Genetics Flashcards
2 factors of a disease?
Environment + genes
What processes occur in a 5’ -3’ direction?
Replication and reading of DNA structure
What is the DNA backbone composed of?
Sugar-phosphate
4 bases in DNA?
Thymine
Adenine
Cytosine
Guanine
What happens when DNA strand associates with proteins (name example of type of proteins)?
Histones
It is wound into a chromosome structure
Explain what can happen to DNA in replication and what it’s defect can result in?
Damaged during replication
-Repair mechanisms exist but when these have defects disease occurs
The stages of cell cycle?
G1, S, G2, M, G1
What stage of cell cycle does DNA synthesis take place in?
S phase
What unzips DNA molecule?
DNA Helicase
Which enzyme copies the 5’-3’ strand?
DNA polymerase
Interphase?
Cell is not dividing the stages of cell cycle included in this is S, G0, G1 & G2
Cell grows and is metabolically active
G2?
After DNA replication the cell continues to grow and produce proteins
M phase?
Mitosis checkpoint
Are chromosomes aligned on the spindle
G1?
Cell may increase in size, produce RNA and synthesize protein
S phase?
Period of DNA replication
Going from 2n- 4n in preparation for mitosis
How does DNA polymerase work with Okazaki fragments?
Copies the 3’-5’ strand which DNA ligase joins
Mitosis outcome?
One diploid cell becomes two identical daughter diploid cells
Meiosis outcome?
One diploid parent cell becomes 4 haploid daughter cells
- crossing over occurs to produce variation
- Gamete formation
Describe an RNA strand?
- Single stranded
- Ribose sugar
- Uracil replaces thymine
Brief description of DNA-> protein?
DNA | Transcribing and splicing RNA | Translation Protein
In detail transcription and translation?
- DNA transcribed to pre-mRNA
- Pre-mRNA pliced (removal of introns) to form mRNA
- mRNA translated to protein (3 bases= 1 amino acid/stop codon)
- Protein is modified and moved around cell
Types of sequence variations within a gene?
Changes in promoter sequence
Changes in exon sequence
Types of sequence changes in DNA between genes?
SNP’s
Larger deletions/duplications
What is a polymorphism?
Any variation in the human genome which has a population frequency of <1%
A polymorphism will cause disease. True or false?
FALSE
It can cause a disease but not in it’s own right, may predispose to a common disease
What is a mutation?
Gene changes that cause a genetic disorder
-any heritable change in the human genome
How many mutations required in a classical genetic disease?
One mutation sufficient to cause disease
Describe multifactorial disease and it’s relation to polymorphisms?
Multiple polymorphisms cause a risk of disease
Chromosome make up of a normal female?
46XX
What consists of an unbalanced chromosome rearrangement?
- Extra or missing chromosomal material
- Usually 1 or 3 copies of some of the genome
- Concerning for development
Aneuploidy?
Whole extra or missing chromosome
Translocation?
Rearrangement of chromosomes
Describe genome defect of Down syndrome in a boy?
Trisomy 21
47XY + 21
What would happen if a genome was 47XY + 14? and what is the formula to describe this?
MIscarraige
Trisomy 14
What is the genome for Edward’s syndrome?
Trisomy 18
47 XY + 18
Which genetic condition is 45X?
Turner’s syndrome
What is 47 XXY?
Klinefelter syndrome
What is a Robertsonian translocation?
2 acrocentric chromosomes stuck end to end
Most common ones are 13 &14, 14&21 and 14&15
What does robertsonian translocation increase the risk of?
Trisomy in pregnancy (Down’s or miscarraige)
Acrocentric?
Having centromere situated so that one chromosomal arm is much shorter than the other
What is a first line chromosome test?
Microarray CGH
What does a microarray CGH detect?
Any missing or duplicated piece of chromosome, finds polymorphisms.
It detects size of imbalances
Gonadal mosaicism other term for it and explanation?
Germline mosaicism
-Causes recurrence risk fro autosomal dominant conditions even if parent unaffected
Somatic mosaicism?
All cells suffer mutations as they divide
-Repair mechanisms exist for this
What is mosaicism?
Different cells have a different genetic constitution
How genes are analysed and how mutations are detected?
PCR
Sequencing
Filtering
Types of mutation?
Missense Premature stop In frame Out of frame Splicing or promoters mutation Mutations that inactivate or activate a gene
Missense?
