GIM Flashcards
(246 cards)
1
Q
Analyse entire genomes across individuals, to identify genetic factors influencing response to a drug
A
Pharmacogenomics
2
Q
Analysing an individuals genetic makeup to identify genetic factors influencing response to a drug
A
Pharmacogenetics
3
Q
4 conditions with an X linked mode of inheritence
A
Duchenne muscular dystrophy
Fragile X syndrome
Red/green colour blindness
Haemophilia
4
Q
3 conditions with an autosomal dominant mode of inheritence
A
Myotonic dystrophy
Marfan syndrome
Huntington’s disease
5
Q
3 conditions with autosomal recessive mode of inheritence
A
Haemachromatosis
Sickle Cell disease
CF
6
Q
An example of a conditions with a mitochondial mode of inheritence
A
Maternally inherited diabetes and deafness
7
Q
2 conditions with a XL-dominant mode of inheritence
A
Rett Syndrome
Fragile X syndrome
8
Q
3 conditions with an XL recessive mode of inheritence
A
Red/green colour blindness
Haemophilia
Duchenne muscular dystrophy
9
Q
Describe the presentation of fragile X syndrome in males and females
A
Variable expressivity in females, fully expressive in males
10
Q
Consanguinity increases the risk of conditions that are inherited in what way?
A
Autosomal recessive
11
Q
3 tests you can carry out to diagnose CF
A
Sweat test (increase in Cl- in sweat) Molecular genetic testing Immunoreactive trypsin (IRT) increases in CF
12
Q
What genetic testing would you if you were suspecting chromosomal imbalance i.e. recurrent miscarriages, abnormal phenotype
A
array CGH
13
Q
What genetic test would you use to confirm arrayCGH findings?
A
FISH or qPCR
14
Q
What genetic test would you use to diagnose Huntingtons?
A
PCR
15
Q
What number of CAG repeats is abnormal and results in the formation of protein aggregates in brain cells, causing progressive cell death?
A
Over 40 CAG repeats
16
Q
How do you describe the fact that HD becomes progressively worse with each consequtive generation?
A
Anticipation
17
Q
How would you prepare an arrayCGH test and what sized imbalances would you discard?
A
3ml blood in EDTA
1ml lithium heparin
Discard imbalances if
18
Q
How do you describe the ‘derivative chromosome’?
A
The chromosome with the distal segment deleted
19
Q
Sizes of 1Mb, Gb and Kb
A
1000 bases= 1Kb
1000Kb=1Mb
1000Mb=1Gb
20
Q
What does array CGH detect?
A
Chromosomal imbalances but not balanced rearrangements
21
Q
What genetic test is best for large translocations?
A
G banding
22
Q
Wolf Hirshorn Syndrome
A
der(4) t4;8
Second most common recurrent chromosomal translocation
23
Q
Mendelian
A
AD, AR, X linked and Mitochondrial inheritence patterns
24
Q
Complex
A
Inherited but not mendelian
25
Polygenic
Multiple genes
26
Multifactorial
Multiple factors (genes and environment)
27
Sequencing 1 gene at a time
Sanger sequencing
28
Sequencing many genes/the entire genome at once
Next generation sequencing
29
A comprehensive database of human genes, genetic traits and disorders. Provides evidence about specific genes in the affected region.
OMIM
30
Consanguinity increases the risk of a birth defect to what? What is normal?
Increases to 5-6% from 2-3%
31
3 ways to determine whether a multifactorial disease has a genetic component
Familial clustering
Twin studies
Adoption studies
32
How do you determine whether a disease has an element of familial clustering?
Lambda s is the relative risk to the 2nd sibling= risk to sibling/risk to general population
33
lambda s
The relative risk to the 2nd sibling
34
Problems with twin studies
Not all monozygotic twins have equal environmental sharing in utero
Dizygotic twins can share more than 50% of their genes
35
Population Attributable Risk
Compare variation in human DNA sequence with disease/trait in patients and controls. Do genetic variants confer susceptibility to complex phenotypes?
