Genetics Flashcards
where is DNA found in a cell?
- mainly in nucleus
- some found in mitochondria
what is the structure of a chromosome?
- chromatin fibres made up of histones wrapped in DNA
- chromosomes come in pairs, one from the father and one from the mother
what would we use to study chromosomes to identify abnormalities, congenital disorders, and cancer development?
- light microscopy
what is the locus?
- the position of a gene on a chromosome
what are the 4 DNA bases?
- Adenine and Thymine
- Cytosine and Guanine
what does the centromere do?
- divides the chromosome into the short arm and longer arm
what is the telomere?
- the structure at the end of a chromosome
what is meant by the term genome?
- all of the DNA found in one cell
- the human genome is made up of nuclear and mitochondrial DNA sequences
what are the aims of the human genome project?
- to determine the nucleotide sequence of the transcriptionally active parts of the human genome
- and to define the position (locus) of each gene on the chromosomes
how many chromosomes do human cells contain?
- 46 chromosomes (23 pairs)
how many protein-coding genes does the human genome contain?
- fewer than 20,000 protein-coding genes, but it also contains many other regulatory elements that affect the transcription and translation of genes
what is meant by the term gene?
- a gene is a particular sequence of DNA found on a locus on a chromosome
What is apoptosis and what is it characterised by?
- programmed cell death (characterised by chromatin degradation)
What are the 3 main changes that occur when a cell becomes tumourigenic?
- Immortilisation: property of indefinite growth
- The cell fails to follow normal growth constraints: cell growth usually relies on the expression of growth factors, tumour cells become independent of these controls
- Invasion: the ability to invade normal tissue and spread to other organs (metastasis)
The cell depends on multiple extracellular signals…
- many cells require multiple signals (green arrows) to survive
- additional signals (red arrows) to divide
- and still other signals (black arrows) to differentiate
The hallmarks of cancer…
What are the 3 types of heritable changes in cancer cells?
- dominant driver mutations in oncogenes
- recessive driver mutations in tumour suppressor genes
- epigenetic changes (the gene is not altered in DNA sequence)
What can the heritable changes of cancer cells lead to in terms of functional change in the operation of the cell?
- a protein might be over expressed or under expressed
- a protein might change its function
- it might produce a change in the regulation of a pathway
Types of changes in cancer genome…
What are the 2 groups which mutations are separated into based on their effect on the function of a cell?
- Driver mutation: an alteration that gives a cancer cell a fundamental growth advantage for its neoplasmic transformation
- Passenger mutation: has no effect on the fitness of a clone but may be associated with a clonal expansion because it occurs in the same genome with a driver mutation
(many more passenger mutations than driver mutations)
How do mutated oncogenes affect the way in which proteins are expressed?
- the protein expressed by a mutated oncogene usually has a lack of regulation or has increased activity
What are leukemias?
- blood cancers
Philadelphia chromosome…
- this is an example of chromosomal translocation
- this upregulates expression of an oncogene by fusing the gene with a promoter region that is always switched on or active
What type of mechanism is seen in the MYC family of oncogenes to mutate/activate them which leads to increased expression of a protein?
- amplification
- this can mean that there are 10 to 100 copies of an oncogene sequence
- multiple copies of the oncogene leads to increased expression of the protein
What is the normal role of tumour suppressor genes?
- to restrain uncontrolled cell division
- eg. controlling the passage through the cell cycle so that any DNA damage can be repaired
- eg. or by triggering apoptosis in response to DNA damage
- (eg. TP53, Retinoblastoma gene)
What is retinoblastoma and what is it caused by?
- Retinoblastoma is a human childhood disease involving a tumour of the retina
- it is caused by loss of both copies of the RB gene on chromosome 13
Are tumour suppressor genes dominant or recessive at cellular level?
- recessive
What is the role of the TP53 gene?
- ‘guardian of the genome’
- regulates cell division
- when there is DNA damage, the p53 protein has a role in deciding whether the cell can be repaired (activates other genes to fix the damage) or needs to be destroyed (p53 stops cell from dividing and signals apoptosis to occur)
- (therefore the TP53 gene is frequently inactivated in cancers)
Li Fraumeni syndrome is a rare autosomal disorder caused by what?
- caused by inherited mutations of TP53
- affected people are likely to develop cancer in their lifetime
What are the 4 main risk factors associated with increased risk of cancer?
- Germline or inherited mutations
- Carcinogens
- Age
- Obesity
(image shows diagram of preventable cancers)
What is the difference between germline mutations and somatic mutations?
- germline mutations: occur in genome of the human body
- somatic mutations: occur in genome of the tumour
What are carcinogens and what are the 2 classes?
- Carcinogens may be chemicals, infectious agents, or different forms of radiation (eg. tobacco smoke, ionising radiation, sunlight etc.)
