A4
(solute carrier family 6 member 4)
chromosome 17
(17q11.1-q12)
172
Lifetime risk of unipolar depression in a member of the general population (unrelated to anyone with affective disorder) (%)
5-10%
173
Lifetime risk of unipolar depression in a first-degree relative of someone with bipolar disorder (%)
10-20%
| 2-3 times higher than general population
174
Lifetime risk of unipolar depression in a monozygotic twin of someone with bipolar disorder (%)
15-25%
| 3-5 times higher than general population
175
Haploid
Diploid
Triploid
Haploid - one set of chromosomes (23)
Diploid - two sets of chromosomes (46)
Triploid - three sets of chromosomes (69)
176
Catechol-O-methyl transferase (COMT) enzyme
- chromosomal locus
22q11
177
Polymorphism
| essence
Polymorphisms are natural variations in a gene, DNA sequence, or chromosome that have no adverse effects on the individual and occur with fairly high frequency in the general population.
-----------------------------------
A gene is said to be polymorphic if more than one allele occupies that gene’s locus within a population.[1] In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to generally be considered polymorphic.
178
Epigenetic variation
| - common processes (2)
DNA methylation
| Histone modification
179
Nucleotide vs Nucleoside
Nucleoside:
- 5-carbon sugar
- nitrogenous base
Nucleotide:
- Five-carbon deoxyribose sugar
- Phosphate group
- Nitrogenous Base
Therefore - Nucleoside + Phosphate = Nucleotide
180
Compared with general population, relative risk of alcoholism is increased by --- if there is a strong family history
x4-6
181
In translation, which enzyme mediates the binding of tRNA with amino acids?
aminoacyl-tRNA synthetase
This synthetic process is called aminoacylation
182
In --- individuals with similar phenotypes mate with one another more frequently than would be expected under a random mating pattern.
Assortive mating
183
What percentage of the human genome is considered to be active with coding sequences?
2%
==============================
More than 98% of the human genome does not encode protein sequences, including most sequences within introns and most intergenic DNA
184
--- is the phenomenon where the effect of one gene (locus) is dependent on the presence of one or more 'modifier genes', i.e. the genetic background.
Epistasis
185
--- is the failure of homologous chromosomes or sister chromatids to separate properly during cell division.
Nondisjunction
186
Down syndrome - 3 kinds
Full trisomy 21
Translocation Down syndrome
Mosaic Down syndrome
187
Down syndrome - Full trisomy 21
- inheritance
- % of down syndrome cases
- cause
Not inherited
95%
Nondisjunction
(extra chromosome comes from the mother 88% of the time, and from the father 12% of the time)
188
Down syndrome - Translocation Down syndrome
- inheritance
- % of down syndrome cases
- cause
Inherited
2-3%
Balanced translocation
189
Down syndrome - Mosaic Down syndrome
- inheritance
- % of down syndrome cases
- cause
Not inherited
2-3%
Occurs as a random event during cell division early in fetal development
190
Risk of Down syndrome, by maternal age:
- 35 yrs
- 40 yrs
- 45 yrs
Maternal age 35 years - 1 in 385
Maternal age 40 years - 1 in 106
Maternal age 45 years - 1 in 30
191
Recombination fraction
- description
- range
a measure of the distance between genetic loci
varies from 0% (extremely close) to 50% (on different chromosomes)
================================
- If two loci are on different chromosomes they will segregate independently.
- If two loci are on the same chromosome they would always segregate together were it not for the process of crossing over.
- The nearer two loci are on a chromosome the less likely they are to be separated by crossing over.
- The further away two loci are on a chromosome the more likely they are to be separated by crossing over.
192
Gene mapping
- essence
- types (2)
Mapping the genome (i.e. establishing what every part of it does)
- Genetic mapping - uses techniques such as pedigree analysis.
- Physical mapping - uses molecular techniques to cut the DNA into pieces (using restriction enzymes) then to look at the pattern of pieces that result.
Physical maps can be divided into three general types:
- chromosomal or cytogenetic maps
- radiation hybrid (RH) maps
- sequence maps
193
Chromosomes - descriptions
- metacentric
- submetacentric
- acrocentric
The position of the centromere divides the chromosome into two arms, the long (q), and the short (p).