36
What type of disease is associated with a genetic mutation that has a high effect but rare in the population
Mendelian
37
What type of disease is associated with a gene that has a less effect (additive) but common in the population?
Multifactorial
38
1mb regions around the mutation are identical to the common ancestor-variants near the mutation present in cases, not controls.
Linkage disequilibrium
39
Give 4 examples of polygenic diseases
Type II Diabetes
Schizophrenia
Age related macular degeneration
Alzheimer's disease
40
DNA repair and carcinogen metabolism
Caretaker genes
41
Cell cycle control, programmed cell death
Gatekeeper genes
42
Degeneration of the macula in age related macular degeneration is characterised by early deposition of what?
Drusen
43
Risk factors for age related macular degeneration
Genetic-CFH, ARMS2
| Environment-Smoking (major effect), light exposure
44
Light exposure and smoking increases the risk of age related macular degeneration by what amount?
70% increase in risk
45
What does the Manhatten Plot show you?
High case;control ratio for variant indicates increased susceptibility to disease
46
To what degree does familial clustering have an effect with regards to alzheimer's disease?
Lambda s=3-10
47
Describe the genetic inheritence pattern of alzheimers
Early onset form is genetically heterogenous
48
In early onset alzheimer's, there is a mutation in what gene and what are these genes normally responsible for?
```
Presenilin 1 (PSEN1) and 2 (PSEN2)
They encode proteases with gamma secretase activity responsible for preteolytic cleavage of amyloid b A4 precursor protein
```
49
Describe a susceptibility allele for Alzheimers
A form of ApoE has a large effect on susceptibility to Alsheimers
50
Which forms of ApoE are protective or increase the susceptibility for alzheimers?
ApoE2-protective
ApoE3
ApoE4-Increased susceptibility (risk factor for late onset alzheimers)
51
How many 'hits' are required for a sporadic mutation?
No inherited mutation so 2 'hits' required
52
Give an example of a gatekeeper gene
TP53
53
What type of gene control surrounding stromal environment
Landscapers
54
Give 4 examples of tumour suppressor genes
APC
BRCA1/2
TP53
Rb
55
Regulate cell growth and differentiation. Gain of function increases the risk of mutations
Oncogene
56
Give 2 examples of oncogenes
Growth and signal transduction factors
| RET gene
57
Familial cancers mostly show what mode of inheritence?
Autosomal Dominant
58
Incorrect amino acid
Missense
59
Incorrect stop codon
Nonsense
60
Frameshift
Splice site, large deletions/duplications, translocation
61
Diagnostic genetic testing
Performed on DNA of affected relative to identify the family mutation
62
Predictive genetic testing
Once the mutation is identified, testing for specific mutation may be offered to other relatives
63
Rare childhood occular cancer- familial cancer
Retinoblastoma
64
The mutation for retinoblastoma affects what gene? Which cancers are typical in patients with retinoblastoma?
Rb1 gene
| Retinal cancers and osteosarcoma
65
FAP accounts for what percentage of bowel cancers and what is the prognosis and preventative treatment? FAP arises from a mutation in what gene?
Accounts for 1% bowel cancers
100% risk bowel cancer if untreated
Colonoscopies=preventative treatment
APC tumour suppressor gene
66
HNPCC accounts for what percentage of bowel cancer? What is the prognosis?
The mutation is present in what gene?
Preventative measures?
How is it diagnosed?
Accounts for 2-3%
60-80% risk of bowel adenoma or cancer from mid 20s onwards.
Mismatch repair genes MLH1 (50%), MSH2 (40%), MSH6 (10%) or PMS1/2
Colonoscopy every 18-24 months from around 25 years
Diagnosed using the Amserdam Criteria of HNPCC
67
Breast/ovarian cancers arise from a mutation in which genes?
BRCA1/BRCA2- tumour suppressor genes
68
A mutation in BRCA1/2 increases the risk of getting breast cancer by what?
80% risk of breast cancer
69
A mutation in BRCA1 increases the risk of getting ovarian cancer by what?
40%
70
A mutation in BRCA2 increases the risk of getting ovarian cancer by what?
