Genetics Flashcards
define the concept of precision medicine
give people the most effective treatment based on their genes as everyone is different
three ways DNA can be damaged?
- DNA strand breaks
- chemical crosslinking
- mismatched bases
which phase of the cell cycle does DNA replication happen?
S phase
four things that determine the amount of protein produced?
- rate of transcription
- rate of splicing of mRNA
- half life of mRNA
- rate of processing polypeptide
define polymorphism
variation in the human genome that has a population frequency of greater than 1% and in itself is not disease-causing.
define mutation
a gene change that causes a genetic disorder
three ways a chromosome can be recognised?
- banding pattern with specific stains
- length
- position of centromere
define acrocentric chromosome
short arm does not matter
describe balanced chromosome arrangement
all chromosomal material is present
describe unbalanced chromosome arrangement
extra or missing chromosome material
four chromosomal mutations
- aneuploidy- extra or missing chromosomes
- translocation- rearrangment of chromosomes
- insertions and deletion- missing or duplicated material
- micro deletions
define robertsonian translocation
two acrocentric chromosomes stuck end to end
molecular cytogenetics
detects small changes
array CGH
detects any size of imbalance but not balanced rearrangements
define mosaicism
different cells have different genetic constitution
define somatic mosaicism
two genetically distinct populations of cells derived from post zygotic mutations
Her2 amplification
monoclonal antibody- trastuzamab
philadelphia chromosome
tyrosine kinase inhibitor- imatinib
what does aCGH analyse for
deletions and duplications, but does not detect balanced arrangements
other methods that mutations can be detected?
PCR, next generation sequencing
what does a promoter mutation cause
- no, or reduced transcription
2. no, or reduced protein
define a missense mutation
single nucleotide change that results in a different amino acid
mutation nomenclature
c. is the effect on the mRNA
p. effect on peptide sequence
three things you may see if there is a genetic change
- disease-causing mutation
- polymorphism
- variant of unknown significance
define penetrance
likelihood of having a disease if you have a gene mutation
define 100% penetrance
you will get the disease if you have the mutation
define mendelian disorders
disease that segregate in families-caused by a change in a single gene.
examples of mendelian inheritance
- autosomal dominant
- autosomal recessive
- X-linked
- mitochondrial
define autosomal dominance
only need one gene to get the disease- passed through families
define autosomal recessive
two copies of the abnormal gene required- passed on through families.
define X-linked
mutation on the X chromosome causes disease
define multifactorial inheritance
many factors are involved in causing the condition.
cancer is a disease of?
somatic mosaicism caused by post-zygotic mutations
characteristics of a successful cancer cell
- proliferation
- evading immune response
- acquiring a vascular supply
- avoiding apoptosis
- metastasis
hall marks of cancer (6)
- self-sufficiency in growth signals
- insensitivity to anti-growth signals
- tissue invasion and metastasis
- limitless replicative potential
- sustained angiogenesis
- evading apoptosis
four genes involved in cancer
oncogenes
tumour suppressors
DNA repair genes
drug metabolism (metabolise carcinogens)
when cancer is sequenced there are two mutations that indicate cancer
- driver mutations
2. passenger mutations
methylation
addition of a methyl group which usually occurs on cytosine bases just before guanine bases
what does methylation cause
de-acetylation by modification of histones repressing transcription
methylation causes the environment to effect our genes?
yes
which mutation does methylation make more likely?
C to T
why do tumours get so many mutations?
the cells have a high rate of mutability and there is a loss of DNA repair
what determines the characteristics of cancer
driver mutations, not the tissue of origin
explain the two hit hypothesis
first hit is inherited mutation
second hit is an acquired mutation. However both can be acquired mutations
three mechanisms of gene activation
- duplication of a gene
- activation of the gene promoter
- change in amino acid sequence
define philadelphia chromosome
abnormal small chromosome
define caveat
female carrier who may have some mild features of an X-linked disease
define X-inactivation
females only have one active X-chromosome
define single nucleotide polymorphism
alteration in DNA sequence that is not in itself disease causing
define copy number variations
extra or missing stretches of DNA
non-mendelian inheritance disease examples
- methylation
- mitochondrial inheritance
- mosaicism
define psychological capability
ability to engage in the necessary mental processes
define physical capability
skill, strength or stamina
define reflective motivation
planning and evaluation
define automatic motivation
emotional reactions, desires, impulses, inhibitions, reflexes
define physical opportunity
opportunity afforded by the environment (time, resources, physical activity)
define social opportunity
opportunity afforded by social and culture norms
