KB Genetics Flashcards
(100 cards)
1
Q
Two types of chromosomal abnormality
A
Structural and numerical
2
Q
What did a mitogen to stimulate cell division
A
Phytohameagglutinin
3
Q
What is a metaphase block
A
Colchicine
4
Q
How is banding produced and what does it identify
A
Trypsin breaking down some of the proteins associated with certain chromosomes that give specific banding patterns
5
Q
What can FISH be used for
A
Whole chromosome pains and viewing reciprocal translocations
6
Q
What is polyploidy?
A
When an egg is fertilised by 2 sperm = triploid = lethal
7
Q
Trisomy 21, 18, 13
A
Downs, Edwards, pataus
8
Q
How does risk of having a child with Down’s syndrome increase with maternal age
A
40 = 1/50
9
Q
Cri-du-chat syndrome
A
5p deletion
10
Q
Wolf-Hirschhorn syndrome
A
4p deletion
11
Q
Mitochondrial defects can be homoplasmic and heteroplasmic what does this mean?
A
Homoplasmic - identical DNA, mutation is all copies of mitochondrial DNA
Heteroplasmic - mutation in some copies, so defect may not be passed onto offspring
12
Q
What is LOHN?
A
Mutation in NADH dehydrogenase
13
Q
Leigh’s syndrome
A
Mutation in ATPase synthase molecule
14
Q
Pearsons syndrome
A
Deletion of mitochondrial DNA
15
Q
Penetrance
A
Chance of inheriting a disease if you carry a mutation
16
Q
Expressivity
A
Variation in phenotype in affected individuals
17
Q
Genomic imprinting
A
Expression of alleles depends on which parent inherited from. Due to epigenetic factors.
18
Q
Hardy Weinburg principle
A
Equation p=A and q=a
19
Q
What are all the germline types of genetic defect?
A
Chromosomal, mitochodrial, monogenic, polygenic
20
Q
Autosomal dominant, all bullet points
A
Affects both sexes, traceable, heterozygous affected, half offspring, gain of function. Huntingtons, dwarfism, hereditary retinoblastoma
21
Q
Autosomal recessive, all bullets
A
Both sexes, not traceable, homozygous, heterozygous are carriers, quarter of offspring affected, loss of function. Sickle cell anaemia, thalassaemia, cystic fibrosis.
22
Q
Xlinked recessive
A
Only males affected, traceable, hemizygous female carrier, half sons affected, loss of function. Haemophilia and duchenne muscular dystrophy.
23
Q
What is classical genetics?
A
Phenotype to genotype
24
Q
What is positional genetics
A
Genotype to phenotype
25
1% recombination frequency is how many cM
1
26
What does a LOD score have to be higher than to indicate linkage?
3
27
If genes are physically close they are...
Co-inherited
28
To tell chromosomes apart use
Polymorphic markers
29
Polymorphic markers include:
Restriction fragment length polymorphisms
Variable number tandem repeats (minisatellites)
Microsatellites (di, tri and tetranucleotide repeats)
Single nucleotide polymorphisms (occur around every 300 bp)
30
Process of pre genome project genome mapping:
Develop regional genetic map
Use markers to select genomic clones
Produce contig map of the region
Search for genes using CpG Islands, zoo blots, Northern blots, cDNA library scanning
31
Post genome project what has been made that makes searching for genes much easier?
Genetic and physical maps available with thousands of mapped genes and expressed sequence tags. Genes are able to be predicted from the genomic sequence which allow rapid identification of candidate genes.
32
To identify a disease gene in silico
Screen affected individuals for the mutation in the candidate genes, or just directly sequence
33
How does next gen sequencing work?
Sequence massive parallel sequencing of small fragments of DNA.
34
Cystic fibrosis symptoms and pathology
Defective secretory mechanisms which affects epithelial cells and causes thick mucus secretions
35
What are the symptoms of cystic fibrosis
Chronic lung disease, bowel obstruction, pancreatic failure, increase sweat electrolytes, blocked testes, premature death.
36
Cystic fibrosis is what type of genetic disease and affects how many people?
Autosomal recessive and affects 1/2000
37
Cystic fibrosis affects what protein?
Cystic fibrosis transmembrane conductance regulator which is a chloride channel and an ATP binding site.
38
The mutations causing CF are
70% ?F508 3bp deletion of phenylalanine
| 30% mutations in more than 60 other sites
39
What chromosome is CF on and when and how was it isolated?
Chromosome 7 isolated in 1989 by positional cloning and chromosome walking.
40
What gene is positionally linked to the CFTR gene?
MET gene
41
Duchenne muscular dystrophy is what type of genetic disorder?
X-linked recessive
42
What are the symptoms of DMD?
Progressive muscle wasting and death pre 30
43
What mutations cause DMD and Becker MD
Large deletions in the dystrophin gene causing absent or highly truncated protein - DMD
small deletions in the dystrophin gene causing partially truncated protein, more mild symptoms BMD
44
What is the dystrophin?
It is a protein that is important in muscle repair as shown in mx mice it accounts for 0.002% of muscle protein that links acting to a protein complex in the plasma membrane.
45
Which chromosome translocation can cause DMD in girls?
Xp21
46
Symptoms of Huntingtons disease
Loss of personality, loss of coordination, spasmodic movements, vegetative state
47
What age of onset is Huntingtons
Average 36
48
What type of genetic disorder is Huntingtons
Autosomal dominant
49
How many haplotypes of Huntingtons are they and what type of genetic feature causes it
4: A, B, C, D
| RFLPs
50
What genetics causes Huntingtons disease?
