IMMS: Week 1 Flashcards
Describe the structure of DNA
Double helix which complementary base pairing (A-T + G-C) -> nucleosomes -> supercoils -> chromosomes
How many chromosomes are there in an individual
46
What is an autosomal chromosome
One that is not sex-determining
What are the sex chromosomes in males and females
Males - XY and Females - XX
What is a karyotype
The number and appearance of a chromosome in a cell, arranged in order of size
How are chromosomes arranged in a karyotype
Pair 1 is the LARGEST, pair 22 is the SMALLEST, sex pair is 23
How many base pairs does each DNA duplex have
10^7 base pairs
How many genes do we have
22,000
Describe the arms of a chromosome
Each has a p (small) and a q (long) arm
What is mitosis
The division of a parent cell into two identical diploid daughter cells
What is DNA not in replication called
chromatin
What is DNA during replication called
Chromosomes
What is DNA following replication called
Chromatids
What stage of the cell cycle do we have to be in so mitosis can occur
Interphase
What is the longest phase of the cell cycle
Interphase
What happens in G1
No visible activity: Rapid Growth Normal Metabolic Function New Organelles produced Protein synthesis of those involved in spindle formation
What happens in synthesis
DNA doubles through DNA replication
Histone proteins double through protein synthesis
Centrosome replication
What happens in G2
Chromosomes condense
Energy stores accumulate
Mitochondria and centrioles double
What happens in prophase
Chromatin condenses into chromosomes
Centrosomes nucleate microtubules and move to opposite poles of the nucleus
What happens in metaphase
Chromosomes line up along the equatorial plane
What happens in anaphase
Sister chromatids separate and are pushed to opposite poles of the cells, centromere first as spindle fibres contract
What happens in telophase
Nuclear membrane forms
Chromosomes unfold into chromatin
Cytokinesis begins
What happens in cytokinesis
Cell organelles are distributes evenly across the two daughter cells
Cytoplasm divides
What is Down Syndrome
An extra chromosome at 21 (trisomy 21)
How can we tell on histological slides if a cell is undergoing mitosis
Dark nuclei and if the nuclei are not all the same size
Is meiosis a cycle?
No
What is the product of meiosis
4 haploid daughter cells which are distinct from each other and the parent cell
Where does crossing over of sister chromatids occur
meiosis 1 when chromosomes pair up into homologous pairs
Where does random assortment of chromosomes occur
In metaphase 1
What is the product of oogenesis
One egg cell and two polar bodies
Define non-disjunction
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division
Name the two types of non-disjunction
Failure of separation of homologous chromosomes - meiosis I
Failure of sister chromatids to separate - meiosis II
What condition can this result in
Down Syndrome
Define Gonadal mosaicism
When precursor germline cells are a mixture of two or more genetically identical cell lines
One cell line is normal, the other is mutated
How can incidence of gonadal mosaicism increase
Increasing paternal age
Is gonadal mosaicism more common in males or females
Males
Is the parent also affected with gonadal mosaicism. Explain your answer
No because it results from mutation of the germline and not via inheritance
What inheritance pattern is usually seen with gonadal mosaicism
Autosomal dominant or X-linked
How common are genetic diseases
Not very rare but enough for us to make services which tailor to these conditions
Four examples of genetic diseases
Huntingtons
Cystic Fibrosis
Downs Syndrome
Haemophilia
What are multifactorial diseases
A combination of genetic and environmental factors
What is the main type of disease affecting developed countries
Multifactorial
Four examples of multifactorial diseases
Diabetes
Spina Bifida
Cleft Lip
Schizophrenia
What is the main cause of disease in third world and A&E
Environmental
What chromosomes are autosomal
1-22 (No sex chromosome)
What is a locus
The position of a gene/DNA on the genetic map
What is a genotype
Genetic constitution of an individual
What is a phenotype
Appearance of an individual which results from the interaction with the environment and genotype
What is an allele
One of several alternative forms of a gene at a specific locus
What is polymorphism
Frequent hereditary variations at a locus that do not cause problems.
How can polymorphisms affect you
Makes you more/less efficient or make you more/less susceptible to disease
Define consanguinity
Reproductive union between two relatives
Define autozygosity
Homozygous by descent (inheritance of the same mutant allele through two branches of a family tree)
Define homozygous
Both alleles at a specific locus are the same
Define heterozygous
Alleles at a locus are different
Define hemizygous
Describe that are carried on an unpaired chromosome (refers to X chromosome on a male)
Define penetrance
Proportion of people with a gene/genotype who show the expected phenotype
Define complete penetrance
Gene or genes for the trait are expressed in all the population
Define incomplete penetrance
Gene or genes for the trait are expressed only in parts of the population
Define variable expression
Variation in clinical features (type and severity) of a genetic disorder between individuals with the same gene alteration
Define sex limitation
Expression of a particular characteristic limited to one of the sexes
Define a multifactorial condition
Due to a combination of genetic and environmental factors
Define late-onset
Condition that hadn’t manifested itself at birth
Define autosomal dominant
A disease that only manifests itself in the heterozygous state
Why can both parents be unaffected by a disease even if the son has it (3 reasons)
- Gonadal mosaicism
- Variable (incomplete) penetrance
- Only way to pass it is from male to male
These are all seen with autosomal dominant conditions
Define autosomal recessive
A disease that manifests itself in the homozygous state only.
