GiM week 2 Flashcards
what is epigenetics?
the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself
which end of a DNA strand is the phosphate group found on?
5’
what is another name for the coding strand of DNA (ie the one that mRNA is a copy of)?
sense strand
what are the small sections of DNA that are synthesised on the lagging strand of replicating DNA called?
and why are such sections only found on the lagging strand and not the leading strand?
okazaki fragments
because of the way the original dna is unzipped, the new daughter strand of dna on the leading strand is synthesised from 5’–>3’ in one long section but, on the lagging strand the dna on the daughter strand needs to be synthesised from 3’–>5’ but, since dna can only be synthesised in 5’–>3’ direction, the lagging strand is synthesised in chunks (okazaki fragments)
do all genes code for proteins?
no, some are just transcribed into RNA which is then used for other purposes like signalling and structure
what is a well known example of a promoter sequence before a gene?
TATA box
what happens after splicing at the 5’ end and the 3’ end of RNA?
5’ - guanine cap added
3’ - polyadenylation
what is the difference between an exon and an intron?
exons are kept in mature RNA and are translated
introns are removed from RNA by splicing
what is the benefit of alternative splicing?
one gene can code for more that one mRNA sequences (and thus more than one protein)
what are the two types of alternative splicing?
exon skipping
mutually exclusive exon choice
what are pseudogenes?
genes that were once functional, in our evolutionary history, but, due to mutation, are no longer functional
what are processed genes?
intronless copies of other genes
(produced by reverse transcription and reintegration [into the dna], for example by retroviruses)
if the processed gene has then undergone mutation, rendering it non-functional, it’s called a pseudo processed gene
occasionally remain functional, most are non-functional
what are the two types of repetitive dna?
satellite DNA - large blocks of repetitive DNA sequence
interspersed repeats - scattered around the genome
what does the word heterochromatic mean?
and what are heterochromatic chromosomal regions?
“differently staining” - ie they stain differently from most DNA
this is because they contain a lot of repeating sequences (satellite dna)
what is alphoid dna? and what is it used for in the study of genetics?
a type of satellite DNA found at centromeres on every chromosome.
but it is slightly different and unique to each chromosome
so if different staining methods are used, you can use the different alphoid DNA to differentiate between chromosomes and identify which is which
what is a SINE?
Short Interspersed Nuclear Element
they make up 5% of the genome
are often dispersed by RETROTRANSPOSITION (reverse transcription followed reintegration into the DNA)
have a role in generation of molecular pathology
what can interspersed repeats cause?
molecular pathology from unequal crossing over
ie during normal recombination between non-sister chromatids at meiosis, if there are interspersed repeats, the section of DNA that is swapped may be reattached at the wrong point (for example leaving chromatid A with two copies of gene 1 while chromatid B has no copies of said gene)
therefore this can lead to a genetic disorder (or there can be no phenotypic change)
Why is the deletion of an exon which has a number of base pairs that is a multiple of 3 less likely to result in a phenotypic change than if the number of base pairs was not a multiple of 3?
if multiple of 3: only causes deletion of whatever amino acids that exon coded for
if not: not only causes deletion of exon but also causes a frame shift for the rest of the gene and possible truncation of the mutated protein (if a premature stop codon is coded for)
what is Charcot-Marie-Tooth disease and what causes it?
CMT is a group of varied inherited disorders of the peripheral nervous system characterised by progressive loss of muscle tissue and touch sensation across various parts of the body. Currently incurable, this disease is the most commonly inherited neurological disorder
The most common cause of CMT (70-80% of the cases) is the duplication of a large region on the short arm of chromosome 17
what is duchenne muscular dystrophy caused by?
deletion of the dystrophin gene on the X chromosome
what is Haemophilia A caused by?
a ‘gross rearrangement’
INTRAchromosomal recombination (instead of INTER) occurs causing a segment of the X chromosome to be inverted
why are a lot of point mutations ‘silent’ in the phenotype?
because there are more codons than there are amino acids so more than one codon codes for each amino acid
so if the point mutation causes GAC to become GAT then both of these code for Asp so there will be no change in the phenotype
why are CG –> TG mutations so common (make up 1/3 of pathogenic mutations)?
because one of the ways that DNA is stabilised is that methylation occurs on C residues that are next to G residues.
