Normal and abnormal development: genetic, congenital and acquired disease Flashcards
When do genetic diseases materialise
Early in childhood
Other than environmental and genetic causes of a disease, what else results in a disease
- Other diseases predisposing you to causative factors
How do other disease pre-dispose you to others
- Pre-neoplastic conditions (diseases pre-disposing to tumours)
- Permissive effect
What is a permissive effect
Environmental agents that are not normally pathogenic will cause a disease.
What two ways other than genetic abnormalities can increase disease risk in a baby
- Nutritional deprivation
2. Transplacental transmission of environmental agents
What four reasons are there for an increase in disease incidence with age
- Probability of contact with an environmental cause increases with duration of exposure risk
- Disease may depend on cumulative effects of one or more environmental agents
- Impaired immunity with ageing increases susceptibility of some infections
- Latent interval between exposure causes appearance of symptoms to take decades
what are two outcomes of polymorphic variations
- Changes in characteristics (brown hair vs blond)
2. No visible effects at all (e.g. blood types)
Name three polymorphic variations that give the greatest disease susceptibility to an individual
- HLA Types
- Blood groups
- Cytokine genes
What are HLA genes normally referred to as
antigens
What are class I antigens
- Expressed on the surface of all nucleated cells (recognised by immune system)
What are class II antigens
- Expressed on the surface of cells that interact with T lymphocytes by physical contact - initiate immune response
Two ways diseases may be associated with HLA types
- Infective microbes may have similar antigens to host cells
- Gene predisposing to a disease is closely linked to HLA gene
What HLA group is found on organs/cells that are subjected to autoimmune attacks
- Express class II types
What two diseases are closely related to blood groups
- Duodenal ulceration - group O
2. Gastric carcinoma - group A
How many gene tend to be involved in most inherited abnormalities
A single gene - these conditions are monogenic
How many base pairs are found in each of the 23 pairs of chromosomes
10^7 base pairs
Describe the structure of DNA
- Wrapped as a double-helix around histone proteins - nucleosomes
- DNA strands then coiled to form a chromatin fibre
How many pairs of chromosomes are called autosomes
22
What proportion of nuclear DNA encodes for functional genes
10%
What is the role of ‘satellite’ DNA
Maintains chromosome structure
Where are telomeres located
Found on the ends of each chromosome
Role of telomeres
Needed for chromosomal replication
What happens to the DNA when there is a lack of telomerase
The telomeres shorten with each mitotic division until the cell is incapable for further replication
define a centrimorgan
the distance between two gene loci
How does the process of gene linkage and recombination show
allows defective genes to be identified by tracking inheritance of neighbouring DNA in affected individuals and families
How many base pairs are found in the homeobox genes
183 base-pairs
What two ways are HOX genes controlled by
- Endocrine regulation
2. Vitamin A
Mitochondrial DNA vs nuclear DNA
- Circular double-stranded conformation
- High rate of spontaneous mutation
- Few introns
- Maternal inheritance
looks liked bacterial dna
Why are mitochondria derived from the cytoplasm of mother’s ovum
- The head of the fertilising spermatozoon consists of the entire nucleus
What gender will mitochondrial disorders effect the most
Male and females equally
What do genes in mitochondrial DNA encode for
Enzymes in oxidative phosphorylation
What would mitochondrial defects tend to effect
tissues with high energy requirements like neurones and muscle cells
Define alleles
Two genes at an identical place on a parr of chromosomes
Define heterozygous
Allele at a particular locus are different
In what genotype are recessive genes expressed in
Homozygous
Define karyotype
The chromosomal constitution of a cell or individual
What colour can we use to see the 46 chromosomes in human nuclei more clearly
Colchicine
How does Colchicine allow the 46 chromosomes show up
Inhibits polymerisation of tubulin, preventing formation of the mitotic spindle along which the chromosomes migrate and block cell division in metaphase.
How does counting the 46 chromosomes help with abnormal chromosomes
SHOW ABNORMAL NUMBERS OF CHROMOSOMES (TRISOMY)
How often do random polymorphic variations occur in nuclear DNA
1 in 200 base pairs
In what two ways can polymorphic variation arise
- Substitution of a single base on the DNA strand
2. Presence of variable numbers of tandem repeats of base sequences
How are variations in DNA detected
By determining variations in size of DNA fragments collected
What is the PCR technique
- Primers bind to complementary base pairs on the DNA template strands
- DAM polymerase amplifies DNA fragment
- High temperature to separate DNA strands
- free nucleotides incorporate not newly synthesised DNA segments.
What two disorders can single gene defects cause
- Structural
2. Metabolic
What genotype do you need to have inherited a single gene defect that results in biochemical abnormalities
Recessive
What genotype do you need to have inherited for a single gene defect that results in structural abnormalities
Dominant
What four ways can result in a single gene defect
- Deletion of a gene
- Point mutation (substitution of a nucleotide)
- Insertion/Deletion
- Translocation
What are the main three outcomes of a genetic alteration
- Loss of function
- Gain of function
- Lethal
Define toxicology
Study of environmental chemicals that cause disease
What is the effect of acid/peroxides on tissues
- Digest or denature proteins
- Damage structural integrity of the tissue
- Necrotic effect on skin cells
How do chemicals cause disease metabolically
They can interrupt the metabolic pathway
How can chemical agents effect DNA
Can cause genetic mutations (mutagens)
- Teratogenic
- Carcinogenic
Define teratogenic
chemical agents effect embryogenesis leading to congenital malformations
How can small molecules act as haptens in the body
They are too small to act as an antigen but accomplish this by binding to a larger molecule
What part of a cigarette causes cancer
The carcinogens (hydrocarbons) in the smoke can cause tumours + carbon monoxide
Define trauma
Mechanical injury to tissues
Define pyrexia
Increased body temperature
Where is pyrexia mediated
Interleukins on the hypothalamus
Why is local heating of the skin dangerous
Coagulates proteins and disrupts structure and function of cells
Define these terms:
First degree burns
Second degree burns
Third degree burns
- Skin redness
- Epidermal necrosis and blistering of skin
- Epidermal and dermal necrosis
How is thermal injury useful in clinical environments
Can be used to coagulate tissues and stop bleeding
Define a congenital disease
Present at birth
Define inherited disease
Caused by inherited genetic abnormality
Define acquired disease
By non-genetic environmental factors
Define hypertrophy
Increase in size of tissue caused by an increase size of the constituent cells
Define hyperplasia
Increase in size of tissue caused by an increase in NUMBER of constituent cells
