Strand 1 - genes Flashcards
Which nitrogenous bases are purine and pyrimidine?
Adenine and guanine are purine
Thymine and cytosine are pyrimidine
Which pair of nitrogenous bases bind via 2 hydrogen bonds and which via 3?
Adenine and thymine bond with 2 hydrogen bonds
Cytosine and guanine bond with 3 hydrogen bonds
What charge are DNA and histones?
DNA is negatively charged and histones are positively charged
What is DNA wrapped round a histone called?
Nucleosome
What do nucleosomes form when coiled?
Chromatin fibres
What do chromatin fibres form?
Arranged on a protein scaffolding to form a chromosome
Name 7 examples for non coding DNA
Introns
Viral DNA
pseudogenes
Genes for RNA
Tandem repeats
Telomeres
Promotor regions
Why do tandem repeats occur?
DNA polymerase III slips during DNA replication
What are telomeres?
Caps at the end of each chromosome for protection which get worn down over time
What are Pseudogenes?
They are mutated genes which have evolved to become inactive
Give 2 examples of coding RNA
MRNA
Viral genomes
Give two examples of structural RNA
RRNA
TRNA
Give two examples of regulatory RNA
MicroRNA
Xist
What is xist
Xist switches off one copy of X chromosome
What is another name for the template strand?
The antisense strand
What do single stranded DNA binding proteins do?
Keep strands unzipped
What does topoisomerase do?
Stops the strands from over coiling
What direction does DNA polymerase III add the bases?
5’-3’
How does DNA polymerase III remove incorrect bases?
Using 3’-5’ exonuclease activity
How is DNA replicated on the lagging strand?
Primer binds close to helicase forming Okazaki fragments which are joined by DNA ligase
What ingredients do you add to the test tube for PCR
DNA sample
Primers
DNA taq polymerase
Nucleotides
Buffer
What are the steps to carrying out PCR?
Denaturing (94-95)
Annealing (50-56)
Extension (72)
Repeat approx 30 times
What is a gene mutation?
An alteration in the nucleic acid sequence of the genome of an organism
How do mutations arise?
Errors during replication (point mutations/replication slippage)
Mutagens (radiation/chemicals)
What is the difference between purine and pyrimidine
Purine has two rings, pyramidine has one
What are the three types of RNA function?
Coding structural regulatory
What are three ways to prevent mutations?
Melanin (to protect DNA in the skin)
Peroxisomes (organelle that makes antioxidant enzymes)
Making good life choices
How do we repair mutations due to nicks (breaks of phosphodiester bonds)?
DNA ligase
How do we repair mutations due to single stranded damage to bases?
Base excision repair for small damage
Nucleotide excision for larger damage
How do we repair damage due to double stranded DNA breaks?
Non-homologous end joining
What does DNA polymerase III do to fix mutations in DNA replication?
Proofreading activity
For the mutations which DNA polymerase III can’t repair what happens?
Mismatch repair (4 proteins detect lack of H bonds between mismatched base pairs)
If there are too many mutations for the cell to repair what happens?
Apoptosis is initiated
What is a frame shift mutation?
Shifts the reading frame. Caused by deletions that are not in multiples of 3
What are the 4 types of mutation?
Frame shift
Silence
Missence
Nonsense
What happens with a silence mutation?
A base is substituted but it still codes for the same amino acid so no effect
What happens with a missense mutation?
Codes for a different amino acid. Only effects one so usually has small effect especially if similar shape/charge
What happens with a nonsense mutation?
Changes to a stop codon. Has big effect if at start of protein
What type of inheritance does cystic fibrosis follow?
Autosomal recessive
Why does cystic fibrosis occur and what does the mutation do?
Caused by mutation in gene encoding the CFTR protein. The CFTR protein is a membrane protein that transports chloride ions
How does the mutation in the gene encoding for the CFTR protein cause thick mucus?
Cl ions can’t exit the cells. Sodium then follows the Cl and exits the mucus into the the cell so there is less water in the mucus making it thick
What effects does having thick mucus cause?
In the lungs there are recurrent infections
In the pancreatic ducts there is malabsorption
What kind of condition is neurofibromatosis?
Autosomal dominant
(Half of the cases aren’t from parents and just occur due to mutation)
What are the two types of neurofibromatosis and what protein is damaged?
NF1 - Neurofibrin
NF2 - Merlin
Both proteins are normally tumour suppressor genes
What tumours are most common in NF1and NF2?
NF1 - neurofibromas
NF2 - schwannomas
What kind of condition is phenylketonuria?
Autosomal recessive
What protein is affected by phenylketonuria?
Phenylalanine hydroxylase
What does phenylalanine hydroxylase do?
Metabolises the amino acid phenylalanine
What kind of diet do you need to follow if you have phenylketonuria?
A strict phenylalanine free diet
What happens if phenylketonuria patients don’t follow a phenylalanine free diet?
Phenylalanine builds up in the body and damages the brain
Effects such as microcephaly (small head), intellectual disability, seizures
What type of condition is Huntington’s disease?
Autosomal dominant
What causes Huntington’s disease?
Caused by CAG repeats in the gene that codes for the huntingtin protein
What affects the severity of your symptoms in Huntington’s?
The amount of repeats on the gene that codes for the huntingtin protein
Gets progressively worse through generations as slipping of polymerase increases
What is genetic anticipation?
