Genetics Flashcards
What direction is the DNA chain read?
5 Carbon — 3 Hydroxyl (strands in antiparallel fashion)
What are the bases in DNA vs RNA
A-T, C-G
A-U, C-G
Describe the formation of a chromosome
Association of the DNA strand with histone proteins which wind together
Define G0 phase of the cell cycle
Most cells are resting, carrying out their normal function
Define G1 phase of the cell cycle
1st growth phase as chromosomes become ready to be replicated
Define S phase of the cell cycle
DNA replication occurs
Define G2 phase of the cell cycle
2nd growth phase involving proteins etc.
Define M phase of the cell cycle
Mitosis - mechanical separation of cell into two daughter cells
Two daughter cells are identical, diploid cells
PMAT: prophase, metaphase, anaphase, telophase
Variation occurs during meiosis by two main methods, which are?
Crossing over
Independent segregation of homologous chromosomes
In meiosis, one diploid cell becomes..
Four haploid daughter cells
Describe the process of transcription and translation from DNA into a protein
DNA is transcribed to pre mRNA
Pre mRNA is spliced to mRNA
mRNA is translated to protein
Protein is modified and modified around the cell
What is the difference between introns vs exons?
INTRONS: non coding sequences of mRNA not in final protein (spliced out)
EXONS: coding sequence of mRNA not in final protein (1-2% codes)
Give examples of sequence variations between genes and within genes respectivey
Single nucleotide polymorphisms (SNPs) Deletions/duplications
Changes in promotor or exon sequence
Copy number variations (CNVs) - extra or missing stretches of DNA
A polymorphism is…
A change in the genome that does not cause disease in its own right, but can predispose to a common disease (has a population frequency 1%)
Each copy of the genome is slightly different. True/False?
True
Everyone has new genetic variants that their parents don’t
New mutations are also acquired during meiosis
What percentage of the human genome is exons?
2-3% of 30 million bases
A chromosome consists of…
Telomeres at each end
Short arm (p)
Centromere
Long arm (q)
A chromosome is acrocentric if…
The p (short) arm is so short it is hard to observe
An aneuploidy is…
An abnormal number of chromosomes
Monosomy - missing chromosome from one pair Trisomy - extra chromosome in a pair
Reciprocal translocations are when…
Segments from two different chromosomes have been exchanged
Robertsonian translocations are when…
A chromosome attaches to another chromosome at the centromere
Only occurs with 13, 14, 15, 21, 22 - two acrocentric chromosomes stuck end-end creating a normal phenotype
Monosomy of the sex chromosomes causes…
Turners syndrome 45XO
Trisomy of chromosome 21 causes…
Downs syndrome
What is FISH?
DNA probes specifically bind to areas of individual chromosomes and apply a fluorescein stain to make the chromosome visible
Useful for detecting aneuploidies
What is Array CGH?
Genomewide search to detect polymorphisms (deletions or duplications) using dye and a scanner to show abnormalities between the sample and a reference
Extra chromosome 18 causes…
Edwards syndrome
Extra Y/X chromosome causes…
Klinefelters syndrome
Give two methods of targeted testing for small genetic changes
PCR - original DNA strand is duplicated and then copies are made increasing the mutation which is detected when compared to the trace
NGS - DNA fragmented and rebuilt using the reference to show mutations
Give types of point mutations
MISSENSE single nucleotide change creates a codon that codes for a different AA
NONSENSE single nucleotide change codes for a premature stop codon
INSERTION (in-frame or out-of-frame)
DELETION (in-frame or out-of-frame)
Autosomal dominant disease occurs when…
There is one faulty copy of the gene
Seen in all generations 50% risk of affected child if parent affected
Autosomal recessive disease occurs when…
There are 2 faulty copies of the gene
Often only one generation affected
25% risk of affected child if parents are carriers Increased likelihood if parents are related
X-linked disease occurs when…
The disease is carried on the X-chromosome
- only 50% of male children of a female carrier affected
- 50% of female children of a female carrier affected
- All male children of a male carrier normal
- All female children of a male carrier will be carriers
What is a caveat?