However methylCytesine is very similar to tyrosine so during the next replication tyrosine can be incorrectly inserted instead of cytesine, thus causing a CG –> TG mutation
what can a point mutation at a splice junction cause?
mRNA insertion (as splicing occurs at wrong point), deletion and/or frame shift mutation
all –> possible pathology
when naming base pairs in a gene, what is number 1 always?
the A of the ATG (which codes for the start aa of methionine)
what does a * mean when talking about genetic codes?
a stop codon
also written as: ter
what is an example of a genetic bottleneck?
migration
The heterochromatic region on chromosome 1 is an example of this type of DNA…
satellite dna
what types of genes are enriched for CNVs?
olfactory receptor genes
huge variation in what things smell like to different people
what are most genes examples of?
single copy sequences
what is the name given to a mutation if it causes a substitution of an amino acid residue in a protein?
missense
what is the name given to a mutation if it causes a premature stop codon in a polypeptide, resulting in a truncated protein?
nonsense
As most amino acids have more than one possible three letter base code, the code is said to be…
degenerate
What is the chemical difference between ribose and deoxyribose sugars?
ribose has one more hydroxyl group than deoxyribose
what is CNV?
People have two copies of most genes, one copy inherited from each parent. In some cases, however, the number of copies varies—meaning that a person can be born with one, three, or more copies of particular genes. Less commonly, one or more genes may be entirely missing. This type of genetic difference is known as copy number variation (CNV).
Copy number variation results from insertions, deletions, and duplications of large segments of DNA. These segments are big enough to include whole genes. Variation in gene copy number can influence the activity of genes and ultimately affect many body functions.
Researchers were surprised to learn that copy number variation accounts for a significant amount of genetic difference between people. More than 10 percent of human DNA appears to contain these differences in gene copy number.
Language acquisition in humans is a consequence of variation in which gene?
FOXP2 gene
If mutation in this gene –> speech and language difficulties
(able to understand spoken words perfectly, but struggled to string words together in order to form a response.)
The FOXP2 gene is highly conserved between species. This means that the gene has a very similar DNA sequence in different species, suggesting it has not evolved much over time. The FOXP2 protein in the mouse only differs from the human version by three amino acids. The chimpanzee version only differs from the human version by two amino acids. These two changes in amino acids may be key steps in the evolution of language in humans.
scientists have concluded that FOXP2 is involved in the brain’s ability to learn sequences of movements. In humans this has translated into the complex muscle movements needed to produce the sounds for speech, whereas in other species it may have a different role, coordinating other movements.
what are the two different types of trinucleotide repeat expansions?
give examples of each
polyglutamine repeats (CAG) - eg huntingtons
large non-coding repeat expansions
- eg fragile X syndrome (transcriptional silencing)
- eg myotonic dystrophy
what is the genetic cause of fragile X syndrome?
CGG repeat expansion in the Fragile X Mental Retardation 1 gene (FMR1 gene)
if there are too many repeats then the gene cannot be transcribed and so is silenced
what general differences are seen between dominant and recessive inherited conditions? 3
(nb there are exceptions though!)
recessive - tend to be LOSS of function
dominant - tend to be GAIN (or alteration) of function
recessive - de novo mutations rare
dominant - de novo mutations common
recessive - often caused by lots of slightly different mutations (sufferers are often compound heterozygotes) - genetic testing hard
dominant - narrower mutational spectrum - genetic testing easier
what two factors may influence the likelihood of someone being a carrier of CF?
consanguinity
caucasian ethnicity more likely
what is familial adenomatous polyposis?
autosomal dominant
mutation in APC gene (tumour suppressor gene)
gene is 99% penetrant by age 40
lots of benign polyps in bowel
–> cancer (incredibly high colon cancer risk)
what are caspases?
a group of enzymes which are released when apoptosis is triggered
what happens to endothelial cells in acute inflammation?
they CONTRACT, thus leaving bigger gaps between them so proteins/cells/etc can get into tissues
