Genetics Flashcards
What percent go the human genome in genes?
2-3%
Genotyope
Genes you have
Phenotype
the manifestation of the genotype
What damage can occur during DNA replication
DNA strands can ,break, chemical cross linking or mismatched bases
What is a chromosome made up of
DNA that is wrapped round proteins called histones and packaged into a chromosome.
Where is the information held in DNA
it’s held in the sequence of bases which are held on a sugar phosphate backbone
What occurs during cell cycle
G0 is the rest phase where the cell is a cell, G1 is where it begins to grow, S is where it synthesises another strand of DNA (DNA replication), G2 is another growth phase and M is where Mitosis occurs.
What occurs during DNA replication?
DNA is unzipped, on one strand DNA replicates in a straight line from its own 5’ to 3’, on the other strand it has to replicate in fragments
What occurs if the DNA repair mechanisms break?
it can cause disease
Mitosis
one parent diploid cell becomes two identical diploid daughter cells
Meiosis
One diploid parent cell becomes four haploid daughter cells
What is different about meiosis than mitosis
- crossing over occurs
- occurs in gamete formation
- diploid cell becomes four haploid cells
How is RNA different than DNA?
- single stranded
- ribose in backbone not deoxyribose
- uracil is used instead of thymine
Amount of protein produced is determined by
rate of transcription, rate of splicing mRNA, half life of mRNA, rate of processing polypeptide
briefly describe how is a gene turned into a protein
DNA is transcribed and spliced into mature mRNA and then it is translated into a protein
Promotor
identify translation start sites on mRNA
Start codon
regions of DNA where translation starts
stop codon
signal the end of polypeptide chain during translation
Stop codon bases
UAG, UAA, UGA
Start codon bases
AUG
Polymorphism
any variation in the human genome that has a population frequency of 1% or any variation in the human genome that does not cause disease
Mutation
A change that causes a genetic disorder or any heritable change in the human genome
How is a chromosome identified?
by its banding pattern, length and position of centromere
How many chromosomes do we have
46
What does the karyotype include?
number of chromosomes and sex chromosome complement
What do the lighter parts of the chromosome suggest?
they have more genes and are more transcriptionally active
Why do chromosomes look stripy?
they are looked at during metaphase
What does balanced chromosomal rearrangement mean?
all chromosomal material is present
What does unbalanced chromosomal rearrangement mean?
extra or missing chromosomal material, usually either 1 or 3 copies of some of the genome which can lead to disease
Aneuploidy
extra or missing chromosome
Translocation
rearrangement of chromosomes
Insertions and deletions
missing or duplicate material
Microdeletions
small parts of genetic material that are too small to be seen down a microscope
Name the parts of a chromosome
Telomere (top) Short arm (top arm) centromere (middle) long arm (bottom arm) telomere (bottom arm)
Acrocentric
the short arm of the chromosome doesn’t matter
What does having missing bits of a chromosome lead to
human disease
Trisomy 21
downsyndrome, caused by extra chromosome on chromosome 21 (47XY + 21)
Robertsonian Translocation
two acrocentric chromosomes stuck end to end
What does robertsonian translocation do?
increases risk of trisomy 21 in pregnancy.
why is X chromosome aneuploidy better tolerated?
because of x inactivation
reciprocal translocation productive risks
miscarriage (large segments), dysmorphic delayed Childs (small segments)
What does FISH allow you to do?
choose one chromosome segment and light it up with fluorescent dye
When is FISH useful
as some defects in chromosomes are so small that FISH has to be used, used widely in molecular analysis of cancers
What is array CGH
first line chromosome testing kit, it is genome wide and finds lots of polymorphisms but it’s technique is ‘DNA based’ and so reflects on underlying chromosomes.
Where does mutation come from
new mutations can happen in gametogenesis
Mosaicism
when a person has multiple genetically different cells
Somatic Mosaicism
genetic variation within the body of an individual
Why is every cell a mosaicism
because all cells suffer mutations as they divide
What can chromosome change lead to ?
activation of an oncogene (a gene that has the potential to cause cancer) or deletion of a tumour suppressor
HER2 gene
growth gene, found in breast cancer
Why is it important to identify chromosome change?
specific chromosome change can indicate treatment in cancer
ACGH
is used to analyse DNA, used for deletions, duplications for imbalance.
PCR
allows us to select one small piece of human genome from a patient and amplify it
disadvantage of PCR
can only sequence a bit of DNA at a time
Whats better than PCR?
Next generation sequencing
What does NGS allow
large scale sequencing, can sequence all exons or whole genome cheaply
Mutation
a genetic variation that causes disease
Polymorphism
a genetic variation that is prevalent in the population and not disease causing
promotor mutation
no or reduced transcription, no or reduced protein
what does altering splice consensus lead to
mRNA decay, abnormal or absent proteins
What does a base change that leads to a new stop codon lead to?
mRNA decay, short or absent proteins
What happens if a base change alters the amino acid sequence?
Different or non functioning protein
Missense
a base is replaced
Insertion
a base is inserted
Deletion (out of frame)
an amino acid is deleted, completely non functioning
deletion (in frame)
shorter than normal protein but still functioning
triplet expansion
one, three base codon repeats itself leaving you with multiple copies of amino acid
What his considered a normal sequence?
The most common sequence in USA
Wild Type
most common sequence
c.
change in mRNA sequence
p.
change in peptide sequence
Del
deletion
Ter/ *
stop and for peptide may be a nonsense
Ins
insertion
Val
Missense
Fs
frameshift
what do promoter and splice site sequence change do?
stop transcription or cause abnormal splicing
What does a base change causing an amino acid change do?
change in protein sequence, not every base change causes disease, this may or may not reduce protein function, some missense mutations make proteins work faster.
Trinucleotide repeat expansion
replicate of trinulcleotide
Advantages and disadvantages of next generation sequencing
advantages, higher sensitivity and cheaper disadvantages , don’t know what the genetic change actually is, it may be a disease causing mutation, a polymorphism or a variant of unknown significance
How to tell if it’s a polymorphism or disease causing mutation
does it match expected inheritance, is it in the right gene, has it been reported before and what does it do to the protein.
How many chromosomes do you have in each cell?
22 pairs of chromosomes and the sex chromosomes
difference between mosaicism and somatic mosaicism
somatic mosaicism can be present in gonadal cells
What things may a variant may be?
a disease causing variant, a variant of uncertain significance and polymorphism
What’s the variant classification
Class 1 is definitely a polymorphism, class 2 is probably s polymorphism, class 3 is unclassifiable, class 4 probably pathogenic and class 5 is definitely pathogenic
Penetrance
the likelihood of having a disease if you have a gene mutation
Mendelian disorders
a disease that is predominantly caused by a change in a single gene
What characteristic of a cancer cell is central allowing it to acquire further new characteristics?
Genomic instability