Female carrier shows mild features of X-linked disease
Process preventing a double dose of gene products
X INACTIVATION: one X chromosome of females randomly inactivated using XIST gene of XQ13 via METHYLATION
Methylation inhibits which process?
DNA transcription - chemic modification that does not change base sequence but interacts with histones on DNA
The term used to describe X inactivation ‘gone wrong’ is….
SKEWING: Inactivation of one X chromosome favoured over another - mutation in XIST gene - results in uneven number of cells with X chromosome inactivation
Penetrance is defined as…
The likelihood of having the disease given you have the genetic mutation
Mendelian inheritance encompasses which disorders?
Autosomal dominant
Autosomal recessive
X-linked
Mitochondrial
Penetrance in…
a) Mendelian disorder
b) Multifactorial disease
a) High - controlled by mutation in single gene with a small environmental input (usually rare disease)
b) Low - genetic change attributed to environmental input (usually relatively common disease)
What is the common disease - common variant hypothesis?
Common disease causing variants will be found in all human populations which show a disease but not necessarily expressed in phenotype
What is imprinting? What is it controlled by?
Variation in gene expression depending on which parent you inherit the gene from e.g. in Angelman’s syndrome, mother’s UBE3A works fine but father’s is methylated - controlled by methylation
What is mosaicism?
Occurs when cells within the same person have a different genetic makeup (causes cancer)
Cancer is most often inherited as a high penetrance Mendelian disorder. True/False?
False
More usually multifactorial
Risk of breast cancer:
a) High
b) Medium
c) Low (population risk)
a) BRCA1 mutation
b) mother/sister breast cancer at 45
c) mother with breast cancer at 70
Chromosome changes indicate treatment in cancer. What is the treatment for Her2 amplification?
Monoclonal antibody
Trastuzamab
Chromosome changes indicate treatment in cancer. What is the treatment for Philadelphia chromosome?
Tyrosine kinase inhibitor
Imatinib
Any genetic change you see may be…
A disease-causing mutation
A polymorphism
A variant of unknown significance
How do you differentiate between a polymorphism and a disease causing mutation?
Is it de-novo? (?Is it present in the child but not both normal parents)
Is it in the right gene?
Has it been reported before? (? % of population)
What does it do to the protein? (?frameshift)
What is the central dogma?
The two-step process, transcription and translation, by which the information in genes flows into proteins: DNA → RNA → protein`
What is the most likely reason that a single base mutation has no effect on protein sequence?
Codon usage shows redundancy
Lots of combinations of bases and less amino acids, so different combinations can make the same amino acid - almost always 3rd base
What is the reason for a person carrying a mutation but not showing features of a disease?
It has variable penetrance
Why is NGS better than sanger sequencing?
It allows sequencing of a much larger number of genes
Why is aCGH preferable to karyotyping?
It has higher resolution
What characteristic of a cancer cell is central to allowing it to acquire further new characteristics?
Genomic instability
Which ethical principle is most important in genetic counselling for your patient if they ask for a test?
Patient autonomy
What is a synonymous mutation?
A change in the DNA sequence that codes for amino acids in a protein sequence, but does not change the encoded amino acid
How do you calculate the pedigree risk of a child being affected?
Carrier risk of parent x population risk x risk of inheritance (AD or AR)
Name the medication that works for carriers of the G551D mutation. How does it work?
Ivecaftor It affects ion channel opening (class 3)
What is the difference between symptomatic and presymptomatic testing?
Symptomatic - clinical presentation
Presymptomatic - risk of inheritance
How do you determine the genetic risk of a child inheriting CF?
Carrier risk e.g. of mother x
Population risk e.g. of husband x
Risk to fetus of inheriting mutation (AD or AR)