Base change causing amino acid change eg Instead of The cat sat on the mat it would be The caR sat on the mat
Premature stop?
Base change causing this **
What causes an in frame or out of frame mutation?
Insertion or deletion of base
What do we use to analyse deletions and duplications?
aCGH - for balanced rearrangements
PCR is used for analysing?
For changes in small number of BP
How does PCR work?
Allows us to select one small piece of human genome from a patient (100-10000 bases) and amplify it to make lots of copies
Example of an insertion mutation in the sentence the cat sat on the mat?
The cat sPa to nth ema t
Example of deletion out of frame and then in frame fro the cat sat on the mat?
Out= The cas ato nt hem at In= The cat on the mat
What are tumour suppresors?
Genes that stop cells dividing if switched on
Oncogenes?
Genes that start cells dividing when switched on
Penetrance?
The likelihood of having a disease if you have a genetic mutation
Expression?
Variation in disease severity if you have a mutation
Polymorphism?
Genetic variation that is prevalent in the population but is not in itself disease causing
Promoter and splice site sequence changes?
Stop transcription or cause abnormal splicing
What effect does a base change causing amino acid change have?
Change in protein sequence. May or may not reduce protein function
What are mendelian disorders?
A disease that is caused by a change in a single gene
Describe characteristic of an autosomal dominant disorder?
- Seen in all generations
- 50% risk of child being affected if parent is affected
- Severity of disease is variable
- Males and females equally likely to be affected
Describe characteristics of an autosomal recessive disease?
- 2 faulty copies of gene are required to cause disease
- Affects only one generation
- 1 in 4 chance of children having it if parents are carriers
- Increased likelihood in incestuous families
- Usually cause loss of function
Fancy term for incestuous?
Consanguineous
Describe characteristics of an X-linked recessive disease?
Recessive
- Y chromosome irrelevant
- Haemophilia
- NO male-male transmission
If a mother is a carrier of an x-linked recessive disease what is the chance her son or daughter is affected?
50% chance of daughter carrier
50% chance male is affected
Describe characteristics of Mitochondrial disease?
Inherited almost exclusively maternally
-point mutations and deletions occur
Symptoms of mitochondrial inherited disease?
- Myopathy
- Diabetes
- Deafness
- Optic atrophy
- Stroke like episodes
- Encephalitis
Which disease is autosomal dominant?
Huntington’s disease
Non-mendelian inheritence?
Methylation/imprinting
Mitochondrial inheritance
Mosaicism
Which inheritance is common in incestuous families?
Autosomal recessive
Why would a female carrier show mild features of an X-linked disease?
X-inactivation
in female cells only one X chromosome is active
What is a CNV?
Copy number variation
They are extra or missing stretches of DNA
How mendelian inheritence works with factors like environment?
High penetrance
Small environmental contribution
Factors involved in multifactorial disease?
Genetic change is just another risk factor
penetrance for an one mutation is low
Individual genetic factors are treated the same as environmental risk factors
What happens in DNA methylation?
Leads to modification of histones which represses transcription
What is imprinting?
The differences in gene expression depending on whether a gene is maternally or paternally inherited
What is angelman syndrome?
Neuro-genetic disorder caused by imprinting on chromosome 15
Symptoms of angelman disorder?
Developmental delay Intellectual disability Ataxia Epilepsy Happy demeanour Frequent laughing and smiling
Heteroplasmy?
Different daughter cells contain different proportions of mutant mitochondria
-severity of phenotype depends on proportion and level of mitochondria/type of mutation
Characteristics gained by cells on progression to cancer?
Proliferation Evasion of immune response Acquire a vascular supply Avoid apoptosis Metastasis
Genes involved in cancer?
Oncogenes
Tumour suppressors
DNA repair genes
Drug metabolism
What are drug metabolism cells?
Genes that metabolise carcinogens
Mechanisms of gene activation?
Duplication of the gene
Activation of the gene promoter
Change into amino acid sequence
What does FISH stand for?
Fluorescence in situ hybrid
What can FISH do?
Light up specific bits of chromosome
What type of mutation causes a small proportion of familial breast cancer?
BRCA 1
What is BRCA 1 gene involved in ?
DNA strand repair
What is multifactorial predisposition?
Everyone is at some risk
Anyone with family history is at increased risk