10-20%
71
LI fraumeni syndrome is a mutation in what gene?
p53
72
What cancers do you most commonly get if you have Li Fraumeni Syndrome?
Breast, sarcoma, brain etc
73
Metaphase chromosome analysis e.g. G banding
Conventional cytogenetics
74
Molecular resolution at all stages in the cell cycle-FISH, microarray CGH, next generation sequencing, MLPA
Molecular cytogenetics
75
What is more detrimental, loss or excess?
Loss
76
What is more detrimental, sex chromosome imbalances or autosomal imbalances
Autosomal imbalances
77
Trisomy or monosomy
Aneuploidy
78
Triploidy or tetraploidy
Polyploidy
79
Aneuploidy and diploidy (normal)
Mosaicism
80
Increasing maternal and paternal age has what effect on numberical chromosome abnormalities
Maternal- increase in aneuploidy
| Paternal- no significant risk
81
What is the result of non dysjunction at meiosis 1?
2 disomic gametes, 2 nullisomic gamets
82
What is the result of non dysjunction at meiosis 2?
2 normal gametess, 1 nullisomic gamete, 1 disomic gamete
83
Trisomy 21 increases your risk of what conditions?
Leukaemia, Alzheminers, hypothyroid, obesity/coeliac, arthritis, hearing loss, seizures
84
Trisomy 18
Edward's syndome
85
Trisomy 13
Pataum syndrome
86
Describe the features of trisomy 18
10% survive >1yr. Microcephaly, cleft lip and palate. Clenched hands, overlapping fingers, rockerbottom feet, severe metnal retardation, umbilical or inguinal hermia, CHD, kidney and eye problems
87
Describe the features of patau syndrome (rarest out of the 3)
Mental retardation, severe microcephaly, deafness, heart problems, polydactyly
88
Is there an age related risk with regards to sex chromosom aneuploidy?
No
89
Supermale
XXY
90
Superfemal
XXX
91
Characteristics of Turner's syndrome
Infertility. Lymphatic obstruction, Short, coarctation of aorta.
92
Characteristics of Klinefelter's syndrome
Infertility/hypogonadism. 80% XXY, 20% mosaic/variant. Gynacomastia (20x Increase in breast cancer), long arms and legs.
93
How does turner's/klinefelters' affect the persons IQ
Doesn't affect it
94
What are the 3 types of triploidy
Digyny
Diplospermy
Dispermy
95
Digyny
1 egg with disomy, 1 sperm
96
Diplospermy
1 egg, 1 sperm with disomy
97
Dispermy
1 egg, 2 sperm
98
Characteristics of double paternal
Large placenta
| Some growth delay
99
Characteristics of double maternal
Tiny placenta
Significant growth delay
'head saving macrocephaly'
100
Describe the way in which a molar pregnancy comes about
Haploid sperm+empty egg>haploid zygote>diploid zygote ('doubling up')>massive cystic placenta
101
What is another way of describing mosaicism
Mitotic not dysjunction
102
What is the end result of non dysjunction at 2nd mitotic division
25% monosmy
25% trisomy
50% normal disomy
103
What does trisomic rescue mean?
A cell with trisomy spontaneously loses 1 chromosome to become disomy
104
What are 5 consequences of mosaicism
```
Variable phenotype, lethality
Non identical twin
Tissue specific lateral asymetry
Uniparental disomy
Recurrence risk (if gonadal)
```
105
What are the 2 major types of chromosome change?
Balanced an unbalanced
106
What are the 2 types of balanced chromosome rearrangements
Translocation and Inversion
107
What are the 2 types of translocation chromosome rearrangements
Reciprocal
| Robertsonian
108
Reciprocal translocation
break and exchange. More common. 5-10% phenotype risk. Reproductive risk.
