Medical molecular genetics

HideShow resource information
What the the steps for producing cells in chromosome banding?
1. Stimulate cells to divide, 2. Culture the cells for up to 72 hours, 3. Arrest the cells during metaphase (homologous chromosomes are joined and positioned at the equator), 4. Swell the cells in hypotonic KCl solution, 5. Drop the cells, 6. Stain
1 of 174
What are the dark bands rich in?
A and T
2 of 174
Why are they dark?
The chromatin is more condensed
3 of 174
Are there lots of genes in the dark bands?
No
4 of 174
When do they replicate?
Late in S phase
5 of 174
What are the light bands rich in?
G and C
6 of 174
Why are they lighter?
They contain less dense chromatin
7 of 174
When do they replicate?
Early in S phase
8 of 174
What does chromosome banding allow you to do?
Identify homologous chromosomes
9 of 174
What is a karyogram used for?
To look at the chromosomes of an individual
10 of 174
What mutations are visible from a karyogram
Large deletions and aneuploidy
11 of 174
What are the 3 shapes of chromosome?
Metacentric, submetacentric and acrocentric
12 of 174
What letter is the short arm?
p
13 of 174
What letter is the long arm?
q
14 of 174
How are bands labelled?
From the centromere outwards
15 of 174
What can FISH show?
The location of particular genes and deletions of those genes
16 of 174
What is different between the procedure of Karyotyping and FISH?
Fish uses fluorescently labelled DNAprobes
17 of 174
What causes aneuploidy?
Chromosome nondisjunction
18 of 174
What is chromosome nondisjunction?
When homologous chromosomes fail to separate properly during anaphase of Meiosis I
19 of 174
When are male gametes produced?
When a boy reaches puberty
20 of 174
Is sperm a continuous process?
Yes
21 of 174
When are female gametes produced?
During the development of the female foetus
22 of 174
When does Meiosis I begin and arrest in females?
Prior to birth
23 of 174
When does Meiosis I restart?
During puberty when the egg is released from the ovary
24 of 174
When Is meiosis II completed?
At ooycte fertilisation
25 of 174
What proteins are involved in increased likelihood of aneuploidy?
Cell cycle-associated proteins and proteins involved in spindle alignment
26 of 174
What is an example of a protein family of a cell adhesion molecule?
SMC family
27 of 174
What i an example of a protein involved in spindle alignment?
Protein E
28 of 174
What is trisomy 21 caused by?
£ copies of chromosome 21 in every cell
29 of 174
What is the frequency of trisomy 21?
1 in 750
30 of 174
What produces a gamete with 2 chromosomes?
Errors in meiosis I due to a lack of chromosome alignment by spindles and chromosomes not seperating
31 of 174
What produces an egg with 3 copies of a chromosome?
When a germ cell contains 2 chromosome copies fuses with a normal germ cell
32 of 174
What are the symptoms of downs syndrome?
Characteristic facial features, Learning disability, speech defect and a heart defect
33 of 174
At what age does the risk of giving birth to a trisomy baby increase rapidly?
40+
34 of 174
What is trisomy 18 also known as?
Edwards syndrome
35 of 174
What are the symptoms of trisomy 18?
A small head, small jaw and bone abnormalities
36 of 174
How are aneuploidys genetically tested?
Using FISH. The fluorescent tag with highlight each gene present on that chromosome
37 of 174
What are microdeletion disorders?
Caused by a deletion of a small part of a chromosome
38 of 174
How are micro deletions diagnosed?
Using FISH
39 of 174
What normally causes microdeletions?
Low copy repeats that flank genes that are normally deleted
40 of 174
What are LCRs?
Pieces of DNA that are found throughout the human genome which have a sequence made up of almost 95% of the same DNA sequence (identical)
41 of 174
What process are LCRs often involve?
Chromosome nondisjunction
42 of 174
What happens during this event?
The LCRs bind at the wrong place and when crossing over occurs, the genes within the LCRs are transferred onto the opposite chromosome
43 of 174
What does this result in?
One chromosome having a gene deleted and the other with an extra gene
44 of 174
What types of diseases are microdeletions related to?
Happloinsufficency
45 of 174
What are the two disorders caused by micro deletions
Williams Beuren syndrome and DiGeorge sundrome
46 of 174
What is the deletion involved in WBS?
A 1.4 Mb deletion on chromosome 7. Point 7q11.23
