IMMS HK Flashcards
Med 1
Describe the structure of DNA?
•Double helix •Complementary base pairs Adenine A= T Thymine Cytosine C G Guanine (3 lines in the bond) -- Coils around nucleosomes -- Coils again into super coils. -- and again into chromosomes > found in -nucleus --> mitochondria.
Describe chromosomes?
•Human genome –> 46 chromosomes–> each contains continuous DNA duplex/double stranded (10⁷ base pairs) –> several 100 genes.
• Centro-mere has Long arm (q) and short arm (p)
• Characterisically stained for identification and analysis with dyes.
> Giemsa - G banding
G banding, or Giemsa banding is a
technique used in cytogenetics to produce a
visible karyotype by staining condensed
chromosomes.
> Quinacrine -Q banding
is the first chromosome banding pattern
reported. It is done by treating the chromosomes
with quinacrine dihydrochloride.
(each band -> 6-8 Mbp mega base pairs)
What is mitosis for?
- Producing 2 daughter cells –>genetically identical to parent cell.
- Growth
- Replace dead cells.
What is the cell cycle?
• Mitosis –> G1 growth phase –> synthesis phase (–>DNA/centrosome replication) –> G2 growth phase –> Mitosis
(Interphase
What is the clinical relevance and pharmacology of mitosis?
- Detecting chromosomal abnormalities.
- Categorising tumours as benign/malignant
- Grading malignant tumours.
• Mitotic spindle
--> Taxol
--> Vinca alkaloids --> vinblastine/vincristine
• Anaphase --> colchicine-like drugs
• Spindle poles --> Ispinesib
What are the steps of mitosis?
PMAT
1) Prophase:
> chromatin condenses to chromosomes > centrosomes nucleate microtubules & move to opposite side of pole.
2) Prometaphase:
> nuclear membrane breaks down
> microtubules invade nuclear space.
> chromatids attach to microtubules.
3) Metaphase:
>chromosomes line up along equatorial plane (metaphase plate).
4) Anaphase:
> sister chromatids separate and are pushed to opposite poles of cell.
5) Telophase:
> nuclear membrane reforms, chromosomes –> chromatin cytokinesis begins
Describe meiosis?
•Similar to mitosis but differences > only in gametes > recombination of genetic material > diversity. • 2 cell divisions • 4 haploid cells • cross over in prophase 1 > genes sort independently. • Meiotic division 1 and meiotic division 2.
What is non-disjunction and how does Downs syndrome arise form it?
•Non-disjunction: > failure of chromosome pairs to separate in meiosis I or sister chromatids to separate in meiosis II. •Downs syndrome 75% maternal meiosis I > 25% maternal meiosis II > 3-5% paternal non-disjunction.
What is gonadal mosaicism?
One cell line normal and one cell line mutated.
• Occurs when precursor germline cells to ova or spermatozoa are a mixture of 2 or more genetically different cell lines. (parent is healthy but fetus has genetic disease).
> incidence increase w/ paternal age.
• Most commonly autosomal dominant/x linked.
• Osteogenesis imprefecta/duchenne muscular dystrophy
What are the different causes of disease?
Genetic (individually rare, cumulatively enough to have regional genetic services). •Downs syndrome •Cystic fibrosis •Huntington disease. •Haemiphilia
Multifactorial (main cause of disease in developed countries).
> Combination of environmental and genetic factors.
•Spina bifida
• Cleft palate
• Diabetes
• Schizophrenia
Environmental (main cause in developing countries + A+E) • Poor diet • Drugs • Infection • Accidents
What is the difference between genotype and phenotype?
- Genotype > genetic constitution of an individual.
- Phenotype > appearance of an individual (physical, biochemcial, physiological) which results from interaction of environment and genotype.
What is an allele and polymorphism?
Allele
•One of the several alternative forms of a gene at a specific locus.
>Normal allele is wild type
>Disease allele is carrying a pathogenic variant.
Polymorphism
•Frequent hereditary variations at a locus.
What are the different ways to describe alleles?
- Homozygous - both alleles the same at a locus.
- Heterozygous - alleles at a locus are different.
