Genetics and Genomics Flashcards
What is genetics?
-study of heredity
-units of info transferred from generation to the next
-passing of traits from parent to child - discrete unit
What is genomics?
-structural and functional mapping of genomes and their evolution
define gene
-a sequence of nucelotides that encode the sequence of amino acids that make up a protein (or nucelic acid molecule)
What is the function of chromatin?
Package DNA in orderly process
What is the function of histones?
Help package and regulate the DNA strand
what nucleic bases are purines and which are pyrimidines?
purines- A, G
Pyrimidines- T or U in RNA, C
What do we mean by DNA holds the code?
-central dogma of molecular biology
-DNA stably transmitted from mother to daughter cells
-uni directional
-two strands - forwards and reverse
What characterisitics differ with each final protein structure of AA?
-Non polar side chains
-acidic side chains
-alkali side chains
-polar side chains
Why are all versions of a gene not the same?
-gain of function mutations
-loss of function mutations
-lethal mutations
-ineffective mutation
alternative gene splicing-some genes produce more than one gene product
Name some structural proteins
-collagen
-elastin
-keratin
-desmoglein
-tubulin
Name some functional proteins
-enzymes
-ion channels
-neurotransmitter receptors
-antibodies
-active transporters
Whats the difference between exons and introns?
exons- coding regions- protein sequence
introns-non coding regions-regulatory sequences
(alternative gene splicing)
What is post- translational modifification?
-adding carbs
-adding lipids
-modifying AA side chains
-Adding chemical regulators
What is a pseudogene?
non functional gene/ damaged gene sequence
What are some key features of pseudogenes?
-lack a start codon
-premature stop codon
-partially deleted gene sequence
-either do not produce protein or is non functional if they do produce some
-lack key regulatory regions (missing introns or promotors)
What is diversity of output?
coding impacting of DNA and its utility in the body
Describe the structure of the chromosome
-short arm- p
-long arm- q
ends are telemeres and p and q join at the centromere
-approx 1400nm
Define genetic variation
non essential areas of the genome have increase variability
Define genotype
someones complete set of genetic material including the various variant genes that they carry
What are some cuases of genetic variation?
1- sexual reproduction ( meiosis, heritable)
2-Genetic recombination events ( random crossovers, independent assortment of alleles)
3-random fertilization ( genetic drift, response to culture and environmental factor)
How do mutagens/ random events cause genetic variation?
-mitosis
-accidental damage to genetic material
-inappropriate DNA repair mechanisms following damage
Give some examples of mutagens
-pollutants
-endogenous mutants
-viral insertions
-UV light
-ionising radiation
Define polymorphism
inheritable change to DNA sequence, simply different from the bulk of the population - variant
inconsequential
Define mutation
pathological change to DNA sequence, impact is detrimental to host
-consequential
What is the difference between somatic and germline?
somatic-passed to dividing cells in tissues
germline-passed from parent to offspring
What are some effects of changes to DNA coding sequences?
-pathogenic
-likely pathogenic
-uncertain significance
-conflicting interpretations
-likely benign
-bengin
loss or gain of function
What are relevant components clinvar?
-databases work from a reference dataset
-predominantly european ancestry to offer global representation for reference
-variants will have a location on the chromosome/mapped
-gene will be identified, type of protein change advised
-associated conditions identified
-sometimes these are theoretical awaiting evidence
What are some physical types of variants?
-single nucleotide variants (base pairs differ)
-insertions/deletions (frameshift)
-substitutions
-structural variants (how many genes)
-repeat variations (Microsatellites)
-chromosomal variations (additional or deficient chromomes)
Describe single nucleotide variants/ single nucleotide polymorphisms
-missense mutation- a single nucleotide has been substituted for a different one
-may impact protein if code change switches AA
-non synonymous/synonymous
-body may compensate with another protein elsewhere - genetic redundancy
-protein imapct may be too severe- pathological
What does non synonymous and synonymous mean?
S-same AA (Impact still possible)
NS-different AA
describe nonsense SNV’s/ SNV is substituted ( stop/gain mutations)
-alteration of base= premature stop
Selection pressures- biological force that influences preference
-nature avoids having too many premature stop codons
-lesser SNP effects are better tolerated and so gaining a stop function is rare
What is the primary cause of AA subs?
replication slippage or slipped strand mispairing
Describe large scale variations if major segments of chromones are alterd in CHD
-variable presentation
-most common cyanotic fomr- TOF
-characterized by a ventricular septal defect
-duplication version-TOF form of CHD odds ratio 30.9 in favour versus a control
deletion version - non TOF form of CHD odds ratio 5.5 in favour versus a control
Name some genetic variations
deletion-loss of genes
-duplication-increase in whole genes
-insertion - new intro of gene that was not previously present
-inversion-direction of the read is different direction
-translocation- complete swap of genes or region
Name some genetic tests
-single gene
-panel (multiple genes/ haplotype)
-clinical exome
-whole exome
-epigenetics
-RNA- expression
-single cell
-whole genome
-karyotyping
Describe the bioinformatical pipelines for analysis (DONT HAVE TO REMEMBER)
- Sample e.g., Cancer Tissue, Blood, Urine
- Selection of optimal test i.e., what is best to answer the question
- Sequencing occurs → Output specialist files (huge)
- Data must be Quality Controlled
- Data undergoes deep analysis
- Results returned → Report generated
- Bioinformation will add context → Results to requesting party
- Clinical interpretation (differential diagnosis, impact)
- Further discussion with MDT (subsequent testing)
- Results and plan
delivered by clinician and counsellor
List some examples of genomic usage areas
-pre- screening
-monitoring of high risk groups
-cost effectiveness
-reduce adverse drug reactions
-reconfigure care servicces
-preventative healthcare
What is long QT syndrome?
-inhertited primary arrythmia syndrome
-malignant arrythmis - rare risk of sudden death
-17 subtypes,15 autosomal dominant genes
What is bioinformatics?
-storage of vast data- 2-14TB depending on format compressed or uncompressed
-annotation - labelling of the sequence map with genes and implication
-identification of variation from reference genomic datasets and different populations
-calculation of risk across population- polygenic score