109
Robertsonian translocation
Whole arm fusion of acrocentric chromosomes (13,14,15,21,22)
| No phenotype/reproductive risk
110
What are the 2 types of inversions
Pericentric and paracentric
111
Pericentric inversion
2 breaks in differen arms of chromosome. Rotate 180 degrees then regions
112
Paracentric inversion
(2 as i.e. the same letter) Both breaks in same half
113
What is the most common cause of unbalanced chromosome rearrangements
Copy number variation- overall net cytogenetic gain and/or loss.
114
What are the 2 main type of unbalanced chromosome rearrangements?
Deletions and duplications
115
What are the 2 types of deletions
Interstitial deletion
| Terminal deletion
116
Segment lost in the middle of the chromosome
Interstitial deletion
117
Segment lost at the end of the chromosome
Terminal deletion
118
What are the 2 types of duplications?
Direct
| Inverted
119
Low copy repeats
Small areas of DNA with 99% homology with other sections of DNA. Results in wrong alignment during pairing in mitosis. Not completely random cause of deletion.duplications.
120
Ring Chromosome
Breakage at both ends of the same chromosome. Terminal ends then join to make a ringed structure.
121
Replication occurs during which phase of the cell cycle?
The S phase
122
Why is DNA more stable than RNA?
It doesn't have an -OH group attached to its 2nd carbon.
123
What do you call the stand of DNA that acts as the template for the mRNA?
Antisense strand- the sense strand makes sense of the antisense strand
124
How many bases are in a double stranded DNA per haploid genome?
3,000mb
125
Which chromosome is the biggest?
1
126
What percentage of DNA is non coding?
90%
127
How many protein coding genes are there?
20,000
128
Average gene size
50-100kb
129
Average mRNA size
2kb
130
Which part of the DNA is the coding region?
Exons
131
Non repetitive sequences
Genes
132
Repetitive sequences
Interspersed repeats e.g. Alu repeats and satellite DNA
133
What parts of DNA replication occurs int he cytoplasm?
Translation, post-translational modification
134
Alternaive splicing
a regulated process during gene expression that results in a single gene coding for multiple proteins.
135
What are the 2 main mechanisms of alternative splicing?
Exon skipping
| Mutually exclusive exon choice
136
Exon skipping
Exons may be spliced together in a variety of patterns. Diversity of genome is increased due to this process.
137
Mutually exclusive exon choice
2 exons within the same gene are put side by side as a result of exon duplication in evolution
138
Describe the mechanisms by which pseudogenes arise
Ancestral gene>duplication>divergence>pseudogene
139
A non functional gene
Pseudogene
140
Processed genes
mRNA is transcibred and re-integrated into the host genome. Introless copies of genes which occasionally remain functional
141
An example of a processed gene that remains functional
PGK2
142
Give 2 exampels of repetitive DNA
Satellite DNA
| Interspersed Repeats
143
Satellite DNA
Large blocks at centromeres e.g. alphoid DNA
144
Alphoid DNA
171bp repeat
145
Interspersed repeats
Scattered around genome e.g. alu repeats.
146
Alu repeats
500,000 copies, 3,000bps, 5% genome
147
Duchenne muscular dystrophy is what type of mutation
Deletion
148
Charcot marie tooth disease (nerve disorder) is what type of mutation?
Duplication
149
Haemophilia A is what type of mutation
Gross rearrangement
150
Describe the mutation in haemophilia A
Coded for by F8C gene- intrachromosomal recombination results in an inversion of the segment of the repeat copies
F8C gene is chopped in 2- no longer functions
151
Polymorphism
Common silent mutation. Splice site mutations, outside exon, likely to be pathogenic
152
Describe the hypermutability fo CpG dinucleotides
CG dinucleotides are particularly susceptible to DNA mutation;
1. methyloation of cystein
2. deamination of methylcysteine- very like thymine
3. mismatch repair proteins struggle to pick this up
Account fo 1/3rd mutation
153
Mutational heterogeneity
Mand different mutations can cause the same disease
154
Loss of function mutations are often recessive or dominant?
recessive
155
Gain of function mutations are often recessive or dominant?
dominant
156
An example of a gain of function mutation
achondroplasia-FGF-R3 gene upregulated-ngative regulator effect on bone growth
157
Give 2 examples of trinucleutide repeat expansions
```
Polyglutamine repeats (CAG)
Large, non coding repeat expansion
```
158
Give examples of conditions that arise due to polyglutamine repeats
Neurodegenerative disorders e.g. Huntington's, spinocerebellar ataxias
159
Give examples of large, non coding repeat exampnsions
Fragile X syndrome-transcriptional silencing with CGG repeats.
