Genetics Flashcards
List the 7 types of congenital abnormalities and birth defects.
Malformation Disruption Dysplasia Sequence Association Deformation Syndrome
Define dysplasia.
Abnormal organisation of cells into tissue
What is the most common cause of Sequence e.g. Potter Sequence?
Oligohydramnios – reduced supply of amniotic fluid
What are the 3 types of chromosome?
Metacentric
Submetacentric
Acrocentric
Describe how chromosome banding works.
Starts at 11 at the centromere – different banding for different stains
What are the three different types of chromosomal abnormality?
Aneuploidy
Structural
Mosaicism
What is mosaicism?
The cells of an individual do not all contain identical chromosomes. There may be two or more genetically different populations of cells. E.g. one cell lineage will be Down Syndrome
What is the difference between a balanced and unbalanced translocation?
Unbalanced – there is a loss of genetic material
What could be the potential future issues for someone who has a balanced translocation?
Balanced translocations lead to the formation of quadravalents (rather than bivalents) during meiosis which can lead to strange exchanges in genetic material which can cause disease
List some clinical features of Down Syndrome.
Excess nuchal skin, sleepy, severe hypotonia Single palmar crease, sandal gap Upwards slanting eye folds, macroglossia Short stature Cardiac abnormalities – ASD and VSD
List three possible causes of Down syndrome.
Non-disjunction during meiosis I or meiosis II
Robertsonian translocation – 2 acrocentric chromosomes break at the centromere and fuses to form a new chromosome
Mosaicism
What is monosomy X in females and what are the clinical features?
Turner Syndrome – webbed neck, infertile, normal intelligence, low posterior hairline
What is polysomy X in males and what are the clinical features?
Kleinfelter’s syndrome – tall, gynaecomastia, infertile, learning disability
How can someone who has sex chromosomes XX be male?
Due to a translocation in which the sex determining region on the Y (SRY) has been translocated onto the X chromosome.
What are genomic disorders?
Disorders in which there is a gain or loss of DNA
Give an examples of two genomic disorders.
Deletion – Di George syndrome
Duplication – Charcot-Marie-Tooth Disease Type 1A
State the differences between monogenic and complex diseases.
Monogenic diseases are rare, have a clear inheritance pattern and are not affected by environmental factors
Complex diseases are the opposite
State the difference between mutations and polymorphisms.
Mutations are any changes in genetic material that are hereditary
Polymorphisms are mutations which occur at >1% frequency in the population
State two different types of point mutations.
Non-sense and mis-sense
State two types of frame shift mutations.
insertion and deletion (InDel)
Give an example of an autosomal dominant disease and the mechanism of action.
Huntingdon’s Disease – mutations in the HTT gene on Chr 4, which codes for huntingtin. Mutation leads to production of a toxic protein that accumulates and forms clumps in organs. Causes cell death in the basal ganglia in the brain. It is caused by an unstable CAG repeat – the more repeats you have the more likely you are to get HD. Severity increases with time and age of onset decreases.
Give an example of an autosomal recessive disease and the mechanism of action.
Cystic Fibrosis – caused by a mutation in the CFTR gene on Chr 7, which affects chloride ion function in epithelial cells. Gives rise to thick mucus.
Give an example of a mutation in the same gene causing two different conditions.
Congenital absence of the vas deferens – caused by mutations in CFTR
Give an example of a X-linked recessive condition.
Haemophilia A and B – A is caused by a mutation in the F8 gene on Chr X which encodes factor VIII.
B – caused by mutation in F9 gene which encodes factor IX
What are the general molecular mechanisms of the different types of genetic disease (autosomal dominant, autosomal recessive, co-dominant)?
Dominant – toxic product produced (treatment aims to neutralise toxic product)
Recessive – absence of functional protein (treatment aims to regain function
What happens if the full genome of an embryo derives from one parent and what is the significance of this finding?
Paternal – hydatidiform mole
Maternal – ovarian teratoma
Shows that the origin of the parental DNA is important
What is the mechanism of imprinting?
DNA Methylation
Which base gets methylated?
5’ position on the pyrimidine ring of the cytosine
What is the general effect of methylation on the gene promoter?
Repressed gene transcription
The loss of function of a gene on which chromosome causes Prader-Willi and Angelman Syndrome?
Chromosome 15
State some symptoms of Prader-Willi Syndrome.
Hyperphagia Obesity Mental Retardedness Short Stature Hypotonia Infertility
State some symptoms of Angelman Syndrome.
Microcephaly
Poor or absent speech
Gait ataxia
Severe developmental delay
What are the three possible causes of Prader-Willi and Angelman Syndrome?
Deletion of the PWS/AS critical region on chromosome 15
Uniparental isodisomy
Other mechanisms e.g. translocations
Describe how uniparental isodisomy can lead to Prader-Willi and Angelman Syndrome.
Non-disjunction in meiosis 2 makes a gamete that has two copies of chromosome 15 resulting in a zygote with three copies of chromosome 15.
Failure to remove the duplicated chromosome results in the zygote having two copies of chromosome 15 from the same parent.
How is PWS and AS diagnosed? Which genes near/in the PWS/AS critical region are used?
FISH – fluorescence in situ hybridisation
PML (promyelocytic leukaemia) gene is just outside the PWS/AS critical region
snRNP (small nuclear ribonucleoprotein) gene is inside the PWS/AS critical region
What phenomenon determines the severity of mitochondrial disease?
Heteroplasmy
State two examples of mitochondrial disease.
MELAS and LHON
