Genetics Flashcards
What is the biggest cause of trisomies?
Maternal Dis-junction - failure of normal chromosomal separation
What is Trisomy 13? and name some symptoms:
Patau Syndrome
congenital heart disease - 50% die before 1 month
What is trisomy 18?
Edward’s syndrome
What kind of tumor suppressor is the BRCA gene?
Stability Gene
What is the main function of BRCA genes?
To code for homologous DNA repair for double stranded breaks
What two less common genes are associated with breast and ovarian cancer?
MLH1
MLH2
What is a prophylactic drug being used to treat ovarian cancer?
Aloparib
Hereditary Non - polyposis Colon cancer is most commonly caused by which genes?
MLH1
MSH2
Familial Adenomatous Polyposis is most commonly caused by which genes?
APC gene on chromosome 5.
What non -clinically significant symptom may a patient with familial adenomatous polyposis have?
Congenital hypertrophy of the retinal pigmented epithelium
Name a autosomal recessive cancer:
MYH Polyposis
What does the MYH gene code for?
Base excession repair
In Huntington’s disease, which gene is affected and what is the cause of pathology?
HHT gene.
CAG repeats - glutamine build up n the protein leading to aggregates forming.
Defects in DMPK gene will cause which disease?
Myotonic dystrophy
In myotonic dystrophy, what gene is affected and how does this cause pathology?
DMPK gene.
3’ CTG repeats - causing faulty DMPK mRNA.
This indirectly causes toxic affect on the splicing of other mRNA.
Name an important mRNA that is indirectly affected by DMPK -causing characteristic myotonia
CLCN-1 mRNA
What is the most common gene mutation in CF?
F508 deletion
What protein does DMD code for?
Dystrophin - an intracellular protein that attaches to the dystroglycoprotein complex and the actin filament - communicating with extracellular of cell
Whats the most common mutation in DMD and what does this cause that leads to such severe symptoms being seen?
Deletion of exons in the DMD gene, causing frame shifting, causing complete protein dysregulation .
Whats implicated in FMR1 gene?
Fragile X - syndrome
How is Fragile X syndrome developed?
tri-nucleotide repeats at the 5’ end of FMR1 gene.
resulting in silencing of the gene - through methylisation
What type of sequencing would be done to search for a point mutation in an unknown gene defect?
Sangers sequencing
What type of sequencing is done for a point mutation of known allele? i.e. the mutation is known.
ARMS sequencing
What time of testing is done for a sub-microscopic mutation, where the gene allele is not known? and how is it interrupted?
aCGH
Green: duplication
Red: deletions
What type of testing is done for a sub-microscopic mutation, where the gene allele is known?
MLPA
With regards to genetic testing what does PGD mean and what are some pros and cons?
Pre- implantation diagnosis
Pros:
- allows implantation of unaffect cells
Cons:
- Not available to all women
- long wait
- 50% take home baby rate
What are polyploidies? and give an example:
Abnormal number of chromosomes in a multiple of 23.
Triploidy: 69 chromosomes
this can occur in hydatidiform changes, where 2 sperm penetrate an egg, resulting in 69 chromosomes.
What syndrome can FISH be useful for identifying?
Williams Syndrome
Name some neonatal screening tests carried out Mass spectrometery:
PKU
MCADD
Name the set of conditions that show genetic anticipation:
Huntington’s
Myotonic dystrophy
Fragile X syndrome (to a degree)
What drug re-opens the Cl- channel in CF, which is a type of precision medicine? what is the mutation it specifically works on?
Ivacaftor
G551D
What gene has been cut out using CRISPR CAS9 and what disease does it cause?
FBN1 - marfan’s syndrome
Which drug targets the HER2 - EGFR2 receptor?
Trastuzumab
The new therapy proposed for DMD is what?
Antisense oligonucleotide therapy
- causes exon skipping to create an inframe mutations - less severe than normal DMD out of frame mutations.
Name some autosomal recessive conditions:
Cystic Fibrosis
PKU
Spinal Muscular Atrophy
Congenital adrenal hypoplasia
In an X-linked recessive condition, what would you expect the disruption to be amongst males and females from a female carrier?
50% daughters carriers
50% sons affected
Name some X-linked dominant conditions:
Vit D deficiency
Rett syndrome
Incontinentia pigmenti
In which type of pattern of inheritance would you expect to see higher rates of females affected?
X-linked dominant
What is the disease, that is a mitochondrial disease leading to lack of ATP synthesis, and what is the gene?
Leigh’s disease
MT-ATP6 gene
Which chromosome is HER2 gene found on? and what is a good analysis tool for looking at it?
chromosome 17
FISH
Which disease shows genetic anticipation if the mother is a carrier?
Myotonic dystrophy
What is some of the symptoms of neurofibromatosis?
Cafe au lait macules
neurofibromas
30% having learning difficulties
List the trinucleotide repeat disease:
Huntington’s
- CAG - glutamine
- anticipation from father
- AutoD
Mytonic Dystrophy
- CTG
- Anticipation from mother
- AutoD
Fragile X
- CCG
- anticipation
- x-linked
What’s the blood markers carried out for carriers and children who have duchene muscular dystrophy?
Serum Creatinase Kinase
What’s the sign called when a child has to use their hands on their knees to push themself up?
Gowen’s sign
List some comparisons between autosomal dominant and autosomal recessive conditions:
Vertical vs Horizontal
Homozygous vs heterozygous
50% vs relatively low risk depending on population risk
Variable expression vs Constant expression
Incomplete penetrance vs Complete penetrance
Define what a Point mutation is:
Single change in the nucleotide sequence
Define what a missense mutation is:
Point mutation in which the single nucleotide change results in codon that codes for a different amino acid.
Define what a silent point mutation is:
Where the single nucleotide change codes for the same amino acid
What is a conservative point mutation?
Where a point mutation leads to a different amino acid being produced, but is very similar to original amino acid.
Define what a Nonsense mutation is?
Were a premature stop codon is formed - causing premature termination of protein synthesis.
What is the symptoms of fragile x syndrome?
It is the most common cause of mendelian inheritance to cause mental impairment
Low IQ Inverted ears Mitral prolapse long facial features enlarged testicles
Variable expression may occur in AS dominant conditions, what is it that causes this?
Variable expression is where there is different severities of the disease.
It may be caused by:
- stability genes
- epigenetics
How is Cystic fibrosis screened for?
Immunoassay
Cl- levels in sweat of the baby.
If these are positive then DNA testing is done.
If a person has myotonic dystrophy, they are at greater risk of developing another disease, what is this and why?
Diabetes and this is because of damage to the mRNA that codes for the insulin
What is a very good test for detecting gene deletions?
MLPA
*the area must be known
What is a very good test for detecting trisomy?
QF - PCR
Mutated Proto-oncogenes are usually not inherited, name one that is and what it is associated with:
RET
MEN2 - pheochromocytoma
What area on the x chromosome is dystrophin coded, and thus is mutated in DMD patients?
Xp21
What drug is good for stopping colorectal cancer?
Aspirin
What serious trisomy is associated with an extra little finger?
Patau syndrome - trisomy of 13