160
how many CGG repeats count as a full mutation in fragile X syndrome?
more than 200
161
Congenital malformations account for what percentage of births?
2-3%
162
Characteristics of Kabuki syndrome
```
Learning difficulties
50% congenital heart defect
Hearing impairment
Poor growth
Cleft palate
Eversion of lateral 1/3rd eyelid
Premature breast development
Finger pads
```
163
Characteristics of Di George syndrome
```
Learning difficulties
75% hypocalcaemia
Seizures
Immunodeficiency
Renal malformations
Cleft palate
Velophalangeal insufficiency-sounds like you have a cold
```
164
Characteristics of achondroplasia
AD
Foramen magnum compression/hydrocephalus
Rhizometric limb shortening (prox. limbs) short stature
165
Characteristics of treacher collins syndorme
AD
Cleft palate
Hearing impairment
166
Charactersitics of Waardenburg Syndrome
```
Sensorineural hearing loss
Congenital malformations (Hirschsprung's/VSD)
Iris heterochromia
Premature greying
Areas of skin hyperpigmentation
```
167
Characterisitsic of William's syndrome
Learning difficulties 'cocktail party' speech
Supravalvular aortic stenosis
Peripheral pulmonary artery stenosis
Hypercalcaemia
168
Characteristics of Beckworth Widermann Syndrome
Exomphalmos (weakness of abdominal wall surrounding umbilicus) Noenatal hypoglycaemia Increased risk of Wilm's tumour (nephrobastoma) Large tongue, ear pits/creases, hemihypertrophy (one side of the body is larger than the other)
169
Characteristics of Peutz Jegher's syndrome
GI polpys
170
The most common chromosomal disorder
Down's syndrome
171
Describe the distribution of pigmentary mosaicism
Pigmented patches that may follow baschko's lines
172
Give 3 examples of whole genome testing
G banding, next generation sequencing, microarrays
173
Give 4 examples of targeted testing
FISH, MLPA, QF-PCR, or qPCR
174
Metaphase chromosomal analysis by light microscopy e.g. G banding
Congentional cytogenetics
175
Chromosome analysis at the molecular resolution at all stages of the cell cycle e.g. FISH, array CGH
Molecular Cytogenetics
176
Describe the process of G banding
Cell culture>mitotic arrest>harvest cells>trypsin digestion>DNA stain (Giermsa or Leishman's)
177
What are 3 types of probe for FISH
Unique sequence
Centromere
Paints
178
What type of probe is used to identify deletions/duplications?
Unique sequences
179
What type of probe is used to identify the total no. of copie e.g. trisomy
Centromere
180
What type of probe is used to identify translocations
Paints
181
What is the clinical presentation of an increased copy number of CCL3LI
Decreased susceptibility to HIV
182
What is the clinical presentation of an increased copy number of FCGR3B
Descreased susceptibility to inflammatory autoimmune disorders
183
Currently the most importnat genome test; compares relative amounts of DNA in sample and control
Microarray CGH
184
What does a haploinsufficiency score tell you in a microarray CGH?
Tells you whether an imbalance is pathogenic
185
How would you prepare the blood sample for a microarray CGH?
3ml blood in EDTA
1-2ml Lithium heparin
Control DNA from same sex
186
How do you determine regions for potential copy number changes?
More than 3 oligonucleotides required for any call
| More than 150kb is significant
187
How are the results from next generation sequencing displayed, to show dosage changes?
Displayed as a karyogram
188
When might you use quantitative fluorescent PCR?
In prenatal sampling when looking for aneuploidy. Relies on differences between maternally and paternally derived alleles.
189
If a mother has a balanced reciprocal translocation, how would the chromosomes pair at meiosis?