- Hemizygous - only 1 allele refers to a locus on an x chromosome in a male.
What is imprinting?
•For some genes, only 1 out of 2 alleles is active (the other is inactive).
> For particular genes, it is always paternal or maternal allele.
How do you classify a disease?
•Chromosomal
•Mendelian
> autosomal dominant - manifest in heterozygous state.
> autosomal recessive - manifest in homozygous state
> X-linked - pathogenic variants in X chromosome.
•Non-traditional.
>mitochondrial
>imprinting
>mosaicism
Discuss altering the germ line?
• Germ cell lineage -eggs and sperm
>alter the germline and affects future generations.
>potential harm unknown.
What is sanger sequencing?
MAYBE THIS CARD IS WRONG.
- Uses PCR to amplify regions of interest followed by sequencing of products.
- Useful for single gene testing
- (primer)
- Single DNA fragment sequnced.
- High cost per gene.
- Time consuming.
- Simple analysis
- Very accurate
- Less noise
What is next generation sequencing (NGS)?
MAYBE WRONG. • Multi gene panels • Can sequence whole genome. • High output/massively parallel sequencing. • Library of DNA fragments --> more noise. • Low cost per gene. • Fast • Huge amounts of raw data to interpret. • Moderately accurate.
What is GWAS?
Genome wide association studies.
• Utilizes the fact that a gene can have several allele variants.
(most genetic variation –> functioning gene) polymorphism.
• SNP (single nucleotide polymorphism) > more frequent in disease population.
What are environmental agents that act on embryogenesis?
- Drugs and chemicals
- Maternal infections
- Physical agents e.g. radiation.
- Maternal illness.
What is the liability/threshold model?
NEED PICTURE USE ZAHRAS FLASHCARD,
• Factors that influence development of a multi factorial disorder, genetic and environmental can be considered as single entity.
• Closer relationship, greater shift to right.
What is hereditability/heritability?`
MAYBE WRONG
• The proportion of aetiology that can be ascribed to genetic factors as proposed to environmental factors.
• Expressed as a proportion of 1 or %
• Can be calculated from concordance of MZ twins
What is the concordance rate?
is a term that is used in statistics and by geneticists to describe the rate of probability that two people with shared genes will develop the same organic disease.
What are family studies
- Compare the incidence of a disease amongst relatives of an affected individual w/ general population.
- (risk dramatically higher than in the general population)
- Risk varies directly w/degree of genetic relationship.
- Risk varies w/ severity of probands illness
- RIsk varies w/ no. of relatives affected.
What are twin studies?
- Compare genetically identical (MZ) w/ genetically non identical (DZ) twins.
- If condition –> genetic component –> concordance rate is high in MZ than DZ
concordance rate gives rough figure of hereditability of multi-factorial disorder.
MZ is found even when reared apart.
What are adoption studies?
- Adopted children of a parent w/ multi-factorial condition –> high risk.
- High compare above w/ group of adoptees w/ normal biological parents and adoptive parent w/condition –> low risk. (high in biological families.)
What are the characteristics of multi factorial inheritance?
- Incidence of condition is greatest amongst relatives of the most severely affected patients.
- Risk is greatest for 1st degree relatives.
- If there is >1 affected close relative, risks high.
What is homoplasmy and heteroplasmy?
• Homoplasmy
> an eukaryotic cell whose copies of mtDNA are all identical (identically normal or identical mutations.)
• Heteroplasmy
> multiple copies of mtDNA in each cell.
> denotes mutations which affect only a proportion of molecules in cell.
> level of heteroplasmy vary between cells in same tissue or organ, from organ –> organ in same person and between individuals in same family.
What is mitochondrial genetic disease?
• Group of disorders caused by dysfunctional mitochondria.
> caused by mutations in mtDNA (15%)
> caused by mutations in nuclear genes, whose gene product –> mitochondria.
> acquired conditions (can be due to drugs)
What are the categories of genetic disorders?
• Chromosome abnormalities
• Single gene disorders.
• Multi-factorial and polygenic disorder
> spina bifida/ cleft palate