47 of 174
Is it inherited?
No, usually occurs sporadically
48 of 174
What major gene is deleted?
The elastin gene
49 of 174
What is the normal function of elastin?
To provide strength and elasticity to extendable its
50 of 174
What are the symptoms of WBS?
Growth retardation, Elfin face, heart abnormalities (SVAS)
51 of 174
What are the characteristic traits obsessed in WBS?
Anxiety, overly charismatic, good verbal skills, poor spacial cognition and problem solving
52 of 174
What is the deletion involved in DiGeorge syndrome?
A 3 MB deletion on chromosome 22. Point 22q11
53 of 174
What types of genes are deleted?
Ones involved in migration and development of cells during metal development
54 of 174
What type of disorder is DiGeorge also viewed as?
An immunodeficiency syndrome
55 of 174
What re the physical features of an affected individual?
A cleft lip, characteristic face and delayed growth
56 of 174
How do you test for microdeletions?
FISH
57 of 174
What are copy number variations (CNVs)?
Alterations of the DNA of a genome that result in abnormal variations of genes number
58 of 174
What mutation causes a-thalassemia?
A mutation in the a-globin gene
59 of 174
Where are the a-globin genes found and how many are present?
Chromosome 16 and 2 copies
60 of 174
Where are the b-globin genes found and how many are present?
Chromosome 11 and 1 copy
61 of 174
What do the a and beta subunits make up?
Haemaglobin HbA
62 of 174
What is HbA made up of?
2 alpha and 2 beta subunits
63 of 174
How many deletions are needed for haemoglobin H disease? (a-thalassemia)
3
64 of 174
What causes mitochondrial disorders?
Dysfunctional mitochondria
65 of 174
What is Lebers hereditary optic neuropathy?
Degeneration of retinal ganglion cells and their axons
66 of 174
What nucleotide substitute causes 50% of LHON?
G to A substitute in the ND4 gene of the mitochondrial genome
67 of 174
What is the ND4 protein involved in?
Oxidative phosphorylation
68 of 174
What is genetic imprinting?
The inheritance of a gene from one parent that is switched off
69 of 174
How are genes silenced?
DNA methylation leads to inactivation of gene promotors
70 of 174
How are genetic disorder caused through genetic imprinting?
Normally you have an active gene that compensates for the silenced gene. When the active gene is stated then there is no protein produced
71 of 174
What are the two disorders connected with imprinting?
Prader- willi syndrome and Angelmans syndrome
72 of 174
How common is prayer-willi syndrome?
1 in 20,000
73 of 174
What chromosome and area of the chromosome is involved?
Chromosome 15q11-13
74 of 174
Are the maternal or paternal genes silenced?
Maternal
75 of 174
The function of what important gene is lost when the paternal gene is mutated?
The SNPRN gene
76 of 174
What is the SNRPN protein involved in?
It is highly expressed in the brain and pays a role in pre-mRNA processing
77 of 174
What are the symptoms of Prader-willi?
Developmental delay, muscle weakness, obesity due to food obsessions and affected feeding behaviours
78 of 174
How common is Angelmanns syndrome?
1 in 15,000
79 of 174
What chromosome and area of the chromosome is involved?
Chromosome 15, 15q11-13
80 of 174
Are the maternal or paternal genes silenced?
Paternal
81 of 174
The function of what important gene is lost when the maternal gene is mutated?
The UBE3A gene
82 of 174
What does UBE3A encode?
Ubiquitin protein ligase
83 of 174
What is ubiquitin used for?
To tag proteins for degradation
84 of 174
If the UBE3A gene is mutated what does that cause?
A loss of protein degradation control
85 of 174
What are symptoms?
Primarily affects the nerves system- seizures, speech defect and developmental disability
86 of 174
What is a triplet repeat?
A codon which is highly repeated in tandem in a DNA sequence
87 of 174
How can triplet repeat expand?
The DNA sequence is very unstable during meiosis, leads to extra codons being added
88 of 174
What is anticipation?
Seen in triplet repeat expansion disorders, its when symptoms worsen down the generations due to an increased length of the repeated region
89 of 174
What type of inheritance does fragile-x show?
X-linked
90 of 174
How common is it?
1 in 4,000
91 of 174
What is the codon involved?
CGG
92 of 174
Where is the triplet repeat found?
In the 5'untranslated region of the FMR1 gene at the 'fragile site'