In a pachytene cross structure (quadrivalent)
190
If reciprocally translocated chromosomes pair in a pachytene cross, what is the chance of the child inheriting unbalanced translocations?
50%
191
give an example of a disease that arises from unbalanced separation of reciprocally translocated chromosomes at meissis
Wolff Hirshom syndrome (t4;11)
192
When would you perform amniocentesis?
16 weeks
193
When do you do chorionic villus sampling?
12 weeks
194
When do you do non invasive prenatal testing?
12 weeks
195
Nuchal thickening greater than what, increases the risk of Down's syndrome?
greater than 3.5mm
196
How do you calculate the combined risk for Down's syndrome?
Nuchal thickening and serum screen
197
What proportion of down's syndrome foetuses sponstaneously abort post 16 weeks?
25%
198
Primary genetic test for trisomy 21
Amniocentesis and chorionic villus-QfPCR
199
If abnormal scan but no trisomy on QF-PCR, what geneteic test would you follow with?
Array CGH
200
What perfecntage of chromosome abnormalities spontaneously abort?
50%
201
What genetic test identifies bcl-abl fusion gene?
FISH
202
What genetic test would you use to diagnose a solid tumour?
FISH or Gbanding
203
Enables you to find genes involved, a comprehensive clinical synopsis and offers you the mode of inheritence
Online mendelian inheritence in man (OMIM)
204
How do you carr out non disclosure testing e.g in Huntingtons?
Look for markers on chromosome 4 to see which alleles come from mum or dad. Allele from mum, if affected parent, has 50% chance that it carrys the mutation. Discard embryos with mother's allele of chromosom
205
What is the role of leptin>
It is produced by fat cells and tells the brain to
decrease food input
Increase thermogenesis
Increase physical activity
206
Genetic cure for leptin deficienciency
Leptin replacement
207
Rare, inherited AR eye disorder causing blindness at birth or infancy
Leber's congenital amaurosis
208
Describe the genetic abnormality in leber's congenital amaurosis
RPE-retinal epithelium 65 gene is involved in teh formation of vit A, that changes retinal to retinol. Defects result in damage to the retina.
209
Treatment for LCA
Subretinal injections; between RPE and photoreceptor, with virus containing RPE65
210
Conditions for subretinal injections to treat LCA
Must be a missens mutation, and the patient's must not have amblyopia (lazy eye) as this inhibits results
211
Role of cytochrome p450 oxidases
Responsible for metabolising drugs in the liver. Also important in converting prodrugs to their active forms
212
Which cytochrome p450 oxidase metabolises 25% drugs?
CYP2D6
213
Describe the pharmacogenetics behind the administration of tamoxifen and its metabolism
CYP2D6 metabolises tamoxifen to its active metabolite endoxifen. Poor metaolisers due to CYP2D6 polymorphisms are associated with worse survival.
214
Reproduction of only males
androgeneisis
215
Reproduction of only females
Parthogeneis
216
Androgenic proliferation of abnormal trophoblast tissue
Hydatidiform mole
217
Benign ovarian teratoma-wide spectrum of tissue (epithelial, no skeletal muscles, no membrane/placenta)
Parthogenesis
218
When are modification of the genome made that determine the sex of the genome
Gaemtogeneis-spermatogeneis/oogenesis
219
Facial dysmorphism- protrusion of jaw, wide mouth, drooling, smiling/laughing appearance. Mental handicap-microcephaly, absent speech. Seizures and ataxia/jerky movements.
Angelman syndrome
220
Infantile hypotonia-feeding problems, motor delay. Mental handicap. Male hypogenitalism. Hyperphagia-obesity/uncontrolled appetite.
Prader Willi Syndrome
221
Angelman syndrome and prader willi syndrome are both associated with what genetica bnormality
A deletion of a part of chromosome 15.
222
Specifically what genetic abnormaility would you find in Angelman syndrome
75% maternal chromosome deletion
1% UPD
2-5% point mutation
223
Specifically what genetic abnormality would you find with prader willi syndrome?
