Genetics Flashcards
DNA is read and replicated in what direction?
5’ to 3’
What is the sugar backbone in DNA?
Deoxyribose
Which base pairs have a stronger bond between them?
CG
DNA strands bind with proteins to form what?
Chromosomes
Where does DNA replication take place in the cell cycle?
S stage
What are different forms of DNA damage?
DNA strands breaking, chemical crosslinking (DNA damage), mismatched bases
What is mitosis?
One diploid parent cell to two identical diploid daughter cells
What is meiosis?
One diploid parent cell to four haploid daughter cells
Where does crossing over occur?
Meiosis
What is crossing over?
Genes segregate independently, even if on the same chromosome
What are the differences of RNA compared to DNA?
Single stranded, ribose sugar, U instead of T
What part of DNA controls if the gene becomes a protein?
Promotor
Transcription and splicing takes out what part of the DNA?
Introns
The amount of protein produced is determined by what?
Rate of transcription
Rate of splicing
Half life of mRNA
Rate of processing of polypeptide
DNA is transcribed to what?
Pre mRNA
Pre mRNA is spliced to what?
mRNA
mRNA is translated to what?
Protein
What is a polymorphism?
Any variation in the human genome that has a population frequency of > 1%
What is a mutation?
A gene change which causes a genetic disorder, or any heritable change in the human genome
What is the total number of human chromosomes?
46
What does it mean if the chromosomal rearrangement is balanced?
All the chromosomal material is present
What does it mean if the chromosomal rearrangement is unbalanced?
There is extra or missing chromosomal material- normally 1 or 3 copies of some of the genome
What is aneuploidy?
Whole extra or missing chromosome
What are some ways the chromosomes can become different?
Translocations, insertions or deletions
What disease is caused by trisomy 21?
Down’s syndrome
What disease is 44 + X?
Turner’s syndrome
What disease is 44 + XXX?
Triple X
What disease is 44 + XXY?
Kleinfelter’s syndrome
Why is X chromosome aneuploidy better tolerated?
X inactivation
How many bases are in the human genome?
3 trillion
How many genes are in the human genome?
30, 000
What are acrocentric chromosomes?
Where the short arm doesn’t really matter
What does Robertsonian translocation involve?
Two acrocentric chromosomes being stuck end to end
What does Robersonian translocation increase the risk of?
Trisomy in a pregnancy
What does trisomy 14 lead to?
Miscarriage
If a first child has Down’s syndrome, what is the chance of a second child having it?
Approximately 1%
What increases the risk of having a second child with Down’s syndrome?
If Robertsonian translocation is involved
What does trisomy 18 give?
Edward’s syndrome
Carriers of Robertsonian or reciprocal chromosomes commonly have what problem?
Can be infertile or have a lot of miscarriages
Modern culture and staining techniques can detect rearrangements of approximately how many base pairs?
5 million or more
What is still the method of choice for analysis of very specific regions e.g. to test if a family to see if they have a mutation found in other relatives?
Sanger sequencing
How does array detect chromosomal imbalance in a patient sample?
By comparing the patient DNA with a control sample
In microarray, if the patient DNA is flagged up, what does this suggest?
Duplication of patient DNA
In microarray, if the control DNA is flagged up, what does this suggest?
Deletion of patient DNA
What technique is used to look for specific micro deletions and also for gross alterations in chromosomal number?
Fluorescence in situ hybridisation (FISH)
If the DNA probe used in FISH matches a region of DNA in the genetic sequence, what happens?
The dye fluoresces
If the DNA probe used in FISH does not match a region of DNA in the genetic sequence, what happens?
No light is emitted
When can FISH only be used?
When clinical parameters have defined which region should be analysed
What is necessary for PCR amplification and Sanger sequencing to work?
Identification of which gene needs to be analysed from the clinical phenotype
If aneuploidy is a whole extra or missing chromosome, what is translocation?
Rearrangement of chromosomes
What happens to acrocentric chromosomes in Robertsonian translocations?
Two of them get stuck together
What will be the outcome of around 50% of reciprocal translocations?
Normal chromosomes or a balances translocation
Unbalanced reciprocal translocations have what outcomes?
Miscarriage or a dysmorphic, delayed child
What is the first line chromosome test?
Array CGH
What is the treatment for someone with a HER2 amplifications?
Monoclonal antibody
What is the treatment for someone with a problem with the Philadelphia chromosome?
Tyrosine kinase inhibitor
How much of the genome is exons?
2-3%
What type of DNA analysis shows big genetic changes?
Array CGH
What types of DNA analysis show small genetic changes?
PCR, Sanger and next generation sequencing
What is the commonest mutation of bases?
Cytosine becomes thymine
What does a promotor mutation cause?
No or little transcription, hence no or little protein
What do splice consensus altered mutations affect?
Translation
What does a base change causing a new stop codon result in?
Shortened or absent protein
What do nonsense mutations result in?
Single point mutation causing early stop codon
What do missense mutations result in?
Single point mutation causing a different or non-functioning protein
What is penetrance?
The likelihood of having a disease if you have a gene mutation
What does 100% penetrance mean?
If you have the mutation, you will definitely have the disease
What are types of Mendelian disorders?
Autosomal dominant/recessive or X linked
In terms of families, how often are autosomal dominant diseases seen?
In every generation
If one parent is affected with an autosomal dominant condition, what is the chance of a child having it?
50%
What is the male to female ratio in autosomal dominant diseases?
Have the same risk
In terms of families, how often are autosomal recessive conditions seen?
Often only 1 generation
If parents are both carriers, what is the risk of a child having an autosomal recessive condition?
25%
What is a caveat?
A female carrier showing mild features of an X linked condition
What causes some female carries to show features of an X linked condition?
X inactivation
Why does X inactivation occur?
Provide gene dosage compensation in females
What are single nucleotide polymorphisms?
Alterations in DNA sequence which occur every 100-300 base pair
How many SNPs are there?
Over 10 million possible
What are copy number variations?
Extra or missing stretches of DNA
What is a genetic change in multifactorial disease?
Just another risk factor
How many genes do monozygotic twins share?
About 100%
How many genes do dizygotic twins share?
About 50%
What does P < 0.05 in a statistical test suggest?
1 in 20 probability that the data seen has happened by chance
What are the 4 types of non-mendelian inheritance?
Mitochondrial, mociacism, multi-factorial, imprinting
What does DNA methylation lead to?
Modification of histones which represses transcription
What causes imprinting?
DNA methylation
Mitochondrial DNA is inherited almost exclusively from who?
Mother
Are sons and daughters equally affected by mitochondrial inheritance?
Yes
When do most of the mutations causing cancer occur?
Post-zygotic
What are driver mutations?
Mutations that drive carcinogenesis
What are passenger mutations?
Incidental mutations which happen because a tumour is unstable
How many copies of retinoblastoma must be mutated for a tumour to develop?
two
Carriers of a BRCA1 mutation have what lifetime risk of cancer?
80%
What is symptomatic testing?
A test to find the cause of a disease in a person
What is pre-symptomatic testing?
Testing in a patient who has a relative with a mutation
When can FISH only be used initially?
If the geneticist knows roughly what they are looking for
What does it mean if you have more than 36 CAG repeats?
At high risk for Huntington’s
What does it mean if you have more than 40 CAG repeats?
Will definitely develop Huntington’s
What does anticipation mean?
A genetic disease gets more severe with succeeding generations