93 of 174
What number of repeats silences the promotor?
200+
94 of 174
What is the mechanism for the promotor silencing?
DNA methylation
95 of 174
Why are CGG highly methylated?
CpG nucleotides are a signal for DNA methylation
96 of 174
What happens the number of repeats increases?
The process of methylation becomes easier and speeds up
97 of 174
What happens when methylated DNA gets close to the promotor?
RNA polymerase can't bind to the promotor
98 of 174
What is the FMR protein normally used for?
Essencial for cognitive development and neural plasticity as it transports mRNA from the nucleus to ribosomes
99 of 174
What are the symptoms of FXS?
Mental retardation, enlarged testicles and a late onset of Parkinson's disease
100 of 174
How is Friedreichs ataxia inherited
An autosomal recessive pattern
101 of 174
What is the frequency of the disease?
1 in 50,000 people
102 of 174
What is the codon in the expansion?
GAA
103 of 174
Where is the tandem repeat found?
Intron 1 of the FXN gene on chromosome 9
104 of 174
What protein does FXN transcribe?
Frataxin
105 of 174
What number of repeats causes symptoms?
Over 200
106 of 174
How does the repeat expansion cause the disorder?
When the expansion gets to a certain length the intron sequence changes shape. It blocks RNA polymerase from moving down the gene past the intron
107 of 174
What is produced?
An incomplete and unstable protein due to the short mRNA sequence
108 of 174
What is frataxin used for?
Its crucial for neural development and is a highly conserved protein in the inner mitochondrial membrane. Its essential for energy production pathways
109 of 174
What does no frataxin in the body do?
It causes neuronal death and thinning of the spinal chord due to a lack of ATP production and increased susceptibility to free radicals
110 of 174
What are the symptoms?
Impaired muscle strength and poor muscle co-ordination. As well as scoliosis
111 of 174
What inheritance pattern does Myotonic dystrophy have?
Autosomal dominant inheritence
112 of 174
How frequent is the disorder?
1 in 8,000 people
113 of 174
What is the codon involved?
CUG
114 of 174
Where is the triplet expansion found?
3' untranslated region of the DMPK1 gene on chromosome 19
115 of 174
What number of repeats causes a phenotype?
over 100 to 1,500
116 of 174
What causes the disease?
When the expansion reaches over 100, the mRNA transcribed is abnormally long and able to form bond within itself. The mRNA aggregate together and so unable to leave
117 of 174
What are the symptoms of a mild form of MD?
Cataracts in eyes
118 of 174
What are the symptoms of a severe form of MD?
Myotonia (prolonged muscle contraction) and problems with muscle relaxation
119 of 174
How many repeats are seen in those with the congenital form?
Over 1000
120 of 174
What symptoms would a baby born with the congenital form show?
Floppy, poor head movement and a cardiac defect
121 of 174
What type of disease is Huntingtons disease?
A polyglutamine disease
122 of 174
What is the codon involved?
CAG
123 of 174
Where is the triplet repeat expansion?
Intron 1 of the Huntington gene on chromosome 4
124 of 174
What happens when the repeat expansion reaches a certain length?
An abnormally long mRNA strains is made producing an elongated protein. It is cut onto smaller toxic fragments which aggregate on neutrons and disrupt function
125 of 174
What is a normal length?
10-26
126 of 174
What length iss reduced penetrance?
40
127 of 174
What length is full penetrance?
40+
128 of 174
At what age is complete penetrance seen?
60 years old
129 of 174
What ar the symptoms
Problems with co-ordination, depression, involuntary head movements and speech problems
130 of 174
What does pre implantation genetic enable us to do?
It enables people with inheritable conditions within their family history to avoid passing it on to their offsrping
131 of 174
Is knowledge of the genetic disorder you are looking for required?
Yes
132 of 174
When can the test be carried out?
1 cell can be taken from the blastomere stage / 2 cells can be taken from the blastocyst stage
133 of 174
What techniques are used in PDG?
PCR for monogenetic disorders or FISh to identify aneuploidy or chromosome abnormalities
134 of 174
At what age is chorionic villus sample taken?
9-14 weeks
135 of 174
What is involved?
Indroducing a catheter into the womb where wells of the placental chorionic villus are taken
