Genetics and Genomics

Question 1

What is genetics?

Answer 1

-study of heredity
-units of info transferred from generation to the next
-passing of traits from parent to child - discrete unit

Question 2

What is genomics?

Answer 2

-structural and functional mapping of genomes and their evolution

Question 3

define gene

Answer 3

-a sequence of nucelotides that encode the sequence of amino acids that make up a protein (or nucelic acid molecule)

Question 4

What is the function of chromatin?

Answer 4

Package DNA in orderly process

Question 5

What is the function of histones?

Answer 5

Help package and regulate the DNA strand

Question 6

what nucleic bases are purines and which are pyrimidines?

Answer 6

purines- A, G
Pyrimidines- T or U in RNA, C

Question 7

What do we mean by DNA holds the code?

Answer 7

-central dogma of molecular biology
-DNA stably transmitted from mother to daughter cells
-uni directional
-two strands - forwards and reverse

Question 8

What characterisitics differ with each final protein structure of AA?

Answer 8

-Non polar side chains
-acidic side chains
-alkali side chains
-polar side chains

Question 8

Why are all versions of a gene not the same?

Answer 8

-gain of function mutations
-loss of function mutations
-lethal mutations
-ineffective mutation

alternative gene splicing-some genes produce more than one gene product

Question 9

Name some structural proteins

Answer 9

-collagen
-elastin
-keratin
-desmoglein
-tubulin

Question 10

Name some functional proteins

Answer 10

-enzymes
-ion channels
-neurotransmitter receptors
-antibodies
-active transporters

Question 11

Whats the difference between exons and introns?

Answer 11

exons- coding regions- protein sequence
introns-non coding regions-regulatory sequences

(alternative gene splicing)

Question 12

What is post- translational modifification?

Answer 12

-adding carbs
-adding lipids
-modifying AA side chains
-Adding chemical regulators

Question 13

What is a pseudogene?

Answer 13

non functional gene/ damaged gene sequence

Question 14

What are some key features of pseudogenes?

Answer 14

-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)

Question 15

What is diversity of output?

Answer 15

coding impacting of DNA and its utility in the body

Question 16

Describe the structure of the chromosome

Answer 16

-short arm- p
-long arm- q
ends are telemeres and p and q join at the centromere

-approx 1400nm

Question 17

Define genetic variation

Answer 17

non essential areas of the genome have increase variability

Question 18

Define genotype

Answer 18

someones complete set of genetic material including the various variant genes that they carry

Question 19

What are some cuases of genetic variation?

Answer 19

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)

Question 20

How do mutagens/ random events cause genetic variation?

Answer 20

-mitosis
-accidental damage to genetic material
-inappropriate DNA repair mechanisms following damage

Question 21

Give some examples of mutagens

Answer 21

-pollutants
-endogenous mutants
-viral insertions
-UV light
-ionising radiation

Question 22

Define polymorphism

Answer 22

inheritable change to DNA sequence, simply different from the bulk of the population - variant

inconsequential

Question 23

Define mutation

Answer 23

pathological change to DNA sequence, impact is detrimental to host

-consequential

Question 24

What is the difference between somatic and germline?

Answer 24

somatic-passed to dividing cells in tissues germline-passed from parent to offspring

Question 25

What are some effects of changes to DNA coding sequences?

Answer 25

-pathogenic -likely pathogenic -uncertain significance -conflicting interpretations -likely benign -bengin loss or gain of function

Question 26

What are relevant components clinvar?

Answer 26

-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

Question 27

What are some physical types of variants?

Answer 27

-single nucleotide variants (base pairs differ) -insertions/deletions (frameshift) -substitutions -structural variants (how many genes) -repeat variations (Microsatellites) -chromosomal variations (additional or deficient chromomes)

Question 28

Describe single nucleotide variants/ single nucleotide polymorphisms

Answer 28

-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

Question 29

What does non synonymous and synonymous mean?

Answer 29

S-same AA (Impact still possible) NS-different AA

Question 30

describe nonsense SNV's/ SNV is substituted ( stop/gain mutations)

Answer 30

-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

Question 31

What is the primary cause of AA subs?

Answer 31

replication slippage or slipped strand mispairing

Question 32

Describe large scale variations if major segments of chromones are alterd in CHD

Answer 32

-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

Question 33

Name some genetic variations

Answer 33

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

Question 34

Name some genetic tests

Answer 34

-single gene -panel (multiple genes/ haplotype) -clinical exome -whole exome -epigenetics -RNA- expression -single cell -whole genome -karyotyping

Question 35

Describe the bioinformatical pipelines for analysis (DONT HAVE TO REMEMBER)

Answer 35

1. Sample e.g., Cancer Tissue, Blood, Urine 2. Selection of optimal test i.e., what is best to answer the question 3. Sequencing occurs → Output specialist files (huge) 4. Data must be Quality Controlled 5. Data undergoes deep analysis 6. Results returned → Report generated 7. Bioinformation will add context → Results to requesting party 8. Clinical interpretation (differential diagnosis, impact) 9. Further discussion with MDT (subsequent testing) 10. Results and plan delivered by clinician and counsellor

Question 36

List some examples of genomic usage areas

Answer 36

-pre- screening -monitoring of high risk groups -cost effectiveness -reduce adverse drug reactions -reconfigure care servicces -preventative healthcare

Question 37

What is long QT syndrome?

Answer 37

-inhertited primary arrythmia syndrome -malignant arrythmis - rare risk of sudden death -17 subtypes,15 autosomal dominant genes

Question 38

What is bioinformatics?

Answer 38

-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