When a disease gets progressively worse through generations
Describe the anatomy of a normal metaphase chromosome
P arm = short arm
Q arm = long arm
Centromere in middle
Telomeres on the ends
Why is the photo of all the chromosomes lined up in order called
Karyotype
How do scientists identify chromosomes?
Size
Banding pattern
Centromere position
Which chromosomes are acrocentric?
13, 14, 15, 21, 22, Y
What abnormalities can be picked up on a karyotype?
Number of chromosomes
Material location
Amount of material
What is the word for having an abnormal number of copies of an individual chromosome?
Aneuploidy
What are the two types of aneuploidy called?
Monosomy - missing one
Trisomy - one extra
What is the word for having an abnormal number of sets of chromosomes?
Polyploidy (e.g monopolid, diploid, triploid)
What is the difference in chromosomes for people with Down syndrome?
They have trisomy 21
What are the clinical features of Down’s syndrome?
Characteristic facial features
Mild-moderate intellectual disability
Short stature
Congenital heart disease
Endocrine problems
Increased risk of leukaemia and Alzheimer’s
What change in the chromosomes causes Edward’s syndrome?
Trisomy 18
What are the clinical features of Edward’s syndrome?
Intra-uterine growth restriction
Most die during pregnancy
Overlapping fingers
Rocker-bottom feet
Congenital heart/kidney disease
Microcephaly (small head)
What change in chromosomes causes patau syndrome?
Trisomy 13
What are the clinical features of patau syndrome?
Intra uterine growth restriction
Most die during pregnancy
Cleft lip/palate
Extra fingers/toes
Brain abnormalities
Congenital heart disease
What syndromes does the 12 week pregnancy screening look for?
Edward’s, Down’s, Patau’s
What changes in chromosomes causes Klinefelter syndrome?
47 XXY
What are the clinical features of klinefelters syndrome?
Tall stature
Normal intellect,
Infertile
Little facial/ body hair
What changes in chromosomes causes turner syndrome?
Monosomy X
What are the clinicial features of turner syndrome?
Infertility
Short stature
Lymphoedema (puffy hands and feet)
Webbed neck
Endocrine abnormalities
Congenital heart disease
Normal intellect
What is a deletion in genetics?
Loss of a segment of genetic material from a chromosome
What is duplication in genetics?
Gain of a segment of genetic material from a chromosome
What genetic change causes di George syndrome?
22q11.2 microdeletion
What are the clinical features of di george syndrome?
Congenital heart and kidney disease
Nasal speech
Characteristic facial features
Hypocalcaemia
Intellectual disability
Increased risk of psychiatric disorders
What genetic change causes Prader Willi syndrome?
15q11 -q13 deletion
What are the clinical features of Prader willi syndrome?
Low tone at birth
Short stature
Characteristic facial features
Challenging behaviours and hyperphagia (excessive eating)
Intellectual disability
Incomplete pubertal development
What is translocation?
The relocation of chromosome material to the wrong place
What are the two types of translocation?
Reciprocal
Robertsonian
What is reciprocal translocation?
When 2 different chromosomes have exchanged segments with each other
What is robertsonian translocation?
An entire acrocentric chromosome attaches at another centromere
What pregnancy complications are associated with balanced reciprocal translocations?
Recurrent miscarriage
Multiple congenital abnormalities
What condition is reciprocal translocation the leading cause for?
Chronic myeloid leukaemia
What is the chromosomal abnormality that is the leading cause of chronic myeloid leukaemia?
Reciprocal translocation between chromosomes 9 and 22
Define locus?
Specific location on a chromosome
Define allele
Alternate forms of as gene at the same locus
Define homozygous
Both alleles at a gene locus are the same
Define homozygous
Both alleles at a gene locus are the same
Define heterozygous
The two alleles at a gene locus are different from one another
Define genotype
A persons DNA sequence at a particular locus
Define genotype
A persons DNA sequence at a particular locus
Define phenotype
A persons clinical features
Define phenotype
A persons clinical features
Define syndrome
A group of traits or conditions that tend to occur together and characterise a recognisable disease
Name 5 common autosomal dominant conditions
Huntingtons
BRCA 1 and 2
Neurofibromatosis
Autosomal dominant polycystic kidney disease
Marfan syndrome
What does it mean if a condition arises de novo?
Occurs for the first time in an affected individual without a family history
Name 4 common autosomal recessive conditions
Cystic fibrosis
Sickle cell anaemia
Spinal muscular atrophy
Phenylketonuria
Name 3 common x linked conditions
Duchenne muscular dystrophy
Fragile X syndrome
Haemophilia A
Name 2 common X linked dominant conditions
Rett syndrome
Craniofrontonasal syndrome
Describe the mitochondrial genome
Circular chromosome containing 37 genes
Why is there increased risk of aneuploidy with advanced maternal age?
Increase in nondisjunction and aneuploidy is often incompatible with life
What are some examples of conditions that become more likely with increased paternal age?
Achondroplasia
Noonan syndrome
Thanatophoric dysplasia
Osteogenesis imperfecta
Apert syndrome
Define penetrance
The likelihood that a clinical condition will occur when a particular genotype is present
E.g Huntingtons is penetrant
What is variable expressivity?
The range in signs and symptoms that can occur in different people with the same genetic condition
What is allelic heterogeneity?
Different pathogenic variants in a single gene associated with multiple different phenotypes
What is locus heterogeneity?
When one phenotype can be caused by pathogenic variants in multiple different genes
What is mosaicism?
When only some of an individuals cells have a specific variant