- Metacentric chromosomes - arms of roughly equal length
- Submetacentric chromosomes - unequal arm lengths
- Acrocentric chromosomes - very short p arms
============================
Acrocentric chromosomes can be involved in Robertsonian translocations.
194
Molecular biology techniques
- Southern blotting
- Northern blotting
- Western blotting
Southern blotting - detects DNA
Northern blotting - detects RNA
Western blotting - detects protein
==============================
SNOW (South - NOrth - West)
DROP (DNA - RNA - Protein)
195
Splicing
- description
takes place after transcription, prior to translation
introns are removed from an mRNA molecule, and the remaining exons are spliced together in different combinations, generating different mRNAs that are translated into distinct proteins
by this process, a single gene can code for multiple proteins
196
Proteasome
- location
- function/process
protein complexes that degrade endogenous proteins (i.e. proteins manufactured by the cell).
They are located both in the nucleus and the cytoplasm.
Proteins are tagged for degradation with a small protein called ubiquitin.
197
Endophenotype
- description
- criteria (5)
a heritable marker for a condition that is invisible to the naked eye and relies on some form of laboratory measurement
To qualify as an endophenotype a marker must fulfil specific criteria:
1 - It is associated with illness in the population
2 - It is heritable
3 - It is state independent (present whether or not disease is present)
4 - Within families, endophenotype and illness co-segregate (the endophenotype is more prevalent among ill relatives of ill probands than healthy ones)
5 - The endophenotype found in affected family members is found in non affected family members at a higher rate than in the general population.
198
Neurofibromatosis type 1 and 2
- inheritance pattern
Autosomal Dominant
199
Tuberous sclerosis
- inheritance pattern
Autosomal Dominant
200
Achondroplasia
- inheritance pattern
Autosomal Dominant
201
Huntington disease
- inheritance pattern
Autosomal Dominant
202
Phenylketonuria
- inheritance pattern
Autosomal Recessive
203
Homocystinuria
- inheritance pattern
Autosomal Recessive
204
Hurler's syndrome
- inheritance pattern
Autosomal Recessive
205
Tay-Sach's disease
- inheritance pattern
Autosomal Recessive
206
Friedrich's ataxia
- inheritance pattern
Autosomal Recessive
207
Wilson's disease
- inheritance pattern
Autosomal Recessive
208
Cystic fibrosis
- inheritance pattern
Autosomal Recessive
209
Vitamin D resistant rickets
- inheritance pattern
X-Linked Dominant
210
Rett syndrome
- inheritance pattern
X-Linked Dominant
211
Cerebellar ataxia
- inheritance pattern
X-Linked Recessive
212
Hunter's syndrome
- inheritance pattern
X-Linked Recessive
213
Lesch-Nyhan syndrome
- inheritance pattern
X-Linked Recessive
214
Leber's hereditary optic neuropathy
- inheritance pattern
Mitochondrial
215
Kearns-Sayre syndrome
- inheritance pattern
Mitochondrial
216
During which phase of meiosis does genetic recombination take place?
Prophase I
217
Schizophrenia
- Candidate genes (4 + chromosomal locations)
DISC1 - chromosome 1
DTNBP1 (dysbindin) - chromosome 6 (6p 22.3)
NRG1 (neuregulin 1) - chromosome 8 (8p 21-22)
COMT - chromosome 22
218
Di George (Velocardiofacial) Syndrome
- clinical features (5)
- chromosome affected
'CATCH-22'
Cardiac abnormalities (tetralogy of Fallot)
Abnormal facies (almond-shaped eyes, low-set ears)
Thymic aplasia (hence recurrent infections)
Cleft palate
Hypocalcemia/Hypoparathyroidism (causing short stature and seizures)
2
2
219
Heterogeneity
- essence
refers to the presence of a variety of genetic defects which cause the same disease.
220
Frontotemporal dementia
- candidate genes (2)
PGRN (progranulin)
| MAPT (tau)
221
Huntington's disease
- candidate genes (1)
IT15 (huntingtin)
222
CADASIL
(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
- candidate genes (1)
Notch3 (notch 3)