136 of 174
At what age is an amniocentesis sample taken?
15-20 weeks
137 of 174
What is involved?
Passing a needle into the amniotic sac, cells are taken from the amniotic fluid to be sampled
138 of 174
What un-invasive test can also be carried out?
Maternal blood sampling
139 of 174
What cytogenetic technique is used on metal cells?
FISH
140 of 174
Describe the genetic test of huntingtons
It involves two counselling session. The first involves discussing the positives and negatives of being tested. The second session is when a blood sample is taken. Then the length of the CAG repeat is measured
141 of 174
Describe the genetic test of myotonic dystrophy
Initial observations are made of the child. It is then sent for an electromyography test which records the electrical activity produced by the skeletal muscle. A blood sample is taken and the CTG repeat is measured using PCR and southern blotting
142 of 174
Wen is PCR more likely to be used?
Identifying smaller expansions in less severe cases
143 of 174
What is the normal length of the CTG repeat?
5-37
144 of 174
What length of the repeat starts showing symptoms?
50+
145 of 174
What inheritance does CF show?
Autosomal recessive
146 of 174
What mutation is it most commonly caused by?
A 3 nucleotide deletion (phenylalanin) F508
147 of 174
What gene is mutation and on which chromosome?
CFTR gene on chromosome 7
148 of 174
What is the frequency of CF?
1 in 25,000
149 of 174
What does the CFTR protein do?
Its a transmembrane protein which is a cl- transporter but also a regulator for na+ and H2O absorption of epithelial cells
150 of 174
What mediates the transporter?
cAMP
151 of 174
What happens when the protein is mutated?
No cl- can leave the cells and hypereabsortion of na+ and H2O
152 of 174
How does CF affect the lungs?
Leads to thick, sticky mucus build up and increase susceptibility to infection due to bacterial growth
153 of 174
How does CF affect the digestive system?
Thick, sticky mucus Bild up in the pancreatic duct blocks the proteolytic enzymes from reaching the intestines, food isn't broken down properly
154 of 174
When was CF introduced onto the neonatal screening program?
In 2007
155 of 174
What are you testing for in CF screening?
Levels of immunoreactive trypsinogen
156 of 174
When causes phenylketonuria?
An absence or deficiency of phenylalanine hydroxylase (PAH)
157 of 174
What does phenylalanine hydroxylase convert phenylalanine into?
tyrosine
158 of 174
When there is no enzyme what happens?
Phenylalanine builds up in the body
159 of 174
What gene is mutated?
PAH
160 of 174
What type of mutation cases the disorder?
There are over 400 different mutations
161 of 174
What inheritance pattern is seen for PKU?
Autosomal recessive
162 of 174
What effects does a build up of phenylalanine in the body have?
Affects the developing brain and leads to mental retardation
163 of 174
What is tested for in PKU neonatal screening?
Levels of phenylalanine
164 of 174
How is a person treated?
Have a diet low in protein and aspartame
165 of 174
What type of inheritance does DMD show?
x-linked recessive
166 of 174
What gene is involved?
The DMD gene
167 of 174
What is special about the gene?
Its the largest gene in the human genome (2.4mb)
168 of 174
Where is the DMD gene?
Xp21
169 of 174
What is dystrophin needed for?
It is needed to make muscles strong enough to withstand impact
170 of 174
Where is dystrophin normally found and what is its structural function?
At the inner membrane of the muscle and it links the actin-based cytoskeleton to the external basement membrane
171 of 174
When was the gene identified?
1987
172 of 174
What are tumour suppressor?
Genes which encode regulatory proteins that suppress growth factors and detect DNA replication errors in the cell
173 of 174
What is their role?
Mediate DNA repair and induce apoptosis of the cell
174 of 174

Other cards in this set

Card 2

Front

What are the dark bands rich in?

Back

A and T

Card 3

Front

Why are they dark?

Back

Preview of the front of card 3

Card 4

Front

Are there lots of genes in the dark bands?

Back

Preview of the front of card 4

Card 5

Front

When do they replicate?

Back

Preview of the front of card 5
View more cards

Comments

No comments have yet been made

Similar Biology resources:

See all Biology resources »See all Genetic diseases resources »