1. Initiators: that predispose cells to develop tumours
2. Promoters: stimulate tumour development
How is obesity a risk factor in causing cancer?
- fat cells make extra hormones and growth factors
- hormones and growth factors tell cells in our body to divide more often
- this increases the chance of cancer cells being produced
- which can then continue to divide and cause a tumour
give two examples of autosomal recessive disorders
- cystic fibrosis
- sickle cell anaemia
give an example of an autosomal dominant disorder
- Huntington’s
what is a gene?
- a long, specific sequence of DNA that usually codes for proteins
describe the structure of a chromosome
- chromatin fibres made up of proteins called histones wrapped in DNA
- centromere divides the chromosome (short and long arm)
how many chromosomes does a person have?
- 46 (23 pairs)
Describe the major modes of Mendelian-monogenic inheritance
- Monogenic inheritance - caused by defects in one particular gene and often simple and predictable inheritance
- but can be variable penetrance (chance that a genotype results in expected phenotype)
- seen with eg Hereditary Heamochromatosis (low penetrance), Huntington’s Chorea (near complete penetrance)
- and can be Mutifactorial (genetic + environmental)
Describe polygenic inheritance, and discuss the contribution of genetic factors to commmon multifactorial diseases
- Polygenic inheritance = inheritance and expression of phenotype determined by many genes at different loci
- traits with continuous distribution (eg. blood pressure and height) often determined by interplay of many alleles at different loci
- Multifactorial: require interaction of environmental and genetic factors (eg. Diabetes, Cardiovascular Disease and Schizophrenia)
- (note: can see in eg. twin studies - same genetic make up)
What are the 3 types of alterations which functionally alter the cell as the cell reproduces which are inherited?
- Inactivation of tumour suppressor genes - normal role is to restrain uncontrolled cell division
- Dominant activation of oncogenes - (oncogenes involved in pathways regulating growth)
- Alterations in regulation of expression of genes (epigenetic changes - do not alter gene sequence but include DNA modifications such as methylation of DNA))
- (note: can lead to gene expression occurring in wrong place at wrong time)
What are the two types of genetic mutation?
- DRIVER mutation: alteration in genome of a cancer cell that gives a growth advantage
- PASSENGER mutation: no effect on fitness of cell but detected as in same cell as mutation in driver gene. Repliactes rapidly as cell multiplying rapidly = hitchhiker in evolutionary biology
Discuss the patterns of inheritance and types of mutation associated with the common muscular dystrophies and ataxias
Duchenne Muscular Dystrophy…
- X-linked recessive
- alterations to Dystrophin coding gene (large gene)
- incidence - 1 in 3500 males.
- Dystrophin stops muscle cell membrane tearing with contraction and relaxation.
- see increase in CK in blood
Becker Muscular Dystrophy…
- X linked
- affects Dystrophin
- milder than DMD therefore later onset
Myotonic Dystrophy: Autosomal dominant
Friedrich’s Ataxia…
- progressive neurodegenerative movement disorder usually onset symptoms from 10-15 years age
- autosomal Recessive 1 in 50 000
- affects ability to co-ordinate voluntary movements
- trinucleotide repeat expansion
Autosomal Dominant Cerebellar Ataxia…
- Trinucleotide repeat expansion
- onset as adult
What are the features of Duchenne Muscular Dystrophy
- X linked recessive
- Progressive degeneration of muscle fibres and Weakness
- Dystrophin affected
- 1 in 3500 males
- Onset 3-5 years
- Difficulty walking and Waddling gait
- Gowers’ sign (getting up from floor by going on all fours and walking hands up legs) and Toe walking
- Pseudohypetropy - especiallly calves as muscle replaced by collagen and adipose tissue
- Scoliosis and Contractures
- Low IQ
- Dilated cardiomyopathy
- Death 15-25 years from cardiac or respiratory failure
What are features of Becker Muscular Dystrophy
- X linked recessive- in frame mutation of Dystrophin gene
- 1 in 30000 males
- Slowly progressive
- Onset from 7 yeras (mean 11y)
- Proximal muscle more affected
- Gowers’ sign and Toe walking
- Severity depends on Dystrophin levels (milder than Duchenne)
- Calf pseudohypertrophy, cardiomyopathy, respiratory muscle involvement, scoliosis, mild learning difficulties
Myotonic Dystrophy
- Autosomal dominant
- 1 in 8000
- Adult onset
- Slowly progressive multisystem - eg. myotonic facies, cardiomyopathy, muscle wasting, cataracts, endocrine - diabetes
- Can show anticipation - disease gets progressively worse / symptoms earlier in generations
Nucleic acids, genes, and genomes quiz Q1…
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Nucleic acids, genes, and genomes quiz Q7…
