Genetic Causes of Fetal Loss and Abnormality Flashcards
What is miscarriage
Natural selection against chromosome inbalances
What are whole chromosome aneuploidies What are the results if you have aneuploidy in -in gonad in meiosis -mitosis within germline -mitosis within embryo
How does the likelihood change with maternal age
Which aneuplodies are viable
Malsegregation
In gonad in meiosis =>abnormal gamete
During mitosis within the germline =>mosaics in the gonad
During mitosis within the embryo => mosaics in the embryo
Likelihood increases with maternal age
13, 18, 21, XY
What are Robertsonian translocation
- which 2 combinations are the most common
- what are the 2 possible outcomes and their viability
Acrosome breaks at centromere
13, 14
14, 21
Alternate => viable but reproductive risk
Adjacent => trisomy or monosomy (genetic material missing or doubled)
What are reciprocal translocations
-what are the 2 possible outcomes and their viability
Non homologous chromosomal exchange
Alternate => viability depends on size of genetic imbalance
Adjacent => unlikely to be viable but depends on size of genetic imbalance
What is a deletion/duplication
-what are the 2 possible outcomes
Misalignment of repeated sequences and crossover
Can be clinically benign
Or linked to pathology
What are the 2 inheritance patterns of monogenic disorders
Inherited
De novo
What is epigenetics
Changes in the genome that affect gene expression but not the DNA sequence
What is DNA methylation
- Which region of DNA is the most methylated
- what happens when you methylate the promoter
- what happens when you methylate the gene body
- what happens when you methylate transposable elements
- how does this link to imprinting
- how does methylation change during development
Addition of methyl to cytosine => 5mC
Clustered in CpG islands
Promotor methylated => silenced
Gene body methylated => expressed
Transposable elements methylated => silenced, prevents movement
If maternal/paternal genes are silenced => imprinted
Demethylated before gamete formation but methylation increases
Demethylation post fertilization
Methylated in embryo development
How can cells differentiate and undifferentiate
Factors can maintain pluripotency
Factors can induce differentiation
What is X chromosome silencing
- what is X skewing
- what 3 diseases can arise if X skewing occurs
Random silencing of 1X
-preferential inactivation of 1X
Haemophilia
Fragile X
DMD
What are imprinting disorders
When the imprinted gene that is expressed is
- absent (UPD)
- deletion/mutation
What is Prader Willi
What is the pathophysiology
What are the signs and symptoms
Maternal copy imprinted, paternal copy faulty
C15
Life threatening obesity Constant hunger Short stature Mild mental retardation Facial dysmorphia
What is Angelman
What is the pathophysiology
What are the signs and symptoms
Paternal copy imprinted, faulty maternal copy
C15
Always happy
Severe mental retardation
Ataxia
Large mouth, wide spaced teeth
What is Beckwith Wiedemann
What is the pathophysiology
What are the signs and symptoms
Dysregulation of imprinting control region on C11
Macrosomia, macroglossia
Overgrowth, asymmetry
Enlarged kidney, liver, spleen, pancreas
CV defects
What os SIlver Russell
What is the pathophysiology
What are the signs and symptoms
Imprinting disruption of C7, 11
Pre, postnatal growth retardation
Growth asymmetry
Incurved little finger