(CAG)n repeat which gives a poly glutamate run. n= 16-36 is normal, n= 42-56 is affected.
51
Fragile X syndrome:
(CGG)n repeats n>200. Increased methylation which causes reduced transcription of the surrounding genes.
52
Neurodegenerative disorders
(CAG)n n
53
Myotonic dystrophy:
(CTG)n n=200-4000. Large expansion in the 3' UTR that directly affects mRNA
54
Friedrichs Ataxia:
(GAA)n n=200-900. Affects the protein mitochondrial frataxin and reduces its transcription.
55
Haemoglobinopathies are inherited disorders of
Structure and synthesis of haemoglobin
56
How do you form a) adult haemoglobin (two types)
B) foetal haemoglobin
C) embryonic haemoglobin
And their percentages in adults
A2B2 97-98%
A2D2 2-3%
A2G2
57
What is the point mutation that can sickle cell anaemia
GAG to GTG
| Glutamate to Valine
58
What type of Hb disorder is caused by uneven crossing over
Hb Lepore
59
What are the commonest group of single gene disorders
Thalassaemias
60
What type of genetic disease are thalassaemias
Autosomal recessive
61
Beta thalassaemia is not due to
Deletions
62
Deltabeta thalassaemias result in
Persistence of foetal haemoglobin
63
Epistasis is
When 1 gene is dependent on the presence of one or more modifier genes
64
Genetic heterogenetiy is
Single phenotype/genetic disorder cause by multiple numbers of alleles or non allele mutations
65
Liability model
All the contributing factors to a disease
66
Heritability
The proportion of risk attributable to genetic factors
67
Phenocopy
Within a family there may be a susceptibility factor for a polygenic disease, but the disease occurs only due to environmental factors rather than genetics.
68
What locus is schizophrenia associated with and what are the problems of linkage analysis
Phenocopy and chromosome 6p which suggests an autoimmune aspect
69
Type I diabetes is what onset and what type of disease
Early onset, autoimmune disease
70
How can you identify type one diabetes
Nonparametric allele sharing, sib pair, whole genome scan, animal models
71
How many loci are now identified for type one diabetes is and what type of genetic action is occurring
>40 loci and HLA cluster is most important, autoimmune diseases. Epistasis and genetic homogeneity are observed
72
Factors contributing to TIID
Diet and obesity
73
How many loci associate with TIID
Around 30
74
Lipid metabolism contributes to cardiovascular disease by
Familial hypercholesterolaemia and behaves like an AD, there is high serum cholesterol and mutation of the low density lipoprotein receptor gene, lipid met is very poor
75
Hypertension is caused by:
Angiotensin - blood vessel constriction
| Angiotensin converting enzyme = activated angiotensin, polymorphism is associated with risk of heart attack
76
Three types of spongiform encephalopathy
1. Creutzfeldt-Jacob disease
2. Kuru
3. Gerstmann-strausller disease
77
Alzheimer's pathology
Neurofibrillary tangles and amyloid protein deposits
78
Symptoms of Alzheimer's
Personality changes, memory loss, veg state, death
79
Amyloid precursor protein
Chromosome 21, mutations in few early onset families
80
Prenisilin 1 & prenisilin 2
Chromosome 14 and chromosome 1 mutations in early onset families
81
Apolipoprotein E
Early and late onset forms, E2 & E3 are protective E4 gives increased Alzheimer's risk
82
Alzheimer's beta and gamma secretases are
Possible drug targets
83
Mosaics
More than one population of cells from the same genetic origin caused by non disjunction in embryogenesis, somatic/gonadal
84
Chimeras
More than one population of cells of different genetic origin. Caused by dispermy or blood exchange in uterine between non-identical twins.
85
Prenatal testing
Aminocentesis 16-18 weeks, removal of amniotic fluid and growth of foetal cells
Chorionic villus sampling, 11-12 weeks, remove chorionic villus, forms part of placenta
Both increased risk of miscarriage, both guided by ultrasound
86
Neonatal testing
Heel prick test
87
Molecular analysis involves
PCR based investigations of specific genes
88
How to find point mutations
Amplification Refractory Mutation System: make PCR primers f or specific mutations
89
DNA sequencing will pick up
New mutations and genes and unknown mutations
90
Treatment of genetic disease
Conventional, environmental, metabolic, gene replacement, surgery, tissue & organ transplant, stem cell therapy
91
Pleuripotent stem cells
Embryonic stem cells, can differentiate into any cells to create organs
92
Multipotent stem cells
Can make many cell types (not all) from mesenchymal stem cells (in bone marrow)
93
How is gene therapy carried out?
Potentially: gene replacement by targeted homologous recombination
Presently: add transgender and leave the defective gene
94
In vivo gene therapy
Transgene introduced directly into the body
95
Ex vivo gene therapy
Transgene introduced to cells outside the body and then inserted (transplanted back)
96
Germline therapy is
Correct the defect in the game or embryo So that all the cells are corrected
97
Somatic therapy
Only correct genes in defective cells/organ
98
Vehicles to introduce a Transgene
Viral - retro, adeno, lenti, efficient, but safety problems, (elaborate)
Physical methods - liposomes or receptor mediated endocytosis or direct DNA injection - inefficient but safe
Problems are inducing and sustaining high level gene expression
99
Targets of gene therapy
Bone marrow, liver, lungs, muscle (elaborate on all)
100
What is an example of gene therapy inducing cancer
SCID curing with retroviral vectors causes leukaemia due to insertion all mutagenesis near LMO2
