Lecture 2: Genetic Disease Flashcards
Meiosis …. the chromosome number (… n), while Fertilization …. the chromosome number (… n)
Meiosis REDUCES the chromosome number (1 n), while Fertilization RESTORES the chromosome number (2 n)
What is the difference between Polyploidy and Aneuploidy?
- Polyploidy is the change in chromosomal number such that every chromosome is affected (Ex. Triploidy; 3n= 69 Total Chromosomes, ;).
- Aneuploidy is the gain or loss of chromosomes where not all chromosomes are affected (Ex. Trisomy 21; 21+= 47 Total Chromosomes)
True or False: Triploidy (3n) results in an early miscarriage due to the massive change to Gene Dosage
True; Triploidy results due to Error in Fertilization
- Foetus will have large head and small trunk due to intrauterine retardation and be inviable
Aneuploidy is due to …. in either Meiosis 1 or 2
Aneuploidy is due to NON-DISJUNCTION in either Meiosis 1 or 2
True or False: Aneuploidy typically occurs in Meiosis 2, but can still occur in Meiosis 1
False; Aneuploidy typically occurs in MEIOSIS 1, but can still occur in Meiosis 2
What is the only viable monosomy?
Turner Syndrome (Female born with only 1 X Chromosome)
The three viable trisomies are…
1) Patau Syndrome (13+)
2) Edward Syndrome (18+)
3) Down Syndrome (21+)
“PEDS”
Aneuploidy risks (increase or decrease) with age and (increase/decrease) after having an aneuploid offspring
Aneuploid risks INCREASE with age (i.e. Old Egg Hypothesis) and INCREASE after having an aneuploid offspring
What are some phenotype qualities associated with a Down Syndrome individual?
- Simian Palmar Crease
- Epicanthic Folds near eyes
- Mental Retardation
- Predisposition to Leukaemia and Early-Onset Alzheimers Disease (100% chance of development)
What are the percentages of offspring genotypes (i.e. Normal, Trisomy and Monosomy) for a Non-Disjunction Event in Meiosis 1 and Meiosis 2?
ND in Meiosis 1 = 50% Monosomy, 50% Trisomy
ND in Meiosis 2= 25% Monosomy, 25% Trisomy and 50% Normal
Is Non-Disjunction more likely to occur in the Female gamete (Egg) or Male gamete (Sperm)
Female gamete (Egg), especially in Meiosis 1 due to increase in Non-Disjunction potential
In Robertsonian Translocations for Down Syndrome, what two chromosomes are translocated?
Chromosome 14 and 21 (Acrocentric stalks of Chromosome 21 break off and translocate to 14)
Why is there a high reoccurrence of Robertsonian Translocations being passed to offspring?
Structural Rearrangement between Chromosomes 14 and 21 causes the two chromosomes not to be separated individually during Meiosis
If the (Mother/Father) is the Robertsonian Translocation carrier, there is a greater risk of recurrence in the offspring
Mother
Down Syndrome Mosaicism (i.e. some cell lines have 21+ and other cell lines are normal) occurs due to …..
Mitotic Non-Disjunction during Embryogenesis
The region on Chromosome 21 where many of the genes associated with the Down Syndrome phenotype is called the …..
Down Syndrome Critical Region (DSCR)
The …. gene on Chromosome …. creates ….. precursor protein which is associated with plaque formation in the Brain and ….. Disease.
The APP gene on Chromosome 21 creates BETA AMYLOID precursor protein which is associated with plaque formation in the Brain and ALZHEIMERS Disease.
Down Syndrome Critical Region (DSCR) genes include ….
1) APP (Important one to know)
2) DYKR1A
3) DSCRI
2) and 3) important genes in signally pathways so just shows how a couple of genes can affect so many others and their protein products downstream
…. Prenatal Screening use cell free Foetal DNA from Mother’s Blood to test for three copies of Chromosome 21
Non-Invasive Prenatal Screening (NIPS)
True or False: Most Down Syndrome Diagnoses are from Second Trimester Screening
False; 85% of Down Syndrome diagnoses are from First Trimester Screening (i.e. Nuchal Translucency Thickness)
What are some key details about Edward Syndrome?
- ND of Chromosome 18
- Rocker Bottom Heel
- More rare and severe than DS (90% mortality rate by 2 years)
What are some key details about Patau Syndrome?
- ND of Chromosome 13
- Facial Malformations (ex. Cleft Palate) and Polydactyl
- Most rare and severe of the three trisomies (10% 1st year survival rate)
Sex Chromosome Disorders are (More common/Less Common) and (More severe/Less severe) than Autosomal Chromosome Disorders.
Sex Chromosome Disorders are MORE COMMON and LESS SEVERE than Autosomal Chromosome Disorders.
Sex Chromosome Disorders are tolerable due to …. of one of the X Chromosomes and the Y Chromosome having little genetic material.
Lyonisation of one of the X Chromosomes
What is Lyonisation?
Process in which one X Chromosome in a female is randomly inactivated and turned into a Barr Body
- Maintains Gene Dosage
- Maternal or Paternal X is inactivated
Would a male with Klinefelters Syndrome (XXY, 47) have a Barr Body
Yes, they would have 1 Barr Body
- Klinefelters Syndrome has the phenotype of being tall, female features and infertility
What is the phenotype of a female with Turner Syndrome (X, 45)?
- Short neck, low posterior hairline and infertility
Clinical features are due to Haploinsufficiency–> Need 2 copies of a gene to illicit proper function
(Ex. SHOX gene on the X Chromosome requires 2 copies to promote long bone growth)
Define Haploinsufficiency?
Haploinsufficiency occurs when only one copy of a gene is not enough to illicit proper gene function.
(Ex. SHOX gene on the X Chromosome requires 2 copies to properly promote long bone growth)