Deletion of paternal chromosome 70%
| UPD 2%
224
COnclusion of angelman and prader willis syndrome
Monoallelic expression of a cluster of genes- UBE3A only expressed on maternal chromosom
225
4 exampels of epigenetic modifications
Ubiquitination
Phosphorylation
Methylation
Acetylation
226
Describe DNA methylation in imprinted genes
Methylating a CpG island (epigenetic modification) is carried out by DNA methyltransferases, and is reversible. Inactivates the gene. Imprinted genes show monoallelicc expression-either maternal/paternal copy is methylated and thus silenced.
227
Briefly outline the foetal-maternal growth conflict
paternal interest-promote foetal growth
| maternal interest-restrain foetal growth
228
Describe the clinical presentation of beckworth weidemann syndrome
foetal overgrowth-organomegaly, exomphalos. Hypoglycaemia. Asymetry, tumour risk, sporadic.
229
Describe the clinical presentation of russel silver syndrome
growth retardation in utero and postnatally- triangular face, asymetry and brain size preserved. Sporadic.
230
Describe the genetic abnormailitys is beckworth weidemann syndrome and russel silver syndrome?
Insulin like growth factor 2- major foetal growth promotor. Usually silenced in maternal chromosome. In BWS, methylation changes activate maternal IGF2 gene. In RS, changes inactivate the IGF2 gene on the paternal chromosome
231
Describe imprint switching
Epigenetics is reversible. Must be 'remembered' before somatic development and 'forgoteten' before gametogenesis- to erase grandparental imprint
232
What makes up most of the Y chromosom?
heterchromatin-no definable function
233
Pseudoautosomal regions
sections of DNA on both the X and Y chromosome
234
Dosage compensation
Ensure functional dosage of gene on X chromosome is equal in males and females. To enable this, in females, monoallelic expression is needed, achieved by epigenetic silencing-x inactivation. Somatic cells remember silenced status. Reversed in germ cells.
235
X linked recessive abnormal sweating disorder. Diagnose with starch/iodine test
Hypohidrotic ectodermal dysplasia
236
Pharmacokinetics
what the body does to the drug
237
Pharmacodynamics
what the drug does to the body
238
Stratified medicine
Selecting therapies fo groups of patients with shared biolocal characteristics.
239
Personalised medicine
Therapies tailored to the individual
240
Describe the interaction between thiopurine methyltransferase and azathioprine
Asathioprine is an immunosupporessant. TPMT inactivates it to limit DNA damage. TPMT polymorphisms decrease the activity of TMPT- more DNA damage
241
Describe the interation ebtween N-actelytransferase and isoniazid
N acetyltransferase is a group of liver enzymes which inactivate drugs. 'fats and slow acetylators' due to SNP variations. Slow acetylators are at increased risks of side effects from isoniazid for TB- including neuritis and liver txicity
242
Describe the interaction between succinylcholine and BCHE gene
Succinylcholine is a muscle relaxant used in anaesthesia. BCHE gene variant inactivates it at a much slower rate-effect may therefore last for an hour or more
243
Describe the interaction between aminoglycosides and mitochondrial MT-RNR1 gene.
Mitochondiral MT-RNR1 gene encodes mitochondrial 12srRNA. Mutations in this gene can make aminoglycoside more likely to bind to rRNA with mutation-maternal inheritence. Accounts for 30% aminoglycosdie toxicity
244
Describe the interaction ebtween warfarin and CYP2C9
Warfarin is inactivated by CYP2D9- cytochrome p450 family, and vit k oxidoreductase complex (VKORC1) these genes explain around 60% of genetic variability of warfarin activity
245
Describe the action of herceptin
Herceptin (Trastuzumab) targes those breast cancers with an overepression of HER2 (human epidermal growth factor receptor 2) (20% breast cancers) Trastuzumab is a monoclonal antibody to HER2
246
Describe the interaction ebtween BRAF inhibitors and vemuratenib
50% melanomas have a mutation in the BRAF gene- vemuratenib shows better response rate to chemo
