Chromosomal and Genomic Basis of Disease Flashcards
What is cytogenetics?
The study of the structure, function and evolution of chromosomes and the changes in them which can result in phenotypes of clinical significance.
Name two things which can explain why similar/ identical chromosomal abnormalities may show a range of variable phenotypes.
- Non-genetic environmental triggeres/ effects
- Genetic variation, either within the site of the abnormality or in other areas which effect them.
What is the most common trisomy in a
- prenatal context?
- postnatal context?
- Trisomy 16
- Trisomy 21 (down syndrome)
What are the three non-mosaic disorders that allow for post-natal survival? What are their incidence of birth?
- Trisomy 21 (Down syndrome) 1/850 births
- Trisomy 18 (Edward’s syndrome) 1/ 6,000 - 8,000 births
- Trisomy 13 (Patau syndrome) 1/ 12,000-20,000 births
What are the three chromosomes which contain the least number of genes?
most - 13, 18, 21 - least
What kind of trisomy is being described?:
Hypotonia, loose skin on nape of the neck, clinodactyly, high risk of leukemia, flat occiput, palmar crease, congenital heart disease.
What is the life expectancy of this individual?
Trisomy 21/ Down Syndrome
55 years
What kind of trisomy is being described?:
Hypertonia, prenatal growth deficiency, Rocker-bottom feet, fist clenching, severe heart malformation.
What is the life expectancy of this individual?
Trisomy 18/ Edward’s Syndrome
< a few months
What kind of trisomy is being described:?
Microcephaly sloping forehead, Rocker-bottom feet, fist clenching, severe CNS malformation, polydactyly, low set ears and receding jaw.
What is the life expectancy of this individual?
Trisomy 13/ Patau Syndrome
< a year
What is the genetic cause of 95% of trisomy 21? In which parent does this event usually occur?
Meiotic nondisjunction during meiosis. In 75% of cases this is in the maternal parent.
Do all down syndrome patients have 47 chromosomes?
No.
Translocation Down Syndrome, Mosaic Down Syndrome and Partial Down Syndrome patients can all have only 45 or 46 chromosomes.
What percentage of Down Syndrome is due to Robertsonian translocations?
3-4%
pg 1
- How does mosaicism in trisomy 21 usually occur?
What percentage of down syndrome cases are mosaic?
- How does a mosaic trisomy 21 phenotype compare to a non-mosaic trisomy 21?
- Generally it occurs through a trisomic conception followed by a loss of the extra chromosome during mitosis in some embryonic cells.
- 2-4%
- Mosaic trisomy 21 results in more milder clinical expression, the exact features of which depend on the type of tissue in which the mitotic anomaly occurred.
Why are partial trisomy down syndrome cases of particular interest to researchers?
Because partial down syndrome is due to a duplication in only a particular part of the chromosome. The study of patients with this disorder can help researchers understand which regions of the genome are responsible for what symptoms, particularly the cardiac phenotype.
What is the most common cause of trisomy 13 (Patau Syndrome)?
Increased maternal age is a risk factor. It is mostly due to a nondisjunction event at meiosis I. However, it can also be caused by an unbalanced translocation.
Depression alert
- What percentage of trisomy 18 conceptions survive to term?
- What percentage of trisomy 18 births survive the first few weeks of life?
- What percentage of trisomy 18 births survive to 1 year?
- What percentage of trisomy 18 births survive within the
- less than 5 %
- 50 %
- 8 %
When is first trimester prenatal screening preformed? What does it entail? What is the goal?
11-13 weeks into gestation.
- Blood test / Serum screening
- Ultrasounds to assess physical features
- maternal age
- maternal blood samples to assess circulating fetal cell-free DNA.
The goal is to inform on the risks for particular birth defects and genetic disorders.
What is a common neural tube defect which can be observed with an ultrasound?
Meningomyelocele sac
What is a feature that can be observed by week 11 in trisomy 21 fetuses?
Nuchal translucency. This leads to the loose skin around the neck.
How are free beta human chorionic gonadotropin (L. beta HCG) levels affected by the three viable types of trisomies?
Increase in Trisomy 21
Decrease in Trisomy 18
Decrease in Trisomy 13
What is some of the information which can be obtained by a Non-Invasive Prenatal Screening (NIPS)?
- Chromosomal aneuploidy detection
- Subchromosomal deletions/duplications
- Whole fetal genome sequencing
- Fetal methylome
- Fetal transcriptome
What are examples of invasive diagnostic tests?
- Chorionic villus sampling (placental tissue)
- Amniocentesis sampling (amniotic fluid)
These carry a 1 in 200-250 chance of causing a spontaneous abortion.
What are the differences and similarities between Chorionic villus sampling (CVS) and Amniocentesis?
- Both are invasive diagnostic tests
- Both can be Trans-abdominal procedures
- Both use real time ultrasound to guide the needle and monitor the procedure
- CVS is done at 10-11 weeks while amniocentesis is done at 15-17 weeks.
- CVS can be a trans-cervical procedure.
with rapid aneuploidy detection, what is a hallmark of trisomy?
three spikes at a certain chromosome value.
What will be the normalized sequence representation of a normal and a trisomy 21 individual in whole genome sequencing?
~1.0 for normal
~1.5 for trisomy 21 at chr21 only.