What is the chance of an offspring getting the disease if its autosomal recessive
25%
What is the chance of offspring being a carrier if its an autosomal recessive disease
50%
What is the chance of a healthy sibling being a carrier
2/3
What is the most common autosomal recessive disease in whites
Cystic Fibrosis
Does cystic fibrosis have complete or variable penetrance
Variable
Incidence of cystic fibrosis in the UK
1 in 25,000
Define X-Linked inheritance
Caused by a mutation in genes on the X-chromosome
Can an X-linked disease be passed on from father-to-son? and why?
No, never not even carriers
Because sons always get their X chromosomes from their mother
What are all daughters from an affected male (X-Linked disease)?
Carriers
NOTE: All males will be unaffected
What gender are X-linked disorders usually transmitted through
Females
Define lyonisation
The process of X chromosome inactivation
When is X chromosome inactivated
During embryological development
Why is the X chromosome inactivated during lyonisation
Prevents them from having a double number of X chromosome gene products compared to males
ONLY ONE X chromosome will be functional
What is a BARRBODY
Inactive X chromosome which is packaged in heterochromatin
What is the result of packaging an X-chromosome into heterochromatin
Prevents it from being transcripted
What is heterochromatin
Chromosome material of greater density than normal chromosome. Here the activity of genes are suppressed
What is imprinting (non-mendelian)
For some genes only 1 out of 2 alleles are active, the other is inactive (could be either that the maternal or paternal allele is inactive)
What is Knudson’s 2-hit hypothesis
Gene mutations may either be inherited or acquired during a person’’s life
What causes a sporadic cancer
2 acquired mutations
What causes hereditary cancers
1 inherited mutation + 1 acquired mutation
What is an ‘ideogram’
Diagrammatic form of chromosome bands, bands are numbered according to distance to the centromere
What is the mendelian classification of genetic disease
Autosomal dominant/recessive or X-linked
What is a non-traditional genetic disease
Mitochondrial (all mitochondria is inherited by the mother), imprinting or mosaicism
What is a square in a genetic pedigree
Square = male Circle = Female
What is epithelia needed for
Protection, absorption and secretion
What are four examples of supporting tissues
Blood, tendons, bones and cartilage
What are three types of muscle
Smooth, skeletal and heart
What does haematoxylin stain
Acids blue
What does eosin stain
Alkaline pink
What substances does haematoxylin stain
Cell nuclei and RNA blue
What does eosin stain
Cytoplasm and colloidal proteins pink
Keratin - Orange/red
ECF
Do water extra-cellular jelly and fat stain
No
What does Alcian Blue stain
GAG rich structures blue
Goblet cells blue
Mast cell granules blue
Stain cartilage matrix blue
What does iron haematoxylin stain
Nuclei and elastic fibres black
What does PAS stain
Hexose sugars (e.g. goblet cell mucous cartilage matrix, glycogen, basement membrane and glycocalyx) pink
What does touluidine blue stain
Nuclei, ribosomes and cytoplasm dark blue
Cartilage matrix and mast cell granules pale blue
GAG bright purple
Role of the nucleus
Houses DNA as chromatin within the nucleolus
Nucleolus produces RNA
Role of the mitochondria
Site of oxidative phosphorylation
Double membrane (highly folded inner)
What happens in the outer membrane of the mitochondria
Lipid synthesis and fatty acid metabolism
What happens in the inner membrane of the mitochondria
Respiratory chain (electron transport) ATP production
What happens in the mitochondrial matrix
Krebs’ cycle
What take place in the mitochondrial intramembranous space
Nucleotide phosphorylation
Role of the RER
Site of protein synthesis
Role of SER
Site of membrane lipid synthesis
Processes and stores synthesised proteins
Role of the cis golgi
Receives SER vesicles and phosphorylates proteins
Role of medial golgi
Modifies products by adding sugars (to form oligosaccharides) to lipids and peptides
Role of the trans golgi network
Proteolysis of peptides into active forms and sorting of molecules into vesicles which bud from the surface
Where is the golgi apparatus located
Close to the cell nucleus
Can I see the golgi apparatus in most cells?
No, but seen clearly in plasma cells
